Automated Gait Analysis Through Hues and Areas (AGATHA): A Method to Characterize the Spatiotemporal Pattern of Rat Gait.

PubMed

Kloefkorn, Heidi E; Pettengill, Travis R; Turner, Sara M F; Streeter, Kristi A; Gonzalez-Rothi, Elisa J; Fuller, David D; Allen, Kyle D

2017-03-01

While rodent gait analysis can quantify the behavioral consequences of disease, significant methodological differences exist between analysis platforms and little validation has been performed to understand or mitigate these sources of variance. By providing the algorithms used to quantify gait, open-source gait analysis software can be validated and used to explore methodological differences. Our group is introducing, for the first time, a fully-automated, open-source method for the characterization of rodent spatiotemporal gait patterns, termed Automated Gait Analysis Through Hues and Areas (AGATHA). This study describes how AGATHA identifies gait events, validates AGATHA relative to manual digitization methods, and utilizes AGATHA to detect gait compensations in orthopaedic and spinal cord injury models. To validate AGATHA against manual digitization, results from videos of rodent gait, recorded at 1000 frames per second (fps), were compared. To assess one common source of variance (the effects of video frame rate), these 1000 fps videos were re-sampled to mimic several lower fps and compared again. While spatial variables were indistinguishable between AGATHA and manual digitization, low video frame rates resulted in temporal errors for both methods. At frame rates over 125 fps, AGATHA achieved a comparable accuracy and precision to manual digitization for all gait variables. Moreover, AGATHA detected unique gait changes in each injury model. These data demonstrate AGATHA is an accurate and precise platform for the analysis of rodent spatiotemporal gait patterns.

Considering our methods: Methodological issues with rodent models of appetite and obesity research.

PubMed

Lutz, Thomas A

2018-08-01

A large number of animal models are currently used in appetite and obesity research. Because the worldwide incidence of obesity continues to climb, it is imperative that animal models sharing characteristics of human obesity and its co-morbidities be used appropriately in the quest for novel preventions or treatments. There is probably no animal model, at least in rodents, that recapitulates all aspects of "common" human obesity and its comorbidities, but rodent models allow insight into specific mechanisms of disease or its consequences. Frequently used obesity models can be partitioned into different categories, the major ones being a) based on mutations or manipulations of one or a few individual genes or b) those in genetically intact animals exposed to obesogenic environments such as, e.g., being maintained on high-fat diets or being raised in small litters. Characteristics of these models include distinct phenotypes of obesity, hyperphagia or changes in energy metabolism, and frequent comorbidities of obesity, like hyperglycemia, insulin resistance or diabetes-like syndromes. This review which is based on a presentation given during the Annual Meeting of the Society for the Study of Ingestive Behavior in July 2017 points out some observations and characteristics of rodent models in obesity and diabetes research. The choice of rodent models discussed here is subjective and based on the author's own experience or on fruitful discussions with colleagues about the pros and cons of specific models. Hence, this review, by no means, is meant to give a complete picture of rodent models used in this type of research, but the review tries to bring up some issues which, in the author's mind, may also be relevant for models not discussed here. For example, by discussing specific mouse and rat models, similarities and differences between mice and rats will be discussed that need to be considered to interpret experimental findings cautiously and in the context of the respective animal model. Knowing which animal model to use means, knowing its limitations. Copyright © 2018 Elsevier Inc. All rights reserved.

An improved cost-effective, reproducible method for evaluation of bone loss in a rodent model.

PubMed

Fine, Daniel H; Schreiner, Helen; Nasri-Heir, Cibele; Greenberg, Barbara; Jiang, Shuying; Markowitz, Kenneth; Furgang, David

2009-02-01

This study was designed to investigate the utility of two "new" definitions for assessment of bone loss in a rodent model of periodontitis. Eighteen rats were divided into three groups. Group 1 was infected by Aggregatibacter actinomycetemcomitans (Aa), group 2 was infected with an Aa leukotoxin knock-out, and group 3 received no Aa (controls). Microbial sampling and antibody titres were determined. Initially, two examiners measured the distance from the cemento-enamel-junction to alveolar bone crest using the three following methods; (1) total area of bone loss by radiograph, (2) linear bone loss by radiograph, (3) a direct visual measurement (DVM) of horizontal bone loss. Two "new" definitions were adopted; (1) any site in infected animals showing bone loss >2 standard deviations above the mean seen at that site in control animals was recorded as bone loss, (2) any animal with two or more sites in any quadrant affected by bone loss was considered as diseased. Using the "new" definitions both evaluators independently found that infected animals had significantly more disease than controls (DVM system; p<0.05). The DVM method provides a simple, cost effective, and reproducible method for studying periodontal disease in rodents.

Approximate analytical modeling of leptospirosis infection

NASA Astrophysics Data System (ADS)

Ismail, Nur Atikah; Azmi, Amirah; Yusof, Fauzi Mohamed; Ismail, Ahmad Izani

2017-11-01

Leptospirosis is an infectious disease carried by rodents which can cause death in humans. The disease spreads directly through contact with feces, urine or through bites of infected rodents and indirectly via water contaminated with urine and droppings from them. Significant increase in the number of leptospirosis cases in Malaysia caused by the recent severe floods were recorded during heavy rainfall season. Therefore, to understand the dynamics of leptospirosis infection, a mathematical model based on fractional differential equations have been developed and analyzed. In this paper an approximate analytical method, the multi-step Laplace Adomian decomposition method, has been used to conduct numerical simulations so as to gain insight on the spread of leptospirosis infection.

Methods to Induce Chronic Ocular Hypertension

PubMed Central

Dey, Ashim; Manthey, Abby L.; Chiu, Kin; Do, Chi-Wai

2018-01-01

Glaucoma, a form of progressive optic neuropathy, is the second leading cause of blindness worldwide. Being a prominent disease affecting vision, substantial efforts are being made to better understand glaucoma pathogenesis and to develop novel treatment options including neuroprotective and neuroregenerative approaches. Cell transplantation has the potential to play a neuroprotective and/or neuroregenerative role for various ocular cell types (e.g., retinal cells, trabecular meshwork). Notably, glaucoma is often associated with elevated intraocular pressure, and over the past 2 decades, several rodent models of chronic ocular hypertension (COH) have been developed that reflect these changes in pressure. However, the underlying pathophysiology of glaucoma in these models and how they compare to the human condition remains unclear. This limitation is the primary barrier for using rodent models to develop novel therapies to manage glaucoma and glaucoma-related blindness. Here, we review the current techniques used to induce COH-related glaucoma in various rodent models, focusing on the strengths and weaknesses of the each, in order to provide a more complete understanding of how these models can be best utilized. To so do, we have separated them based on the target tissue (pre-trabecular, trabecular, and post-trabecular) in order to provide the reader with an encompassing reference describing the most appropriate rodent COH models for their research. We begin with an initial overview of the current use of these models in the evaluation of cell transplantation therapies. PMID:29637819

Lurking in the Shadows: Emerging Rodent Infectious Diseases

PubMed Central

Besselsen, David G.; Franklin, Craig L.; Livingston, Robert S.; Riley, Lela K.

2013-01-01

Rodent parvoviruses, Helicobacter spp., murine norovirus, and several other previously unknown infectious agents have “emerged” in laboratory rodents relatively recently. These agents have been discovered serendipitously or through active investigation of atypical serology results, cell culture contamination, unexpected histopathology, or previously unrecognized clinical disease syndromes. The potential research impact of these agents is not fully known. Infected rodents have demonstrated immunomodulation, tumor suppression, clinical disease (particularly in immunodeficient rodents), and histopathology. Perturbations of organismal and cellular physiology also likely occur. These agents posed unique challenges to laboratory animal resource programs once discovered; it was necessary to develop specific diagnostic assays and an understanding of their epidemiology and transmission routes before attempting eradication, and then evaluate eradication methods for efficacy. Even then management approaches varied significantly, from apathy to total exclusion, and such inconsistency has hindered the sharing and transfer of rodents among institutions, particularly for genetically modified rodent models that may not be readily available. As additional infectious agents are discovered in laboratory rodents in coming years, much of what researchers have learned from experiences with the recently identified pathogens will be applicable. This article provides an overview of the discovery, detection, and research impact of infectious agents recently identified in laboratory rodents. We also discuss emerging syndromes for which there is a suspected infectious etiology, and the unique challenges of managing newly emerging infectious agents. PMID:18506061

A reproducible radiation delivery method for unanesthetized rodents during periods of hind limb unloading

NASA Astrophysics Data System (ADS)

Walb, M. C.; Black, P. J.; Payne, V. S.; Munley, M. T.; Willey, J. S.

2015-07-01

Exposure to the spaceflight environment has long been known to be a health challenge concerning many body systems. Both microgravity and/or ionizing radiation can cause acute and chronic effects in multiple body systems. The hind limb unloaded (HLU) rodent model is a ground-based analogue for microgravity that can be used to simulate and study the combined biologic effects of reduced loading with spaceflight radiation exposure. However, studies delivering radiation to rodents during periods of HLU are rare. Herein we report the development of an irradiation protocol using a clinical linear accelerator that can be used with hind limb unloaded, unanesthetized rodents that is capable of being performed at most academic medical centers. A 30.5 cm × 30.5 cm × 40.6 cm rectangular chamber was constructed out of polymethyl methacrylate (PMMA) sheets (0.64 cm thickness). Five centimeters of water-equivalent material were placed outside of two PMMA inserts on either side of the rodent that permitted the desired radiation dose buildup (electronic equilibrium) and helped to achieve a flatter dose profile. Perforated aluminum strips permitted the suspension dowel to be placed at varying heights depending on the rodent size. Radiation was delivered using a medical linear accelerator at an accelerating potential of 10 MV. A calibrated PTW Farmer ionization chamber, wrapped in appropriately thick tissue-equivalent bolus material to simulate the volume of the rodent, was used to verify a uniform dose distribution at various regions of the chamber. The dosimetry measurements confirmed variances typically within 3%, with maximum variance <10% indicated through optically stimulated luminescent dosimeter (OSLD) measurements, thus delivering reliable spaceflight-relevant total body doses and ensuring a uniform dose regardless of its location within the chamber. Due to the relative abundance of LINACs at academic medical centers and the reliability of their dosimetry properties, this method may find great utility in the implementation of future ground-based studies that examine the combined spaceflight challenges of reduced loading and radiation while using the HLU rodent model.

Cardiac Radionuclide Imaging in Rodents: A Review of Methods, Results, and Factors at Play

PubMed Central

Cicone, Francesco; Viertl, David; Quintela Pousa, Ana Maria; Denoël, Thibaut; Gnesin, Silvano; Scopinaro, Francesco; Vozenin, Marie-Catherine; Prior, John O.

2017-01-01

The interest around small-animal cardiac radionuclide imaging is growing as rodent models can be manipulated to allow the simulation of human diseases. In addition to new radiopharmaceuticals testing, often researchers apply well-established probes to animal models, to follow the evolution of the target disease. This reverse translation of standard radiopharmaceuticals to rodent models is complicated by technical shortcomings and by obvious differences between human and rodent cardiac physiology. In addition, radionuclide studies involving small animals are affected by several extrinsic variables, such as the choice of anesthetic. In this paper, we review the major cardiac features that can be studied with classical single-photon and positron-emitting radiopharmaceuticals, namely, cardiac function, perfusion and metabolism, as well as the results and pitfalls of small-animal radionuclide imaging techniques. In addition, we provide a concise guide to the understanding of the most frequently used anesthetics such as ketamine/xylazine, isoflurane, and pentobarbital. We address in particular their mechanisms of action and the potential effects on radionuclide imaging. Indeed, cardiac function, perfusion, and metabolism can all be significantly affected by varying anesthetics and animal handling conditions. PMID:28424774

Analgesic and Anti-Inflammatory Effects of 80% Methanol Extract of Leonotis ocymifolia (Burm.f.) Iwarsson Leaves in Rodent Models

PubMed Central

Alemu, Asnakech

2018-01-01

Background Pain and inflammation are the major health problems commonly treated with traditional remedies mainly using medicinal plants. Leonotis ocymifolia is one of such medicinal plants used in folkloric medicine of Ethiopia. However, the plant has not been scientifically evaluated. The aim of this study was to evaluate analgesic and anti-inflammatory effects of the 80% methanol leaves extract of Leonotis ocymifolia using rodent models. Method The central and peripheral analgesic effect of the extract at 100, 200, and 400 mg/kg dose levels was evaluated using hot plate and acetic acid induced writhing rodent models, whereas carrageenan induced paw edema and cotton pellet granuloma methods were used to screen anti-inflammatory effect of the extract at the same dose levels. Acute toxicity test was also done. Data were analyzed using one-way ANOVA followed by Tukey's post hoc test and p < 0.05 was considered significant. Results The extract did not produce mortality up to 2000 mg/kg. All tested doses of the extract showed significant analgesic effect with maximum latency response of 62.8% and inhibition of acetic acid induced writhing. Maximum anti-inflammatory effect was recorded at 6 h after induction, with 75.88% reduction in carrageenan induced paw edema. Moreover, all tested doses of extract significantly inhibited the formation of inflammatory exudates and granuloma formation (p < 0.001). Conclusion The study indicated that the extract was safe in mice and it has both analgesic and anti-inflammatory effect in rodent models. PMID:29675050

The hindlimb unloading rat model: literature overview, technique update and comparison with space flight data

NASA Technical Reports Server (NTRS)

Morey-Holton, Emily; Globus, Ruth K.; Kaplansky, Alexander; Durnova, Galina

2005-01-01

The hindlimb unloading rodent model is used extensively to study the response of many physiological systems to certain aspects of space flight, as well as to disuse and recovery from disuse for Earth benefits. This chapter describes the evolution of hindlimb unloading, and is divided into three sections. The first section examines the characteristics of 1064 articles using or reviewing the hindlimb unloading model, published between 1976 and April 1, 2004. The characteristics include number of publications, journals, countries, major physiological systems, method modifications, species, gender, genetic strains and ages of rodents, experiment duration, and countermeasures. The second section provides a comparison of results between space flown and hindlimb unloading animals from the 14-day Cosmos 2044 mission. The final section describes modifications to hindlimb unloading required by different experimental paradigms and a method to protect the tail harness for long duration studies. Hindlimb unloading in rodents has enabled improved understanding of the responses of the musculoskeletal, cardiovascular, immune, renal, neural, metabolic, and reproductive systems to unloading and/or to reloading on Earth with implications for both long-duration human space flight and disuse on Earth.

Natural Intestinal Protozoa in Rodents (Rodentia: Gerbillinae, Murinae, Cricetinae) in Northwestern Iran

PubMed Central

MOHEBALI, Mehdi; ZAREI, Zabiholah; Khanaliha, Khadijeh; KIA, Eshrat Beigom; MOTAVALLI-HAGHI, Afsaneh; DAVOODI, Jaber; REZAEIAN, Tahereh; TARIGHI, Fathemeh; REZAEIAN, Mostafa

2017-01-01

Background: Majority of parasitic infections in rodents have zoonotic importance. This study aimed to determine the frequency and intensity of intestinal protozoa infections of rodents including Meriones persicus, Mus musculus and, Cricetulus migratorius. Methods: This survey was conducted in Meshkin Shahr district in northwestern Iran from Mar. to Dec. of 2014. Intestinal samples of 204 rodents including M. persicus (n=117), M. musculus (n=63) and C. migratorius (n=24) were parasitologically examined. Formalin-ether concentration method was done for all of rodents stool samples and observed with light microscope. All of suspected cases were stained with trichorome staining Method. Cultivation in dichromate potassium 2.5% was carried out for all of coccidian positive samples. Acid fast and aniline blue staining methods were used for detecting of coccidian oocysts and intestinal microsporidial spores, respectively. Results: About 121(59.3%) of the caught rodents were generally infected with intestinal protozoa. Entamoeba muris 14(6.9%), Trichomonas muris 55(27.0%), Chilomastix betencourtti 17 (8.3%), Giardia muris 19(9.3%), Eimeria spp. 46(22.5%), Isospora spp. 4(2%) and Cryptosporidium spp. 1(0.5%) were found from the collected rodents. Microsporidian spores were identified in 63 (31%) out of the 204 collected rodents using aniline blue staining method. Conclusion: Since some of the infections are zoonotic importance thus, control of rodents can be decreased new cases of the parasitic zoonoses in humans. PMID:28979348

Neurobiology of rodent self-grooming and its value for translational neuroscience

PubMed Central

Kalueff, Allan V.; Stewart, Adam Michael; Song, Cai; Berridge, Kent C.; Graybiel, Ann M.; Fentress, John C.

2016-01-01

Self-grooming is a complex innate behaviour with an evolutionary conserved sequencing pattern and is one of the most frequently performed behavioural activities in rodents. In this Review, we discuss the neurobiology of rodent self-grooming, and we highlight studies of rodent models of neuropsychiatric disorders — including models of autism spectrum disorder and obsessive compulsive disorder — that have assessed self-grooming phenotypes. We suggest that rodent self-grooming may be a useful measure of repetitive behaviour in such models, and therefore of value to translational psychiatry. Assessment of rodent self-grooming may also be useful for understanding the neural circuits that are involved in complex sequential patterns of action. PMID:26675822

A new method to model electroconvulsive therapy in rats with increased construct validity and enhanced translational value.

PubMed

Theilmann, Wiebke; Löscher, Wolfgang; Socala, Katarzyna; Frieling, Helge; Bleich, Stefan; Brandt, Claudia

2014-06-01

Electroconvulsive therapy is the most effective therapy for major depressive disorder (MDD). The remission rate is above 50% in previously pharmacoresistant patients but the mechanisms of action are not fully understood. Electroconvulsive stimulation (ECS) in rodents mimics antidepressant electroconvulsive therapy (ECT) in humans and is widely used to investigate the underlying mechanisms of ECT. For the translational value of findings in animal models it is essential to establish models with the highest construct, face and predictive validity possible. The commonly used model for ECT in rodents does not meet the demand for high construct validity. For ECT, cortical surface electrodes are used to induce therapeutic seizures whereas ECS in rodents is exclusively performed by auricular or corneal electrodes. However, the stimulation site has a major impact on the type and spread of the induced seizure activity and its antidepressant effect. We propose a method in which ECS is performed by screw electrodes placed above the motor cortex of rats to closely simulate the clinical situation and thereby increase the construct validity of the model. Cortical ECS in rats induced reliably seizures comparable to human ECT. Cortical ECS was more effective than auricular ECS to reduce immobility in the forced swim test. Importantly, auricular stimulation had a negative influence on the general health condition of the rats with signs of fear during the stimulation sessions. These results suggest that auricular ECS in rats is not a suitable ECT model. Cortical ECS in rats promises to be a valid method to mimic ECT. Copyright © 2014 Elsevier Ltd. All rights reserved.

Probing for Neuroadaptations to Unpredictable Stressors in Addiction: Translational Methods and Emerging Evidence

PubMed Central

Kaye, Jesse T.; Bradford, Daniel E.; Magruder, Katherine P.; Curtin, John J.

2017-01-01

Stressors clearly contribute to addiction etiology and relapse in humans, but our understanding of specific mechanisms remains limited. Rodent models of addiction offer the power, flexibility, and precision necessary to delineate the causal role and specific mechanisms through which stressors influence alcohol and other drug use. This review describes a program of research using startle potentiation to unpredictable stressors that is well positioned to translate between animal models and clinical research with humans on stress neuroadaptations in addiction. This research rests on a solid foundation provided by three separate pillars of evidence from (a) rodent behavioral neuroscience on stress neuroadaptations in addiction, (b) rodent affective neuroscience on startle potentiation, and (c) human addiction and affective science with startle potentiation. Rodent stress neuroadaptation models implicate adaptations in corticotropin-releasing factor and norepinephrine circuits within the central extended amygdala following chronic alcohol and other drug use that mediate anxious behaviors and stress-induced reinstatement among drug-dependent rodents. Basic affective neuroscience indicates that these same neural mechanisms are involved in startle potentiation to unpredictable stressors in particular (vs. predictable stressors). We believe that synthesis of these evidence bases should focus us on the role of unpredictable stressors in addiction etiology and relapse. Startle potentiation in unpredictable stressor tasks is proposed to provide an attractive and flexible test bed to encourage tight translation and reverse translation between animal models and human clinical research on stress neuroadaptations. Experimental therapeutics approaches focused on unpredictable stressors hold high promise to identify, repurpose, or refine pharmacological and psychosocial interventions for addiction. PMID:28499100

Probing for Neuroadaptations to Unpredictable Stressors in Addiction: Translational Methods and Emerging Evidence.

PubMed

Kaye, Jesse T; Bradford, Daniel E; Magruder, Katherine P; Curtin, John J

2017-05-01

Stressors clearly contribute to addiction etiology and relapse in humans, but our understanding of specific mechanisms remains limited. Rodent models of addiction offer the power, flexibility, and precision necessary to delineate the causal role and specific mechanisms through which stressors influence alcohol and other drug use. This review describes a program of research using startle potentiation to unpredictable stressors that is well positioned to translate between animal models and clinical research with humans on stress neuroadaptations in addiction. This research rests on a solid foundation provided by three separate pillars of evidence from (a) rodent behavioral neuroscience on stress neuroadaptations in addiction, (b) rodent affective neuroscience on startle potentiation, and (c) human addiction and affective science with startle potentiation. Rodent stress neuroadaptation models implicate adaptations in corticotropin-releasing factor and norepinephrine circuits within the central extended amygdala following chronic alcohol and other drug use that mediate anxious behaviors and stress-induced reinstatement among drug-dependent rodents. Basic affective neuroscience indicates that these same neural mechanisms are involved in startle potentiation to unpredictable stressors in particular (vs. predictable stressors). We believe that synthesis of these evidence bases should focus us on the role of unpredictable stressors in addiction etiology and relapse. Startle potentiation in unpredictable stressor tasks is proposed to provide an attractive and flexible test bed to encourage tight translation and reverse translation between animal models and human clinical research on stress neuroadaptations. Experimental therapeutics approaches focused on unpredictable stressors hold high promise to identify, repurpose, or refine pharmacological and psychosocial interventions for addiction.

The touchscreen operant platform for testing learning and memory in rats and mice

PubMed Central

Horner, Alexa E.; Heath, Christopher J.; Hvoslef-Eide, Martha; Kent, Brianne A.; Kim, Chi Hun; Nilsson, Simon R. O.; Alsiö, Johan; Oomen, Charlotte A.; Holmes, Andrew; Saksida, Lisa M.; Bussey, Timothy J.

2014-01-01

Summary An increasingly popular method of assessing cognitive functions in rodents is the automated touchscreen platform, on which a number of different cognitive tests can be run in a manner very similar to touchscreen methods currently used to test human subjects. This methodology is low stress (using appetitive, rather than aversive reinforcement), has high translational potential, and lends itself to a high degree of standardisation and throughput. Applications include the study of cognition in rodent models of psychiatric and neurodegenerative diseases (e.g., Alzheimer’s disease, schizophrenia, Huntington’s disease, frontotemporal dementia), and characterisation of the role of select brain regions, neurotransmitter systems and genes in rodents. This protocol describes how to perform four touchscreen assays of learning and memory: Visual Discrimination, Object-Location Paired-Associates Learning, Visuomotor Conditional Learning and Autoshaping. It is accompanied by two further protocols using the touchscreen platform to assess executive function, working memory and pattern separation. PMID:24051959

Rodent Models of Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis

PubMed Central

Imajo, Kento; Yoneda, Masato; Kessoku, Takaomi; Ogawa, Yuji; Maeda, Shin; Sumida, Yoshio; Hyogo, Hideyuki; Eguchi, Yuichiro; Wada, Koichiro; Nakajima, Atsushi

2013-01-01

Research in nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH), has been limited by the availability of suitable models for this disease. A number of rodent models have been described in which the relevant liver pathology develops in an appropriate metabolic context. These models are promising tools for researchers investigating one of the key issues of NASH: not so much why steatosis occurs, but what causes the transition from simple steatosis to the inflammatory, progressive fibrosing condition of steatohepatitis. The different rodent models can be classified into two large groups. The first includes models in which the disease is acquired after dietary or pharmacological manipulation, and the second, genetically modified models in which liver disease develops spontaneously. To date, no single rodent model has encompassed the full spectrum of human disease progression, but individual models can imitate particular characteristics of human disease. Therefore, it is important that researchers choose the appropriate rodent models. The purpose of the present review is to discuss the metabolic abnormalities present in the currently available rodent models of NAFLD, summarizing the strengths and weaknesses of the established models and the key findings that have furthered our understanding of the disease’s pathogenesis. PMID:24192824

In vivo transgenic bioassays and assessment of the carcinogenic potential of pharmaceuticals.

PubMed Central

Contrera, J F; DeGeorge, J J

1998-01-01

There is general agreement in the scientific community on the need to improve carcinogenicity testing and the assessment of human carcinogenic risk and to incorporate more information on mechanisms and modes of action into the risk assessment process. Advances in molecular biology have identified a growing number of genes such as protooncogenes and tumor-suppressor genes that are highly conserved across species and are associated with a wide variety of human and animal cancers. In vivo transgenic rodent models incorporating such mechanisms are used to identify mechanisms involved in tumor formation and as selective tests for carcinogens. Transgenic methods can be considered an extension of genetic manipulation by selective breeding, which long has been employed in science and agriculture. The use of two rodent species in carcinogenicity testing is especially important for identifying transspecies carcinogens. The capacity of a substance to induce neoplasia across species suggests that the mechanism(s) involved in the induction of the neoplasia are conserved and therefore may have significance for humans. Based on available information there is sufficient experience with some in vivo transgenic rodent carcinogenicity models to support their application as complementary second species studies in conjunction with a single 2-year rodent carcinogenicity study. The optional substitution of a second 2-year rodent carcinogenicity study with an alternative study such as an in vivo transgenic carcinogenicity study is part of the International Conference on Harmonization guidance S1B: Testing for Carcinogenicity of Pharmaceuticals. This guidance is intended to be flexible enough to accommodate a wide range of possible carcinogenicity assessment models currently under consideration or models that may be developed in the future. The use of an in vivo transgenic mouse model in place of a second 2-year mouse study will improve the assessment of carcinogenic risk by contributing insights into the mechanisms of tumorigenesis and potential human relevance not available from a standard 2-year bioassay. It is envisioned that this will stimulate the further development of more efficient and relevant methods for identifying and assessing potential human carcinogenic risk, which will benefit public health. PMID:9539006

Natural Intestinal Protozoa in Rodents (Rodentia: Gerbillinae, Murinae, Cricetinae) in Northwestern Iran.

PubMed

Mohebali, Mehdi; Zarei, Zabiholah; Khanaliha, Khadijeh; Kia, Eshrat Beigom; Motavalli-Haghi, Afsaneh; Davoodi, Jaber; Rezaeian, Tahereh; Tarighi, Fathemeh; Rezaeian, Mostafa

2017-01-01

Majority of parasitic infections in rodents have zoonotic importance. This study aimed to determine the frequency and intensity of intestinal protozoa infections of rodents including Meriones persicus, Mus musculus and, C ricetulus migratorius . This survey was conducted in Meshkin Shahr district in northwestern Iran from Mar. to Dec. of 2014. Intestinal samples of 204 rodents including M. persicus (n=117), M. musculus (n=63) and C. migratorius (n=24) were parasitologically examined. Formalin-ether concentration method was done for all of rodents stool samples and observed with light microscope. All of suspected cases were stained with trichorome staining Method. Cultivation in dichromate potassium 2.5% was carried out for all of coccidian positive samples. Acid fast and aniline blue staining methods were used for detecting of coccidian oocysts and intestinal microsporidial spores, respectively. About 121(59.3%) of the caught rodents were generally infected with intestinal protozoa. Entamoeba muris 14(6.9%), Trichomonas muris 55(27.0%), Chilomastix betencourtti 17 (8.3%), Giardia muris 19(9.3%), Eimeria spp. 46(22.5%) , Isospora spp. 4(2%) and Cryptosporidium spp. 1(0.5%) were found from the collected rodents. Microsporidian spores were identified in 63 (31%) out of the 204 collected rodents using aniline blue staining method. Since some of the infections are zoonotic importance thus, control of rodents can be decreased new cases of the parasitic zoonoses in humans.

Behavioral testing in rodent models of orofacial neuropathic and inflammatory pain

PubMed Central

Krzyzanowska, Agnieszka; Avendaño, Carlos

2012-01-01

Orofacial pain conditions are often very debilitating to the patient and difficult to treat. While clinical interest is high, the proportion of studies performed in the orofacial region in laboratory animals is relatively low, compared with other body regions. This is partly due to difficulties in testing freely moving animals and therefore lack of reliable testing methods. Here we present a comprehensive review of the currently used rodent models of inflammatory and neuropathic pain adapted to the orofacial areas, taking into account the difficulties and drawbacks of the existing approaches. We examine the available testing methods and procedures used for assessing the behavioral responses in the face in both mice and rats and provide a summary of some pharmacological agents used in these paradigms to date. The use of these agents in animal models is also compared with outcomes observed in the clinic. PMID:23139912

Predictive Models for Carcinogenicity and Mutagenicity ...

EPA Pesticide Factsheets

Mutagenicity and carcinogenicity are endpoints of major environmental and regulatory concern. These endpoints are also important targets for development of alternative methods for screening and prediction due to the large number of chemicals of potential concern and the tremendous cost (in time, money, animals) of rodent carcinogenicity bioassays. Both mutagenicity and carcinogenicity involve complex, cellular processes that are only partially understood. Advances in technologies and generation of new data will permit a much deeper understanding. In silico methods for predicting mutagenicity and rodent carcinogenicity based on chemical structural features, along with current mutagenicity and carcinogenicity data sets, have performed well for local prediction (i.e., within specific chemical classes), but are less successful for global prediction (i.e., for a broad range of chemicals). The predictivity of in silico methods can be improved by improving the quality of the data base and endpoints used for modelling. In particular, in vitro assays for clastogenicity need to be improved to reduce false positives (relative to rodent carcinogenicity) and to detect compounds that do not interact directly with DNA or have epigenetic activities. New assays emerging to complement or replace some of the standard assays include VitotoxTM, GreenScreenGC, and RadarScreen. The needs of industry and regulators to assess thousands of compounds necessitate the development of high-t

Large scale serial two-photon microscopy to investigate local vascular changes in whole rodent brain models of Alzheimer's disease

NASA Astrophysics Data System (ADS)

Delafontaine-Martel, P.; Lefebvre, J.; Damseh, R.; Castonguay, A.; Tardif, P.; Lesage, F.

2018-02-01

In this study, an automated serial two-photon microscope was used to image a fluorescent gelatin filled rodent's brain in 3D. A method to compute vascular density using automatic segmentation was combined with coregistration techniques to build group-level vasculature metrics. By studying the medial prefrontal cortex and the hippocampal formation of 3 age groups (2, 4.5 and 8 months old), we compared vascular density for both WT and an Alzheimer model transgenic brain (APP/PS1). We observe a loss of vascular density caused by the ageing process and we propose further analysis to confirm our results.

Translational Rodent Models for Research on Parasitic Protozoa—A Review of Confounders and Possibilities

PubMed Central

Ehret, Totta; Torelli, Francesca; Klotz, Christian; Pedersen, Amy B.; Seeber, Frank

2017-01-01

Rodents, in particular Mus musculus, have a long and invaluable history as models for human diseases in biomedical research, although their translational value has been challenged in a number of cases. We provide some examples in which rodents have been suboptimal as models for human biology and discuss confounders which influence experiments and may explain some of the misleading results. Infections of rodents with protozoan parasites are no exception in requiring close consideration upon model choice. We focus on the significant differences between inbred, outbred and wild animals, and the importance of factors such as microbiota, which are gaining attention as crucial variables in infection experiments. Frequently, mouse or rat models are chosen for convenience, e.g., availability in the institution rather than on an unbiased evaluation of whether they provide the answer to a given question. Apart from a general discussion on translational success or failure, we provide examples where infections with single-celled parasites in a chosen lab rodent gave contradictory or misleading results, and when possible discuss the reason for this. We present emerging alternatives to traditional rodent models, such as humanized mice and organoid primary cell cultures. So-called recombinant inbred strains such as the Collaborative Cross collection are also a potential solution for certain challenges. In addition, we emphasize the advantages of using wild rodents for certain immunological, ecological, and/or behavioral questions. The experimental challenges (e.g., availability of species-specific reagents) that come with the use of such non-model systems are also discussed. Our intention is to foster critical judgment of both traditional and newly available translational rodent models for research on parasitic protozoa that can complement the existing mouse and rat models. PMID:28638807

Translational Rodent Models for Research on Parasitic Protozoa-A Review of Confounders and Possibilities.

PubMed

Ehret, Totta; Torelli, Francesca; Klotz, Christian; Pedersen, Amy B; Seeber, Frank

2017-01-01

Rodents, in particular Mus musculus , have a long and invaluable history as models for human diseases in biomedical research, although their translational value has been challenged in a number of cases. We provide some examples in which rodents have been suboptimal as models for human biology and discuss confounders which influence experiments and may explain some of the misleading results. Infections of rodents with protozoan parasites are no exception in requiring close consideration upon model choice. We focus on the significant differences between inbred, outbred and wild animals, and the importance of factors such as microbiota, which are gaining attention as crucial variables in infection experiments. Frequently, mouse or rat models are chosen for convenience, e.g., availability in the institution rather than on an unbiased evaluation of whether they provide the answer to a given question. Apart from a general discussion on translational success or failure, we provide examples where infections with single-celled parasites in a chosen lab rodent gave contradictory or misleading results, and when possible discuss the reason for this. We present emerging alternatives to traditional rodent models, such as humanized mice and organoid primary cell cultures. So-called recombinant inbred strains such as the Collaborative Cross collection are also a potential solution for certain challenges. In addition, we emphasize the advantages of using wild rodents for certain immunological, ecological, and/or behavioral questions. The experimental challenges (e.g., availability of species-specific reagents) that come with the use of such non-model systems are also discussed. Our intention is to foster critical judgment of both traditional and newly available translational rodent models for research on parasitic protozoa that can complement the existing mouse and rat models.

Rodent models of diabetic nephropathy: their utility and limitations

PubMed Central

Kitada, Munehiro; Ogura, Yoshio; Koya, Daisuke

2016-01-01

Diabetic nephropathy is the most common cause of end-stage renal disease. Therefore, novel therapies for the suppression of diabetic nephropathy must be developed. Rodent models are useful for elucidating the pathogenesis of diseases and testing novel therapies, and many type 1 and type 2 diabetic rodent models have been established for the study of diabetes and diabetic complications. Streptozotocin (STZ)-induced diabetic animals are widely used as a model of type 1 diabetes. Akita diabetic mice that have an Ins2+/C96Y mutation and OVE26 mice that overexpress calmodulin in pancreatic β-cells serve as a genetic model of type 1 diabetes. In addition, db/db mice, KK-Ay mice, Zucker diabetic fatty rats, Wistar fatty rats, Otsuka Long-Evans Tokushima Fatty rats and Goto-Kakizaki rats serve as rodent models of type 2 diabetes. An animal model of diabetic nephropathy should exhibit progressive albuminuria and a decrease in renal function, as well as the characteristic histological changes in the glomeruli and the tubulointerstitial lesions that are observed in cases of human diabetic nephropathy. A rodent model that strongly exhibits all these features of human diabetic nephropathy has not yet been developed. However, the currently available rodent models of diabetes can be useful in the study of diabetic nephropathy by increasing our understanding of the features of each diabetic rodent model. Furthermore, the genetic background and strain of each mouse model result in differences in susceptibility to diabetic nephropathy with albuminuria and the development of glomerular and tubulointerstitial lesions. Therefore, the validation of an animal model reproducing human diabetic nephropathy will significantly facilitate our understanding of the underlying genetic mechanisms that contribute to the development of diabetic nephropathy. In this review, we focus on rodent models of diabetes and discuss the utility and limitations of these models for the study of diabetic nephropathy. PMID:27881924

Phylogenetic place of guinea pigs: no support of the rodent-polyphyly hypothesis from maximum-likelihood analyses of multiple protein sequences.

PubMed

Cao, Y; Adachi, J; Yano, T; Hasegawa, M

1994-07-01

Graur et al.'s (1991) hypothesis that the guinea pig-like rodents have an evolutionary origin within mammals that is separate from that of other rodents (the rodent-polyphyly hypothesis) was reexamined by the maximum-likelihood method for protein phylogeny, as well as by the maximum-parsimony and neighbor-joining methods. The overall evidence does not support Graur et al.'s hypothesis, which radically contradicts the traditional view of rodent monophyly. This work demonstrates that we must be careful in choosing a proper method for phylogenetic inference and that an argument based on a small data set (with respect to the length of the sequence and especially the number of species) may be unstable.

Titanium wound chambers for wound healing research.

PubMed

Nuutila, Kristo; Singh, Mansher; Kruse, Carla; Philip, Justin; Caterson, Edward J; Eriksson, Elof

2016-11-01

Standardized and reproducible animal models are crucial in medical research. Rodents are commonly used in wound healing studies since, they are easily available, affordable and simple to handle and house. However, the most significant limitation of rodent models is that the wounds heal by contraction while in humans the primary mechanisms of healing are reepithelialization and granulation tissue formation. The robust contraction results in faster wound closure that complicates the reproducibility of rodent studies in clinical trials. We have developed a titanium wound chamber for rodent wound healing research. The chamber is engineered from two pieces of titanium and is placed transcutaneously on the dorsum of a rodent. The chamber inhibits wound contraction and provides a means for controlled monitoring and sampling of the wound environment in vivo with minimal foreign body reaction. This technical report introduces two modalities utilizing the titanium chambers in rats: (1) Wound in a skin island model and, (2) Wound without skin model. Here, we demonstrate in rats how the "wound in a skin island model" slows down wound contraction and how the "wound without skin" model completely prevents the closure. The titanium wound chamber provides a reproducible standardized models for wound healing research in rodents. © 2016 by the Wound Healing Society.

New rodent models for studies of chemopreventive agents.

PubMed

Lipkin, M

1997-01-01

Some recent studies of the effects of chemopreventive agents have begun to use new rodent models to improve the analysis of stages of colonic preneoplasia, and how chemopreventive agents modify progressive abnormal cell development. In one of the models of inherited predisposition to colon cancer, mice carrying a truncated Apc allele with a nonsense mutation in exon 15 have been generated by gene targeting and embryonic stem cell technology (Apc1638 mice). These mice develop multiple gastrointestinal lesions, including adenomas and carcinomas, focal areas of high-grade dysplasia (FAD), and polypoid hyperplasias with FADS. The incidence of inherited colonic neoplasms has now been modulated by a chemopreventive regimen. Colonic lesions significantly increased in Apc1638 mice on a Western-style diet, which has higher fat content and lower calcium and vitamin D compared to the same mice on AIN-76A diet. In another rodent model, Min mice were treated with sulindac, which markedly reduced the incidence of intestinal tumors. A third new rodent model containing a targeted mutation in the gene Mcc (mutated in colorectal cancer) recently became available for chemoprevention studies. These mice develop multiple types of neoplasms including adenocarcinomas, focal areas of gastrointestinal dysplasia, papillomas of the forestomach, and tumors in other organs including lung, liver, and lymphoid tissue. Feeding a Western-style diet to the Mcc mutant mice also resulted in significantly increased gastrointestinal lesions. These nutrient modifications also have been given to normal mice, demonstrating without any chemical carcinogen that a Western-style diet induced colonic tumorigenesis. Western-style diets also have now induced modulation of cell proliferation in other organs including mammary gland, pancreas, and prostate. These findings help develop new preclinical rodent models to aid the analysis of genetic and environmental factors leading to neoplasia, as well as new methods for evaluating the chemopreventive efficacy of specific nutrients and pharmacological agents.

Translating Research from Animal Models: Does It Matter that Our Rodents are So Cold?

EPA Science Inventory

Does it matter that preclinical rodent models are routinely housed below their thermoneutral zone and are thereby cold-stressed? We compile evidence showing that rodents housed below their thermoneutral zone are cold-stressed, hypermetalbolic, hypertensive, sleep-deprived, obesi...

The touchscreen operant platform for testing learning and memory in rats and mice.

PubMed

Horner, Alexa E; Heath, Christopher J; Hvoslef-Eide, Martha; Kent, Brianne A; Kim, Chi Hun; Nilsson, Simon R O; Alsiö, Johan; Oomen, Charlotte A; Holmes, Andrew; Saksida, Lisa M; Bussey, Timothy J

2013-10-01

An increasingly popular method of assessing cognitive functions in rodents is the automated touchscreen platform, on which a number of different cognitive tests can be run in a manner very similar to touchscreen methods currently used to test human subjects. This methodology is low stress (using appetitive rather than aversive reinforcement), has high translational potential and lends itself to a high degree of standardization and throughput. Applications include the study of cognition in rodent models of psychiatric and neurodegenerative diseases (e.g., Alzheimer's disease, schizophrenia, Huntington's disease, frontotemporal dementia), as well as the characterization of the role of select brain regions, neurotransmitter systems and genes in rodents. This protocol describes how to perform four touchscreen assays of learning and memory: visual discrimination, object-location paired-associates learning, visuomotor conditional learning and autoshaping. It is accompanied by two further protocols (also published in this issue) that use the touchscreen platform to assess executive function, working memory and pattern separation.

Mycobacterial lesions in fish, amphibians, reptiles, rodents, lagomorphs, and ferrets with reference to animal models.

PubMed

Reavill, Drury R; Schmidt, Robert E

2012-01-01

Mycobacteriosis is a serious disease across many animal species. Approximately more than 120 species are currently recognized in the genus Mycobacterium. This article describes the zoonotic potential of mycobacteria and mycobacteriosis in fish, amphibians, rodents, rabbits, and ferrets. It considers clinical signs; histology; molecular methods of identification, such as polymerase chain reaction and DNA sequencing; routes of infection; and disease progression. Studying the disease in animals may aid in understanding the pathogenesis of mycobacterial infections in humans and identify better therapy and preventative options such as vaccines.

Estimation of Wildlife Hazard Levels Using Interspecies Correlation Models and Standard Laboratory Rodent Toxicity Data

EPA Science Inventory

Toxicity data from laboratory rodents are widely available and frequently used in human health assessments as an animal model. We explore the possibility of using single rodent acute toxicity values to predict chemical toxicity to a diversity of wildlife species and to estimate ...

PREDICTIVE SIMULATION MODELING FOR ANTIANDROGEN IMPACTS ON RODENT PROSTATE

EPA Science Inventory

Predictive simulation modeling for antiandrogen impacts on rodent prostate
HA Barton1, RW Setzer1, LK Potter1,2
1US EPA, ORD, NHEERL, ETD, PKB, Research Triangle Park, NC and 2Curriculum in Toxicology, UNC, Chapel Hill, NC

Changes in rodent prostate weight and functi...

An integrated analysis of genes and functional pathways for aggression in human and rodent models.

PubMed

Zhang-James, Yanli; Fernàndez-Castillo, Noèlia; Hess, Jonathan L; Malki, Karim; Glatt, Stephen J; Cormand, Bru; Faraone, Stephen V

2018-06-01

Human genome-wide association studies (GWAS), transcriptome analyses of animal models, and candidate gene studies have advanced our understanding of the genetic architecture of aggressive behaviors. However, each of these methods presents unique limitations. To generate a more confident and comprehensive view of the complex genetics underlying aggression, we undertook an integrated, cross-species approach. We focused on human and rodent models to derive eight gene lists from three main categories of genetic evidence: two sets of genes identified in GWAS studies, four sets implicated by transcriptome-wide studies of rodent models, and two sets of genes with causal evidence from online Mendelian inheritance in man (OMIM) and knockout (KO) mice reports. These gene sets were evaluated for overlap and pathway enrichment to extract their similarities and differences. We identified enriched common pathways such as the G-protein coupled receptor (GPCR) signaling pathway, axon guidance, reelin signaling in neurons, and ERK/MAPK signaling. Also, individual genes were ranked based on their cumulative weights to quantify their importance as risk factors for aggressive behavior, which resulted in 40 top-ranked and highly interconnected genes. The results of our cross-species and integrated approach provide insights into the genetic etiology of aggression.

Leptin- and Leptin Receptor-Deficient Rodent Models: Relevance for Human Type 2 Diabetes

PubMed Central

Wang, Bingxuan; P., Charukeshi Chandrasekera; Pippin, John J.

2014-01-01

Among the most widely used animal models in obesity-induced type 2 diabetes mellitus (T2DM) research are the congenital leptin- and leptin receptor-deficient rodent models. These include the leptin-deficient ob/ob mice and the leptin receptor-deficient db/db mice, Zucker fatty rats, Zucker diabetic fatty rats, SHR/N-cp rats, and JCR:LA-cp rats. After decades of mechanistic and therapeutic research schemes with these animal models, many species differences have been uncovered, but researchers continue to overlook these differences, leading to untranslatable research. The purpose of this review is to analyze and comprehensively recapitulate the most common leptin/leptin receptor-based animal models with respect to their relevance and translatability to human T2DM. Our analysis revealed that, although these rodents develop obesity due to hyperphagia caused by abnormal leptin/leptin receptor signaling with the subsequent appearance of T2DM-like manifestations, these are in fact secondary to genetic mutations that do not reflect disease etiology in humans, for whom leptin or leptin receptor deficiency is not an important contributor to T2DM. A detailed comparison of the roles of genetic susceptibility, obesity, hyperglycemia, hyperinsulinemia, insulin resistance, and diabetic complications as well as leptin expression, signaling, and other factors that confound translation are presented here. There are substantial differences between these animal models and human T2DM that limit reliable, reproducible, and translatable insight into human T2DM. Therefore, it is imperative that researchers recognize and acknowledge the limitations of the leptin/leptin receptor-based rodent models and invest in research methods that would be directly and reliably applicable to humans in order to advance T2DM management. PMID:24809394

Leptin- and leptin receptor-deficient rodent models: relevance for human type 2 diabetes.

PubMed

Wang, Bingxuan; Chandrasekera, P Charukeshi; Pippin, John J

2014-03-01

Among the most widely used animal models in obesity-induced type 2 diabetes mellitus (T2DM) research are the congenital leptin- and leptin receptor-deficient rodent models. These include the leptin-deficient ob/ob mice and the leptin receptor-deficient db/db mice, Zucker fatty rats, Zucker diabetic fatty rats, SHR/N-cp rats, and JCR:LA-cp rats. After decades of mechanistic and therapeutic research schemes with these animal models, many species differences have been uncovered, but researchers continue to overlook these differences, leading to untranslatable research. The purpose of this review is to analyze and comprehensively recapitulate the most common leptin/leptin receptor-based animal models with respect to their relevance and translatability to human T2DM. Our analysis revealed that, although these rodents develop obesity due to hyperphagia caused by abnormal leptin/leptin receptor signaling with the subsequent appearance of T2DM-like manifestations, these are in fact secondary to genetic mutations that do not reflect disease etiology in humans, for whom leptin or leptin receptor deficiency is not an important contributor to T2DM. A detailed comparison of the roles of genetic susceptibility, obesity, hyperglycemia, hyperinsulinemia, insulin resistance, and diabetic complications as well as leptin expression, signaling, and other factors that confound translation are presented here. There are substantial differences between these animal models and human T2DM that limit reliable, reproducible, and translatable insight into human T2DM. Therefore, it is imperative that researchers recognize and acknowledge the limitations of the leptin/leptin receptor- based rodent models and invest in research methods that would be directly and reliably applicable to humans in order to advance T2DM management.

High-throughput 3D whole-brain quantitative histopathology in rodents

PubMed Central

Vandenberghe, Michel E.; Hérard, Anne-Sophie; Souedet, Nicolas; Sadouni, Elmahdi; Santin, Mathieu D.; Briet, Dominique; Carré, Denis; Schulz, Jocelyne; Hantraye, Philippe; Chabrier, Pierre-Etienne; Rooney, Thomas; Debeir, Thomas; Blanchard, Véronique; Pradier, Laurent; Dhenain, Marc; Delzescaux, Thierry

2016-01-01

Histology is the gold standard to unveil microscopic brain structures and pathological alterations in humans and animal models of disease. However, due to tedious manual interventions, quantification of histopathological markers is classically performed on a few tissue sections, thus restricting measurements to limited portions of the brain. Recently developed 3D microscopic imaging techniques have allowed in-depth study of neuroanatomy. However, quantitative methods are still lacking for whole-brain analysis of cellular and pathological markers. Here, we propose a ready-to-use, automated, and scalable method to thoroughly quantify histopathological markers in 3D in rodent whole brains. It relies on block-face photography, serial histology and 3D-HAPi (Three Dimensional Histology Analysis Pipeline), an open source image analysis software. We illustrate our method in studies involving mouse models of Alzheimer’s disease and show that it can be broadly applied to characterize animal models of brain diseases, to evaluate therapeutic interventions, to anatomically correlate cellular and pathological markers throughout the entire brain and to validate in vivo imaging techniques. PMID:26876372

The MAM rodent model of schizophrenia

PubMed Central

Lodge, Daniel J.

2013-01-01

Rodent models of human disease are essential to obtain a better understanding of disease pathology, the mechanism of action underlying conventional treatments, as well as for the generation of novel therapeutic approaches. There are a number of rodent models of schizophrenia based on either genetic manipulations, acute or sub-chronic drug administration, or developmental disturbances. The prenatal methylazoxymethanol acetate (MAM) rodent model is a developmental disruption model gaining increased attention because it displays a number of histological, neurophysiological and behavioral deficits analogous to those observed in schizophrenia patients. This unit describes the procedures required to safely induce the MAM phenotype in rats. In addition, we describe a simple behavioral procedure, amphetamine-induced hyper-locomotion, which can be utilized to verify the MAM phenotype. PMID:23559309

Estimating sources of Valley Fever pathogen propagation in southern Arizona: A remote sensing approach

NASA Astrophysics Data System (ADS)

Pianalto, Frederick S.

Coccidioidomycosis (Valley Fever) is an environmentally-mediated respiratory disease caused by the inhalation of airborne spores from the fungi Coccidioides spp. The fungi reside in arid and semi-arid soils of the Americas. The disease has increased epidemically in Arizona and other areas within the last two decades. Despite this increase, the ecology of the fungi remains obscure, and environmental antecedents of the disease are largely unstudied. Two sources of soil disturbance, hypothesized to affect soil ecology and initiate spore dissemination, are investigated. Nocturnal desert rodents interact substantially with the soil substrate. Rodents are hypothesized to act as a reservoir of coccidioidomycosis, a mediator of soil properties, and a disseminator of fungal spores. Rodent distributions are poorly mapped for the study area. We build automated multi-linear regression models and decision tree models for ten rodent species using rodent trapping data from the Organ Pipe Cactus National Monument (ORPI) in southwest Arizona with a combination of surface temperature, a vegetation index and its texture, and a suite of topographic rasters. Surface temperature, derived from Landsat TM thermal images, is the most widely selected predictive variable in both automated methods. Construction-related soil disturbance (e.g. road construction, trenching, land stripping, and earthmoving) is a significant source of fugitive dust, which decreases air quality and may carry soil pathogens. Annual differencing of Landsat Thematic Mapper (TM) mid-infrared images is used to create change images, and thresholded change areas are associated with coordinates of local dust inspections. The output metric identifies source areas of soil disturbance, and it estimates the annual amount of dust-producing surface area for eastern Pima County spanning 1994 through 2009. Spatially explicit construction-related soil disturbance and rodent abundance data are compared with coccidioidomycosis incidence data using rank order correlation and regression methods. Construction-related soil disturbance correlates strongly with annual county-wide incidence. It also correlates with Tucson periphery incidence aggregated to zip codes. Abundance values for the desert pocket mouse (Chaetodipus penicillatus), derived from a soil-adjusted vegetation index, aspect (northing) and thermal radiance, correlate with total study period incidence aggregated to zip code.

DEVELOPING A PREDICTIVE SIMULATION MODEL FOR ANTIANDROGEN IMPACTS ON RODENT PROSTATE

EPA Science Inventory

Developing a predictive simulation model for antiandrogen impacts on rodent prostate
HA Barton1, RW Setzer1, LK Potter1,2
1US EPA, ORD, NHEERL, ETD, PKB, Research Triangle Park, NC and 2Curriculum in Toxicology, UNC, Chapel Hill, NC

Alterations in rodent prostate wei...

Rodent Brain Microinjection to Study Molecular Substrates of Motivated Behavior

PubMed Central

Poland, Ryan S.; Bull, Cecilia; Syed, Wahab A.; Bowers, M. Scott

2015-01-01

Brain microinjection can aid elucidation of the molecular substrates of complex behaviors, such as motivation. For this purpose rodents can serve as appropriate models, partly because the response to behaviorally relevant stimuli and the circuitry parsing stimulus-action outcomes is astonishingly similar between humans and rodents. In studying molecular substrates of complex behaviors, the microinjection of reagents that modify, augment, or silence specific systems is an invaluable technique. However, it is crucial that the microinjection site is precisely targeted in order to aid interpretation of the results. We present a method for the manufacture of surgical implements and microinjection needles that enables accurate microinjection and unlimited customizability with minimal cost. Importantly, this technique can be successfully completed in awake rodents if conducted in conjunction with other JoVE articles that covered requisite surgical procedures. Additionally, there are many behavioral paradigms that are well suited for measuring motivation. The progressive ratio is a commonly used method that quantifies the efficacy of a reinforcer to maintain responding despite an (often exponentially) increasing work requirement. This assay is sensitive to reinforcer magnitude and pharmacological manipulations, which allows reinforcing efficacy and/ or motivation to be determined. We also present a straightforward approach to program operant software to accommodate a progressive ratio reinforcement schedule. PMID:26437131

Transformation of the rodent malaria parasite Plasmodium chabaudi.

PubMed

Spence, Philip J; Cunningham, Deirdre; Jarra, William; Lawton, Jennifer; Langhorne, Jean; Thompson, Joanne

2011-04-01

The rodent malaria parasite Plasmodium chabaudi chabaudi shares many features with human malaria species, including P. falciparum, and is the in vivo model of choice for many aspects of malaria research in the mammalian host, from sequestration of parasitized erythrocytes, to antigenic variation and host immunity and immunopathology. This protocol describes an optimized method for the transformation of mature blood-stage P.c. chabaudi and a description of a vector that targets efficient, single crossover integration into the P.c. chabaudi genome. Transformed lines are reproducibly generated and selected within 14-20 d, and show stable long-term protein expression even in the absence of drug selection. This protocol, therefore, provides the scientific community with a robust and reproducible method to generate transformed P.c. chabaudi parasites expressing fluorescent, bioluminescent and model antigens that can be used in vivo to dissect many of the fundamental principles of malaria infection.

Transformation of the rodent malaria parasite Plasmodium chabaudi

PubMed Central

Spence, Philip J; Cunningham, Deirdre; Jarra, William; Lawton, Jennifer

2014-01-01

The rodent malaria parasite Plasmodium chabaudi chabaudi shares many features with human malaria species, including P. falciparum, and is the in vivo model of choice for many aspects of malaria research in the mammalian host, from sequestration of parasitized erythrocytes, to antigenic variation and host immunity and immunopathology. this protocol describes an optimized method for the transformation of mature blood-stage P.c. chabaudi and a description of a vector that targets efficient, single crossover integration into the P.c. chabaudi genome. Transformed lines are reproducibly generated and selected within 4–20 d, and show stable long-term protein expression even in the absence of drug selection. this protocol, therefore, provides the scientific community with a robust and reproducible method to generate transformed P.c. chabaudi parasites expressing fluorescent, bioluminescent and model antigens that can be used in vivo to dissect many of the fundamental principles of malaria infection. PMID:21455190

Rodent models of glaucoma and their applicability for drug discovery.

PubMed

Agarwal, Renu; Agarwal, Puneet

2017-03-01

Rodents have widely been used to represent glaucomatous changes both in the presence and absence of elevated intraocular pressure (IOP) as they offer clear advantages over other animal species. IOP elevation is commonly achieved by creating an obstruction in the aqueous outflow pathways, consequently leading to retinal ganglion cell and optic nerve (ON) damage, the hallmark of glaucoma. These changes may also be achieved in the absence of elevated IOP by directly inflicting injury to retina or ON. Areas covered: This paper presents a summary of currently used rodent models of glaucoma. The characteristics of these models from several studies are summarized. The benefits and shortcomings of these models are also discussed. Expert opinion: The choice of animal model that closely represents human disease is key for successful translational of preclinical research to clinical practice. Rodent models of rapid IOP elevation are likely to be least representative, whereas models such as steroid-induced glaucoma models more closely resemble the trabecular meshwork changes seen in glaucomatous human eyes. However, this model needs further characterization. Rodent models based on direct retinal and ON injury are also useful tools to investigate molecular mechanisms involved at the site of final common pathology and neuroprotective strategies.

Non-human Primate and Rat Cardiac Fibroblasts show similar Extracellular Matrix-related and Cellular Adhesion Gene Responses to Substance P

PubMed Central

Meléndez, Giselle C.; Manteufel, Edward J.; Dehlin, Heather M.; Register, Thomas C.; Levick, Scott P.

2015-01-01

Background The sensory nerve neuropeptide substance P (SP) regulates cardiac fibrosis in rodents under pressure overload conditions. Interestingly, SP induces transient increase expression of specific genes in isolated rat cardiac fibroblasts, without resultant changes in cell function. This suggests that SP ‘primes’ fibroblasts, but does not directly activate them. We investigated whether these unusual findings are specific to rodent fibroblasts or are translatable to a larger animal model more closely related to humans. Methods We compared the effects of SP on genes associated with extracellular matrix (ECM) regulation, cell-cell adhesion, cell-matrix adhesion and ECM in cardiac fibroblasts isolated from a non-human primate and Sprague-Dawley rats. Results We found that rodent and non-human primate cardiac fibroblasts showed similar ECM regulation and cell adhesion gene expression responses to SP. There were, however, large discrepancies in ECM genes which did not result in collagen or laminin synthesis in rat or non-human primate fibroblasts in response to SP. Conclusions This study further supports the notion that SP serves as a ‘primer’ for fibroblasts rather than initiating direct effects and suggests that rodent fibroblasts are a suitable model for studying gene and functional responses to SP in the absence of human or non-human primate fibroblasts. PMID:25550118

Numerical solution of a spatio-temporal gender-structured model for hantavirus infection in rodents.

PubMed

Bürger, Raimund; Chowell, Gerardo; Gavilán, Elvis; Mulet, Pep; Villada, Luis M

2018-02-01

In this article we describe the transmission dynamics of hantavirus in rodents using a spatio-temporal susceptible-exposed-infective-recovered (SEIR) compartmental model that distinguishes between male and female subpopulations [L.J.S. Allen, R.K. McCormack and C.B. Jonsson, Bull. Math. Biol. 68 (2006), 511--524]. Both subpopulations are assumed to differ in their movement with respect to local variations in the densities of their own and the opposite gender group. Three alternative models for the movement of the male individuals are examined. In some cases the movement is not only directed by the gradient of a density (as in the standard diffusive case), but also by a non-local convolution of density values as proposed, in another context, in [R.M. Colombo and E. Rossi, Commun. Math. Sci., 13 (2015), 369--400]. An efficient numerical method for the resulting convection-diffusion-reaction system of partial differential equations is proposed. This method involves techniques of weighted essentially non-oscillatory (WENO) reconstructions in combination with implicit-explicit Runge-Kutta (IMEX-RK) methods for time stepping. The numerical results demonstrate significant differences in the spatio-temporal behavior predicted by the different models, which suggest future research directions.

[Dynamic model of seasonal breeding rodent pest population controlled with short-acting sterilant].

PubMed

Liu, Han-wu; Jin, Zhen; Zhang, Feng-qin; Li, Qiu-ying

2013-04-01

Rodent pests bring great damage to human beings, while rodenticide and sterilant can be used to control the pests. After ingesting sterilant, rodent pests lose their fertility, but in some cases, the sterile individuals may gain their fertility again, produce offspring, and enlarge population size. In this paper, the dynamic models of rodent pest population under lethal control and shortacting contraception control were formulated, and, with the prerequisite of the seasonal breeding of rodent pest population, the models were used to regularly analyze their behaviors and the effects of the contraception rate, lethal rate, control interval, and sterilant valid period on the dynamics of the pest population. The results showed that larger contraception rate and lethal rate and shorter control interval could have better control effect, making the controlled population become smaller and even died out. Short-acting sterilant limited the control effect. At the later period of breeding season, the rodent pest population controlled with short-acting sterilant would have a weak recovery.

Induction of Maternal Immune Activation in Mice at Mid-gestation Stage with Viral Mimic Poly(I:C)

PubMed Central

Wu, Wei-Li

2016-01-01

Maternal immune activation (MIA) model is increasingly well appreciated as a rodent model for the environmental risk factor of various psychiatric disorders. Numerous studies have demonstrated that MIA model is able to show face, construct, and predictive validity that are relevant to autism and schizophrenia. To model MIA, investigators often use viral mimic polyinosinic:polycytidylic acid (poly(I:C)) to activate the immune system in pregnant rodents. Generally, the offspring from immune activated dam exhibit behavioral abnormalities and physiological alterations that are associated with autism and schizophrenia. However, poly(I:C) injection with different dosages and at different time points could lead to different outcomes by perturbing brain development at different stages. Here we provide a detailed method of inducing MIA by intraperitoneal (i.p.) injection of 20 mg/kg poly(I:C) at mid-gestational embryonic 12.5 days (E12.5). This method has been shown to induce acute inflammatory response in the maternal-placental-fetal axis, which ultimately results in the brain perturbations and behavioral phenotypes that are associated with autism and schizophrenia. PMID:27078638

Induction of Maternal Immune Activation in Mice at Mid-gestation Stage with Viral Mimic Poly(I:C).

PubMed

Chow, Ke-Huan; Yan, Zihao; Wu, Wei-Li

2016-03-25

Maternal immune activation (MIA) model is increasingly well appreciated as a rodent model for the environmental risk factor of various psychiatric disorders. Numerous studies have demonstrated that MIA model is able to show face, construct, and predictive validity that are relevant to autism and schizophrenia. To model MIA, investigators often use viral mimic polyinosinic:polycytidylic acid (poly(I:C)) to activate the immune system in pregnant rodents. Generally, the offspring from immune activated dam exhibit behavioral abnormalities and physiological alterations that are associated with autism and schizophrenia. However, poly(I:C) injection with different dosages and at different time points could lead to different outcomes by perturbing brain development at different stages. Here we provide a detailed method of inducing MIA by intraperitoneal (i.p.) injection of 20 mg/kg poly(I:C) at mid-gestational embryonic 12.5 days (E12.5). This method has been shown to induce acute inflammatory response in the maternal-placental-fetal axis, which ultimately results in the brain perturbations and behavioral phenotypes that are associated with autism and schizophrenia.

Application of MODIS GPP to Forecast Risk of Hantavirus Pulmonary Syndrome Based on Fluctuations in Reservoir Population Density

NASA Astrophysics Data System (ADS)

Loehman, R.; Heinsch, F. A.; Mills, J. N.; Wagoner, K.; Running, S.

2003-12-01

Recent predictive models for hantavirus pulmonary syndrome (HPS) have used remotely sensed spectral reflectance data to characterize risk areas with limited success. We present an alternative method using gross primary production (GPP) from the MODIS sensor to estimate the effects of biomass accumulation on population density of Peromyscus maniculatus (deer mouse), the principal reservoir species for Sin Nombre virus (SNV). The majority of diagnosed HPS cases in North America are attributed to SNV, which is transmitted to humans through inhalation of excretions and secretions from infected rodents. A logistic model framework is used to evaluate MODIS GPP, temperature, and precipitation as predictors of P. maniculatus density at established trapping sites across the western United States. Rodent populations are estimated using monthly minimum number alive (MNA) data for 2000 through 2002. Both local meteorological data from nearby weather stations and 1.25 degree x 1 degree gridded data from the NASA DAO were used in the regression model to determine the spatial sensitivity of the response. MODIS eight-day GPP data (1-km resolution) were acquired and binned to monthly average and monthly sum GPP for 3km x 3km grids surrounding each rodent trapping site. The use of MODIS GPP to forecast HPS risk may result in a marked improvement over past reflectance-based risk area characterizations. The MODIS GPP product provides a vegetation dynamics estimate that is unique to disease models, and targets the fundamental ecological processes responsible for increased rodent density and amplified disease risk.

Molecular Hydrogen as an Emerging Therapeutic Medical Gas for Neurodegenerative and Other Diseases

PubMed Central

Ohno, Kinji; Ito, Mikako; Ichihara, Masatoshi; Ito, Masafumi

2012-01-01

Effects of molecular hydrogen on various diseases have been documented for 63 disease models and human diseases in the past four and a half years. Most studies have been performed on rodents including two models of Parkinson's disease and three models of Alzheimer's disease. Prominent effects are observed especially in oxidative stress-mediated diseases including neonatal cerebral hypoxia; Parkinson's disease; ischemia/reperfusion of spinal cord, heart, lung, liver, kidney, and intestine; transplantation of lung, heart, kidney, and intestine. Six human diseases have been studied to date: diabetes mellitus type 2, metabolic syndrome, hemodialysis, inflammatory and mitochondrial myopathies, brain stem infarction, and radiation-induced adverse effects. Two enigmas, however, remain to be solved. First, no dose-response effect is observed. Rodents and humans are able to take a small amount of hydrogen by drinking hydrogen-rich water, but marked effects are observed. Second, intestinal bacteria in humans and rodents produce a large amount of hydrogen, but an addition of a small amount of hydrogen exhibits marked effects. Further studies are required to elucidate molecular bases of prominent hydrogen effects and to determine the optimal frequency, amount, and method of hydrogen administration for each human disease. PMID:22720117

Advancing Cardiovascular, Neurovascular, and Renal Magnetic Resonance Imaging in Small Rodents Using Cryogenic Radiofrequency Coil Technology

PubMed Central

Niendorf, Thoralf; Pohlmann, Andreas; Reimann, Henning M.; Waiczies, Helmar; Peper, Eva; Huelnhagen, Till; Seeliger, Erdmann; Schreiber, Adrian; Kettritz, Ralph; Strobel, Klaus; Ku, Min-Chi; Waiczies, Sonia

2015-01-01

Research in pathologies of the brain, heart and kidney have gained immensely from the plethora of studies that have helped shape new methods in magnetic resonance (MR) for characterizing preclinical disease models. Methodical probing into preclinical animal models by MR is invaluable since it allows a careful interpretation and extrapolation of data derived from these models to human disease. In this review we will focus on the applications of cryogenic radiofrequency (RF) coils in small animal MR as a means of boosting image quality (e.g., by supporting MR microscopy) and making data acquisition more efficient (e.g., by reducing measuring time); both being important constituents for thorough investigational studies on animal models of disease. This review attempts to make the (bio)medical imaging, molecular medicine, and pharmaceutical communities aware of this productive ferment and its outstanding significance for anatomical and functional MR in small rodents. The goal is to inspire a more intense interdisciplinary collaboration across the fields to further advance and progress non-invasive MR methods that ultimately support thorough (patho)physiological characterization of animal disease models. In this review, current and potential future applications for the RF coil technology in cardiovascular, neurovascular, and renal disease will be discussed. PMID:26617515

A systematic review on the anxiolytic effects of aromatherapy on rodents under experimentally induced anxiety models.

PubMed

Tsang, Hector W H; Ho, Timothy Y C

2010-01-01

We reviewed studies from 1999 to 2009 on anxiolytic effects of different essential oils toward rodents in anxiety-related behavioral models. Journal papers that evaluated the anxiolytic effects of essential oils for rodents were extracted from available electronic data bases. The results based on 14 studies showed that different rodent species were recruited including ICR mice and Swiss mice. Most of studies applied the Elevated Plus Maze (EPM) as the animal behavioral model. Lavender oil was the most popular within the 14 studies. Lavender and rose oils were found to be effective in some of the studies. Only one study reported the underlying neurophysiological mechanism in terms of concentrations of emotionally related neuro-transmitters such as dopamine, serotonin, and their derivatives, in various brain regions. Some essential oils are found to be effective to induce anxiolytic effect in rodents under different animal anxiety models. However, more standardized experimental procedures and outcome measures are needed in future studies. Translational research to human subjects is also recommended.

Does age matter? The impact of rodent age on study outcomes.

PubMed

Jackson, Samuel J; Andrews, Nick; Ball, Doug; Bellantuono, Ilaria; Gray, James; Hachoumi, Lamia; Holmes, Alan; Latcham, Judy; Petrie, Anja; Potter, Paul; Rice, Andrew; Ritchie, Alison; Stewart, Michelle; Strepka, Carol; Yeoman, Mark; Chapman, Kathryn

2017-04-01

Rodent models produce data which underpin biomedical research and non-clinical drug trials, but translation from rodents into successful clinical outcomes is often lacking. There is a growing body of evidence showing that improving experimental design is key to improving the predictive nature of rodent studies and reducing the number of animals used in research. Age, one important factor in experimental design, is often poorly reported and can be overlooked. The authors conducted a survey to assess the age used for a range of models, and the reasoning for age choice. From 297 respondents providing 611 responses, researchers reported using rodents most often in the 6-20 week age range regardless of the biology being studied. The age referred to as 'adult' by respondents varied between six and 20 weeks. Practical reasons for the choice of rodent age were frequently given, with increased cost associated with using older animals and maintenance of historical data comparability being two important limiting factors. These results highlight that choice of age is inconsistent across the research community and often not based on the development or cellular ageing of the system being studied. This could potentially result in decreased scientific validity and increased experimental variability. In some cases the use of older animals may be beneficial. Increased scientific rigour in the choice of the age of rodent may increase the translation of rodent models to humans.

Does age matter? The impact of rodent age on study outcomes

PubMed Central

Andrews, Nick; Ball, Doug; Bellantuono, Ilaria; Gray, James; Hachoumi, Lamia; Holmes, Alan; Latcham, Judy; Petrie, Anja; Potter, Paul; Rice, Andrew; Ritchie, Alison; Stewart, Michelle; Strepka, Carol; Yeoman, Mark; Chapman, Kathryn

2016-01-01

Rodent models produce data which underpin biomedical research and non-clinical drug trials, but translation from rodents into successful clinical outcomes is often lacking. There is a growing body of evidence showing that improving experimental design is key to improving the predictive nature of rodent studies and reducing the number of animals used in research. Age, one important factor in experimental design, is often poorly reported and can be overlooked. The authors conducted a survey to assess the age used for a range of models, and the reasoning for age choice. From 297 respondents providing 611 responses, researchers reported using rodents most often in the 6–20 week age range regardless of the biology being studied. The age referred to as ‘adult’ by respondents varied between six and 20 weeks. Practical reasons for the choice of rodent age were frequently given, with increased cost associated with using older animals and maintenance of historical data comparability being two important limiting factors. These results highlight that choice of age is inconsistent across the research community and often not based on the development or cellular ageing of the system being studied. This could potentially result in decreased scientific validity and increased experimental variability. In some cases the use of older animals may be beneficial. Increased scientific rigour in the choice of the age of rodent may increase the translation of rodent models to humans. PMID:27307423

Screening of nanoparticulate delivery systems for the photodetection of cancer in a simple and cost-effective model.

PubMed

Zeisser-Labouèbe, Magali; Delie, Florence; Gurny, Robert; Lange, Norbert

2009-02-01

In urology, fluorescence-based imaging methods have been proven to significantly improve the detection of small, barely visible tumors and reduce the recurrence rate. Under ethical and economical pressure, new effective screening systems have to be developed to exploit and assess novel strategies for fluorescence photodetection in other areas. For this purpose, the chorioallantoic membrane (CAM) of the developing chick embryo is an attractive alternative model to the mammalian models. Hypericin encapsulated into nanoparticles for the photodetection of ovarian metastases was evaluated in the CAM model with respect to vascular extravazation and tumor targeting and compared with free drug following intravenous administration. To validate the CAM model as a valuable screening system for photodetection of cancer, we drew a comparison with results obtained on a conventional rodent model. Rodent and CAM models led to the same conclusion regarding the benefits of nanoencapsulation to improve selective accumulation of drug in ovarian micrometastases.

Application of FDA-Approved Memantine and Newer NitroMemantine Derivatives to Treat Neurological Manifestations in Rodent Models of Tuberous Sclerosis Complex

DTIC Science & Technology

2014-05-01

Memantine and Newer NitroMemantine Derivatives to Treat Neurological Manifestations in Rodent Models of Tuberous Sclerosis Complex PRINCIPAL...Approved Memantine and Newer NitroMemantine Derivatives to Treat 5a. CONTRACT NUMBER W81XWH-13-1-0053 Neurological Manifestations in Rodent Models of...to investigate if administration of the FDA-approved drug, Memantine , an uncompetitive/fast off-rate antagonist of the N- methyl-D-aspartate-type

Rodents and climate: A new model for estimating past temperatures [rapid communication

NASA Astrophysics Data System (ADS)

Legendre, Serge; Montuire, Sophie; Maridet, Olivier; Escarguel, Gilles

2005-06-01

Based on the high correlation between species richness in sigmodontine rodents and temperatures, we propose a new model in order to quantify past climates. Because of the close phylogenetic relationship and the tooth morphological similarity between extant New World cricetids (Sigmodontinae) and fossil European cricetids (Cricetinae s.l.), extant New World sigmodontines are taken as analogues for Old World fossil cricetines. Sigmodontine species richness has been compiled for 282 extant local faunas from North, Central and South America, with corresponding climatic data (temperatures and precipitations). There is almost no correlation between areas covered by local faunas (ranging from 1 km 2 up to 46,000 km 2) and numbers of sigmodontine species in localities ( R2 = 0.027). Number of sigmodontine species in local faunas and mean annual daily temperatures are highly correlated ( R2 = 0.88). The relationships of species richness and precipitation is low ( R2 = 0.19 for mean annual precipitation). The method is exemplified for Old World cricetines using well documented Miocene rodent faunas located in the Lyon area (France MN4-5 to MN10).

Evaluating social defeat as a model for psychopathology in adult female rodents.

PubMed

Solomon, Matia B

2017-01-02

Social conflict is a predominant stressor in humans and is associated with increased risk for developing psychological illnesses including depression and anxiety. Overwhelmingly, more women suffer from these disorders, which may be due to increased stress sensitivity. Like humans, rodents experience a myriad of physiological and behavioral sequelae due to prolonged stress exposure. Although the motivation for social conflict may differ between humans and rodents, female rodents may provide an opportunity to explore the underlying mechanisms by which stress confers risk for psychopathology in women. Because most female rodents do not express spontaneous aggression, the majority of basic research examines the physiological and behavioral outcomes of social conflict in male rodents. However, there are instances where female rodents exhibit territorial (California mice and Syrian hamsters) and maternal aggression (rats, mice, and hamsters) creating a venue to examine sex differences in physiology and behavior in response to stress. While many studies rely upon nonsocial behavioral assays (e.g., elevated plus maze, forced swim test) to assess the impact of stress on emotionality, here we primarily focus on behavioral outcomes in social-based assays in rodents. This is critically important given that disruptions in social relationships can be a cause and consequence of neuropsychiatric diseases. Next, we briefly discuss how sex differences in the recruitment of neural circuitry and/or neurochemistry in response to stress may underlie sex differences in neuroendocrine and behavioral stress responses. Finally, the translational value of females in rodent stress models and considerations regarding behavioral interpretations of these models are discussed. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Rat-atouille: A Mixed Method Study to Characterize Rodent Hunting and Consumption in the Context of Lassa Fever.

PubMed

Bonwitt, Jesse; Kelly, Ann H; Ansumana, Rashid; Agbla, Schadrac; Sahr, Foday; Saez, Almudena Mari; Borchert, Matthias; Kock, Richard; Fichet-Calvet, Elisabeth

2016-06-01

Lassa fever is a zoonotic hemorrhagic illness predominant in areas across Nigeria, Sierra Leone, Guinea, Liberia, and southern Mali. The reservoir of Lassa virus is the multimammate mouse (Mastomys natalensis), a highly commensal species in West Africa. Primary transmission to humans occurs through direct or indirect contact with rodent body fluids such as urine, feces, saliva, or blood. Our research draws together qualitative and quantitative methods to provide a fuller and more nuanced perspective on these varied points of human-animal contact. In this article, we focus on the hunting, preparation, and consumption of rodents as possible routes of exposure in Bo, Sierra Leone. We found that the consumption of rodents, including the reservoir species, is widespread and does not neatly tally against generational or gender lines. Further, we found that the reasons for rodent consumption are multifactorial, including taste preferences, food security, and opportunistic behavior. We argue that on certain topics, such as rodent consumption, establishing trust with communities, and using qualitative research methods, is key to investigate sensitive issues and situate them in their wider context. To conclude, we recommend ways to refine sensitization campaigns to account for these socio-cultural contexts.

Relationships between Rodent White Adipose Fat Pads and Human White Adipose Fat Depots

PubMed Central

Chusyd, Daniella E.; Wang, Donghai; Huffman, Derek M.; Nagy, Tim R.

2016-01-01

The objective of this review was to compare and contrast the physiological and metabolic profiles of rodent white adipose fat pads with white adipose fat depots in humans. Human fat distribution and its metabolic consequences have received extensive attention, but much of what has been tested in translational research has relied heavily on rodents. Unfortunately, the validity of using rodent fat pads as a model of human adiposity has received less attention. There is a surprisingly lack of studies demonstrating an analogous relationship between rodent and human adiposity on obesity-related comorbidities. Therefore, we aimed to compare known similarities and disparities in terms of white adipose tissue (WAT) development and distribution, sexual dimorphism, weight loss, adipokine secretion, and aging. While the literature supports the notion that many similarities exist between rodents and humans, notable differences emerge related to fat deposition and function of WAT. Thus, further research is warranted to more carefully define the strengths and limitations of rodent WAT as a model for humans, with a particular emphasis on comparable fat depots, such as mesenteric fat. PMID:27148535

Hydrophobic Sand Is a Non-Toxic Method of Urine Collection, Appropriate for Urinary Metal Analysis in the Rat

PubMed Central

Hoffman, Jessica F.; Vergara, Vernieda B.; Mog, Steven R.; Kalinich, John F.

2017-01-01

Hydrophobic sand is a relatively new method of urine collection in the rodent, comparable to the established method using a metabolic cage. Urine samples are often used in rodent research, especially for biomarkers of health changes after internal contamination from embedded metals, such as in a model of a military shrapnel wound. However, little research has been done on the potential interference of hydrophobic sand with urine metal concentrations either by contamination from the sand particulate, or adsorption of metals from the urine. We compare urine collected from rats using the metabolic cage method and the hydrophobic sand method for differences in metal concentration of common urinary metals, and examine physical properties of the sand material for potential sources of contamination. We found minimal risk of internal contamination of the rat by hydrophobic sand, and no interference of the sand with several common metals of interest (cobalt, strontium, copper, and manganese), although we advise caution in studies of aluminum in urine. PMID:29051457

Multi-object model-based multi-atlas segmentation for rodent brains using dense discrete correspondences

NASA Astrophysics Data System (ADS)

Lee, Joohwi; Kim, Sun Hyung; Styner, Martin

2016-03-01

The delineation of rodent brain structures is challenging due to low-contrast multiple cortical and subcortical organs that are closely interfacing to each other. Atlas-based segmentation has been widely employed due to its ability to delineate multiple organs at the same time via image registration. The use of multiple atlases and subsequent label fusion techniques has further improved the robustness and accuracy of atlas-based segmentation. However, the accuracy of atlas-based segmentation is still prone to registration errors; for example, the segmentation of in vivo MR images can be less accurate and robust against image artifacts than the segmentation of post mortem images. In order to improve the accuracy and robustness of atlas-based segmentation, we propose a multi-object, model-based, multi-atlas segmentation method. We first establish spatial correspondences across atlases using a set of dense pseudo-landmark particles. We build a multi-object point distribution model using those particles in order to capture inter- and intra- subject variation among brain structures. The segmentation is obtained by fitting the model into a subject image, followed by label fusion process. Our result shows that the proposed method resulted in greater accuracy than comparable segmentation methods, including a widely used ANTs registration tool.

Modeling the Western Diet for Preclinical Investigations.

PubMed

Hintze, Korry J; Benninghoff, Abby D; Cho, Clara E; Ward, Robert E

2018-05-01

Rodent models have been invaluable for biomedical research. Preclinical investigations with rodents allow researchers to investigate diseases by using study designs that are not suitable for human subjects. The primary criticism of preclinical animal models is that results are not always translatable to humans. Some of this lack of translation is due to inherent differences between species. However, rodent models have been refined over time, and translatability to humans has improved. Transgenic animals have greatly aided our understanding of interactions between genes and disease and have narrowed the translation gap between humans and model animals. Despite the technological innovations of animal models through advances in genetics, relatively little attention has been given to animal diets. Namely, developing diets that replicate what humans eat will help make animal models more relevant to human populations. This review focuses on commonly used rodent diets that are used to emulate the Western dietary pattern in preclinical studies of obesity and type 2 diabetes, nonalcoholic liver disease, maternal nutrition, and colorectal cancer.

An in-vitro–in-vivo model for the transdermal delivery of cholecalciferol for the purposes of rodent management

PubMed Central

Davies, J.; Ingham, A.

2015-01-01

The natural selection of anticoagulant resistant rats has resulted in a need for an alternative to anticoagulant rodenticides which differs in both active ingredient and in the method of dosing. Cholecalciferol toxicity to rodents using the dermal route is demonstrated using a variety of penetration enhancing formulations in two in-vitro models and finally in-vivo. A 1 ml dose of 50/50 (v/v) DMSO/ethanol containing 15% (v/v) PEG 200 and 20% (w/v) cholecalciferol was judged as ‘sufficiently effective’ in line with the European Union’s Biocidal Products Regulation (No. 528/2012) during in-vivo studies. This dose was found to cause 100% mortality in a rat population in 64.4 h (±22 h). PMID:25835266

Quantifying light-dependent circadian disruption in humans and animal models.

PubMed

Rea, Mark S; Figueiro, Mariana G

2014-12-01

Although circadian disruption is an accepted term, little has been done to develop methods to quantify the degree of disruption or entrainment individual organisms actually exhibit in the field. A variety of behavioral, physiological and hormonal responses vary in amplitude over a 24-h period and the degree to which these circadian rhythms are synchronized to the daily light-dark cycle can be quantified with a technique known as phasor analysis. Several studies have been carried out using phasor analysis in an attempt to measure circadian disruption exhibited by animals and by humans. To perform these studies, species-specific light measurement and light delivery technologies had to be developed based upon a fundamental understanding of circadian phototransduction mechanisms in the different species. When both nocturnal rodents and diurnal humans, experienced different species-specific light-dark shift schedules, they showed, based upon phasor analysis of the light-dark and activity-rest patterns, similar levels of light-dependent circadian disruption. Indeed, both rodents and humans show monotonically increasing and quantitatively similar levels of light-dependent circadian disruption with increasing shift-nights per week. Thus, phasor analysis provides a method for quantifying circadian disruption in the field and in the laboratory as well as a bridge between ecological measurements of circadian entrainment in humans and parametric studies of circadian disruption in animal models, including nocturnal rodents.

Comparison between Surrogate Indexes of Insulin Sensitivity/Resistance and Hyperinsulinemic Euglycemic Glucose Clamps in Rhesus Monkeys

PubMed Central

Lee, Ho-Won; Muniyappa, Ranganath; Yan, Xu; Yue, Lilly Q.; Linden, Ellen H.; Chen, Hui; Hansen, Barbara C.

2011-01-01

The euglycemic glucose clamp is the reference method for assessing insulin sensitivity in humans and animals. However, clamps are ill-suited for large studies because of extensive requirements for cost, time, labor, and technical expertise. Simple surrogate indexes of insulin sensitivity/resistance including quantitative insulin-sensitivity check index (QUICKI) and homeostasis model assessment (HOMA) have been developed and validated in humans. However, validation studies of QUICKI and HOMA in both rats and mice suggest that differences in metabolic physiology between rodents and humans limit their value in rodents. Rhesus monkeys are a species more similar to humans than rodents. Therefore, in the present study, we evaluated data from 199 glucose clamp studies obtained from a large cohort of 86 monkeys with a broad range of insulin sensitivity. Data were used to evaluate simple surrogate indexes of insulin sensitivity/resistance (QUICKI, HOMA, Log HOMA, 1/HOMA, and 1/Fasting insulin) with respect to linear regression, predictive accuracy using a calibration model, and diagnostic performance using receiver operating characteristic. Most surrogates had modest linear correlations with SIClamp (r ≈ 0.4–0.64) with comparable correlation coefficients. Predictive accuracy determined by calibration model analysis demonstrated better predictive accuracy of QUICKI than HOMA and Log HOMA. Receiver operating characteristic analysis showed equivalent sensitivity and specificity of most surrogate indexes to detect insulin resistance. Thus, unlike in rodents but similar to humans, surrogate indexes of insulin sensitivity/resistance including QUICKI and log HOMA may be reasonable to use in large studies of rhesus monkeys where it may be impractical to conduct glucose clamp studies. PMID:21209021

Helminth Infections of Rodents and Their Zoonotic Importance in Boyer-Ahmad District, Southwestern Iran

PubMed Central

RANJBAR, Mohammad Javad; SARKARI, Bahador; MOWLAVI, Gholam Reza; SEIFOLLAHI, Zeinab; MOSHFE, Abdolali; ABDOLAHI KHABISI, Samaneh; MOBEDI, Iraj

2017-01-01

Background: Rodents are considered as reservoirs of various zoonotic diseases including helminthic infections. The current study aimed to evaluate the prevalence of helminth infections in rodents, in Boyer-Ahmad district, Southwestern Iran. Methods: Overall, 52 rodents were captured from various areas of the district by Sherman live traps. The animals were then euthanized and dissected. During necropsy, each organ was examined macroscopically for presence of any cyst or visible parasite. The gastrointestinal tract was removed and their contents were evaluated for larva or adult worms. Trichinella larvae in the rodents’ muscles were investigated by both digestion and pathological methods. Results: Twenty-eight (53.8%) of the trapped rodents were male. The rodents were including 25 (48.1%) Meriones persicus, 1(1.9%) Calomyscus bailwardi, 1 (1.9%) Arvicola terresterris, 7 (13.5%) Rattus rattus, 8 (15.4%) R. norvegicus, and 10 (19.2%) Apodemus sylvaticus. Of them, 38 (73.0%) were infected with at least one helminth. Collected rodents were infected with Hymenolepis diminuta (50%), Hymenolepis nana fraterna (28.8%), Skrjabinotaenia sp. (15.4%), Anoplocephalidae sp. (15.4%), Cysticercus fasciolaris (5.8%), Trichuris muris (36.5%), Aspiculuris tetraptera (15.4%), Syphacia sp. (5.7%), Rictularia sp. (15.4%), Trichostrongylus sp. (3.8%), and Gongylonema sp. (3.8%). M. persicus was the most (84%) infected rodent, yet the differences between rodent genus and helminth infectivity were not statistically significant (P>0.05). Conclusion: The rodents in Boyer-Ahmad district are infected with different helminths infections that some of them are recognized as threat to human health. PMID:29317882

Identifying Rodent Resting-State Brain Networks with Independent Component Analysis

PubMed Central

Bajic, Dusica; Craig, Michael M.; Mongerson, Chandler R. L.; Borsook, David; Becerra, Lino

2017-01-01

Rodent models have opened the door to a better understanding of the neurobiology of brain disorders and increased our ability to evaluate novel treatments. Resting-state functional magnetic resonance imaging (rs-fMRI) allows for in vivo exploration of large-scale brain networks with high spatial resolution. Its application in rodents affords researchers a powerful translational tool to directly assess/explore the effects of various pharmacological, lesion, and/or disease states on known neural circuits within highly controlled settings. Integration of animal and human research at the molecular-, systems-, and behavioral-levels using diverse neuroimaging techniques empowers more robust interrogations of abnormal/ pathological processes, critical for evolving our understanding of neuroscience. We present a comprehensive protocol to evaluate resting-state brain networks using Independent Component Analysis (ICA) in rodent model. Specifically, we begin with a brief review of the physiological basis for rs-fMRI technique and overview of rs-fMRI studies in rodents to date, following which we provide a robust step-by-step approach for rs-fMRI investigation including data collection, computational preprocessing, and brain network analysis. Pipelines are interwoven with underlying theory behind each step and summarized methodological considerations, such as alternative methods available and current consensus in the literature for optimal results. The presented protocol is designed in such a way that investigators without previous knowledge in the field can implement the analysis and obtain viable results that reliably detect significant differences in functional connectivity between experimental groups. Our goal is to empower researchers to implement rs-fMRI in their respective fields by incorporating technical considerations to date into a workable methodological framework. PMID:29311770

Intestinal Helminths in Different Species of Rodents in North Khorasan Province, Northeast of Iran

PubMed Central

ARZAMANI, Kourosh; SALEHI, Mitra; MOBEDI, Iraj; ADINEZADE, Amir; HASANPOUR, Hamid; ALAVINIA, Mohammad; DARVISH, Jamshid; SHIRZADI, Mohammad Reza; MOHAMMADI, Zeinolabedin

2017-01-01

Background: Rodents are an important source of zoonotic diseases for human. The aim of this study was to determine the infectivity of rodents with intestinal helminths in North Khorasan Province, Iran. Methods: One hundred and thirteen rodents were collected using different collection methods such as kill and live traps, digging of their burrow, filling of their hiding places with water and hand net during 2011–2013. Their alimentary canals were removed in the laboratory and helminths were determined in the department of parasitology, Tehran University of Medical Sciences. Results: Thirteen species of helminths parasites were found in 13 species of rodents, including Aspiculuris tetraptera, Hymenolepis diminuta, Nippostrongylus brasiliensis, Protospirura Seurat, Rictolaria ratti, Skrjabinitaenia lobata, Streptopharagus kuntzi, Syphacia obvelata, Taenia taeniaeformis, Trichuris muris, Cysticercus fasciolaris, Acanthocephal. spp and Trichuris spp. Some of them were reported for the first time in new host in Iran. S. obvelata and A. tetraptera were the most frequent parasites and P. Seurat, R. ratti and C. fasciolaris were found only in one rodent. Conclusion: This is the first study to investigate the intestinal parasites in rodents in this area. Among different species identified, some of helminths were reported in new host. PMID:28761488

Hantavirus reservoir Oligoryzomys longicaudatus spatial distribution sensitivity to climate change scenarios in Argentine Patagonia

PubMed Central

Carbajo, Aníbal E; Vera, Carolina; González, Paula LM

2009-01-01

Background Oligoryzomys longicaudatus (colilargo) is the rodent responsible for hantavirus pulmonary syndrome (HPS) in Argentine Patagonia. In past decades (1967–1998), trends of precipitation reduction and surface air temperature increase have been observed in western Patagonia. We explore how the potential distribution of the hantavirus reservoir would change under different climate change scenarios based on the observed trends. Methods Four scenarios of potential climate change were constructed using temperature and precipitation changes observed in Argentine Patagonia between 1967 and 1998: Scenario 1 assumed no change in precipitation but a temperature trend as observed; scenario 2 assumed no changes in temperature but a precipitation trend as observed; Scenario 3 included changes in both temperature and precipitation trends as observed; Scenario 4 assumed changes in both temperature and precipitation trends as observed but doubled. We used a validated spatial distribution model of O. longicaudatus as a function of temperature and precipitation. From the model probability of the rodent presence was calculated for each scenario. Results If changes in precipitation follow previous trends, the probability of the colilargo presence would fall in the HPS transmission zone of northern Patagonia. If temperature and precipitation trends remain at current levels for 60 years or double in the future 30 years, the probability of the rodent presence and the associated total area of potential distribution would diminish throughout Patagonia; the areas of potential distribution for colilargos would shift eastwards. These results suggest that future changes in Patagonia climate may lower transmission risk through a reduction in the potential distribution of the rodent reservoir. Conclusion According to our model the rates of temperature and precipitation changes observed between 1967 and 1998 may produce significant changes in the rodent distribution in an equivalent period of time only in certain areas. Given that changes maintain for 60 years or double in 30 years, the hantavirus reservoir Oligoryzomys longicaudatus may contract its distribution in Argentine Patagonia extensively. PMID:19607707

Efficient monitoring of the blood-stage infection in a malaria rodent model by the rotating-crystal magneto-optical method

NASA Astrophysics Data System (ADS)

Orbán, Ágnes; Rebelo, Maria; Molnár, Petra; Albuquerque, Inês S.; Butykai, Adam; Kézsmárki, István

2016-03-01

Intense research efforts have been focused on the improvement of the efficiency and sensitivity of malaria diagnostics, especially in resource-limited settings for the detection of asymptomatic infections. Our recently developed magneto-optical (MO) method allows the accurate quantification of malaria pigment crystals (hemozoin) in blood by their magnetically induced rotation. First evaluations of the method using β-hematin crystals and in vitro P. falciparum cultures implied its potential for high-sensitivity malaria diagnosis. To further investigate this potential, here we study the performance of the method in monitoring the in vivo onset and progression of the blood-stage infection in a rodent malaria model. Our results show that the MO method can detect the first generation of intraerythrocytic P. berghei parasites 66-76 hours after sporozoite injection, demonstrating similar sensitivity to Giesma-stained light microscopy and exceeding that of flow cytometric techniques. Magneto-optical measurements performed during and after the treatment of P. berghei infections revealed that both the follow up under treatment and the detection of later reinfections are feasible with this new technique. The present study demonstrates that the MO method - besides being label and reagent-free, automated and rapid - has a high in vivo sensitivity and is ready for in-field evaluation.

The Need for Speed in Rodent Locomotion Analyses

PubMed Central

Batka, Richard J.; Brown, Todd J.; Mcmillan, Kathryn P.; Meadows, Rena M.; Jones, Kathryn J.; Haulcomb, Melissa M.

2016-01-01

Locomotion analysis is now widely used across many animal species to understand the motor defects in disease, functional recovery following neural injury, and the effectiveness of various treatments. More recently, rodent locomotion analysis has become an increasingly popular method in a diverse range of research. Speed is an inseparable aspect of locomotion that is still not fully understood, and its effects are often not properly incorporated while analyzing data. In this hybrid manuscript, we accomplish three things: (1) review the interaction between speed and locomotion variables in rodent studies, (2) comprehensively analyze the relationship between speed and 162 locomotion variables in a group of 16 wild-type mice using the CatWalk gait analysis system, and (3) develop and test a statistical method in which locomotion variables are analyzed and reported in the context of speed. Notable results include the following: (1) over 90% of variables, reported by CatWalk, were dependent on speed with an average R2 value of 0.624, (2) most variables were related to speed in a nonlinear manner, (3) current methods of controlling for speed are insufficient, and (4) the linear mixed model is an appropriate and effective statistical method for locomotion analyses that is inclusive of speed-dependent relationships. Given the pervasive dependency of locomotion variables on speed, we maintain that valid conclusions from locomotion analyses cannot be made unless they are analyzed and reported within the context of speed. PMID:24890845

2015 Summer Series - Ruth Globus - Flying Through the Ages: Rodent Research for Human Health

NASA Image and Video Library

2015-06-16

Rodents are a model organism to study the short and long term effects of space travel. Building on its space shuttle experience, NASA Ames has developed the Rodent Research Habitat for the International Space Station to implement space biology investigations. Dr. Ruth Globus' seminar takes us into the world of rodent research in space and explains how it can support human health.

Perceptual and neural responses to sweet taste in humans and rodents.

PubMed

Lemon, Christian H

2015-08-01

This mini-review discusses some of the parallels between rodent neurophysiological and human psychophysical data concerning temperature effects on sweet taste. "Sweet" is an innately rewarding taste sensation that is associated in part with foods that contain calories in the form of sugars. Humans and other mammals can show unconditioned preference for select sweet stimuli. Such preference is poised to influence diet selection and, in turn, nutritional status, which underscores the importance of delineating the physiological mechanisms for sweet taste with respect to their influence on human health. Advances in our knowledge of the biology of sweet taste in humans have arisen in part through studies on mechanisms of gustatory processing in rodent models. Along this line, recent work has revealed there are operational parallels in neural systems for sweet taste between mice and humans, as indexed by similarities in the effects of temperature on central neurophysiological and psychophysical responses to sucrose in these species. Such association strengthens the postulate that rodents can serve as effective models of particular mechanisms of appetitive taste processing. Data supporting this link are discussed here, as are rodent and human data that shed light on relationships between mechanisms for sweet taste and ingestive disorders, such as alcohol abuse. Rodent models have utility for understanding mechanisms of taste processing that may pertain to human flavor perception. Importantly, there are limitations to generalizing data from rodents, albeit parallels across species do exist.

Ultra High-Resolution In vivo Computed Tomography Imaging of Mouse Cerebrovasculature Using a Long Circulating Blood Pool Contrast Agent

PubMed Central

Starosolski, Zbigniew; Villamizar, Carlos A.; Rendon, David; Paldino, Michael J.; Milewicz, Dianna M.; Ghaghada, Ketan B.; Annapragada, Ananth V.

2015-01-01

Abnormalities in the cerebrovascular system play a central role in many neurologic diseases. The on-going expansion of rodent models of human cerebrovascular diseases and the need to use these models to understand disease progression and treatment has amplified the need for reproducible non-invasive imaging methods for high-resolution visualization of the complete cerebral vasculature. In this study, we present methods for in vivo high-resolution (19 μm isotropic) computed tomography imaging of complete mouse brain vasculature. This technique enabled 3D visualization of large cerebrovascular networks, including the Circle of Willis. Blood vessels as small as 40 μm were clearly delineated. ACTA2 mutations in humans cause cerebrovascular defects, including abnormally straightened arteries and a moyamoya-like arteriopathy characterized by bilateral narrowing of the internal carotid artery and stenosis of many large arteries. In vivo imaging studies performed in a mouse model of Acta2 mutations demonstrated the utility of this method for studying vascular morphometric changes that are practically impossible to identify using current histological methods. Specifically, the technique demonstrated changes in the width of the Circle of Willis, straightening of cerebral arteries and arterial stenoses. We believe the use of imaging methods described here will contribute substantially to the study of rodent cerebrovasculature. PMID:25985192

Rodent Models of Genetic Contributions to Motivation to Abuse Alcohol

PubMed Central

Crabbe, John C.

2016-01-01

The distinction between alcohol use (normative) and abuse (unfortunately common) implies dysregulation of motivation directed toward the drug. Genetic contributions to abuse risk are mediated through personality differences, other predispositions to drink excessively, and differences in sensitivity to the acute and chronic consequences of the drug. How to assess motivation in laboratory animals is not straightforward but risk factors for and consequences of alcohol abuse can be modeled with reasonable fidelity in laboratory rodents. Remarkably few rodent studies focus on the genetic contributions to alcohol’s reinforcing value: almost all examine preferential drinking of unflavored alcohol over water. Such studies will likely never avoid the confounding role of taste preferences and most often yield intake levels insufficient to yield a pharmacologically significant blood alcohol level. Genotypes that avoid alcohol probably do so based on pre-ingestive sensory cues; however, post-ingestive consequences are also important. Thus, the quest for improved measures of reinforcing value continues. We have genetic differences aplenty, but still lack evidence that any genotype will readily self-administer alcohol to the devastating extent that many alcoholics will. Encouraging results that are emerging include improved behavioral methods for elevating alcohol intake and inferring alcohol reinforcement, as well as new genetic animal models. Several ingenious assays to index alcohol’s motivational effects have been used extensively. Alcoholic drinking that attempts to prevent or to alleviate withdrawal symptoms has been modeled. Another characteristic of alcoholic drinking is its persistence despite abundant evidence to the drinker of the damaging effects of the excessive drinking on work, relationships, and/or health. Modeling such persistence in rodents has been uncommon to date. New genetic animal models include lines of mice selectively bred for chronic high drinking, and other bred for high binge-like drinking. We have a much more clear idea now about some important experiments remaining to be performed. PMID:25306777

Prediction of thyroid C-cell carcinogenicity after chronic administration of GLP1-R agonists in rodents.

PubMed

van den Brink, Willem; Emerenciana, Annette; Bellanti, Francesco; Della Pasqua, Oscar; van der Laan, Jan Willem

2017-04-01

Increased incidence of C-cell carcinogenicity has been observed for glucagon-like-protein-1 receptor (GLP-1r) agonists in rodents. It is suggested that the duration of exposure is an indicator of carcinogenic potential in rodents of the different products on the market. Furthermore, the role of GLP-1-related mechanisms in the induction of C-cell carcinogenicity has gained increased attention by regulatory agencies. This study proposes an integrative pharmacokinetic/pharmacodynamic (PKPD) framework to identify explanatory factors and characterize differences in carcinogenic potential of the GLP-1r agonist products. PK models for four products (exenatide QW (once weekly), exenatide BID (twice daily), liraglutide and lixisenatide) were developed using nonlinear mixed effects modelling. Predicted exposure was subsequently linked to GLP-1r stimulation using in vitro GLP-1r potency data. A logistic regression model was then applied to exenatide QW and liraglutide data to assess the relationship between GLP-1r stimulation and thyroid C-cell hyperplasia incidence as pre-neoplastic predictor of a carcinogenic response. The model showed a significant association between predicted GLP-1r stimulation and C-cell hyperplasia after 2years of treatment. The predictive performance of the model was evaluated using lixisenatide, for which hyperplasia data were accurately described during the validation step. The use of a model-based approach provided insight into the relationship between C-cell hyperplasia and GLP-1r stimulation for all four products, which is not possible with traditional data analysis methods. It can be concluded that both pharmacokinetics (exposure) and pharmacodynamics (potency for GLP-1r) factors determine C-cell hyperplasia incidence in rodents. Our work highlights the pharmacological basis for GLP-1r agonist-induced C-cell carcinogenicity. The concept is promising for application to other drug classes. Copyright © 2017 Elsevier Inc. All rights reserved.

Cognitive and behavioral evaluation of nutritional interventions in rodent models of brain aging and dementia

PubMed Central

Wahl, Devin; Coogan, Sean CP; Solon-Biet, Samantha M; de Cabo, Rafael; Haran, James B; Raubenheimer, David; Cogger, Victoria C; Mattson, Mark P; Simpson, Stephen J; Le Couteur, David G

2017-01-01

Evaluation of behavior and cognition in rodent models underpins mechanistic and interventional studies of brain aging and neurodegenerative diseases, especially dementia. Commonly used tests include Morris water maze, Barnes maze, object recognition, fear conditioning, radial arm water maze, and Y maze. Each of these tests reflects some aspects of human memory including episodic memory, recognition memory, semantic memory, spatial memory, and emotional memory. Although most interventional studies in rodent models of dementia have focused on pharmacological agents, there are an increasing number of studies that have evaluated nutritional interventions including caloric restriction, intermittent fasting, and manipulation of macronutrients. Dietary interventions have been shown to influence various cognitive and behavioral tests in rodents indicating that nutrition can influence brain aging and possibly neurodegeneration. PMID:28932108

The roots of empathy: through the lens of rodent models

PubMed Central

Meyza, K.Z.; Bartal, I. Ben-Ami; Monfils, M.H.; Panksepp, J.B.; Knapska, E.

2016-01-01

Empathy is a phenomenon often considered dependent on higher-order emotional control and an ability to relate to the emotional state of others. It is, by many, attributed only to species having well-developed cortical circuits capable of performing such complex tasks. However, over the years, a wealth of data has been accumulated showing that rodents are capable not only of sharing emotional states of their conspecifics, but also of prosocial behavior driven by such shared experiences. The study of rodent empathic behaviors is only now becoming an independent research field. Relevant animal models allow precise manipulation of neural networks, thereby offering insight into the foundations of empathy in the mammalian brains. Here we review the data on empathic behaviors in rat and mouse models, their neurobiological and neurophysiological correlates, and the factors influencing these behaviors. We discuss how simple rodent models of empathy enhance our understanding of how brain controls empathic behaviors. PMID:27825924

A Systematic Review of Fetal Genes as Biomarkers of Cardiac Hypertrophy in Rodent Models of Diabetes

PubMed Central

2014-01-01

Pathological cardiac hypertrophy activates a suite of genes called the fetal gene program (FGP). Pathological hypertrophy occurs in diabetic cardiomyopathy (DCM); therefore, the FGP is widely used as a biomarker of DCM in animal studies. However, it is unknown whether the FGP is a consistent marker of hypertrophy in rodent models of diabetes. Therefore, we analyzed this relationship in 94 systematically selected studies. Results showed that diabetes induced with cytotoxic glucose analogs such as streptozotocin was associated with decreased cardiac weight, but genetic or diet-induced models of diabetes were significantly more likely to show cardiac hypertrophy (P<0.05). Animal strain, sex, age, and duration of diabetes did not moderate this effect. There were no correlations between the heart weight:body weight index and mRNA or protein levels of the fetal genes α-myosin heavy chain (α-MHC) or β-MHC, sarco/endoplasmic reticulum Ca2+-ATPase, atrial natriuretic peptide (ANP), or brain natriuretic peptide. The only correlates of non-indexed heart weight were the protein levels of α-MHC (Spearman's ρ = 1, P<0.05) and ANP (ρ = −0.73, P<0.05). These results indicate that most commonly measured genes in the FGP are confounded by diabetogenic methods, and are not associated with cardiac hypertrophy in rodent models of diabetes. PMID:24663494

Modelling cognitive affective biases in major depressive disorder using rodents

PubMed Central

Hales, Claire A; Stuart, Sarah A; Anderson, Michael H; Robinson, Emma S J

2014-01-01

Major depressive disorder (MDD) affects more than 10% of the population, although our understanding of the underlying aetiology of the disease and how antidepressant drugs act to remediate symptoms is limited. Major obstacles include the lack of availability of good animal models that replicate aspects of the phenotype and tests to assay depression-like behaviour in non-human species. To date, research in rodents has been dominated by two types of assays designed to test for depression-like behaviour: behavioural despair tests, such as the forced swim test, and measures of anhedonia, such as the sucrose preference test. These tests have shown relatively good predictive validity in terms of antidepressant efficacy, but have limited translational validity. Recent developments in clinical research have revealed that cognitive affective biases (CABs) are a key feature of MDD. Through the development of neuropsychological tests to provide objective measures of CAB in humans, we have the opportunity to use ‘reverse translation’ to develop and evaluate whether similar methods are suitable for research into MDD using animals. The first example of this approach was reported in 2004 where rodents in a putative negative affective state were shown to exhibit pessimistic choices in a judgement bias task. Subsequent work in both judgement bias tests and a novel affective bias task suggest that these types of assay may provide translational methods for studying MDD using animals. This review considers recent work in this area and the pharmacological and translational validity of these new animal models of CABs. Linked Articles This article is part of a themed section on Animal Models in Psychiatry Research. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-20 PMID:24467454

Detection of an enzootic plague focus by serological methods

PubMed Central

Cavanaugh, D. C.; Thorpe, B. D.; Bushman, J. B.; Nicholes, P. S.; Rust, J. H.

1965-01-01

Complement-fixation and haemagglutination tests, utilizing a highly purified, specific Fraction 1 antigen of Pasteurella pestis, have been employed to detect specific plague antibody in the sera of rodents resident in a sylvatic plague focus. The data show that while the isolation of P. pestis is seasonal and rather rare, antibodies can be detected for long periods of time and with great frequency in rodents surviving infection. The authors recommend that serological methods be incorporated into epidemiological surveys and control programmes involving rodent plague. PMID:14310906

DETECTION OF AN ENZOOTIC PLAGUE FOCUS BY SEROLOGICAL METHODS.

PubMed

CAVANAUGH, D C; THORPE, B D; BUSHMAN, J B; NICHOLES, P S; RUST, J H

1965-01-01

Complement-fixation and haemagglutination tests, utilizing a highly purified, specific Fraction 1 antigen of Pasteurella pestis, have been employed to detect specific plague antibody in the sera of rodents resident in a sylvatic plague focus. The data show that while the isolation of P. pestis is seasonal and rather rare, antibodies can be detected for long periods of time and with great frequency in rodents surviving infection. The authors recommend that serological methods be incorporated into epidemiological surveys and control programmes involving rodent plague.

Habitat evaluation for outbreak of Yangtze voles (Microtus fortis) and management implications.

PubMed

Xu, Zhenggang; Zhao, Yunlin; Li, Bo; Zhang, Meiwen; Shen, Guo; Wang, Yong

2015-05-01

Rodent pests severely damage agricultural crops. Outbreak risk models of rodent pests often do not include sufficient information regarding geographic variation. Habitat plays an important role in rodent-pest outbreak risk, and more information about the relationship between habitat and crop protection is urgently needed. The goal of the present study was to provide an outbreak risk map for the Dongting Lake region and to understand the relationship between rodent-pest outbreak variation and habitat distribution. The main rodent pests in the Dongting Lake region are Yangtze voles (Microtus fortis). These pests cause massive damage in outbreak years, most notably in 2007. Habitat evaluation and ecological details were obtained by analyzing the correlation between habitat suitability and outbreak risk, as indicated by population density and historical events. For the source-sink population, 96.18% of Yangtze vole disaster regions were covered by a 10-km buffer zone of suitable habitat in 2007. Historical outbreak frequency and peak population density were significantly correlated with the proportion of land covered by suitable habitat (r = 0.68, P = 0.04 and r = 0.76, P = 0.03, respectively). The Yangtze vole population tends to migrate approximately 10 km in outbreak years. Here, we propose a practical method for habitat evaluation that can be used to create integrated pest management plans for rodent pests when combined with basic information on the biology, ecology and behavior of the target species. © 2014 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and Wiley Publishing Asia Pty Ltd.

Evaluation on the effectiveness of actions for controlling infestation by rodents in Campo Limpo region, Sao Paulo Municipality, Brazil.

PubMed

de Masi, Eduardo; Vilaça, Pedro José; Razzolini, Maria Tereza Pepe

2009-08-01

Rodents are responsible for the transmission of more than 60 diseases both to human beings and to domestic animals. The increase in rodent infestation in a given area brings several health problems to the nearby population. Thus, when infestation increases, it is time to take intervention measures. Although many countries have implemented programs aimed at controlling rodent infestation, literature on studies evaluating the effectiveness of intervention measures in urban areas is scarce. Aimed at contributing to the understanding of rodents' population dynamics in urban areas, the objective of this study was to evaluate the effectiveness of the control methods proposed by "Programa de Vigilancia e Controle de Roedores do Municipio de Sao Paulo" (Program for Rodents Surveillance and Control in Sao Paulo Municipality), conducted on Jardim Comercial District. As a first step, a survey to assess infestation rates was conducted in 1529 dwellings located in the area studied. After that, a chemical control upon rodents was accomplished in every dwelling infested. One week and six months after completion of control measures, a new evaluation on infestation rates was carried out, in order to verify the effectiveness of the procedures taken and to estimate the re-infestation capacity. Initial infestation rate was 40.0%, and the final infestation rate, 14.4%. Therefore, the effectiveness of the control methods utilized was 63.8%. It can thus be concluded that the control methods applied were quite effective.

Testing the limits of Rodent Sperm Analysis: azoospermia in an otherwise healthy wild rodent population.

PubMed

Tannenbaum, Lawrence V; Thran, Brandolyn H; Willams, Keith J

2009-01-01

By comparing the sperm parameters of small rodents trapped at contaminated terrestrial sites and nearby habitat-matched noncontaminated locations, the patent-pending Rodent Sperm Analysis (RSA) method provides a direct health status appraisal for the maximally chemical-exposed mammalian ecological receptor in the wild. RSA outcomes have consistently allowed for as definitive determinations of receptor health as are possible at the present time, thereby streamlining the ecological risk assessment (ERA) process. Here, we describe the unanticipated discovery, at a contaminated US EPA Superfund National Priorities List site, of a population of Hispid cotton rats (Sigmodon hispidus), with a high percentage of adult males lacking sperm entirely (azoospermia). In light of the RSA method's role in streamlining ERAs and in bringing contaminated Superfund-type site investigations to closure, we consider the consequences of the discovery. The two matters specifically discussed are (1) the computation of a population's average sperm count where azoospermia is present and (2) the merits of the RSA method and its sperm parameter thresholds-for-effect when azoospermia is masked in an otherwise apparently healthy rodent population.

Methods Used to Evaluate Pain Behaviors in Rodents

PubMed Central

Deuis, Jennifer R.; Dvorakova, Lucie S.; Vetter, Irina

2017-01-01

Rodents are commonly used to study the pathophysiological mechanisms of pain as studies in humans may be difficult to perform and ethically limited. As pain cannot be directly measured in rodents, many methods that quantify “pain-like” behaviors or nociception have been developed. These behavioral methods can be divided into stimulus-evoked or non-stimulus evoked (spontaneous) nociception, based on whether or not application of an external stimulus is used to elicit a withdrawal response. Stimulus-evoked methods, which include manual and electronic von Frey, Randall-Selitto and the Hargreaves test, were the first to be developed and continue to be in widespread use. However, concerns over the clinical translatability of stimulus-evoked nociception in recent years has led to the development and increasing implementation of non-stimulus evoked methods, such as grimace scales, burrowing, weight bearing and gait analysis. This review article provides an overview, as well as discussion of the advantages and disadvantages of the most commonly used behavioral methods of stimulus-evoked and non-stimulus-evoked nociception used in rodents. PMID:28932184

Learning to recognize rat social behavior: Novel dataset and cross-dataset application.

PubMed

Lorbach, Malte; Kyriakou, Elisavet I; Poppe, Ronald; van Dam, Elsbeth A; Noldus, Lucas P J J; Veltkamp, Remco C

2018-04-15

Social behavior is an important aspect of rodent models. Automated measuring tools that make use of video analysis and machine learning are an increasingly attractive alternative to manual annotation. Because machine learning-based methods need to be trained, it is important that they are validated using data from different experiment settings. To develop and validate automated measuring tools, there is a need for annotated rodent interaction datasets. Currently, the availability of such datasets is limited to two mouse datasets. We introduce the first, publicly available rat social interaction dataset, RatSI. We demonstrate the practical value of the novel dataset by using it as the training set for a rat interaction recognition method. We show that behavior variations induced by the experiment setting can lead to reduced performance, which illustrates the importance of cross-dataset validation. Consequently, we add a simple adaptation step to our method and improve the recognition performance. Most existing methods are trained and evaluated in one experimental setting, which limits the predictive power of the evaluation to that particular setting. We demonstrate that cross-dataset experiments provide more insight in the performance of classifiers. With our novel, public dataset we encourage the development and validation of automated recognition methods. We are convinced that cross-dataset validation enhances our understanding of rodent interactions and facilitates the development of more sophisticated recognition methods. Combining them with adaptation techniques may enable us to apply automated recognition methods to a variety of animals and experiment settings. Copyright © 2017 Elsevier B.V. All rights reserved.

A NEW METHOD TO QUANTIFY CORE TEMPERATURE INSTABILITY IN RODENTS.

EPA Science Inventory

Methods to quantify instability of autonomic systems such as temperature regulation should be important in toxicant and drug safety studies. Stability of core temperature (Tc) in laboratory rodents is susceptible to a variety of stimuli. Calculating the temperature differential o...

Long-term Continuous EEG Monitoring in Small Rodent Models of Human Disease Using the Epoch Wireless Transmitter System

PubMed Central

Zayachkivsky, Andrew; Lehmkuhle, Mark J.; Dudek, F. Edward

2015-01-01

Many progressive neurologic diseases in humans, such as epilepsy, require pre-clinical animal models that slowly develop the disease in order to test interventions at various stages of the disease process. These animal models are particularly difficult to implement in immature rodents, a classic model organism for laboratory study of these disorders. Recording continuous EEG in young animal models of seizures and other neurological disorders presents a technical challenge due to the small physical size of young rodents and their dependence on the dam prior to weaning. Therefore, there is not only a clear need for improving pre-clinical research that will better identify those therapies suitable for translation to the clinic but also a need for new devices capable of recording continuous EEG in immature rodents. Here, we describe the technology behind and demonstrate the use of a novel miniature telemetry system, specifically engineered for use in immature rats or mice, which is also effective for use in adult animals. PMID:26274779

The valproic acid-induced rodent model of autism.

PubMed

Nicolini, Chiara; Fahnestock, Margaret

2018-01-01

Autism is a lifelong neurodevelopmental disorder characterized by impairments in social communication and interaction and by repetitive patterns of behavior, interests and activities. While autism has a strong genetic component, environmental factors including toxins, pesticides, infection and drugs are known to confer autism susceptibility, likely by inducing epigenetic changes. In particular, exposure to valproic acid (VPA) during pregnancy has been demonstrated to increase the risk of autism in children. Furthermore, rodents prenatally exposed to this drug display behavioral phenotypes characteristics of the human condition. Indeed, in utero exposure of rodents to VPA represents a robust model of autism exhibiting face, construct and predictive validity. This model might better represent the many cases of idiopathic autism which are of environmental/epigenetic origins than do transgenic models carrying mutations in single autism-associated genes. The VPA model provides a valuable tool to investigate the neurobiology underlying autistic behavior and to screen for novel therapeutics. Here we review the VPA-induced rodent model of autism, highlighting its importance and reliability as an environmentally-induced animal model of autism. Copyright © 2017 Elsevier Inc. All rights reserved.

An in-vitro-in-vivo model for the transdermal delivery of cholecalciferol for the purposes of rodent management.

PubMed

Davies, J; Ingham, A

2015-06-20

The natural selection of anticoagulant resistant rats has resulted in a need for an alternative to anticoagulant rodenticides which differs in both active ingredient and in the method of dosing. Cholecalciferol toxicity to rodents using the dermal route is demonstrated using a variety of penetration enhancing formulations in two in-vitro models and finally in-vivo. A 1 ml dose of 50/50 (v/v) DMSO/ethanol containing 15% (v/v) PEG 200 and 20% (w/v) cholecalciferol was judged as 'sufficiently effective' in line with the European Union's Biocidal Products Regulation (No. 528/2012) during in-vivo studies. This dose was found to cause 100% mortality in a rat population in 64.4h (± 22h). Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

The Serotonin Transporter and Early Life Stress: Translational Perspectives

PubMed Central

Houwing, Danielle J.; Buwalda, Bauke; van der Zee, Eddy A.; de Boer, Sietse F.; Olivier, Jocelien D. A.

2017-01-01

The interaction between the serotonin transporter (SERT) linked polymorphic region (5-HTTLPR) and adverse early life stressing (ELS) events is associated with enhanced stress susceptibility and risk to develop mental disorders like major depression, anxiety, and aggressiveness. In particular, human short allele carriers are at increased risk. This 5-HTTLPR polymorphism is absent in the rodent SERT gene, but heterozygous SERT knockout rodents (SERT+/−) show several similarities to the human S-allele carrier, therefore creating an animal model of the human situation. Many rodent studies investigated ELS interactions in SERT knockout rodents combined with ELS. However, underlying neuromolecular mechanisms of the (mal)adaptive responses to adversity displayed by SERT rodents remain to be elucidated. Here, we provide a comprehensive review including studies describing mechanisms underlying SERT variation × ELS interactions in rodents. Alterations at the level of translation and transcription but also epigenetic alterations considerably contribute to underlying mechanisms of SERT variation × ELS interactions. In particular, SERT+/− rodents exposed to adverse early rearing environment may be of high translational and predictive value to the more stress sensitive human short-allele carrier, considering the similarity in neurochemical alterations. Therefore, SERT+/− rodents are highly relevant in research that aims to unravel the complex psychopathology of mental disorders. So far, most studies fail to show solid evidence for increased vulnerability to develop affective-like behavior after ELS in SERT+/− rodents. Several reasons may underlie these failures, e.g., (1) stressors used might not be optimal or severe enough to induce maladaptations, (2) effects in females are not sufficiently studied, and (3) few studies include both behavioral manifestations and molecular correlates of ELS-induced effects in SERT+/− rodents. Of course, one should not exclude the (although unlikely) possibility of SERT+/− rodents not being sensitive to ELS. In conclusion, future studies addressing ELS-induced effects in the SERT+/− rodents should extensively study both long-term behavioral and (epi)genetic aspects in both sexes. Finally, further research is warranted using more severe stressors in animal models. From there on, we should be able to draw solid conclusions whether the SERT+/− exposed to ELS is a suitable translational animal model for studying 5-HTTLPR polymorphism and stress interactions. PMID:28491024

Studies into abnormal aggression in humans and rodents: Methodological and translational aspects.

PubMed

Haller, Jozsef

2017-05-01

Here we review the principles based on which aggression is rendered abnormal in humans and laboratory rodents, and comparatively overview the main methodological approaches based on which this behavior is studied in the two categories of subjects. It appears that the discriminating property of abnormal aggression is rule breaking, which renders aggression dysfunctional from the point of view of the perpetrator. We show that rodent models of abnormal aggression were created by the translation of human conditions into rodent equivalents, and discuss how findings obtained with such models may be "translated back" to human conditions when the mechanisms underlying aggression and its possibilities of treatment are investigated. We suggest that the complementary nature of human and rodent research approaches invite a more intense cross-talk between the two sides of aggression research than the one presently observed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Computer simulation analysis of normal and abnormal development of the mammalian diaphragm

PubMed Central

Fisher, Jason C; Bodenstein, Lawrence

2006-01-01

Background Congenital diaphragmatic hernia (CDH) is a birth defect with significant morbidity and mortality. Knowledge of diaphragm morphogenesis and the aberrations leading to CDH is limited. Although classical embryologists described the diaphragm as arising from the septum transversum, pleuroperitoneal folds (PPF), esophageal mesentery and body wall, animal studies suggest that the PPF is the major, if not sole, contributor to the muscular diaphragm. Recently, a posterior defect in the PPF has been identified when the teratogen nitrofen is used to induce CDH in fetal rodents. We describe use of a cell-based computer modeling system (Nudge++™) to study diaphragm morphogenesis. Methods and results Key diaphragmatic structures were digitized from transverse serial sections of paraffin-embedded mouse embryos at embryonic days 11.5 and 13. Structure boundaries and simulated cells were combined in the Nudge++™ software. Model cells were assigned putative behavioral programs, and these programs were progressively modified to produce a diaphragm consistent with the observed anatomy in rodents. Homology between our model and recent anatomical observations occurred under the following simulation conditions: (1) cell mitoses are restricted to the edge of growing tissue; (2) cells near the chest wall remain mitotically active; (3) mitotically active non-edge cells migrate toward the chest wall; and (4) movement direction depends on clonal differentiation between anterior and posterior PPF cells. Conclusion With the PPF as the sole source of mitotic cells, an early defect in the PPF evolves into a posteromedial diaphragm defect, similar to that of the rodent nitrofen CDH model. A posterolateral defect, as occurs in human CDH, would be more readily recreated by invoking other cellular contributions. Our results suggest that recent reports of PPF-dominated diaphragm morphogenesis in the rodent may not be strictly applicable to man. The ability to recreate a CDH defect using a combination of experimental data and testable hypotheses gives impetus to simulation modeling as an adjunct to experimental analysis of diaphragm morphogenesis. PMID:16483386

Structured networks support sparse traveling waves in rodent somatosensory cortex.

PubMed

Moldakarimov, Samat; Bazhenov, Maxim; Feldman, Daniel E; Sejnowski, Terrence J

2018-05-15

Neurons responding to different whiskers are spatially intermixed in the superficial layer 2/3 (L2/3) of the rodent barrel cortex, where a single whisker deflection activates a sparse, distributed neuronal population that spans multiple cortical columns. How the superficial layer of the rodent barrel cortex is organized to support such distributed sensory representations is not clear. In a computer model, we tested the hypothesis that sensory representations in L2/3 of the rodent barrel cortex are formed by activity propagation horizontally within L2/3 from a site of initial activation. The model explained the observed properties of L2/3 neurons, including the low average response probability in the majority of responding L2/3 neurons, and the existence of a small subset of reliably responding L2/3 neurons. Sparsely propagating traveling waves similar to those observed in L2/3 of the rodent barrel cortex occurred in the model only when a subnetwork of strongly connected neurons was immersed in a much larger network of weakly connected neurons.

Automated 3-D cell counting method for grading uveitis of rodent eye in vivo with optical coherence tomograph.

PubMed

Choi, Woo June; Pepple, Kathryn L; Wang, Ruikang K

2018-05-24

In preclinical vision research, cell grading in small animal models is essential for the quantitative evaluation of intraocular inflammation. Here, we present a new and practical optical coherence tomography (OCT) image analysis method for the automated detection and counting of aqueous cells in the anterior chamber (AC) of a rodent model of uveitis. Anterior segment OCT (AS-OCT) images are acquired with a 100kHz swept-source OCT (SS-OCT) system. The proposed method consists of two steps. In the first step, we first despeckle and binarize each OCT image. After removing AS structures in the binary image, we then apply area thresholding to isolate cell-like objects. Potential cell candidates are selected based on their best fit to roundness. The second step performs the cell counting within the whole AC, in which additional cell tracking analysis is conducted on the successive OCT images to eliminate redundancy in cell counting. Finally, 3-D cell grading using the proposed method is demonstrated in longitudinal OCT imaging of a mouse model of anterior uveitis in vivo. Rendering of anterior segment (orange) of mouse eye and automatically counted anterior chamber cells (green). Inset is a top view of the rendering, showing the cell distribution across the anterior chamber. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Impact of parity on ewe vaginal mechanical properties relative to the nonhuman primate and rodent

PubMed Central

Knight, Katrina M.; Moalli, Pamela A.; Nolfi, Alexis; Palcsey, Stacy; Barone, William R.

2016-01-01

Introduction and hypothesis Parity is the leading risk factor for the development of pelvic organ prolapse. To assess the impact of pregnancy and delivery on vaginal tissue, researchers commonly use nonhuman primate (NHP) and rodent models. The purpose of this study was to evaluate the ewe as an alternative model by investigating the impact of parity on the ewe vaginal mechanical properties and collagen structure. Methods Mechanical properties of 15 nulliparous and parous ewe vaginas were determined via uniaxial tensile tests. Collagen content was determined by hydroxyproline assay and collagen fiber thickness was analyzed using picrosirius red staining. Outcome measures were compared using Independent samples t or Mann–Whitney U tests. ANOVA (Gabriel’s pairwise post-hoc test) or the Welch Alternative for the F-ratio (Games Howell post-hoc test) was used to compare data with previously published NHP and rodent data. Results Vaginal tissue from the nulliparous ewe had a higher tangent modulus and tensile strength compared with the parous ewe (p < 0.025). The parous ewe vagina elongated 42 % more than the nulliparous ewe vagina (p = 0.015). No significant differences were observed in collagen structure among ewe vaginas. The tangent modulus of the nulliparous ewe vagina was not different from that of the NHP or rodent (p = 0.290). Additionally, the tangent moduli of the parous ewe and NHP vaginas did not differ (p = 0.773). Conclusions Parity has a negative impact on the mechanical properties of the ewe vagina, as also observed in the NHP. The ewe may serve as an alternative model for studying parity and ultimately prolapse development. PMID:26872644

Evaluating rodent motor functions: Which tests to choose?

PubMed

Schönfeld, Lisa-Maria; Dooley, Dearbhaile; Jahanshahi, Ali; Temel, Yasin; Hendrix, Sven

2017-12-01

Damage to the motor cortex induced by stroke or traumatic brain injury (TBI) can result in chronic motor deficits. For the development and improvement of therapies, animal models which possess symptoms comparable to the clinical population are used. However, the use of experimental animals raises valid ethical and methodological concerns. To decrease discomfort by experimental procedures and to increase the quality of results, non-invasive and sensitive rodent motor tests are needed. A broad variety of rodent motor tests are available to determine deficits after stroke or TBI. The current review describes and evaluates motor tests that fall into three categories: Tests to evaluate fine motor skills and grip strength, tests for gait and inter-limb coordination and neurological deficit scores. In this review, we share our thoughts on standardized data presentation to increase data comparability between studies. We also critically evaluate current methods and provide recommendations for choosing the best behavioral test for a new research line. Copyright © 2017 Elsevier Ltd. All rights reserved.

Protozoan Parasites of Rodents and Their Zoonotic Significance in Boyer-Ahmad District, Southwestern Iran

PubMed Central

Seifollahi, Zeinab; Motazedian, Mohammad Hossein; Asgari, Qasem; Ranjbar, Mohammad Javad; Abdolahi Khabisi, Samaneh

2016-01-01

Backgrounds. Wild rodents are reservoirs of various zoonotic diseases, such as toxoplasmosis, babesiosis, and leishmaniasis. The current study aimed to assess the protozoan infection of rodents in Boyer-Ahmad district, southwestern Iran. Materials and Methods. A total of 52 rodents were collected from different parts of Boyer-Ahmad district, in Kohgiluyeh and Boyer-Ahmad province, using Sherman live traps. Each rodent was anesthetized with ether, according to the ethics of working with animals, and was dissected. Samples were taken from various tissues and stool samples were collected from the contents of the colon and small intestines. Moreover, 2 to 5 mL of blood was taken from each of the rodents and the sera were examined for anti-Leishmania antibodies, by ELISA, or anti-T. gondii antibodies, by modified agglutination test (MAT). DNA was extracted from brain tissue samples of each rodent and PCR was used to identify the DNA of T. gondii. Results. Of the 52 stool samples of rodents studied by parasitological methods, intestinal protozoa infection was seen in 28 cases (53.8%). From 52 rodents, 19 (36.5%) were infected with Trichomonas, 10 (19.2%) with Giardia muris, and 11 (21.2%) with Entamoeba spp. Also, 10 cases (19.2%) were infected with Blastocystis, 3 (5.8%) were infected with Chilomastix, 7 (13.5%) were infected with Endolimax, 1 (1.9%) was infected with Retortamonas, 3 (5.77%) were infected with T. gondii, and 6 (11.54%) were infected with Trypanosoma lewisi. Antibodies to T. gondii were detected in the sera of 5 (9.61%) cases. Results of the molecular study showed T. gondii infection in 3 (5.77%) of the rodents. Findings of this study showed that rodents in Kohgiluyeh and Boyer-Ahmad province, southwestern Iran, are infected with several blood and intestinal parasites; some of them might be potential risks to residents and domestic animals in the region. PMID:26998380

Integrative rodent models for assessing male reproductive toxicity of environmental endocrine active substances

PubMed Central

Auger, Jacques; Eustache, Florence; Rouiller-Fabre, Virginie; Canivenc-Lavier, Marie Chantal; Livera, Gabriel

2014-01-01

In the present review, we first summarize the main benefits, limitations and pitfalls of conventional in vivo approaches to assessing male reproductive structures and functions in rodents in cases of endocrine active substance (EAS) exposure from the postulate that they may provide data that can be extrapolated to humans. Then, we briefly present some integrated approaches in rodents we have recently developed at the organism level. We particularly focus on the possible effects and modes of action (MOA) of these substances at low doses and in mixtures, real-life conditions and at the organ level, deciphering the precise effects and MOA on the fetal testis. It can be considered that the in vivo experimental EAS exposure of rodents remains the first choice for studies and is a necessary tool (together with the epidemiological approach) for understanding the reproductive effects and MOA of EASs, provided the pitfalls and limitations of the rodent models are known and considered. We also provide some evidence that classical rodent models may be refined for studying the multiple consequences of EAS exposure, not only on the reproductive axis but also on various hormonally regulated organs and tissues, among which several are implicated in the complex process of mammalian reproduction. Such models constitute an interesting way of approaching human exposure conditions. Finally, we show that organotypic culture models are powerful complementary tools, especially when focusing on the MOA. All these approaches have contributed in a combinatorial manner to a better understanding of the impact of EAS exposure on human reproduction. PMID:24369134

Unpredictability of escape trajectory explains predator evasion ability and microhabitat preference of desert rodents.

PubMed

Moore, Talia Y; Cooper, Kimberly L; Biewener, Andrew A; Vasudevan, Ramanarayan

2017-09-05

Mechanistically linking movement behaviors and ecology is key to understanding the adaptive evolution of locomotion. Predator evasion, a behavior that enhances fitness, may depend upon short bursts or complex patterns of locomotion. However, such movements are poorly characterized by existing biomechanical metrics. We present methods based on the entropy measure of randomness from Information Theory to quantitatively characterize the unpredictability of non-steady-state locomotion. We then apply the method by examining sympatric rodent species whose escape trajectories differ in dimensionality. Unlike the speed-regulated gait use of cursorial animals to enhance locomotor economy, bipedal jerboa (family Dipodidae) gait transitions likely enhance maneuverability. In field-based observations, jerboa trajectories are significantly less predictable than those of quadrupedal rodents, likely increasing predator evasion ability. Consistent with this hypothesis, jerboas exhibit lower anxiety in open fields than quadrupedal rodents, a behavior that varies inversely with predator evasion ability. Our unpredictability metric expands the scope of quantitative biomechanical studies to include non-steady-state locomotion in a variety of evolutionary and ecologically significant contexts.Biomechanical understanding of animal gait and maneuverability has primarily been limited to species with more predictable, steady-state movement patterns. Here, the authors develop a method to quantify movement predictability, and apply the method to study escape-related movement in several species of desert rodents.

The NEWMEDS rodent touchscreen test battery for cognition relevant to schizophrenia.

PubMed

Hvoslef-Eide, M; Mar, A C; Nilsson, S R O; Alsiö, J; Heath, C J; Saksida, L M; Robbins, T W; Bussey, T J

2015-11-01

The NEWMEDS initiative (Novel Methods leading to New Medications in Depression and Schizophrenia, http://www.newmeds-europe.com ) is a large industrial-academic collaborative project aimed at developing new methods for drug discovery for schizophrenia. As part of this project, Work package 2 (WP02) has developed and validated a comprehensive battery of novel touchscreen tasks for rats and mice for assessing cognitive domains relevant to schizophrenia. This article provides a review of the touchscreen battery of tasks for rats and mice for assessing cognitive domains relevant to schizophrenia and highlights validation data presented in several primary articles in this issue and elsewhere. The battery consists of the five-choice serial reaction time task and a novel rodent continuous performance task for measuring attention, a three-stimulus visual reversal and the serial visual reversal task for measuring cognitive flexibility, novel non-matching to sample-based tasks for measuring spatial working memory and paired-associates learning for measuring long-term memory. The rodent (i.e. both rats and mice) touchscreen operant chamber and battery has high translational value across species due to its emphasis on construct as well as face validity. In addition, it offers cognitive profiling of models of diseases with cognitive symptoms (not limited to schizophrenia) through a battery approach, whereby multiple cognitive constructs can be measured using the same apparatus, enabling comparisons of performance across tasks. This battery of tests constitutes an extensive tool package for both model characterisation and pre-clinical drug discovery.

Problems associated with the control of rodents in tropical Africa

PubMed Central

Gratz, N. G.; Arata, A. A.

1975-01-01

As elsewhere in the world, rodents are responsible for very considerable economic losses in tropical Africa because of their depredations on both growing crops and stored food products. Unfortunately, few accurate data are available on the extent of these losses but there is evidence that they are considerable. The public health importance of rodents, both as reservoirs and vectors of disease in tropical Africa, is also great; plague, leptospirosis, murine typhus, and Lassa fever are among the diseases associated with rodent hosts. Scientifically based rodent control programmes have been carried out in very few areas of Africa and there is urgent need for studies and demonstrations on rodent control in both urban and rural areas. The problems likely to be encountered are reviewed and methods of control proposed. PMID:1085224

Neuromuscular electrical stimulation of the hindlimb muscles for movement therapy in a rodent model.

PubMed

Ichihara, Kazuhiko; Venkatasubramanian, Ganapriya; Abbas, James J; Jung, Ranu

2009-01-30

Neuromuscular electrical stimulation (NMES) can provide functional movements in people after central nervous system injury. The neuroplastic effects of long-term NMES-induced repetitive limb movement are not well understood. A rodent model of neurotrauma in which NMES can be implemented may be effective for such investigations. We present a rodent model for NMES of the flexor and extensor muscles of the hip, knee, and ankle hindlimb muscles. Custom fabricated intramuscular stimulating electrodes for rodents were implanted near identified motor points of targeted muscles in ten adult, female Long Evans rats. The effects of altering NMES pulse stimulation parameters were characterized using strength duration curves, isometric joint torque recruitment curves and joint angle measures. The data indicate that short pulse widths have the advantage of producing graded torque recruitment curves when current is used as the control parameter. A stimulus frequency of 75 Hz or more produces fused contractions. The data demonstrate ability to accurately implant the electrodes and obtain selective, graded, repeatable, strong muscle contractions. Knee and ankle angular excursions comparable to those obtained in normal treadmill walking in the same rodent species can be obtained by stimulating the target muscles. Joint torques (normalized to body weight) obtained were larger than those reported in the literature for small tailed therian mammals and for peak isometric ankle plantarflexion in a different rodent species. This model system could be used for investigations of NMES assisted hindlimb movement therapy.

Can we use mice to study schizophrenia?

PubMed

Canetta, Sarah; Kellendonk, Christoph

2018-03-19

The validity of rodent models for the study of psychiatric disorders is controversial. Despite great efforts from academic institutions and pharmaceutical companies, as of today, no major therapeutic intervention has been developed for the treatment of psychiatric disorders based on mechanistic insights from rodent models. Here, we argue that despite these historical shortcomings, rodent studies are nevertheless instrumental for identifying neuronal circuit mechanisms underlying behaviours that are affected in psychiatric disorders. Focusing on schizophrenia, we will give four examples of rodent models that were generated based on genetic and environmental risk factors or pathophysiological evidence as entry points. We will then discuss how circuit analysis in these specific examples can be used for testing hypotheses about neuronal mechanisms underlying symptoms of schizophrenia, which will then guide the development of new therapies.This article is part of a discussion meeting issue 'Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists'. © 2018 The Author(s).

A Novel Two-Step Hierarchical Quantitative Structure–Activity Relationship Modeling Work Flow for Predicting Acute Toxicity of Chemicals in Rodents

PubMed Central

Zhu, Hao; Ye, Lin; Richard, Ann; Golbraikh, Alexander; Wright, Fred A.; Rusyn, Ivan; Tropsha, Alexander

2009-01-01

Background Accurate prediction of in vivo toxicity from in vitro testing is a challenging problem. Large public–private consortia have been formed with the goal of improving chemical safety assessment by the means of high-throughput screening. Objective A wealth of available biological data requires new computational approaches to link chemical structure, in vitro data, and potential adverse health effects. Methods and results A database containing experimental cytotoxicity values for in vitro half-maximal inhibitory concentration (IC50) and in vivo rodent median lethal dose (LD50) for more than 300 chemicals was compiled by Zentralstelle zur Erfassung und Bewertung von Ersatz- und Ergaenzungsmethoden zum Tierversuch (ZEBET; National Center for Documentation and Evaluation of Alternative Methods to Animal Experiments). The application of conventional quantitative structure–activity relationship (QSAR) modeling approaches to predict mouse or rat acute LD50 values from chemical descriptors of ZEBET compounds yielded no statistically significant models. The analysis of these data showed no significant correlation between IC50 and LD50. However, a linear IC50 versus LD50 correlation could be established for a fraction of compounds. To capitalize on this observation, we developed a novel two-step modeling approach as follows. First, all chemicals are partitioned into two groups based on the relationship between IC50 and LD50 values: One group comprises compounds with linear IC50 versus LD50 relationships, and another group comprises the remaining compounds. Second, we built conventional binary classification QSAR models to predict the group affiliation based on chemical descriptors only. Third, we developed k-nearest neighbor continuous QSAR models for each subclass to predict LD50 values from chemical descriptors. All models were extensively validated using special protocols. Conclusions The novelty of this modeling approach is that it uses the relationships between in vivo and in vitro data only to inform the initial construction of the hierarchical two-step QSAR models. Models resulting from this approach employ chemical descriptors only for external prediction of acute rodent toxicity. PMID:19672406

Costs of rodent control in pine regeneration in California

Treesearch

Richard D. Cosens; David Tackle

1950-01-01

The control of seed-eating rodents, combined with the proper method of cutting and site preparation, appears essential to get the maximum results of natural seeding of pine. One method of control is by treating the area to be regenerated with lethal bait prior to seedfall. This note describes such a method and costs of treatment for the westside and eastside Sierran...

CHEMICAL AND RADIATION LEUKEMOGENESIS IN HUMANS AND RODENTS AND THE VALUE OF RODENT MODELS FOR ASSESSING RISKS OF LYMPHOHEMATOPOIETIC CANCERS

EPA Science Inventory

This report is intended to provide an up-to-date overview of the lymphoid and hematopoietic diseases induced in humans and rodents following exposure to chemical agents. It includes a brief introduction to hematopoiesis and leukemia-inducing agents and their effects in mice and r...

Vaccines and Animal Models for Arboviral Encephalitides

DTIC Science & Technology

2003-01-01

equine encephalitis Rodents Aedes, Culex mosquitoes and other species Central and South America, southern Florida IND Western equine encephalitis Birds...former Soviet Union Licensed Louping ill Birds Britain Murray Valley encephalitis Birds Culex mosquitoes Australia, New Guinea None Powassan Rodents ...Birds Culex mosquitoes North and South America None Tick-borne encephalitis Rodents Ixodes, Dermacentor, Haemaphysalis ticks Europe, Russia, former

Rodent repellent studies. IV. Preparation and properties of trinitrobenzene-aryl amine complexes

USGS Publications Warehouse

DeWitt, J.B.; Bellack, E.; Welch, J.F.

1953-01-01

Data are presented on methods of preparation, chemical arid physical characteristics, toxicity, and repellency to rodents of complexes of symmetrical trinitrohenzene with various aromatic amines: When applied in suitable carriers or incorporated in plastic .films, members of this series ofmaterials were shown to offer significant increases in time required by wild rodents to damage common packaging materials.

Behavioral methods to study anxiety in rodents

PubMed Central

Lezak, Kimberly R.; Missig, Galen; Carlezon Jr, William A.

2017-01-01

Stress is a precipitating factor for anxiety-related disorders, which are among the leading forms of psychiatric illness and impairment in the modern world. Rodent-based behavioral tests and models are widely used to understand the mechanisms by which stress triggers anxiety-related behaviors and to identify new treatments for anxiety-related disorders. Although substantial progress has been made and many of the key neural circuits and molecular pathways mediating stress responsiveness have been characterized, these advances have thus far failed to translate into fundamentally new treatments that are safer and more efficacious in humans. The purpose of this article is to describe methods that have been historically used for this type of research and to highlight new approaches that align with recent conceptualizations of disease symptomatology and that may ultimately prove to be more fruitful in facilitating the development of improved therapeutics. PMID:28867942

Construction and Evaluation of Rodent-Specific rTMS Coils.

PubMed

Tang, Alexander D; Lowe, Andrea S; Garrett, Andrew R; Woodward, Robert; Bennett, William; Canty, Alison J; Garry, Michael I; Hinder, Mark R; Summers, Jeffery J; Gersner, Roman; Rotenberg, Alexander; Thickbroom, Gary; Walton, Joseph; Rodger, Jennifer

2016-01-01

Rodent models of transcranial magnetic stimulation (TMS) play a crucial role in aiding the understanding of the cellular and molecular mechanisms underlying TMS induced plasticity. Rodent-specific TMS have previously been used to deliver focal stimulation at the cost of stimulus intensity (12 mT). Here we describe two novel TMS coils designed to deliver repetitive TMS (rTMS) at greater stimulation intensities whilst maintaining spatial resolution. Two circular coils (8 mm outer diameter) were constructed with either an air or pure iron-core. Peak magnetic field strength for the air and iron-cores were 90 and 120 mT, respectively, with the iron-core coil exhibiting less focality. Coil temperature and magnetic field stability for the two coils undergoing rTMS, were similar at 1 Hz but varied at 10 Hz. Finite element modeling of 10 Hz rTMS with the iron-core in a simplified rat brain model suggests a peak electric field of 85 and 12.7 V/m, within the skull and the brain, respectively. Delivering 10 Hz rTMS to the motor cortex of anaesthetized rats with the iron-core coil significantly increased motor evoked potential amplitudes immediately after stimulation (n = 4). Our results suggest these novel coils generate modest magnetic and electric fields, capable of altering cortical excitability and provide an alternative method to investigate the mechanisms underlying rTMS-induced plasticity in an experimental setting.

A Novel Two-Step Hierarchial Quantitative Structure-Activity Relationship Modeling Workflow for Predicting Acute Toxicity of Chemicals in Rodents

EPA Science Inventory

Background: Accurate prediction of in vivo toxicity from in vitro testing is a challenging problem. Large public–private consortia have been formed with the goal of improving chemical safety assessment by the means of high-throughput screening. Methods and results: A database co...

Development of a High-Content Image Analysis Method for Quantifying Synaptic Contacts in Rodent Primary Neuronal Cultures

EPA Science Inventory

Development of the nervous system occurs through a series of critical processes, each of which may be sensitive to disruption by environmental contaminants. In vitro culture of neurons can be used to model these processes and evaluate the potential of chemicals to act as develop...

Prediction of thyroid C-cell carcinogenicity after chronic administration of GLP1-R agonists in rodents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brink, Willem van den; Emerenciana, Annette

Increased incidence of C-cell carcinogenicity has been observed for glucagon-like-protein-1 receptor (GLP-1r) agonists in rodents. It is suggested that the duration of exposure is an indicator of carcinogenic potential in rodents of the different products on the market. Furthermore, the role of GLP-1-related mechanisms in the induction of C-cell carcinogenicity has gained increased attention by regulatory agencies. This study proposes an integrative pharmacokinetic/pharmacodynamic (PKPD) framework to identify explanatory factors and characterize differences in carcinogenic potential of the GLP-1r agonist products. PK models for four products (exenatide QW (once weekly), exenatide BID (twice daily), liraglutide and lixisenatide) were developed using nonlinearmore » mixed effects modelling. Predicted exposure was subsequently linked to GLP-1r stimulation using in vitro GLP-1r potency data. A logistic regression model was then applied to exenatide QW and liraglutide data to assess the relationship between GLP-1r stimulation and thyroid C-cell hyperplasia incidence as pre-neoplastic predictor of a carcinogenic response. The model showed a significant association between predicted GLP-1r stimulation and C-cell hyperplasia after 2 years of treatment. The predictive performance of the model was evaluated using lixisenatide, for which hyperplasia data were accurately described during the validation step. The use of a model-based approach provided insight into the relationship between C-cell hyperplasia and GLP-1r stimulation for all four products, which is not possible with traditional data analysis methods. It can be concluded that both pharmacokinetics (exposure) and pharmacodynamics (potency for GLP-1r) factors determine C-cell hyperplasia incidence in rodents. Our work highlights the pharmacological basis for GLP-1r agonist-induced C-cell carcinogenicity. The concept is promising for application to other drug classes. - Highlights: • An integrative PKPD model is applied to study GLP-1r agonist carcinogenicity. • C-cell carcinogenicity is impacted by both pharmacokinetics and pharmacodynamics. • The relation of GLP-1r stimulation and C-cell hyperplasia appears drug-independent. • Understanding carcinogenic risk needs a pharmacological basis.« less

A Review of Applied Aspects of Dealing with Gut Microbiota Impact on Rodent Models.

PubMed

Hansen, Axel Kornerup; Krych, Łukasz; Nielsen, Dennis Sandris; Hansen, Camilla Hartmann Friis

2015-01-01

The gut microbiota (GM) affects numerous human diseases, as well as rodent models for these. We will review this impact and summarize ways to handle this challenge in animal research. The GM is complex, with the largest fractions being the gram-positive phylum Firmicutes and the gram-negative phylum Bacteroidetes. Other important phyla are the gram-negative phyla Proteobacteria and Verrucomicrobia, and the gram-positive phylum Actinobacteria. GM members influence models for diseases, such as inflammatory bowel diseases, allergies, autoimmunity, cancer, and neuropsychiatric diseases. GM characterization of all individual animals and incorporation of their GM composition in data evaluation may therefore be considered in future protocols. Germfree isolator-housed rodents or rodents made virtually germ free by antibiotic cocktails can be used to study diverse microbial influences on disease expression. Through subsequent inoculation with selected strains or cocktails of microbes, new "defined flora" models can yield valuable knowledge on the impact of the GM, and of specific GM members and their interactions, on important disease phenotypes and mechanisms. Rodent husbandry and microbial quality assurance practices will be important to ensure and confirm appropriate and research relevant GM. © The Author 2015. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Use of Cell Viability Assay Data Improves the Prediction Accuracy of Conventional Quantitative Structure–Activity Relationship Models of Animal Carcinogenicity

PubMed Central

Zhu, Hao; Rusyn, Ivan; Richard, Ann; Tropsha, Alexander

2008-01-01

Background To develop efficient approaches for rapid evaluation of chemical toxicity and human health risk of environmental compounds, the National Toxicology Program (NTP) in collaboration with the National Center for Chemical Genomics has initiated a project on high-throughput screening (HTS) of environmental chemicals. The first HTS results for a set of 1,408 compounds tested for their effects on cell viability in six different cell lines have recently become available via PubChem. Objectives We have explored these data in terms of their utility for predicting adverse health effects of the environmental agents. Methods and results Initially, the classification k nearest neighbor (kNN) quantitative structure–activity relationship (QSAR) modeling method was applied to the HTS data only, for a curated data set of 384 compounds. The resulting models had prediction accuracies for training, test (containing 275 compounds together), and external validation (109 compounds) sets as high as 89%, 71%, and 74%, respectively. We then asked if HTS results could be of value in predicting rodent carcinogenicity. We identified 383 compounds for which data were available from both the Berkeley Carcinogenic Potency Database and NTP–HTS studies. We found that compounds classified by HTS as “actives” in at least one cell line were likely to be rodent carcinogens (sensitivity 77%); however, HTS “inactives” were far less informative (specificity 46%). Using chemical descriptors only, kNN QSAR modeling resulted in 62.3% prediction accuracy for rodent carcinogenicity applied to this data set. Importantly, the prediction accuracy of the model was significantly improved (72.7%) when chemical descriptors were augmented by HTS data, which were regarded as biological descriptors. Conclusions Our studies suggest that combining NTP–HTS profiles with conventional chemical descriptors could considerably improve the predictive power of computational approaches in toxicology. PMID:18414635

Tularemia and plague survey in rodents in an earthquake zone in southeastern Iran

PubMed Central

Gyuranecz, Miklós

2015-01-01

OBJECTIVES: Earthquakes are one the most common natural disasters that lead to increased mortality and morbidity from transmissible diseases, partially because the rodents displaced by an earthquake can lead to an increased rate of disease transmission. The aim of this study was to evaluate the prevalence of plague and tularemia in rodents in the earthquake zones in southeastern Iran. METHODS: In April 2013, a research team was dispatched to explore the possible presence of diseases in rodents displaced by a recent earthquake magnitude 7.7 around the cities of Khash and Saravan in Sistan and Baluchestan Province. Rodents were trapped near and in the earthquake zone, in a location where an outbreak of tularemia was reported in 2007. Rodent serums were tested for a serological survey using an enzyme-linked immunosorbent assay. RESULTS: In the 13 areas that were studied, nine rodents were caught over a total of 200 trap-days. Forty-eight fleas and 10 ticks were obtained from the rodents. The ticks were from the Hyalomma genus and the fleas were from the Xenopsylla genus. All the trapped rodents were Tatera indica. Serological results were negative for plague, but the serum agglutination test was positive for tularemia in one of the rodents. Tatera indica has never been previously documented to be involved in the transmission of tularemia. CONCLUSIONS: No evidence of the plague cycle was found in the rodents of the area, but evidence was found of tularemia infection in rodents, as demonstrated by a positive serological test for tularemia in one rodent. PMID:26602769

Ancient Anxiety Pathways Influence Drosophila Defense Behaviors.

PubMed

Mohammad, Farhan; Aryal, Sameer; Ho, Joses; Stewart, James Charles; Norman, Nurul Ayuni; Tan, Teng Li; Eisaka, Agnese; Claridge-Chang, Adam

2016-04-04

Anxiety helps us anticipate and assess potential danger in ambiguous situations [1-3]; however, the anxiety disorders are the most prevalent class of psychiatric illness [4-6]. Emotional states are shared between humans and other animals [7], as observed by behavioral manifestations [8], physiological responses [9], and gene conservation [10]. Anxiety research makes wide use of three rodent behavioral assays-elevated plus maze, open field, and light/dark box-that present a choice between sheltered and exposed regions [11]. Exposure avoidance in anxiety-related defense behaviors was confirmed to be a correlate of rodent anxiety by treatment with known anxiety-altering agents [12-14] and is now used to characterize anxiety systems. Modeling anxiety with a small neurogenetic animal would further aid the elucidation of its neuronal and molecular bases. Drosophila neurogenetics research has elucidated the mechanisms of fundamental behaviors and implicated genes that are often orthologous across species. In an enclosed arena, flies stay close to the walls during spontaneous locomotion [15, 16], a behavior proposed to be related to anxiety [17]. We tested this hypothesis with manipulations of the GABA receptor, serotonin signaling, and stress. The effects of these interventions were strikingly concordant with rodent anxiety, verifying that these behaviors report on an anxiety-like state. Application of this method was able to identify several new fly anxiety genes. The presence of conserved neurogenetic pathways in the insect brain identifies Drosophila as an attractive genetic model for the study of anxiety and anxiety-related disorders, complementing existing rodent systems. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Rodent phylogeny revised: analysis of six nuclear genes from all major rodent clades

PubMed Central

Blanga-Kanfi, Shani; Miranda, Hector; Penn, Osnat; Pupko, Tal; DeBry, Ronald W; Huchon, Dorothée

2009-01-01

Background Rodentia is the most diverse order of placental mammals, with extant rodent species representing about half of all placental diversity. In spite of many morphological and molecular studies, the family-level relationships among rodents and the location of the rodent root are still debated. Although various datasets have already been analyzed to solve rodent phylogeny at the family level, these are difficult to combine because they involve different taxa and genes. Results We present here the largest protein-coding dataset used to study rodent relationships. It comprises six nuclear genes, 41 rodent species, and eight outgroups. Our phylogenetic reconstructions strongly support the division of Rodentia into three clades: (1) a "squirrel-related clade", (2) a "mouse-related clade", and (3) Ctenohystrica. Almost all evolutionary relationships within these clades are also highly supported. The primary remaining uncertainty is the position of the root. The application of various models and techniques aimed to remove non-phylogenetic signal was unable to solve the basal rodent trifurcation. Conclusion Sequencing and analyzing a large sequence dataset enabled us to resolve most of the evolutionary relationships among Rodentia. Our findings suggest that the uncertainty regarding the position of the rodent root reflects the rapid rodent radiation that occurred in the Paleocene rather than the presence of conflicting phylogenetic and non-phylogenetic signals in the dataset. PMID:19341461

Facial Nerve Repair: Fibrin Adhesive Coaptation versus Epineurial Suture Repair in a Rodent Model

PubMed Central

Knox, Christopher J.; Hohman, Marc H.; Kleiss, Ingrid J.; Weinberg, Julie S.; Heaton, James T.; Hadlock, Tessa A.

2013-01-01

Objectives/Hypothesis Repair of the transected facial nerve has traditionally been accomplished with microsurgical neurorrhaphy; however, fibrin adhesive coaptation (FAC) of peripheral nerves has become increasingly popular over the past decade. We compared functional recovery following suture neurorrhaphy to FAC in a rodent facial nerve model. Study Design Prospective, randomized animal study. Methods Sixteen rats underwent transection and repair of the facial nerve proximal to the pes anserinus. Eight animals underwent epineurial suture (ES) neurorrhaphy, and eight underwent repair with fibrin adhesive (FA). Surgical times were documented for all procedures. Whisking function was analyzed on a weekly basis for both groups across 15 weeks of recovery. Results Rats experienced whisking recovery consistent in time course and degree with prior studies of rodent facial nerve transection and repair. There were no significant differences in whisking amplitude, velocity, or acceleration between suture and FA groups. However, the neurorrhaphy time with FA was 70% shorter than for ES (P < 0.05). Conclusion Although we found no difference in whisking recovery between suture and FA repair of the main trunk of the rat facial nerve, the significantly shorter operative time for FA repair makes this technique an attractive option. The relative advantages of both techniques are discussed. PMID:23188676

Progress in the development of animal models of acute kidney injury and its impact on drug discovery.

PubMed

Sanz, Ana B; Sanchez-Niño, María Dolores; Martín-Cleary, Catalina; Ortiz, Alberto; Ramos, Adrián M

2013-07-01

Acute kidney injury (AKI) is a clinical syndrome characterized by the acute loss of kidney function. AKI is increasingly frequent and is associated with impaired survival and chronic kidney disease progression. Experimental AKI models have contributed to a better understanding of pathophysiological mechanisms but they have not yet resulted in routine clinical application of novel therapeutic approaches. The authors present the advances in experimental AKI models over the last decade. Furthermore, the authors review their current and expected impact on novel drug discovery. New AKI models have been developed in rodents and non-rodents. Non-rodents allow the evaluation of specific aspects of AKI in both bigger animals and simpler organisms such as drosophila and zebrafish. New rodent models have recently reproduced described clinical entities, such as aristolochic and warfarin nephropathies, and have also provided better models for old entities such as thrombotic microangiopathy-induced AKI. Several therapies identified in animal models are now undergoing clinical trials in human AKI, including p53 RNAi and bone-marrow derived mesenchymal stem cells. It is conceivable that further refinement of animal models in combination with ongoing trials and novel trials based on already identified potential targets will eventually yield effective therapies for clinical AKI.

Differential effects of subcutaneous electrical stimulation (SQS) and transcutaneous electrical nerve stimulation (TENS) in rodent models of chronic neuropathic or inflammatory pain.

PubMed

Vera-Portocarrero, Louis P; Cordero, Toni; Billstrom, Tina; Swearingen, Kim; Wacnik, Paul W; Johanek, Lisa M

2013-01-01

Electrical stimulation has been used for many years for the treatment of pain. Present-day research demonstrates that stimulation targets and parameters impact the induction of specific pain-modulating mechanisms. New targets are increasingly being investigated clinically, but the scientific rationale for a particular target is often not well established. This present study compares the behavioral effects of targeting peripheral axons by electrode placement in the subcutaneous space vs. electrode placement on the surface of the skin in a rodent model. Rodent models of inflammatory and neuropathic pain were used to investigate subcutaneous electrical stimulation (SQS) vs. transcutaneous electrical nerve stimulation (TENS). Electrical parameters and relative location of the leads were held constant under each condition. SQS had cumulative antihypersensitivity effects in both inflammatory and neuropathic pain rodent models, with significant inhibition of mechanical hypersensitivity observed on days 3-4 of treatment. In contrast, reduction of thermal hyperalgesia in the inflammatory model was observed during the first four days of treatment with SQS, and reduction of cold allodynia in the neuropathic pain model was seen only on the first day with SQS. TENS was effective in the inflammation model, and in agreement with previous studies, tolerance developed to the antihypersensitivity effects of TENS. With the exception of a reversal of cold hypersensitivity on day 1 of testing, TENS did not reveal significant analgesic effects in the neuropathic pain rodent model. The results presented show that TENS and SQS have different effects that could point to unique biologic mechanisms underlying the analgesic effect of each therapy. Furthermore, this study is the first to demonstrate in an animal model that SQS attenuates neuropathic and inflammatory-induced pain behaviors. © 2013 Medtronic, Inc.

A Syrian golden hamster model recapitulating ebola hemorrhagic fever.

PubMed

Ebihara, Hideki; Zivcec, Marko; Gardner, Donald; Falzarano, Darryl; LaCasse, Rachel; Rosenke, Rebecca; Long, Dan; Haddock, Elaine; Fischer, Elizabeth; Kawaoka, Yoshihiro; Feldmann, Heinz

2013-01-15

Ebola hemorrhagic fever (EHF) is a severe viral infection for which no effective treatment or vaccine is currently available. While the nonhuman primate (NHP) model is used for final evaluation of experimental vaccines and therapeutic efficacy, rodent models have been widely used in ebolavirus research because of their convenience. However, the validity of rodent models has been questioned given their low predictive value for efficacy testing of vaccines and therapeutics, a result of the inconsistent manifestation of coagulopathy seen in EHF. Here, we describe a lethal Syrian hamster model of EHF using mouse-adapted Ebola virus. Infected hamsters displayed most clinical hallmarks of EHF, including severe coagulopathy and uncontrolled host immune responses. Thus, the hamster seems to be superior to the existing rodent models, offering a better tool for understanding the critical processes in pathogenesis and providing a new model for evaluating prophylactic and postexposure interventions prior to testing in NHPs.

A Syrian Golden Hamster Model Recapitulating Ebola Hemorrhagic Fever

PubMed Central

Ebihara, Hideki; Zivcec, Marko; Gardner, Donald; Falzarano, Darryl; LaCasse, Rachel; Rosenke, Rebecca; Long, Dan; Haddock, Elaine; Fischer, Elizabeth; Kawaoka, Yoshihiro; Feldmann, Heinz

2013-01-01

Ebola hemorrhagic fever (EHF) is a severe viral infection for which no effective treatment or vaccine is currently available. While the nonhuman primate (NHP) model is used for final evaluation of experimental vaccines and therapeutic efficacy, rodent models have been widely used in ebolavirus research because of their convenience. However, the validity of rodent models has been questioned given their low predictive value for efficacy testing of vaccines and therapeutics, a result of the inconsistent manifestation of coagulopathy seen in EHF. Here, we describe a lethal Syrian hamster model of EHF using mouse-adapted Ebola virus. Infected hamsters displayed most clinical hallmarks of EHF, including severe coagulopathy and uncontrolled host immune responses. Thus, the hamster seems to be superior to the existing rodent models, offering a better tool for understanding the critical processes in pathogenesis and providing a new model for evaluating prophylactic and postexposure interventions prior to testing in NHPs. PMID:23045629

Dietary Factors Modulate Helicobacter-Associated Gastric Cancer in Rodent Models

PubMed Central

Fox, James G.; Wang, Timothy C.

2014-01-01

Since its discovery in 1982, the global importance of H. pylori-induced disease, particularly in developing countries, remains high. The use of rodent models particularly mice, and the unanticipated usefulness of the gerbil to study H. pylori pathogenesis have been used extensively to study the interactions of the host, the pathogen and the environmental conditions influencing the outcome of persistent H. pylori infection. Dietary factors in humans are increasingly recognized as being important factors in modulating progression and severity of H. pylori-induced gastric cancer. Studies using rodent models to verify and help explain mechanisms whereby various dietary ingredients impact disease outcome should continue to be extremely productive. PMID:24301796

25 years of research on global asphyxia in the immature rat brain.

PubMed

Barkhuizen, M; van den Hove, D L A; Vles, J S H; Steinbusch, H W M; Kramer, B W; Gavilanes, A W D

2017-04-01

Hypoxic-ischemic encephalopathy remains a common cause of brain damage in neonates. Preterm infants have additional complications, as prematurity by itself increases the risk of encephalopathy. Currently, therapy for this subset of asphyxiated infants is limited to supportive care. There is an urgent need for therapies in preterm infants - and for representative animal models for preclinical drug development. In 1991, a novel rodent model of global asphyxia in the preterm infant was developed in Sweden. This method was based on the induction of asphyxia during the birth processes itself by submerging pups, still in the uterine horns, in a water bath followed by C-section. This insult occurs at a time-point when the rodent brain maturity resembles the brain of a 22-32 week old human fetus. This model has developed over the past 25 years as an established model of perinatal global asphyxia in the early preterm brain. Here we summarize the knowledge gained on the short- and long-term neuropathological and behavioral effects of asphyxia on the immature central nervous system. Copyright © 2017 Elsevier Ltd. All rights reserved.

Vision in laboratory rodents-Tools to measure it and implications for behavioral research.

PubMed

Leinonen, Henri; Tanila, Heikki

2017-07-29

Mice and rats are nocturnal mammals and their vision is specialized for detection of motion and contrast in dim light conditions. These species possess a large proportion of UV-sensitive cones in their retinas and the majority of their optic nerve axons target superior colliculus rather than visual cortex. Therefore, it was a widely held belief that laboratory rodents hardly utilize vision during day-time behavior. This dogma is being questioned as accumulating evidence suggests that laboratory rodents are able to perform complex visual functions, such as perceiving subjective contours, and that declined vision may affect their performance in many behavioral tasks. For instance, genetic engineering may have unexpected consequences on vision as mouse models of Alzheimer's and Huntington's diseases have declined visual function. Rodent vision can be tested in numerous ways using operant training or reflex-based behavioral tasks, or alternatively using electrophysiological recordings. In this article, we will first provide a summary of visual system and explain its characteristics unique to rodents. Then, we present well-established techniques to test rodent vision, with an emphasis on pattern vision: visual water test, optomotor reflex test, pattern electroretinography and pattern visual evoked potentials. Finally, we highlight the importance of visual phenotyping in rodents. As the number of genetically engineered rodent models and volume of behavioral testing increase simultaneously, the possibility of visual dysfunctions needs to be addressed. Neglect in this matter potentially leads to crude biases in the field of neuroscience and beyond. Copyright © 2017 Elsevier B.V. All rights reserved.

The Manufacture, Shipping and Receiving and Quality Control of Rodent Bedding Materials

NASA Technical Reports Server (NTRS)

Kraft, Lisbeth M.

1980-01-01

The criteria for rodent bedding and nesting materials are discussed. The literature is reviewed regarding sources of bedding materials, manufacturing methods, quality control, procedures (microbiological, physical and chemical), storage, methods, shipment, methods of use and disposal, current knowledge concerning bedding effects on animals as related to research and testing and legal aspects. Future needs, especially with respect to the promulgation of standards, also are addressed.

Modeling the Lymphocytic Choriomeningitis Virus: Insights into understanding its epidemiology in the wild

NASA Astrophysics Data System (ADS)

Contreras, Christy; McKay, John; Blattman, Joseph; Holechek, Susan

2015-03-01

The lymphocytic choriomenigitis virus (LCMV) is a rodent-spread virus commonly recognized as causing neurological disease that exhibits asymptomatic pathology. The virus is a pathogen normally carried among rodents that can be transmitted to humans by direct or indirect contact with the virus in excretions and secretions from rodents and can cause aseptic meningitis and other conditions in humans. We consider an epidemiological system within rodent populations modeled by a system of ordinary differential equations that captures the dynamics of the diseases transmission and present our findings. The asymptotic nature of the pathogen plays a large role in its spread within a given population, which has motivated us to expand upon an existing SIRC model (Holechek et al in preparation) that accounts for susceptible-, infected-, recovered-, and carrier-mice on the basis of their gender. We are interested in observing and determining the conditions under which the carrier population will reach a disease free equilibrium, and we focus our investigation on the sensitivity of our model to gender, pregnancy related infection, and reproduction rate conditions.

A SMALL FISH MULTI-ENDPOINT BIOASSAY FOR ASSESSING THE EFFECTS OF WATER CONTAMINANTS PRESENT IN LOW CONCENTRATIONS: MEDAKA AND DICHLOROACETIC ACID

EPA Science Inventory

In regulating the safety of water under SDWA and the CWA, the EPA makes decisions on what chemical contaminants to regulate and at what levels. To make these decisions the EPA needs hazard identification and dose-response information. Current methods that rely on rodent models fo...

Translational Neuromodulation: Approximating Human Transcranial Magnetic Stimulation Protocols In Rats

PubMed Central

Vahabzadeh-Hagh, Andrew M.; Muller, Paul A.; Gersner, Roman; Zangen, Abraham; Rotenberg, Alexander

2015-01-01

Objective Transcranial magnetic stimulation (TMS) is a well-established clinical protocol with numerous potential therapeutic and diagnostic applications. Yet, much work remains in the elucidation of TMS mechanisms, optimization of protocols, and in development of novel therapeutic applications. As with many technologies, the key to these issues lies in the proper experimentation and translation of TMS methods to animal models, among which rat models have proven popular. A significant increase in the number of rat TMS publications has necessitated analysis of their relevance to human work. We therefore review the essential principles necessary for the approximation of human TMS protocols in rats as well as specific methods that addressed these issues in published studies. Materials and Methods We performed an English language literature search combined with our own experience and data. We address issues that we see as important in the translation of human TMS methods to rat models and provide a summary of key accomplishments in these areas. Results An extensive literature review illustrated the growth of rodent TMS studies in recent years. Current advances in the translation of single, paired-pulse, and repetitive stimulation paradigms to rodent models are presented. The importance of TMS in the generation of data for preclinical trials is also highlighted. Conclusions Rat TMS has several limitations when considering parallels between animal and human stimulation. However, it has proven to be a useful tool in the field of translational brain stimulation and will likely continue to aid in the design and implementation of stimulation protocols for therapeutic and diagnostic applications. PMID:22780329

Anaerobic threshold employed on exercise training prescription and performance assessment for laboratory rodents: A short review.

PubMed

Abreu, Phablo; Mendes, Sávio Victor Diogenes; Leal-Cardoso, José Henrique; Ceccatto, Vânia Marilande

2016-04-15

Several studies have generated numerous terms in the field of exercise training prescription and performance assessment that often do not match the information previously demonstrated by many other works, generating much debate and resulting in an immense pool of scientific results. Several protocols in exercise training prescription and performance assessment have been proposed for these purposes by many reasons. In the field of exercise science, the protocol must be thoroughly investigated and provide real tools to be reproducible. Many laboratories have been adapting and developing evaluation protocols and testing on physical training of rodents in different experimental conditions. In this context, mice, rats and rabbits are preferentially chosen due to easy manipulation and good response to exercise, and comparable at results obtained with humans in compatible effort intensities. But, the exercise training programs and aerobic-anaerobic transition assessment proposed for animal models vary extensively, depending on the species, gender, age, type of stimulus, type of exercise, type of method and also on the specific objectives of the program. This short review demonstrates the need in offering tools performed by invasive measurement to assess the anaerobic threshold by blood lactate employed on evolution of aerobic-anaerobic parameters of rodents. The objective of this short review was to present and to discuss physical evaluation protocols applications to rodents. The table submitted may give a basis for anaerobic threshold employed on exercise training prescription and performance assessment for laboratory rodents in future research. Copyright © 2016 Elsevier Inc. All rights reserved.

Bardoxolone methyl analogs RTA 405 and dh404 are well tolerated and exhibit efficacy in rodent models of Type 2 diabetes and obesity.

PubMed

Chin, Melanie; Lee, Chun-Yue Ivy; Chuang, Jen-Chieh; Bumeister, Ron; Wigley, W Christian; Sonis, Stephen T; Ward, Keith W; Meyer, Colin

2013-06-15

Bardoxolone methyl and related triterpenoids are well tolerated and efficacious in numerous animal models potentially relevant to patients with Type 2 diabetes and chronic kidney disease. These agents enhance glucose control and regulate lipid accumulation in rodent models of diabetes and obesity, and improve renal function, reduce inflammation, and prevent structural injury in models of renal disease. However, a recent study in Zucker diabetic fatty (ZDF) rats noted poor tolerability with the bardoxolone methyl analog RTA 405 within 1 mo after treatment initiation, although this study was confounded in part by the use of an impure RTA 405 batch. To investigate these discordant observations, the present studies were conducted to further characterize triterpenoids in rodent models of diabetes and obesity. A follow-up study was conducted in ZDF rats with two related triterpenoids (RTA 405 and dh404) for 1.5 mo. Consistent with previous rodent experience, and in contrast to the more recent ZDF report, ZDF rats administered RTA 405 or dh404 exhibited no adverse clinical signs, had laboratory values similar to controls, and exhibited no evidence of adverse liver or kidney histopathology. Additionally, RTA 405 was well tolerated in streptozotocin-induced Type 1 diabetic rats and high-fat-diet-induced obese mice. The present results are consistent with the overall published body of data obtained with triterpenoids and provide further evidence that these molecules are well tolerated without adverse effects on hepatobiliary or renal function in rodent models of diabetes and obesity.

Genetic Rodent Models of Obesity-Associated Ovarian Dysfunction and Subfertility: Insights into Polycystic Ovary Syndrome

PubMed Central

Huang-Doran, Isabel; Franks, Stephen

2016-01-01

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women and a leading cause of female infertility worldwide. Defined clinically by the presence of hyperandrogenemia and oligomenorrhoea, PCOS represents a state of hormonal dysregulation, disrupted ovarian follicle dynamics, and subsequent oligo- or anovulation. The syndrome’s prevalence is attributed, at least partly, to a well-established association with obesity and insulin resistance (IR). Indeed, the presence of severe PCOS in human genetic obesity and IR syndromes supports a causal role for IR in the pathogenesis of PCOS. However, the molecular mechanisms underlying this causality, as well as the important role of hyperandrogenemia, remain poorly elucidated. As such, treatment of PCOS is necessarily empirical, focusing on symptom alleviation. The generation of knockout and transgenic rodent models of obesity and IR offers a promising platform in which to address mechanistic questions about reproductive dysfunction in the context of metabolic disease. Similarly, the impact of primary perturbations in rodent gonadotrophin or androgen signaling has been interrogated. However, the insights gained from such models have been limited by the relatively poor fidelity of rodent models to human PCOS. In this mini review, we evaluate the ovarian phenotypes associated with rodent models of obesity and IR, including the extent of endocrine disturbance, ovarian dysmorphology, and subfertility. We compare them to both human PCOS and other animal models of the syndrome (genetic and hormonal), explore reasons for their discordance, and consider the new opportunities that are emerging to better understand and treat this important condition. PMID:27375552

The past, present, and future of National Aeronautics and Space Administration spaceflight diet in support of microgravity rodent experiments.

PubMed

Sun, Gwo-Shing; Tou, Janet C; Yu, Diane; Girten, Beverly E; Cohen, Jacob

2014-02-01

Rodents have been the most frequently flown animal model used to study physiological responses to the space environment. In support of future of space exploration, the National Aeronautics and Space Administration (NASA) envisions an animal research program focused on rodents. Therefore, the development of a rodent diet that is suitable for the spaceflight environment including long duration spaceflight is a high priority. Recognizing the importance of nutrition in affecting spaceflight physiological responses and ensuring reliable biomedical and biological science return, NASA developed the nutrient-upgraded rodent food bar (NuRFB) as a standard diet for rodent spaceflight. Depending on future animal habitat hardware and planned spaceflight experiments, modification of the NuRFB or development of a new diet formulation may be needed, particularly for long term spaceflights. Research in this area consists primarily of internal technical reports that are not readily accessible. Therefore, the aims of this contribution are to provide a brief history of the development of rodent spaceflight diets, to review the present diet used in rodent spaceflight studies, and to discuss some of the challenges and potential solutions for diets to be used in future long-term rodent spaceflight studies. Copyright © 2014 Elsevier Inc. All rights reserved.

Optimizing Cardiovascular Benefits of Exercise: A Review of Rodent Models

PubMed Central

Davis, Brittany; Moriguchi, Takeshi; Sumpio, Bauer

2013-01-01

Although research unanimously maintains that exercise can ward off cardiovascular disease (CVD), the optimal type, duration, intensity, and combination of forms are yet not clear. In our review of existing rodent-based studies on exercise and cardiovascular health, we attempt to find the optimal forms, intensities, and durations of exercise. Using Scopus and Medline, a literature review of English language comparative journal studies of cardiovascular benefits and exercise was performed. This review examines the existing literature on rodent models of aerobic, anaerobic, and power exercise and compares the benefits of various training forms, intensities, and durations. The rodent studies reviewed in this article correlate with reports on human subjects that suggest regular aerobic exercise can improve cardiac and vascular structure and function, as well as lipid profiles, and reduce the risk of CVD. Findings demonstrate an abundance of rodent-based aerobic studies, but a lack of anaerobic and power forms of exercise, as well as comparisons of these three components of exercise. Thus, further studies must be conducted to determine a truly optimal regimen for cardiovascular health. PMID:24436579

Evaluation of molecular brain changes associated with environmental stress in rodent models compared to human major depressive disorder: A proteomic systems approach.

PubMed

Cox, David Alan; Gottschalk, Michael Gerd; Stelzhammer, Viktoria; Wesseling, Hendrik; Cooper, Jason David; Bahn, Sabine

2016-11-25

Rodent models of major depressive disorder (MDD) are indispensable when screening for novel treatments, but assessing their translational relevance with human brain pathology has proved difficult. Using a novel systems approach, proteomics data obtained from post-mortem MDD anterior prefrontal cortex tissue (n = 12) and matched controls (n = 23) were compared with equivalent data from three commonly used preclinical models exposed to environmental stressors (chronic mild stress, prenatal stress and social defeat). Functional pathophysiological features associated with depression-like behaviour were identified in these models through enrichment of protein-protein interaction networks. A cross-species comparison evaluated which model(s) represent human MDD pathology most closely. Seven functional domains associated with MDD and represented across at least two models such as "carbohydrate metabolism and cellular respiration" were identified. Through statistical evaluation using kernel-based machine learning techniques, the social defeat model was found to represent MDD brain changes most closely for four of the seven domains. This is the first study to apply a method for directly evaluating the relevance of the molecular pathology of multiple animal models to human MDD on the functional level. The methodology and findings outlined here could help to overcome translational obstacles of preclinical psychiatric research.

Structural Magnetic Resonance Imaging Markers of Alzheimer's Disease and Its Retranslation to Rodent Models.

PubMed

Kincses, Zsigmond Tamas; Király, András; Veréb, Dániel; Vécsei, László

2015-01-01

The importance of imaging biomarkers has been acknowledged in the diagnosis and in the follow-up of Alzheimer's disease (AD), one of the major causes of dementia. Next to the molecular biomarkers and PET imaging investigations, structural MRI approaches provide important information about the disease progression and about the pathomechanism. Furthermore,a growing body of literature retranslates these imaging biomarkers to various rodent models of the disease. The goal of this review is to provide an overview of the macro- and microstructural imaging biomarkers of AD, concentrating on atrophy measures and diffusion MRI alterations. A survey is also given of the imaging approaches used in rodent models of dementias that can promote drug development.

Distributional ecology of Andes hantavirus: a macroecological approach.

PubMed

Astorga, Francisca; Escobar, Luis E; Poo-Muñoz, Daniela; Escobar-Dodero, Joaquin; Rojas-Hucks, Sylvia; Alvarado-Rybak, Mario; Duclos, Melanie; Romero-Alvarez, Daniel; Molina-Burgos, Blanca E; Peñafiel-Ricaurte, Alexandra; Toro, Frederick; Peña-Gómez, Francisco T; Peterson, A Townsend

2018-06-22

Hantavirus pulmonary syndrome (HPS) is an infection endemic in Chile and Argentina, caused by Andes hantavirus (ANDV). The rodent Oligoryzomys longicaudatus is suggested as the main reservoir, although several other species of Sigmodontinae are known hosts of ANDV. Here, we explore potential ANDV transmission risk to humans in southern South America, based on eco-epidemiological associations among: six rodent host species, seropositive rodents, and human HPS cases. We used ecological niche modeling and macroecological approaches to determine potential geographic distributions and assess environmental similarity among rodents and human HPS cases. Highest numbers of rodent species (five) were in Chile between 35° and 41°S latitude. Background similarity tests showed niche similarity in 14 of the 56 possible comparisons: similarity between human HPS cases and the background of all species and seropositive rodents was supported (except for Abrothrix sanborni). Of interest among the results is the likely role of O. longicaudatus, Loxodontomys micropus, Abrothrix olivaceus, and Abrothrix longipilis in HPS transmission to humans. Our results support a role of rodent species' distributions as a risk factor for human HPS at coarse scales, and suggest that the role of the main reservoir (O. longicaudatus) may be supported by the broader rodent host community in some areas.

Ground-based rodent control in a remote Hawaiian rainforest on Maui

USGS Publications Warehouse

Malcolm, T.R.; Swinnerton, K.J.; Groombridge, J.J.; Sparklin, B.D.; Brosius, C.N.; Vetter, J.P.; Foster, J.T.

2008-01-01

Effective control of introduced mammalian predators is essential to the recovery of native bird species in Hawai'i. Between August 1996 and December 2004, introduced rodents were controlled within three home ranges of the Po'ouli Melamprosops phaeosoma, a critically endangered Hawaiian honeycreeper. Rats were controlled using a combination of ground-based rodenticide (0.005% diphacinone) application and snap traps. Beginning in August 2001, we monitored the effectiveness of these rodent control efforts. Relative abundances of Black Rats Rattus rattus and Polynesian Rats R. exulans were measured in each of five snap-trapping grids seven times over a 35-month period. Rat populations decreased inside of the rodent control areas, but control effectiveness differed between rat species. During the first year of monitoring, target control levels for R. rattus were consistently achieved in only one of the rodent control areas. Control techniques were refined in areas failing to meet targets. Subsequently, we achieved target control levels for R. rattus more consistently in all three rodent control areas. However, relative abundances of R. exulans did not differ between rodent control and reference areas, indicating that our rodent control techniques were insufficient to reduce population levels of this species. These findings signify a need for further improvement of rodent control methods in Hawai'i, especially for Polynesian Rats, and demonstrate the critical importance of periodic monitoring of the response of rodent populations to management. In the future, managers may need to design rodent control operations targeting R. rattus and R. exulans independently to achieve best results.

Helminth Infections of Rodents and Their Zoonotic Importance in Boyer-Ahmad District, Southwestern Iran.

PubMed

Ranjbar, Mohammad Javad; Sarkari, Bahador; Mowlavi, Gholam Reza; Seifollahi, Zeinab; Moshfe, Abdolali; Abdolahi Khabisi, Samaneh; Mobedi, Iraj

2017-01-01

Rodents are considered as reservoirs of various zoonotic diseases including helminthic infections. The current study aimed to evaluate the prevalence of helminth infections in rodents, in Boyer-Ahmad district, Southwestern Iran. Overall, 52 rodents were captured from various areas of the district by Sherman live traps. The animals were then euthanized and dissected. During necropsy, each organ was examined macroscopically for presence of any cyst or visible parasite. The gastrointestinal tract was removed and their contents were evaluated for larva or adult worms. Trichinella larvae in the rodents' muscles were investigated by both digestion and pathological methods. Twenty-eight (53.8%) of the trapped rodents were male. The rodents were including 25 (48.1%) Meriones persicus , 1(1.9%) Calomyscus bailwardi , 1 (1.9%) Arvicola terresterris , 7 (13.5%) Rattus rattus , 8 (15.4%) R. norvegicus , and 10 (19.2%) Apodemus sylvaticus . Of them, 38 (73.0%) were infected with at least one helminth. Collected rodents were infected with Hymenolepis diminuta (50%), Hymenolepis nana fraterna (28.8%), Skrjabinotaenia sp. (15.4%), Anoplocephalidae sp. (15.4%), Cysticercus fasciolaris (5.8%), Trichuris muris (36.5%), Aspiculuris tetraptera (15.4%), Syphacia sp. (5.7%), Rictularia sp. (15.4%), Trichostrongylus sp. (3.8%), and Gongylonema sp. (3.8%). M. persicus was the most (84%) infected rodent, yet the differences between rodent genus and helminth infectivity were not statistically significant ( P >0.05). The rodents in Boyer-Ahmad district are infected with different helminths infections that some of them are recognized as threat to human health.

Global and 3D Spatial Assessment of Neuroinflammation in Rodent Models of Multiple Sclerosis

PubMed Central

Gupta, Shashank; Utoft, Regine; Hasseldam, Henrik; Schmidt-Christensen, Anja; Hannibal, Tine Dahlbaek; Hansen, Lisbeth; Fransén-Pettersson, Nina; Agarwal-Gupta, Noopur; Rozell, Björn; Andersson, Åsa; Holmberg, Dan

2013-01-01

Multiple Sclerosis (MS) is a progressive autoimmune inflammatory and demyelinating disease of the central nervous system (CNS). T cells play a key role in the progression of neuroinflammation in MS and also in the experimental autoimmune encephalomyelitis (EAE) animal models for the disease. A technology for quantitative and 3 dimensional (3D) spatial assessment of inflammation in this and other CNS inflammatory conditions is much needed. Here we present a procedure for 3D spatial assessment and global quantification of the development of neuroinflammation based on Optical Projection Tomography (OPT). Applying this approach to the analysis of rodent models of MS, we provide global quantitative data of the major inflammatory component as a function of the clinical course. Our data demonstrates a strong correlation between the development and progression of neuroinflammation and clinical disease in several mouse and a rat model of MS refining the information regarding the spatial dynamics of the inflammatory component in EAE. This method provides a powerful tool to investigate the effect of environmental and genetic forces and for assessing the therapeutic effects of drug therapy in animal models of MS and other neuroinflammatory/neurodegenerative disorders. PMID:24124545

A glimpse on the pattern of rodent diversification: a phylogenetic approach

PubMed Central

2012-01-01

Background Development of phylogenetic methods that do not rely on fossils for the study of evolutionary processes through time have revolutionized the field of evolutionary biology and resulted in an unprecedented expansion of our knowledge about the tree of life. These methods have helped to shed light on the macroevolution of many taxonomic groups such as the placentals (Mammalia). However, despite the increase of studies addressing the diversification patterns of organisms, no synthesis has addressed the case of the most diversified mammalian clade: the Rodentia. Results Here we present a rodent maximum likelihood phylogeny inferred from a molecular supermatrix. It is based on 11 mitochondrial and nuclear genes that covers 1,265 species, i.e., respectively 56% and 81% of the known specific and generic rodent diversity. The inferred topology recovered all Rodentia clades proposed by recent molecular works. A relaxed molecular clock dating approach provided a time framework for speciation events. We found that the Myomorpha clade shows a greater degree of variation in diversification rates than Sciuroidea, Caviomorpha, Castorimorpha and Anomaluromorpha. We identified a number of shifts in diversification rates within the major clades: two in Castorimorpha, three in Ctenohystrica, 6 within the squirrel-related clade and 24 in the Myomorpha clade. The majority of these shifts occurred within the most recent familial rodent radiations: the Cricetidae and Muridae clades. Using the topological imbalances and the time line we discuss the potential role of different diversification factors that might have shaped the rodents radiation. Conclusions The present glimpse on the diversification pattern of rodents can be used for further comparative meta-analyses. Muroid lineages have a greater degree of variation in their diversification rates than any other rodent group. Different topological signatures suggest distinct diversification processes among rodent lineages. In particular, Muroidea and Sciuroidea display widespread distribution and have undergone evolutionary and adaptive radiation on most of the continents. Our results show that rodents experienced shifts in diversification rate regularly through the Tertiary, but at different periods for each clade. A comparison between the rodent fossil record and our results suggest that extinction led to the loss of diversification signal for most of the Paleogene nodes. PMID:22697210

Evaluation of porcine reproductive and respiratory syndrome virus replication in laboratory rodents

PubMed Central

Rosenfeld, Paul; Turner, Patricia V.; MacInnes, Janet I.; Nagy, Éva; Yoo, Dongwan

2009-01-01

Porcine reproductive and respiratory syndrome virus (PRRSV) is a major cause of economic losses in the swine industry. The disease is widespread worldwide, and so PRRSV-negative pigs are often difficult to find for the study of PRRSV in vivo. To determine if a small animal model could be developed for PRRSV, 3 strains of laboratory rodent were examined for their susceptibility to the virus. No virus replication was detected in BALB/c or SCID (severe combined immunodeficiency) mice after intraperitoneal inoculation. Moderate replication of PRRSV was detected in primary cotton rat lung cell cultures, but no viral replication was detected following intranasal or intraperitoneal inoculation. Following intratracheal inoculation, viral transcripts were detected in the lungs of cotton rats, but only for 1 day. This study indicates that PRRSV replication in common laboratory rodent species is inefficient, and suggests that a rodent model for this virus is not appropriate. PMID:20046635

Spatial Segregation between Invasive and Native Commensal Rodents in an Urban Environment: A Case Study in Niamey, Niger

PubMed Central

Garba, Madougou; Dalecky, Ambroise; Kadaoure, Ibrahima; Kane, Mamadou; Hima, Karmadine; Veran, Sophie; Gagare, Sama; Gauthier, Philippe; Tatard, Caroline; Rossi, Jean-Pierre; Dobigny, Gauthier

2014-01-01

Invasive rodents have been responsible for the diffusion worldwide of many zoonotic agents, thus representing major threats for public health. Cities are important hubs for people and goods exchange and are thus expected to play a pivotal role in invasive commensal rodent dissemination. Yet, data about urban rodents' ecology, especially invasive vs. native species interactions, are dramatically scarce. Here, we provide results of an extensive survey of urban rodents conducted in Niamey, Niger, depicting the early stages of rodent bioinvasions within a city. We explore the species-specific spatial distributions throughout the city using contrasted approaches, namely field sampling, co-occurrence analysis, occupancy modelling and indicator geostatistics. We show that (i) two species (i.e. rural-like vs. truly commensal) assemblages can be identified, and that (ii) within commensal rodents, invasive (Rattus rattus and Mus musculus) and native (Mastomys natalensis) species are spatially segregated. Moreover, several pieces of arguments tend to suggest that these exclusive distributions reflect an ongoing native-to-invasive species turn over. The underlying processes as well as the possible consequences for humans are discussed. PMID:25379785

In vitro perturbations of targets in cancer hallmark processes predict rodent chemical carcinogenesis.

PubMed

Kleinstreuer, Nicole C; Dix, David J; Houck, Keith A; Kavlock, Robert J; Knudsen, Thomas B; Martin, Matthew T; Paul, Katie B; Reif, David M; Crofton, Kevin M; Hamilton, Kerry; Hunter, Ronald; Shah, Imran; Judson, Richard S

2013-01-01

Thousands of untested chemicals in the environment require efficient characterization of carcinogenic potential in humans. A proposed solution is rapid testing of chemicals using in vitro high-throughput screening (HTS) assays for targets in pathways linked to disease processes to build models for priority setting and further testing. We describe a model for predicting rodent carcinogenicity based on HTS data from 292 chemicals tested in 672 assays mapping to 455 genes. All data come from the EPA ToxCast project. The model was trained on a subset of 232 chemicals with in vivo rodent carcinogenicity data in the Toxicity Reference Database (ToxRefDB). Individual HTS assays strongly associated with rodent cancers in ToxRefDB were linked to genes, pathways, and hallmark processes documented to be involved in tumor biology and cancer progression. Rodent liver cancer endpoints were linked to well-documented pathways such as peroxisome proliferator-activated receptor signaling and TP53 and novel targets such as PDE5A and PLAUR. Cancer hallmark genes associated with rodent thyroid tumors were found to be linked to human thyroid tumors and autoimmune thyroid disease. A model was developed in which these genes/pathways function as hypothetical enhancers or promoters of rat thyroid tumors, acting secondary to the key initiating event of thyroid hormone disruption. A simple scoring function was generated to identify chemicals with significant in vitro evidence that was predictive of in vivo carcinogenicity in different rat tissues and organs. This scoring function was applied to an external test set of 33 compounds with carcinogenicity classifications from the EPA's Office of Pesticide Programs and successfully (p = 0.024) differentiated between chemicals classified as "possible"/"probable"/"likely" carcinogens and those designated as "not likely" or with "evidence of noncarcinogenicity." This model represents a chemical carcinogenicity prioritization tool supporting targeted testing and functional validation of cancer pathways.

Effects of glyphosate exposure on sperm concentration in rodents: A systematic review and meta-analysis.

PubMed

Cai, Wenyan; Ji, Ying; Song, Xianping; Guo, Haoran; Han, Lei; Zhang, Feng; Liu, Xin; Zhang, Hengdong; Zhu, Baoli; Xu, Ming

2017-10-01

Correlation between exposure to glyphosate and sperm concentrations is important in reproductive toxicity risk assessment for male reproductive functions. Many studies have focused on reproductive toxicity on glyphosate, however, results are still controversial. We conducted a systematic review of epidemiological studies on the association between glyphosate exposure and sperm concentrations of rodents. The aim of this study is to explore the potential adverse effects of glyphosate on reproductive function of male rodents. Systematic and comprehensive literature search was performed in MEDLINE, TOXLINE, Embase, WANFANG and CNKI databases with different combinations of glyphosate exposure and sperm concentration. 8 studies were eventually identified and random-effect model was conducted. Heterogeneity among study results was calculated via chi-square tests. Ten independent experimental datasets from these eight studies were acquired to synthesize the random-effect model. A decrease in sperm concentrations was found with mean difference of sperm concentrations(MDsperm)=-2.774×10 6 /sperm/g/testis(95%CI=-0.969 to -4.579) in random-effect model after glyphosate exposure. There was also a significant decrease after fitting the random-effect model: MDsperm=-1.632×10 6 /sperm/g/testis (95%CI=-0.662 to -2.601). The results of meta-analysis support the hypothesis that glyphosate exposure decreased sperm concentration in rodents. Therefore, we conclude that glyphosate is toxic to male rodent's reproductive system. Copyright © 2017. Published by Elsevier B.V.

Climate variability, animal reservoir and transmission of scrub typhus in Southern China

PubMed Central

Li, Xiaoning; Ma, Yu; Tao, Xia; Wu, Xinwei

2017-01-01

Objectives We aimed to evaluate the relationships between climate variability, animal reservoirs and scrub typhus incidence in Southern China. Methods We obtained data on scrub typhus cases in Guangzhou every month from 2006 to 2014 from the Chinese communicable disease network. Time-series Poisson regression models and distributed lag nonlinear models (DLNM) were used to evaluate the relationship between risk factors and scrub typhus. Results Wavelet analysis found the incidence of scrub typhus cycled with a period of approximately 8–12 months and long-term trends with a period of approximately 24–36 months. The DLNM model shows that relative humidity, rainfall, DTR, MEI and rodent density were associated with the incidence of scrub typhus. Conclusions Our findings suggest that the incidence scrub typhus has two main temporal cycles. Determining the reason for this trend and how it can be used for disease control and prevention requires additional research. The transmission of scrub typhus is highly dependent on climate factors and rodent density, both of which should be considered in prevention and control strategies for scrub typhus. PMID:28273079

Gene Delivery to the Airway

PubMed Central

Keiser, Nicholas W.; Engelhardt, John F.

2013-01-01

This unit describes generation of and gene transfer to several commonly used airway models. Isolation and transduction of primary airway epithelial cells are first described. Next, the preparation of polarized airway epithelial monolayers is outlined. Transduction of these polarized cells is also described. Methods are presented for generation of tracheal xenografts as well as both ex vivo and in vivo gene transfer to these xenografts. Finally, a method for in vivo gene delivery to the lungs of rodents is included. Methods for evaluating transgene expression are given in the support protocols. PMID:23853081

A low-cost touchscreen operant chamber using a Raspberry Pi™.

PubMed

O'Leary, James D; O'Leary, Olivia F; Cryan, John F; Nolan, Yvonne M

2018-03-08

The development of a touchscreen platform for rodent testing has allowed new methods for cognitive testing that have been back-translated from clinical assessment tools to preclinical animal models. This platform for cognitive assessment in animals is comparable to human neuropsychological tests such as those employed by the Cambridge Neuropsychological Test Automated Battery, and thus has several advantages compared to the standard maze apparatuses typically employed in rodent behavioral testing, such as the Morris water maze. These include improved translation of preclinical models, as well as high throughput and the automation of animal testing. However, these systems are relatively expensive, which can impede progress for researchers with limited resources. Here we describe a low-cost touchscreen operant chamber based on the single-board computer, Raspberry Pi TM , which is capable of performing tasks similar to those supported by current state-of-the-art systems. This system provides an affordable alternative for cognitive testing in a touchscreen operant paradigm for researchers with limited funding.

Methods for measuring populations of arboreal rodents.

Treesearch

Andrew B. Carey; Brian L. Biswell; Joseph W. Witt

1991-01-01

Three arboreal rodents are sensitive indicators of forest ecosystem function in the Pacific Northwest. The northern flying squirrel (Glaucomys sabrinus) is mycophagous, cavity-nesting, and a major prey of the spotted owl (Strix occidentalis). The red tree vole (Phenacomys longicaudus) is restricted to trees...

A rodent model for the study of invariant visual object recognition

PubMed Central

Zoccolan, Davide; Oertelt, Nadja; DiCarlo, James J.; Cox, David D.

2009-01-01

The human visual system is able to recognize objects despite tremendous variation in their appearance on the retina resulting from variation in view, size, lighting, etc. This ability—known as “invariant” object recognition—is central to visual perception, yet its computational underpinnings are poorly understood. Traditionally, nonhuman primates have been the animal model-of-choice for investigating the neuronal substrates of invariant recognition, because their visual systems closely mirror our own. Meanwhile, simpler and more accessible animal models such as rodents have been largely overlooked as possible models of higher-level visual functions, because their brains are often assumed to lack advanced visual processing machinery. As a result, little is known about rodents' ability to process complex visual stimuli in the face of real-world image variation. In the present work, we show that rats possess more advanced visual abilities than previously appreciated. Specifically, we trained pigmented rats to perform a visual task that required them to recognize objects despite substantial variation in their appearance, due to changes in size, view, and lighting. Critically, rats were able to spontaneously generalize to previously unseen transformations of learned objects. These results provide the first systematic evidence for invariant object recognition in rats and argue for an increased focus on rodents as models for studying high-level visual processing. PMID:19429704

Nutraceuticals in rodent models as potential treatments for human Inflammatory Bowel Disease.

PubMed

Ghattamaneni, Naga K R; Panchal, Sunil K; Brown, Lindsay

2018-04-20

Inflammatory Bowel Disease (IBD) is characterized by chronic inflammation of all or part of the digestive tract. Nutraceuticals include bioactive compounds such as polyphenols with anti-inflammatory activities, thus these products have the potential to treat chronic inflammatory diseases. We have emphasized the role of nutraceuticals in ameliorating the symptoms of IBD in rodent models of human IBD through modulation of key pathogenic mechanisms including dysbiosis, oxidative stress, increased inflammatory cytokines, immune system dysregulation, and inflammatory cell signaling pathways. Nutraceuticals have an important role in IBD patients as a preventive approach to extend remission phases and as a therapeutic intervention to suppress active IBD. Further clinical trials on nutraceuticals with positive results in rodent models are warranted. Copyright © 2018. Published by Elsevier Ltd.

Using Geographic Information System-based Ecologic Niche Models to Forecast the Risk of Hantavirus Infection in Shandong Province, China

PubMed Central

Wei, Lan; Qian, Quan; Wang, Zhi-Qiang; Glass, Gregory E.; Song, Shao-Xia; Zhang, Wen-Yi; Li, Xiu-Jun; Yang, Hong; Wang, Xian-Jun; Fang, Li-Qun; Cao, Wu-Chun

2011-01-01

Hemorrhagic fever with renal syndrome (HFRS) is an important public health problem in Shandong Province, China. In this study, we combined ecologic niche modeling with geographic information systems (GIS) and remote sensing techniques to identify the risk factors and affected areas of hantavirus infections in rodent hosts. Land cover and elevation were found to be closely associated with the presence of hantavirus-infected rodent hosts. The averaged area under the receiver operating characteristic curve was 0.864, implying good performance. The predicted risk maps based on the model were validated both by the hantavirus-infected rodents' distribution and HFRS human case localities with a good fit. These findings have the applications for targeting control and prevention efforts. PMID:21363991

Brain development in rodents and humans: Identifying benchmarks of maturation and vulnerability to injury across species

PubMed Central

Semple, Bridgette D.; Blomgren, Klas; Gimlin, Kayleen; Ferriero, Donna M.; Noble-Haeusslein, Linda J.

2013-01-01

Hypoxic-ischemic and traumatic brain injuries are leading causes of long-term mortality and disability in infants and children. Although several preclinical models using rodents of different ages have been developed, species differences in the timing of key brain maturation events can render comparisons of vulnerability and regenerative capacities difficult to interpret. Traditional models of developmental brain injury have utilized rodents at postnatal day 7–10 as being roughly equivalent to a term human infant, based historically on the measurement of post-mortem brain weights during the 1970s. Here we will examine fundamental brain development processes that occur in both rodents and humans, to delineate a comparable time course of postnatal brain development across species. We consider the timing of neurogenesis, synaptogenesis, gliogenesis, oligodendrocyte maturation and age-dependent behaviors that coincide with developmentally regulated molecular and biochemical changes. In general, while the time scale is considerably different, the sequence of key events in brain maturation is largely consistent between humans and rodents. Further, there are distinct parallels in regional vulnerability as well as functional consequences in response to brain injuries. With a focus on developmental hypoxicischemic encephalopathy and traumatic brain injury, this review offers guidelines for researchers when considering the most appropriate rodent age for the developmental stage or process of interest to approximate human brain development. PMID:23583307

Adjustment of the dynamic weight distribution as a sensitive parameter for diagnosis of postural alteration in a rodent model of vestibular deficit

PubMed Central

Tighilet, Brahim; Péricat, David; Frelat, Alais; Cazals, Yves; Rastoldo, Guillaume; Boyer, Florent; Dumas, Olivier

2017-01-01

Vestibular disorders, by inducing significant posturo-locomotor and cognitive disorders, can significantly impair the most basic tasks of everyday life. Their precise diagnosis is essential to implement appropriate therapeutic countermeasures. Monitoring their evolution is also very important to validate or, on the contrary, to adapt the undertaken therapeutic actions. To date, the diagnosis methods of posturo-locomotor impairments are restricted to examinations that most often lack sensitivity and precision. In the present work we studied the alterations of the dynamic weight distribution in a rodent model of sudden and complete unilateral vestibular loss. We used a system of force sensors connected to a data analysis system to quantify in real time and in an automated way the weight bearing of the animal on the ground. We show here that sudden, unilateral, complete and permanent loss of the vestibular inputs causes a severe alteration of the dynamic ground weight distribution of vestibulo lesioned rodents. Characteristics of alterations in the dynamic weight distribution vary over time and follow the sequence of appearance and disappearance of the various symptoms that compose the vestibular syndrome. This study reveals for the first time that dynamic weight bearing is a very sensitive parameter for evaluating posturo-locomotor function impairment. Associated with more classical vestibular examinations, this paradigm can considerably enrich the methods for assessing and monitoring vestibular disorders. Systematic application of this type of evaluation to the dizzy or unstable patient could improve the detection of vestibular deficits and allow predicting better their impact on posture and walk. Thus it could also allow a better follow-up of the therapeutic approaches for rehabilitating gait and balance. PMID:29112981

Adjustment of the dynamic weight distribution as a sensitive parameter for diagnosis of postural alteration in a rodent model of vestibular deficit.

PubMed

Tighilet, Brahim; Péricat, David; Frelat, Alais; Cazals, Yves; Rastoldo, Guillaume; Boyer, Florent; Dumas, Olivier; Chabbert, Christian

2017-01-01

Vestibular disorders, by inducing significant posturo-locomotor and cognitive disorders, can significantly impair the most basic tasks of everyday life. Their precise diagnosis is essential to implement appropriate therapeutic countermeasures. Monitoring their evolution is also very important to validate or, on the contrary, to adapt the undertaken therapeutic actions. To date, the diagnosis methods of posturo-locomotor impairments are restricted to examinations that most often lack sensitivity and precision. In the present work we studied the alterations of the dynamic weight distribution in a rodent model of sudden and complete unilateral vestibular loss. We used a system of force sensors connected to a data analysis system to quantify in real time and in an automated way the weight bearing of the animal on the ground. We show here that sudden, unilateral, complete and permanent loss of the vestibular inputs causes a severe alteration of the dynamic ground weight distribution of vestibulo lesioned rodents. Characteristics of alterations in the dynamic weight distribution vary over time and follow the sequence of appearance and disappearance of the various symptoms that compose the vestibular syndrome. This study reveals for the first time that dynamic weight bearing is a very sensitive parameter for evaluating posturo-locomotor function impairment. Associated with more classical vestibular examinations, this paradigm can considerably enrich the methods for assessing and monitoring vestibular disorders. Systematic application of this type of evaluation to the dizzy or unstable patient could improve the detection of vestibular deficits and allow predicting better their impact on posture and walk. Thus it could also allow a better follow-up of the therapeutic approaches for rehabilitating gait and balance.

Multiplex array proteomics detects increased MMP-8 in CSF after spinal cord injury.

PubMed

Light, Matthew; Minor, Kenneth H; DeWitt, Peter; Jasper, Kyle H; Davies, Stephen J A

2012-06-11

A variety of methods have been used to study inflammatory changes in the acutely injured spinal cord. Recently novel multiplex assays have been used in an attempt to overcome limitations in numbers of available targets studied in a single experiment. Other technical challenges in developing pre-clinical rodent models to investigate biomarkers in cerebrospinal fluid (CSF) include relatively small volumes of sample and low concentrations of target proteins. The primary objective of this study was to characterize the inflammatory profile present in CSF at a subacute time point in a clinically relevant rodent model of traumatic spinal cord injury (SCI). Our other aim was to test a microarray proteomics platform specifically for this application. A 34 cytokine sandwich ELISA microarray was used to study inflammatory changes in CSF samples taken 12 days post-cervical SCI in adult rats. The difference between the median foreground signal and the median background signal was measured. Bonferroni and Benjamini-Hochburg multiple testing corrections were applied to limit the False Discovery Rate (FDR), and a linear mixed model was used to account for repeated measures in the array. We report a novel subacute SCI biomarker, elevated levels of matrix metalloproteinase-8 protein in CSF, and discuss application of statistical models designed for multiplex testing. Major advantages of this assay over conventional methods include high-throughput format, good sensitivity, and reduced sample consumption. This method can be useful for creating comprehensive inflammatory profiles, and biomarkers can be used in the clinic to assess injury severity and to objectively grade response to therapy.

A Review of the Molecular Mechanisms of Chemically-Induced Neoplasia in Rat and Mouse Models in National Toxicology Program Bioassays and Their Relevance to Human Cancer

PubMed Central

Hoenerhoff, Mark J.; Hong, Hue Hua; Ton, Tai-Vu; Lahousse, Stephanie A.; Sills, Robert C.

2012-01-01

Tumor response in the B6C3F1 mouse, F344 rat, and other animal models following exposure to various compounds provides evidence that people exposed to these or similar compounds may be at risk for developing cancer. Although tumors in rodents and humans are often morphologically similar, underlying mechanisms of tumorigenesis are often unknown and may be different between the species. Therefore, the relevance of an animal tumor response to human health would be better determined if the molecular pathogenesis were understood. The underlying molecular mechanisms leading to carcinogenesis are complex and involve multiple genetic and epigenetic events and other factors. To address the molecular pathogenesis of environmental carcinogens, we examine rodent tumors (e.g., lung, colon, mammary gland, skin, brain, mesothelioma) for alterations in cancer genes and epigenetic events that are associated with human cancer. Our NTP studies have identified several genetic alterations in chemically induced rodent neoplasms that are important in human cancer. Identification of such alterations in rodent models of chemical carcinogenesis caused by exposure to environmental contaminants, occupational chemicals, and other compounds lends further support that they are of potential human health risk. These studies also emphasize the importance of molecular evaluation of chemically induced rodent tumors for providing greater public health significance for NTP evaluated compounds. PMID:19846892

Intestinal Helminths in Different Species of Rodents in North Khorasan Province, Northeast of Iran.

PubMed

Arzamani, Kourosh; Salehi, Mitra; Mobedi, Iraj; Adinezade, Amir; Hasanpour, Hamid; Alavinia, Mohammad; Darvish, Jamshid; Shirzadi, Mohammad Reza; Mohammadi, Zeinolabedin

2017-01-01

Rodents are an important source of zoonotic diseases for human. The aim of this study was to determine the infectivity of rodents with intestinal helminths in North Khorasan Province, Iran. One hundred and thirteen rodents were collected using different collection methods such as kill and live traps, digging of their burrow, filling of their hiding places with water and hand net during 2011-2013. Their alimentary canals were removed in the laboratory and helminths were determined in the department of parasitology, Tehran University of Medical Sciences. Thirteen species of helminths parasites were found in 13 species of rodents, including Aspiculuris tetraptera, Hymenolepis diminuta, Nippostrongylus brasiliensis, Protospirura Seurat, Rictolaria ratti, Skrjabinitaenia lobata, Streptopharagus kuntzi, Syphacia obvelata, Taenia taeniaeformis, Trichuris muris, Cysticercus fasciolaris, Acanthocephal. spp and Trichuris spp . Some of them were reported for the first time in new host in Iran. S. obvelata and A. tetraptera were the most frequent parasites and P. Seurat, R. ratti and C. fasciolaris were found only in one rodent. This is the first study to investigate the intestinal parasites in rodents in this area. Among different species identified, some of helminths were reported in new host.

Highly impulsive rats: modelling an endophenotype to determine the neurobiological, genetic and environmental mechanisms of addiction

PubMed Central

Jupp, Bianca; Caprioli, Daniele; Dalley, Jeffrey W.

2013-01-01

Impulsivity describes the tendency of an individual to act prematurely without foresight and is associated with a number of neuropsychiatric co-morbidities, including drug addiction. As such, there is increasing interest in the neurobiological mechanisms of impulsivity, as well as the genetic and environmental influences that govern the expression of this behaviour. Tests used on rodent models of impulsivity share strong parallels with tasks used to assess this trait in humans, and studies in both suggest a crucial role of monoaminergic corticostriatal systems in the expression of this behavioural trait. Furthermore, rodent models have enabled investigation of the causal relationship between drug abuse and impulsivity. Here, we review the use of rodent models of impulsivity for investigating the mechanisms involved in this trait, and how these mechanisms could contribute to the pathogenesis of addiction. PMID:23355644

Automated assessment of pain in rats using a voluntarily accessed static weight-bearing test

PubMed Central

Kim, Hung Tae; Uchimoto, Kazuhiro; Duellman, Tyler; Yang, Jay

2015-01-01

The weight-bearing test is one method to assess pain in rodent animal models; however, the acceptance of this convenient method is limited by the low throughput data acquisition and necessity of confining the rodents to a small chamber. New methods We developed novel data acquisition hardware and software, data analysis software, and a conditioning protocol for an automated high throughput static weight-bearing assessment of pain. With this device, the rats voluntarily enter the weighing chamber, precluding the necessity to restrain the animals and thereby removing the potential stress-induced confounds as well as operator selection bias during data collection. We name this device the Voluntarily Accessed Static Incapacitance Chamber (VASIC). Results Control rats subjected to the VASIC device provided hundreds of weight-bearing data points in a single behavioral assay. Chronic constriction injury (CCI) surgery and paw pad injection of complete Freund's adjuvant (CFA) or carrageenan in rats generated hundreds of weight-bearing data during a 30 minute recording session. Rats subjected to CCI, CFA, or carrageenan demonstrated the expected bias in weight distribution favoring the un-operated leg, and the analgesic effect of i.p. morphine was demonstrated. In comparison with existing methods, brief water restriction encouraged the rats to enter the weighing chamber to access water, and an infrared detector confirmed the rat position with feet properly positioned on the footplates, triggering data collection. This allowed hands-off measurement of weight distribution data reducing operator selection bias. Conclusion The VASIC device should enhance the hands-free parallel collection of unbiased weight-bearing data in a high throughput manner, allowing further testing of this behavioral measure as an effective assessment of pain in rodents. PMID:26143745

Mathematical Modeling for Scrub Typhus and Its Implications for Disease Control.

PubMed

Min, Kyung Duk; Cho, Sung Il

2018-03-19

The incidence rate of scrub typhus has been increasing in the Republic of Korea. Previous studies have suggested that this trend may have resulted from the effects of climate change on the transmission dynamics among vectors and hosts, but a clear explanation of the process is still lacking. In this study, we applied mathematical models to explore the potential factors that influence the epidemiology of tsutsugamushi disease. We developed mathematical models of ordinary differential equations including human, rodent and mite groups. Two models, including simple and complex models, were developed, and all parameters employed in the models were adopted from previous articles that represent epidemiological situations in the Republic of Korea. The simulation results showed that the force of infection at the equilibrium state under the simple model was 0.236 (per 100,000 person-months), and that in the complex model was 26.796 (per 100,000 person-months). Sensitivity analyses indicated that the most influential parameters were rodent and mite populations and contact rate between them for the simple model, and trans-ovarian transmission for the complex model. In both models, contact rate between humans and mites is more influential than morality rate of rodent and mite group. The results indicate that the effect of controlling either rodents or mites could be limited, and reducing the contact rate between humans and mites is more practical and effective strategy. However, the current level of control would be insufficient relative to the growing mite population. © 2018 The Korean Academy of Medical Sciences.

Irradiation Design for an Experimental Murine Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ballesteros-Zebadua, P.; Moreno-Jimenez, S.; Suarez-Campos, J. E.

2010-12-07

In radiotherapy and stereotactic radiosurgery, small animal experimental models are frequently used, since there are still a lot of unsolved questions about the biological and biochemical effects of ionizing radiation. This work presents a method for small-animal brain radiotherapy compatible with a dedicated 6MV Linac. This rodent model is focused on the research of the inflammatory effects produced by ionizing radiation in the brain. In this work comparisons between Pencil Beam and Monte Carlo techniques, were used in order to evaluate accuracy of the calculated dose using a commercial planning system. Challenges in this murine model are discussed.

Hepatozoon parasites (Apicomplexa: Adeleorina) in bats.

PubMed

Pinto, C Miguel; Helgen, Kristofer M; Fleischer, Robert C; Perkins, Susan L

2013-08-01

We provide the first evidence of Hepatozoon parasites infecting bats. We sequenced a short fragment of the 18S rRNA gene (~600 base pairs) of Hepatozoon parasites from 3 Hipposideros cervinus bats from Borneo. Phylogenies inferred by model-based methods place these Hepatozoon within a clade formed by parasites of reptiles, rodents, and marsupials. We discuss the scenario that bats might be common hosts of Hepatozoon.

Experimental evaluation of rodent exclusion methods to reduce hantavirus transmission to residents in a Native American community in New Mexico.

PubMed

Hopkins, Andrew S; Whitetail-Eagle, Joe; Corneli, Amy L; Person, Bobbie; Ettestad, Paul J; DiMenna, Mark; Norstog, Jon; Creswell, Jacob; Khan, Ali S; Olson, James G; Cavallaro, Kathleen F; Bryan, Ralph T; Cheek, James E; Begay, Bruce; Hoddenbach, Gerard A; Ksiazek, Thomas G; Mills, James N

2002-01-01

We conducted a pilot study to evaluate the efficacy of rodent proofing continuously occupied homes as a method for lowering the risk for hantavirus pulmonary syndrome (HPS) among residents of a Native American community in northwestern New Mexico. Rodent proofing of dwellings was paired with culturally appropriate health education. Seventy homes were randomly assigned to treatment or control categories. Treatment homes were rodent-proofed by sealing openings around foundations, doors, roofs, and pipes and repairing screens and windows. Repairs to each dwelling were limited to $500 US. After repairs were completed, 15-20 snap traps were placed in each treatment and control home and checked approximately every 2 days for an average of 3-4 weeks. During 23,373 trap nights, one house mouse (Mus musculus) was captured in one treatment home, and 20 mice (16 deer mice, Peromyscus maniculatus, two Pinyon mice, Peromyscus truei, and two unidentified mice) were captured in five control homes (one house had 14 captures, two had two captures, and two had one capture). Trap success was 0.01% in treatment homes and 0.15% in controls. Intensity of infestation (mean number of mice captured per infested home) was 1 in treatment homes and 4 in controls. Observations of evidence of infestation (feces, nesting material, gnaw marks, or reports of infestation by occupant) per 100 days of observation were 1.2 in treatment homes and 3.1 in controls. Statistical power of the experiment was limited because it coincided with a period of low rodent abundance (August-November 2000). Nevertheless, these results suggest that inexpensive rodent proofing of occupied rural homes can decrease the frequency and intensity of rodent intrusion, thereby reducing the risk of HPS among rural residents in the southwestern United States.

Species-specific vesicular monoamine transporter 2 (VMAT2) expression in mammalian pancreatic beta cells: implications for optimising radioligand-based human beta cell mass (BCM) imaging in animal models

PubMed Central

Hartwig, N. R.; Kalmbach, N.; Klietz, M.; Anlauf, M.; Eiden, L. E.; Weihe, E.

2014-01-01

Aims/hypothesis Imaging of beta cell mass (BCM) is a major challenge in diabetes research. The vesicular monoamine transporter 2 (VMAT2) is abundantly expressed in human beta cells. Radiolabelled analogues of tetrabenazine (TBZ; a low-molecular-weight, cell-permeant VMAT2-selective ligand) have been employed for pancreatic islet imaging in humans. Since reports on TBZ-based VMAT2 imaging in rodent pancreas have been fraught with confusion, we compared VMAT2 gene expression patterns in the mouse, rat, pig and human pancreas, to identify appropriate animal models with which to further validate and optimise TBZ imaging in humans. Methods We used a panel of highly sensitive VMAT2 antibodies developed against equivalently antigenic regions of the transporter from each species in combination with immunostaining for insulin and species-specific in situ hybridisation probes. Individual pancreatic islets were obtained by laser-capture microdissection and subjected to analysis of mRNA expression of VMAT2. Results The VMAT2 protein was not expressed in beta cells in the adult pancreas of common mouse or rat laboratory strains, in contrast to its expression in beta cells (but not other pancreatic endocrine cell types) in the pancreas of pigs and humans. VMAT2- and tyrosine hydroxylase co-positive (catecholaminergic) innervation was less abundant in humans than in rodents. VMAT2-positive mast cells were identified in the pancreas of all species. Conclusions/interpretation Primates and pigs are suitable models for TBZ imaging of beta cells. Rodents, because of a complete lack of VMAT2 expression in the endocrine pancreas, are a ‘null’ model for assessing interference with BCM measurements by VMAT2-positive mast cells and sympathetic innervation in the pancreas. PMID:23404442

Chromosomal evolution in Rodentia

PubMed Central

Romanenko, S A; Perelman, P L; Trifonov, V A; Graphodatsky, A S

2012-01-01

Rodentia is the most species-rich mammalian order and includes several important laboratory model species. The amount of new information on karyotypic and phylogenetic relations within and among rodent taxa is rapidly increasing, but a synthesis of these data is currently lacking. Here, we have integrated information drawn from conventional banding studies, recent comparative painting investigations and molecular phylogenetic reconstructions of different rodent taxa. This permitted a revision of several ancestral karyotypic reconstructions, and a more accurate depiction of rodent chromosomal evolution. PMID:22086076

High-resolution in vivo Wistar rodent brain atlas based on T1 weighted image

NASA Astrophysics Data System (ADS)

Huang, Su; Lu, Zhongkang; Huang, Weimin; Seramani, Sankar; Ramasamy, Boominathan; Sekar, Sakthivel; Guan, Cuntai; Bhakoo, Kishore

2016-03-01

Image based atlases for rats brain have a significant impact on pre-clinical research. In this project we acquired T1-weighted images from Wistar rodent brains with fine 59μm isotropical resolution for generation of the atlas template image. By applying post-process procedures using a semi-automatic brain extraction method, we delineated the brain tissues from source data. Furthermore, we applied a symmetric group-wise normalization method to generate an optimized template of T1 image of rodent brain, then aligned our template to the Waxholm Space. In addition, we defined several simple and explicit landmarks to corresponding our template with the well known Paxinos stereotaxic reference system. Anchoring at the origin of the Waxholm Space, we applied piece-wise linear transformation method to map the voxels of the template into the coordinates system in Paxinos' stereotoxic coordinates to facilitate the labelling task. We also cross-referenced our data with both published rodent brain atlas and image atlases available online, methodologically labelling the template to produce a Wistar brain atlas identifying more than 130 structures. Particular attention was paid to the cortex and cerebellum, as these areas encompass the most researched aspects of brain functions. Moreover, we adopted the structure hierarchy and naming nomenclature common to various atlases, so that the names and hierarchy structure presented in the atlas are readily recognised for easy use. It is believed the atlas will present a useful tool in rodent brain functional and pharmaceutical studies.

Effects of Humidity Variation on the Hantavirus Infection and Hemorrhagic Fever with Renal Syndrome Occurrence in Subtropical China

PubMed Central

Xiao, Hong; Huang, Ru; Gao, Li-Dong; Huang, Cun-Rui; Lin, Xiao-Ling; Li, Na; Liu, Hai-Ning; Tong, Shi-Lu; Tian, Huai-Yu

2016-01-01

Infection rates of rodents have a significant influence on the transmission of hemorrhagic fever with renal syndrome (HFRS). In this study, four cities and two counties with high HFRS incidence in eastern Hunan Province in China were studied, and surveillance data of rodents, as well as HFRS cases and related environmental variables from 2007 to 2010, were collected. Results indicate that the distribution and infection rates of rodents are closely associated with environmental conditions. Hantavirus infections in rodents were positively correlated with temperature vegetation dryness index and negatively correlated with elevation. The predictive risk maps based on multivariate regression model revealed that the annual variation of infection risks is small, whereas monthly variation is large and corresponded well to the seasonal variation of human HFRS incidence. The identification of risk factors and risk prediction provides decision support for rodent surveillance and the prevention and control of HFRS. PMID:26711521

Bone morphology of the hind limbs in two caviomorph rodents.

PubMed

de Araújo, F A P; Sesoko, N F; Rahal, S C; Teixeira, C R; Müller, T R; Machado, M R F

2013-04-01

In order to evaluate the hind limbs of caviomorph rodents a descriptive analysis of the Cuniculus paca (Linnaeus, 1766) and Hydrochoerus hydrochaeris (Linnaeus, 1766) was performed using anatomical specimens, radiography, computed tomography (CT) and full-coloured prototype models to generate bone anatomy data. The appendicular skeleton of the two largest rodents of Neotropical America was compared with the previously reported anatomical features of Rattus norvegicus (Berkenhout, 1769) and domestic Cavia porcellus (Linnaeus, 1758). The structures were analyzed macroscopically and particular findings of each species reported. Features including the presence of articular fibular projection and lunulae were observed in the stifle joint of all rodents. Imaging aided in anatomical description and, specifically in the identification of bone structures in Cuniculus paca and Hydrochoerus hydrochaeris. The imaging findings were correlated with the anatomical structures observed. The data may be used in future studies comparing these animals to other rodents and mammalian species. © 2012 Blackwell Verlag GmbH.

A NEW AUTOCLAVE SYSTEM FOR STERILIZING VITAMIN-FORTIFIED, COMMERCIAL RODENT DIETS WITH LOWER NUTRIENT LOSS.

DTIC Science & Technology

would (a) require less time and (b) not destroy vitamins. Feed contaminated with Bacillus stearothermophilus and B. subtilis was sterilized in high...The study was designed to develop a method for sterilizing vitamin-fortified commercial diets for feeding germ-free and defined-flora rodents that...high-prevacuum autoclaves makes possible a reduction in the time required to sterilize autoclavable, commercial diets. Previous methods have required

The impact of fossil calibrations, codon positions and relaxed clocks on the divergence time estimates of the native Australian rodents (Conilurini).

PubMed

Nilsson, Maria A; Härlid, Anna; Kullberg, Morgan; Janke, Axel

2010-05-01

The native rodents are the most species-rich placental mammal group on the Australian continent. Fossils of native Australian rodents belonging to the group Conilurini are known from Northern Australia at 4.5Ma. These fossil assemblages already display a rich diversity of rodents, but the exact timing of their arrival on the Australian continent is not yet established. The complete mitochondrial genomes of two native Australian rodents, Leggadina lakedownensis (Lakeland Downs mouse) and Pseudomys chapmani (Western Pebble-mound mouse) were sequenced for investigating their evolutionary history. The molecular data were used for studying the phylogenetic position and divergence times of the Australian rodents, using 12 calibration points and various methods. Phylogenetic analyses place the native Australian rodents as the sister-group to the genus Mus. The Mus-Conilurini calibration point (7.3-11.0Ma) is highly critical for estimating rodent divergence times, while the influence of the different algorithms on estimating divergence times is negligible. The influence of the data type was investigated, indicating that amino acid data are more likely to reflect the correct divergence times than nucleotide sequences. The study on the problems related to estimating divergence times in fast-evolving lineages such as rodents, emphasize the choice of data and calibration points as being critical. Furthermore, it is essential to include accurate calibration points for fast-evolving groups, because the divergence times can otherwise be estimated to be significantly older. The divergence times of the Australian rodents are highly congruent and are estimated to 6.5-7.2Ma, a date that is compatible with their fossil record.

Magnetic Capture of a Molecular Biomarker from Synovial Fluid in a Rat Model of Knee Osteoarthritis

PubMed Central

Yarmola, Elena G.; Shah, Yash; Arnold, David P.; Dobson, Jon; Allen, Kyle D.

2015-01-01

Biomarker development for osteoarthritis (OA) often begins in rodent models, but can be limited by an inability to aspirate synovial fluid from a rodent stifle (similar to the human knee). To address this limitation, we have developed a magnetic nanoparticle-based technology to collect biomarkers from a rodent stifle, termed magnetic capture. Using a common OA biomarker - the c-terminus telopeptide of type II collagen (CTXII) - magnetic capture was optimized in vitro using bovine synovial fluid and then tested in a rat model of knee OA. Anti-CTXII antibodies were conjugated to the surface of superparamagnetic iron oxide-containing polymeric particles. Using these anti-CTXII particles, magnetic capture was able to estimate the level of CTXII in 25 µL aliquots of bovine synovial fluid; and under controlled conditions, this estimate was unaffected by synovial fluid viscosity. Following in vitro testing, anti-CTXII particles were tested in a rat monoiodoacetate model of knee OA. CTXII could be magnetically captured from a rodent stifle without the need to aspirate fluid and showed 10 fold changes in CTXII levels from OA-affected joints relative to contralateral control joints. Combined, these data demonstrate the ability and sensitivity of magnetic capture for post-mortem analysis of OA biomarkers in the rat. PMID:26136062

Magnetic Capture of a Molecular Biomarker from Synovial Fluid in a Rat Model of Knee Osteoarthritis.

PubMed

Yarmola, Elena G; Shah, Yash; Arnold, David P; Dobson, Jon; Allen, Kyle D

2016-04-01

Biomarker development for osteoarthritis (OA) often begins in rodent models, but can be limited by an inability to aspirate synovial fluid from a rodent stifle (similar to the human knee). To address this limitation, we have developed a magnetic nanoparticle-based technology to collect biomarkers from a rodent stifle, termed magnetic capture. Using a common OA biomarker--the c-terminus telopeptide of type II collagen (CTXII)--magnetic capture was optimized in vitro using bovine synovial fluid and then tested in a rat model of knee OA. Anti-CTXII antibodies were conjugated to the surface of superparamagnetic iron oxide-containing polymeric particles. Using these anti-CTXII particles, magnetic capture was able to estimate the level of CTXII in 25 μL aliquots of bovine synovial fluid; and under controlled conditions, this estimate was unaffected by synovial fluid viscosity. Following in vitro testing, anti-CTXII particles were tested in a rat monoiodoacetate model of knee OA. CTXII could be magnetically captured from a rodent stifle without the need to aspirate fluid and showed tenfold changes in CTXII levels from OA-affected joints relative to contralateral control joints. Combined, these data demonstrate the ability and sensitivity of magnetic capture for post-mortem analysis of OA biomarkers in the rat.

Map making in the 21st century: charting breast cancer susceptibility pathways in rodent models.

PubMed

Blackburn, Anneke C; Jerry, D Joseph

2011-04-01

Genetic factors play an important role in determining risk and resistance to increased breast cancer. Recent technological advances have made it possible to analyze hundreds of thousands of single nucleotide polymorphisms in large-scale association studies in humans and have resulted in identification of alleles in over 20 genes that influence breast cancer risk. Despite these advances, the challenge remains in identifying what the functional polymorphisms are that confer the increased risk, and how these genetic variants interact with each other and with environmental factors. In rodents, the incidence of mammary tumors varies among strains, such that they can provide alternate ideas for candidate pathways involved in humans. Mapping studies in animals have unearthed numerous loci for breast cancer susceptibility that have been validated in human populations. In a reciprocal manner, knockin and knockout mice have been used to validate the tumorigenicity of risk alleles found in population studies. Rodent studies also underscore the complexity of interactions among alleles. The fact that genes affecting risk and resistance to mammary tumors in rodents depend greatly upon the carcinogenic challenge emphasizes the importance of gene x environment interactions. The challenge to rodent geneticists now is to capitalize on the ability to control the genetics and environment in rodent models of tumorigenesis to better understand the biology of breast cancer development, to identify those polymorphisms most relevant to human susceptibility and to identify compensatory pathways that can be targeted for improved prevention in women at highest risk of developing breast cancer.

COMPARATIVE MICROARRAY EXPRESSION ANALYSIS OF SELECTED CANCER RELEVANT GENES IN HYPERTENSIVE RESISTANT VERSUS SUSCEPTIBLE RODENT STRAINS

EPA Science Inventory

Hypertension and cancer are prevalent diseases. Epidemiological studies suggest that hypertension may increase the long term risk of cancer. Identification of resistance and/or susceptibility genes using rodent models could provide important insights into the management and treat...

Two new rodent models for actinide toxicity studies. [/sup 237/Pu, /sup 241/Am

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taylor, G.N.; Jones, C.W.; Gardner, P.A.

1981-04-01

Two small rodent species, the grasshopper mouse (Onychomys leucogaster) and the deer mouse (Peromyscus maniculatus), have tenacious and high retention in the liver and skeleton of plutonium and americium following intraperitoneal injection of Pu and Am in citrate solution. Liver retention of Pu and Am in the grasshopper mouse is higher than liver retention in the deer mouse. Both of these rodents are relatively long-lived, breed well in captivity, and adapt suitably to laboratory conditions. It is suggested that these two species of mice, in which plutonium retention is high and prolonged in both the skeleton and liver, as itmore » is in man, may be useful animal models for actinide toxicity studies.« less

The need to implement the landscape of fear within rodent pest management strategies

PubMed Central

Belmain, Steven R; Singleton, Grant R; Groot Koerkamp, Peter WG; Meerburg, Bastiaan G

2017-01-01

Abstract Current reactive pest management methods have serious drawbacks such as the heavy reliance on chemicals, emerging genetic rodenticide resistance and high secondary exposure risks. Rodent control needs to be based on pest species ecology and ethology to facilitate the development of ecologically based rodent management (EBRM). An important aspect of EBRM is a strong understanding of rodent pest species ecology, behaviour and spatiotemporal factors. Gaining insight into the behaviour of pest species is a key aspect of EBRM. The landscape of fear (LOF) is a mapping of the spatial variation in the foraging cost arising from the risk of predation, and reflects the levels of fear a prey species perceives at different locations within its home range. In practice, the LOF maps habitat use as a result of perceived fear, which shows where bait or traps are most likely to be encountered and used by rodents. Several studies have linked perceived predation risk of foraging animals with quitting‐harvest rates or giving‐up densities (GUDs). GUDs have been used to reflect foraging behaviour strategies of predator avoidance, but to our knowledge very few papers have directly used GUDs in relation to pest management strategies. An opportunity for rodent control strategies lies in the integration of the LOF of rodents in EBRM methodologies. Rodent management could be more efficient and effective by concentrating on those areas where rodents perceive the least levels of predation risk. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. PMID:28556521

Isolation of invasive Plasmodium yoelii merozoites with a long half-life to evaluate invasion dynamics and potential invasion inhibitors.

PubMed

Mutungi, Joe Kimanthi; Yahata, Kazuhide; Sakaguchi, Miako; Kaneko, Osamu

2015-11-01

Malaria symptoms and pathogenesis are caused by blood stage parasite burdens of Plasmodium spp., for which invasion of red blood cells (RBCs) by merozoites is essential. Successful targeting by either drugs or vaccines directed against the whole merozoite or its antigens during its transient extracellular status would contribute to malaria control by impeding RBC invasion. To understand merozoite invasion biology and mechanisms, it is desired to obtain merozoites that retain their invasion activity in vitro. Accordingly, methods have been developed to isolate invasive Plasmodium knowlesi and Plasmodium falciparum merozoites. Rodent malaria parasite models offer ease in laboratory maintenance and experimental genetic modifications; however, no methods have been reported regarding isolation of high numbers of invasive rodent malaria merozoites. In this study, Plasmodium yoelii-infected RBCs were obtained from infected mice, and mature schizont-infected RBCs enriched via Histodenz™ density gradients. Merozoites retaining invasion activity were then isolated by passing the preparations through a filter membrane. RBC-invaded parasites developed to mature stages in vitro in a synchronous manner. Isolated merozoites were evaluated for retention of invasion activity following storage at different temperatures prior to incubation with uninfected mouse RBCs. Isolated merozoites retained their invasion activity 4h after isolation at 10 or 15 °C, whereas their invasion activity reduced to 0-10% within 30 min when incubated on ice or at 37 °C prior to RBC invasion assay. Images of merozoites at successive steps during RBC invasion were captured by light and transmission electron microscopy. Synthetic peptides derived from the amino acid sequence of the P. yoelii invasion protein RON2 efficiently inhibited RBC invasion. The developed method to isolate and keep invasive P. yoelii merozoites for up to 4h is a powerful tool to study the RBC invasion biology of this parasite. This method provides an important platform to evaluate the mode of action of drugs and vaccine candidates targeting the RBC invasion steps using rodent malaria model. Copyright © 2015 Elsevier B.V. All rights reserved.

Post-traumatic stress disorder and beyond: an overview of rodent stress models.

PubMed

Schöner, Johanna; Heinz, Andreas; Endres, Matthias; Gertz, Karen; Kronenberg, Golo

2017-10-01

Post-traumatic stress disorder (PTSD) is a psychiatric disorder of high prevalence and major socioeconomic impact. Patients suffering from PTSD typically present intrusion and avoidance symptoms and alterations in arousal, mood and cognition that last for more than 1 month. Animal models are an indispensable tool to investigate underlying pathophysiological pathways and, in particular, the complex interplay of neuroendocrine, genetic and environmental factors that may be responsible for PTSD induction. Since the 1960s, numerous stress paradigms in rodents have been developed, based largely on Seligman's seminal formulation of 'learned helplessness' in canines. Rodent stress models make use of physiological or psychological stressors such as foot shock, underwater trauma, social defeat, early life stress or predator-based stress. Apart from the brief exposure to an acute stressor, chronic stress models combining a succession of different stressors for a period of several weeks have also been developed. Chronic stress models in rats and mice may elicit characteristic PTSD-like symptoms alongside, more broadly, depressive-like behaviours. In this review, the major existing rodent models of PTSD are reviewed in terms of validity, advantages and limitations; moreover, significant results and implications for future research-such as the role of FKBP5, a mediator of the glucocorticoid stress response and promising target for therapeutic interventions-are discussed. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Effects of Excitotoxic Lesion with Inhaled Anesthetics on Nervous System Cells of Rodents.

PubMed

Quiroz-Padilla, Maria Fernanda; Guillazo-Blanch, Gemma; Sanchez, Magdy Y; Dominguez-Sanchez, Maria Andrea; Gomez, Rosa Margarita

2018-01-01

Different anesthesia methods can variably influence excitotoxic lesion effects on the brain. The main purpose of this review is to identify potential differences in the toxicity to nervous system cells of two common inhalation anesthesia methods, isoflurane and sevoflurane, used in combination with an excitotoxic lesion procedure in rodents. The use of bioassays in animal models has provided the opportunity to examine the role of specific molecules and cellular interactions that underlie important aspects of neurotoxic effects relating to calcium homeostasis and apoptosis activation. Processes induced by NMDA antagonist drugs involve translocation of Bax protein to mitochondrial membranes, allowing extra-mitochondrial leakage of cytochrome C, followed by sequence of changes that ending in activation of CASP-3. The literature demonstrates that the use of these anesthetics in excitotoxic surgery increases neuroinflammation activity facilitating the effects of apoptosis and necrosis on nervous system cells, depending on the concentration and exposure duration of the anesthetic. High numbers of microglia and astrocytes and high levels of proinflammatory cytokines and caspase activation possibly mediate these inflammatory responses. However, it is necessary to continue studies in rodents to understand the effect of the use of inhaled anesthetics with excitotoxic lesions in different developmental stages, including newborns, juveniles and adults. Understanding the mechanisms of regulation of cell death during development can potentially provide tools to promote neuroprotection and eventually achieve the repair of the nervous system in pathological conditions. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Temporal distribution and weather correlates of Norway rat (Rattus norvegicus) infestations in the city of Madrid, Spain.

PubMed

Tamayo Uria, Ibon; Mateu Mahiques, Jorge; Mughini Gras, Lapo

2013-06-01

Urban Norway rats are challenging pests, posing significant health and economic threats. Implementing ecologically based integrated rodent management (EBIRM) programmes relies primarily on the understanding of ecological relationships between rodents and their environments, with emphasis on the processes influencing rodent populations in the target ecosystem. We investigated the temporal distribution of urban Norway rat infestations in Madrid, Spain, and tested for the association of such infestations with temperature, relative humidity and precipitation by fitting a multivariate Poisson generalized linear model to a 3-year (2006-2008) daily time series of 4,689 Norway rat sightings. Norway rat infestations showed a marked seasonality, peaking in the summer. Most Norway rat sightings were reported on Mondays. Minimum temperature and relative humidity were positively associated with Norway rat infestation, whereas the association with precipitation was negative. The time series was adequately explained by the model. We identified previously unrecognized time periods that are more prone to Norway rat infestation than others and generated hypotheses about the association between weather, human outdoor activity, resource availability, rodent activity and population size. This provided local authorities engaged in preserving urban ecosystem health with basic research information to predict future rodent outbreaks and support the implementation of EBIRM programmes in urban areas.

Zebrafish as a model for acetylcholinesterase-inhibiting organophosphorus agent exposure and oxime reactivation

PubMed Central

Koenig, Jeffrey A.; Dao, Thuy L.; Kan, Robert K.; Shih, Tsung-Ming

2016-01-01

The current research progression efforts for investigating novel treatments for exposure to organophosphorus (OP) compounds that inhibit acetylcholinesterase (AChE), including pesticides and chemical warfare nerve agents (CWNAs), rely solely on in vitro cell assays and in vivo rodent models. The zebrafish (Danio rerio) is a popular, well-established vertebrate model in biomedical research that offers high-throughput capabilities and genetic manipulation not readily available with rodents. A number of research studies have investigated the effects of subacute developmental exposure to OP pesticides in zebrafish, observing detrimental effects on gross morphology, neuronal development, and behavior. Few studies, however, have utilized this model to evaluate treatments, such as oxime reactivators, anticholinergics, or anticonvulsants, following acute exposure. Preliminary work has investigated the effects of CWNA exposure. The results clearly demonstrated relative toxicity and oxime efficacy similar to that reported for the rodent model. This review surveys the current literature utilizing zebrafish as a model for OP exposure and highlights its potential use as a high-throughput system for evaluating AChE reactivator antidotal treatments to acute pesticide and CWNA exposure. PMID:27123828

The relevance of non-human primate and rodent malaria models for humans

PubMed Central

2011-01-01

At the 2010 Keystone Symposium on "Malaria: new approaches to understanding Host-Parasite interactions", an extra scientific session to discuss animal models in malaria research was convened at the request of participants. This was prompted by the concern of investigators that skepticism in the malaria community about the use and relevance of animal models, particularly rodent models of severe malaria, has impacted on funding decisions and publication of research using animal models. Several speakers took the opportunity to demonstrate the similarities between findings in rodent models and human severe disease, as well as points of difference. The variety of malaria presentations in the different experimental models parallels the wide diversity of human malaria disease and, therefore, might be viewed as a strength. Many of the key features of human malaria can be replicated in a variety of nonhuman primate models, which are very under-utilized. The importance of animal models in the discovery of new anti-malarial drugs was emphasized. The major conclusions of the session were that experimental and human studies should be more closely linked so that they inform each other, and that there should be wider access to relevant clinical material. PMID:21288352

A novel method for deriving thresholds of toxicological concern for vaccine constituents.

PubMed

White, Jennifer; Wrzesinski, Claudia; Green, Martin; Johnson, Giffe T; McCluskey, James D; Abritis, Alison; Harbison, Raymond D

2016-05-01

Safety assessment evaluating the presence of impurities, residual materials, and contaminants in vaccines is a focus of current research. Thresholds of toxicological concern (TTCs) are mathematically modeled levels used for assessing the safety of many food and medication constituents. In this study, six algorithms are selected from the open-access ToxTree software program to derive a method for calculating TTCs for vaccine constituents: In Vivo Rodent Micronucleus assay/LD50, Benigni-Bossa/LD50, Cramer Extended/LD50, In Vivo Rodent Micronucleus assay/TDLo, Benigni-Bossa/TDLo, and the Cramer Extended/TDLo. Using an initial dataset (n = 197) taken from INCHEM, RepDose, RTECS, and TOXNET, the chemicals were divided into two families: "positive" - based on the presence of structures associated with adverse outcomes, or "negative" - no such structures or having structures that appear to be protective of health. The final validation indicated that the Benigni-Bossa/LD50 method is the most appropriate for calculating TTCs for vaccine constituents. Final TTCs were designated as 18.06 μg/person and 20.61 μg/person for the Benigni-Bossa/LD50 positive and negative structural families, respectively.

Midbrain dopamine receptor availability is inversely associated with novelty-seeking traits in humans.

PubMed

Zald, David H; Cowan, Ronald L; Riccardi, Patrizia; Baldwin, Ronald M; Ansari, M Sib; Li, Rui; Shelby, Evan S; Smith, Clarence E; McHugo, Maureen; Kessler, Robert M

2008-12-31

Novelty-seeking personality traits are a major risk factor for the development of drug abuse and other unsafe behaviors. Rodent models of temperament indicate that high novelty responding is associated with decreased inhibitory autoreceptor control of midbrain dopamine neurons. It has been speculated that individual differences in dopamine functioning also underlie the personality trait of novelty seeking in humans. However, differences in the dopamine system of rodents and humans, as well as the methods for assessing novelty responding/seeking across species leave unclear to what extent the animal models inform our understanding of human personality. In the present study we examined the correlation between novelty-seeking traits in humans and D(2)-like (D(2)/D(3)) receptor availability in the substantia nigra/ventral tegmental area. Based on the rodent literature we predicted that novelty seeking would be characterized by lowered levels of D(2)-like (auto)receptor availability in the midbrain. Thirty-four healthy adults (18 men, 16 women) completed the Tridimensional Personality Questionnaire-Novelty-Seeking Scale and PET scanning with the D(2)/D(3) ligand [(18)F]fallypride. Novelty-Seeking personality traits were inversely associated with D(2)-like receptor availability in the ventral midbrain, an effect that remained significant after controlling for age. We speculate that the lower midbrain (auto)receptor availability seen in high novelty seekers leads to accentuated dopaminergic responses to novelty and other conditions that induce dopamine release.

Midbrain dopamine receptor availability is inversely associated with novelty seeking traits in humans

PubMed Central

Zald, David H.; Cowan, Ronald L.; Riccardi, Patrizia; Baldwin, Ronald M.; Ansari, M. Sib; Li, Rui; Shelby, Evan S.; Smith, Clarence E.; McHugo, Maureen; Kessler, Robert M.

2009-01-01

Novelty seeking personality traits are a major risk factor for the development of drug abuse and other unsafe behaviors. Rodent models of temperament indicate that high novelty responding is associated with decreased inhibitory autoreceptor control of midbrain dopamine neurons. It has been speculated that individual differences in dopamine functioning also underlie the personality trait of novelty seeking in humans. However, differences in the dopamine system of rodents and humans, as well as the methods for assessing novelty responding/seeking across species leave unclear to what extent the animal models inform our understanding of human personality. In the present study we examined the correlation between novelty seeking traits in humans and D2-like (D2/D3) receptor availability in the substantia nigra/ventral tegmental area. Based on the rodent literature we predicted that novelty seeking would be characterized by lowered levels of D2-like (auto)receptor availability in the midbrain. 34 healthy adults (18 men, 16 women) completed the Tridimensional Personality Questionnaire-Novelty Seeking Scale and PET scanning with the D2/D3 ligand [18F]fallypride. Novelty seeking personality traits were inversely associated with D2-like receptor availability in the ventral midbrain, an effect that remained significant after controlling for age. We speculate that the lower midbrain (auto)receptor availability seen in high novelty seekers leads to accentuated dopaminergic responses to novelty and other conditions that induce DA release. PMID:19118170

Safety assessment for hair-spray resins: risk assessment based on rodent inhalation studies.

PubMed

Carthew, Philip; Griffiths, Heather; Keech, Stephen; Hartop, Peter

2002-04-01

The methods involved in the safety assessment of resins used in hair-spray products have received little peer review, or debate in the published literature, despite their widespread use, in both hairdressing salons and the home. The safety assessment for these resins currently involves determining the type of lung pathology that can be caused in animal inhalation exposure studies, and establishing the no-observable-effect level (NOEL) for these pathologies. The likely human consumer exposure is determined by techniques that model the simulated exposure under "in use" conditions. From these values it is then possible to derive the likely safety factors for human exposure. An important part of this process would be to recognize the intrinsic differences between rodents and humans in terms of the respiratory doses that each species experiences during inhalation exposures, for the purpose of the safety assessment. Interspecies scaling factors become necessary when comparing the exposure doses experienced by rats, compared to humans, because of basic differences between species in lung clearance rates and the alveolar area in the lungs. The rodent inhalation data and modeled human exposure to Resin 6965, a resin polymer that is based on vinyl acetate, has been used to calculate the safety factor for human consumer exposure to this resin, under a range of "in use" exposure conditions. The use of this safety assessment process clearly demonstrates that Resin 6965 is acceptable for human consumer exposure under the conditions considered in this risk assessment.

Quadrupedal rodent gait compensations in a low dose monoiodoacetate model of osteoarthritis.

PubMed

Lakes, Emily H; Allen, Kyle D

2018-06-01

Rodent gait analysis provides robust, quantitative results for preclinical musculoskeletal and neurological models. In prior work, surgical models of osteoarthritis have been found to result in a hind limb shuffle-stepping gait compensation, while a high dose monoiodoacetate (MIA, 3 mg) model resulted in a hind limb antalgic gait. However, it is unknown whether the antalgic gait caused by MIA is associated with severity of degeneration from the high dosage or the whole-joint degeneration associated with glycolysis inhibition. This study evaluates rodent gait changes resulting from a low dose, 1 mg unilateral intra-articular injection of MIA compared to saline injected and naïve rats. Spatiotemporal and dynamic gait parameters were collected from a total of 42 male Lewis rats spread across 3 time points: 1, 2, and 4 weeks post-injection. To provide a detailed analysis of this low dose MIA model, gait analysis was used to uniquely quantify both fore and hind limb gait parameters. Our data indicate that 1 mg of MIA caused relatively minor degeneration and a shuffle-step gait compensation, similar to the compensation observed in prior surgical models. These data from a 1 mg MIA model show a different gait compensation compared to a previously studied 3 mg model. This 1 mg MIA model resulted in gait compensations more similar to a previously studied surgical model of osteoarthritis. Additionally, this study provides detailed 4 limb analysis of rodent gait that includes spatiotemporal and dynamic data from the same gait trial. These data highlight the importance of measuring dynamic data in combination with spatiotemporal data, since compensatory gait patterns may not be captured by spatial, temporal, or dynamic characterizations alone. Copyright © 2018 Elsevier B.V. All rights reserved.

Determination of adrenaline, noradrenaline and corticosterone in rodent blood by ion pair reversed phase UHPLC-MS/MS.

PubMed

Bergh, Marianne Skov-Skov; Bogen, Inger Lise; Andersen, Jannike Mørch; Øiestad, Åse Marit Leere; Berg, Thomas

2018-01-01

A novel ion pair reversed phase ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for simultaneous determination of the stress hormones adrenaline, noradrenaline and corticosterone in rodent blood was developed and fully validated. Separations were performed on an Acquity HSS T3 column (2.1mm i.d.×100mm, 1.8μm) with gradient elution and a runtime of 5.5min. The retention of adrenaline and noradrenaline was substantially increased by employing the ion pair reagent heptafluorobutyric acid (HFBA). Ion pair reagents are usually added to the mobile phase only, but we demonstrate for the first time that including HFBA to the sample reconstitution solvent as well, has a major impact on the chromatography of these compounds. The stability of adrenaline and corticosterone in rodent blood was investigated using the surrogate analytes adrenaline-d 3 and corticosterone-d 8 . The applicability of the described method was demonstrated by measuring the concentration of stress hormones in rodent blood samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of environment on the long-term consequences of chronic pain

PubMed Central

Bushnell, MC; Case, LK; Ceko, M; Cotton, VA; Gracely, JL; Low, LA; Pitcher, MH; Villemure, C

2014-01-01

Much evidence from pain patients and animal models shows that chronic pain does not exist in a vacuum, but has varied co-morbidities and far-reaching consequences. Patients with long-term pain often develop anxiety and depression and can manifest changes in cognitive functioning, particularly with working memory. Longitudinal studies in rodent models also show the development of anxiety-like behavior and cognitive changes weeks to months after an injury causing long-term pain. Brain imaging studies in pain patients and rodent models find that chronic pain is associated with anatomical and functional alterations in the brain. Nevertheless, studies in humans reveal that life-style choices, such as the practice of meditation or yoga, can reduce pain perception and have the opposite effect on the brain as does chronic pain. In rodent models, studies show that physical activity and a socially enriched environment reduce pain behavior and normalize brain function. Together, these studies suggest that the burden of chronic pain can be reduced by non-pharmacological interventions. PMID:25789436

In vivo efficacy of acyl CoA: diacylglycerol acyltransferase (DGAT) 1 inhibition in rodent models of postprandial hyperlipidemia.

PubMed

King, Andrew J; Segreti, Jason A; Larson, Kelly J; Souers, Andrew J; Kym, Philip R; Reilly, Regina M; Collins, Christine A; Voorbach, Martin J; Zhao, Gang; Mittelstadt, Scott W; Cox, Bryan F

2010-07-10

Postprandial serum triglyceride concentrations have recently been identified as a major, independent risk factor for future cardiovascular events. As a result, postprandial hyperlipidemia has emerged as a potential therapeutic target. The purpose of this study was two-fold. Firstly, to describe and characterize a standardized model of postprandial hyperlipidemia in multiple rodent species; and secondly, apply these rodent models to the evaluation of a novel class of pharmacologic agent; acyl CoA:diacylglycerol acyltransferase (DGAT) 1 inhibitors. Serum triglycerides were measured before and for 4h after oral administration of a standardized volume of corn oil, to fasted C57BL/6, ob/ob, apoE(-/-) and CD-1 mice; Sprague-Dawley and JCR/LA-cp rats; and normolipidemic and hyperlipidemic hamsters. Intragastric administration of corn oil increased serum triglycerides in all animals evaluated, however the magnitude and time-course of the postprandial triglyceride excursion varied. The potent and selective DGAT-1 inhibitor A-922500 (0.03, 0.3 and 3 mg/kg, p.o.), dose-dependently attenuated the maximal postprandial rise in serum triglyceride concentrations in all species tested. At the highest dose of DGAT-1 inhibitor, the postprandial triglyceride response was abolished. This study provides a comprehensive characterization of the time-course of postprandial hyperlipidemia in rodents. In addition, the ability of DGAT-1 inhibitors to attenuate postprandial hyperlipidemia in multiple rodent models, including those that feature insulin resistance, is documented. Exaggerated postprandial hyperlipidemia is inherent to insulin-resistant states in humans and contributes to the substantially elevated cardiovascular risk observed in these patients. Therefore, by attenuating postprandial hyperlipidemia, DGAT-1 inhibition may represent a novel therapeutic approach to reduce cardiovascular risk. Copyright 2010 Elsevier B.V. All rights reserved.

A novel two-step hierarchical quantitative structure-activity relationship modeling work flow for predicting acute toxicity of chemicals in rodents.

PubMed

Zhu, Hao; Ye, Lin; Richard, Ann; Golbraikh, Alexander; Wright, Fred A; Rusyn, Ivan; Tropsha, Alexander

2009-08-01

Accurate prediction of in vivo toxicity from in vitro testing is a challenging problem. Large public-private consortia have been formed with the goal of improving chemical safety assessment by the means of high-throughput screening. A wealth of available biological data requires new computational approaches to link chemical structure, in vitro data, and potential adverse health effects. A database containing experimental cytotoxicity values for in vitro half-maximal inhibitory concentration (IC(50)) and in vivo rodent median lethal dose (LD(50)) for more than 300 chemicals was compiled by Zentralstelle zur Erfassung und Bewertung von Ersatz- und Ergaenzungsmethoden zum Tierversuch (ZEBET; National Center for Documentation and Evaluation of Alternative Methods to Animal Experiments). The application of conventional quantitative structure-activity relationship (QSAR) modeling approaches to predict mouse or rat acute LD(50) values from chemical descriptors of ZEBET compounds yielded no statistically significant models. The analysis of these data showed no significant correlation between IC(50) and LD(50). However, a linear IC(50) versus LD(50) correlation could be established for a fraction of compounds. To capitalize on this observation, we developed a novel two-step modeling approach as follows. First, all chemicals are partitioned into two groups based on the relationship between IC(50) and LD(50) values: One group comprises compounds with linear IC(50) versus LD(50) relationships, and another group comprises the remaining compounds. Second, we built conventional binary classification QSAR models to predict the group affiliation based on chemical descriptors only. Third, we developed k-nearest neighbor continuous QSAR models for each subclass to predict LD(50) values from chemical descriptors. All models were extensively validated using special protocols. The novelty of this modeling approach is that it uses the relationships between in vivo and in vitro data only to inform the initial construction of the hierarchical two-step QSAR models. Models resulting from this approach employ chemical descriptors only for external prediction of acute rodent toxicity.

Imaging Tumor Cell Movement In Vivo

PubMed Central

Entenberg, David; Kedrin, Dmitriy; Wyckoff, Jeffrey; Sahai, Erik; Condeelis, John; Segall, Jeffrey E.

2013-01-01

This unit describes the methods that we have been developing for analyzing tumor cell motility in mouse and rat models of breast cancer metastasis. Rodents are commonly used both to provide a mammalian system for studying human tumor cells (as xenografts in immunocompromised mice) as well as for following the development of tumors from a specific tissue type in transgenic lines. The Basic Protocol in this unit describes the standard methods used for generation of mammary tumors and imaging them. Additional protocols for labeling macrophages, blood vessel imaging, and image analysis are also included. PMID:23456602

Morphological and Molecular Characterization of a New Trichuris Species (Nematoda- Trichuridae), and Phylogenetic Relationships of Trichuris Species of Cricetid Rodents from Argentina

PubMed Central

Robles, María del Rosario; Cutillas, Cristina; Panei, Carlos Javier; Callejón, Rocío

2014-01-01

Populations of Trichuris spp. isolated from six species of sigmodontine rodents from Argentina were analyzed based on morphological characteristics and ITS2 (rDNA) region sequences. Molecular data provided an opportunity to discuss the phylogenetic relationships among the Trichuris spp. from Noth and South America (mainly from Argentina). Trichuris specimens were identified morphologically as Trichuris pardinasi, T. navonae, Trichuris sp. and Trichuris new species, described in this paper. Sequences analyzed by Maximum Parsimony, Maximum Likelihood and Bayesian inference methods showed four main clades corresponding with the four different species regardless of geographical origin and host species. These four species from sigmodontine rodents clustered together and separated from Trichuris species isolated from murine and arvicoline rodents (outgroup). Different genetic lineages observed among Trichuris species from sigmodontine rodents which supported the proposal of a new species. Moreover, host distribution showed correspondence with the different tribes within the subfamily Sigmodontinae. PMID:25393618

Rodent models of congenital and hereditary cataract in man.

PubMed

Tripathi, B J; Tripathi, R C; Borisuth, N S; Dhaliwal, R; Dhaliwal, D

1991-01-01

Because the organogenesis and physiology of the lens are essentially similar in various mammals, an understanding of the etiology and pathogenesis of the formation of cataract in an animal model will enhance our knowledge of cataractogenesis in man. In this review, we summarize the background, etiology, and pathogenesis of cataracts that occur in rodents. The main advantages of using rodent mutants include the well-researched genetics of the animals and the comparative ease of breeding of large litters. Numerous rodent models of congenital and hereditary cataracts have been studied extensively. In mice, the models include the Cts strain, Fraser mouse, lens opacity gene (Lop) strain, Lop-2 and Lop-3 strains, Philly mouse, Nakano mouse, Nop strain, Deer mouse, Emory mouse, Swiss Webster strain, Balb/c-nct/nct mouse, and SAM-R/3 strain. The rat models include BUdR, ICR, Sprague-Dawley, and Wistar rats, the spontaneously hypertensive rat (SHR), the John Rapp inbred strain of Dahl salt-sensitive rat, as well as WBN/Kob, Royal College of Surgeons (RCS), and Brown-Norway rats. Other proposed models for the study of hereditary cataract include the degu and the guinea pig. Because of the ease of making clinical observations in vivo and the subsequent availability of the intact lens for laboratory analyses at different stages of cataract formation, these animals provide excellent models for clinicopathologic correlations, for monitoring of the natural history of the aging process and of metabolic defects, as well as for investigations on the effect of cataract-modulating agents and drugs, including the prospect of gene therapy.

New Exposure Biomarkers as Tools for Breast Cancer Epidemiology, Biomonitoring, and Prevention: A Systematic Approach Based on Animal Evidence

PubMed Central

Ackerman, Janet M.; Attfield, Kathleen R.; Brody, Julia Green

2014-01-01

Background: Exposure to chemicals that cause rodent mammary gland tumors is common, but few studies have evaluated potential breast cancer risks of these chemicals in humans. Objective: The goal of this review was to identify and bring together the needed tools to facilitate the measurement of biomarkers of exposure to potential breast carcinogens in breast cancer studies and biomonitoring. Methods: We conducted a structured literature search to identify measurement methods for exposure biomarkers for 102 chemicals that cause rodent mammary tumors. To evaluate concordance, we compared human and animal evidence for agents identified as plausibly linked to breast cancer in major reviews. To facilitate future application of exposure biomarkers, we compiled information about relevant cohort studies. Results: Exposure biomarkers have been developed for nearly three-quarters of these rodent mammary carcinogens. Analytical methods have been published for 73 of the chemicals. Some of the remaining chemicals could be measured using modified versions of existing methods for related chemicals. In humans, biomarkers of exposure have been measured for 62 chemicals, and for 45 in a nonoccupationally exposed population. The Centers for Disease Control and Prevention has measured 23 in the U.S. population. Seventy-five of the rodent mammary carcinogens fall into 17 groups, based on exposure potential, carcinogenicity, and structural similarity. Carcinogenicity in humans and rodents is generally consistent, although comparisons are limited because few agents have been studied in humans. We identified 44 cohort studies, with a total of > 3.5 million women enrolled, that have recorded breast cancer incidence and stored biological samples. Conclusions: Exposure measurement methods and cohort study resources are available to expand biomonitoring and epidemiology related to breast cancer etiology and prevention. Citation: Rudel RA, Ackerman JM, Attfield KR, Brody JG. 2014. New exposure biomarkers as tools for breast cancer epidemiology, biomonitoring, and prevention: a systematic approach based on animal evidence. Environ Health Perspect 122:881–895; http://dx.doi.org/10.1289/ehp.1307455 PMID:24818537

Rodent models of adaptive decision making.

PubMed

Izquierdo, Alicia; Belcher, Annabelle M

2012-01-01

Adaptive decision making affords the animal the ability to respond quickly to changes in a dynamic environment: one in which attentional demands, cost or effort to procure the reward, and reward contingencies change frequently. The more flexible the organism is in adapting choice behavior, the more command and success the organism has in navigating its environment. Maladaptive decision making is at the heart of much neuropsychiatric disease, including addiction. Thus, a better understanding of the mechanisms that underlie normal, adaptive decision making helps achieve a better understanding of certain diseases that incorporate maladaptive decision making as a core feature. This chapter presents three general domains of methods that the experimenter can manipulate in animal decision-making tasks: attention, effort, and reward contingency. Here, we present detailed methods of rodent tasks frequently employed within these domains: the Attentional Set-Shift Task, Effortful T-maze Task, and Visual Discrimination Reversal Learning. These tasks all recruit regions within the frontal cortex and the striatum, and performance is heavily modulated by the neurotransmitter dopamine, making these assays highly valid measures in the study of psychostimulant addiction.

ProTox: a web server for the in silico prediction of rodent oral toxicity

PubMed Central

Drwal, Malgorzata N.; Banerjee, Priyanka; Dunkel, Mathias; Wettig, Martin R.; Preissner, Robert

2014-01-01

Animal trials are currently the major method for determining the possible toxic effects of drug candidates and cosmetics. In silico prediction methods represent an alternative approach and aim to rationalize the preclinical drug development, thus enabling the reduction of the associated time, costs and animal experiments. Here, we present ProTox, a web server for the prediction of rodent oral toxicity. The prediction method is based on the analysis of the similarity of compounds with known median lethal doses (LD50) and incorporates the identification of toxic fragments, therefore representing a novel approach in toxicity prediction. In addition, the web server includes an indication of possible toxicity targets which is based on an in-house collection of protein–ligand-based pharmacophore models (‘toxicophores’) for targets associated with adverse drug reactions. The ProTox web server is open to all users and can be accessed without registration at: http://tox.charite.de/tox. The only requirement for the prediction is the two-dimensional structure of the input compounds. All ProTox methods have been evaluated based on a diverse external validation set and displayed strong performance (sensitivity, specificity and precision of 76, 95 and 75%, respectively) and superiority over other toxicity prediction tools, indicating their possible applicability for other compound classes. PMID:24838562

Automated assessment of pain in rats using a voluntarily accessed static weight-bearing test.

PubMed

Kim, Hung Tae; Uchimoto, Kazuhiro; Duellman, Tyler; Yang, Jay

2015-11-01

The weight-bearing test is one method to assess pain in rodent animal models; however, the acceptance of this convenient method is limited by the low throughput data acquisition and necessity of confining the rodents to a small chamber. We developed novel data acquisition hardware and software, data analysis software, and a conditioning protocol for an automated high throughput static weight-bearing assessment of pain. With this device, the rats voluntarily enter the weighing chamber, precluding the necessity to restrain the animals and thereby removing the potential stress-induced confounds as well as operator selection bias during data collection. We name this device the Voluntarily Accessed Static Incapacitance Chamber (VASIC). Control rats subjected to the VASIC device provided hundreds of weight-bearing data points in a single behavioral assay. Chronic constriction injury (CCI) surgery and paw pad injection of complete Freund's adjuvant (CFA) or carrageenan in rats generated hundreds of weight-bearing data during a 30 minute recording session. Rats subjected to CCI, CFA, or carrageenan demonstrated the expected bias in weight distribution favoring the un-operated leg, and the analgesic effect of i.p. morphine was demonstrated. In comparison with existing methods, brief water restriction encouraged the rats to enter the weighing chamber to access water, and an infrared detector confirmed the rat position with feet properly positioned on the footplates, triggering data collection. This allowed hands-off measurement of weight distribution data reducing operator selection bias. The VASIC device should enhance the hands-free parallel collection of unbiased weight-bearing data in a high throughput manner, allowing further testing of this behavioral measure as an effective assessment of pain in rodents. Copyright © 2015. Published by Elsevier Inc.

The need to implement the landscape of fear within rodent pest management strategies.

PubMed

Krijger, Inge M; Belmain, Steven R; Singleton, Grant R; Groot Koerkamp, Peter Wg; Meerburg, Bastiaan G

2017-12-01

Current reactive pest management methods have serious drawbacks such as the heavy reliance on chemicals, emerging genetic rodenticide resistance and high secondary exposure risks. Rodent control needs to be based on pest species ecology and ethology to facilitate the development of ecologically based rodent management (EBRM). An important aspect of EBRM is a strong understanding of rodent pest species ecology, behaviour and spatiotemporal factors. Gaining insight into the behaviour of pest species is a key aspect of EBRM. The landscape of fear (LOF) is a mapping of the spatial variation in the foraging cost arising from the risk of predation, and reflects the levels of fear a prey species perceives at different locations within its home range. In practice, the LOF maps habitat use as a result of perceived fear, which shows where bait or traps are most likely to be encountered and used by rodents. Several studies have linked perceived predation risk of foraging animals with quitting-harvest rates or giving-up densities (GUDs). GUDs have been used to reflect foraging behaviour strategies of predator avoidance, but to our knowledge very few papers have directly used GUDs in relation to pest management strategies. An opportunity for rodent control strategies lies in the integration of the LOF of rodents in EBRM methodologies. Rodent management could be more efficient and effective by concentrating on those areas where rodents perceive the least levels of predation risk. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Concerns about the widespread use of rodent models for human risk assessments of endocrine disruptors

PubMed Central

Habert, René; Muczynski, Vincent; Grisin, Tiphany; Moison, Delphine; Messiaen, Sébastien; Frydman, René; Benachi, Alexandra; Delbes, Géraldine; Lambrot, Romain; Lehraiki, Abdelali; N'Tumba-Byn, Thierry; Guerquin, Marie-Justine; Levacher, Christine; Rouiller-Fabre, Virginie; Livera, Gabriel

2014-01-01

Fetal testis is a major target of endocrine disruptors (EDs). During the last 20 years, we have developed an organotypic culture system that maintains the function of the different fetal testis cell types and have used this approach as a toxicological test to evaluate the effects of various compounds on gametogenesis and steroidogenesis in rat, mouse and human testes. We named this test rat, mouse and human fetal testis assay. With this approach, we compared the effects of six potential EDs ((mono-(2-ethylhexyl) phthalate (MEHP), cadmium, depleted uranium, diethylstilboestrol (DES), bisphenol A (BPA) and metformin) and one signalling molecule (retinoic acid (RA)) on the function of rat, mouse and human fetal testis at a comparable developmental stage. We found that the response is similar in humans and rodents for only one third of our analyses. For instance, RA and MEHP have similar negative effects on gametogenesis in the three species. For another third of our analyses, the threshold efficient concentrations that disturb gametogenesis and/or steroidogenesis differ as a function of the species. For instance, BPA and metformin have similar negative effects on steroidogenesis in human and rodents, but at different threshold doses. For the last third of our analyses, the qualitative response is species specific. For instance, MEHP and DES affect steroidogenesis in rodents, but not in human fetal testis. These species differences raise concerns about the extrapolation of data obtained in rodents to human health risk assessment and highlight the need of rigorous comparisons of the effects in human and rodent models, when assessing ED risk. PMID:24497529

Long-term Hyperglycemia Naturally Induces Dental Caries but Not Periodontal Disease in Type 1 and Type 2 Diabetic Rodents.

PubMed

Nakahara, Yutaka; Ozaki, Kiyokazu; Matsuura, Tetsuro

2017-11-01

Periodontal disease (PD) in patients with diabetes is described as the sixth complication of diabetes. We have previously shown that diabetes increases dental caries, and carious inflammation might have a strong effect on the adjacent periodontal tissue in diabetic rodent models. However, the possibility that hyperglycemia may induce PD in diabetic animals could not be completely eliminated. The goal of this study was to confirm the presence of PD in diabetic animal models by preventing carious inflammation with fluoride administration. F344 rats injected with alloxan (type 1 diabetic model) and db/db mice (type 2 diabetic model) were given either tap water alone or tap water containing fluoride. A cariostatic effect of fluoride was evident in the diabetic animals. Meanwhile, fluoride treatment drastically attenuated periodontal inflammation in addition to preventing dental caries. Furthermore, with fluoride treatment, periodontitis was notably nonexistent in the periodontal tissue surrounding the normal molars, whereas the caries-forming process was clearly observed in the teeth that were enveloped with persistent periodontitis, suggesting that enhanced periodontal inflammation might have been derived from the dental caries in the diabetic rodents rather than from the PD. In conclusion, long-term hyperglycemia naturally induces dental caries but not PD in type 1 and type 2 diabetic rodents. © 2017 by the American Diabetes Association.

New Rodent Population Models May Inform Human Health Risk Assessment and Identification of Genetic Susceptibility to Environmental Exposures

PubMed Central

Harrill, Alison H.

2017-01-01

Background: This paper provides an introduction for environmental health scientists to emerging population-based rodent resources. Mouse reference populations provide an opportunity to model environmental exposures and gene–environment interactions in human disease and to inform human health risk assessment. Objectives: This review will describe several mouse populations for toxicity assessment, including older models such as the Mouse Diversity Panel (MDP), and newer models that include the Collaborative Cross (CC) and Diversity Outbred (DO) models. Methods: This review will outline the features of the MDP, CC, and DO mouse models and will discuss published case studies investigating the use of these mouse population resources in each step of the risk assessment paradigm. Discussion: These unique resources have the potential to be powerful tools for generating hypotheses related to gene–environment interplay in human disease, performing controlled exposure studies to understand the differential responses in humans for susceptibility or resistance to environmental exposures, and identifying gene variants that influence sensitivity to toxicity and disease states. Conclusions: These new resources offer substantial advances to classical toxicity testing paradigms by including genetically sensitive individuals that may inform toxicity risks for sensitive subpopulations. Both in vivo and complementary in vitro resources provide platforms with which to reduce uncertainty by providing population-level data around biological variability. https://doi.org/10.1289/EHP1274 PMID:28886592

Efficacy of ipamorelin, a ghrelin mimetic, on gastric dysmotility in a rodent model of postoperative ileus

PubMed Central

Greenwood-Van Meerveld, Beverley; Tyler, Karl; Mohammadi, Ehsan; Pietra, Claudio

2012-01-01

Background Delayed gastric emptying is a common disorder with few effective therapeutic options. The goal of this study was to investigate whether ipamorelin, a synthetic peptidomimetic that acts on the ghrelin receptor, accelerates gastric emptying in a rodent model of gastroparesis induced by abdominal surgery and intestinal manipulation. Methods Fasted adult male rats were subjected to laparotomy and intestinal manipulation. Following the surgery rats received ipamorelin (0.014–0.14 µmol/kg) or vehicle control via intravenous administration. Gastric emptying was measured by the percent of total recovered radioactivity remaining in the stomach 15 minutes after intragastric gavage of 1.5 mL of 99mTc (technicium-99m) sulfur colloid in 0.5% methylcellulose. In a separate group of rats subjected to laparotomy and intestinal manipulation, the gastric fundus was isolated and tissue segments were suspended in an organ bath to assess the effect of ipamorelin (1 µM) on gastric smooth muscle contractility induced by acetylcholine and electrical field stimulation. Results Abdominal surgery caused a delay in gastric emptying with 78% ± 5% of the meal remaining in the stomach in vehicle controls. Ipamorelin (0.014 µmol/kg intravenous) resulted in a significant acceleration (P < 0.05 vs vehicle-treated rat) of gastric emptying with 52% ± 11% of the meal remaining in the stomach compared to nonsurgical control animals with 44% ± 6%. Following abdominal surgery and intestinal manipulation, isolated preparations of gastric smooth muscle exhibited a marked inhibition of acetylcholine and electrical field stimulation-induced contractile responses, which were reversed by ipamorelin and ghrelin. Conclusion These results suggest that ipamorelin accelerates gastric emptying in a rodent model of postoperative ileus through the stimulation of gastric contractility by activating a ghrelin receptor-mediated mechanism involving cholinergic excitatory neurons. PMID:27186127

The corpus cavernosum after treatment with dutasteride or finasteride: A histomorphometric study in a benign prostatic hyperplasia rodent model.

PubMed

Da Silva, Marcello H A; Costa, Waldemar S; B Sampaio, Francisco J; De Souza, Diogo B

2018-06-08

Erectile dysfunction is a common side effect of finasteride and dutasteride treatments. The objective of this study was to investigate the structural changes in the penis using a benign prostatic hyperplasia (BPH) rodent model treated with dutasteride or finasteride. Sixty male rats were divided into the following groups: C, untreated control rats; C + D, control rats receiving dutasteride; C + F, control rats receiving finasteride; H, untreated spontaneously hypertensive rats (SHRs); H + D, SHRs treated with dutasteride; and H + F, SHRs treated with finasteride. Treatments were performed for 40 days, and penises were collected immediately thereafter. The organs were analyzed using histomorphometric methods to determine the cross-sectional penile area, as well as the surface density (Sv) of smooth muscle fibers, connective tissue, elastic system fibers, and sinusoidal spaces of the corpus cavernosum. The results were compared using a one-way ANOVA with Bonferroni's posttest. Groups C + D and C + F had a significantly smaller penile cross-sectional area, but more elastic system fiber Sv compared to Group C. Group C + D showed less smooth muscle Sv, and Group H showed more connective tissue but a smaller sinusoidal space Sv in the corpus cavernosum compared to Group C. Groups H + D and H + F had less smooth muscle Sv than Group H. Group H + D also had more connective tissue and elastic system fiber Sv than Group H. Both dutasteride and finasteride promoted penile modifications in the control rat penis, although this affect was greater in Group H animals. In this rodent model, dutasteride was the drug that most affected the corpus cavernosum.

Lyme disease bacterium does not affect attraction to rodent odour in the tick vector.

PubMed

Berret, Jérémy; Voordouw, Maarten Jeroen

2015-04-28

Vector-borne pathogens experience a conflict of interest when the arthropod vector chooses a vertebrate host that is incompetent for pathogen transmission. The qualitative manipulation hypothesis suggests that vector-borne pathogens can resolve this conflict in their favour by manipulating the host choice behaviour of the arthropod vector. European Lyme disease is a model system for studying this conflict because Ixodes ricinus is a generalist tick species that vectors Borrelia pathogens that are specialized on different classes of vertebrate hosts. Avian specialists like B. garinii cannot survive in rodent reservoir hosts and vice versa for rodent specialists like B. afzelii. The present study tested whether Borrelia genospecies influenced the attraction of field-collected I. ricinus nymphs to rodent odours. Nymphs were significantly attracted to questing perches that had been scented with mouse odours. However, there was no difference in questing behaviour between nymphs infected with rodent- versus bird-specialized Borrelia genospecies. Our study suggests that the tick, and not the pathogen, controls the early stages of host choice behaviour.

An assessment of the utilization of the preclinical rodent model literature in clinical trials of putative therapeutics for the treatment of alcohol use disorders.

PubMed

Barajaz, Ashley M; Kliethermes, Christopher L

2017-12-01

Rodent models of Alcohol Use Disorders (AUD) are used extensively by preclinical researchers to develop new therapeutics for the treatment of AUD. Although these models play an important role in the development of novel, targeted therapeutics, their role in bringing therapeutics to clinical trials is unclear, as off-label use of existing medications not approved for the treatment of AUD is commonly seen in the clinic and clinical trials. In the current study, we used the Clinicaltrials.gov database to obtain a list of drugs that have been tested for efficacy in a clinical trial between 1997 and 2017. We then conducted a set of literature searches to determine which of the 98 unique drugs we identified had shown efficacy in a rodent model of an AUD prior to being tested in a clinical trial. We found that slightly less than half of the drugs tested in clinical trials (48%) had shown prior efficacy in any rodent model of an AUD, while the remaining 52% of drugs were used off-label, or in some cases, following non-published studies. This study raises the question of how clinical researchers incorporate results from preclinical studies in the decision to bring a drug to a clinical trial. Our results underscore the need for ongoing communication among preclinical and clinical researchers. Copyright © 2017 Elsevier B.V. All rights reserved.

Rodent model for assessing the long term safety and performance of peripheral nerve recording electrodes

NASA Astrophysics Data System (ADS)

Vasudevan, Srikanth; Patel, Kunal; Welle, Cristin

2017-02-01

Objective. In the US alone, there are approximately 185 000 cases of limb amputation annually, which can reduce the quality of life for those individuals. Current prosthesis technology could be improved by access to signals from the nervous system for intuitive prosthesis control. After amputation, residual peripheral nerves continue to convey motor signals and electrical stimulation of these nerves can elicit sensory percepts. However, current technology for extracting information directly from peripheral nerves has limited chronic reliability, and novel approaches must be vetted to ensure safe long-term use. The present study aims to optimize methods to establish a test platform using rodent model to assess the long term safety and performance of electrode interfaces implanted in the peripheral nerves. Approach. Floating Microelectrode Arrays (FMA, Microprobes for Life Sciences) were implanted into the rodent sciatic nerve. Weekly in vivo recordings and impedance measurements were performed in animals to assess performance and physical integrity of electrodes. Motor (walking track analysis) and sensory (Von Frey) function tests were used to assess change in nerve function due to the implant. Following the terminal recording session, the nerve was explanted and the health of axons, myelin and surrounding tissues were assessed using immunohistochemistry (IHC). The explanted electrodes were visualized under high magnification using scanning electrode microscopy (SEM) to observe any physical damage. Main results. Recordings of axonal action potentials demonstrated notable session-to-session variability. Impedance of the electrodes increased upon implantation and displayed relative stability until electrode failure. Initial deficits in motor function recovered by 2 weeks, while sensory deficits persisted through 6 weeks of assessment. The primary cause of failure was identified as lead wire breakage in all of animals. IHC indicated myelinated and unmyelinated axons near the implanted electrode shanks, along with dense cellular accumulations near the implant site. Scanning electron microscopy (SEM) showed alterations of the electrode insulation and deformation of electrode shanks. Significance. We describe a comprehensive testing platform with applicability to electrodes that record from the peripheral nerves. This study assesses the long term safety and performance of electrodes in the peripheral nerves using a rodent model. Under this animal test platform, FMA electrodes record single unit action potentials but have limited chronic reliability due to structural weaknesses. Future work will apply these methods to other commercially-available and novel peripheral electrode technologies. This research was carried out in the Division of Biomedical Physics, Office of Science and Engineering Laboratory, Center for Devices and Radiological Health, US Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.

Genetically Engineered Cancer Models, But Not Xenografts, Faithfully Predict Anticancer Drug Exposure in Melanoma Tumors

PubMed Central

Combest, Austin J.; Roberts, Patrick J.; Dillon, Patrick M.; Sandison, Katie; Hanna, Suzan K.; Ross, Charlene; Habibi, Sohrab; Zamboni, Beth; Müller, Markus; Brunner, Martin; Sharpless, Norman E.

2012-01-01

Background. Rodent studies are a vital step in the development of novel anticancer therapeutics and are used in pharmacokinetic (PK), toxicology, and efficacy studies. Traditionally, anticancer drug development has relied on xenograft implantation of human cancer cell lines in immunocompromised mice for efficacy screening of a candidate compound. The usefulness of xenograft models for efficacy testing, however, has been questioned, whereas genetically engineered mouse models (GEMMs) and orthotopic syngeneic transplants (OSTs) may offer some advantages for efficacy assessment. A critical factor influencing the predictability of rodent tumor models is drug PKs, but a comprehensive comparison of plasma and tumor PK parameters among xenograft models, OSTs, GEMMs, and human patients has not been performed. Methods. In this work, we evaluated the plasma and tumor dispositions of an antimelanoma agent, carboplatin, in patients with cutaneous melanoma compared with four different murine melanoma models (one GEMM, one human cell line xenograft, and two OSTs). Results. Using microdialysis to sample carboplatin tumor disposition, we found that OSTs and xenografts were poor predictors of drug exposure in human tumors, whereas the GEMM model exhibited PK parameters similar to those seen in human tumors. Conclusions. The tumor PKs of carboplatin in a GEMM of melanoma more closely resembles the tumor disposition in patients with melanoma than transplanted tumor models. GEMMs show promise in becoming an improved prediction model for intratumoral PKs and response in patients with solid tumors. PMID:22993143

PCP-induced deficits in murine nest building activity: employment of an ethological rodent behavior to mimic negative-like symptoms of schizophrenia.

PubMed

Pedersen, Christian Spang; Sørensen, Dorte Bratbo; Parachikova, Anna I; Plath, Niels

2014-10-15

Schizophrenia is a severe psychiatric disorder characterized by three symptom domains, positive (hallucinations, obsession), negative (social withdrawal, apathy, self-neglect) and cognitive (impairment in attention, memory and executive function). Whereas current medication ameliorates positive symptomatology, negative symptoms as well as cognitive dysfunctions remain untreated. The development of improved therapies for negative symptoms has proven particularly difficult, in part due to the inability of mimicking these in rodents. Here, we address the predictive validity of combining an ethologically well preserved behavior in rodents, namely nest building activity, with an established animal model of schizophrenia, the sub-chronic PCP model, for negative symptoms. Decline in rodent nesting activity has been suggested to mirror domains of negative symptoms of schizophrenia, including social withdrawal, anhedonia and self-neglect, whereas repeated treatment with the NMDAR antagonist PCP induces and exacerbates schizophrenia-like symptoms in rodents and human subjects. Using a back-translational approach of pharmacological validation, we tested the effects of two agents targeting the nicotinic α7 receptor (EVP-6124 and TC-5619) that were reported to exert some beneficial effect on negative symptoms in schizophrenic patients. Sub-chronic PCP treatment resulted in a significant nest building deficit in mice and treatment with EVP-6124 and TC-5619 reversed this PCP-induced deficit. In contrast, the atypical antipsychotic drug risperidone remained ineffective in this assay. In addition, EVP-6124, TC-5619 and risperidone were tested in the Social Interaction Test (SIT), an assay suggested to address negative-like symptoms. Results obtained in SIT were comparable to results in the nest building test (NEST). Based on these findings, we propose nest building in combination with the sub-chronic PCP model as a novel approach to assess negative-like symptoms of schizophrenia in rodents. Copyright © 2014 Elsevier B.V. All rights reserved.

A systematic review of rodent pest research in Afro-Malagasy small-holder farming systems: Are we asking the right questions?

PubMed

Swanepoel, Lourens H; Swanepoel, Corrie M; Brown, Peter R; Eiseb, Seth J; Goodman, Steven M; Keith, Mark; Kirsten, Frikkie; Leirs, Herwig; Mahlaba, Themb'alilahlwa A M; Makundi, Rhodes H; Malebane, Phanuel; von Maltitz, Emil F; Massawe, Apia W; Monadjem, Ara; Mulungu, Loth S; Singleton, Grant R; Taylor, Peter J; Soarimalala, Voahangy; Belmain, Steven R

2017-01-01

Rodent pests are especially problematic in terms of agriculture and public health since they can inflict considerable economic damage associated with their abundance, diversity, generalist feeding habits and high reproductive rates. To quantify rodent pest impacts and identify trends in rodent pest research impacting on small-holder agriculture in the Afro-Malagasy region we did a systematic review of research outputs from 1910 to 2015, by developing an a priori defined set of criteria to allow for replication of the review process. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We reviewed 162 publications, and while rodent pest research was spatially distributed across Africa (32 countries, including Madagascar), there was a disparity in number of studies per country with research biased towards four countries (Tanzania [25%], Nigeria [9%], Ethiopia [9%], Kenya [8%]) accounting for 51% of all rodent pest research in the Afro-Malagasy region. There was a disparity in the research themes addressed by Tanzanian publications compared to publications from the rest of the Afro-Malagasy region where research in Tanzania had a much more applied focus (50%) compared to a more basic research approach (92%) in the rest of the Afro-Malagasy region. We found that pest rodents have a significant negative effect on the Afro-Malagasy small-holder farming communities. Crop losses varied between cropping stages, storage and crops and the highest losses occurred during early cropping stages (46% median loss during seedling stage) and the mature stage (15% median loss). There was a scarcity of studies investigating the effectiveness of various management actions on rodent pest damage and population abundance. Our analysis highlights that there are inadequate empirical studies focused on developing sustainable control methods for rodent pests and rodent pests in the Africa-Malagasy context is generally ignored as a research topic.

A systematic review of rodent pest research in Afro-Malagasy small-holder farming systems: Are we asking the right questions?

PubMed Central

Swanepoel, Corrie M.; Brown, Peter R.; Eiseb, Seth J.; Goodman, Steven M.; Keith, Mark; Kirsten, Frikkie; Leirs, Herwig; Mahlaba, Themb’alilahlwa A. M.; Makundi, Rhodes H.; Malebane, Phanuel; von Maltitz, Emil F.; Massawe, Apia W.; Monadjem, Ara; Mulungu, Loth S.; Singleton, Grant R.; Taylor, Peter J.; Soarimalala, Voahangy; Belmain, Steven R.

2017-01-01

Rodent pests are especially problematic in terms of agriculture and public health since they can inflict considerable economic damage associated with their abundance, diversity, generalist feeding habits and high reproductive rates. To quantify rodent pest impacts and identify trends in rodent pest research impacting on small-holder agriculture in the Afro-Malagasy region we did a systematic review of research outputs from 1910 to 2015, by developing an a priori defined set of criteria to allow for replication of the review process. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We reviewed 162 publications, and while rodent pest research was spatially distributed across Africa (32 countries, including Madagascar), there was a disparity in number of studies per country with research biased towards four countries (Tanzania [25%], Nigeria [9%], Ethiopia [9%], Kenya [8%]) accounting for 51% of all rodent pest research in the Afro-Malagasy region. There was a disparity in the research themes addressed by Tanzanian publications compared to publications from the rest of the Afro-Malagasy region where research in Tanzania had a much more applied focus (50%) compared to a more basic research approach (92%) in the rest of the Afro-Malagasy region. We found that pest rodents have a significant negative effect on the Afro-Malagasy small-holder farming communities. Crop losses varied between cropping stages, storage and crops and the highest losses occurred during early cropping stages (46% median loss during seedling stage) and the mature stage (15% median loss). There was a scarcity of studies investigating the effectiveness of various management actions on rodent pest damage and population abundance. Our analysis highlights that there are inadequate empirical studies focused on developing sustainable control methods for rodent pests and rodent pests in the Africa-Malagasy context is generally ignored as a research topic. PMID:28358899

Arvicanthis ansorgei, a Novel Model for the Study of Sleep and Waking in Diurnal Rodents

PubMed Central

Hubbard, Jeffrey; Ruppert, Elisabeth; Calvel, Laurent; Robin-Choteau, Ludivine; Gropp, Claire-Marie; Allemann, Caroline; Reibel, Sophie; Sage-Ciocca, Dominique; Bourgin, Patrice

2015-01-01

Study Objectives: Sleep neurobiology studies use nocturnal species, mainly rats and mice. However, because their daily sleep/wake organization is inverted as compared to humans, a diurnal model for sleep studies is needed. To fill this gap, we phenotyped sleep and waking in Arvicanthis ansorgei, a diurnal rodent widely used for the study of circadian rhythms. Design: Video-electroencephalogram (EEG), electromyogram (EMG), and electrooculogram (EOG) recordings. Setting: Rodent sleep laboratory. Participants: Fourteen male Arvicanthis ansorgei, aged 3 mo. Interventions: 12 h light (L):12 h dark (D) baseline condition, 24-h constant darkness, 6-h sleep deprivation. Measurements and Results: Wake and rapid eye movement (REM) sleep showed similar electrophysiological characteristics as nocturnal rodents. On average, animals spent 12.9 h ± 0.4 awake per 24-h cycle, of which 6.88 h ± 0.3 was during the light period. NREM sleep accounted for 9.63 h ± 0.4, which of 5.13 h ± 0.2 during dark period, and REM sleep for 89.9 min ± 6.7, which of 52.8 min ± 4.4 during dark period. The time-course of sleep and waking across the 12 h light:12 h dark was overall inverted to that observed in rats or mice, though with larger amounts of crepuscular activity at light and dark transitions. A dominant crepuscular regulation of sleep and waking persisted under constant darkness, showing the lack of a strong circadian drive in the absence of clock reinforcement by external cues, such as a running wheel. Conservation of the homeostatic regulation was confirmed with the observation of higher delta power following sustained waking periods and a 6-h sleep deprivation, with subsequent decrease during recovery sleep. Conclusions: Arvicanthis ansorgei is a valid diurnal rodent model for studying the regulatory mechanisms of sleep and so represents a valuable tool for further understanding the nocturnality/diurnality switch. Citation: Hubbard J, Ruppert E, Calvel L, Robin-Choteau L, Gropp CM, Allemann C, Reibel S, Sage-Ciocca D, Bourgin P. Arvicanthis ansorgei, a novel model for the study of sleep and waking in diurnal rodents. SLEEP 2015;38(6):979–988. PMID:25409107

New Developments in NASA's Rodent Research Hardware for Conducting Long Duration Biomedical and Basic Research in Space

NASA Technical Reports Server (NTRS)

Shirazi, Yasaman; Choi, S.; Harris, C.; Gong, C.; Fisher, R. J.; Beegle, J. E.; Stube, K. C.; Martin, K. J.; Nevitt, R. G.; Globus, R. K.

2017-01-01

Animal models, particularly rodents, are the foundation of pre-clinical research to understand human diseases and evaluate new therapeutics, and play a key role in advancing biomedical discoveries both on Earth and in space. The National Research Councils Decadal survey emphasized the importance of expanding NASA's life sciences research to perform long duration, rodent experiments on the International Space Station (ISS) to study effects of the space environment on the musculoskeletal and neurological systems of mice as model organisms of human health and disease, particularly in areas of muscle atrophy, bone loss, and fracture healing. To accomplish this objective, flight hardware, operations, and science capabilities were developed at NASA Ames Research Center (ARC) to enhance science return for both commercial (CASIS) and government-sponsored rodent research. The Rodent Research Project at NASA ARC has pioneered a new research capability on the International Space Station and has progressed toward translating research to the ISS utilizing commercial rockets, collaborating with academia and science industry, while training crewmembers to assist in performing research on orbit. The Rodent Research Habitat provides a living environment for animals on ISS according to standard animal welfare requirements, and daily health checks can be performed using the habitats camera system. Results from these studies contribute to the science community via both the primary investigation and banked samples that are shared in publicly available data repository such as GeneLab. Following each flight, through the Biospecimen Sharing Program (BSP), numerous tissues and thousands of samples will be harvested, and distributed from the Space Life and Physical Sciences (SLPS) to Principal Investigators (PIs) through the Ames Life Science Data Archive (ALSDA). Every completed mission sets a foundation to build and design greater complexity into future research and answer questions about common human diseases. Together, the hardware improvements (enrichment, telemetry sensors, cameras), new capabilities (live animal return), and experience that the Rodent Research team has gained working with principal investigator teams and ISS crew to conduct complex experiments on orbit are expanding capabilities for long duration rodent research on the ISS to achieve both basic science and biomedical research objectives.

The Neonatal Ventral Hippocampal Lesion (NVHL) Rodent Model of Schizophrenia

PubMed Central

Brady, Anne Marie

2016-01-01

Animal models are crucial to the study of the neurobiological bases of psychiatric disorders, but schizophrenia is a particularly challenging disorder to model given the complexity and heavily verbal nature of its symptoms. This article describes a developmental surgical rodent model of schizophrenia, the neonatal ventral hippocampal lesion (NVHL) model. This widely used model produces reliable behavioral abnormalities that are comparable to those observed in patients, as well as anatomical and neurophysiological disruptions in forebrain areas that are also implicated in schizophrenia. A brief background of the development and validity of the NVHL model is discussed here, along with detailed procedures for producing the model in rats. Critical issues particular to neonatal surgery are discussed, and representative histological and behavioral results are presented. PMID:27696361

Modeling of mouse eye and errors in ocular parameters affecting refractive state

NASA Astrophysics Data System (ADS)

Bawa, Gurinder

Rodents eye are particularly used to study refractive error state of an eye and development of refractive eye. Genetic organization of rodents is similar to that of humans, which makes them interesting candidates to be researched upon. From rodents family mice models are encouraged over rats because of availability of genetically engineered models. Despite of extensive work that has been performed on mice and rat models, still no one is able to quantify an optical model, due to variability in the reported ocular parameters. In this Dissertation, we have extracted ocular parameters and generated schematics of eye from the raw data from School of Medicine, Detroit. In order to see how the rays would travel through an eye and the defects associated with an eye; ray tracing has been performed using ocular parameters. Finally we have systematically evaluated the contribution of various ocular parameters, such as radii of curvature of ocular surfaces, thicknesses of ocular components, and refractive indices of ocular refractive media, using variational analysis and a computational model of the rodent eye. Variational analysis revealed that variation in all the ocular parameters does affect the refractive status of the eye, but depending upon the magnitude of the impact those parameters are listed as critical or non critical. Variation in the depth of the vitreous chamber, thickness of the lens, radius of the anterior surface of the cornea, radius of the anterior surface of the lens, as well as refractive indices for the lens and vitreous, appears to have the largest impact on the refractive error and thus are categorized as critical ocular parameters. The radii of the posterior surfaces of the cornea and lens have much smaller contributions to the refractive state, while the radii of the anterior and posterior surfaces of the retina have no effect on the refractive error. These data provide the framework for further refinement of the optical models of the rat and mouse eye and suggest that extra efforts should be directed towards increasing the linear resolution of the rodent eye biometry and obtaining more accurate data for the refractive indices of the lens and vitreous.

A Quantitative and Standardized Method for the Evaluation of Choroidal Neovascularization Using MICRON III Fluorescein Angiograms in Rats

PubMed Central

Wigg, Jonathan P.; Zhang, Hong; Yang, Dong

2015-01-01

Introduction In-vivo imaging of choroidal neovascularization (CNV) has been increasingly recognized as a valuable tool in the investigation of age-related macular degeneration (AMD) in both clinical and basic research applications. Arguably the most widely utilised model replicating AMD is laser generated CNV by rupture of Bruch’s membrane in rodents. Heretofore CNV evaluation via in-vivo imaging techniques has been hamstrung by a lack of appropriate rodent fundus camera and a non-standardised analysis method. The aim of this study was to establish a simple, quantifiable method of fluorescein fundus angiogram (FFA) image analysis for CNV lesions. Methods Laser was applied to 32 Brown Norway Rats; FFA images were taken using a rodent specific fundus camera (Micron III, Phoenix Laboratories) over 3 weeks and compared to conventional ex-vivo CNV assessment. FFA images acquired with fluorescein administered by intraperitoneal injection and intravenous injection were compared and shown to greatly influence lesion properties. Utilising commonly used software packages, FFA images were assessed for CNV and chorioretinal burns lesion area by manually outlining the maximum border of each lesion and normalising against the optic nerve head. Net fluorescence above background and derived value of area corrected lesion intensity were calculated. Results CNV lesions of rats treated with anti-VEGF antibody were significantly smaller in normalised lesion area (p<0.001) and fluorescent intensity (p<0.001) than the PBS treated control two weeks post laser. The calculated area corrected lesion intensity was significantly smaller (p<0.001) in anti-VEGF treated animals at 2 and 3 weeks post laser. The results obtained using FFA correlated with, and were confirmed by conventional lesion area measurements from isolectin stained choroidal flatmounts, where lesions of anti-VEGF treated rats were significantly smaller at 2 weeks (p = 0.049) and 3 weeks (p<0.001) post laser. Conclusion The presented method of in-vivo FFA quantification of CNV, including acquisition variable corrections, using the Micron III system and common use software establishes a reliable method for detecting and quantifying CNV enabling longitudinal studies and represents an important alternative to conventional CNV quantification methods. PMID:26024231

Modeling menopause: The utility of rodents in translational behavioral endocrinology research.

PubMed

Koebele, Stephanie V; Bimonte-Nelson, Heather A

2016-05-01

The human menopause transition and aging are each associated with an increase in a variety of health risk factors including, but not limited to, cardiovascular disease, osteoporosis, cancer, diabetes, stroke, sexual dysfunction, affective disorders, sleep disturbances, and cognitive decline. It is challenging to systematically evaluate the biological underpinnings associated with the menopause transition in the human population. For this reason, rodent models have been invaluable tools for studying the impact of gonadal hormone fluctuations and eventual decline on a variety of body systems. While it is essential to keep in mind that some of the mechanisms associated with aging and the transition into a reproductively senescent state can differ when translating from one species to another, animal models provide researchers with opportunities to gain a fundamental understanding of the key elements underlying reproduction and aging processes, paving the way to explore novel pathways for intervention associated with known health risks. Here, we discuss the utility of several rodent models used in the laboratory for translational menopause research, examining the benefits and drawbacks in helping us to better understand aging and the menopause transition in women. The rodent models discussed are ovary-intact, ovariectomy, and 4-vinylcylohexene diepoxide for the menopause transition. We then describe how these models may be implemented in the laboratory, particularly in the context of cognition. Ultimately, we aim to use these animal models to elucidate novel perspectives and interventions for maintaining a high quality of life in women, and to potentially prevent or postpone the onset of negative health consequences associated with these significant life changes during aging. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Multiple Approaches to the Investigation of Cell Assembly in Memory Research-Present and Future.

PubMed

Sakurai, Yoshio; Osako, Yuma; Tanisumi, Yuta; Ishihara, Eriko; Hirokawa, Junya; Manabe, Hiroyuki

2018-01-01

In this review article we focus on research methodologies for detecting the actual activity of cell assemblies, which are populations of functionally connected neurons that encode information in the brain. We introduce and discuss traditional and novel experimental methods and those currently in development and briefly discuss their advantages and disadvantages for the detection of cell-assembly activity. First, we introduce the electrophysiological method, i.e., multineuronal recording, and review former and recent examples of studies showing models of dynamic coding by cell assemblies in behaving rodents and monkeys. We also discuss how the firing correlation of two neurons reflects the firing synchrony among the numerous surrounding neurons that constitute cell assemblies. Second, we review the recent outstanding studies that used the novel method of optogenetics to show causal relationships between cell-assembly activity and behavioral change. Third, we review the most recently developed method of live-cell imaging, which facilitates the simultaneous observation of firings of a large number of neurons in behaving rodents. Currently, all these available methods have both advantages and disadvantages, and no single measurement method can directly and precisely detect the actual activity of cell assemblies. The best strategy is to combine the available methods and utilize each of their advantages with the technique of operant conditioning of multiple-task behaviors in animals and, if necessary, with brain-machine interface technology to verify the accuracy of neural information detected as cell-assembly activity.

PPARα siRNA–Treated Expression Profiles Uncover the Causal Sufficiency Network for Compound-Induced Liver Hypertrophy

PubMed Central

Dai, Xudong; Souza, Angus T. De; Dai, Hongyue; Lewis, David L; Lee, Chang-kyu; Spencer, Andy G; Herweijer, Hans; Hagstrom, Jim E; Linsley, Peter S; Bassett, Douglas E; Ulrich, Roger G; He, Yudong D

2007-01-01

Uncovering pathways underlying drug-induced toxicity is a fundamental objective in the field of toxicogenomics. Developing mechanism-based toxicity biomarkers requires the identification of such novel pathways and the order of their sufficiency in causing a phenotypic response. Genome-wide RNA interference (RNAi) phenotypic screening has emerged as an effective tool in unveiling the genes essential for specific cellular functions and biological activities. However, eliciting the relative contribution of and sufficiency relationships among the genes identified remains challenging. In the rodent, the most widely used animal model in preclinical studies, it is unrealistic to exhaustively examine all potential interactions by RNAi screening. Application of existing computational approaches to infer regulatory networks with biological outcomes in the rodent is limited by the requirements for a large number of targeted permutations. Therefore, we developed a two-step relay method that requires only one targeted perturbation for genome-wide de novo pathway discovery. Using expression profiles in response to small interfering RNAs (siRNAs) against the gene for peroxisome proliferator-activated receptor α (Ppara), our method unveiled the potential causal sufficiency order network for liver hypertrophy in the rodent. The validity of the inferred 16 causal transcripts or 15 known genes for PPARα-induced liver hypertrophy is supported by their ability to predict non-PPARα–induced liver hypertrophy with 84% sensitivity and 76% specificity. Simulation shows that the probability of achieving such predictive accuracy without the inferred causal relationship is exceedingly small (p < 0.005). Five of the most sufficient causal genes have been previously disrupted in mouse models; the resulting phenotypic changes in the liver support the inferred causal roles in liver hypertrophy. Our results demonstrate the feasibility of defining pathways mediating drug-induced toxicity from siRNA-treated expression profiles. When combined with phenotypic evaluation, our approach should help to unleash the full potential of siRNAs in systematically unveiling the molecular mechanism of biological events. PMID:17335344

[Spatio-temporal distribution of scrub typhus and related influencing factors in coastal beach area of Yancheng, China].

PubMed

Chen, Y Z; Li, F; Xu, H; Huang, L C; Gu, Z G; Sun, Z Y; Yan, G J; Zhu, Y J; Tang, C

2016-02-01

In order to provide better programs on monitoring, early warning and prevention of Scrub Typhus in the coastal beach area, temporal-spatial distribution characteristics of scrub typhus were summarized. Relationships between temporal-spatial clustering of Scrub Typhus, meteorological factors, rodent distribution and the biological characteristics in coastal beach area of Yancheng city, were studied. Reports on network-based Scrub Typhus epidemics and information on population, weather situation through monitoring those stations, from 2005 to 2014 were collected and processed, in the coastal beach area of Yancheng city. Distribution, density of the population concerned and seasonal fluctuation on rodents were monitored in coastal beach area, from April 2011 to December, 2013. METHODS as descriptive statistics, space-time permutation scantistics, autocorrelation and Cross-correlation analysis etc, were used to analyze the temporal-spatial distribution of Scrub Typhus and correlation with rodent distribution, density fluctuation and meteorological indexes. Zero-inflated Pearson (ZIP) regression model was contributed according to the distribution of related data. All methods were calculated under Excel 2003, SPSS 16.0, Mapinfo 11.0, Satscan 9.0 and Stata/SE 10.0 softwares. (1) The incidence of Scrub Typhus was gradually increasing and the highest incidence of the year was seen in 2014, as 5.81/10 million. There was an autumn peak of Scrub typhus, with the highest incidence rate as 12.02/10 million in November. The incidence rate of Scrub typhus appeared high in Binhai, Dafeng and Xiangshui, with the average incidence rates appeared as 3.30/10 million, 3.21/10 million and 2.79/10 million, respectively. There were 12 towns with high incidence rates in the coastal beach area, with incidence rate showed between 4.41/10 and 10.03/10 million. (2) There were three incidence clusters of Scrub typhus seen in 25 towns, between October 2012 and November 2012 in Dongtai, Dafeng, Sheyang areas and 5 towns between October and November, 2014 in Xiangshui area, together with another 6 towns in November of 2006, in Binhai area. (3) Apodemus agrarius appeared the dominant species in the coastal area, with the constituent ratio as 89.19%. The rodent density appeared two peaks in winter and summer in 2011 and 2013. The winter peak was seen in January and the summer peak lasting for 5-8 months. Scrub Typhus was seen 10-11 months in a year and the incidence was increasing, parallel with the peak of the rodent density. The peak incidence of Scrub Typhus showed a temperature/rainfall-related peak. Rodent density, temperature, rainfalls were correlated with the incidence of Scrub Typhus, under the Cross correlation analysis. Rains, Mean minimum temperature of a 3-month lagging were directly correlated but the duration of sunshine and relative humidity were negatively correlated with the incidence of Scrub Typhus, under the Zero-inflated Pearson (ZIP) regression model. Temporal-spatial clustering and factors as media creature and weather condition of Scrub Typhu were discovered, which provided evidence for effective measures on prevention and control of the disease.

Enhanced cortical thickness measurements for rodent brains via Lagrangian-based RK4 streamline computation

NASA Astrophysics Data System (ADS)

Lee, Joohwi; Kim, Sun Hyung; Oguz, Ipek; Styner, Martin

2016-03-01

The cortical thickness of the mammalian brain is an important morphological characteristic that can be used to investigate and observe the brain's developmental changes that might be caused by biologically toxic substances such as ethanol or cocaine. Although various cortical thickness analysis methods have been proposed that are applicable for human brain and have developed into well-validated open-source software packages, cortical thickness analysis methods for rodent brains have not yet become as robust and accurate as those designed for human brains. Based on a previously proposed cortical thickness measurement pipeline for rodent brain analysis,1 we present an enhanced cortical thickness pipeline in terms of accuracy and anatomical consistency. First, we propose a Lagrangian-based computational approach in the thickness measurement step in order to minimize local truncation error using the fourth-order Runge-Kutta method. Second, by constructing a line object for each streamline of the thickness measurement, we can visualize the way the thickness is measured and achieve sub-voxel accuracy by performing geometric post-processing. Last, with emphasis on the importance of an anatomically consistent partial differential equation (PDE) boundary map, we propose an automatic PDE boundary map generation algorithm that is specific to rodent brain anatomy, which does not require manual labeling. The results show that the proposed cortical thickness pipeline can produce statistically significant regions that are not observed in the previous cortical thickness analysis pipeline.

Shared Ancestry between a Newfound Mole-Borne Hantavirus and Hantaviruses Harbored by Cricetid Rodents ▿†

PubMed Central

Kang, Hae Ji; Bennett, Shannon N.; Hope, Andrew G.; Cook, Joseph A.; Yanagihara, Richard

2011-01-01

Discovery of genetically distinct hantaviruses in multiple species of shrews (order Soricomorpha, family Soricidae) and moles (family Talpidae) contests the conventional view that rodents (order Rodentia, families Muridae and Cricetidae) are the principal reservoir hosts and suggests that the evolutionary history of hantaviruses is far more complex than previously hypothesized. We now report on Rockport virus (RKPV), a hantavirus identified in archival tissues of the eastern mole (Scalopus aquaticus) collected in Rockport, TX, in 1986. Pairwise comparison of the full-length S, M, and L genomic segments indicated moderately low sequence similarity between RKPV and other soricomorph-borne hantaviruses. Phylogenetic analyses, using maximum-likelihood and Bayesian methods, showed that RKPV shared a most recent common ancestor with cricetid-rodent-borne hantaviruses. Distributed widely across the eastern United States, the fossorial eastern mole is sympatric and syntopic with cricetid rodents known to harbor hantaviruses, raising the possibility of host-switching events in the distant past. Our findings warrant more-detailed investigations on the dynamics of spillover and cross-species transmission of present-day hantaviruses within communities of rodents and moles. PMID:21632770

Development and Assessment of Transgenic Rodent Parasites for the Preclinical Evaluation of Malaria Vaccines.

PubMed

Espinosa, Diego A; Radtke, Andrea J; Zavala, Fidel

2016-01-01

Rodent transgenic parasites are useful tools for the preclinical evaluation of malaria vaccines. Over the last decade, several studies have reported the development of transgenic rodent parasites expressing P. falciparum antigens for the assessment of vaccine-induced immune responses, which traditionally have been limited to in vitro assays. However, the genetic manipulation of rodent Plasmodium species can have detrimental effects on the parasite's infectivity and development. In this chapter, we present a few guidelines for designing transfection plasmids, which should improve transfection efficiency and facilitate the generation of functional transgenic parasite strains. In addition, we provide a transfection protocol for the development of transgenic P. berghei parasites as well as practical methods to assess the viability and infectivity of these newly generated strains throughout different stages of their life cycle. These techniques should allow researchers to develop novel rodent malaria parasites expressing antigens from human malaria species and to determine whether these transgenic strains are fully infectious and thus represent stringent platforms for the in vivo evaluation of malaria vaccine candidates.

Maintaining and Monitoring the Defined Microbiota Status of Gnotobiotic Rodents.

PubMed

Nicklas, Werner; Keubler, Lydia; Bleich, André

2015-01-01

Gnotobiotic (germfree, defined colonized) rodents have become powerful tools to advance our understanding of the host-microbiome relationship. However, the maintenance and ultimately the monitoring of gnotobiotic rodents is a critical, labor-intensive, and costly process (e.g., sterility, not absence of specific pathogens, must be demonstrated in germfree animals). Here, we provide information on the housing and maintenance of gnotobiotic animals, elucidate prophylactic measurements to avoid contamination, and make specific recommendations for sampling procedures, sampling frequencies, and test methods. © The Author 2015. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Rodent analgesia: Assessment and therapeutics.

PubMed

Flecknell, Paul

2018-02-01

Current use of analgesics to control procedure-related pain in laboratory rodents is unacceptably low. Almost all currently available analgesics were developed in small rodents, prior to use in man, so that safety and efficacy data in laboratory assays are available. Greater use of analgesics would be encouraged by critical evaluation of the potential interactions of these compounds with the outcomes of specific research studies. As in other species, effective post-procedural analgesia requires reliable 'cage-side' methods of assessing pain. Recent advances in pain assessment should lead to both more extensive and more effective use of analgesics in these species. Copyright © 2017 Elsevier Ltd. All rights reserved.

Oral chronic ethanol administration to rodents by agar gel diet.

PubMed

Bykov, I; Palmén, M; Piirainen, L; Lindros, K O

2004-01-01

Chronic ethanol administration to rodents requires specially designed equipment and is labor intensive. Here we report a new procedure. A commercial liquid diet preparation was made into a gel by addition of 0.5% agar. The gel, containing 5.3% ethanol, was offered in Falcon tubes equipped with a feeding opening. The gel consumption by C57/Bl mice resulted in high blood ethanol levels (average 43 mM). After 6 weeks, marked liver steatosis and significantly increased serum alanine aminotransferase levels had developed. Administration of ethanol in a nutritionally adequate gel provides a simple method for studies on chronic ethanol effects in rodents.

Mutation Analysis in Cultured Cells of Transgenic Rodents

PubMed Central

Zheng, Albert; Bates, Steven E.; Tommasi, Stella

2018-01-01

To comply with guiding principles for the ethical use of animals for experimental research, the field of mutation research has witnessed a shift of interest from large-scale in vivo animal experiments to small-sized in vitro studies. Mutation assays in cultured cells of transgenic rodents constitute, in many ways, viable alternatives to in vivo mutagenicity experiments in the corresponding animals. A variety of transgenic rodent cell culture models and mutation detection systems have been developed for mutagenicity testing of carcinogens. Of these, transgenic Big Blue® (Stratagene Corp., La Jolla, CA, USA, acquired by Agilent Technologies Inc., Santa Clara, CA, USA, BioReliance/Sigma-Aldrich Corp., Darmstadt, Germany) mouse embryonic fibroblasts and the λ Select cII Mutation Detection System have been used by many research groups to investigate the mutagenic effects of a wide range of chemical and/or physical carcinogens. Here, we review techniques and principles involved in preparation and culturing of Big Blue® mouse embryonic fibroblasts, treatment in vitro with chemical/physical agent(s) of interest, determination of the cII mutant frequency by the λ Select cII assay and establishment of the mutation spectrum by DNA sequencing. We describe various approaches for data analysis and interpretation of the results. Furthermore, we highlight representative studies in which the Big Blue® mouse cell culture model and the λ Select cII assay have been used for mutagenicity testing of diverse carcinogens. We delineate the advantages of this approach and discuss its limitations, while underscoring auxiliary methods, where applicable. PMID:29337872

Entry of substances into perilymph through the bone of the otic capsule following intratympanic applicatons in guinea pigs: Implications for local drug delivery in humans

PubMed Central

Mikulec, Anthony A; Plontke, Stefan K.; Hartsock, Jared J.; Salt, Alec N.

2008-01-01

Introduction Drugs applied intratympanically in humans are believed to enter the cochlea primarily through the round window membrane (RWM). Local drug treatments of the ear are commonly evaluated in rodent models. The otic capsule is much thinner at the cochlear apex in rodents than in humans. We therefore investigated whether drugs applied to the middle ear could enter perilymph through the otic capsule as well as through the RWM. Methods The distribution of gentamicin and the marker trimethylphenylammonium (TMPA) along the guinea pig cochlea was assessed with sequential apical perilymph sampling following two delivery paradigms that included i) completely filling the tympanic bulla with solution, and ii) applying the solution to the RWM only. In addition, TMPA entry into perilymph of the third turn was measured with ion-selective electrodes while the bulla was filled with TMPA solution. Results In application protocols that allowed drug to contact the otic capsule (by completely filling the bulla) markedly higher drug concentrations were found in the apical, low-frequency regions of the cochlea compared with drug applications to the RWM only. Conclusions Gentamicin and TMPA can enter perilymph of guinea pigs through the RWM and simultaneously through the bony otic capsule. Drug distribution along the cochlea following intratympanic applications will therefore be dramatically different in rodents and humans. Results obtained from intratympanic drug treatments of animals, in which the bulla is filled with solution and contacts the bony capsule of the cochlea, do not provide a good model for the human situation. PMID:19180674

A PK-PD model of ketamine-induced high-frequency oscillations

NASA Astrophysics Data System (ADS)

Flores, Francisco J.; Ching, ShiNung; Hartnack, Katharine; Fath, Amanda B.; Purdon, Patrick L.; Wilson, Matthew A.; Brown, Emery N.

2015-10-01

Objective. Ketamine is a widely used drug with clinical and research applications, and also known to be used as a recreational drug. Ketamine produces conspicuous changes in the electrocorticographic (ECoG) signals observed both in humans and rodents. In rodents, the intracranial ECoG displays a high-frequency oscillation (HFO) which power is modulated nonlinearly by ketamine dose. Despite the widespread use of ketamine there is no model description of the relationship between the pharmacokinetic-pharmacodynamics (PK-PDs) of ketamine and the observed HFO power. Approach. In the present study, we developed a PK-PD model based on estimated ketamine concentration, its known pharmacological actions, and observed ECoG effects. The main pharmacological action of ketamine is antagonism of the NMDA receptor (NMDAR), which in rodents is accompanied by an HFO observed in the ECoG. At high doses, however, ketamine also acts at non-NMDAR sites, produces loss of consciousness, and the transient disappearance of the HFO. We propose a two-compartment PK model that represents the concentration of ketamine, and a PD model based in opposing effects of the NMDAR and non-NMDAR actions on the HFO power. Main results. We recorded ECoG from the cortex of rats after two doses of ketamine, and extracted the HFO power from the ECoG spectrograms. We fit the PK-PD model to the time course of the HFO power, and showed that the model reproduces the dose-dependent profile of the HFO power. The model provides good fits even in the presence of high variability in HFO power across animals. As expected, the model does not provide good fits to the HFO power after dosing the pure NMDAR antagonist MK-801. Significance. Our study provides a simple model to relate the observed electrophysiological effects of ketamine to its actions at the molecular level at different concentrations. This will improve the study of ketamine and rodent models of schizophrenia to better understand the wide and divergent range of effects that ketamine has.

Glutamate and GABA in autism spectrum disorder-a translational magnetic resonance spectroscopy study in man and rodent models.

PubMed

Horder, Jamie; Petrinovic, Marija M; Mendez, Maria A; Bruns, Andreas; Takumi, Toru; Spooren, Will; Barker, Gareth J; Künnecke, Basil; Murphy, Declan G

2018-05-25

Autism spectrum disorder (ASD) is a pervasive neurodevelopmental syndrome with a high human and economic burden. The pathophysiology of ASD is largely unclear, thus hampering development of pharmacological treatments for the core symptoms of the disorder. Abnormalities in glutamate and GABA signaling have been hypothesized to underlie ASD symptoms, and may form a therapeutic target, but it is not known whether these abnormalities are recapitulated in humans with ASD, as well as in rodent models of the disorder. We used translational proton magnetic resonance spectroscopy ([1H]MRS) to compare glutamate and GABA levels in adult humans with ASD and in a panel of six diverse rodent ASD models, encompassing genetic and environmental etiologies. [1H]MRS was performed in the striatum and the medial prefrontal cortex, of the humans, mice, and rats in order to allow for direct cross-species comparisons in specific cortical and subcortical brain regions implicated in ASD. In humans with ASD, glutamate concentration was reduced in the striatum and this was correlated with the severity of social symptoms. GABA levels were not altered in either brain region. The reduction in striatal glutamate was recapitulated in mice prenatally exposed to valproate, and in mice and rats carrying Nlgn3 mutations, but not in rodent ASD models with other etiologies. Our findings suggest that glutamate/GABA abnormalities in the corticostriatal circuitry may be a key pathological mechanism in ASD; and may be linked to alterations in the neuroligin-neurexin signaling complex.

Endoparasites of Wild Rodents in Southeastern Iran

PubMed Central

Nateghpour, Mehdi; Motevalli-Haghi, Afsaneh; Akbarzadeh, Kamran; Akhavan, Amir Ahmad; Mohebali, Mehdi; Mobedi, Iraj; Farivar, Leila

2015-01-01

Background: This study was aimed to collect wild rodents for endoparasites determination in some parts of Sistan and Baluchistan Province, southeastern Iran nearby Pakistan and Afghanistan countries. Methods: A total of 100 wild rodents were captured alive with cage traps. Various samples were collected from blood and feces, also impression smear prepared from different organs. The samples were prepared by formalin-ether or stained with Giemsa, after that were examined under microscope. Results: All the caught rodents (47 Tatera indica, 44 Meriones hurriana, 5 Gerbilus nanus and 4 Meriones libycus) were studied for endoparasites emphasizing to their zoonotic aspects. Endoparasites including Spirurida, Hymenolepis diminuta, Hymenolepis nana feraterna, Trichuris trichiura, Skerjabino taenia, Trichostrongylus spp, Entamoeba muris, Chilomastix mesnili and Leishmania spp were parasitologically identified. Conclusion: Among 9 genera or species of the identified parasites at least 5 of them have zoonotic and public health importance. PMID:26114139

[Morphology, biology and life-cycle of Plasmodium parasites].

PubMed

Hommel, Marcel

2007-10-01

Laveran first discovered that an infectious agent was responsible for malaria by using a simple microscope, without the assistance of specific stains. Our knowledge of the Plasmodium life cycle and cellular biology has progressed with each technological advance, from Romanovsky staining and histology to electron microscopy, immunocytochemistry, molecular methods and modern imaging techniques. The use of bird, primate and rodent models also made a major contribution, notably in the development of antimalarial drugs that are still in use today.

Neurogenetics of Aggressive Behavior – Studies in Rodents

PubMed Central

Takahashi, Aki; Miczek, Klaus A.

2014-01-01

Aggressive behavior is observed in many animal species, such as insects, fish, lizards, frogs, and most mammals including humans. This wide range of conservation underscores the importance of aggressive behavior in the animals’ survival and fitness, and the likely heritability of this behavior. Although typical patterns of aggressive behavior differ between species, there are several concordances in the neurobiology of aggression among rodents, primates, and humans. Studies with rodent models may eventually help us to understand the neurogenetic architecture of aggression in humans. However, it is important to recognize the difference between the ecological and ethological significance of aggressive behavior (species-typical aggression) and maladaptive violence (escalated aggression) when applying the findings of aggression research using animal models to human or veterinary medicine. Well-studied rodent models for aggressive behavior in the laboratory setting include the mouse (Mus musculus), rat (Rattus norvegicus), hamster (Mesocricetus auratus), and prairie vole (Microtus ochrogaster). The neural circuits of rodent aggression have been gradually elucidated by several techniques e.g. immunohistochemistry of immediate-early gene (c-Fos) expression, intracranial drug microinjection, in vivo microdialysis, and optogenetics techniques. Also, evidence accumulated from the analysis of gene-knockout mice shows the involvement of several genes in aggression. Here we review the brain circuits that have been implicated in aggression, such as the hypothalamus, prefrontal cortex (PFC), dorsal raphe nucleus (DRN), nucleus accumbens (NAc), and olfactory system. We then discuss the roles of glutamate and γ-aminobutyric acid (GABA), major inhibitory and excitatory amino acids in the brain, as well as their receptors, in controlling aggressive behavior, focusing mainly on recent findings. At the end of this chapter, we discuss how genes can be identified that underlie individual differences in aggression, using the so-called forward genetics approach. PMID:24318936

Yucca brevifolia fruit production, predispersal seed predation, and fruit removal by rodents during two years of contrasting reproduction

USGS Publications Warehouse

Borchert, Mark I.; DeFalco, Lesley

2016-01-01

PREMISE OF THE STUDY: The distribution of Yucca brevifolia, a keystone species of the Mojave Desert, may contract with climate change, yet reproduction and dispersal are poorly understood. We tracked reproduction, seed predation, and fruit dispersal for two years and discuss whether Y. brevifolia is a masting species. METHODS: Fruit maturation, seed predation (larval yucca moths), and fruit dispersal (rodents) were monitored on a random sample of panicles during 2013 and 2014, which were years of high and low reproduction, respectively. Fates of fruits placed on the ground and in canopies were also tracked. Rodents were live-trapped to assess abundance and species composition. KEY RESULTS: In 2013, 66% of inflorescences produced fruit of which 53% escaped larval predation; 19.5% of seeds were destroyed in infested fruits. Total seed production was estimated to be >100 times greater in 2013 than 2014. One-third of the fruit crop fell to the ground and was removed by rodents over the course of 120 d. After ground fruits became scarce, rodents exploited canopy fruits. Rodent numbers were low in 2013, so fruits remained in canopies for 370 d. In 2014, fruit production was approximately 20% lower. Larvae infested the majority of fruits, and almost twice the number of seeds were damaged. Fruits were exploited by rodents within 65 d. CONCLUSIONS: High fertilization, prolific seed production, and low predispersal predation in 2013 suggests that pollinator attraction and satiation of seed predators influence masting in Y. brevifolia. Abundant, prolonged fruit availability to seed-dispersing rodents likely extends recruitment opportunities during mast years.

Long-term Potentiation Decay and Poor Long-lasting Memory Process in the Wild Rodents Proechimys from Brazil’s Amazon Rainforest

PubMed Central

Guimarães Marques, Marcia J.; Reyes-Garcia, Selvin Z.; Marques-Carneiro, José E.; Lopes-Silva, Leonardo B.; Andersen, Monica L.; Cavalheiro, Esper A.; Scorza, Fulvio A.; Scorza, Carla A.

2018-01-01

Proechimys are small terrestrial rodents from Amazon rainforest. Each animal species is adapted to a specific environment in which the animal evolved therefore without comparative approaches unique characteristics of distinct species cannot be fully recognized. Laboratory rodents are exceedingly inbred strains dissociated from their native habitats and their fundamental ecological aspects are abstracted. Thus, the employment of exotic non-model species can be informative and complement conventional animal models. With the aim of promoting comparative studies between the exotic wildlife populations in the laboratory and traditional rodent model, we surveyed a type of synaptic plasticity intimately related to memory encoding in animals. Using theta-burst paradigm, in vitro long-term potentiation (LTP) in the CA1 subfield of hippocampal slices was assessed in the Amazon rodents Proechimys and Wistar rats. Memory, learning and anxiety were investigated through the plus-maze discriminative avoidance task (PM-DAT) and object recognition test. In PM-DAT, both animal species were submitted to two test sessions (3-h and 24-h) after the conditioning training. Proechimys exhibited higher anxiety-like behavior in the training session but during test sessions both species exhibited similar patterns of anxiety-related behavior. After 3-h of the training, Proechimys and Wistar spent significantly less time in the aversive enclosed arm than in the non-aversive arm. But, at 24-h after training, Wistar rats remained less time in the aversive closed arm in comparison with the non-aversive one, while Proechimys rodents spent the same amount of time in both enclosed arms. In the object recognition test, both species were evaluated at 24-h after the acquisition session and similar findings than those of the PM-DAT (24-h) were obtained, suggesting that long-term memory duration did not persist for 24-h in the Amazon rodent. Field excitatory post-synaptic potentials recordings revealed that LTP decays rapidly over time reaching basal levels at 90 min after theta-burst stimulation in Proechimys, contrasting to the stable LTP found in the Wistar rats which was observed throughout 3-h recording period. These findings suggest a link between the LTP decay and the lack of 24-h long-lasting memory process in Proechimys. Nevertheless, why early-phase LTP in Proechimys decays very rapidly remains to be elucidated. PMID:29410617

Long-term Potentiation Decay and Poor Long-lasting Memory Process in the Wild Rodents Proechimys from Brazil's Amazon Rainforest.

PubMed

Guimarães Marques, Marcia J; Reyes-Garcia, Selvin Z; Marques-Carneiro, José E; Lopes-Silva, Leonardo B; Andersen, Monica L; Cavalheiro, Esper A; Scorza, Fulvio A; Scorza, Carla A

2018-01-01

Proechimys are small terrestrial rodents from Amazon rainforest. Each animal species is adapted to a specific environment in which the animal evolved therefore without comparative approaches unique characteristics of distinct species cannot be fully recognized. Laboratory rodents are exceedingly inbred strains dissociated from their native habitats and their fundamental ecological aspects are abstracted. Thus, the employment of exotic non-model species can be informative and complement conventional animal models. With the aim of promoting comparative studies between the exotic wildlife populations in the laboratory and traditional rodent model, we surveyed a type of synaptic plasticity intimately related to memory encoding in animals. Using theta-burst paradigm, in vitro long-term potentiation (LTP) in the CA1 subfield of hippocampal slices was assessed in the Amazon rodents Proechimys and Wistar rats. Memory, learning and anxiety were investigated through the plus-maze discriminative avoidance task (PM-DAT) and object recognition test. In PM-DAT, both animal species were submitted to two test sessions (3-h and 24-h) after the conditioning training. Proechimys exhibited higher anxiety-like behavior in the training session but during test sessions both species exhibited similar patterns of anxiety-related behavior. After 3-h of the training, Proechimys and Wistar spent significantly less time in the aversive enclosed arm than in the non-aversive arm. But, at 24-h after training, Wistar rats remained less time in the aversive closed arm in comparison with the non-aversive one, while Proechimys rodents spent the same amount of time in both enclosed arms. In the object recognition test, both species were evaluated at 24-h after the acquisition session and similar findings than those of the PM-DAT (24-h) were obtained, suggesting that long-term memory duration did not persist for 24-h in the Amazon rodent. Field excitatory post-synaptic potentials recordings revealed that LTP decays rapidly over time reaching basal levels at 90 min after theta-burst stimulation in Proechimys , contrasting to the stable LTP found in the Wistar rats which was observed throughout 3-h recording period. These findings suggest a link between the LTP decay and the lack of 24-h long-lasting memory process in Proechimys . Nevertheless, why early-phase LTP in Proechimys decays very rapidly remains to be elucidated.

Pharmacology of a Central Nervous System Delivered 2′-O-Methoxyethyl–Modified Survival of Motor Neuron Splicing Oligonucleotide in Mice and Nonhuman Primates

PubMed Central

Chun, Seung J.; Norris, Daniel A.; Hung, Gene; Lee, Sam; Matson, John; Fey, Robert A.; Gaus, Hans; Hua, Yimin; Grundy, John S.; Krainer, Adrian R.; Henry, Scott P.; Bennett, C. Frank

2014-01-01

Spinal muscular atrophy (SMA) is a debilitating neuromuscular disease caused by the loss of survival of motor neuron (SMN) protein. Previously, we demonstrated that ISIS 396443, an antisense oligonucleotide (ASO) targeted to the SMN2 pre-mRNA, is a potent inducer of SMN2 exon 7 inclusion and SMN protein expression, and improves function and survival of mild and severe SMA mouse models. Here, we demonstrate that ISIS 396443 is the most potent ASO in central nervous system (CNS) tissues of adult mice, compared with several other chemically modified ASOs. We evaluated methods of ISIS 396443 delivery to the CNS and characterized its pharmacokinetics and pharmacodynamics in rodents and nonhuman primates (NHPs). Intracerebroventricular bolus injection is a more efficient method of delivering ISIS 396443 to the CNS of rodents, compared with i.c.v. infusion. For both methods of delivery, the duration of ISIS 396443–mediated SMN2 splicing correction is long lasting, with maximal effects still observed 6 months after treatment discontinuation. Administration of ISIS 396443 to the CNS of NHPs by a single intrathecal bolus injection results in widespread distribution throughout the spinal cord. Based upon these preclinical studies, we have advanced ISIS 396443 into clinical development. PMID:24784568

Maripa Hantavirus in French Guiana: Phylogenetic Position and Predicted Spatial Distribution of Rodent Hosts

PubMed Central

de Thoisy, Benoît; Matheus, Séverine; Catzeflis, François; Clément, Luc; Barrioz, Sébastien; Guidez, Amandine; Donato, Damien; Cornu, Jean-François; Brunaux, Olivier; Guitet, Stéphane; Lacoste, Vincent; Lavergne, Anne

2014-01-01

A molecular screening of wild-caught rodents was conducted in French Guiana, South America to identify hosts of the hantavirus Maripa described in 2008 in a hantavirus pulmonary syndrome (HPS) case. Over a 9-year period, 418 echimyids and murids were captured. Viral RNA was detected in two sigmodontine rodents, Oligoryzomys fulvescens and Zygodontomys brevicauda, trapped close to the house of a second HPS case that occurred in 2009 and an O. fulvescens close to the fourth HPS case identified in 2013. Sequences from the rodents had 96% and 97% nucleotide identity (fragment of S and M segments, respectively) with the sequence of the first human HPS case. Phylogenetic reconstructions based on the complete sequence of the S segment show that Maripa virus is closely related to Rio Mamore hantavirus. Using environmental descriptors of trapping sites, including vegetation, landscape units, rain, and human disturbance, a maximal entropy-based species distribution model allowed for identification of areas of higher predicted occurrence of the two rodents, where emergence risks of Maripa virus are expected to be higher. PMID:24752689

Maripa hantavirus in French Guiana: phylogenetic position and predicted spatial distribution of rodent hosts.

PubMed

de Thoisy, Benoît; Matheus, Séverine; Catzeflis, François; Clément, Luc; Barrioz, Sébastien; Guidez, Amandine; Donato, Damien; Cornu, Jean-François; Brunaux, Olivier; Guitet, Stéphane; Lacoste, Vincent; Lavergne, Anne

2014-06-01

A molecular screening of wild-caught rodents was conducted in French Guiana, South America to identify hosts of the hantavirus Maripa described in 2008 in a hantavirus pulmonary syndrome (HPS) case. Over a 9-year period, 418 echimyids and murids were captured. Viral RNA was detected in two sigmodontine rodents, Oligoryzomys fulvescens and Zygodontomys brevicauda, trapped close to the house of a second HPS case that occurred in 2009 and an O. fulvescens close to the fourth HPS case identified in 2013. Sequences from the rodents had 96% and 97% nucleotide identity (fragment of S and M segments, respectively) with the sequence of the first human HPS case. Phylogenetic reconstructions based on the complete sequence of the S segment show that Maripa virus is closely related to Rio Mamore hantavirus. Using environmental descriptors of trapping sites, including vegetation, landscape units, rain, and human disturbance, a maximal entropy-based species distribution model allowed for identification of areas of higher predicted occurrence of the two rodents, where emergence risks of Maripa virus are expected to be higher. © The American Society of Tropical Medicine and Hygiene.

Rat infestation associated with environmental deficiencies in an urban slum community with high risk of leptospirosis transmission.

PubMed

Santos, Norlan de Jesus; Sousa, Erica; Reis, Mitermayer G; Ko, Albert I; Costa, Federico

2017-03-09

We analyzed environmental factors that provide food, water and harborage to rodents and the risk of household rodent infestation in a slum community with a high risk of leptospirosis transmission. Detailed environmental surveys were performed in 221 households. Multivariate regression models evaluated the association between rodent infestation and socioeconomic status and environmental attributes obtained from Geographical Information System surveys. The general household infestation rate was 45.9%. Rattus norvegicus signs were the most prevalent, present in 74% of the infested households. The risk for rodent infestation was associated with environmental factors supporting harborage for rats, such as dilapidated fences/walls (OR: 8.95; 95%CI: 2.42-33.12) and households built on an earthen slope (OR: 4.68; 95%CI: 2.23-9.81). An increase of 1 meter from the nearest sewer was associated with a 3% (95%CI: 1%-5%) decrease in the risk of rodent infestation. A lack of sanitation where poor people live provides factors for rat infestation and could the target of educational interventions.

Mouse Social Interaction Test (MoST): a quantitative computer automated analysis of behavior.

PubMed

Thanos, Panayotis K; Restif, Christophe; O'Rourke, Joseph R; Lam, Chiu Yin; Metaxas, Dimitris

2017-01-01

Rodents are the most commonly used preclinical model of human disease assessing the mechanism(s) involved as well as the role of genetics, epigenetics, and pharmacotherapy on this disease as well as identifying vulnerability factors and risk assessment for disease critical in the development of improved treatment strategies. Unfortunately, the majority of rodent preclinical studies utilize single housed approaches where animals are either entirely housed and tested in solitary environments or group housed but tested in solitary environments. This approach, however, ignores the important contribution of social interaction and social behavior. Social interaction in rodents is found to be a major criterion for the ethological validity of rodent species-specific behavioral characteristics (Zurn et al. 2007; Analysis 2011). It is also well established that there is significant and growing number of reports, which illustrates the important role of social environment and social interaction in all diseases, with particularly significance in all neuropsychiatric diseases. Thus, it is imperative that research studies be able to add large-scale evaluations of social interaction and behavior in mice and benefit from automated tracking of behaviors and measurements by removing user bias and by quantifying aspects of behaviors that cannot be assessed by a human observer. Single mouse setups have been used routinely, but cannot be easily extended to multiple-animal studies where social behavior is key, e.g., autism, depression, anxiety, substance and non-substance addictive disorders, aggression, sexual behavior, or parenting. While recent efforts are focusing on multiple-animal tracking alone, a significant limitation remains the lack of insightful measures of social interactions. We present a novel, non-invasive single camera-based automated tracking method described as Mouse Social Test (MoST) and set of measures designed for estimating the interactions of multiple mice at the same time in the same environment interacting freely. Our results show measurement of social interactions and designed to be adaptable and applicable to most existing home cage systems used in research, and provide a greater level of detailed analysis of social behavior than previously possible. The present study describes social behaviors assessed in a home cage environment setup containing six mice that interact freely over long periods of time, and we illustrate how these measures can be interpreted and combined to classify rodent social behaviors. In addition, we illustrate how these measures can be interpreted and combined to classify and analyze comprehensively rodent behaviors involved in several neuropsychiatric diseases as well as provide opportunity for the basic research of rodent behavior previously not possible.

Chronic Unpredictable Stress (CUS)-Induced Anxiety and Related Mood Disorders in a Zebrafish Model: Altered Brain Proteome Profile Implicates Mitochondrial Dysfunction

PubMed Central

Chakravarty, Sumana; Reddy, Bommana R.; Sudhakar, Sreesha R.; Saxena, Sandeep; Das, Tapatee; Meghah, Vuppalapaty; Brahmendra Swamy, Cherukuvada V.; Kumar, Arvind; Idris, Mohammed M.

2013-01-01

Anxiety and depression are major chronic mood disorders, and the etiopathology for each appears to be repeated exposure to diverse unpredictable stress factors. Most of the studies on anxiety and related mood disorders are performed in rodents, and a good model is chronic unpredictable stress (CUS). In this study, we have attempted to understand the molecular basis of the neuroglial and behavioral changes underlying CUS-induced mood disorders in the simplest vertebrate model, the zebrafish, Danio rerio. Zebrafish were subjected to a CUS paradigm in which two different stressors were used daily for 15 days, and thorough behavioral analyses were performed to assess anxiety and related mood disorder phenotypes using the novel tank test, shoal cohesion and scototaxis. Fifteen days of exposure to chronic stressors appears to induce an anxiety and related mood disorder phenotype. Decreased neurogenesis, another hallmark of anxiety and related disorders in rodents, was also observed in this zebrafish model. The common molecular markers of rodent anxiety and related disorders, corticotropin-releasing factor (CRF), calcineurin (ppp3r1a) and phospho cyclic AMP response element binding protein (pCREB), were also replicated in the fish model. Finally, using 2DE FTMS/ITMSMS proteomics analyses, 18 proteins were found to be deregulated in zebrafish anxiety and related disorders. The most affected process was mitochondrial function, 4 of the 18 differentially regulated proteins were mitochondrial proteins: PHB2, SLC25A5, VDAC3 and IDH2, as reported in rodent and clinical samples. Thus, the zebrafish CUS model and proteomics can facilitate not only uncovering new molecular targets of anxiety and related mood disorders but also the routine screening of compounds for drug development. PMID:23691016

Evolving Communicative Complexity: Insight from Rodents and Beyond

DTIC Science & Technology

2012-01-01

Group size in animal societies: the potential role of social and ecological limitations in the group-living fish , Paragobiodon xanthosomus. Ethology... Ecology and Evolutionary Biology, University of California, Los Angeles, CA 90095, USA 2Human Research and Engineering Directorate, Perceptual Sciences...evolve is an active question in behavioural ecology . Sciurid rodents (ground squirrels, prairie dogs and marmots) provide an excellent model system for

State-dependent μ-opioid modulation of social motivation

PubMed Central

Loseth, Guro E.; Ellingsen, Dan-Mikael; Leknes, Siri

2014-01-01

Social mammals engage in affiliative interactions both when seeking relief from negative affect and when searching for pleasure and joy. These two motivational states are both modulated by μ-opioid transmission. The μ-opioid receptor (MOR) system in the brain mediates pain relief and reward behaviors, and is implicated in social reward processing and affiliative bonding across mammalian species. However, pharmacological manipulation of the μ-opioid system has yielded opposite effects on rodents and primates: in rodents, social motivation is generally increased by MOR agonists and reduced by antagonists, whereas the opposite pattern has been shown in primates. Here, we address this paradox by taking into account differences in motivational state. We first review evidence for μ-opioid mediation of reward processing, emotion regulation, and affiliation in humans, non-human primates, rodents and other species. Based on the consistent cross-species similarities in opioid functioning, we propose a unified, state-dependent model for μ-opioid modulation of affiliation across the mammalian species. Finally, we show that this state-dependent model is supported by evidence from both rodent and primate studies, when species and age differences in social separation response are taken into account. PMID:25565999

Rodentia and lagomorpha

USGS Publications Warehouse

Sheffield, S.R.; Sawicka-Kapusta, K.; Cohen, J.B.; Rattner, B.A.; Shore, Richard F.; Rattner, Barnett A.

2001-01-01

This comprehensive review examines the extensive literature on wild rodents and lagomorphs as biomonitors of environmental contamination. This chapter covers studies dealing with exposure and effects of environmental contaminants on rodent and lagomorph species, including pesticides (organochlorines, organophosphorus and carbamate compounds, herbicides, plant growth regulators, fungicides, and rodenticides), other organic chemicals, metals, radionuclides, and other miscellaneous contaminants. Many research needs become evident when reviewing ecotoxicological data for rodents and lagomorphs, the most striking being the paucity of information on rodent families other than Muridae (mice and rats). While our ability to qualitatively extrapolate effects observed in laboratory studies to field situations is good for a variety of contaminants, quantitative predictions of dose-response relationships are poor because inter-specific variation and differences in exposure patterns between laboratory and wild species to toxicants are for the most part unknown. More sophisticated comparative toxicity studies need to be undertaken that build on previous work in order to develop a database of information, to account for and model differences in exposure pathways, to document interactions among multiple stressors, to generate data establishing thresholds, critical concentrations, and diagnostic guidelines, and even to develop physiologically-based toxicokinetic models. Such efforts may enhance our ability to predict effects on wild populations, including threatened and endangered species.

Head-twitch response in rodents induced by the hallucinogen 2,5-dimethoxy-4-iodoamphetamine: a comprehensive history, a re-evaluation of mechanisms, and its utility as a model

PubMed Central

Canal, Clint E.; Morgan, Drake

2013-01-01

Two primary animal models persist for assessing hallucinogenic potential of novel compounds and for examining the pharmacological and neurobiological substrates underlying the actions of classical hallucinogens, the two-lever drug discrimination procedure and the drug-induced head-twitch response (HTR) in rodents. The substituted amphetamine hallucinogen, serotonin 2 (5-HT2) receptor agonist, 2,5-dimethoxy-4-iodoamphetamine (DOI) has emerged as the most popular pharmacological tool used in HTR studies of hallucinogens. Synthesizing classic, recent, and relatively overlooked findings, addressing ostensibly conflicting observations, and considering contemporary theories in receptor and behavioural pharmacology, this review provides an up-to-date and comprehensive synopsis of DOI and the HTR model, from neural mechanisms to utility for understanding psychiatric diseases. Also presented is support for the argument that, although both the two-lever drug discrimination and the HTR models in rodents are useful for uncovering receptors, interacting proteins, intracellular signalling pathways, and neurochemical processes affected by DOI and related classical hallucinogens, results from both models suggest they are not reporting hallucinogenic experiences in animals. PMID:22517680

Acute and chronic animal models for the evaluation of anti-diabetic agents

PubMed Central

2012-01-01

Diabetes mellitus is a potentially morbid condition with high prevalence worldwide thus being a major medical concern. Experimental induction of diabetes mellitus in animal models is essential for the advancement of our knowledge and understanding of the various aspects of its pathogenesis and ultimately finding new therapies and cure. Experimental diabetes mellitus is generally induced in laboratory animals by several methods that include: chemical, surgical and genetic (immunological) manipulations. Most of the experiments in diabetes are carried out in rodents, although some studies are still performed in larger animals. The present review highlights the various methods of inducing diabetes in experimental animals in order to test the newer drugs for their anti-diabetic potential. PMID:22257465

Landscape epidemiology in urban environments: The example of rodent-borne Trypanosoma in Niamey, Niger.

PubMed

Rossi, Jean-Pierre; Kadaouré, Ibrahima; Godefroid, Martin; Dobigny, Gauthier

2017-10-05

Trypanosomes are protozoan parasites found worldwide, infecting humans and animals. In the past decade, the number of reports on atypical human cases due to Trypanosoma lewisi or T. lewisi-like has increased urging to investigate the multiple factors driving the disease dynamics, particularly in cities where rodents and humans co-exist at high densities. In the present survey, we used a species distribution model, Maxent, to assess the spatial pattern of Trypanosoma-positive rodents in the city of Niamey. The explanatory variables were landscape metrics describing urban landscape composition and physiognomy computed from 8 land-cover classes. We computed the metrics around each data location using a set of circular buffers of increasing radii (20m, 40m, 60m, 80m and 100m). For each spatial resolution, we determined the optimal combination of feature class and regularization multipliers by fitting Maxent with the full dataset. Since our dataset was small (114 occurrences) we expected an important uncertainty associated to data partitioning into calibration and evaluation datasets. We thus performed 350 independent model runs with a training dataset representing a random subset of 80% of the occurrences and the optimal Maxent parameters. Each model yielded a map of habitat suitability over Niamey, which was transformed into a binary map implementing a threshold maximizing the sensitivity and the specificity. The resulting binary maps were combined to display the proportion of models that indicated a good environmental suitability for Trypanosoma-positive rodents. Maxent performed better with landscape metrics derived from buffers of 80m. Habitat suitability for Trypanosoma-positive rodents exhibited large patches linked to urban features such as patch richness and the proportion of landscape covered by concrete or tarred areas. Such inferences could be helpful in assessing areas at risk, setting of monitoring programs, public and medical staff awareness or even vaccination campaigns. Copyright © 2017 Elsevier B.V. All rights reserved.

The yin and yang of cannabis-induced psychosis: the actions of Δ(9)-tetrahydrocannabinol and cannabidiol in rodent models of schizophrenia.

PubMed

Arnold, J C; Boucher, A A; Karl, T

2012-01-01

The link between cannabis and psychosis has often been debated with polarized views on the topic. There is substantial epidemiological evidence showing that cannabis increases the risk of psychosis, whereas other research suggests that schizophrenia patients self-medicate with the substance. These conflicting accounts may at least be partially explained by the two phytocannabinoids cannabidiol (CBD) and Δ(9)-tetrahydrocannabinol (THC) and their opposing actions on schizophrenia-related symptoms. In the present review we will first focus on how traditional rodent models of schizophrenia have been used to improve our understanding of the propsychotic actions of THC and the antipsychotic actions of CBD. We will also review novel rodent models used to address genetic vulnerability to cannabis-induced schizophrenia and show that specific genes are being uncovered that modulate cannabinoid action (e.g. the schizophrenia susceptibility gene neuregulin 1). We will also review rodent studies that have addressed interactions between THC and CBD. These animal studies underscore great complexity with some studies showing that CBD antagonises the neurobehavioural effects of THC, while others show the opposite, that CBD potentiates the actions of THC. Various mechanisms are put forth to explain these divergent effects such as CBD antagonism at central CB1 receptors or that CBD inhibits proteins that regulate THC disposition and metabolism (e.g. the ABC transporter, P-glycoprotein).

ProTox: a web server for the in silico prediction of rodent oral toxicity.

PubMed

Drwal, Malgorzata N; Banerjee, Priyanka; Dunkel, Mathias; Wettig, Martin R; Preissner, Robert

2014-07-01

Animal trials are currently the major method for determining the possible toxic effects of drug candidates and cosmetics. In silico prediction methods represent an alternative approach and aim to rationalize the preclinical drug development, thus enabling the reduction of the associated time, costs and animal experiments. Here, we present ProTox, a web server for the prediction of rodent oral toxicity. The prediction method is based on the analysis of the similarity of compounds with known median lethal doses (LD50) and incorporates the identification of toxic fragments, therefore representing a novel approach in toxicity prediction. In addition, the web server includes an indication of possible toxicity targets which is based on an in-house collection of protein-ligand-based pharmacophore models ('toxicophores') for targets associated with adverse drug reactions. The ProTox web server is open to all users and can be accessed without registration at: http://tox.charite.de/tox. The only requirement for the prediction is the two-dimensional structure of the input compounds. All ProTox methods have been evaluated based on a diverse external validation set and displayed strong performance (sensitivity, specificity and precision of 76, 95 and 75%, respectively) and superiority over other toxicity prediction tools, indicating their possible applicability for other compound classes. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Euthanasia using gaseous agents in laboratory rodents.

PubMed

Valentim, A M; Guedes, S R; Pereira, A M; Antunes, L M

2016-08-01

Several questions have been raised in recent years about the euthanasia of laboratory rodents. Euthanasia using inhaled agents is considered to be a suitable aesthetic method for use with a large number of animals simultaneously. Nevertheless, its aversive potential has been criticized in terms of animal welfare. The data available regarding the use of carbon dioxide (CO2), inhaled anaesthetics (such as isoflurane, sevoflurane, halothane and enflurane), as well as carbon monoxide and inert gases are discussed throughout this review. Euthanasia of fetuses and neonates is also addressed. A table listing currently available information to ease access to data regarding euthanasia techniques using gaseous agents in laboratory rodents was compiled. Regarding better animal welfare, there is currently insufficient evidence to advocate banning or replacing CO2 in the euthanasia of rodents; however, there are hints that alternative gases are more humane. The exposure to a volatile anaesthetic gas before loss of consciousness has been proposed by some scientific studies to minimize distress; however, the impact of such a measure is not clear. Areas of inconsistency within the euthanasia literature have been highlighted recently and stem from insufficient knowledge, especially regarding the advantages of the administration of isoflurane or sevoflurane over CO2, or other methods, before loss of consciousness. Alternative methods to minimize distress may include the development of techniques aimed at inducing death in the home cage of animals. Scientific outcomes have to be considered before choosing the most suitable euthanasia method to obtain the best results and accomplish the 3Rs (replacement, reduction and refinement). © The Author(s) 2015.

Associations of Pet Ownership with Wheezing and Lung Function in Childhood: Findings from a UK Birth Cohort

PubMed Central

Collin, Simon M.; Granell, Raquel; Westgarth, Carri; Murray, Jane; Paul, Elizabeth S.; Sterne, Jonathan A. C.; Henderson, A. John

2015-01-01

Background Asthma is a heterogeneous condition and differential effects of pet ownership on non-atopic versus atopic asthma have been reported. The aim of this study was to investigate whether pet ownership during pregnancy and early childhood was associated with wheezing from birth to age 7 years and with lung function at age 8 years in a UK population-based birth cohort. Methods Data from the Avon Longitudinal Study of Parents and Children (ALSPAC) were used to investigate associations of pet ownership at six time-points from pregnancy to age 7 years with concurrent episodes of wheezing, wheezing trajectories (phenotypes) and lung function at age 8 years using logistic regression models adjusted for child’s sex, maternal history of asthma/atopy, maternal smoking during pregnancy, and family adversity. Results 4,706 children had complete data on pet ownership and wheezing. From birth to age 7 years, cat ownership was associated with an overall 6% lower odds of wheezing (OR=0.94 (0.89-0.99)). Rabbit and rodent ownership was associated with 21% (OR=1.21 (1.12-1.31)) and 11% (OR=1.11 (1.02–1.21)) higher odds of wheezing, respectively, with strongest effects evident during infancy. Rabbit and rodent ownership was positively associated with a ‘persistent wheeze’ phenotype. Pet ownership was not associated with lung function at age 8 years, with the exception of positive associations of rodent and bird ownership with better lung function. Conclusions Cat ownership was associated with reduced risk, and rabbit and rodent ownership with increased risk, of wheezing during childhood. The mechanisms behind these differential effects warrant further investigation. PMID:26061067

Brain and Behavioral Pathology in an Animal Model of Wernicke’s Encephalopathy and Wernicke-Korsakoff Syndrome

PubMed Central

Vetreno, Ryan P.; Ramos, Raddy L.; Anzalone, Steven; Savage, Lisa M.

2012-01-01

Animal models provide the opportunity for in-depth and experimental investigation into the anatomical and physiological underpinnings of human neurological disorders. Rodent models of thiamine deficiency have yielded significant insight into the structural, neurochemical and cognitive deficits associated with thiamine deficiency as well as proven useful toward greater understanding of memory function in the intact brain. In this review, we discuss the anatomical, neurochemical and behavioral changes that occur during the acute and chronic phases of thiamine deficiency and describe how rodent models of Wernicke-Korsakoff Syndrome aid in developing a more detailed picture of brain structures involved in learning and memory. PMID:22192411

Brain and behavioral pathology in an animal model of Wernicke's encephalopathy and Wernicke-Korsakoff Syndrome.

PubMed

Vetreno, Ryan P; Ramos, Raddy L; Anzalone, Steven; Savage, Lisa M

2012-02-03

Animal models provide the opportunity for in-depth and experimental investigation into the anatomical and physiological underpinnings of human neurological disorders. Rodent models of thiamine deficiency have yielded significant insight into the structural, neurochemical and cognitive deficits associated with thiamine deficiency as well as proven useful toward greater understanding of memory function in the intact brain. In this review, we discuss the anatomical, neurochemical and behavioral changes that occur during the acute and chronic phases of thiamine deficiency and describe how rodent models of Wernicke-Korsakoff Syndrome aid in developing a more detailed picture of brain structures involved in learning and memory. Copyright © 2011 Elsevier B.V. All rights reserved.

Investigating the Mechanisms of Action and the Identification of Breast Carcinogens by Computational Analysis of Female Rodent Carcinogens

DTIC Science & Technology

2005-08-01

QSAR in Environmental Researth was accepted and published in April of 2005. The manuscript described the cat -SAR program in detail. We note the...analysis of this data yielded a very good model. As such, this was a suitable dataset on which to develop and test the cat -SAR program. A copy of the...developed and validated (i.e., a-c) as planned in MCASE and then with the cat -SAR program. We have also updated rodent carcinogenicity models so that

Material Characterization and Computer Model Simulation of Low Density Polyurethane Foam Used in a Rodent Traumatic Brain Injury Model

PubMed Central

Zhang, Liying; Gurao, Manish; Yang, King H.; King, Albert I.

2011-01-01

Computer models of the head can be used to simulate the events associated with traumatic brain injury (TBI) and quantify biomechanical response within the brain. Marmarou’s impact acceleration rodent model is a widely used experimental model of TBI mirroring axonal pathology in humans. The mechanical properties of the low density polyurethane (PU) foam, an essential piece of energy management used in Marmarou’s impact device, has not been fully characterized. The foam used in Marmarou’s device was tested at seven strain rates ranging from quasi-static to dynamic (0.014 ~ 42.86 s−1) to quantify the stress-strain relationships in compression. Recovery rate of the foam after cyclic compression was also determined through the periods of recovery up to three weeks. The experimentally determined stress-strain curves were incorporated into a material model in an explicit Finite Element (FE) solver to validate the strain rate dependency of the FE foam model. Compression test results have shown that the foam used in the rodent impact acceleration model is strain rate dependent. The foam has been found to be reusable for multiple impacts. However the stress resistance of used foam is reduced to 70% of the new foam. The FU_CHANG_FOAM material model in an FE solver has been found to be adequate to simulate this rate sensitive foam. PMID:21459114

Material characterization and computer model simulation of low density polyurethane foam used in a rodent traumatic brain injury model.

PubMed

Zhang, Liying; Gurao, Manish; Yang, King H; King, Albert I

2011-05-15

Computer models of the head can be used to simulate the events associated with traumatic brain injury (TBI) and quantify biomechanical response within the brain. Marmarou's impact acceleration rodent model is a widely used experimental model of TBI mirroring axonal pathology in humans. The mechanical properties of the low density polyurethane (PU) foam, an essential piece of energy management used in Marmarou's impact device, has not been fully characterized. The foam used in Marmarou's device was tested at seven strain rates ranging from quasi-static to dynamic (0.014-42.86 s⁻¹) to quantify the stress-strain relationships in compression. Recovery rate of the foam after cyclic compression was also determined through the periods of recovery up to three weeks. The experimentally determined stress-strain curves were incorporated into a material model in an explicit Finite Element (FE) solver to validate the strain rate dependency of the FE foam model. Compression test results have shown that the foam used in the rodent impact acceleration model is strain rate dependent. The foam has been found to be reusable for multiple impacts. However the stress resistance of used foam is reduced to 70% of the new foam. The FU_CHANG_FOAM material model in an FE solver has been found to be adequate to simulate this rate sensitive foam. Copyright © 2011 Elsevier B.V. All rights reserved.

Animal models of serotonergic psychedelics.

PubMed

Hanks, James B; González-Maeso, Javier

2013-01-16

The serotonin 5-HT(2A) receptor is the major target of psychedelic drugs such as lysergic acid diethylamide (LSD), mescaline, and psilocybin. Serotonergic psychedelics induce profound effects on cognition, emotion, and sensory processing that often seem uniquely human. This raises questions about the validity of animal models of psychedelic drug action. Nonetheless, recent findings suggest behavioral abnormalities elicited by psychedelics in rodents that predict such effects in humans. Here we review the behavioral effects induced by psychedelic drugs in rodent models, discuss the translational potential of these findings, and define areas where further research is needed to better understand the molecular mechanisms and neuronal circuits underlying their neuropsychological effects.

Animal Models of Serotonergic Psychedelics

PubMed Central

2012-01-01

The serotonin 5-HT2A receptor is the major target of psychedelic drugs such as lysergic acid diethylamide (LSD), mescaline, and psilocybin. Serotonergic psychedelics induce profound effects on cognition, emotion, and sensory processing that often seem uniquely human. This raises questions about the validity of animal models of psychedelic drug action. Nonetheless, recent findings suggest behavioral abnormalities elicited by psychedelics in rodents that predict such effects in humans. Here we review the behavioral effects induced by psychedelic drugs in rodent models, discuss the translational potential of these findings, and define areas where further research is needed to better understand the molecular mechanisms and neuronal circuits underlying their neuropsychological effects. PMID:23336043

Evidence for Personal Protective Measures to Reduce Human Contact With Blacklegged Ticks and for Environmentally Based Control Methods to Suppress Host-Seeking Blacklegged Ticks and Reduce Infection with Lyme Disease Spirochetes in Tick Vectors and Rodent Reservoirs

PubMed Central

Eisen, Lars; Dolan, Marc C.

2018-01-01

In the 1980s, the blacklegged tick, Ixodes scapularis Say, and rodents were recognized as the principal vector and reservoir hosts of the Lyme disease spirochete Borrelia burgdorferi in the eastern United States, and deer were incriminated as principal hosts for I. scapularis adults. These realizations led to pioneering studies aiming to reduce the risk for transmission of B. burgdorferi to humans by attacking host-seeking ticks with acaricides, interrupting the enzootic transmission cycle by killing immatures infesting rodent reservoirs by means of acaricide-treated nesting material, or reducing deer abundance to suppress tick numbers. We review the progress over the past three decades in the fields of: 1) prevention of human–tick contact with repellents and permethrin-treated clothing, and 2) suppression of I. scapularis and disruption of enzootic B. burgdorferi transmission with environmentally based control methods. Personal protective measures include synthetic and natural product-based repellents that can be applied to skin and clothing, permethrin sprays for clothing and gear, and permethrin-treated clothing. A wide variety of approaches and products to suppress I. scapularis or disrupt enzootic B. burgdorferi transmission have emerged and been evaluated in field trials. Application of synthetic chemical acaricides is a robust method to suppress host-seeking I. scapularis ticks within a treated area for at least 6–8 wk. Natural product-based acaricides or entomopathogenic fungi have emerged as alternatives to kill host-seeking ticks for homeowners who are unwilling to use synthetic chemical acaricides. However, as compared with synthetic chemical acaricides, these approaches appear less robust in terms of both their killing efficacy and persistence. Use of rodent-targeted topical acaricides represents an alternative for homeowners opposed to open distribution of acaricides to the ground and vegetation on their properties. This host-targeted approach also provides the benefit of the intervention impacting the entire rodent home range. Rodent-targeted oral vaccines against B. burgdorferi and a rodent-targeted antibiotic bait have been evaluated in laboratory and field trials but are not yet commercially available. Targeting of deer—via deer reduction or treatment of deer with topical acaricides—can provide area-wide suppression of host-seeking I. scapularis. These two deer-targeted approaches combine great potential for protection that impacts the entire landscape with severe problems relating to public acceptance or implementation logistics. Integrated use of two or more methods has unfortunately been evaluated in very few published studies, but additional field evaluations of integrated tick and pathogen strategies are underway. PMID:27439616

Effects of experimental sleep deprivation on anxiety-like behavior in animal research: Systematic review and meta-analysis.

PubMed

Pires, Gabriel Natan; Bezerra, Andréia Gomes; Tufik, Sergio; Andersen, Monica Levy

2016-09-01

Increased acute anxiety is a commonly reported behavioral consequence of sleep deprivation in humans. However, rodent studies conducted so far produced inconsistent results, failing to reproduce the same sleep deprivation induced-anxiety observed in clinical experiments. While some presented anxiogenesis as result of sleep deprivation, others reported anxiolysis. In face of such inconsistencies, this article explores the effects of experimental sleep deprivation on anxiety-like behavior in animal research through a systematic review and a series of meta-analyses. A total of 50 of articles met our inclusion criteria, 30 on mice, 19 on rats and one on Zebrafish. Our review shows that sleep deprivation induces a decrease in anxiety-like behavior in preclinical models, which is opposite to results observed in human settings. These results were corroborated in stratified analyses according to species, sleep deprivation method and anxiety measurement technique. In conclusion, the use of animal models for the evaluation of the relationship between sleep deprivation lacks translational applicability and new experimental tools are needed to properly evaluate sleep deprivation-induced anxiogenesis in rodents. Copyright © 2016 Elsevier Ltd. All rights reserved.

Scopolamine provocation-based pharmacological MRI model for testing procognitive agents.

PubMed

Hegedűs, Nikolett; Laszy, Judit; Gyertyán, István; Kocsis, Pál; Gajári, Dávid; Dávid, Szabolcs; Deli, Levente; Pozsgay, Zsófia; Tihanyi, Károly

2015-04-01

There is a huge unmet need to understand and treat pathological cognitive impairment. The development of disease modifying cognitive enhancers is hindered by the lack of correct pathomechanism and suitable animal models. Most animal models to study cognition and pathology do not fulfil either the predictive validity, face validity or construct validity criteria, and also outcome measures greatly differ from those of human trials. Fortunately, some pharmacological agents such as scopolamine evoke similar effects on cognition and cerebral circulation in rodents and humans and functional MRI enables us to compare cognitive agents directly in different species. In this paper we report the validation of a scopolamine based rodent pharmacological MRI provocation model. The effects of deemed procognitive agents (donepezil, vinpocetine, piracetam, alpha 7 selective cholinergic compounds EVP-6124, PNU-120596) were compared on the blood-oxygen-level dependent responses and also linked to rodent cognitive models. These drugs revealed significant effect on scopolamine induced blood-oxygen-level dependent change except for piracetam. In the water labyrinth test only PNU-120596 did not show a significant effect. This provocational model is suitable for testing procognitive compounds. These functional MR imaging experiments can be paralleled with human studies, which may help reduce the number of false cognitive clinical trials. © The Author(s) 2015.

Evaluation of Purine Salvage as a Chemotherapeutic Target in the Plasmodium yoelii Rodent Model

DTIC Science & Technology

2008-03-01

total RNA was extracted from the WT and the B3 and D1 clones of the KO parasite lines using the Trizol method on saponin lysed parasites. For each...group, RNA originating from the two mice was pooled. Total RNA integrity was checked using the Agilent Bioanalyzer (Agilent Technologies , Santa Clara...twice on the array. The array has been developed and previously evaluated with hybridizations of total RNA extracted from blood stages. Probe

Systemic RNAi-mediated Gene Silencing in Nonhuman Primate and Rodent Myeloid Cells

PubMed Central

Novobrantseva, Tatiana I; Borodovsky, Anna; Wong, Jamie; Klebanov, Boris; Zafari, Mohammad; Yucius, Kristina; Querbes, William; Ge, Pei; Ruda, Vera M; Milstein, Stuart; Speciner, Lauren; Duncan, Rick; Barros, Scott; Basha, Genc; Cullis, Pieter; Akinc, Akin; Donahoe, Jessica S; Narayanannair Jayaprakash, K; Jayaraman, Muthusamy; Bogorad, Roman L; Love, Kevin; Whitehead, Katie; Levins, Chris; Manoharan, Muthiah; Swirski, Filip K; Weissleder, Ralph; Langer, Robert; Anderson, Daniel G; de Fougerolles, Antonin; Nahrendorf, Matthias; Koteliansky, Victor

2012-01-01

Leukocytes are central regulators of inflammation and the target cells of therapies for key diseases, including autoimmune, cardiovascular, and malignant disorders. Efficient in vivo delivery of small interfering RNA (siRNA) to immune cells could thus enable novel treatment strategies with broad applicability. In this report, we develop systemic delivery methods of siRNA encapsulated in lipid nanoparticles (LNP) for durable and potent in vivo RNA interference (RNAi)-mediated silencing in myeloid cells. This work provides the first demonstration of siRNA-mediated silencing in myeloid cell types of nonhuman primates (NHPs) and establishes the feasibility of targeting multiple gene targets in rodent myeloid cells. The therapeutic potential of these formulations was demonstrated using siRNA targeting tumor necrosis factor-α (TNFα) which induced substantial attenuation of disease progression comparable to a potent antibody treatment in a mouse model of rheumatoid arthritis (RA). In summary, we demonstrate a broadly applicable and therapeutically relevant platform for silencing disease genes in immune cells. PMID:23344621

Network Analysis of Rodent Transcriptomes in Spaceflight

NASA Technical Reports Server (NTRS)

Ramachandran, Maya; Fogle, Homer; Costes, Sylvain

2017-01-01

Network analysis methods leverage prior knowledge of cellular systems and the statistical and conceptual relationships between analyte measurements to determine gene connectivity. Correlation and conditional metrics are used to infer a network topology and provide a systems-level context for cellular responses. Integration across multiple experimental conditions and omics domains can reveal the regulatory mechanisms that underlie gene expression. GeneLab has assembled rich multi-omic (transcriptomics, proteomics, epigenomics, and epitranscriptomics) datasets for multiple murine tissues from the Rodent Research 1 (RR-1) experiment. RR-1 assesses the impact of 37 days of spaceflight on gene expression across a variety of tissue types, such as adrenal glands, quadriceps, gastrocnemius, tibalius anterior, extensor digitorum longus, soleus, eye, and kidney. Network analysis is particularly useful for RR-1 -omics datasets because it reinforces subtle relationships that may be overlooked in isolated analyses and subdues confounding factors. Our objective is to use network analysis to determine potential target nodes for therapeutic intervention and identify similarities with existing disease models. Multiple network algorithms are used for a higher confidence consensus.

Tick parasites of rodents in Romania: host preferences, community structure and geographical distribution

PubMed Central

2012-01-01

Background Ticks are among the most important vectors of zoonotic diseases in temperate regions of Europe, with widespread distribution and high densities, posing an important medical risk. Most ticks feed on a variety of progressively larger hosts, with a large number of small mammal species typically harbouring primarily the immature stages. However, there are certain Ixodidae that characteristically attack micromammals also during their adult stage. Rodents are widespread hosts of ticks, important vectors and competent reservoirs of tick-borne pathogens. Micromammal-tick associations have been poorly studied in Romania, and our manuscript shows the results of a large scale study on tick infestation epidemiology in rodents from Romania. Methods Rodents were caught using snap-traps in a variety of habitats in Romania, between May 2010 and November 2011. Ticks were individually collected from these rodents and identified to species and development stage. Frequency, mean intensity, prevalence and its 95% confidence intervals were calculated using the EpiInfo 2000 software. A p value of <0.05 was considered statistically significant. Results We examined 423 rodents (12 species) collected from six counties in Romania for the presence of ticks. Each collected tick was identified to species level and the following epidemiological parameters were calculated: prevalence, mean intensity and mean abundance. The total number of ticks collected from rodents was 483, with eight species identified: Ixodes ricinus, I. redikorzevi, I. apronophorus, I. trianguliceps, I. laguri, Dermacentor marginatus, Rhipicephalus sanguineus and Haemaphysalis sulcata. The overall prevalence of tick infestation was 29.55%, with a mean intensity of 3.86 and a mean abundance of 1.14. Only two polyspecific infestations were found: I. ricinus + I. redikorzevi and I. ricinus + D. marginatus. Conclusions Our study showed a relatively high diversity of ticks parasitizing rodents in Romania. The most common tick in rodents was I. ricinus, followed by I. redikorzevi. Certain rodents seem to host a significantly higher number of tick species than others, the most important within this view being Apodemus flavicollis and Microtus arvalis. The same applies for the overall prevalence of tick parasitism, with some species more commonly infected (M. arvalis, A. uralensis, A. flavicollis and M. glareolus) than others. Two rodent species (Mus musculus, Rattus norvegicus) did not harbour ticks at all. Based on our results we may assert that rodents generally can act as good indicators for assessing the distribution of certain tick species. PMID:23171665

Development of a reliable method for determining sex for a primitive rodent, the Point Arena mountain beaver (Aplodontia rufa nigra)

Treesearch

Kristine L. Pilgrim; William J. Zielinski; Fredrick V. Schlexer; Michael K. Schwartz

2012-01-01

The mountain beaver (Aplodontia rufa) is a primitive species of rodent, often considered a living fossil. The Point Arena mountain beaver (Aplodontia rufa nigra) is an endangered subspecies that occurs in a very restricted range in northern California. Efforts to recover this taxon have been limited by the lack of knowledge on their demography, particularly sex and age...

Cytotoxic and aryl hydrocarbon hydroxylase-inducing effects of laboratory rodent diets. A cell culture study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Toerroenen, R.; Pelkonen, K.; Kaerenlampi, S.

1991-01-01

Extracts of several rodent diets were studied for their cytotoxic and aryl hydrocarbon hydroxylase-inducing properties by an in vitro method. The cell culture system based on a mouse hepatoma cell line (Hepa-1) was shown to be convenient and sensitive method for screening of diets for these parameters implying the presence of compounds potentially harmful in vivo. Considerable differences among diets and batches were detected. Smallest effects were observed with a semipurified diet and with the unrefined diet which - contrary to other four unrefined diets - contained no fish.

Construction of vapor chambers used to expose mice to alcohol during the equivalent of all three trimesters of human development.

PubMed

Morton, Russell A; Diaz, Marvin R; Topper, Lauren A; Valenzuela, C Fernando

2014-07-13

Exposure to alcohol during development can result in a constellation of morphological and behavioral abnormalities that are collectively known as Fetal Alcohol Spectrum Disorders (FASDs). At the most severe end of the spectrum is Fetal Alcohol Syndrome (FAS), characterized by growth retardation, craniofacial dysmorphology, and neurobehavioral deficits. Studies with animal models, including rodents, have elucidated many molecular and cellular mechanisms involved in the pathophysiology of FASDs. Ethanol administration to pregnant rodents has been used to model human exposure during the first and second trimesters of pregnancy. Third trimester ethanol consumption in humans has been modeled using neonatal rodents. However, few rodent studies have characterized the effect of ethanol exposure during the equivalent to all three trimesters of human pregnancy, a pattern of exposure that is common in pregnant women. Here, we show how to build vapor chambers from readily obtainable materials that can each accommodate up to six standard mouse cages. We describe a vapor chamber paradigm that can be used to model exposure to ethanol, with minimal handling, during all three trimesters. Our studies demonstrate that pregnant dams developed significant metabolic tolerance to ethanol. However, neonatal mice did not develop metabolic tolerance and the number of fetuses, fetus weight, placenta weight, number of pups/litter, number of dead pups/litter, and pup weight were not significantly affected by ethanol exposure. An important advantage of this paradigm is its applicability to studies with genetically-modified mice. Additionally, this paradigm minimizes handling of animals, a major confound in fetal alcohol research.

The Feasibility of HIFU Liver Ablation Through the Ribcage and Cartilage in a Rodent Model

NASA Astrophysics Data System (ADS)

King, Randy; Rieke, Viola; Pauly, Kim Butts

2009-04-01

We examined the feasibility of the rat model for the study of HIFU treatment of liver cancer. Significance: HIFU is being developed for the minimally invasive treatment of primary and metastatic liver cancer. In patients, obstruction of the ultrasound by the ribs poses a significant problem, and current studies are under way which investigate the efficacy of focusing around or sonicating between the ribs. Such techniques show promise for patient treatments, but are not feasible when using rodent models. Results: Six recently euthanized (within the hour) Sprague-Dewey rats were used. The hair over the anterior surface was removed. Sonications were performed with the InSightec ExAblate system at 0.95 MHz, 1.1 MHz, and 1.35MHz through the rib cage. Temperature rise was monitored with MRI-based thermometry. Lesions were created in the livers of 5/6 rats. In the five rats, energy levels between 572-1194 Joules produced lesions every time. With energies greater than 1393 Joules, skin damaged was observed which prevented the ultrasound from propagating to the liver on subsequent sonications, accounting for the one study that failed to produce lesions. No thermal damage was observed at the skin with sonications that resulted in liver lesions, and no significant heating was observed at or near the skin in the MRI temperature maps. Conclusions: It is possible to ignore the effect of ribs and sternum in rodents and create lesions within the rat liver. This technique opens the door to using hepatocellular carcinoma rodent models in HIFU studies.

INHALATION EXPOSURE TO CARBON NANOTUBES (CNT) AND CARBON NANOFIBERS (CNF): METHODOLOGY AND DOSIMETRY

PubMed Central

Oberdörster, Günter; Castranova, Vincent; Asgharian, Bahman; Sayre, Phil

2015-01-01

Carbon nanotubes (CNT) and nanofibers (CNF) are used increasingly in a broad array of commercial products. Given current understandings, the most significant life-cycle exposures to CNT/CNF occur from inhalation when they become airborne at different stages of their life cycle, including workplace, use, and disposal. Increasing awareness of the importance of physicochemical properties as determinants of toxicity of CNT/CNF and existing difficulties in interpreting results of mostly acute rodent inhalation studies to date necessitate a reexamination of standardized inhalation testing guidelines. The current literature on pulmonary exposure to CNT/CNF and associated effects is summarized; recommendations and conclusions are provided that address test guideline modifications for rodent inhalation studies that will improve dosimetric extrapolation modeling for hazard and risk characterization based on the analysis of exposure-dose-response relationships. Several physicochemical parameters for CNT/CNF, including shape, state of agglomeration/aggregation, surface properties, impurities, and density, influence toxicity. This requires an evaluation of the correlation between structure and pulmonary responses. Inhalation, using whole-body exposures of rodents, is recommended for acute to chronic pulmonary exposure studies. Dry powder generator methods for producing CNT/CNF aerosols are preferred, and specific instrumentation to measure mass, particle size and number distribution, and morphology in the exposure chambers are identified. Methods are discussed for establishing experimental exposure concentrations that correlate with realistic human exposures, such that unrealistically high experimental concentrations need to be identified that induce effects under mechanisms that are not relevant for workplace exposures. Recommendations for anchoring data to results seen for positive and negative benchmark materials are included, as well as periods for postexposure observation. A minimum data set of specific bronchoalveolar lavage parameters is recommended. Retained lung burden data need to be gathered such that exposure-dose-response correlations may be analyzed and potency comparisons between materials and mammalian species are obtained considering dose metric parameters for interpretation of results. Finally, a list of research needs is presented to fill data gaps for further improving design, analysis, and interpretation and extrapolation of results of rodent inhalation studies to refine meaningful risk assessments for humans. PMID:26361791

Gut microbiome may contribute to insulin resistance and systemic inflammation in obese rodents: a meta-analysis.

PubMed

Jiao, Na; Baker, Susan S; Nugent, Colleen A; Tsompana, Maria; Cai, Liting; Wang, Yong; Buck, Michael J; Genco, Robert J; Baker, Robert D; Zhu, Ruixin; Zhu, Lixin

2018-04-01

A number of studies have associated obesity with altered gut microbiota, although results are discordant regarding compositional changes in the gut microbiota of obese animals. Herein we used a meta-analysis to obtain an unbiased evaluation of structural and functional changes of the gut microbiota in diet-induced obese rodents. The raw sequencing data of nine studies generated from high-fat diet (HFD)-induced obese rodent models were processed with QIIME to obtain gut microbiota compositions. Biological functions were predicted and annotated with KEGG pathways with PICRUSt. No significant difference was observed for alpha diversity and Bacteroidetes-to-Firmicutes ratio between obese and lean rodents. Bacteroidia, Clostridia, Bacilli, and Erysipelotrichi were dominant classes, but gut microbiota compositions varied among studies. Meta-analysis of the nine microbiome data sets identified 15 differential taxa and 57 differential pathways between obese and lean rodents. In obese rodents, increased abundance was observed for Dorea, Oscillospira, and Ruminococcus, known for fermenting polysaccharide into short chain fatty acids (SCFAs). Decreased Turicibacter and increased Lactococcus are consistent with elevated inflammation in the obese status. Differential functional pathways of the gut microbiome in obese rodents included enriched pyruvate metabolism, butanoate metabolism, propanoate metabolism, pentose phosphate pathway, fatty acid biosynthesis, and glycerolipid metabolism pathways. These pathways converge in the function of carbohydrate metabolism, SCFA metabolism, and biosynthesis of lipid. HFD-induced obesity results in structural and functional dysbiosis of gut microbiota. The altered gut microbiome may contribute to obesity development by promoting insulin resistance and systemic inflammation.

Investigation of brain science and neurological/psychiatric disorders using genetically modified non-human primates.

PubMed

Okano, Hideyuki; Kishi, Noriyuki

2018-06-01

Although mice have been the most frequently used experimental animals in many research fields due to well-established gene manipulation techniques, recent evidence has revealed that rodent models do not always recapitulate pathophysiology of human neurological and psychiatric diseases due to the differences between humans and rodents. The recent developments in gene manipulation of non-human primate have been attracting much attention in the biomedical research field, because non-human primates have more applicable brain structure and function than rodents. In this review, we summarize recent progress on genetically-modified non-human primates including transgenic and knockout animals using genome editing technology. Copyright © 2017 Elsevier Ltd. All rights reserved.

Measuring Motivation and Reward-Related Decision Making in the Rodent Operant Touchscreen System.

PubMed

Heath, Christopher J; Phillips, Benjamin U; Bussey, Timothy J; Saksida, Lisa M

2016-01-04

This unit is designed to facilitate implementation of the fixed and progressive ratio paradigms and the effort-related choice task in the rodent touchscreen apparatus to permit direct measurement of motivation and reward-related decision making in this equipment. These protocols have been optimized for use in the mouse and reliably yield stable performance levels that can be enhanced or suppressed by systemic pharmacological manipulation. Instructions are also provided for the adjustment of task parameters to permit use in mouse models of neurodegenerative disease. These tasks expand the utility of the rodent touchscreen apparatus beyond the currently available battery of cognitive assessment paradigms. Copyright © 2016 John Wiley & Sons, Inc.

Animal Models for the Study of Rodent-Borne Hemorrhagic Fever Viruses: Arenaviruses and Hantaviruses

PubMed Central

Golden, Joseph W.; Hammerbeck, Christopher D.; Mucker, Eric M.; Brocato, Rebecca L.

2015-01-01

Human pathogenic hantaviruses and arenaviruses are maintained in nature by persistent infection of rodent carrier populations. Several members of these virus groups can cause significant disease in humans that is generically termed viral hemorrhagic fever (HF) and is characterized as a febrile illness with an increased propensity to cause acute inflammation. Human interaction with rodent carrier populations leads to infection. Arenaviruses are also viewed as potential biological weapons threat agents. There is an increased interest in studying these viruses in animal models to gain a deeper understating not only of viral pathogenesis, but also for the evaluation of medical countermeasures (MCM) to mitigate disease threats. In this review, we examine current knowledge regarding animal models employed in the study of these viruses. We include analysis of infection models in natural reservoirs and also discuss the impact of strain heterogeneity on the susceptibility of animals to infection. This information should provide a comprehensive reference for those interested in the study of arenaviruses and hantaviruses not only for MCM development but also in the study of viral pathogenesis and the biology of these viruses in their natural reservoirs. PMID:26266264

In situ enzymatic activity of transglutaminase isoforms on brain tissue sections of rodents: A new approach to monitor differences in post-translational protein modifications during neurodegeneration.

PubMed

Schulze-Krebs, Anja; Canneva, Fabio; Schnepf, Rebecca; Dobner, Julia; Dieterich, Walburga; von Hörsten, Stephan

2016-01-15

Mammalian transglutaminases (TGs) catalyze the irreversible post-translational modifications of proteins, the most prominent of which is the calcium-dependent formation of covalent acyl transfers between the γ-carboxamide group of glutamine and the ε-amino-group of lysine (GGEL-linkage). In the central nervous system, at least four TG isoforms are present and some of them are differentially expressed under pathological conditions in human patients. However, the precise TG-isoform-dependent enzymatic activities in the brain as well as their anatomical distribution are unknown. Specificity of the used biotinylated peptides was analyzed using an in vitro assay. Isoform-specific TG activity was evaluated in in vitro and in situ studies, using brain extracts and native brain tissue obtained from rodents. Our method allowed us to reveal in vitro and in situ TG-isoform-dependent enzymatic activity in brain extracts and tissue of rats and mice, with a specific focus on TG6. In situ activity of this isoform varied between BACHD mice in comparison to their wt controls. TG isozyme-specific activity can be detected by isoform-specific biotinylated peptides in brain tissue sections of rodents to reveal differences in the anatomical and/or subcellular distribution of TG activity. Our findings yield the basis for a broader application of this method for the screening of pathological expression and activity of TGs in a variety of animal models of human diseases, as in the case of neurodegenerative conditions such as Huntington׳s, Parkinson׳s and Alzheimer׳s, where protein modification is involved as a key mechanism of disease progression. Copyright © 2015 Elsevier B.V. All rights reserved.

DNA Barcoding of Sigmodontine Rodents: Identifying Wildlife Reservoirs of Zoonoses

PubMed Central

Müller, Lívia; Gonçalves, Gislene L.; Cordeiro-Estrela, Pedro; Marinho, Jorge R.; Althoff, Sérgio L.; Testoni, André. F.; González, Enrique M.; Freitas, Thales R. O.

2013-01-01

Species identification through DNA barcoding is a tool to be added to taxonomic procedures, once it has been validated. Applying barcoding techniques in public health would aid in the identification and correct delimitation of the distribution of rodents from the subfamily Sigmodontinae. These rodents are reservoirs of etiological agents of zoonoses including arenaviruses, hantaviruses, Chagas disease and leishmaniasis. In this study we compared distance-based and probabilistic phylogenetic inference methods to evaluate the performance of cytochrome c oxidase subunit I (COI) in sigmodontine identification. A total of 130 sequences from 21 field-trapped species (13 genera), mainly from southern Brazil, were generated and analyzed, together with 58 GenBank sequences (24 species; 10 genera). Preliminary analysis revealed a 9.5% rate of misidentifications in the field, mainly of juveniles, which were reclassified after examination of external morphological characters and chromosome numbers. Distance and model-based methods of tree reconstruction retrieved similar topologies and monophyly for most species. Kernel density estimation of the distance distribution showed a clear barcoding gap with overlapping of intraspecific and interspecific densities < 1% and 21 species with mean intraspecific distance < 2%. Five species that are reservoirs of hantaviruses could be identified through DNA barcodes. Additionally, we provide information for the description of a putative new species, as well as the first COI sequence of the recently described genus Drymoreomys. The data also indicated an expansion of the distribution of Calomys tener. We emphasize that DNA barcoding should be used in combination with other taxonomic and systematic procedures in an integrative framework and based on properly identified museum collections, to improve identification procedures, especially in epidemiological surveillance and ecological assessments. PMID:24244670

Conspecific Interactions in Adult Laboratory Rodents: Friends or Foes?

PubMed

Lukas, Michael; de Jong, Trynke R

2017-01-01

Interactions between adult conspecifics, including sexual behaviors, affiliation, and aggression are crucial for the well-being, survival, and reproduction of mammals. This holds true for any mammalian species, but certainly for humans: An inability to optimally navigate the social system can have a strong negative impact on physical and mental health. Translational rodent models have been used for decades to unravel the neural pathways and substrates involved in normal and abnormal conspecific interactions. Researchers in the field of translational social neuroscience face a double challenge: Not only do they need to pay considerable attention to the behavioral ecology of their model species or their ancestors, they also have to expect a relatively large variability in behavior and adjust their experimental design accordingly. In this chapter, we will lay out traditional and novel rodent models and paradigms to study sexual, affiliative, and aggressive interactions among adult conspecifics. We will discuss the merits and main findings and briefly consider the most promising novel directions. Finally, we review the modulatory involvement of two major players in mammal social interaction: the central oxytocin and vasopressin system.

Optical imaging of oxidative stress in retinitis pigmentosa (RP) in rodent model

NASA Astrophysics Data System (ADS)

Ghanian, Zahra; Maleki, Sepideh; Gopalakrishnan, Sandeep; Sepehr, Reyhaneh; Eells, Janis T.; Ranji, Mahsa

2013-02-01

Oxidative stress (OS), which increases during retinal degenerative disorders, contributes to photoreceptor cell loss. The objective of this study was to investigate the changes in the metabolic state of the eye tissue in rodent models of retinitis pigmentosa by using the cryofluorescence imaging technique. The mitochondrial metabolic coenzymes NADH and FADH2 are autofluorescent and can be monitored without exogenous labels using optical techniques. The NADH redox ratio (RR), which is the ratio of the fluorescence intensity of these fluorophores (NADH/FAD), was used as a quantitative diagnostic marker. The NADH RR was examined in an established rodent model of retinitis pigmentosa (RP), the P23H rat, and compared to that of control Sprague-Dawley (SD) rats and P23H NIR treated rats. Our results demonstrated 24% decrease in the mean NADH RR of the eyes from P23H transgenic rats compared to normal rats and 20% increase in the mean NADH RR of the eyes from the P23H NIR treated rats compared to P23H non-treated rats.

[Biological and neural bases of partner preferences in rodents: models to understand human pair bonds].

PubMed

Coria-Avila, G A; Hernández-Aguilar, M E; Toledo-Cárdenas, R; García-Hernández, L I; Manzo, J; Pacheco, P; Miquel, M; Pfaus, J G

To analyse the biological and neural bases of partner preference formation in rodents as models to understand human pair bonding. Rodents are social individuals, capable of forming short- or long-lasting partner preferences that develop slowly by stimuli like cohabitation, or rapidly by stimuli like sex and stress. Dopamine, corticosteroids, oxytocin, vasopressin, and opioids form the neurochemical substrate for pair bonding in areas like the nucleus accumbens, the prefrontal cortex, the piriform cortex, the medial preoptic area, the ventral tegmental area and the medial amygdala, among others. Additional areas may participate depending on the nature of the conditioned stimuli by which and individual recognizes a preferred partner. Animal models help us understand that the capacity of an individual to display long-lasting and selective preferences depends on neural bases, selected throughout evolution. The challenge in neuroscience is to use this knowledge to create new solutions for mental problems associated with the incapacity of an individual to display a social bond, keep one, or cope with the disruption of a consolidated one.

The cognitive cost of sleep lost

PubMed Central

McCoy, John G.; Strecker, Robert E.

2013-01-01

A substantial body of literature supports the intuitive notion that a good night’s sleep can facilitate human cognitive performance the next day. Deficits in attention, learning & memory, emotional reactivity, and higher-order cognitive processes, such as executive function and decision making, have all been documented following sleep disruption in humans. Thus, whilst numerous clinical and experimental studies link human sleep disturbance to cognitive deficits, attempts to develop valid and reliable rodent models of these phenomena are fewer, and relatively more recent. This review focuses primarily on the cognitive impairments produced by sleep disruption in rodent models of several human patterns of sleep loss/sleep disturbance. Though not an exclusive list, this review will focus on four specific types of sleep disturbance: total sleep deprivation, experimental sleep fragmentation, selective REM sleep deprivation, and chronic sleep restriction. The use of rodent models can provide greater opportunities to understand the neurobiological changes underlying sleep loss induced cognitive impairments. Thus, this review concludes with a description of recent neurobiological findings concerning the neuroplastic changes and putative brain mechanisms that may underlie the cognitive deficits produced by sleep disturbances. PMID:21875679

Childhood-Adolescent Obesity in the Cardiorenal Syndrome: Lessons from Animal Models

PubMed Central

Hayden, Melvin R.; Sowers, James R.

2011-01-01

Background/Aims Childhood-adolescent overweight and obesity have grown to pandemic proportions during the past decade. The onset of obesity in younger adults will likely be manifested as earlier onset of myocardial and renal end-organ disease in younger adults. For the first time, it is estimated that the current generation may not live to be as old as their parents. Thus, it is important to develop animal models of childhood obesity to understand fundamental pathological organ changes. Methods In this regard, we utilize transmission electron microscopy evaluation to evaluate early remodeling changes of two adolescent rodent obesity models: the Zucker obese (fa/fa) rat and the db/db mouse models of obesity. We have concentrated on the initial ultrastructural remodeling (obese adipose tissue, skeletal muscle, and islet remodeling) and the associated changes in target end organs (including the myocardium and kidney) in young rodent models of obesity and insulin resistance, collectively manifesting as the cardiorenal metabolic syndrome (CRS). Results Briefly, tissues revealed the following ultrastructural remodeling abnormalities: inflammation, hypertrophy, and early fibrosis in adipose tissue; loss of mitochondria in skeletal muscles, hyperplasia, fibrosis, and depletion of insulin-secretory granules in pancreatic islets; increased intramyocardial lipid accumulation, fibrosis, and mitochondrial deposition in the myocardium, and obesity-related glomerulopathy and tubulopathy in the kidney. Conclusion Based on the current knowledge and ultrastructural observations of organ pathology, we propose mechanisms whereby obesity appears to be the driving force behind the development of the CRS. PMID:22294984

A simplified up-down method (SUDO) for measuring mechanical nociception in rodents using von Frey filaments

PubMed Central

2014-01-01

Background The measurement of mechanosensitivity is a key method for the study of pain in animal models. This is often accomplished with the use of von Frey filaments in an up-down testing paradigm. The up-down method described by Chaplan et al. (J Neurosci Methods 53:55–63, 1994) for mechanosensitivity testing in rodents remains one of the most widely used methods for measuring pain in animals. However, this method results in animals receiving a varying number of stimuli, which may lead to animals in different groups receiving different testing experiences that influences their later responses. To standardize the measurement of mechanosensitivity we developed a simplified up-down method (SUDO) for estimating paw withdrawal threshold (PWT) with von Frey filaments that uses a constant number of five stimuli per test. We further refined the PWT calculation to allow the estimation of PWT directly from the behavioral response to the fifth stimulus, omitting the need for look-up tables. Results The PWT estimates derived using SUDO strongly correlated (r > 0.96) with the PWT estimates determined with the conventional up-down method of Chaplan et al., and this correlation remained very strong across different levels of tester experience, different experimental conditions, and in tests from both mice and rats. The two testing methods also produced similar PWT estimates in prospective behavioral tests of mice at baseline and after induction of hyperalgesia by intraplantar capsaicin or complete Freund’s adjuvant. Conclusion SUDO thus offers an accurate, fast and user-friendly replacement for the widely used up-down method of Chaplan et al. PMID:24739328

Evaluation of the percentage of ganglion cells in the ganglion cell layer of the rodent retina

PubMed Central

Schlamp, Cassandra L.; Montgomery, Angela D.; Mac Nair, Caitlin E.; Schuart, Claudia; Willmer, Daniel J.

2013-01-01

Purpose Retinal ganglion cells comprise a percentage of the neurons actually residing in the ganglion cell layer (GCL) of the rodent retina. This estimate is useful to extrapolate ganglion cell loss in models of optic nerve disease, but the values reported in the literature are highly variable depending on the methods used to obtain them. Methods We tested three retrograde labeling methods and two immunostaining methods to calculate ganglion cell number in the mouse retina (C57BL/6). Additionally, a double-stain retrograde staining method was used to label rats (Long-Evans). The number of total neurons was estimated using a nuclear stain and selecting for nuclei that met specific criteria. Cholinergic amacrine cells were identified using transgenic mice expressing Tomato fluorescent protein. Total neurons and total ganglion cell numbers were measured in microscopic fields of 104 µm2 to determine the percentage of neurons comprising ganglion cells in each field. Results Historical estimates of the percentage of ganglion cells in the mouse GCL range from 36.1% to 67.5% depending on the method used. Experimentally, retrograde labeling methods yielded a combined estimate of 50.3% in mice. A retrograde method also yielded a value of 50.21% for rat retinas. Immunolabeling estimates were higher at 64.8%. Immunolabeling may introduce overestimates, however, with non-specific labeling effects, or ectopic expression of antigens in neurons other than ganglion cells. Conclusions Since immunolabeling methods may overestimate ganglion cell numbers, we conclude that 50%, which is consistently derived from retrograde labeling methods, is a reliable estimate of the ganglion cells in the neuronal population of the GCL. PMID:23825918

Advances in cytogenetics of Brazilian rodents: cytotaxonomy, chromosome evolution and new karyotypic data

PubMed Central

Di-Nizo, Camilla Bruno; Banci, Karina Rodrigues da Silva; Sato-Kuwabara, Yukie; Silva, Maria José de J.

2017-01-01

Abstract Rodents constitute one of the most diversified mammalian orders. Due to the morphological similarity in many of the groups, their taxonomy is controversial. Karyotype information proved to be an important tool for distinguishing some species because some of them are species-specific. Additionally, rodents can be an excellent model for chromosome evolution studies since many rearrangements have been described in this group.This work brings a review of cytogenetic data of Brazilian rodents, with information about diploid and fundamental numbers, polymorphisms, and geographical distribution. We point out that, even with the recent efforts on cytogenetic studies in this group, many species lack karyotypic data. Moreover, we describe for the first time the karyotype of Carterodon sulcidens (Lund, 1838) (Family Echimyidae), a new fundamental number for an undescribed species of Neacomys Thomas, 1900 (Family Cricetidae, Subfamily Sigmodontinae), and illustrate the karyotype of a Brazilian specimen of Mus musculus Linnaeus, 1758 (Family Muridae). This review compiles the cytogenetic data on Brazilian rodents reported in the last three decades, after the last revision published in 1984, including synonyms, chromosomal variations, and geographic distribution. Additionally, it also reinforces that Brazilian biodiversity is still poorly known, considering the new data reported here. PMID:29362668

Effects of rodent community diversity and composition on prevalence of an endemic bacterial pathogen - Bartonella

USGS Publications Warehouse

Bai, Y.; Kosoy, M.Y.; Calisher, C.H.; Cully, J.F.; Collinge, S.K.

2009-01-01

By studying Bartonella prevalence in rodent communities from 23 geographic sites in the western United States and one site in northern Mexico, the present study focused on the effects of rodent community diversity (measured by richness and Shannon index) and composition on prevalence of Bartonella infections. The analysis showed negative correlations of Bartonella prevalence with rodent richness and Shannon index. Further, Bartonella prevalence varied among rodent genera/species. Three models were applied to explain the observations. (1) Within-species/genus transmission: Bartonella strains usually are host-specific and adding non-host species would decrease Bartonella prevalence in its principal host through reduction of host contact (encounter reduction); (2) Frequency-dependence: Adding hosts would decrease the proportion of all infected individuals in the community, resulting in a reduction in the number of contacts between susceptible and infected individuals that usually leads to transmission (transmission reduction); and (3) Dominant species effect: Dominant species, if not susceptible to Bartonellae, can constrain the abundance of susceptible hosts (susceptible host regulation). These mechanisms work in concert; and the level of Bartonella prevalence is an outcome of regulation of all of these mechanisms on the entire system.

Temporal and spatial host abundance and prevalence of Andes hantavirus in southern Argentina.

PubMed

Polop, Francisco J; Provensal, María C; Pini, Noemí; Levis, Silvana C; Priotto, José W; Enría, Delia; Calderón, Gladys E; Costa, Federico; Polop, Jaime J

2010-06-01

Andes virus (AND) is a hantavirus hosted by the sigmodontine rodent Oligoryzomys longicaudatus in southern Argentina, where it is responsible for most cases of hantavirus pulmonary syndrome (HPS). Our study provides data about the spatial variation in abundance of the rodent host of AND hantavirus. We report results of a longitudinal study performed in a locality of the Andean region of Chubut Province. From November 2003 (spring) to July 2006 (winter), O. longicaudatus was the most common species captured (63%) and it showed significant differences in abundance among habitats and seasons. Most antibody-positive rodents were O. longicaudatus (9.2%), followed by A. longipilis (3.6%) and A. olivaceus (1.5%). The highest number of antibody-positive animals was observed for males that belonged to the heaviest mass classes. Antibody-positive O. longicaudatus were more abundant in brush habitats. We found low richness of rodents and abundance of O. longicaudatus in areas affected by anthropogenic activity. The infection seems to be regionally persistent, but the risk to humans in a landscape would be localized. To develop accurate models for predicting HPS outbreaks, further research is needed to characterize rodent movement patterns across the landscape.

Understanding spatio-temporal strategies of adult zebrafish exploration in the open field test.

PubMed

Stewart, Adam Michael; Gaikwad, Siddharth; Kyzar, Evan; Kalueff, Allan V

2012-04-27

Zebrafish (Danio rerio) are emerging as a useful model organism for neuroscience research. Mounting evidence suggests that various traditional rodent paradigms may be adapted for testing zebrafish behavior. The open field test is a popular rodent test of novelty exploration, recently applied to zebrafish research. To better understand fish novelty behavior, we exposed adult zebrafish to two different open field arenas for 30 min, assessing the amount and temporal patterning of their exploration. While (similar to rodents) zebrafish scale their locomotory activity depending on the size of the tank, the temporal patterning of their activity was independent of arena size. These observations strikingly parallel similar rodent behaviors, suggesting that spatio-temporal strategies of animal exploration may be evolutionarily conserved across vertebrate species. In addition, we found interesting oscillations in zebrafish exploration, with the per-minute distribution of their horizontal activity demonstrating sinusoidal-like patterns. While such patterning is not reported for rodents and other higher vertebrates, a nonlinear regression analysis confirmed the oscillation patterning of all assessed zebrafish behavioral endpoints in both open field arenas, revealing a potentially important aspect of novelty exploration in lower vertebrates. Copyright © 2012 Elsevier B.V. All rights reserved.

Response of brown treesnakes to reduction of their rodent prey

USGS Publications Warehouse

Gragg, J.E.; Rodda, G.H.; Savidge, J.A.; White, Gary C.; Dean-Bradley, K.; Ellingson, A.R.

2007-01-01

Trapping brown treesnakes (Boiga irregularis; BTS) with live-mouse (Mus domesticus) lures is the principal control technique for this invasive species on Guam. Lure-based trapping is also used on other islands as a precaution against undetected arrivals and in response to verified BTS sightings. However, the effectiveness of lure-based trapping on other islands is questionable, as it has yielded no BTS despite other evidence of their presence. Some evidence suggests that high rodent numbers may interfere with BTS control. To test the relationship between rodent abundance and snake trappability, we conducted a controlled, replicated field experiment incorporating a rodenticide treatment during a BTS mark-recapture study. Using open population modeling in Program MARK, we estimated BTS apparent survival and recapture probabilities. Rodent reduction increased BTS recapture probabilities by 52-65% in 2002 and 22-36% in 2003, and it decreased apparent survival by <1% both years. This appears to be the first published instance of manipulating wild prey to influence snake behavior. Rodent reduction may enhance detection and control of BTS with traps on Guam and other islands. It may also amplify the effectiveness of oral toxicants against BTS.

Translational Mouse Models of Autism: Advancing Toward Pharmacological Therapeutics

PubMed Central

Kazdoba, Tatiana M.; Leach, Prescott T.; Yang, Mu; Silverman, Jill L.; Solomon, Marjorie

2016-01-01

Animal models provide preclinical tools to investigate the causal role of genetic mutations and environmental factors in the etiology of autism spectrum disorder (ASD). Knockout and humanized knock-in mice, and more recently knockout rats, have been generated for many of the de novo single gene mutations and copy number variants (CNVs) detected in ASD and comorbid neurodevelopmental disorders. Mouse models incorporating genetic and environmental manipulations have been employed for preclinical testing of hypothesis-driven pharmacological targets, to begin to develop treatments for the diagnostic and associated symptoms of autism. In this review, we summarize rodent behavioral assays relevant to the core features of autism, preclinical and clinical evaluations of pharmacological interventions, and strategies to improve the translational value of rodent models of autism. PMID:27305922

Neuropeptides and the social brain: potential rodent models of autism.

PubMed

Lim, Miranda M; Bielsky, Isadora F; Young, Larry J

2005-01-01

Conducting basic scientific research on a complex psychiatric disorder, such as autism, is a challenging prospect. It is difficult to dissociate the fundamental neurological and psychological processes that are disturbed in autism and, therefore, it is a challenge to discover accurate and reliable animal models of the disease. Because of their role in animal models of social processing and social bonding, the neuropeptides oxytocin and vasopressin are strong candidates for dysregulation in autism. In this review, we discuss the current animal models which have investigated oxytocin and vasopressin systems in the brain and their effects on social behavior. For example, mice lacking the oxytocin gene have profound deficits in social processing and social recognition, as do rats lacking vasopressin or mice lacking the vasopressin V1a receptor (V1aR). In another rodent model, monogamous prairie voles are highly social and form strong pair bonds with their mates. Pair bonds can be facilitated or disrupted by perturbing the oxytocin and vasopressin systems. Non-monogamous vole species that do not pair bond have different oxytocin and V1aR distribution patterns in the brain than monogamous vole species. Potential ties from these rodent models to the human autistic condition are then discussed. Given the hallmark disturbances in social function, the study of animal models of social behavior may provide novel therapeutic targets for the treatment of autism.

Revised taxonomy and nomenclature of rodent Pasteurellaceae: Implications for monitoring.

PubMed

Boot, R; Nicklas, W; Christensen, H

2018-01-01

Pasteurellosis is a well-recognized disease with similar pathology in all laboratory rodent species. Pasteurella pneumotropica is the most frequently mentioned member of the Pasteurellaceae isolated from mice and rats. Numerous other Pasteurellaceae taxa have been obtained from mice, rats, and other rodent species. Recently, rodent Pasteurellaceae have been submitted to comprehensive genetic and phenotypic (polyphasic) taxonomic studies. As a result they are now classed within six validly published new genera, namely Cricetibacter, Mesocricetibacter, Mannheimia, Muribacter, Necropsobacter, and Rodentibacter. All previously used names such as P. pneumotropica have become obsolete. The new classification forms a firm basis for the correct phenotypic identification of Pasteurellaceae from laboratory animals and for the selection of strains for pathogenicity studies. Consequences of taxonomic changes notably involve molecular methods used for the detection of Pasteurellaceae infection in laboratory animal colonies. Testing may be done using primer sets that detect all Pasteurellaceae taxa or sets developed to detect host-specific members of the family.

Finite element modelling of squirrel, guinea pig and rat skulls: using geometric morphometrics to assess sensitivity.

PubMed

Cox, P G; Fagan, M J; Rayfield, E J; Jeffery, N

2011-12-01

Rodents are defined by a uniquely specialized dentition and a highly complex arrangement of jaw-closing muscles. Finite element analysis (FEA) is an ideal technique to investigate the biomechanical implications of these specializations, but it is essential to understand fully the degree of influence of the different input parameters of the FE model to have confidence in the model's predictions. This study evaluates the sensitivity of FE models of rodent crania to elastic properties of the materials, loading direction, and the location and orientation of the models' constraints. Three FE models were constructed of squirrel, guinea pig and rat skulls. Each was loaded to simulate biting on the incisors, and the first and the third molars, with the angle of the incisal bite varied over a range of 45°. The Young's moduli of the bone and teeth components were varied between limits defined by findings from our own and previously published tests of material properties. Geometric morphometrics (GMM) was used to analyse the resulting skull deformations. Bone stiffness was found to have the strongest influence on the results in all three rodents, followed by bite position, and then bite angle and muscle orientation. Tooth material properties were shown to have little effect on the deformation of the skull. The effect of bite position varied between species, with the mesiodistal position of the biting tooth being most important in squirrels and guinea pigs, whereas bilateral vs. unilateral biting had the greatest influence in rats. A GMM analysis of isolated incisor deformations showed that, for all rodents, bite angle is the most important parameter, followed by elastic properties of the tooth. The results here elucidate which input parameters are most important when defining the FE models, but also provide interesting glimpses of the biomechanical differences between the three skulls, which will be fully explored in future publications. © 2011 The Authors. Journal of Anatomy © 2011 Anatomical Society of Great Britain and Ireland.

Long-term oral kinetin does not protect against α-synuclein-induced neurodegeneration in rodent models of Parkinson's disease.

PubMed

Orr, Adam L; Rutaganira, Florentine U; de Roulet, Daniel; Huang, Eric J; Hertz, Nicholas T; Shokat, Kevan M; Nakamura, Ken

2017-10-01

Mutations in the mitochondrial kinase PTEN-induced putative kinase 1 (PINK1) cause Parkinson's disease (PD), likely by disrupting PINK1's kinase activity. Although the mechanism(s) underlying how this loss of activity causes degeneration remains unclear, increasing PINK1 activity may therapeutically benefit some forms of PD. However, we must first learn whether restoring PINK1 function prevents degeneration in patients harboring PINK1 mutations, or whether boosting PINK1 function can offer protection in more common causes of PD. To test these hypotheses in preclinical rodent models of PD, we used kinetin triphosphate, a small-molecule that activates both wild-type and mutant forms of PINK1, which affects mitochondrial function and protects neural cells in culture. We chronically fed kinetin, the precursor of kinetin triphosphate, to PINK1-null rats in which PINK1 was reintroduced into their midbrain, and also to rodent models overexpressing α-synuclein. The highest tolerated dose of oral kinetin increased brain levels of kinetin for up to 6 months, without adversely affecting the survival of nigrostriatal dopamine neurons. However, there was no degeneration of midbrain dopamine neurons lacking PINK1, which precluded an assessment of neuroprotection and raised questions about the robustness of the PINK1 KO rat model of PD. In two rodent models of α-synuclein-induced toxicity, boosting PINK1 activity with oral kinetin provided no protective effects. Our results suggest that oral kinetin is unlikely to protect against α-synuclein toxicity, and thus fail to provide evidence that kinetin will protect in sporadic models of PD. Kinetin may protect in cases of PINK1 deficiency, but this possibility requires a more robust PINK1 KO model that can be validated by proof-of-principle genetic correction in adult animals. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Therapeutic Potential of Induced Pluripotent Stem Cells After Stroke: Evidence from Rodent Models.

PubMed

Zents, Karlijn; Copray, Sjef

2016-01-01

Stroke is the second most common cause of death and the leading cause of disability in the world. About 30% of the people that are affected by stroke die within a year; 25% of the patients that survive stroke remain in need of care after a year. Therefore, stroke is a major burden for health care costs. The most common subtype is ischemic stroke. This type is characterized by a reduced and insufficient blood supply to a certain part of the brain. Despite the high prevalence of stroke, the currently used therapeutic interventions are limited. No therapies that aim to restore damaged neuronal tissue or to promote recovery are available nowadays. Transplantation of stem cell-derived cells has been investigated as a potential regenerative and protective treatment. Embryonic stem cell (ESC)-based cell therapy in rodent models of stroke has been shown to improve functional outcome. However, the clinical use of ESCs still raises ethical questions and implantation of ESC-derived cells requires continuous immunosuppression. The groundbreaking detection of induced pluripotent stem cells (iPSCs) has provided a most promising alternative. This mini-review summarizes current literature in which the potential use of iPSC-derived cells has been tested in rodent models of stroke. iPSC-based cell therapy has been demonstrated to improve motor function, decrease stroke volume, promote neurogenesis and angiogenesis and to exert immunomodulatory, anti-inflammatory effects in the brain of stroke-affected rodents.

New Insights from Rodent Models of Fatty Liver Disease

PubMed Central

2011-01-01

Abstract Rodent models of fatty liver disease are essential research tools that provide a window into disease pathogenesis and a testing ground for prevention and treatment. Models come in many varieties involving dietary and genetic manipulations, and sometimes both. High-energy diets that induce obesity do not uniformly cause fatty liver disease; this has prompted close scrutiny of specific macronutrients and nutrient combinations to determine which have the greatest potential for hepatotoxicity. At the same time, diets that do not cause obesity or the metabolic syndrome but do cause severe steatohepatitis have been exploited to study factors important to progressive liver injury, including cell death, oxidative stress, and immune activation. Rodents with a genetic predisposition to overeating offer yet another model in which to explore the evolution of fatty liver disease. In some animals that overeat, steatohepatitis can develop even without resorting to a high-energy diet. Importantly, these models and others have been used to document that aerobic exercise can prevent or reduce fatty liver disease. This review focuses primarily on lessons learned about steatohepatitis from manipulations of diet and eating behavior. Numerous additional insights about hepatic lipid metabolism, which have been gained from genetically engineered mice, are also mentioned. Antioxid. Redox Signal. 15, 535–550. PMID:21126212

OBscure but not OBsolete: Perturbations of the frontal cortex in common between rodent olfactory bulbectomy model and major depression.

PubMed

Rajkumar, Ramamoorthy; Dawe, Gavin S

2018-04-07

Olfactory bulbectomy (OBX) has been used as a model of depression over several decades. This model presupposes a mechanism that is still not proven in clinical depression. A wealth of clinical literature has focused on the derangements in frontal cortex (prefrontal, orbitofrontal and anterior cingulate cortices) associated with depression. In this comprehensive review, anatomical, electrophysiological and molecular sequelae of bulbectomy in the rodent frontal cortex are explored and compared with findings on brains of humans with major depression. Certain commonalities in neurobiological features of the perturbed frontal cortex in the bulbectomised rodent and the depressed human brain are evident. Also, meta-analysis reports on clinical studies on depressed patients provide prima facie evidence that perturbations in the frontal cortex are associated with major depression. Analysing the pattern of perturbations in the chemical neuroanatomy of the frontal cortex will contribute to understanding of the neurobiology of depression. Revisiting the OBX model of depression to examine these neurobiological changes in frontal cortex with contemporary imaging, proteomics, lipidomics, metabolomics and epigenomics technologies is proposed as an approach to enhance the translational value of this animal model to facilitate identification of targets and biomarkers for clinical depression. Copyright © 2018 Elsevier B.V. All rights reserved.

Preparation of Nonhuman Primate Eyes for Histological Evaluation After Retinal Gene Transfer.

PubMed

Bell, Peter; Yu, Hongwei; Kuntz, Leah; Ahonkhai, Omua; Tretiakova, Anna; Limberis, Maria P; Wilson, James M

2018-06-01

To evaluate gene therapy for retinal disorders, appropriate models of the human eye are needed. Nonhuman primate eyes offer significant advantages over rodent eyes. However, current preparation methods have limitations. Here, a protocol is described for histological processing of nonhuman primate eyes after gene transfer. The user dissects unfixed eyes, flattens the globe parts within filter paper, and performs formalin fixation and paraffin embedding. This method obviates the need for harsh fixatives, allowing subsequent immunostaining or in situ hybridization while preserving tissue integrity for histopathological evaluation. Moreover, the straight orientation of the retinal cell layers is ideal for image analysis.

A PK-PD Model of Ketamine-Induced High-Frequency Oscillations

PubMed Central

Flores, Francisco J.; Ching, ShiNung; Hartnack, Katharine; Fath, Amanda B.; Purdon, Patrick L.; Wilson, Matthew A.; Brown, Emery N.

2017-01-01

Objective Ketamine is a widely used drug with clinical and research applications, and also known to be used as a recreational drug. Ketamine produces conspicuous changes in the electrocorticographic (ECoG) signals observed both in humans and rodents. In rodents, the intracranial ECoG displays a High-Frequency Oscillation (HFO) which power is modulated non-linearly by ketamine dose. Despite the widespread use of ketamine there is no model description of the relationship between the pharmacokinetic-pharmacodynamics (PK-PD) of ketamine and the observed HFO power. Approach In the present study, we developed a PK-PD model based on estimated ketamine concentration, its known pharmacological actions, and observed ECoG effects. The main pharmacological action of ketamine is antagonism of the NMDA receptor (NMDAR), which in rodents is accompanied by a high-frequency oscillation (HFO) observed in the ECoG. At high doses, however, ketamine also acts at non-NMDAR sites, produces loss of consciousness, and the transient disappearance of the HFO. We propose a two-compartment PK model that represents the concentration of ketamine, and a PD model based in opposing effects of the NMDAR and non-NMDAR actions on the HFO power. Main results We recorded ECoG from the cortex of rats after two doses of ketamine, and extracted the HFO power from the ECoG spectrograms. We fit the PK-PD model to the time course of the HFO power, and showed that the model reproduces the dose-dependent profile of the HFO power. The model provides good fits even in the presence of high variability in HFO power across animals. As expected, the model does not provide good fits to the HFO power after dosing the pure NMDAR antagonist MK-801. Significance Our study provides a simple model to relate the observed electrophysiological effects of ketamine to its actions at the molecular level at different concentrations. This will improve the study of ketamine and rodent models of schizophrenia to better understand the wide and divergent range of effects that ketamine has. PMID:26268223

The Bile Acid Receptor GPBAR-1 (TGR5) Modulates Integrity of Intestinal Barrier and Immune Response to Experimental Colitis

PubMed Central

Cipriani, Sabrina; Mencarelli, Andrea; Chini, Maria Giovanna; Distrutti, Eleonora; Renga, Barbara; Bifulco, Giuseppe; Baldelli, Franco; Donini, Annibale; Fiorucci, Stefano

2011-01-01

Background GP-BAR1, a member G protein coupled receptor superfamily, is a cell surface bile acid-activated receptor highly expressed in the ileum and colon. In monocytes, ligation of GP-BAR1 by secondary bile acids results in a cAMP-dependent attenuation of cytokine generation. Aims To investigate the role GP-BAR1 in regulating intestinal homeostasis and inflammation-driven immune dysfunction in rodent models of colitis. Methods Colitis was induced in wild type and GP-BAR1−/− mice by DSS and TNBS administration. Potential GP-BAR1 agonists were identified by in silico screening and computational docking studies. Results GP-BAR1−/− mice develop an abnormal morphology of colonic mucous cells and an altered molecular architecture of epithelial tight junctions with increased expression and abnormal subcellular distribution of zonulin 1 resulting in increased intestinal permeability and susceptibility to develop severe colitis in response to DSS at early stage of life. By in silico screening and docking studies we identified ciprofloxacin as a GP-BAR1 ligand. In monocytes, ciprofloxacin increases cAMP concentrations and attenuates TNFα release induced by TLR4 ligation in a GP-BAR1 dependent manner. Treating mice rendered colitic by TNBS with ciprofloxacin and oleanolic acid, a well characterized GP-BAR1 ligand, abrogates signs and symptoms of colitis. Colonic expression of GP-BAR1 mRNA increases in rodent models of colitis and tissues from Crohn's disease patients. Flow cytometry analysis demonstrates that ≈90% of CD14+ cells isolated from the lamina propria of TNBS-treated mice stained positively for GP-BAR1. Conclusions GP-BAR1 regulates intestinal barrier structure. Its expression increases in rodent models of colitis and Crohn's disease. Ciprofloxacin is a GP-BAR1 ligand. PMID:22046243

Rodent Models of Experimental Endometriosis: Identifying Mechanisms of Disease and Therapeutic Targets

PubMed Central

Bruner-Tran, Kaylon L.; Mokshagundam, Shilpa; Herington, Jennifer L.; Ding, Tianbing; Osteen, Kevin G.

2018-01-01

Background: Although it has been more than a century since endometriosis was initially described in the literature, understanding the etiology and natural history of the disease has been challenging. However, the broad utility of murine and rat models of experimental endometriosis has enabled the elucidation of a number of potentially targetable processes which may otherwise promote this disease. Objective: To review a variety of studies utilizing rodent models of endometriosis to illustrate their utility in examining mechanisms associated with development and progression of this disease. Results: Use of rodent models of endometriosis has provided a much broader understanding of the risk factors for the initial development of endometriosis, the cellular pathology of the disease and the identification of potential therapeutic targets. Conclusion: Although there are limitations with any animal model, the variety of experimental endometriosis models that have been developed has enabled investigation into numerous aspects of this disease. Thanks to these models, our under-standing of the early processes of disease development, the role of steroid responsiveness, inflammatory processes and the peritoneal environment has been advanced. More recent models have begun to shed light on how epigenetic alterations con-tribute to the molecular basis of this disease as well as the multiple comorbidities which plague many patients. Continued de-velopments of animal models which aid in unraveling the mechanisms of endometriosis development provide the best oppor-tunity to identify therapeutic strategies to prevent or regress this enigmatic disease.

Multiple infections of rodents with zoonotic pathogens in Austria.

PubMed

Schmidt, Sabrina; Essbauer, Sandra S; Mayer-Scholl, Anne; Poppert, Sven; Schmidt-Chanasit, Jonas; Klempa, Boris; Henning, Klaus; Schares, Gereon; Groschup, Martin H; Spitzenberger, Friederike; Richter, Dania; Heckel, Gerald; Ulrich, Rainer G

2014-07-01

Rodents are important reservoirs for a large number of zoonotic pathogens. We examined the occurrence of 11 viral, bacterial, and parasitic agents in rodent populations in Austria, including three different hantaviruses, lymphocytic choriomeningitis virus, orthopox virus, Leptospira spp., Borrelia spp., Rickettsia spp., Bartonella spp., Coxiella burnetii, and Toxoplasma gondii. In 2008, 110 rodents of four species (40 Clethrionomys glareolus, 29 Apodemus flavicollis, 26 Apodemus sylvaticus, and 15 Microtus arvalis) were trapped at two rural sites in Lower Austria. Chest cavity fluid and samples of lung, spleen, kidney, liver, brain, and ear pinna skin were collected. We screened selected tissue samples for hantaviruses, lymphocytic choriomeningitis virus, orthopox viruses, Leptospira, Borrelia, Rickettsia, Bartonella spp., C. burnetii, and T. gondii by RT-PCR/PCR and detected nucleic acids of Tula hantavirus, Leptospira spp., Borrelia afzelii, Rickettsia spp., and different Bartonella species. Serological investigations were performed for hantaviruses, lymphocytic choriomeningitis virus, orthopox viruses, and Rickettsia spp. Here, Dobrava-Belgrade hantavirus-, Tula hantavirus-, lymphocytic choriomeningitis virus-, orthopox virus-, and rickettsia-specific antibodies were demonstrated. Puumala hantavirus, C. burnetii, and T. gondii were neither detected by RT-PCR/PCR nor by serological methods. In addition, multiple infections with up to three pathogens were shown in nine animals of three rodent species from different trapping sites. In conclusion, these results show that rodents in Austria may host multiple zoonotic pathogens. Our observation raises important questions regarding the interactions of different pathogens in the host, the countermeasures of the host's immune system, the impact of the host-pathogen interaction on the fitness of the host, and the spread of infectious agents among wild rodents and from those to other animals or humans.

Multiple Infections of Rodents with Zoonotic Pathogens in Austria

PubMed Central

Schmidt, Sabrina; Essbauer, Sandra S.; Mayer-Scholl, Anne; Poppert, Sven; Schmidt-Chanasit, Jonas; Klempa, Boris; Henning, Klaus; Schares, Gereon; Groschup, Martin H.; Spitzenberger, Friederike; Richter, Dania; Heckel, Gerald

2014-01-01

Abstract Rodents are important reservoirs for a large number of zoonotic pathogens. We examined the occurrence of 11 viral, bacterial, and parasitic agents in rodent populations in Austria, including three different hantaviruses, lymphocytic choriomeningitis virus, orthopox virus, Leptospira spp., Borrelia spp., Rickettsia spp., Bartonella spp., Coxiella burnetii, and Toxoplasma gondii. In 2008, 110 rodents of four species (40 Clethrionomys glareolus, 29 Apodemus flavicollis, 26 Apodemus sylvaticus, and 15 Microtus arvalis) were trapped at two rural sites in Lower Austria. Chest cavity fluid and samples of lung, spleen, kidney, liver, brain, and ear pinna skin were collected. We screened selected tissue samples for hantaviruses, lymphocytic choriomeningitis virus, orthopox viruses, Leptospira, Borrelia, Rickettsia, Bartonella spp., C. burnetii, and T. gondii by RT-PCR/PCR and detected nucleic acids of Tula hantavirus, Leptospira spp., Borrelia afzelii, Rickettsia spp., and different Bartonella species. Serological investigations were performed for hantaviruses, lymphocytic choriomeningitis virus, orthopox viruses, and Rickettsia spp. Here, Dobrava-Belgrade hantavirus-, Tula hantavirus-, lymphocytic choriomeningitis virus-, orthopox virus-, and rickettsia-specific antibodies were demonstrated. Puumala hantavirus, C. burnetii, and T. gondii were neither detected by RT-PCR/PCR nor by serological methods. In addition, multiple infections with up to three pathogens were shown in nine animals of three rodent species from different trapping sites. In conclusion, these results show that rodents in Austria may host multiple zoonotic pathogens. Our observation raises important questions regarding the interactions of different pathogens in the host, the countermeasures of the host's immune system, the impact of the host–pathogen interaction on the fitness of the host, and the spread of infectious agents among wild rodents and from those to other animals or humans. PMID:24915446

Non-linear auto-regressive models for cross-frequency coupling in neural time series

PubMed Central

Tallot, Lucille; Grabot, Laetitia; Doyère, Valérie; Grenier, Yves; Gramfort, Alexandre

2017-01-01

We address the issue of reliably detecting and quantifying cross-frequency coupling (CFC) in neural time series. Based on non-linear auto-regressive models, the proposed method provides a generative and parametric model of the time-varying spectral content of the signals. As this method models the entire spectrum simultaneously, it avoids the pitfalls related to incorrect filtering or the use of the Hilbert transform on wide-band signals. As the model is probabilistic, it also provides a score of the model “goodness of fit” via the likelihood, enabling easy and legitimate model selection and parameter comparison; this data-driven feature is unique to our model-based approach. Using three datasets obtained with invasive neurophysiological recordings in humans and rodents, we demonstrate that these models are able to replicate previous results obtained with other metrics, but also reveal new insights such as the influence of the amplitude of the slow oscillation. Using simulations, we demonstrate that our parametric method can reveal neural couplings with shorter signals than non-parametric methods. We also show how the likelihood can be used to find optimal filtering parameters, suggesting new properties on the spectrum of the driving signal, but also to estimate the optimal delay between the coupled signals, enabling a directionality estimation in the coupling. PMID:29227989

Emergence of transformation-tolerant representations of visual objects in rat lateral extrastriate cortex

PubMed Central

Tafazoli, Sina; Safaai, Houman; De Franceschi, Gioia; Rosselli, Federica Bianca; Vanzella, Walter; Riggi, Margherita; Buffolo, Federica; Panzeri, Stefano; Zoccolan, Davide

2017-01-01

Rodents are emerging as increasingly popular models of visual functions. Yet, evidence that rodent visual cortex is capable of advanced visual processing, such as object recognition, is limited. Here we investigate how neurons located along the progression of extrastriate areas that, in the rat brain, run laterally to primary visual cortex, encode object information. We found a progressive functional specialization of neural responses along these areas, with: (1) a sharp reduction of the amount of low-level, energy-related visual information encoded by neuronal firing; and (2) a substantial increase in the ability of both single neurons and neuronal populations to support discrimination of visual objects under identity-preserving transformations (e.g., position and size changes). These findings strongly argue for the existence of a rat object-processing pathway, and point to the rodents as promising models to dissect the neuronal circuitry underlying transformation-tolerant recognition of visual objects. DOI: http://dx.doi.org/10.7554/eLife.22794.001 PMID:28395730

Potent and Selective Amidopyrazole Inhibitors of IRAK4 That Are Efficacious in a Rodent Model of Inflammation

DOE Office of Scientific and Technical Information (OSTI.GOV)

McElroy, William T.; Tan, Zheng; Ho, Ginny

IRAK4 is a critical upstream kinase in the IL-1R/TLR signaling pathway. Inhibition of IRAK4 is hypothesized to be beneficial in the treatment of autoimmune related disorders. A screening campaign identified a pyrazole class of IRAK4 inhibitors that were determined by X-ray crystallography to exhibit an unusual binding mode. SAR efforts focused on the identification of a potent and selective inhibitor with good aqueous solubility and rodent pharmacokinetics. Pyrazole C-3 piperidines were well tolerated, with N-sulfonyl analogues generally having good rodent oral exposure but poor solubility. N-Alkyl piperidines exhibited excellent solubility and reduced exposure. Pyrazoles possessing N-1 pyridine and fluorophenyl substituentsmore » were among the most active. Piperazine 32 was a potent enzyme inhibitor with good cellular activity. Compound 32 reduced the in vivo production of proinflammatory cytokines and was orally efficacious in a mouse antibody induced arthritis disease model of inflammation.« less

Arvicanthis ansorgei, a Novel Model for the Study of Sleep and Waking in Diurnal Rodents.

PubMed

Hubbard, Jeffrey; Ruppert, Elisabeth; Calvel, Laurent; Robin-Choteau, Ludivine; Gropp, Claire-Marie; Allemann, Caroline; Reibel, Sophie; Sage-Ciocca, Dominique; Bourgin, Patrice

2015-06-01

Sleep neurobiology studies use nocturnal species, mainly rats and mice. However, because their daily sleep/wake organization is inverted as compared to humans, a diurnal model for sleep studies is needed. To fill this gap, we phenotyped sleep and waking in Arvicanthis ansorgei, a diurnal rodent widely used for the study of circadian rhythms. Video-electroencephalogram (EEG), electromyogram (EMG), and electrooculogram (EOG) recordings. Rodent sleep laboratory. Fourteen male Arvicanthis ansorgei, aged 3 mo. 12 h light (L):12 h dark (D) baseline condition, 24-h constant darkness, 6-h sleep deprivation. Wake and rapid eye movement (REM) sleep showed similar electrophysiological characteristics as nocturnal rodents. On average, animals spent 12.9 h ± 0.4 awake per 24-h cycle, of which 6.88 h ± 0.3 was during the light period. NREM sleep accounted for 9.63 h ± 0.4, which of 5.13 h ± 0.2 during dark period, and REM sleep for 89.9 min ± 6.7, which of 52.8 min ± 4.4 during dark period. The time-course of sleep and waking across the 12 h light:12 h dark was overall inverted to that observed in rats or mice, though with larger amounts of crepuscular activity at light and dark transitions. A dominant crepuscular regulation of sleep and waking persisted under constant darkness, showing the lack of a strong circadian drive in the absence of clock reinforcement by external cues, such as a running wheel. Conservation of the homeostatic regulation was confirmed with the observation of higher delta power following sustained waking periods and a 6-h sleep deprivation, with subsequent decrease during recovery sleep. Arvicanthis ansorgei is a valid diurnal rodent model for studying the regulatory mechanisms of sleep and so represents a valuable tool for further understanding the nocturnality/diurnality switch. © 2015 Associated Professional Sleep Societies, LLC.

Increased visceral tissue perfusion with heated, humidified carbon dioxide insufflation during open abdominal surgery in a rodent model.

PubMed

Robson, Jonathan P; Kokhanenko, Pavlo; Marshall, Jean K; Phillips, Anthony R; van der Linden, Jan

2018-01-01

Tissue perfusion during surgery is important in reducing surgical site infections and promoting healing. This study aimed to determine if insufflation of the open abdomen with heated, humidified (HH) carbon dioxide (CO2) increased visceral tissue perfusion and core body temperature during open abdominal surgery in a rodent model. Using two different rodent models of open abdominal surgery, visceral perfusion and core temperature were measured. Visceral perfusion was investigated using a repeated measures crossover experiment with rodents receiving the same sequence of two alternating treatments: exposure to ambient air (no insufflation) and insufflation with HH CO2. Core body temperature was measured using an independent experimental design with three treatment groups: ambient air, HH CO2 and cold, dry (CD) CO2. Visceral perfusion was measured by laser speckle contrast analysis (LASCA) and core body temperature was measured with a rectal thermometer. Insufflation with HH CO2 into a rodent open abdominal cavity significantly increased visceral tissue perfusion (2.4 perfusion units (PU)/min (95% CI 1.23-3.58); p<0.0001) compared with ambient air, which significantly reduced visceral blood flow (-5.20 PU/min (95% CI -6.83- -3.58); p<0.0001). Insufflation of HH CO2 into the open abdominal cavity significantly increased core body temperature (+1.15 ± 0.14°C) compared with open cavities exposed to ambient air (-0.65 ± 0.52°C; p = 0.037), or cavities insufflated with CD CO2 (-0.73 ± 0.33°C; p = 0.006). Abdominal visceral temperatures also increased with HH CO2 insufflation compared with ambient air or CD CO2, as shown by infrared thermography. This study reports for the first time the use of LASCA to measure visceral perfusion in open abdominal surgery and shows that insufflation of open abdominal cavities with HH CO2 significantly increases visceral tissue perfusion and core body temperature.

How many food additives are rodent carcinogens?

PubMed

Johnson, F M

2002-01-01

One generally assumes that chemical agents added to foods are reasonably free of risks to human health, and practically everyone consumes some additives in his or her food daily throughout life. In the United States, the 1958 Food Additives Amendment to the Federal Food, Drug and Cosmetic Act of 1938 requires food manufacturers to demonstrate the safety of food additives to the Food and Drug Administration (FDA). The Amendment contains a provision that prohibits approval of an additive if it is found to cause cancer in humans or animals. In the present study, data from the National Toxicology Program rodent bioassay (NTPRB) were used to identify a sample of approximately 50 rodent-tested additives and other chemicals added to food that had been evaluated independently of the FDA/food industry. Surprisingly, the sample shows more than 40% of these food chemicals to be carcinogenic in one or more rodent groups. If this percentage is extrapolated to all substances added to food in the United States, it would imply that more than 1000 of such substances are potential rodent carcinogens. The NTP and FDA test guidelines use similar, though not necessarily identical, rodent test procedures, including near lifetime exposures to the maximum tolerated dose. The FDA specifies that test chemicals should be administered by the oral route. However, the oral route includes three methods of delivering chemicals, that is, mixed in the food or water or delivered by stomach tube (gavage). The NTP data show only 1 of 18 food chemicals mixed in the food are rodent carcinogens, but 16 of 23 gavage-administered food chemicals are carcinogenic to rodents. The distribution suggests that among orally delivered chemicals, those administered in the feed will more likely prove to be noncarcinogens than chemicals given by gavage. The rodent data also reveal that effects may vary according to dose and genotype, as well as by route of administration, to further complicate extrapolation to humans. Human experience with known carcinogens such as tobacco, asbestos, and benzidine convinces us that environmental carcinogens constitute a real threat to human health, although predicting human carcinogens from rodent tests involves a number of uncertainties. These uncertainties do not mean that we should simply ignore the presence of carcinogens. Rather, in the interests of public safety, a serious effort should be made to resolve the questions surrounding the presence of chemicals identified as rodent carcinogens in our food. Environ. Mol. Mutagen. 39:69-80, 2002 Published 2002 Wiley-Liss, Inc.

Using animal models to evaluate the functional consequences of anesthesia during early neurodevelopment.

PubMed

Maloney, Susan E; Creeley, Catherine E; Hartman, Richard E; Yuede, Carla M; Zorumski, Charles F; Jevtovic-Todorovic, Vesna; Dikranian, Krikor; Noguchi, Kevin K; Farber, Nuri B; Wozniak, David F

2018-03-14

Fifteen years ago Olney and colleagues began using animal models to evaluate the effects of anesthetic and sedative agents (ASAs) on neurodevelopment. The results from ongoing studies indicate that, under certain conditions, exposure to these drugs during development induces an acute elevated apoptotic neurodegenerative response in the brain and long-term functional impairments. These animal models have played a significant role in bringing attention to the possible adverse effects of exposing the developing brain to ASAs when few concerns had been raised previously in the medical community. The apoptotic degenerative response resulting from neonatal exposure to ASAs has been replicated in many studies in both rodents and non-human primates, suggesting that a similar effect may occur in humans. In both rodents and non-human primates, significantly increased levels of apoptotic degeneration are often associated with functional impairments later in life. However, behavioral deficits following developmental ASA exposure have not been consistently reported even when significantly elevated levels of apoptotic degeneration have been documented in animal models. In the present work, we review this literature and propose a rodent model for assessing potential functional deficits following neonatal ASA exposure with special reference to experimental design and procedural issues. Our intent is to improve test sensitivity and replicability for detecting subtle behavioral effects, and thus enhance the translational significance of ASA models. Copyright © 2018 Elsevier Inc. All rights reserved.

Assessing the Diversity of Rodent-Borne Viruses: Exploring of High-Throughput Sequencing and Classical Amplification/Sequencing Approaches.

PubMed

Drewes, Stephan; Straková, Petra; Drexler, Jan F; Jacob, Jens; Ulrich, Rainer G

2017-01-01

Rodents are distributed throughout the world and interact with humans in many ways. They provide vital ecosystem services, some species are useful models in biomedical research and some are held as pet animals. However, many rodent species can have adverse effects such as damage to crops and stored produce, and they are of health concern because of the transmission of pathogens to humans and livestock. The first rodent viruses were discovered by isolation approaches and resulted in break-through knowledge in immunology, molecular and cell biology, and cancer research. In addition to rodent-specific viruses, rodent-borne viruses are causing a large number of zoonotic diseases. Most prominent examples are reemerging outbreaks of human hemorrhagic fever disease cases caused by arena- and hantaviruses. In addition, rodents are reservoirs for vector-borne pathogens, such as tick-borne encephalitis virus and Borrelia spp., and may carry human pathogenic agents, but likely are not involved in their transmission to human. In our days, next-generation sequencing or high-throughput sequencing (HTS) is revolutionizing the speed of the discovery of novel viruses, but other molecular approaches, such as generic RT-PCR/PCR and rolling circle amplification techniques, contribute significantly to the rapidly ongoing process. However, the current knowledge still represents only the tip of the iceberg, when comparing the known human viruses to those known for rodents, the mammalian taxon with the largest species number. The diagnostic potential of HTS-based metagenomic approaches is illustrated by their use in the discovery and complete genome determination of novel borna- and adenoviruses as causative disease agents in squirrels. In conclusion, HTS, in combination with conventional RT-PCR/PCR-based approaches, resulted in a drastically increased knowledge of the diversity of rodent viruses. Future improvements of the used workflows, including bioinformatics analysis, will further enhance our knowledge and preparedness in case of the emergence of novel viruses. Classical virological and additional molecular approaches are needed for genome annotation and functional characterization of novel viruses, discovered by these technologies, and evaluation of their zoonotic potential. © 2017 Elsevier Inc. All rights reserved.

Cryptic herbivores mediate the strength and form of ungulate impacts on a long-lived savanna tree.

PubMed

Maclean, Janet E; Goheen, Jacob R; Doak, Daniel F; Palmer, Todd M; Young, Truman P

2011-08-01

Plant populations are regulated by a diverse array of herbivores that impose demographic filters throughout their life cycle. Few studies, however, simultaneously quantify the impacts of multiple herbivore guilds on the lifetime performance or population growth rate of plants. In African savannas, large ungulates (such as elephants) are widely regarded as important drivers of woody plant population dynamics, while the potential impacts of smaller, more cryptic herbivores (such as rodents) have largely been ignored. We combined a large-scale ungulate exclusion experiment with a five-year manipulation of rodent densities to quantify the impacts of three herbivore guilds (wild ungulates, domestic cattle, and rodents) on all life stages of a widespread savanna tree. We utilized demographic modeling to reveal the overall role of each guild in regulating tree population dynamics, and to elucidate the importance of different demographic hurdles in driving population growth under contrasting consumer communities. We found that wild ungulates dramatically reduced population growth, shifting the population trajectory from increase to decline, but that the mechanisms driving these effects were strongly mediated by rodents. The impact of wild ungulates on population growth was predominantly driven by their negative effect on tree reproduction when rodents were excluded, and on adult tree survival when rodents were present. By limiting seedling survival, rodents also reduced population growth; however, this effect was strongly dampened where wild ungulates were present. We suggest that these complex interactions between disparate consumer guilds can have important consequences for the population demography of long-lived species, and that the effects of a single consumer group are often likely to vary dramatically depending on the larger community in which interactions are embedded.

Convection-enhanced delivery of SN-38-loaded polymeric micelles (NK012) enables consistent distribution of SN-38 and is effective against rodent intracranial brain tumor models.

PubMed

Zhang, Rong; Saito, Ryuta; Mano, Yui; Sumiyoshi, Akira; Kanamori, Masayuki; Sonoda, Yukihiko; Kawashima, Ryuta; Tominaga, Teiji

2016-10-01

Convection-enhanced delivery (CED) of therapeutic agents is a promising local delivery technique that has been extensively studied as a treatment for CNS diseases over the last two decades. One continuing challenge of CED is accurate and consistent delivery of the agents to the target. The present study focused on a new type of therapeutic agent, NK012, a novel SN-38-loaded polymeric micelle. Local delivery profiles of NK012 and SN-38 were studied using rodent brain and intracranial rodent brain tumor models. First, the cytotoxicity of NK012 against glioma cell lines was determined in vitro. Proliferations of glioma cells were significantly reduced after exposure to NK012. Then, the distribution and local toxicity after CED delivery of NK012 and SN-38 were evaluated in vivo. Volume of distribution of NK012 after CED was much larger than that of SN-38. Histological examination revealed minimum brain tissue damage in rat brains after delivery of 40 µg NK012 but severe damage with SN-38 at the same dose. Subsequently, the efficacy of NK012 delivered via CED was tested in 9L and U87MG rodent orthotopic brain tumor models. CED of NK012 displayed excellent efficacy in the 9L and U87MG orthotopic brain tumor models. Furthermore, NK012 and gadolinium diamide were co-delivered via CED to monitor the NK012 distribution using MRI. Volume of NK012 distribution evaluated by histology and MRI showed excellent agreement. CED of NK012 represents an effective treatment option for malignant gliomas. MRI-guided CED of NK012 has potential for clinical application.

Diet before and during Pregnancy and Offspring Health: The Importance of Animal Models and What Can Be Learned from Them.

PubMed

Chavatte-Palmer, Pascale; Tarrade, Anne; Rousseau-Ralliard, Delphine

2016-06-14

This review article outlines epidemiologic studies that support the hypothesis that maternal environment (including early nutrition) plays a seminal role in determining the offspring's long-term health and metabolism, known as the concept of Developmental Origins of Health and Diseases (DOHaD). In this context, current concerns are particularly focused on the increased incidence of obesity and diabetes, particularly in youth and women of child-bearing age. We summarize key similarities, differences and limitations of various animal models used to study fetal programming, with a particular focus on placentation, which is critical for translating animal findings to humans. This review will assist researchers and their scientific audience in recognizing the pros and cons of various rodent and non-rodent animal models used to understand mechanisms involved in fetal programming. Knowledge gained will lead to improved translation of proposed interventional therapies before they can be implemented in humans. Although rodents are essential for fundamental exploration of biological processes, other species such as rabbits and other domestic animals offer more tissue-specific physiological (rabbit placenta) or physical (ovine maternal and lamb birth weight) resemblances to humans. We highlight the important maternal, placental, and fetal/neonatal characteristics that contribute to developmentally programmed diseases, specifically in offspring that were affected in utero by undernutrition, overnutrition or maternal diabetes. Selected interventions aimed at prevention are summarized with a specific focus on the 1000 days initiative in humans, and maternal exercise or modification of the n-3/n-6 polyunsaturated fatty acid (PUFA) balance in the diet, which are currently being successfully tested in animal models to correct or reduce adverse prenatal programming. Animal models are essential to understand mechanisms involved in fetal programming and in order to propose interventional therapies before they can be implemented in humans. Non-rodent animals are particularly important and should not be neglected, as they are often more physiologically-appropriate models to mimic the human situation.

Diet before and during Pregnancy and Offspring Health: The Importance of Animal Models and What Can Be Learned from Them

PubMed Central

Chavatte-Palmer, Pascale; Tarrade, Anne; Rousseau-Ralliard, Delphine

2016-01-01

This review article outlines epidemiologic studies that support the hypothesis that maternal environment (including early nutrition) plays a seminal role in determining the offspring’s long-term health and metabolism, known as the concept of Developmental Origins of Health and Diseases (DOHaD). In this context, current concerns are particularly focused on the increased incidence of obesity and diabetes, particularly in youth and women of child-bearing age. We summarize key similarities, differences and limitations of various animal models used to study fetal programming, with a particular focus on placentation, which is critical for translating animal findings to humans. This review will assist researchers and their scientific audience in recognizing the pros and cons of various rodent and non-rodent animal models used to understand mechanisms involved in fetal programming. Knowledge gained will lead to improved translation of proposed interventional therapies before they can be implemented in humans. Although rodents are essential for fundamental exploration of biological processes, other species such as rabbits and other domestic animals offer more tissue-specific physiological (rabbit placenta) or physical (ovine maternal and lamb birth weight) resemblances to humans. We highlight the important maternal, placental, and fetal/neonatal characteristics that contribute to developmentally programmed diseases, specifically in offspring that were affected in utero by undernutrition, overnutrition or maternal diabetes. Selected interventions aimed at prevention are summarized with a specific focus on the 1000 days initiative in humans, and maternal exercise or modification of the n-3/n-6 polyunsaturated fatty acid (PUFA) balance in the diet, which are currently being successfully tested in animal models to correct or reduce adverse prenatal programming. Animal models are essential to understand mechanisms involved in fetal programming and in order to propose interventional therapies before they can be implemented in humans. Non-rodent animals are particularly important and should not be neglected, as they are often more physiologically-appropriate models to mimic the human situation. PMID:27314367

Effects of space flight conditions on the function of the immune system and catecholamine production simulated in a rodent model of hindlimb unloading

NASA Technical Reports Server (NTRS)

Aviles, Hernan; Belay, Tesfaye; Vance, Monique; Sonnenfeld, Gerald

2005-01-01

The rodent model of hindlimb unloading has been successfully used to simulate some of the effects of space flight conditions. Previous studies have indicated that mice exposed to hindlimb-unloading conditions have decreased resistance to infections compared to restrained and normally housed control mice. OBJECTIVE: The purpose of this study was to clarify the mechanisms involved in resistance to infection in this model by examining the effects of hindlimb unloading on the function of the immune system and its impact on the production of catecholamines. METHODS: Female Swiss Webster mice were hindlimb-unloaded during 48 h and the function of the immune system was assessed in spleen and peritoneal cells immediately after this period. In addition, the kinetics of catecholamine production was measured throughout the hindlimb-unloading period. RESULTS: The function of the immune system was significantly suppressed in the hindlimb-unloaded group compared to restrained and normally housed control mice. Levels of catecholamines were increased in the hindlimb-unloaded group and peaked at 12 h following the commencement of unloading. CONCLUSION: These results suggest that physiological responses of mice are altered early after hindlimb unloading and that catecholamines may play a critical role in the modulation of the immune system. These changes may affect the ability of mice to resist infections. Copyright (c) 2005 S. Karger AG, Basel.

Preclinical Magnetic Resonance Fingerprinting (MRF) at 7 T: Effective Quantitative Imaging for Rodent Disease Models

PubMed Central

Gao, Ying; Chen, Yong; Ma, Dan; Jiang, Yun; Herrmann, Kelsey A.; Vincent, Jason A.; Dell, Katherine M.; Drumm, Mitchell L.; Brady-Kalnay, Susann M.; Griswold, Mark A.; Flask, Chris A.; Lu, Lan

2015-01-01

High field, preclinical magnetic resonance imaging (MRI) scanners are now commonly used to quantitatively assess disease status and efficacy of novel therapies in a wide variety of rodent models. Unfortunately, conventional MRI methods are highly susceptible to respiratory and cardiac motion artifacts resulting in potentially inaccurate and misleading data. We have developed an initial preclinical, 7.0 T MRI implementation of the highly novel Magnetic Resonance Fingerprinting (MRF) methodology that has been previously described for clinical imaging applications. The MRF technology combines a priori variation in the MRI acquisition parameters with dictionary-based matching of acquired signal evolution profiles to simultaneously generate quantitative maps of T1 and T2 relaxation times and proton density. This preclinical MRF acquisition was constructed from a Fast Imaging with Steady-state Free Precession (FISP) MRI pulse sequence to acquire 600 MRF images with both evolving T1 and T2 weighting in approximately 30 minutes. This initial high field preclinical MRF investigation demonstrated reproducible and differentiated estimates of in vitro phantoms with different relaxation times. In vivo preclinical MRF results in mouse kidneys and brain tumor models demonstrated an inherent resistance to respiratory motion artifacts as well as sensitivity to known pathology. These results suggest that MRF methodology may offer the opportunity for quantification of numerous MRI parameters for a wide variety of preclinical imaging applications. PMID:25639694

Preclinical MR fingerprinting (MRF) at 7 T: effective quantitative imaging for rodent disease models.

PubMed

Gao, Ying; Chen, Yong; Ma, Dan; Jiang, Yun; Herrmann, Kelsey A; Vincent, Jason A; Dell, Katherine M; Drumm, Mitchell L; Brady-Kalnay, Susann M; Griswold, Mark A; Flask, Chris A; Lu, Lan

2015-03-01

High-field preclinical MRI scanners are now commonly used to quantitatively assess disease status and the efficacy of novel therapies in a wide variety of rodent models. Unfortunately, conventional MRI methods are highly susceptible to respiratory and cardiac motion artifacts resulting in potentially inaccurate and misleading data. We have developed an initial preclinical 7.0-T MRI implementation of the highly novel MR fingerprinting (MRF) methodology which has been described previously for clinical imaging applications. The MRF technology combines a priori variation in the MRI acquisition parameters with dictionary-based matching of acquired signal evolution profiles to simultaneously generate quantitative maps of T1 and T2 relaxation times and proton density. This preclinical MRF acquisition was constructed from a fast imaging with steady-state free precession (FISP) MRI pulse sequence to acquire 600 MRF images with both evolving T1 and T2 weighting in approximately 30 min. This initial high-field preclinical MRF investigation demonstrated reproducible and differentiated estimates of in vitro phantoms with different relaxation times. In vivo preclinical MRF results in mouse kidneys and brain tumor models demonstrated an inherent resistance to respiratory motion artifacts as well as sensitivity to known pathology. These results suggest that MRF methodology may offer the opportunity for the quantification of numerous MRI parameters for a wide variety of preclinical imaging applications. Copyright © 2015 John Wiley & Sons, Ltd.

Evidence for Personal Protective Measures to Reduce Human Contact With Blacklegged Ticks and for Environmentally Based Control Methods to Suppress Host-Seeking Blacklegged Ticks and Reduce Infection with Lyme Disease Spirochetes in Tick Vectors and Rodent Reservoirs.

PubMed

Eisen, Lars; Dolan, Marc C

2016-07-20

In the 1980s, the blacklegged tick, Ixodes scapularis Say, and rodents were recognized as the principal vector and reservoir hosts of the Lyme disease spirochete Borrelia burgdorferi in the eastern United States, and deer were incriminated as principal hosts for I. scapularis adults. These realizations led to pioneering studies aiming to reduce the risk for transmission of B. burgdorferi to humans by attacking host-seeking ticks with acaricides, interrupting the enzootic transmission cycle by killing immatures infesting rodent reservoirs by means of acaricide-treated nesting material, or reducing deer abundance to suppress tick numbers. We review the progress over the past three decades in the fields of: 1) prevention of human-tick contact with repellents and permethrin-treated clothing, and 2) suppression of I. scapularis and disruption of enzootic B. burgdorferi transmission with environmentally based control methods. Personal protective measures include synthetic and natural product-based repellents that can be applied to skin and clothing, permethrin sprays for clothing and gear, and permethrin-treated clothing. A wide variety of approaches and products to suppress I. scapularis or disrupt enzootic B. burgdorferi transmission have emerged and been evaluated in field trials. Application of synthetic chemical acaricides is a robust method to suppress host-seeking I. scapularis ticks within a treated area for at least 6-8 wk. Natural product-based acaricides or entomopathogenic fungi have emerged as alternatives to kill host-seeking ticks for homeowners who are unwilling to use synthetic chemical acaricides. However, as compared with synthetic chemical acaricides, these approaches appear less robust in terms of both their killing efficacy and persistence. Use of rodent-targeted topical acaricides represents an alternative for homeowners opposed to open distribution of acaricides to the ground and vegetation on their properties. This host-targeted approach also provides the benefit of the intervention impacting the entire rodent home range. Rodent-targeted oral vaccines against B. burgdorferi and a rodent-targeted antibiotic bait have been evaluated in laboratory and field trials but are not yet commercially available. Targeting of deer-via deer reduction or treatment of deer with topical acaricides-can provide area-wide suppression of host-seeking I. scapularis These two deer-targeted approaches combine great potential for protection that impacts the entire landscape with severe problems relating to public acceptance or implementation logistics. Integrated use of two or more methods has unfortunately been evaluated in very few published studies, but additional field evaluations of integrated tick and pathogen strategies are underway. Published by Oxford University Press on behalf of Journal of Medical Entomology 2016. This work is written by US Government employees and is in the public domain in the US.

Variance of molecular datings, evolution of rodents and the phylogenetic affinities between Ctenodactylidae and Hystricognathi.

PubMed Central

Huchon, D; Catzeflis, F M; Douzery, E J

2000-01-01

The von Willebrand factor (vWF) gene has been used to understand the origin and timing of Rodentia evolution in the context of placental phylogeny vWF exon 28 sequences of 15 rodent families and eight non-rodent eutherian clades are analysed with two different molecular dating methods (uniform clock on a linearized tree; quartet dating). Three main conclusions are drawn from the study of this nuclear exon. First, Ctenodactylidae (gundis) and Hystricognathi (e.g. porcupines, guinea-pigs, chinchillas) robustly cluster together in a newly recognized clade, named 'Ctenohystrica'. The Sciurognathi monophyly is subsequently rejected. Pedetidae (springhares) is an independent and early diverging rodent lineage, suggesting a convergent evolution of the multiserial enamel of rodent incisors. Second, molecular date estimates are here more influenced by accuracy and choice of the palaeontological temporal references used to calibrate the molecular clock than by either characters analysed (nucleotides versus amino acids) or species sampling. The caviomorph radiation at 31 million years (Myr) and the pig porpoise split at 63 Myr appear to be reciprocally compatible dates. Third, during the radiation of Rodentia, at least three lineages (Gliridae, Sciuroidea and Ctenohystrica) emerged close to the Cretaceous-Tertiary boundary, and their common ancestor separated from other placental orders in the Late Cretaceous. PMID:10722222

High Drinking in the Dark Mice: A genetic model of drinking to intoxication

PubMed Central

Barkley-Levenson, Amanda M.; Crabbe, John C.

2014-01-01

Drinking to intoxication is a critical component of risky drinking behaviors in humans, such as binge drinking. Previous rodent models of alcohol consumption largely failed to demonstrate that animals were patterning drinking in such a way as to experience intoxication. Therefore, few rodent models of binge-like drinking and no specifically genetic models were available to study possible predisposing genes. The High Drinking in the Dark (HDID) selective breeding project was started to help fill this void, with HDID mice selected for reaching high blood alcohol levels in a limited access procedure. HDID mice now represent a genetic model of drinking to intoxication and can be used to help answer questions regarding predisposition toward this trait as well as potential correlated responses. They should also prove useful for the eventual development of better therapeutic strategies. PMID:24360287

Experimental Models of Vaginal Candidiasis and Their Relevance to Human Candidiasis

PubMed Central

Sobel, Jack D.

2016-01-01

Vulvovaginal candidiasis (VVC) is a high-incidence disease seriously affecting the quality of life of women worldwide, particularly in its chronic, recurrent forms (RVVC), and with no definitive cure or preventive measure. Experimental studies in currently used rat and mouse models of vaginal candidiasis have generated a large mass of data on pathogenicity determinants and inflammation and immune responses of potential importance for the control of human pathology. However, reflection is necessary about the relevance of these rodent models to RVVC. Here we examine the chemical, biochemical, and biological factors that determine or contrast the forms of the disease in rodent models and in women and highlight the differences between them. We also appeal for approaches to improve or replace the current models in order to enhance their relevance to human infection. PMID:26883592

HORSE SPECIES SYMPOSIUM: Use of mesenchymal stem cells in fracture repair in horses.

PubMed

Govoni, K E

2015-03-01

Equine bone fractures are often catastrophic, potentially fatal, and costly to repair. Traditional methods of healing fractures have limited success, long recovery periods, and a high rate of reinjury. Current research in the equine industry has demonstrated that stem cell therapy is a promising novel therapy to improve fracture healing and reduce the incidence of reinjury; however, reports of success in horses have been variable and limited. Stem cells can be derived from embryonic, fetal, and adult tissue. Based on the ease of collection, opportunity for autologous cells, and proven success in other models, adipose- or bone marrow-derived mesenchymal stem cells (MSC) are often used in equine therapies. Methods for isolation, proliferation, and differentiation of MSC are well established in rodent and human models but are not well characterized in horses. There is recent evidence that equine bone marrow MSC are able to proliferate in culture for several passages in the presence of autologous and fetal bovine serum, which is important for expansion of cells. Mesenchymal stem cells have the capacity to differentiate into osteoblasts, the bone forming cells, and this complex process is regulated by a number of transcription factors including runt-related transcription factor 2 (Runx2) and osterix (Osx). However, it has not been well established if equine MSC are regulated in a similar manner. The data presented in this review support the view that equine bone marrow MSC are regulated by the same transcription factors that control the differentiation of rodent and human MSC into osteoblasts. Although stem cell therapy is promising in equine bone repair, additional research is needed to identify optimal methods for reintroduction and potential manipulations to improve their ability to form new bone.

Three-dimensional quantification of orthodontic root resorption with time-lapsed imaging of micro-computed tomography in a rodent model.

PubMed

Yang, Chongshi; Zhang, Yuanyuan; Zhang, Yan; Fan, Yubo; Deng, Feng

2015-01-01

Despite various X-ray approaches have been widely used to monitor root resorption after orthodontic treatment, a non-invasive and accurate method is highly desirable for long-term follow up. The aim of this study was to build a non-invasive method to quantify longitudinal orthodontic root resorption with time-lapsed images of micro-computed tomography (micro-CT) in a rodent model. Twenty male Sprague Dawley (SD) rats (aged 6-8 weeks, weighing 180-220 g) were used in this study. A 25 g orthodontic force generated by nickel-titanium coil spring was applied to the right maxillary first molar for each rat, while contralateral first molar was severed as a control. Micro-CT scan was performed at day 0 (before orthodontic load) and days 3, 7, 14, and 28 after orthodontic load. Resorption of mesial root of maxillary first molars at bilateral sides was calculated from micro-CT images with registration algorithm via reconstruction, superimposition and partition operations. Obvious resorption of mesial root of maxillary first molar can be detected at day 14 and day 28 at orthodontic side. Most of the resorption occurred in the apical region at distal side and cervical region at mesiolingual side. Desirable development of molar root of rats was identified from day 0 to day 28 at control side. The development of root concentrated on apical region. This non-invasive 3D quantification method with registration algorithm can be used in longitudinal study of root resorption. Obvious root resorption in rat molar can be observed three-dimensionally at day 14 and day 28 after orthodontic load. This indicates that registration algorithm combined with time-lapsed images provides clinic potential application in detection and quantification of root contour.

Postdispersal seed predation limits the abundance of a long-lived perennial forb (Lithospermum ruderale).

PubMed

Bricker, Mary; Maron, John

2012-03-01

Loss of seeds to consumers is common in plant communities, but the degree to which these losses influence plant abundance or population growth is often unclear. This is particularly the case for postdispersal seed predation by rodents, as most studies of rodent seed predation have focused on the sources of spatiotemporal variation in seed loss but not quantified the population consequences of this loss. In previous work we showed that seed predation by deer mice (Peromyscus maniculatus) substantially reduced seedling recruitment and establishment of Lithospermum ruderale (Boraginaceae), a long-lived perennial forb. To shed light on how rodent seed predation and the near-term effects on plant recruitment might influence longer-term patterns of L. ruderale population growth, we combined experimental results with demographic data in stage-based population models. Model outputs revealed that rodent seed predation had a significant impact on L. ruderale population growth rate (lambda). With the removal of postdispersal seed predation, the projected population growth rates increased between 0.06 and 0.12, depending on site (mean deltalambda across sites = 0.08). Seed predation shifted the projected stable stage distribution of populations from one with a high proportion of young plants to one in which larger adult size classes dominate. Elasticities of vital rates also changed, with germination and growth of seedlings and young plants becoming more important with the removal of seed predation. Simulations varying the magnitude of seed predation pressure while holding other vital rates constant showed that seed predation could lower lambda even if only 40% of available seeds were consumed. These results demonstrate that rodent granivory can be a potent force limiting the abundance of a long-lived perennial forb.

Rat-bites of an epidemic proportion in Peshawar vale; a GIS based approach in risk assessment.

PubMed

Fatima, Syeda Hira; Zaidi, Farrah; Adnan, Muhammad; Ali, Asad; Jamal, Qaiser; Khisroon, Muhammad

2018-03-19

Contemporary studies demonstrate that rodent bites do not occur frequently. However, a huge number of cases were reported from Peshawar vale, Pakistan during 2016. Two species, the local black rat Rattus rattus (Linnaeus, 1758) and the invasive brown rat Rattus norvegicus (Berkenhout, 1769) might be the suspected cause. Several studies indicated the invasion of brown rats into Pakistan presumably via port city of Karachi. In this study, we modeled geospatial distribution of rodent bites for risk assessment in the region. Bite cases reported to tertiary care lady reading hospital were monitored from January 1 to August 31, 2016. Among 1747 cases, statistically informative data (n = 1295) was used for analyses. MaxEnt algorithm was employed for geospatial modeling, taking into account various environmental variables (temperature, precipitation, humidity, and elevation) and anthropogenic factors (human population density, distance from roads, distance from water channels, and land use/land cover). MaxEnt results revealed that urban slums (84.5%) are at highest risk followed by croplands (10.9%) and shrublands (2.7%). Anthropogenic factors affecting incidence of rodent bites included host density (contribution: 34.7), distance from water channels (3.2), land use/land cover (2.8), and distance from roads (2). Most of the cases occurred within a radius of 0.3 km from roads and 5 km from water channels. Rodent bite incidence is currently at its peak in Peshawar vale. Factors significantly affecting rodents' bite activity and their distribution and dispersal include urbanization, distance from roads, and water channels. Further studies are needed to determine the impact of invasion by brown rat on bite incidence.

Lessons From the First Comprehensive Molecular Characterization of Cell Cycle Control in Rodent Insulinoma Cell Lines

PubMed Central

Cozar-Castellano, Irene; Harb, George; Selk, Karen; Takane, Karen; Vasavada, Rupangi; Sicari, Brian; Law, Brian; Zhang, Pili; Scott, Donald K.; Fiaschi-Taesch, Nathalie; Stewart, Andrew F.

2008-01-01

OBJECTIVE—Rodent insulinoma cell lines may serve as a model for designing continuously replicating human β-cell lines and provide clues as to the central cell cycle regulatory molecules in the β-cell. RESEARCH DESIGN AND METHODS—We performed a comprehensive G1/S proteome analysis on the four most widely studied rodent insulinoma cell lines and defined their flow cytometric profiles and growth characteristics. RESULTS—1) Despite their common T-antigen–derived origins, MIN6 and BTC3 cells display markedly different G1/S expression profiles; 2) despite their common radiation origins, RINm5F and INS1 cells display striking differences in cell cycle protein profiles; 3) phosphorylation of pRb is absent in INS1 and RINm5F cells; 4) cyclin D2 is absent in RINm5F and BTC3 cells and therefore apparently dispensable for their proliferation; 5) every cell cycle inhibitor is upregulated, presumably in a futile attempt to halt proliferation; 6) among the G1/S proteome members, seven are pro-proliferation molecules: cyclin-dependent kinase-1, -2, -4, and -6 and cyclins A, E, and D3; and 7) overexpression of the combination of these seven converts arrested proliferation rates in primary rat β-cells to those in insulinoma cells. Unfortunately, this therapeutic overexpression appears to mildly attenuate β-cell differentiation and function. CONCLUSIONS—These studies underscore the importance of characterizing the cell cycle at the protein level in rodent insulinoma cell lines. They also emphasize the hazards of interpreting data from rodent insulinoma cell lines as modeling normal cell cycle progression. Most importantly, they provide seven candidate targets for inducing proliferation in human β-cells. PMID:18650366

A review of the proposed role of neutrophils in rodent amebic liver abscess models

PubMed Central

Campos-Rodríguez, Rafael; Gutiérrez-Meza, Manuel; Jarillo-Luna, Rosa Adriana; Drago-Serrano, María Elisa; Abarca-Rojano, Edgar; Ventura-Juárez, Javier; Cárdenas-Jaramillo, Luz María; Pacheco-Yepez, Judith

2016-01-01

Host invasion by Entamoeba histolytica, the pathogenic agent of amebiasis, can lead to the development of amebic liver abscess (ALA). Due to the difficulty of exploring host and amebic factors involved in the pathogenesis of ALA in humans, most studies have been conducted with animal models (e.g., mice, gerbils, and hamsters). Histopathological findings reveal that the chronic phase of ALA in humans corresponds to lytic or liquefactive necrosis, whereas in rodent models there is granulomatous inflammation. However, the use of animal models has provided important information on molecules and mechanisms of the host/parasite interaction. Hence, the present review discusses the possible role of neutrophils in the effector immune response in ALA in rodents. Properly activated neutrophils are probably successful in eliminating amebas through oxidative and non-oxidative mechanisms, including neutrophil degranulation, the generation of free radicals (O2−, H2O2, HOCl) and peroxynitrite, the activation of NADPH-oxidase and myeloperoxidase (MPO) enzymes, and the formation of neutrophil extracellular traps (NETs). On the other hand, if amebas are not eliminated in the early stages of infection, they trigger a prolonged and exaggerated inflammatory response that apparently causes ALAs. Genetic differences in animals and humans are likely to be key to a successful host immune response. PMID:26880421

Climate Change-Induced Range Expansion of a Subterranean Rodent: Implications for Rangeland Management in Qinghai-Tibetan Plateau

PubMed Central

Su, Junhu; Aryal, Achyut; Nan, Zhibiao; Ji, Weihong

2015-01-01

Disturbances, both human-induced and natural, may re-shape ecosystems by influencing their composition, structure, and functional processes. Plateau zokor (Eospalax baileyi) is a typical subterranean rodent endemic to Qinghai-Tibetan Plateau (QTP), which are considered ecosystem engineers influencing the alpine ecosystem function. It is also regarded as a pest aggravating the degradation of overgrazed grassland and subject to regular control in QTP since 1950s. Climate change has been predicted in this region but little research exists exploring its impact on such subterranean rodent populations. Using plateau zokor as a model, through maximum entropy niche-based modeling (Maxent) and sustainable habitat models, we investigate zokor habitat dynamics driven by the future climate scenarios. Our models project that zokor suitable habitat will increase by 6.25% in 2050 in QTP. The predication indicated more threats in terms of grassland degradation as zokor suitable habitat will increase in 2050. Distribution of zokors will shift much more in their southern range with lower elevation compare to northern range with higher elevation. The estimated distance of shift ranges from 1 km to 94 km from current distribution. Grassland management should take into account such predictions in order to design mitigation measures to prevent further grassland degradation in QTP under climate change scenarios. PMID:26406891

Transmission and adaptation of chronic wasting disease to hamsters and transgenic mice: evidence for strains.

PubMed

Raymond, Gregory J; Raymond, Lynne D; Meade-White, Kimberly D; Hughson, Andrew G; Favara, Cynthia; Gardner, Donald; Williams, Elizabeth S; Miller, Michael W; Race, Richard E; Caughey, Byron

2007-04-01

In vitro screening using the cell-free prion protein conversion system indicated that certain rodents may be susceptible to chronic wasting disease (CWD). Therefore, CWD isolates from mule deer, white-tailed deer, and elk were inoculated intracerebrally into various rodent species to assess the rodents' susceptibility and to develop new rodent models of CWD. The species inoculated were Syrian golden, Djungarian, Chinese, Siberian, and Armenian hamsters, transgenic mice expressing the Syrian golden hamster prion protein, and RML Swiss and C57BL10 wild-type mice. The transgenic mice and the Syrian golden, Chinese, Siberian, and Armenian hamsters had limited susceptibility to certain of the CWD inocula, as evidenced by incomplete attack rates and long incubation periods. For serial passages of CWD isolates in Syrian golden hamsters, incubation periods rapidly stabilized, with isolates having either short (85 to 89 days) or long (408 to 544 days) mean incubation periods and distinct neuropathological patterns. In contrast, wild-type mouse strains and Djungarian hamsters were not susceptible to CWD. These results show that CWD can be transmitted and adapted to some species of rodents and suggest that the cervid-derived CWD inocula may have contained or diverged into at least two distinct transmissible spongiform encephalopathy strains.

Visualization of small lesions in rat cartilage by means of laboratory-based x-ray phase contrast imaging

NASA Astrophysics Data System (ADS)

Marenzana, Massimo; Hagen, Charlotte K.; Das Neves Borges, Patricia; Endrizzi, Marco; Szafraniec, Magdalena B.; Ignatyev, Konstantin; Olivo, Alessandro

2012-12-01

Being able to quantitatively assess articular cartilage in three-dimensions (3D) in small rodent animal models, with a simple laboratory set-up, would prove extremely important for the development of pre-clinical research focusing on cartilage pathologies such as osteoarthritis (OA). These models are becoming essential tools for the development of new drugs for OA, a disease affecting up to 1/3 of the population older than 50 years for which there is no cure except prosthetic surgery. However, due to limitations in imaging technology, high-throughput 3D structural imaging has not been achievable in small rodent models, thereby limiting their translational potential and their efficiency as research tools. We show that a simple laboratory system based on coded-aperture x-ray phase contrast imaging (CAXPCi) can correctly visualize the cartilage layer in slices of an excised rat tibia imaged both in air and in saline solution. Moreover, we show that small, surgically induced lesions are also correctly detected by the CAXPCi system, and we support this finding with histopathology examination. Following these successful proof-of-concept results in rat cartilage, we expect that an upgrade of the system to higher resolutions (currently underway) will enable extending the method to the imaging of mouse cartilage as well. From a technological standpoint, by showing the capability of the system to detect cartilage also in water, we demonstrate phase sensitivity comparable to other lab-based phase methods (e.g. grating interferometry). In conclusion, CAXPCi holds a strong potential for being adopted as a routine laboratory tool for non-destructive, high throughput assessment of 3D structural changes in murine articular cartilage, with a possible impact in the field similar to the revolution that conventional microCT brought into bone research.

Phencyclidine and Scopolamine for Modeling Amnesia in Rodents: Direct Comparison with the Use of Barnes Maze Test and Contextual Fear Conditioning Test in Mice.

PubMed

Malikowska-Racia, Natalia; Podkowa, Adrian; Sałat, Kinga

2018-04-21

Nowadays cognitive impairments are a growing unresolved medical issue which may accompany many diseases and therapies, furthermore, numerous researchers investigate various neurobiological aspects of human memory to find possible ways to improve it. Until any other method is discovered, in vivo studies remain the only available tool for memory evaluation. At first, researchers need to choose a model of amnesia which may strongly influence observed results. Thereby a deeper insight into a model itself may increase the quality and reliability of results. The most common method to impair memory in rodents is the pretreatment with drugs that disrupt learning and memory. Taking this into consideration, we compared the activity of agents commonly used for this purpose. We investigated effects of phencyclidine (PCP), a non-competitive NMDA receptor antagonist, and scopolamine (SCOP), an antagonist of muscarinic receptors, on short-term spatial memory and classical fear conditioning in mice. PCP (3 mg/kg) and SCOP (1 mg/kg) were administrated intraperitoneally 30 min before behavioral paradigms. To assess the influence of PCP and SCOP on short-term spatial memory, the Barnes maze test in C57BL/J6 mice was used. Effects on classical conditioning were evaluated using contextual fear conditioning test. Additionally, spontaneous locomotor activity of mice was measured. These two tests were performed in CD-1 mice. Our study reports that both tested agents disturbed short-term spatial memory in the Barnes maze test, however, SCOP revealed a higher activity. Surprisingly, learning in contextual fear conditioning test was impaired only by SCOP. Graphical Abstract ᅟ.

Adapting Human Videofluoroscopic Swallow Study Methods to Detect and Characterize Dysphagia in Murine Disease Models

PubMed Central

Lever, Teresa E.; Braun, Sabrina M.; Brooks, Ryan T.; Harris, Rebecca A.; Littrell, Loren L.; Neff, Ryan M.; Hinkel, Cameron J.; Allen, Mitchell J.; Ulsas, Mollie A.

2015-01-01

This study adapted human videofluoroscopic swallowing study (VFSS) methods for use with murine disease models for the purpose of facilitating translational dysphagia research. Successful outcomes are dependent upon three critical components: test chambers that permit self-feeding while standing unrestrained in a confined space, recipes that mask the aversive taste/odor of commercially-available oral contrast agents, and a step-by-step test protocol that permits quantification of swallow physiology. Elimination of one or more of these components will have a detrimental impact on the study results. Moreover, the energy level capability of the fluoroscopy system will determine which swallow parameters can be investigated. Most research centers have high energy fluoroscopes designed for use with people and larger animals, which results in exceptionally poor image quality when testing mice and other small rodents. Despite this limitation, we have identified seven VFSS parameters that are consistently quantifiable in mice when using a high energy fluoroscope in combination with the new murine VFSS protocol. We recently obtained a low energy fluoroscopy system with exceptionally high imaging resolution and magnification capabilities that was designed for use with mice and other small rodents. Preliminary work using this new system, in combination with the new murine VFSS protocol, has identified 13 swallow parameters that are consistently quantifiable in mice, which is nearly double the number obtained using conventional (i.e., high energy) fluoroscopes. Identification of additional swallow parameters is expected as we optimize the capabilities of this new system. Results thus far demonstrate the utility of using a low energy fluoroscopy system to detect and quantify subtle changes in swallow physiology that may otherwise be overlooked when using high energy fluoroscopes to investigate murine disease models. PMID:25866882

Single calcium channel domain gating of synaptic vesicle fusion at fast synapses; analysis by graphic modeling

PubMed Central

Stanley, Elise F

2015-01-01

At fast-transmitting presynaptic terminals Ca2+ enter through voltage gated calcium channels (CaVs) and bind to a synaptic vesicle (SV) -associated calcium sensor (SV-sensor) to gate fusion and discharge. An open CaV generates a high-concentration plume, or nanodomain of Ca2+ that dissipates precipitously with distance from the pore. At most fast synapses, such as the frog neuromuscular junction (NMJ), the SV sensors are located sufficiently close to individual CaVs to be gated by single nanodomains. However, at others, such as the mature rodent calyx of Held (calyx of Held), the physiology is more complex with evidence that CaVs that are both close and distant from the SV sensor and it is argued that release is gated primarily by the overlapping Ca2+ nanodomains from many CaVs. We devised a 'graphic modeling' method to sum Ca2+ from individual CaVs located at varying distances from the SV-sensor to determine the SV release probability and also the fraction of that probability that can be attributed to single domain gating. This method was applied first to simplified, low and high CaV density model release sites and then to published data on the contrasting frog NMJ and the rodent calyx of Held native synapses. We report 3 main predictions: the SV-sensor is positioned very close to the point at which the SV fuses with the membrane; single domain-release gating predominates even at synapses where the SV abuts a large cluster of CaVs, and even relatively remote CaVs can contribute significantly to single domain-based gating. PMID:26457441

The Epileptic Thalamocortical Network is a Macroscopic Self-Sustained Oscillator: Evidence from Frequency-Locking Experiments in Rat Brains

NASA Astrophysics Data System (ADS)

Velazquez, J. L. Perez; Erra, R. Guevara; Rosenblum, M.

2015-02-01

The rhythmic activity observed in nervous systems, in particular in epilepsies and Parkinson's disease, has often been hypothesized to originate from a macroscopic self-sustained neural oscillator. However, this assumption has not been tested experimentally. Here we support this viewpoint with in vivo experiments in a rodent model of absence seizures, by demonstrating frequency locking to external periodic stimuli and finding the characteristic Arnold tongue. This result has important consequences for developing methods for the control of brain activity, such as seizure cancellation.

Stress in adolescence and drugs of abuse in rodent models: Role of dopamine, CRF, and HPA axis

PubMed Central

Burke, Andrew R.; Miczek, Klaus A.

2014-01-01

Rationale Research on adolescence and drug abuse increased substantially in the past decade. However, drug-addiction related behaviors following stressful experiences during adolescence are less studied. We focus on rodent models of adolescent stress cross-sensitization to drugs of abuse. Objectives Review the ontogeny of behavior, dopamine, corticotropin-releasing factor (CRF), and the hypothalamic pituitary adrenal (HPA) axis in adolescent rodents. We evaluate evidence that stressful experiences during adolescence engender hypersensitivity to drugs of abuse and offer potential neural mechanisms. Results and Conclusions Much evidence suggests that final maturation of behavior, dopamine systems, and HPA axis occurs during adolescence. Stress during adolescence increases amphetamine- and ethanol-stimulated locomotion, preference, and self-administration under many conditions. The influence of adolescent stress on subsequent cocaine- and nicotine-stimulated locomotion and preference is less clear. The type of adolescent stress, temporal interval between stress and testing, species, sex, and the drug tested are key methodological determinants for successful cross-sensitization procedures. The sensitization of the mesolimbic dopamine system is proposed to underlie stress cross-sensitization to drugs of abuse in both adolescents and adults through modulation by CRF. Reduced levels of mesocortical dopamine appear to be a unique consequence of social stress during adolescence. Adolescent stress may reduce the final maturation of cortical dopamine through D2 dopamine receptor regulation of dopamine synthesis or glucocorticoid-facilitated pruning of cortical dopamine fibers. Certain rodent models of adolescent adversity are useful for determining neural mechanisms underlying the cross-sensitization to drugs of abuse. PMID:24370534

Impact of parity on ewe vaginal mechanical properties relative to the nonhuman primate and rodent.

PubMed

Knight, Katrina M; Moalli, Pamela A; Nolfi, Alexis; Palcsey, Stacy; Barone, William R; Abramowitch, Steven D

2016-08-01

Parity is the leading risk factor for the development of pelvic organ prolapse. To assess the impact of pregnancy and delivery on vaginal tissue, researchers commonly use nonhuman primate (NHP) and rodent models. The purpose of this study was to evaluate the ewe as an alternative model by investigating the impact of parity on the ewe vaginal mechanical properties and collagen structure. Mechanical properties of 15 nulliparous and parous ewe vaginas were determined via uniaxial tensile tests. Collagen content was determined by hydroxyproline assay and collagen fiber thickness was analyzed using picrosirius red staining. Outcome measures were compared using Independent samples t or Mann-Whitney U tests. ANOVA (Gabriel's pairwise post-hoc test) or the Welch Alternative for the F-ratio (Games Howell post-hoc test) was used to compare data with previously published NHP and rodent data. Vaginal tissue from the nulliparous ewe had a higher tangent modulus and tensile strength compared with the parous ewe (p < 0.025). The parous ewe vagina elongated 42 % more than the nulliparous ewe vagina (p = 0.015). No significant differences were observed in collagen structure among ewe vaginas. The tangent modulus of the nulliparous ewe vagina was not different from that of the NHP or rodent (p = 0.290). Additionally, the tangent moduli of the parous ewe and NHP vaginas did not differ (p = 0.773). Parity has a negative impact on the mechanical properties of the ewe vagina, as also observed in the NHP. The ewe may serve as an alternative model for studying parity and ultimately prolapse development.

Three-dimensional culture of buffalo granulosa cells in hanging drop mimics the preovulatory follicle stage.

PubMed

Yadav, Monica; Agrawal, Himanshu; Pandey, Mamta; Singh, Dheer; Onteru, Suneel K

2018-03-01

Granulosa cell (GC) culture models mimicking the intrafollicular environment are limited. Such models have a great potential in reproductive toxicity studies. The buffalo, a monovulatory species like humans, could be a better model than polyovulatory rodents. Therefore, we targeted the development and characterization of three-dimensional (3D) culture systems for buffalo GCs. The GCs from small ovarian follicles (SF) maintained the CYP19 gene expression for 144 hr in a 2D culture system. Hence, GCs from SF were cultured directly in 3D using hanging drop and Poly-([2-hydroxyethyl methacrylate]) (polyHEMA) methods in the DMEM media containing 1 ng/ml FSH and 10 ng/ml IGF-1 for 144 hr. The expression profile of nine GC-specific transcripts; CYP19, TNFAIP6, AMH, PTI, NR4A1, FSHR, RUNX, LHR, and COX2/PTGS2; revealed that 3D-spheroids developed in hanging drop method maintained the GC phenotype of preovulatory follicles. Therefore, hanging drop method is a best method for culturing GCs to mimic the intrafollicular environment. © 2017 Wiley Periodicals, Inc.

Spatial memory tasks in rodents: what do they model?

PubMed

Morellini, Fabio

2013-10-01

The analysis of spatial learning and memory in rodents is commonly used to investigate the mechanisms underlying certain forms of human cognition and to model their dysfunction in neuropsychiatric and neurodegenerative diseases. Proper interpretation of rodent behavior in terms of spatial memory and as a model of human cognitive functions is only possible if various navigation strategies and factors controlling the performance of the animal in a spatial task are taken into consideration. The aim of this review is to describe the experimental approaches that are being used for the study of spatial memory in rats and mice and the way that they can be interpreted in terms of general memory functions. After an introduction to the classification of memory into various categories and respective underlying neuroanatomical substrates, I explain the concept of spatial memory and its measurement in rats and mice by analysis of their navigation strategies. Subsequently, I describe the most common paradigms for spatial memory assessment with specific focus on methodological issues relevant for the correct interpretation of the results in terms of cognitive function. Finally, I present recent advances in the use of spatial memory tasks to investigate episodic-like memory in mice.

Unique inhibitory cascade pattern of molars in canids contributing to their potential to evolutionary plasticity of diet

PubMed Central

Asahara, Masakazu

2013-01-01

Developmental origins that guide the evolution of dental morphology and dental formulae are fundamental subjects in mammalian evolution. In a previous study, a developmental model termed the inhibitory cascade model was established. This model could explain variations in relative molar sizes and loss of the lower third molars, which sometimes reflect diet, in murine rodents and other mammals. Here, I investigated the pattern of relative molar sizes (inhibitory cascade pattern) in canids, a taxon exhibiting a wide range of dietary habits. I found that interspecific variation in canid molars suggests a unique inhibitory cascade pattern that differs from that in murine rodents and other previously reported mammals, and that this variation reflects dietary habits. This unique variability in molars was also observed in individual variation in canid species. According to these observations, canid species have greater variability in the relative sizes of first molars (carnassials), which are functionally important for dietary adaptation in the Carnivora. In conclusion, an inhibitory cascade that differs from that in murine rodents and other mammals may have contributed to diverse dietary patterns and to their parallel evolution in canids. PMID:23467478

Considerations for the Optimization of Induced White Matter Injury Preclinical Models

PubMed Central

Ahmad, Abdullah Shafique; Satriotomo, Irawan; Fazal, Jawad; Nadeau, Stephen E.; Doré, Sylvain

2015-01-01

White matter (WM) injury in relation to acute neurologic conditions, especially stroke, has remained obscure until recently. Current advances in imaging technologies in the field of stroke have confirmed that WM injury plays an important role in the prognosis of stroke and suggest that WM protection is essential for functional recovery and post-stroke rehabilitation. However, due to the lack of a reproducible animal model of WM injury, the pathophysiology and mechanisms of this injury are not well studied. Moreover, producing selective WM injury in animals, especially in rodents, has proven to be challenging. Problems associated with inducing selective WM ischemic injury in the rodent derive from differences in the architecture of the brain, most particularly, the ratio of WM to gray matter in rodents compared to humans, the agents used to induce the injury, and the location of the injury. Aging, gender differences, and comorbidities further add to this complexity. This review provides a brief account of the techniques commonly used to induce general WM injury in animal models (stroke and non-stroke related) and highlights relevance, optimization issues, and translational potentials associated with this particular form of injury. PMID:26322013

Therapeutic targeting of oxygen-sensing prolyl hydroxylases abrogates ATF4-dependent neuronal death and improves outcomes after brain hemorrhage in several rodent models

PubMed Central

Karuppagounder, Saravanan S.; Alim, Ishraq; Khim, Soah J.; Bourassa, Megan W.; Sleiman, Sama F.; John, Roseleen; Thinnes, Cyrille C.; Yeh, Tzu-Lan; Demetriades, Marina; Neitemeier, Sandra; Cruz, Dana; Gazaryan, Irina; Killilea, David W.; Morgenstern, Lewis; Xi, Guohua; Keep, Richard F.; Schallert, Timothy; Tappero, Ryan V.; Zhong, Jian; Cho, Sunghee; Maxfield, Frederick R.; Holman, Theodore R.; Culmsee, Carsten; Fong, Guo-Hua; Su, Yijing; Ming, Guo-li; Song, Hongjun; Cave, John W.; Schofield, Christopher J.; Colbourne, Frederick; Coppola, Giovanni; Ratan, Rajiv R.

2017-01-01

Disability or death due to intracerebral hemorrhage (ICH) is attributed to blood lysis, liberation of iron, and consequent oxidative stress. Iron chelators bind to free iron and prevent neuronal death induced by oxidative stress and disability due to ICH, but the mechanisms for this effect remain unclear. We show that the hypoxia-inducible factor prolyl hydroxylase domain (HIF-PHD) family of iron-dependent, oxygen-sensing enzymes are effectors of iron chelation. Molecular reduction of the three HIF-PHD enzyme isoforms in the mouse striatum improved functional recovery after ICH. A low-molecular-weight hydroxyquinoline inhibitor of the HIF-PHD enzymes, adaptaquin, reduced neuronal death and behavioral deficits after ICH in several rodent models without affecting total iron or zinc distribution in the brain. Unexpectedly, protection from oxidative death in vitro or from ICH in vivo by adaptaquin was associated with suppression of activity of the prodeath factor ATF4 rather than activation of an HIF-dependent prosurvival pathway. Together, these findings demonstrate that brain-specific inactivation of the HIF-PHD metalloenzymes with the blood-brain barrier-permeable inhibitor adaptaquin can improve functional outcomes after ICH in several rodent models. PMID:26936506

An Automated Test of Rat Forelimb Supination Quantifies Motor Function Loss and Recovery After Corticospinal Injury.

PubMed

Sindhurakar, Anil; Butensky, Samuel D; Meyers, Eric; Santos, Joshua; Bethea, Thelma; Khalili, Ashley; Sloan, Andrew P; Rennaker, Robert L; Carmel, Jason B

2017-02-01

Rodents are the primary animal model of corticospinal injury and repair, yet current behavioral tests do not show the large deficits after injury observed in humans. Forearm supination is critical for hand function and is highly impaired by corticospinal injury in both humans and rats. Current tests of rodent forelimb function do not measure this movement. To determine if quantification of forelimb supination in rats reveals large-scale functional loss and partial recovery after corticospinal injury. We developed a knob supination device that quantifies supination using automated and objective methods. Rats in a reaching box have to grasp and turn a knob in supination in order to receive a food reward. Performance on this task and the single pellet reaching task were measured before and after 2 manipulations of the pyramidal tract: a cut lesion of 1 pyramid and inactivation of motor cortex using 2 different drug doses. A cut lesion of the corticospinal tract produced a large deficit in supination. In contrast, there was no change in pellet retrieval success. Supination function recovered partially over 6 weeks after injury, and a large deficit remained. Motor cortex inactivation produced a dose-dependent loss of knob supination; the effect on pellet reaching was more subtle. The knob supination task reveals in rodents 3 signature hand function changes observed in humans with corticospinal injury: (1) large-scale loss with injury, (2) partial recovery in the weeks after injury, and (3) loss proportional to degree of dysfunction.

Intermittent Hypoxia and Stem Cell Implants Preserve Breathing Capacity in a Rodent Model of Amyotrophic Lateral Sclerosis

PubMed Central

Nichols, Nicole L.; Gowing, Genevieve; Satriotomo, Irawan; Nashold, Lisa J.; Dale, Erica A.; Suzuki, Masatoshi; Avalos, Pablo; Mulcrone, Patrick L.; McHugh, Jacalyn

2013-01-01

Rationale: Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease causing paralysis and death from respiratory failure. Strategies to preserve and/or restore respiratory function are critical for successful treatment. Although breathing capacity is maintained until late in disease progression in rodent models of familial ALS (SOD1G93A rats and mice), reduced numbers of phrenic motor neurons and decreased phrenic nerve activity are observed. Decreased phrenic motor output suggests imminent respiratory failure. Objectives: To preserve or restore phrenic nerve activity in SOD1G93A rats at disease end stage. Methods: SOD1G93A rats were injected with human neural progenitor cells (hNPCs) bracketing the phrenic motor nucleus before disease onset, or exposed to acute intermittent hypoxia (AIH) at disease end stage. Measurements and Main Results: The capacity to generate phrenic motor output in anesthetized rats at disease end stage was: (1) transiently restored by a single presentation of AIH; and (2) preserved ipsilateral to hNPC transplants made before disease onset. hNPC transplants improved ipsilateral phrenic motor neuron survival. Conclusions: AIH-induced respiratory plasticity and stem cell therapy have complementary translational potential to treat breathing deficits in patients with ALS. PMID:23220913

Standard dose valproic acid does not cause additional cognitive impact in a rodent model of intractable epilepsy.

PubMed

Jellett, Adam P; Jenks, Kyle; Lucas, Marcella; Scott, Rod C

2015-02-01

Children with epilepsy face significant cognitive and behavioral impairments. These impairments are due to a poorly characterized interaction between the underlying etiology, the effect of seizures and the effect of medication. The large variation in these factors make understanding the main drivers of cognitive impairment in humans extremely difficult. Therefore, we investigated the cognitive effect of seizures and the antiepileptic drug valproic acid in a rodent model of cortical dysplasia. Rats were divided into seizure-receiving and non-receiving groups. Rats experienced frequent early life seizures using the flurothyl inhalation method: 50 seizures between postnatal day 5 and 15 and then one seizure a day following that. Rats were further divided into drug-treated and vehicle treated groups. Valproic acid treated animals were treated from 5 days preceding behavioral testing in the Morris water maze at a clinically relevant concentration. We show here that the main driver of cognitive impairments are the brain malformations, and that persistent seizures in animals with brain malformations and valproic acid caused no additional impact. These findings suggest that neither an appropriate dose of a standard antiepileptic drug or intractable seizures worsen cognition associated with a malformation of cortical development and that alternative treatment strategies to improve cognition are required. Copyright © 2014 Elsevier B.V. All rights reserved.

Development of Novel Combinatorial Treatment to Prevent Chemotherapeutic Resistance and Enhance Efficacy of Riluzole in a Rodent Model of SCI

DTIC Science & Technology

2016-10-01

site as well as in the cervical and lumbar cords out to at least 10 months post-injury. While our rodent study was ongoing, a multi-center clinical...lead to a preservation of motor function and an attenuation in long-term pathologies like neuropathic pain in rats following an acute therapeutic...chemotherapeutic resistance, mass spectrometry, riluzole, licofelone, neuropathic pain , locomotor, bioavailability 11 University of Mississippi

Anatomy and histology of the lower urinary tract.

PubMed

Pradidarcheep, Wisuit; Wallner, Christian; Dabhoiwala, Noshir F; Lamers, Wouter H

2011-01-01

The function of the lower urinary tract is basically storage of urine in the bladder and the at-will periodic evacuation of the stored urine. Urinary incontinence is one of the most common lower urinary tract disorders in adults, but especially in the elderly female. The urethra, its sphincters, and the pelvic floor are key structures in the achievement of continence, but their basic anatomy is little known and, to some extent, still incompletely understood. Because questions with respect to continence arise from human morbidity, but are often investigated in rodent animal models, we present findings in human and rodent anatomy and histology. Differences between males and females in the role that the pelvic floor plays in the maintenance of continence are described. Furthermore, we briefly describe the embryologic origin of ureters, bladder, and urethra, because the developmental origin of structures such as the vesicoureteral junction, the bladder trigone, and the penile urethra are often invoked to explain (clinical) observations. As the human pelvic floor has acquired features in evolution that are typical for a species with bipedal movement, we also compare the pelvic floor of humans with that of rodents to better understand the rodent (or any other quadruped, for that matter) as an experimental model species. The general conclusion is that the "Bauplan" is well conserved, even though its common features are sometimes difficult to discern.

Wernicke-Korsakoff Syndrome

MedlinePlus

... Coordinating Committees CounterACT Rigor & Transparency Scientific Resources Animal Models Cell/Tissue/DNA Clinical and Translational Resources Gene ... modulation of certain nerve cells in a rodent model of amnesia produced by by thiamine deficiency. The ...

A Physiologically-based Model for Methylmercury Uptake and Accumulation in Female American Kestrels

EPA Science Inventory

A physiologically-based model was developed to describe the uptake, distribution, and elimination of methylmercury in female American Kestrels (Falco sparverius). The model was adapted from established models for methylmercury in rodents. Features unique to the model include meth...

The JCR:LA-cp rat: a novel rodent model of cystic medial necrosis.

PubMed

Pung, Yuh Fen; Chilian, William M; Bennett, Martin R; Figg, Nichola; Kamarulzaman, Mohd Hamzah

2017-03-01

Although there are multiple rodent models of the metabolic syndrome, very few develop vascular complications. In contrast, the JCR:LA-cp rat develops both metabolic syndrome and early atherosclerosis in predisposed areas. However, the pathology of the normal vessel wall has not been described. We examined JCR:LA control (+/+) or cp/cp rats fed normal chow diet for 6 or 18 mo. JCR:LA-cp rats developed multiple features of advanced cystic medial necrosis including "cysts," increased collagen formation and proteoglycan deposition around cysts, apoptosis of vascular smooth muscle cells, and spotty medial calcification. These appearances began within 6 mo and were extensive by 18 mo. JCR:LA-cp rats had reduced medial cellularity, increased medial thickness, and vessel hypoxia that was most marked in the adventitia. In conclusion, the normal chow-fed JCR:LA-cp rat represents a novel rodent model of cystic medial necrosis, associated with multiple metabolic abnormalities, vascular smooth muscle cell apoptosis, and vessel hypoxia. NEW & NOTEWORTHY Triggers for cystic medial necrosis (CMN) have been difficult to study due to lack of animal models to recapitulate the pathologies seen in humans. Our study is the first description of CMN in the rat. Thus the JCR:LA-cp rat represents a useful model to investigate the underlying molecular changes leading to the development of CMN. Copyright © 2017 the American Physiological Society.

Modeling the Disease Course of Zaire ebolavirus Infection in the Outbred Guinea Pig.

PubMed

Cross, Robert W; Fenton, Karla A; Geisbert, Joan B; Mire, Chad E; Geisbert, Thomas W

2015-10-01

Rodent models that accurately reflect human filovirus infection are needed as early screens for medical countermeasures. Prior work in rodents with the Zaire species of Ebola virus (ZEBOV) primarily used inbred mice and guinea pigs to model disease. However, these inbred species do not show some of the important features of primate ZEBOV infection, most notably, coagulation abnormalities. Thirty-six outbred guinea pigs were infected with guinea pig-adapted ZEBOV and examined sequentially over an 8-day period to investigate the pathologic events that lead to death. Features of disease in ZEBOV-infected outbred guinea pigs were largely consistent with disease in humans and nonhuman primates and included early infection of macrophages and dendritiform cells, apoptosis of bystander lymphocytes, and increases in levels of proinflammatory cytokines. Most importantly, dysregulation of circulating levels of fibrinogen, protein C activity, and antifibrinolytic proteins and deposition of fibrin in tissues demonstrated both biochemical and microscopic evidence of disseminated intravascular coagulation. These findings suggest that the outbred guinea pig model recapitulates ZEBOV infection of primates better than inbred rodent models, is useful for dissecting key events in the pathogenesis of ZEBOV, and is useful for evaluating candidate interventions prior to assessment in primates. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Molecular identification of Taenia mustelae cysts in subterranean rodent plateau zokors (Eospalax baileyi).

PubMed

Zhao, Fang; Ma, Jun-Ying; Cai, Hui-Xia; Su, Jian-Ping; Hou, Zhi-Bin; Zhang, Tong-Zuo; Lin, Gong-Hua

2014-07-01

Cestode larvae spend one phase of their two-phase life cycle in the viscera of rodents, but cases of cestodes infecting subterranean rodents have only been rarely observed. To experimentally gain some insight into this phenomenon, we captured approximately 300 plateau zokors (Eospalax baileyi), a typical subterranean rodent inhabiting the Qinghai-Tibet Plateau, and examined their livers for the presence of cysts. Totally, we collected five cysts, and using a mitochondrial gene (cox1) and two nuclear genes (pepck and pold) as genetic markers, we were able to analyze the taxonomy of the cysts. Both the maximum likelihood and Bayesian methods showed that the cysts share a monophyly with Taenia mustelae, while Kimura 2-parameter distances and number of different sites between our sequences and T. mustelae were far less than those found between the examined sequences and other Taeniidae species. These results, alongside supporting paraffin section histology, imply that the cysts found in plateau zokors can be regarded as larvae of T. mustelae, illustrating that zokors are a newly discovered intermediate host record of this parasite.

Molecular identification of Taenia mustelae cysts in subterranean rodent plateau zokors (Eospalax baileyi)

PubMed Central

ZHAO, Fang; ZHANG, Ming-Xia; MA, Jun-Ying; CAI, Hui-Xia; SU, Jian-Ping; CAI, Hui-Xia; HOU, Zhi-Bin; ZHANG, Tong-Zuo; LIN, Gong-Hua

2014-01-01

Cestode larvae spend one phase of their two-phase life cycle in the viscera of rodents, but cases of cestodes infecting subterranean rodents have only been rarely observed. To experimentally gain some insight into this phenomenon, we captured approximately 300 plateau zokors (Eospalax baileyi), a typical subterranean rodent inhabiting the Qinghai-Tibet Plateau, and examined their livers for the presence of cysts. Totally, we collected five cysts, and using a mitochondrial gene (cox1) and two nuclear genes (pepck and pold) as genetic markers, we were able to analyze the taxonomy of the cysts. Both the maximum likelihood and Bayesian methods showed that the cysts share a monophyly with Taenia mustelae, while Kimura 2-parameter distances and number of different sites between our sequences and T. mustelae were far less than those found between the examined sequences and other Taeniidae species. These results, alongside supporting paraffin section histology, imply that the cysts found in plateau zokors can be regarded as larvae of T. mustelae, illustrating that zokors are a newly discovered intermediate host record of this parasite. PMID:25017751

Isolation and characterization of Listeria species from rodents in natural environments in China.

PubMed

Wang, Yan; Lu, Liang; Lan, Ruiting; Salazar, Joelle K; Liu, Jingli; Xu, Jianguo; Ye, Changyun

2017-06-07

Listeria is ubiquitous in a variety of environments and can be isolated from a wide range of animal hosts. Rodents are capable of carrying pathogenic bacteria in their intestines, such as Listeria, and can disseminate those pathogens into the natural environment and to where human activity occurs. In this study, we investigated the occurrence and antimicrobial susceptibility of Listeria spp. isolated from wild rodents found in natural environments in China. We collected 341 intestinal fecal samples of rodents from five different regions of China, all representing different rodent habitats. The antimicrobial susceptibility of the Listeria spp. isolates obtained were firstly assessed using the Kirby-Bauer disk diffusion method. Thirty-one samples were positive for Listeria spp., of which 11 were positive for Listeria monocytogenes and seven were positive for Listeria ivanovii. Other species identified include Listeria innocua, Listeria fleischmannii and Listeria floridensis. All Listeria spp. isolates were sensitive to the majority of the antimicrobials tested, but largely resistant to oxacillin (94.1%) and cefuroxime (70.6%). All L. monocytogenes isolates were further characterized by serotyping, multi-locus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). L. monocytogenes strains were grouped into three serotypes, five sequence types and five pulsotypes (PTs) by serotyping, MLST and PFGE, respectively. Almost half of the isolates (five of 11) belonged to serotype 1/2b, ST87 and PT1. This study determined that Listeria is carried in the intestinal tracts of wild rodents from multiple regions at a low rate, filling an epidemiological data gap on Listeria in natural environments in China.

Isolation and characterization of Listeria species from rodents in natural environments in China

PubMed Central

Wang, Yan; Lu, Liang; Lan, Ruiting; Salazar, Joelle K; Liu, Jingli; Xu, Jianguo; Ye, Changyun

2017-01-01

Listeria is ubiquitous in a variety of environments and can be isolated from a wide range of animal hosts. Rodents are capable of carrying pathogenic bacteria in their intestines, such as Listeria, and can disseminate those pathogens into the natural environment and to where human activity occurs. In this study, we investigated the occurrence and antimicrobial susceptibility of Listeria spp. isolated from wild rodents found in natural environments in China. We collected 341 intestinal fecal samples of rodents from five different regions of China, all representing different rodent habitats. The antimicrobial susceptibility of the Listeria spp. isolates obtained were firstly assessed using the Kirby–Bauer disk diffusion method. Thirty-one samples were positive for Listeria spp., of which 11 were positive for Listeria monocytogenes and seven were positive for Listeria ivanovii. Other species identified include Listeria innocua, Listeria fleischmannii and Listeria floridensis. All Listeria spp. isolates were sensitive to the majority of the antimicrobials tested, but largely resistant to oxacillin (94.1%) and cefuroxime (70.6%). All L. monocytogenes isolates were further characterized by serotyping, multi-locus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). L. monocytogenes strains were grouped into three serotypes, five sequence types and five pulsotypes (PTs) by serotyping, MLST and PFGE, respectively. Almost half of the isolates (five of 11) belonged to serotype 1/2b, ST87 and PT1. This study determined that Listeria is carried in the intestinal tracts of wild rodents from multiple regions at a low rate, filling an epidemiological data gap on Listeria in natural environments in China. PMID:28588285

Differences in Ultrasonic Vocalizations between Wild and Laboratory California Mice (Peromyscus californicus)

PubMed Central

Kalcounis-Rueppell, Matina C.; Petric, Radmila; Briggs, Jessica R.; Carney, Catherine; Marshall, Matthew M.; Willse, John T.; Rueppell, Olav; Ribble, David O.; Crossland, Janet P.

2010-01-01

Background Ultrasonic vocalizations (USVs) emitted by muroid rodents, including laboratory mice and rats, are used as phenotypic markers in behavioral assays and biomedical research. Interpretation of these USVs depends on understanding the significance of USV production by rodents in the wild. However, there has never been a study of muroid rodent ultrasound function in the wild and comparisons of USVs produced by wild and laboratory rodents are lacking to date. Here, we report the first comparison of wild and captive rodent USVs recorded from the same species, Peromyscus californicus. Methodology and Principal Findings We used standard ultrasound recording techniques to measure USVs from California mice in the laboratory (Peromyscus Genetic Stock Center, SC, USA) and the wild (Hastings Natural History Reserve, CA, USA). To determine which California mouse in the wild was vocalizing, we used a remote sensing method that used a 12-microphone acoustic localization array coupled with automated radio telemetry of all resident Peromyscus californicus in the area of the acoustic localization array. California mice in the laboratory and the wild produced the same types of USV motifs. However, wild California mice produced USVs that were 2–8 kHz higher in median frequency and significantly more variable in frequency than laboratory California mice. Significance The similarity in overall form of USVs from wild and laboratory California mice demonstrates that production of USVs by captive Peromyscus is not an artifact of captivity. Our study validates the widespread use of USVs in laboratory rodents as behavioral indicators but highlights that particular characteristics of laboratory USVs may not reflect natural conditions. PMID:20368980

Model-based analysis of pattern motion processing in mouse primary visual cortex

PubMed Central

Muir, Dylan R.; Roth, Morgane M.; Helmchen, Fritjof; Kampa, Björn M.

2015-01-01

Neurons in sensory areas of neocortex exhibit responses tuned to specific features of the environment. In visual cortex, information about features such as edges or textures with particular orientations must be integrated to recognize a visual scene or object. Connectivity studies in rodent cortex have revealed that neurons make specific connections within sub-networks sharing common input tuning. In principle, this sub-network architecture enables local cortical circuits to integrate sensory information. However, whether feature integration indeed occurs locally in rodent primary sensory areas has not been examined directly. We studied local integration of sensory features in primary visual cortex (V1) of the mouse by presenting drifting grating and plaid stimuli, while recording the activity of neuronal populations with two-photon calcium imaging. Using a Bayesian model-based analysis framework, we classified single-cell responses as being selective for either individual grating components or for moving plaid patterns. Rather than relying on trial-averaged responses, our model-based framework takes into account single-trial responses and can easily be extended to consider any number of arbitrary predictive models. Our analysis method was able to successfully classify significantly more responses than traditional partial correlation (PC) analysis, and provides a rigorous statistical framework to rank any number of models and reject poorly performing models. We also found a large proportion of cells that respond strongly to only one stimulus class. In addition, a quarter of selectively responding neurons had more complex responses that could not be explained by any simple integration model. Our results show that a broad range of pattern integration processes already take place at the level of V1. This diversity of integration is consistent with processing of visual inputs by local sub-networks within V1 that are tuned to combinations of sensory features. PMID:26300738

Neurobehavioral testing in subarachnoid hemorrhage: A review of methods and current findings in rodents.

PubMed

Turan, Nefize; Miller, Brandon A; Heider, Robert A; Nadeem, Maheen; Sayeed, Iqbal; Stein, Donald G; Pradilla, Gustavo

2017-11-01

The most important aspect of a preclinical study seeking to develop a novel therapy for neurological diseases is whether the therapy produces any clinically relevant functional recovery. For this purpose, neurobehavioral tests are commonly used to evaluate the neuroprotective efficacy of treatments in a wide array of cerebrovascular diseases and neurotrauma. Their use, however, has been limited in experimental subarachnoid hemorrhage studies. After several randomized, double-blinded, controlled clinical trials repeatedly failed to produce a benefit in functional outcome despite some improvement in angiographic vasospasm, more rigorous methods of neurobehavioral testing became critical to provide a more comprehensive evaluation of the functional efficacy of proposed treatments. While several subarachnoid hemorrhage studies have incorporated an array of neurobehavioral assays, a standardized methodology has not been agreed upon. Here, we review neurobehavioral tests for rodents and their potential application to subarachnoid hemorrhage studies. Developing a standardized neurobehavioral testing regimen in rodent studies of subarachnoid hemorrhage would allow for better comparison of results between laboratories and a better prediction of what interventions would produce functional benefits in humans.

Scaling law in free walking of mice in circular open fields of various diameters.

PubMed

Shoji, Hiroto

2016-03-01

Open-field tests are routinely used to study locomotor activity in rodents. I studied the effects of apparatus size on rodent locomotor activity, specifically with respect to how resting and walking periods are interwoven. I explored the open-field behavior of mice utilizing circular open fields of various diameters. When the diameter of the test apparatus was greater than 75 cm, the durations of the resting and moving periods of free walking behavior obeyed bounded power-law distribution functions. I found that the properties of the scaling exponents and model selection became similar for test apparatus diameters greater than 75 cm. These results can provide a guide for the selection of the size of the test apparatus for use in the study of the open-field behavior of rodents.

Effects of sex and locality on the abundance of lice on the wild rodent Oligoryzomys nigripes.

PubMed

Fernandes, Fernanda Rodrigues; Cruz, Leonardo Dominici; Linhares, Arício Xavier

2012-10-01

Various factors can affect the parasite distribution on a host. In this study, the influence of sex, body size, and locality of a rodent host, Oligoryzomys nigripes, on lice abundance was investigated. A generalized linear model indicated that the sex and locality of O. nigripes significantly contributed to the variation in lice abundance on the host. The male bias of lice parasitizing the rodent host O. nigripes may be associated with intersexual differences in physiology and behavior, while locality differences in lice abundance may be associated with differences in host density and diversity between the two localities sampled. Studies of host-parasite associations improve the understanding of the ecology of infectious diseases, as well as the evolution of these host-parasite interactions.

ANIMAL MODELS OF COGNITIVE DEVELOPMENT IN NEUROTOXICITY

EPA Science Inventory

The thesis of this chapter has been that spatial delayed alternation versus position discrimination learning can serve as a valuable rodent model of cognitive development in neurotoxicology. his model captures dual process conceptualizations of memory in human neuropsychology and...

Morphological and functional maturation of Leydig cells: from rodent models to primates.

PubMed

Teerds, Katja J; Huhtaniemi, Ilpo T

2015-01-01

Leydig cells (LC) are the sites of testicular androgen production. Development of LC occurs in the testes of most mammalian species as two distinct growth phases, i.e. as fetal and pubertal/adult populations. In primates there are indications of a third neonatal growth phase. LC androgen production begins in embryonic life and is crucial for the intrauterine masculinization of the male fetal genital tract and brain, and continues until birth after which it rapidly declines. A short post-natal phase of LC activity in primates (including human) termed 'mini-puberty' precedes the period of juvenile quiescence. The adult population of LC evolves, depending on species, in mid- to late-prepuberty upon reawakening of the hypothalamic-pituitary-testicular axis, and these cells are responsible for testicular androgen production in adult life, which continues with a slight gradual decline until senescence. This review is an updated comparative analysis of the functional and morphological maturation of LC in model species with special reference to rodents and primates. Pubmed, Scopus, Web of Science and Google Scholar databases were searched between December 2012 and October 2014. Studies published in languages other than English or German were excluded, as were data in abstract form only. Studies available on primates were primarily examined and compared with available data from specific animal models with emphasis on rodents. Expression of different marker genes in rodents provides evidence that at least two distinct progenitor lineages give rise to the fetal LC (FLC) population, one arising from the coelomic epithelium and the other from specialized vascular-associated cells along the gonad-mesonephros border. There is general agreement that the formation and functioning of the FLC population in rodents is gonadotrophin-responsive but not gonadotrophin-dependent. In contrast, although there is in primates some controversy on the role of gonadotrophins in the formation of the FLC population, there is consensus about the essential role of gonadotrophins in testosterone production. Like the FLC population, adult Leydig cells (ALC) in rodents arise from stem cells, which have their origin in the fetal testis. In contrast, in primates the ALC population is thought to originate from FLC, which undergo several cycles of regression and redifferentiation before giving rise to the mature ALC population, as well as from differentiation of stem cells/precursor cells. Despite this difference in origin, both in primates and rodents the formation of the mature and functionally active ALC population is critically dependent on the pituitary gonadotrophin, LH. From studies on rodents considerable knowledge has emerged on factors that are involved besides LH in the regulation of this developmental process. Whether the same factors also play a role in the development of the mature primate LC population awaits further investigation. Distinct populations of LC develop along the life span of males, including fetal, neonatal (primates) and ALC. Despite differences in the LC lineages of rodents and primates, the end product is a mature population of LC with the main function to provide androgens necessary for the maintenance of spermatogenesis and extra-gonadal androgen actions. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Autoclave sterilization produces acrylamide in rodent diets: implications for toxicity testing.

PubMed

Twaddle, Nathan C; Churchwell, Mona I; McDaniel, L Patrice; Doerge, Daniel R

2004-06-30

Acrylamide (AA) is a neurotoxic and carcinogenic contaminant that is formed during the cooking of starchy foods. Assessment of human risks from toxicants is routinely performed using laboratory rodents, and such testing requires careful control of unintended exposures, particularly through the diet. This study describes an analytical method based on liquid chromatography with electrospray tandem mass spectrometry that was used to measure endogenous AA in rodent diets and to survey a number of commercial products for contamination. Method sensitivity permitted accurate quantification of endogenous levels of AA in raw diets below 20 ppb. Autoclaving a standard rodent diet (NIH-31) increased the AA content 14-fold, from 17 to 240 ppb. A nutritionally equivalent diet that was sterilized by irradiation was found to contain approximately 10 ppb of AA (NIH-31IR). A toxicokinetic study of AA and its epoxide metabolite, glycidamide, was performed by switching mice from NIH-31IR to the autoclaved diet for a 30 min feeding period (average AA dose administered was 4.5 microg/kg of body weight). The concentrations of AA and glycidamide were measured in serum collected at various times. The elimination half-lives and the areas under the respective concentration-time curves were similar for AA and glycidamide. Mice maintained on autoclaved NIH-31 diet, but otherwise untreated, showed elevated steady state levels of a glycidamide-derived DNA adduct in liver relative to mice maintained on the irradiated diet. This study demonstrates that a heat sterilization procedure used in laboratory animal husbandry (i.e., autoclaving) can lead to the formation of significant levels of AA in basal diets used for toxicity testing. AA in rodent diets is bioavailable, is distributed to tissues, and is metabolically activated to a genotoxic metabolite, which produces quantifiable cumulative DNA damage. Although the contribution of endogenous AA to the incidence of tumors in multiple organs of rodents otherwise untreated in chronic carcinogenicity bioassays (i.e., control groups) is not known, the reduction of endogenous AA through the use of a suitable irradiated diet was deemed to be critical for ongoing studies of AA carcinogenicity and neurotoxicity.

Computer simulation analysis of normal and abnormal development of the mammalian diaphragm.

PubMed

Fisher, Jason C; Bodenstein, Lawrence

2006-02-17

Congenital diaphragmatic hernia (CDH) is a birth defect with significant morbidity and mortality. Knowledge of diaphragm morphogenesis and the aberrations leading to CDH is limited. Although classical embryologists described the diaphragm as arising from the septum transversum, pleuroperitoneal folds (PPF), esophageal mesentery and body wall, animal studies suggest that the PPF is the major, if not sole, contributor to the muscular diaphragm. Recently, a posterior defect in the PPF has been identified when the teratogen nitrofen is used to induce CDH in fetal rodents. We describe use of a cell-based computer modeling system (Nudge++) to study diaphragm morphogenesis. Key diaphragmatic structures were digitized from transverse serial sections of paraffin-embedded mouse embryos at embryonic days 11.5 and 13. Structure boundaries and simulated cells were combined in the Nudge++ software. Model cells were assigned putative behavioral programs, and these programs were progressively modified to produce a diaphragm consistent with the observed anatomy in rodents. Homology between our model and recent anatomical observations occurred under the following simulation conditions: (1) cell mitoses are restricted to the edge of growing tissue; (2) cells near the chest wall remain mitotically active; (3) mitotically active non-edge cells migrate toward the chest wall; and (4) movement direction depends on clonal differentiation between anterior and posterior PPF cells. With the PPF as the sole source of mitotic cells, an early defect in the PPF evolves into a posteromedial diaphragm defect, similar to that of the rodent nitrofen CDH model. A posterolateral defect, as occurs in human CDH, would be more readily recreated by invoking other cellular contributions. Our results suggest that recent reports of PPF-dominated diaphragm morphogenesis in the rodent may not be strictly applicable to man. The ability to recreate a CDH defect using a combination of experimental data and testable hypotheses gives impetus to simulation modeling as an adjunct to experimental analysis of diaphragm morphogenesis.

11β-Hydroxysteroid Dehydrogenase Type 1 Regulates Glucocorticoid-Induced Insulin Resistance in Skeletal Muscle

PubMed Central

Morgan, Stuart A.; Sherlock, Mark; Gathercole, Laura L.; Lavery, Gareth G.; Lenaghan, Carol; Bujalska, Iwona J.; Laber, David; Yu, Alice; Convey, Gemma; Mayers, Rachel; Hegyi, Krisztina; Sethi, Jaswinder K.; Stewart, Paul M.; Smith, David M.; Tomlinson, Jeremy W.

2009-01-01

OBJECTIVE Glucocorticoid excess is characterized by increased adiposity, skeletal myopathy, and insulin resistance, but the precise molecular mechanisms are unknown. Within skeletal muscle, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts cortisone (11-dehydrocorticosterone in rodents) to active cortisol (corticosterone in rodents). We aimed to determine the mechanisms underpinning glucocorticoid-induced insulin resistance in skeletal muscle and indentify how 11β-HSD1 inhibitors improve insulin sensitivity. RESEARCH DESIGN AND METHODS Rodent and human cell cultures, whole-tissue explants, and animal models were used to determine the impact of glucocorticoids and selective 11β-HSD1 inhibition upon insulin signaling and action. RESULTS Dexamethasone decreased insulin-stimulated glucose uptake, decreased IRS1 mRNA and protein expression, and increased inactivating pSer307 insulin receptor substrate (IRS)-1. 11β-HSD1 activity and expression were observed in human and rodent myotubes and muscle explants. Activity was predominantly oxo-reductase, generating active glucocorticoid. A1 (selective 11β-HSD1 inhibitor) abolished enzyme activity and blocked the increase in pSer307 IRS1 and reduction in total IRS1 protein after treatment with 11DHC but not corticosterone. In C57Bl6/J mice, the selective 11β-HSD1 inhibitor, A2, decreased fasting blood glucose levels and improved insulin sensitivity. In KK mice treated with A2, skeletal muscle pSer307 IRS1 decreased and pThr308 Akt/PKB increased. In addition, A2 decreased both lipogenic and lipolytic gene expression. CONCLUSIONS Prereceptor facilitation of glucocorticoid action via 11β-HSD1 increases pSer307 IRS1 and may be crucial in mediating insulin resistance in skeletal muscle. Selective 11β-HSD1 inhibition decreases pSer307 IRS1, increases pThr308 Akt/PKB, and decreases lipogenic and lipolytic gene expression that may represent an important mechanism underpinning their insulin-sensitizing action. PMID:19675138

Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications

PubMed Central

Freeman, Sara M.; Young, Larry J.

2016-01-01

In the last several decades, sophisticated experimental techniques have been used to determine the neurobiology of the oxytocin and vasopressin systems in rodents. Using a suite of methodologies, including electrophysiology, site-specific selective pharmacology, receptor autoradiography, in vivo microdialysis, and genetic and optogenetic manipulations, we have gained unprecedented knowledge about how these neuropeptides engage neural circuits to regulate behaviour, particularly social behaviour. Based on this foundation of information from rodent studies, we have started generating new hypotheses and frameworks about how the oxytocin and vasopressin systems could be acting in humans to influence social cognition. However, despite the recent inundation of publications using intranasal oxytocin in humans, we still know very little about the neurophysiology of the oxytocin system in primates more broadly. Furthermore, the design and analysis of these human studies have remained largely uninformed of the potential neurobiological mechanisms underlying their findings. Although the methods available for studying the oxytocin and vasopressin systems in humans are incredibly limited as a result of practical and ethical considerations, there is great potential to fill the gaps in our knowledge by developing better nonhuman primate models of social functioning. Behavioural pharmacology and receptor autoradiography have been used to study the oxytocin and vasopressin systems in nonhuman primates, and there is now great potential to broaden our understanding of the neurobiology of these systems. In this review, we discuss comparative findings in receptor distributions in rodents and primates, with perspectives on the functionality of conserved regions of expression in these distinct mammalian clades. We also identify specific ways that established technologies can be used to answer basic research questions in primates. Finally, we highlight areas of future research in nonhuman primates that are experimentally poised to yield critical insights into the anatomy, physiology and behavioural effects of the oxytocin system, given its remarkable translational potential. PMID:26940141

Analysis of the sensitivity properties of a model of vector-borne bubonic plague.

PubMed

Buzby, Megan; Neckels, David; Antolin, Michael F; Estep, Donald

2008-09-06

Model sensitivity is a key to evaluation of mathematical models in ecology and evolution, especially in complex models with numerous parameters. In this paper, we use some recently developed methods for sensitivity analysis to study the parameter sensitivity of a model of vector-borne bubonic plague in a rodent population proposed by Keeling & Gilligan. The new sensitivity tools are based on a variational analysis involving the adjoint equation. The new approach provides a relatively inexpensive way to obtain derivative information about model output with respect to parameters. We use this approach to determine the sensitivity of a quantity of interest (the force of infection from rats and their fleas to humans) to various model parameters, determine a region over which linearization at a specific parameter reference point is valid, develop a global picture of the output surface, and search for maxima and minima in a given region in the parameter space.

Gene Therapy for the Treatment of Diabetic Neuropathy

PubMed Central

Mata, Marina; Chattopadhyay, Munmun; Fink, David J

2009-01-01

Neuropathy is a common, untreatable complication of both type 1 and type 2 diabetes. In animal models peptide neurotrophic factors can be used to protect against the development of neuropathy, but the combination of short half-life and off-target effects of these potent pleiotropic peptides has limited translation to human therapy. Gene transfer is a promising strategy that might circumvent these limitations. In this essay we review the basic methods of gene transfer and the preclinical data in rodent models that support the utility of this approach in the treatment of diabetic neuropathy. The path to a clinical applications and potential pitfalls in developing gene therapy for the treatment of diabetic neuropathy are considered. PMID:18990298

Exercise offers anxiolytic potential: A role for stress and brain noradrenergic-galaninergic mechanisms

PubMed Central

Sciolino, Natale R.; Holmes, Philip V.

2016-01-01

Although physical activity reduces anxiety in humans, the neural basis for this response is unclear. Rodent models are essential to understand the mechanisms that underlie the benefits of exercise. However, it is controversial whether exercise exerts anxiolytic-like potential in rodents. Evidence is reviewed to evaluate the effects of wheel running, an experimental mode of exercise in rodents, on behavior in tests of anxiety and on norepinephrine and galanin systems in neural circuits that regulate stress. Stress is proposed to account for mixed behavioral findings in this literature. Indeed, running promotes an adaptive response to stress and alters anxiety-like behaviors in a manner dependent on stress. Running amplifies galanin expression in noradrenergic locus coeruleus (LC) and suppresses stress-induced activity of the LC and norepinephrine output in LC-target regions. Thus, enhanced galanin-mediated suppression of brain norepinephrine in runners is supported by current literature as a mechanism that may contribute to the stress-protective effects of exercise. These data support the use of rodents to study the emotional and neurobiological consequences of exercise. PMID:22771334

STUDY OF THE PREVALENCE OF Capillaria hepatica IN HUMANS AND RODENTS IN AN URBAN AREA OF THE CITY OF PORTO VELHO, RONDÔNIA, BRAZIL

PubMed Central

da Rocha, Elierson José Gomes; Basano, Sérgio de Almeida; de Souza, Márcia Maria; Honda, Eduardo Resende; de Castro, Márcio Botelho; Colodel, Edson Moleta; Silva, Jéssica Carolinne Damasceno e; Barros, Lauro Prado; Rodrigues, Elisa Sousa; Camargo, Luís Marcelo Aranha

2015-01-01

Introduction: Hepatic capillariosis, caused by Capillaria hepatica (Calodium hepaticum) (Bancroft, 1893), Travassos, 1915 (Nematoda, Trichinelloidea, Capillariidae), is a common zoonosis in rodents but is rare in humans. Seventy-two cases in humans have been reported worldwide since the first case was described by MACARTHUR in 192417,27. This study aimed to determine the prevalence of Capillaria hepatica in humans and rodents in an urban area of Porto Velho, the capital of Rondônia, in Brazil. Methods: After conducting a census of the area, 490 residents were randomly selected, and, after signing a term of consent, provided blood samples that were screened for anti-Capillaria hepatica antibodies. Simultaneously, rats were captured to assess the prevalence of this parasite in rodents by histopathological examination in liver sections. Results: A prevalence of 1.8% was found among residents who had specific antibodies at a dilution of 1:150, indicating exposure to parasite eggs; 0.8% of the subjects also had positive titers at a dilution of 1:400, indicating true infection. The prevalence in rats was 2%. Conclusions: The prevalence of infection with this parasite among humans and rats was low. While the prevalence encountered among humans was within the limits reported in the literature, the prevalence among rodents was much lower. PMID:25651325

Automated evaluation of liver fibrosis in thioacetamide, carbon tetrachloride, and bile duct ligation rodent models using second-harmonic generation/two-photon excited fluorescence microscopy.

PubMed

Liu, Feng; Chen, Long; Rao, Hui-Ying; Teng, Xiao; Ren, Ya-Yun; Lu, Yan-Qiang; Zhang, Wei; Wu, Nan; Liu, Fang-Fang; Wei, Lai

2017-01-01

Animal models provide a useful platform for developing and testing new drugs to treat liver fibrosis. Accordingly, we developed a novel automated system to evaluate liver fibrosis in rodent models. This system uses second-harmonic generation (SHG)/two-photon excited fluorescence (TPEF) microscopy to assess a total of four mouse and rat models, using chemical treatment with either thioacetamide (TAA) or carbon tetrachloride (CCl 4 ), and a surgical method, bile duct ligation (BDL). The results obtained by the new technique were compared with that using Ishak fibrosis scores and two currently used quantitative methods for determining liver fibrosis: the collagen proportionate area (CPA) and measurement of hydroxyproline (HYP) content. We show that 11 shared morphological parameters faithfully recapitulate Ishak fibrosis scores in the models, with high area under the receiver operating characteristic (ROC) curve (AUC) performance. The AUC values of 11 shared parameters were greater than that of the CPA (TAA: 0.758-0.922 vs 0.752-0.908; BDL: 0.874-0.989 vs 0.678-0.966) in the TAA mice and BDL rat models and similar to that of the CPA in the TAA rat and CCl 4 mouse models. Similarly, based on the trends in these parameters at different time points, 9, 10, 7, and 2 model-specific parameters were selected for the TAA rats, TAA mice, CCl 4 mice, and BDL rats, respectively. These parameters identified differences among the time points in the four models, with high AUC accuracy, and the corresponding AUC values of these parameters were greater compared with those of the CPA in the TAA rat and mouse models (rats: 0.769-0.894 vs 0.64-0.799; mice: 0.87-0.93 vs 0.739-0.836) and similar to those of the CPA in the CCl 4 mouse and BDL rat models. Similarly, the AUC values of 11 shared parameters and model-specific parameters were greater than those of HYP in the TAA rats, TAA mice, and CCl 4 mouse models and were similar to those of HYP in the BDL rat models. The automated evaluation system, combined with 11 shared parameters and model-specific parameters, could specifically, accurately, and quantitatively stage liver fibrosis in animal models.

Applicator Training Manual for: Public Health Pest Control.

ERIC Educational Resources Information Center

Moore, E. E.

This manual gives the life cycle and habitats, public health importance, methods of non-chemical control, and pesticides and methods of application for mosquitoes, flies, bedbugs, fleas, lice, cockroaches, venomous anthropods, ticks and chiggers, and rodents. (BB)

New Development in NASA's Rodent Research Hardware for Conducting Long Duration Biomedical and Basic Research in Space

NASA Technical Reports Server (NTRS)

Shirazi-Fard, Y.; Choi, S.; Harris, C.; Gong, C.; Beegle, J. E.; Stube, K. C.; Martin, K. J.; Nevitt, R. G.; Globus, R. G.

2017-01-01

Animal models, particularly rodents, are the foundation of pre-clinical research to understand human diseases and evaluate new therapeutics, and play a key role in advancing biomedical discoveries both on Earth and in space. The National Research Councils Decadal survey emphasized the importance of expanding NASAs life sciences research to perform long duration, rodent experiments on the International Space Station (ISS). To accomplish this objective, flight hardware, operations, and science capabilities were developed at NASA Ames Research Center (ARC) to enhance science return for both commercial (CASIS) and government-sponsored rodent research. The Rodent Research program at NASA ARC has pioneered a new research capability on the International Space Station and has progressed toward translating research to the ISS utilizing commercial rockets, collaborating with academia and science industry, while training crewmembers to assist in performing research on orbit. Throughout phases of these missions, our practices, hardware and operations have evolved from tested to developed standards, and we are able to modify and customize our procedure and operations for mission specific requirements. The Rodent Research Habitat is capable of providing a living environment for animals on ISS according to standard animal welfare requirements. Using the cameras in the Habitat, the Rodent Research team has the ability to perform daily health checks on animals, and further analyze the collected videos for behavioral studies. A recent development of the Rodent Research hardware is inclusion of enrichment, to provide the animals the ability to rest and huddle. The Enrichment Hut is designed carefully for adult mice (up to 35 week old) within animal welfare, engineering, and operations constraints. The Hut is made out of the same stainless steel mesh as the cage interior, it has an ingress and an egress to allow animals move freely, and a hinge door to allow crewmembers remove the animals easily. The Rodent Research team has also developed Live Animal Return (LAR) capability, which will be implemented during Rodent Research-5 mission for the first time. The animals will be transported from the Habitat to a Transporter, which will return on the Dragon capsule and splashes down in the Pacific Ocean. Once SpaceX retrieves the Dragon, all powered payloads will be transferred to a SeaVan and transferred to the Long Beach pier. The NASA team then receives the transporter and delivers to a PI-designated laboratory within 120 mile radius of Long Beach. This is a significant improvement allowing researchers to examine animals within 72 hrs. of reentry or to conduct recovery experiments. Together, the hardware improvements and experience that the Rodent Research team has gained working with principal investigators and ISS crew to conduct complex experiments on orbit are expanding capabilities for long duration rodent research on the ISS to achieve both basic science and biomedical objectives.

A rodent brain-machine interface paradigm to study the impact of paraplegia on BMI performance.

PubMed

Bridges, Nathaniel R; Meyers, Michael; Garcia, Jonathan; Shewokis, Patricia A; Moxon, Karen A

2018-05-31

Most brain machine interfaces (BMI) focus on upper body function in non-injured animals, not addressing the lower limb functional needs of those with paraplegia. A need exists for a novel BMI task that engages the lower body and takes advantage of well-established rodent spinal cord injury (SCI) models to study methods to improve BMI performance. A tilt BMI task was designed that randomly applies different types of tilts to a platform, decodes the tilt type applied and rights the platform if the decoder correctly classifies the tilt type. The task was tested on female rats and is relatively natural such that it does not require the animal to learn a new skill. It is self-rewarding such that there is no need for additional rewards, eliminating food or water restriction, which can be especially hard on spinalized rats. Finally, task difficulty can be adjusted by making the tilt parameters. This novel BMI task bilaterally engages the cortex without visual feedback regarding limb position in space and animals learn to improve their performance both pre and post-SCI.Comparison with Existing Methods: Most BMI tasks primarily engage one hemisphere, are upper-body, rely heavily on visual feedback, do not perform investigations in animal models of SCI, and require nonnaturalistic extrinsic motivation such as water rewarding for performance improvement. Our task addresses these gaps. The BMI paradigm presented here will enable researchers to investigate the interaction of plasticity after SCI and plasticity during BMI training on performance. Copyright © 2018. Published by Elsevier B.V.

Control of Domestic Rats & Mice, Training Guide--Rodent Control Series.

ERIC Educational Resources Information Center

Bjornson, Bayard F.; And Others

As one booklet in a series on rodent control, this training guide has been developed to assist administrators, rodent-control operators, and others responsible for rodent-control operations in the training of employees in this field. Topics covered include rodents and human welfare, description and habits of domestic rats and mice, rodent-borne…

Optimal decision-making in mammals: insights from a robot study of rodent texture discrimination

PubMed Central

Lepora, Nathan F.; Fox, Charles W.; Evans, Mathew H.; Diamond, Mathew E.; Gurney, Kevin; Prescott, Tony J.

2012-01-01

Texture perception is studied here in a physical model of the rat whisker system consisting of a robot equipped with a biomimetic vibrissal sensor. Investigations of whisker motion in rodents have led to several explanations for texture discrimination, such as resonance or stick-slips. Meanwhile, electrophysiological studies of decision-making in monkeys have suggested a neural mechanism of evidence accumulation to threshold for competing percepts, described by a probabilistic model of Bayesian sequential analysis. For our robot whisker data, we find that variable reaction-time decision-making with sequential analysis performs better than the fixed response-time maximum-likelihood estimation. These probabilistic classifiers also use whatever available features of the whisker signals aid the discrimination, giving improved performance over a single-feature strategy, such as matching the peak power spectra of whisker vibrations. These results cast new light on how the various proposals for texture discrimination in rodents depend on the whisker contact mechanics and suggest the possibility of a common account of decision-making across mammalian species. PMID:22279155

Brain Stimulation Reward Supports More Consistent and Accurate Rodent Decision-Making than Food Reward.

PubMed

McMurray, Matthew S; Conway, Sineadh M; Roitman, Jamie D

2017-01-01

Animal models of decision-making rely on an animal's motivation to decide and its ability to detect differences among various alternatives. Food reinforcement, although commonly used, is associated with problematic confounds, especially satiety. Here, we examined the use of brain stimulation reward (BSR) as an alternative reinforcer in rodent models of decision-making and compared it with the effectiveness of sugar pellets. The discriminability of various BSR frequencies was compared to differing numbers of sugar pellets in separate free-choice tasks. We found that BSR was more discriminable and motivated greater task engagement and more consistent preference for the larger reward. We then investigated whether rats prefer BSR of varying frequencies over sugar pellets. We found that animals showed either a clear preference for sugar reward or no preference between reward modalities, depending on the frequency of the BSR alternative and the size of the sugar reward. Overall, these results suggest that BSR is an effective reinforcer in rodent decision-making tasks, removing food-related confounds and resulting in more accurate, consistent, and reliable metrics of choice.

Molecular evidence of Rickettsia spp. in ixodid ticks and rodents in suburban, natural and rural habitats in Slovakia.

PubMed

Minichová, Lenka; Hamšíková, Zuzana; Mahríková, Lenka; Slovák, Mirko; Kocianová, Elena; Kazimírová, Mária; Škultéty, Ľudovít; Štefanidesová, Katarína; Špitalská, Eva

2017-03-24

Natural foci of tick-borne spotted fever group (SFG) rickettsiae of public health concern have been found in Slovakia, but the role of rodents in their circulation is unclear. Ticks (Ixodes ricinus, Ixodes trianguliceps, Dermacentor marginatus, Dermacentor reticulatus, Haemaphysalis concinna and Haemaphysalis inermis) and tissues of rodents (Apodemus flavicollis, Apodemus sylvaticus, Myodes glareolus, Microtus arvalis, Microtus subterraneus and Micromys minutus) were examined for the presence of SFG rickettsiae and Coxiella burnetii by molecular methods. Suburban, natural and rural habitats were monitored to acquire information on the role of ticks and rodents in the agents' maintenance in various habitat types of Slovakia. The overall prevalence of rickettsial infection in questing I. ricinus and D. marginatus was 6.6% and 21.4%, respectively. Rickettsia helvetica, R. monacensis and non-identified rickettsial species were detected in I. ricinus, whereas R. slovaca and R. raoultii were identified in D. marginatus. Rickettsia spp.-infected I. ricinus occurred during the whole tick questing period. Rickettsia helvetica dominated (80.5%) followed by R. monacensis (6.5%). The species were present in all studied habitats. Rickettsia slovaca (66.7%) and R. raoultii (33.3%) were identified in D. marginatus from the rural habitat. Apodemus flavicollis was the most infested rodent species with I. ricinus, but My. glareolus carried the highest proportion of Rickettsia-positive I. ricinus larvae. Only 0.5% of rodents (A. flavicollis) and 5.2% of engorged I. ricinus removed from My. glareolus, A. flavicollis and M. arvalis were R. helvetica- and R. monacensis-positive. Coxiella burnetii was not detected in any of the tested samples. We hypothesize that rodents could play a role as carriers of infected ticks and contribute to the maintenance of rickettsial pathogens in natural foci. Long-term presence of SFG Rickettsia spp. was confirmed in questing ticks from different habitat types of Slovakia. The results suggest a human risk for infection with the pathogenic R. helvetica, R. monacensis, R. slovaca and R. raoultii.

Prevention of chemotherapy-induced alopecia in rodent models

PubMed Central

Jimenez, Joaquin J.; Roberts, Stephen M.; Mejia, Jessica; Mauro, Lucia M.; Munson, John W.; Elgart, George W.; Connelly, Elizabeth Alvarez; Chen, Qingbin; Zou, Jiangying; Goldenberg, Carlos

2008-01-01

Alopecia (hair loss) is experienced by thousands of cancer patients every year. Substantial-to-severe alopecia is induced by anthracyclines (e.g., adriamycin), taxanes (e.g., taxol), alkylating compounds (e.g., cyclophosphamide), and the topisomerase inhibitor etoposide, agents that are widely used in the treatment of leukemias and breast, lung, ovarian, and bladder cancers. Currently, no treatment appears to be generally effective in reliably preventing this secondary effect of chemotherapy. We observed in experiments using different rodent models that localized administration of heat or subcutaneous/intradermal injection of geldanamycin or 17-(allylamino)-17-demethoxygeldanamycin induced a stress protein response in hair follicles and effectively prevented alopecia from adriamycin, cyclophosphamide, taxol, and etoposide. Model tumor therapy experiments support the presumption that such localized hair-saving treatment does not negatively affect chemotherapy efficacy. PMID:18347939

A comparison of the biological properties of small molecular weight agonists and antagonists of CD200:CD200R interactions.

PubMed

Gorczynski, Reg; Boudakov, Ivo; Khatri, Ismat

2008-11-01

Our laboratory and others have documented in some detail the immunological consequences which follow from interaction of the ubiquitously expressed molecule CD200 with its receptor(s) CD200R (expressed predominantly on cells of myeloid and lymphoid origin). In particular, there is evidence that these interactions lead to immunosuppressive signals which modulate graft rejection responses; decrease the manifestations of arthritis in rodent models; diminish mast cell mediator release in models of allergic disease; and favour the growth of tumors in both mice and humans. The development of small molecular weight agonists (and/or antagonists) of these interactions would thus likely have significant clinical importance. The data reported herein characterizes several such molecules in a number of rodent models.

Borrelia afzelii ospC genotype diversity in Ixodes ricinus questing ticks and ticks from rodents in two Lyme borreliosis endemic areas: contribution of co-feeding ticks.

PubMed

Pérez, David; Kneubühler, Yvan; Rais, Olivier; Jouda, Fatima; Gern, Lise

2011-09-01

In Europe, the Lyme borreliosis (LB) agents like Borrelia burgdorferi sensu stricto (ss), B. afzelii, and B. garinii are maintained in nature by enzoonotic transmission cycles between vertebrate hosts and Ixodes ricinus ticks. The outer surface protein C is a highly antigenic protein expressed by spirochaetes during transmission from ticks to mammals as well as during dissemination in the vertebrate hosts. Previous studies based on analysis of ospC gene sequences have led to the classification of ospC genotypes into ospC groups. The aim of this study was to analyse and compare ospC group distribution among isolates of the rodent-associated genospecies, B. afzelii, at 3 levels (questing ticks, ticks feeding on rodents, and xenodiagnostic ticks). Isolates were obtained during a study carried out in 2 LB endemic areas located on the Swiss Plateau [Portes-Rouges (PR) and Staatswald (SW)], where rodents were differently infested by co-feeding ticks (Pérez et al., unpublished data). Overall, we identified 10 different ospC groups with different distributions among isolates from questing ticks, ticks that detached from rodents, and xenodiagnostic ticks at the 2 sites. We observed a higher ospC diversity among isolates from ticks that fed on rodents at SW, and mixed infections with 2 ospC groups were also more frequent among isolates from ticks that fed on rodents at SW (n=18) than at PR (n=1). At both sites, B. afzelii isolates obtained from larvae that were feeding on the rodents simultaneously with nymphs displayed a higher diversity of ospC groups (mean number of ospC groups: 2.25 for PR and 1.75 for SW) than isolates from larvae feeding without nymphs (mean number of ospC groups: 1.17 for PR and 1 for SW). We suggest that co-feeding transmission of Borrelia, previously described in laboratory models, contributes in nature in promoting and maintaining ospC diversity within local tick populations. Copyright © 2011 Elsevier GmbH. All rights reserved.

Modeling zoonotic cutaneous leishmaniasis incidence in central Tunisia from 2009-2015: Forecasting models using climate variables as predictors

PubMed Central

Bellali, Hedia; Ben-Alaya, Nissaf; Saez, Marc; Malouche, Dhafer; Chahed, Mohamed Kouni

2017-01-01

Transmission of zoonotic cutaneous leishmaniasis (ZCL) depends on the presence, density and distribution of Leishmania major rodent reservoir and the development of these rodents is known to have a significant dependence on environmental and climate factors. ZCL in Tunisia is one of the most common forms of leishmaniasis. The aim of this paper was to build a regression model of ZCL cases to identify the relationship between ZCL occurrence and possible risk factors, and to develop a predicting model for ZCL's control and prevention purposes. Monthly reported ZCL cases, environmental and bioclimatic data were collected over 6 years (2009–2015). Three rural areas in the governorate of Sidi Bouzid were selected as the study area. Cross-correlation analysis was used to identify the relevant lagged effects of possible risk factors, associated with ZCL cases. Non-parametric modeling techniques known as generalized additive model (GAM) and generalized additive mixed models (GAMM) were applied in this work. These techniques have the ability to approximate the relationship between the predictors (inputs) and the response variable (output), and express the relationship mathematically. The goodness-of-fit of the constructed model was determined by Generalized cross-validation (GCV) score and residual test. There were a total of 1019 notified ZCL cases from July 2009 to June 2015. The results showed seasonal distribution of reported ZCL cases from August to January. The model highlighted that rodent density, average temperature, cumulative rainfall and average relative humidity, with different time lags, all play role in sustaining and increasing the ZCL incidence. The GAMM model could be applied to predict the occurrence of ZCL in central Tunisia and could help for the establishment of an early warning system to control and prevent ZCL in central Tunisia. PMID:28841642

Modeling zoonotic cutaneous leishmaniasis incidence in central Tunisia from 2009-2015: Forecasting models using climate variables as predictors.

PubMed

Talmoudi, Khouloud; Bellali, Hedia; Ben-Alaya, Nissaf; Saez, Marc; Malouche, Dhafer; Chahed, Mohamed Kouni

2017-08-01

Transmission of zoonotic cutaneous leishmaniasis (ZCL) depends on the presence, density and distribution of Leishmania major rodent reservoir and the development of these rodents is known to have a significant dependence on environmental and climate factors. ZCL in Tunisia is one of the most common forms of leishmaniasis. The aim of this paper was to build a regression model of ZCL cases to identify the relationship between ZCL occurrence and possible risk factors, and to develop a predicting model for ZCL's control and prevention purposes. Monthly reported ZCL cases, environmental and bioclimatic data were collected over 6 years (2009-2015). Three rural areas in the governorate of Sidi Bouzid were selected as the study area. Cross-correlation analysis was used to identify the relevant lagged effects of possible risk factors, associated with ZCL cases. Non-parametric modeling techniques known as generalized additive model (GAM) and generalized additive mixed models (GAMM) were applied in this work. These techniques have the ability to approximate the relationship between the predictors (inputs) and the response variable (output), and express the relationship mathematically. The goodness-of-fit of the constructed model was determined by Generalized cross-validation (GCV) score and residual test. There were a total of 1019 notified ZCL cases from July 2009 to June 2015. The results showed seasonal distribution of reported ZCL cases from August to January. The model highlighted that rodent density, average temperature, cumulative rainfall and average relative humidity, with different time lags, all play role in sustaining and increasing the ZCL incidence. The GAMM model could be applied to predict the occurrence of ZCL in central Tunisia and could help for the establishment of an early warning system to control and prevent ZCL in central Tunisia.

Rodent consumption in Khon Kaen Province, Thailand.

PubMed

Suwannarong, Kanokwan; Chapman, Robert S

2014-09-01

Rodents are important reservoirs of rodent-borne infections worldwide, including Southeast Asia and Northeast Thailand (Isaan), where rodent consumption may be a source of rodent-borne diseases. The behavior of consuming rodents is related to a population's traditions, knowledge, cultural, and household contexts, among other factors. This cross-sectional survey was conducted in Khon Kaen Province, Thailand during November-December 2011. It aimed to elicit information about rodent consumption among residents of this province, and to identify factors associated with rodent consumption there. Multiple logistic regression analysis indicated that male gender, large family size, and use of rainwater as the main source of drinking water were positively associated with reported rodent consumption in this province, while having proper knowledge/attitudes towards animal-borne disease was negatively associated. These results provide evidence-base information for further studies, such as participatory ac- tion research, to further explore how people interact with rodents in different contexts. Further research is also needed to characterize risk of zoonotic diseases in relation to rodent consumption.

Traffic-related air pollution and brain development.

PubMed

Woodward, Nicholas; Finch, Caleb E; Morgan, Todd E

Automotive traffic-related air pollution (TRP) imposes an increasing health burden with global urbanization. Gestational and early child exposure to urban TRP is associated with higher risk of autism spectrum disorders and schizophrenia, as well as low birth weight. While cardio-respiratory effects from exposure are well documented, cognitive effects are only recently becoming widely recognized. This review discusses effects of TRP on brain and cognition in human and animal studies. The mechanisms underlying these epidemiological associations are studied with rodent models of pre- and neonatal exposure to TRP, which show persisting inflammatory changes and altered adult behaviors and cognition. Some behavioral and inflammatory changes show male bias. Rodent models may identify dietary and other interventions for neuroprotection to TRP.

Rodent Auditory Perception: Critical Band Limitations and Plasticity

PubMed Central

King, Julia; Insanally, Michele; Jin, Menghan; Martins, Ana Raquel O.; D'amour, James A.; Froemke, Robert C.

2015-01-01

What do animals hear? While it remains challenging to adequately assess sensory perception in animal models, it is important to determine perceptual abilities in model systems to understand how physiological processes and plasticity relate to perception, learning, and cognition. Here we discuss hearing in rodents, reviewing previous and recent behavioral experiments querying acoustic perception in rats and mice, and examining the relation between behavioral data and electrophysiological recordings from the central auditory system. We focus on measurements of critical bands, which are psychoacoustic phenomena that seem to have a neural basis in the functional organization of the cochlea and the inferior colliculus. We then discuss how behavioral training, brain stimulation, and neuropathology impact auditory processing and perception. PMID:25827498

The pathogenesis of bleomycin-induced lung injury in animals and its applicability to human idiopathic pulmonary fibrosis.

PubMed

Williamson, James D; Sadofsky, Laura R; Hart, Simon P

2015-03-01

Idiopathic pulmonary fibrosis (IPF) is a devastating disease of unknown etiology, for which there is no curative pharmacological therapy. Bleomycin, an anti-neoplastic agent that causes lung fibrosis in human patients has been used extensively in rodent models to mimic IPF. In this review, we compare the pathogenesis and histological features of human IPF and bleomycin-induced pulmonary fibrosis (BPF) induced in rodents by intratracheal delivery. We discuss the current understanding of IPF and BPF disease development, from the contribution of alveolar epithelial cells and inflammation to the role of fibroblasts and cytokines, and draw conclusions about what we have learned from the intratracheal bleomycin model of lung fibrosis.

Social defeat models in animal science: What we have learned from rodent models.

PubMed

Toyoda, Atsushi

2017-07-01

Studies on stress and its impacts on animals are very important in many fields of science, including animal science, because various stresses influence animal production and animal welfare. In particular, the social stresses within animal groups have profound impact on animals, with the potential to induce abnormal behaviors and health problems. In humans, social stress induces several health problems, including psychiatric disorders. In animal stress models, social defeat models are well characterized and used in various research fields, particularly in studies concerning mental disorders. Recently, we have focused on behavior, nutrition and metabolism in rodent models of social defeat to elucidate how social stresses affect animals. In this review, recent significant progress in studies related to animal social defeat models are described. In the field of animal science, these stress models may contribute to advances in the development of functional foods and in the management of animal welfare. © 2017 The Authors. Animal Science Journal published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Animal Science.

Rodent model choice has major impact on variability of standard preclinical readouts associated with diabetes and obesity research

PubMed Central

Jensen, Victoria S; Porsgaard, Trine; Lykkesfeldt, Jens; Hvid, Henning

2016-01-01

Laboratory rodents are available as either genetically defined inbred strains or genetically undefined outbred stocks. As outbred rodents are generally thought to display a higher level of phenotypic variation compared to inbred strains, it has been argued that experimental studies should preferentially be performed by using inbred rodents. However, very few studies with adequate sample sizes have in fact compared phenotypic variation between inbred strains and outbred stocks of rodents and moreover, these studies have not reached consistent conclusions. The aim of the present study was to compare the phenotypic variation in commonly used experimental readouts within obesity and diabetes research, for four of the most frequently used mouse strains: inbred C57BL/6 and BALB/c and outbred NMRI and CD-1 mice. The variation for all readouts was examined by calculating the coefficient of variation (CV), i.e., the relative variation, including a 95% confidence interval for the CV. We observed that for the majority of the selected readouts, inbred and outbred mice showed comparable phenotypic variation. The observed variation appeared highly influenced by strain choice and type of readout, which suggests that these collectively would serve as more predictive of the phenotypic variation than the more general classification of mice as inbred or outbred based on genetic heterogeneity. PMID:27648148

The application and limitations of mathematical modelling in the prediction of permeability across mammalian skin and polydimethylsiloxane membranes.

PubMed

Moss, Gary P; Sun, Yi; Wilkinson, Simon C; Davey, Neil; Adams, Rod; Martin, Gary P; Prapopopolou, M; Brown, Marc B

2011-11-01

Predicting the rate of percutaneous absorption of a drug is an important issue with the increasing use of the skin as a means of moderating and controlling drug delivery. One key feature of this problem domain is that human skin permeability (as K(p)) has been shown to be inherently non-linear when mathematically related to the physicochemical parameters of penetrants. As such, the aims of this study were to apply and evaluate Gaussian process (GP) regression methods to datasets for membranes other than human skin, and to explore how the nature of the dataset may influence its analysis. Permeability data for absorption across rodent and pig skin, and artificial membranes (polydimethylsiloxane, PDMS, i.e. Silastic) membranes was collected from the literature. Two quantitative structure-permeability relationship (QSPR) models were used to compare with the GP models. Further performance metrics were computed in terms of all predictions, and a range of covariance functions were examined: the squared exponential (SE), neural network (NNone) and rational quadratic (QR) covariance functions, along with two simple cases of Matern covariance function (Matern3 and Matern5) where the polynomial order is set to 1 and 2, respectively. As measures of performance, the correlation coefficient (CORR), negative log estimated predictive density (NLL, or negative log loss) and mean squared error (MSE) were employed. The results demonstrated that GP models with different covariance functions outperform QSPR models for human, pig and rodent datasets. For the artificial membranes, GPs perform better in one instance, and give similar results in other experiments (where different covariance parameters produce similar results). In some cases, the GP predictions for some of the artificial membrane dataset are poorly correlated, suggesting that the physicochemical parameters employed in this study might not be appropriate for developing models that represent this membrane. While the results of this study indicate that permeation across rodent (mouse and rat) and pig skin is, in a statistical sense, similar, and that the artificial membranes are poor replacements of human or animal skin, the overriding issue raised in this study is the nature of the dataset and how it can influence the results, and subsequent interpretation, of any model produced for particular membranes. The size of the datasets, in both absolute and comparative senses, appears to influence model quality. Ideally, to generate viable cross-comparisons the datasets for different mammalian membranes should, wherever possible, exhibit as much commonality as possible. © 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.

Testing episodic memory in animals: a new approach.

PubMed

Griffiths, D P; Clayton, N S

2001-08-01

Episodic memory involves the encoding and storage of memories concerned with unique personal experiences and their subsequent recall, and it has long been the subject of intensive investigation in humans. According to Tulving's classical definition, episodic memory "receives and stores information about temporally dated episodes or events and temporal-spatial relations among these events." Thus, episodic memory provides information about the 'what' and 'when' of events ('temporally dated experiences') and about 'where' they happened ('temporal-spatial relations'). The storage and subsequent recall of this episodic information was thought to be beyond the memory capabilities of nonhuman animals. Although there are many laboratory procedures for investigating memory for discrete past episodes, until recently there were no previous studies that fully satisfied the criteria of Tulving's definition: they can all be explained in much simpler terms than episodic memory. However, current studies of memory for cache sites in food-storing jays provide an ethologically valid model for testing episodic-like memory in animals, thereby bridging the gap between human and animal studies memory. There is now a pressing need to adapt these experimental tests of episodic memory for other animals. Given the potential power of transgenic and knock-out procedures for investigating the genetic and molecular bases of learning and memory in laboratory rodents, not to mention the wealth of knowledge about the neuroanatomy and neurophysiology of the rodent hippocampus (a brain area heavily implicated in episodic memory), an obvious next step is to develop a rodent model of episodic-like memory based on the food-storing bird paradigm. The development of a rodent model system could make an important contribution to our understanding of the neural, molecular, and behavioral mechanisms of mammalian episodic memory.

Quantitative Structure--Activity Relationship Modeling of Rat Acute Toxicity by Oral Exposure

EPA Science Inventory

Background: Few Quantitative Structure-Activity Relationship (QSAR) studies have successfully modeled large, diverse rodent toxicity endpoints. Objective: In this study, a combinatorial QSAR approach has been employed for the creation of robust and predictive models of acute toxi...

Risk estimates for CO exposure in man based on behavioral and physiological responses in rodents

NASA Technical Reports Server (NTRS)

Gross, M. K.

1983-01-01

An examination of animal response to CO is studied along with potential models for extrapolating animal test data to humans. The best models for extrapolating data were found to be the Probit and Weibull models.

Lassa fever or lassa hemorrhagic fever risk to humans from rodent-borne zoonoses.

PubMed

El-Bahnasawy, Mamdouh M; Megahed, Laila Abdel-Mawla; Abdalla Saleh, Hala Ahmed; Morsy, Tosson A

2015-04-01

Viral hemorrhagic fevers (VHFs) typically manifest as rapidly progressing acute febrile syndromes with profound hemorrhagic manifestations and very high fatality rates. Lassa fever, an acute hemorrhagic fever characterized by fever, muscle aches, sore throat, nausea, vomiting, diarrhea and chest and abdominal pain. Rodents are important reservoirs of rodent-borne zoonosis worldwide. Transmission rodents to humans occur by aerosol spread, either from the genus Mastomys rodents' excreta (multimammate rat) or through the close contact with infected patients (nosocomial infection). Other rodents of the genera Rattus, Mus, Lemniscomys, and Praomys are incriminated rodents hosts. Now one may ask do the rodents' ectoparasites play a role in Lassa virus zoonotic transmission. This paper summarized the update knowledge on LHV; hopping it might be useful to the clinicians, nursing staff, laboratories' personals as well as those concerned zoonoses from rodents and rodent control.

A Geographic Information Systems (GIS)-based analysis of modern South African rodent distributions, habitat use, and environmental tolerances.

PubMed

Campbell, Timothy L; Lewis, Patrick J; Thies, Monte L; Williams, Justin K

2012-11-01

GOALS OF THIS STUDY WERE TO: (1) develop distributional maps of modern rodent genera throughout the countries of South Africa, Lesotho, and Swaziland by georeferencing museum specimens; (2) assess habitat preferences for genera by cross-referencing locality position with South African vegetation; and (3) identify mean annual precipitation and temperature range where the genera are located. Conterminous South Africa including the countries of Lesotho and Swaziland Digital databases of rodent museum specimens housed in the Ditsong National Museum of Natural History, South Africa (DM), and the Division of Mammals, National Museum of Natural History, Smithsonian Institution, United States (NMNH), were acquired and then sorted into a subset of specimens with associated coordinate data. The coordinate data were then used to develop distributional maps for the rodent genera present within the study area. Percent habitat occupation and descriptive statistics for six climatic variables were then determined for each genus by cross-referencing locality positions with vegetation and climatic maps. This report presents a series of maps illustrating the distribution of 35 rodent genera based on 19,471 geo-referenced specimens obtained from two major collections. Inferred habitat use by taxon is provided for both locality and specimen percent occurrence at three hierarchical habitat levels: biome, bioregion, and vegetation unit. Descriptive statistics for six climatic variables are also provided for each genus based on locality and specimen percent incidence. As rodent faunas are commonly used in paleoenvironmental reconstructions, an accurate assessment of rodent environmental tolerance ranges is necessary before confidence can be placed in an actualistic model. While the data presented here represent only a subset of the modern geographic distributions for many of the taxa examined, a wide range of environmental regimes are observed, suggesting that more research is necessary in order to accurately reconstruct an environmental signature when these taxa are found in the fossil record.

Surfaces and spaces: troubleshooting the study of dietary niche space overlap between North American stem primates and rodents

NASA Astrophysics Data System (ADS)

Prufrock, Kristen A.; López-Torres, Sergi; Silcox, Mary T.; Boyer, Doug M.

2016-06-01

Dental topographic metrics provide quantitative, biologically meaningful data on the three-dimensional (3D) form of teeth. In this study, three dental topographic metrics (Dirichlet normal energy (DNE), relief index (RFI), and orientation patch count rotated (OPCR)) are used to evaluate the presence of dietary niche overlap between North American plesiadapoid primates (Plesiadapidae, Carpolestidae, and Saxonellidae) and early rodents. Calculation of these metrics requires researchers to modify the 3D surface models of the teeth by cropping them to a region of interest and/or orienting them. The current study therefore also examines the error introduced by cropping and orientation, and evaluates the contribution of these metrics to the niche overlap hypothesis. Our results indicate that cropping creates significantly more variation in RFI than DNE. Furthermore, orientation is an even larger source of variation in the calculation of RFI than cropping. Orientation does not strongly influence OPCR values. However, none of these sources of error are significant enough to undermine the extent to which these metrics can speak to the niche overlap hypothesis. The DNE and RFI results suggest that carpolestids and saxonellids had very different molar morphologies from early rodents, and thus these groups were not adapted to consume the same resources. Some plesiadapids show similar levels of occlusal curvature, relief, and complexity to early rodents. The plesiadapid Chiromyoides, which has distinctively low cusps and weak shearing crest development, has molars that are the most rodent-like of all taxa compared. This suggests that Chiromyoides had a dietary niche that overlapped with early rodents and would have been the most likely to be competing over food resources. Results from the plesiadapoid-rodent dental topographic analysis highlight the utility of DNE for detecting more fine-scaled differences in occlusal surface morphology than OPCR, whereas RFI provided valuable data on the degree to which teeth were high crowned.

Are Synonymous Sites in Primates and Rodents Functionally Constrained?

PubMed

Price, Nicholas; Graur, Dan

2016-01-01

It has been claimed that synonymous sites in mammals are under selective constraint. Furthermore, in many studies the selective constraint at such sites in primates was claimed to be more stringent than that in rodents. Given the larger effective population sizes in rodents than in primates, the theoretical expectation is that selection in rodents would be more effective than that in primates. To resolve this contradiction between expectations and observations, we used processed pseudogenes as a model for strict neutral evolution, and estimated selective constraint on synonymous sites using the rate of substitution at pseudosynonymous and pseudononsynonymous sites in pseudogenes as the neutral expectation. After controlling for the effects of GC content, our results were similar to those from previous studies, i.e., synonymous sites in primates exhibited evidence for higher selective constraint that those in rodents. Specifically, our results indicated that in primates up to 24% of synonymous sites could be under purifying selection, while in rodents synonymous sites evolved neutrally. To further control for shifts in GC content, we estimated selective constraint at fourfold degenerate sites using a maximum parsimony approach. This allowed us to estimate selective constraint using mutational patterns that cause a shift in GC content (GT ↔ TG, CT ↔ TC, GA ↔ AG, and CA ↔ AC) and ones that do not (AT ↔ TA and CG ↔ GC). Using this approach, we found that synonymous sites evolve neutrally in both primates and rodents. Apparent deviations from neutrality were caused by a higher rate of C → A and C → T mutations in pseudogenes. Such differences are most likely caused by the shift in GC content experienced by pseudogenes. We conclude that previous estimates according to which 20-40% of synonymous sites in primates were under selective constraint were most likely artifacts of the biased pattern of mutation.

Rational development of a protective P. vivax vaccine evaluated with transgenic rodent parasite challenge models

PubMed Central

Salman, Ahmed M.; Montoya-Díaz, Eduardo; West, Heather; Lall, Amar; Atcheson, Erwan; Lopez-Camacho, Cesar; Ramesar, Jai; Bauza, Karolis; Collins, Katharine A.; Brod, Florian; Reis, Fernando; Pappas, Leontios; González-Cerón, Lilia; Janse, Chris J.; Hill, Adrian V. S.; Khan, Shahid M.; Reyes-Sandoval, Arturo

2017-01-01

Development of a protective and broadly-acting vaccine against the most widely distributed human malaria parasite, Plasmodium vivax, will be a major step towards malaria elimination. However, a P. vivax vaccine has remained elusive by the scarcity of pre-clinical models to test protective efficacy and support further clinical trials. In this study, we report the development of a highly protective CSP-based P. vivax vaccine, a virus-like particle (VLP) known as Rv21, able to provide 100% sterile protection against a stringent sporozoite challenge in rodent models to malaria, where IgG2a antibodies were associated with protection in absence of detectable PvCSP-specific T cell responses. Additionally, we generated two novel transgenic rodent P. berghei parasite lines, where the P. berghei csp gene coding sequence has been replaced with either full-length P. vivax VK210 or the allelic VK247 csp that additionally express GFP-Luciferase. Efficacy of Rv21 surpassed viral-vectored vaccination using ChAd63 and MVA. We show for the first time that a chimeric VK210/247 antigen can elicit high level cross-protection against parasites expressing either CSP allele, which provide accessible and affordable models suitable to support the development of P. vivax vaccines candidates. Rv21 is progressing to GMP production and has entered a path towards clinical evaluation. PMID:28417968

Population-level consequences of antipredator behavior: a metaphysiological model based on the functional ecology of the leaf-eared mouse.

PubMed

Ramos-Jiliberto, Rodrigo; González-Olivares, Eduardo; Bozinovic, Francisco

2002-08-01

We present a predator-prey metaphysiological model, based on the available behavioral and physiological information of the sigmodontine rodent Phyllotis darwini. The model is focused on the population-level consequences of the antipredator behavior, performed by the rodent population, which is assumed to be an inducible response of predation avoidance. The decrease in vulnerability is explicitly considered to have two associated costs: a decreasing foraging success and an increasing metabolic loss. The model analysis was carried out on a reduced form of the system by means of numerical and analytical tools. We evaluated the stability properties of equilibrium points in the phase plane, and carried out bifurcation analyses of rodent equilibrium density under varying conditions of three relevant parameters. The bifurcation parameters chosen represent predator avoidance effectiveness (A), foraging cost of antipredator behavior (C(1)'), and activity-metabolism cost (C(4)'). Our analysis suggests that the trade-offs involved in antipredator behavior plays a fundamental role in the stability properties of the system. Under conditions of high foraging cost, stability decreases as antipredator effectiveness increases. Under the complementary scenario (not considering the highest foraging costs), the equilibria are either stable when both costs are low, or unstable when both costs are higher, independent of antipredator effectiveness. No evidence of stabilizing effects of antipredator behavior was found. Copyright 2002 Elsevier Science (USA).

Bile acid-induced necrosis in primary human hepatocytes and in patients with obstructive cholestasis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Woolbright, Benjamin L.; Dorko, Kenneth; Antoine, Daniel J.

Accumulation of bile acids is a major mediator of cholestatic liver injury. Recent studies indicate bile acid composition between humans and rodents is dramatically different, as humans have a higher percent of glycine conjugated bile acids and increased chenodeoxycholate content, which increases the hydrophobicity index of bile acids. This increase may lead to direct toxicity that kills hepatocytes, and promotes inflammation. To address this issue, this study assessed how pathophysiological concentrations of bile acids measured in cholestatic patients affected primary human hepatocytes. Individual bile acid levels were determined in serum and bile by UPLC/QTOFMS in patients with extrahepatic cholestasis with,more » or without, concurrent increases in serum transaminases. Bile acid levels increased in serum of patients with liver injury, while biliary levels decreased, implicating infarction of the biliary tracts. To assess bile acid-induced toxicity in man, primary human hepatocytes were treated with relevant concentrations, derived from patient data, of the model bile acid glycochenodeoxycholic acid (GCDC). Treatment with GCDC resulted in necrosis with no increase in apoptotic parameters. This was recapitulated by treatment with biliary bile acid concentrations, but not serum concentrations. Marked elevations in serum full-length cytokeratin-18, high mobility group box 1 protein (HMGB1), and acetylated HMGB1 confirmed inflammatory necrosis in injured patients; only modest elevations in caspase-cleaved cytokeratin-18 were observed. These data suggest human hepatocytes are more resistant to human-relevant bile acids than rodent hepatocytes, and die through necrosis when exposed to bile acids. These mechanisms of cholestasis in humans are fundamentally different to mechanisms observed in rodent models. - Highlights: • Cholestatic liver injury is due to cytoplasmic bile acid accumulation in hepatocytes. • Primary human hepatocytes are resistant to BA-induced injury compared to rodents. • Primary human hepatocytes largely undergo necrosis in response to BA toxicity. • Cholestatic liver injury in vivo is predominantly necrotic with minor apoptosis. • Rodent models of bile acid toxicity may not recapitulate the injury in man.« less

Rodent reservoirs of future zoonotic diseases

PubMed Central

Han, Barbara A.; Schmidt, John Paul; Bowden, Sarah E.; Drake, John M.

2015-01-01

The increasing frequency of zoonotic disease events underscores a need to develop forecasting tools toward a more preemptive approach to outbreak investigation. We apply machine learning to data describing the traits and zoonotic pathogen diversity of the most speciose group of mammals, the rodents, which also comprise a disproportionate number of zoonotic disease reservoirs. Our models predict reservoir status in this group with over 90% accuracy, identifying species with high probabilities of harboring undiscovered zoonotic pathogens based on trait profiles that may serve as rules of thumb to distinguish reservoirs from nonreservoir species. Key predictors of zoonotic reservoirs include biogeographical properties, such as range size, as well as intrinsic host traits associated with lifetime reproductive output. Predicted hotspots of novel rodent reservoir diversity occur in the Middle East and Central Asia and the Midwestern United States. PMID:26038558

Improved inhalation technology for setting safe exposure levels for workplace chemicals

NASA Technical Reports Server (NTRS)

Stuart, Bruce O.

1993-01-01

Threshold Limit Values recommended as allowable air concentrations of a chemical in the workplace are often based upon a no-observable-effect-level (NOEL) determined by experimental inhalation studies using rodents. A 'safe level' for human exposure must then be estimated by the use of generalized safety factors in attempts to extrapolate from experimental rodents to man. The recent development of chemical-specific physiologically-based toxicokinetics makes use of measured physiological, biochemical, and metabolic parameters to construct a validated model that is able to 'scale-up' rodent response data to predict the behavior of the chemical in man. This procedure is made possible by recent advances in personal computer software and the emergence of appropriate biological data, and provides an analytical tool for much more reliable risk evaluation and airborne chemical exposure level setting for humans.

Conversion of sagebrush shrublands to exotic annual grasslands negatively impacts small mammal communities

USGS Publications Warehouse

Ostoja, S.M.; Schupp, E.W.

2009-01-01

Aim The exotic annual cheatgrass (Bromus tectorum) is fast replacing sagebrush (Artemisia tridentata) communities throughout the Great Basin Desert and nearby regions in the Western United States, impacting native plant communities and altering fire regimes, which contributes to the long-term persistence of this weedy species. The effect of this conversion on native faunal communities remains largely unexamined. We assess the impact of conversion from native perennial to exotic annual plant communities on desert rodent communities. Location Wyoming big sagebrush shrublands and nearby sites previously converted to cheatgrass-dominated annual grasslands in the Great Basin Desert, Utah, USA. Methods At two sites in Tooele County, Utah, USA, we investigated with Sherman live trapping whether intact sagebrush vegetation and nearby converted Bromus tectorum-dominated vegetation differed in rodent abundance, diversity and community composition. Results Rodent abundance and species richness were considerably greater in sagebrush plots than in cheatgrass-dominated plots. Nine species were captured in sagebrush plots; five of these were also trapped in cheatgrass plots, all at lower abundances than in the sagebrush. In contrast, cheatgrass-dominated plots had no species that were not found in sagebrush. In addition, the site that had been converted to cheatgrass longer had lower abundances of rodents than the site more recently converted to cheatgrass-dominated plots. Despite large differences in abundances and species richness, Simpson's D diversity and Shannon-Wiener diversity and Brillouin evenness indices did not differ between sagebrush and cheatgrass-dominated plots. Main conclusions This survey of rodent communities in native sagebrush and in converted cheatgrass-dominated vegetation suggests that the abundances and community composition of rodents may be shifting, potentially at the larger spatial scale of the entire Great Basin, where cheatgrass continues to invade and dominate more landscape at a rapid rate. ?? 2009 Blackwell Publishing Ltd.

Ecomorphological characterization of murines and non-arvicoline cricetids (Rodentia) from south-western Europe since the latest Middle Miocene to the Mio-Pliocene boundary (MN 7/8–MN13)

PubMed Central

Kimura, Yuri; Blanco, Fernando; Menéndez, Iris; Álvarez-Sierra, María A.; Hernández Fernández, Manuel

2017-01-01

Rodents are the most speciose group of mammals and display a great ecological diversity. Despite the greater amount of ecomorphological information compiled for extant rodent species, studies usually lack of morphological data on dentition, which has led to difficulty in directly utilizing existing ecomorphological data of extant rodents for paleoecological reconstruction because teeth are the most common or often the only micromammal fossils. Here, we infer the environmental ranges of extinct rodent genera by extracting habitat information from extant relatives and linking it to extinct taxa based on the phenogram of the cluster analysis, in which variables are derived from the principal component analysis on outline shape of the upper first molars. This phenotypic “bracketing” approach is particularly useful in the study of the fossil record of small mammals, which is mostly represented by isolated teeth. As a case study, we utilize extinct genera of murines and non-arvicoline cricetids, ranging from the Iberoccitanian latest middle Miocene to the Mio-Pliocene boundary, and compare our results thoroughly with previous paleoecological reconstructions inferred by different methods. The resultant phenogram shows a predominance of ubiquitous genera among the Miocene taxa, and the presence of a few forest specialists in the two rodent groups (Murinae and Cricetidae), along with the absence of open environment specialists in either group of rodents. This appears to be related to the absence of enduring grassland biomes in the Iberian Peninsula during the late Miocene. High consistency between our result and previous studies suggests that this phenotypic “bracketing” approach is a very useful tool. PMID:28966888

Effect of prescribed fire for tick control in California chaparral.

PubMed

Padgett, K A; Casher, L E; Stephens, S L; Lane, R S

2009-09-01

Prescribed fire was investigated as a method for controlling ixodid and argasid ticks in chaparral habitats in northern California. Two experimental and two adjacent control plots within a wildlife preserve were monitored for 1 yr postburn. Ticks were collected by flagging vegetation, by CO2-baited pitfall trap, and by live-trapping rodents. Twice as many rodents were caught at control sites compared with burn sites and no dusky-footed woodrats, Neotoma fuscipes Baird, were found in the treatment sites postburn. This species is known to be a reservoir of the agents of Lyme disease, Borrelia burgdorferi sensu stricto Johnson, Schmid, Hyde, Steigerwalt & Brenner, and human granulocytic anaplasmosis, Anaplasma phagocytophilum Dumler, Barbet, Bekker, Dasch, Palmer, Ray, Rikihisa, Rurangirwa. Six ixodid tick species were removed from rodents (Ixodes pacificus Cooley & Kohls, Ixodes jellisoni Cooley & Kohls, Ixodes spinipalpis Hadwen & Nuttall, Ixodes woodi Bishopp, Dermacentor occidentalis Marx, and Dermacentor parumapertus Neumann), two of which transmit bacterial zoonotic agents to people in the far-western United States. There was no decrease in number of ticks per animal trapped at either burn site compared with controls; in fact, the mean number of immature I. pacificus per rodent was significantly higher at one burn site than its control site. Soil refugia may protect ticks from fire-induced mortality; the argasid tick Ornithodoros coriaceus Koch, which lives in soil, was unaffected by the prescribed fire as were I. pacificus and D. occidentalis buried in packets 2.5 cm below ground. We conclude that although prescribed fires in chaparral habitats may diminish local rodent abundance, it does not decrease tick loads on rodents. Furthermore, burning chaparral does not result in a decreased abundance of adult ixodid ticks on vegetation and apparently does not affect argasid or ixodid ticks that are sheltered within soil refugia.

Pathobiology and management of laboratory rodents administered CDC category A agents.

PubMed

He, Yongqun; Rush, Howard G; Liepman, Rachel S; Xiang, Zuoshuang; Colby, Lesley A

2007-02-01

The Centers for Disease Control and Prevention Category A infectious agents include Bacillus anthracis (anthrax), Clostridium botulinum toxin (botulism), Yersinia pestis (plague), variola major virus (smallpox), Francisella tularensis (tularemia), and the filoviruses and arenaviruses that induce viral hemorrhagic fevers. These agents are regarded as having the greatest potential for adverse impact on public health and therefore are a focus of renewed attention in infectious disease research. Frequently rodent models are used to study the pathobiology of these agents. Although much is known regarding naturally occurring infections in humans, less is documented on the sources of exposures and potential risks of infection to researchers and animal care personnel after the administration of these hazardous substances to laboratory animals. Failure to appropriately manage the animals can result both in the creation of workplace hazards if human exposures occur and in disruption of the research if unintended animal exposures occur. Here we review representative Category A agents, with a focus on comparing the biologic effects in naturally infected humans and rodent models and on considerations specific to the management of infected rodent subjects. The information reviewed for each agent has been curated manually and stored in a unique Internet-based database system called HazARD (Hazards in Animal Research Database, http://helab.bioinformatics.med.umich.edu/hazard/) that is designed to assist researchers, administrators, safety officials, Institutional Biosafety Committees, and veterinary personnel seeking information on the management of risks associated with animal studies involving hazardous substances.

A revised model of ex-vivo reduction of hexavalent chromium in human and rodent gastric juices

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schlosser, Paul M., E-mail: schlosser.paul@epa.gov; Sasso, Alan F.

Chronic oral exposure to hexavalent chromium (Cr-VI) in drinking water has been shown to induce tumors in the mouse gastrointestinal (GI) tract and rat oral cavity. The same is not true for trivalent chromium (Cr-III). Thus reduction of Cr-VI to Cr-III in gastric juices is considered a protective mechanism, and it has been suggested that the difference between the rate of reduction among mice, rats, and humans could explain or predict differences in sensitivity to Cr-VI. We evaluated previously published models of gastric reduction and believe that they do not fully describe the data on reduction as a function ofmore » Cr-VI concentration, time, and (in humans) pH. The previous models are parsimonious in assuming only a single reducing agent in rodents and describing pH-dependence using a simple function. We present a revised model that assumes three pools of reducing agents in rats and mice with pH-dependence based on known speciation chemistry. While the revised model uses more fitted parameters than the original model, they are adequately identifiable given the available data, and the fit of the revised model to the full range of data is shown to be significantly improved. Hence the revised model should provide better predictions of Cr-VI reduction when integrated into a corresponding PBPK model. - Highlights: • Hexavalent chromium (Cr-VI) reduction in gastric juices is a key detoxifying step. • pH-dependent Cr-VI reduction rates are explained using known chemical speciation. • Reduction in rodents appears to involve multiple pools of electron donors. • Reduction appears to continue after 60 min, although more slowly than initial rates.« less

Establishing the ferret as a gyrencephalic animal model of traumatic brain injury: Optimization of controlled cortical impact procedures.

PubMed

Schwerin, Susan C; Hutchinson, Elizabeth B; Radomski, Kryslaine L; Ngalula, Kapinga P; Pierpaoli, Carlo M; Juliano, Sharon L

2017-06-15

Although rodent TBI studies provide valuable information regarding the effects of injury and recovery, an animal model with neuroanatomical characteristics closer to humans may provide a more meaningful basis for clinical translation. The ferret has a high white/gray matter ratio, gyrencephalic neocortex, and ventral hippocampal location. Furthermore, ferrets are amenable to behavioral training, have a body size compatible with pre-clinical MRI, and are cost-effective. We optimized the surgical procedure for controlled cortical impact (CCI) using 9 adult male ferrets. We used subject-specific brain/skull morphometric data from anatomical MRIs to overcome across-subject variability for lesion placement. We also reflected the temporalis muscle, closed the craniotomy, and used antibiotics. We then gathered MRI, behavioral, and immunohistochemical data from 6 additional animals using the optimized surgical protocol: 1 control, 3 mild, and 1 severely injured animals (surviving one week) and 1 moderately injured animal surviving sixteen weeks. The optimized surgical protocol resulted in consistent injury placement. Astrocytic reactivity increased with injury severity showing progressively greater numbers of astrocytes within the white matter. The density and morphological changes of microglia amplified with injury severity or time after injury. Motor and cognitive impairments scaled with injury severity. The optimized surgical methods differ from those used in the rodent, and are integral to success using a ferret model. We optimized ferret CCI surgery for consistent injury placement. The ferret is an excellent animal model to investigate pathophysiological and behavioral changes associated with TBI. Published by Elsevier B.V.

Spatial clustering of Borrelia burgdorferi sensu lato within populations of Allen's chipmunks and dusky-footed woodrats in northwestern California

PubMed Central

Brown, Richard N.; Fedorova, Natalia; Girard, Yvette A.; Higley, Mark; Clueit, Bernadette; Lane, Robert S.

2018-01-01

The ecology of Lyme borreliosis is complex in northwestern California, with several potential reservoir hosts, tick vectors, and genospecies of Borrelia burgdorferi sensu lato. The primary objective of this study was to determine the fine-scale spatial distribution of different genospecies in four rodent species, the California ground squirrel (Otospermophilus beecheyi), northern flying squirrel (Glaucomys sabrinus), dusky-footed woodrat (Neotoma fuscipes), and Allen’s chipmunk (Neotamias senex). Rodents were live-trapped between June 2004 and May 2005 at the Hoopa Valley Tribal Reservation (HVTR) in Humboldt County, California. Ear-punch biopsies obtained from each rodent were tested by polymerase chain reaction (PCR) and sequencing analysis. The programs ArcGIS and SaTScan were used to examine the spatial distribution of genospecies. Multinomial log-linear models were used to model habitat and host-specific characteristics and their effect on the presence of each borrelial genospecies. The Akaike information criterion (AICc) was used to compare models and determine model fit. Borrelia burgdorferi sensu stricto was primarily associated with chipmunks and B. bissettiae largely with woodrats. The top model included the variables “host species”, “month”, and “elevation” (weight = 0.84). Spatial clustering of B. bissettiae was detected in the northwestern section of the HVTR, whereas B. burgdorferi sensu stricto was clustered in the southeastern section. We conclude that the spatial distribution of these borreliae are driven at least in part by host species, time-of-year, and elevation. PMID:29634745

Spatial clustering of Borrelia burgdorferi sensu lato within populations of Allen's chipmunks and dusky-footed woodrats in northwestern California.

PubMed

Hacker, Gregory M; Brown, Richard N; Fedorova, Natalia; Girard, Yvette A; Higley, Mark; Clueit, Bernadette; Lane, Robert S

2018-01-01

The ecology of Lyme borreliosis is complex in northwestern California, with several potential reservoir hosts, tick vectors, and genospecies of Borrelia burgdorferi sensu lato. The primary objective of this study was to determine the fine-scale spatial distribution of different genospecies in four rodent species, the California ground squirrel (Otospermophilus beecheyi), northern flying squirrel (Glaucomys sabrinus), dusky-footed woodrat (Neotoma fuscipes), and Allen's chipmunk (Neotamias senex). Rodents were live-trapped between June 2004 and May 2005 at the Hoopa Valley Tribal Reservation (HVTR) in Humboldt County, California. Ear-punch biopsies obtained from each rodent were tested by polymerase chain reaction (PCR) and sequencing analysis. The programs ArcGIS and SaTScan were used to examine the spatial distribution of genospecies. Multinomial log-linear models were used to model habitat and host-specific characteristics and their effect on the presence of each borrelial genospecies. The Akaike information criterion (AICc) was used to compare models and determine model fit. Borrelia burgdorferi sensu stricto was primarily associated with chipmunks and B. bissettiae largely with woodrats. The top model included the variables "host species", "month", and "elevation" (weight = 0.84). Spatial clustering of B. bissettiae was detected in the northwestern section of the HVTR, whereas B. burgdorferi sensu stricto was clustered in the southeastern section. We conclude that the spatial distribution of these borreliae are driven at least in part by host species, time-of-year, and elevation.

Chemistry and Antihypertensive Effects of Tempol and Other Nitroxides

PubMed Central

WILCOX, CHRISTOPHER S.; PEARLMAN, ADAM

2009-01-01

Nitroxides can undergo one- or two-electron reduction reactions to hydroxylamines or oxammonium cations, respectively, which themselves are interconvertible, thereby providing redox metabolic actions. 4-Hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (tempol) is the most extensively studied nitroxide. It is a cell membrane-permeable amphilite that dismutates superoxide catalytically, facilitates hydrogen peroxide metabolism by catalase-like actions, and limits formation of toxic hydroxyl radicals produced by Fenton reactions. It is broadly effective in detoxifying these reactive oxygen species in cell and animal studies. When administered intravenously to hypertensive rodent models, tempol caused rapid and reversible dose-dependent reductions in blood pressure in 22 of 26 studies. This was accompanied by vasodilation, increased nitric oxide activity, reduced sympathetic nervous system activity at central and peripheral sites, and enhanced potassium channel conductance in blood vessels and neurons. When administered orally or by infusion over days or weeks to hypertensive rodent models, it reduced blood pressure in 59 of 68 studies. This was accompanied by correction of salt sensitivity and endothelial dysfunction and reduced agonist-evoked oxidative stress and contractility of blood vessels, reduced renal vascular resistance, and increased renal tissue oxygen tension. Thus, tempol is broadly effective in reducing blood pressure, whether given by acute intravenous injection or by prolonged administration, in a wide range of rodent models of hypertension. PMID:19112152

Mammary gland neoplasia in long-term rodent studies.

PubMed Central

Russo, I H; Russo, J

1996-01-01

Breast cancer, the most frequent spontaneous malignancy diagnosed in women in the western world, is continuously increasing in incidence in industrialized nations. Although breast cancer develops in women as the result of a combination of external and endogenous factors such as exposure to ionizing radiation, diet, socioeconomic status, and endocrinologic, familial, or genetic factors, no specific etiologic agent(s) or the mechanisms responsible of the disease has been identified as yet. Thus, experimental models that exhibit the same complex interactions are needed for testing various mechanisms and for assessing the carcinogenic potential of given chemicals. Rodent mammary carcinomas represent such a model to a great extent because, in these species, mammary cancer is a multistep complex process that can be induced by either chemicals, radiation, viruses, or genetic factors. Long-term studies in rodent models have been particularly useful for dissecting the initiation, promotion, and progression steps of carcinogenesis. The susceptibility of the rodent mammary gland to develop neoplasms has made this organ a unique target for testing the carcinogenic potential of specific genotoxic chemicals and environmental agents. Mammary tumors induced by indirect- or direct-acting carcinogens such as 7, 12-dimethlbenz(a)anthracene or N-methyl-N-nitrosourea are, in general, hormone dependent adenocarcinomas whose incidence, number of tumors per animal, tumor latency, and tumor type are influenced by the age, reproductive history, and endocarinologic milieu of the host at the time of carcinogen exposure. Rodent models are informative in the absence of human data. They have provided valuable information on the dose and route of administration to be used and optimal host conditions for eliciting maximal tumorigenic response. Studies of the influence of normal gland development on the pathogenesis of chemically induced mammary carcinomas have clarified the role of differentiation in cancer initiation. Comparative studies with the development of the human breast and the pathogenesis of breast cancer have contributed to validate rodent-to-human extrapolations. However, it has not been definitively established what type of information is necessary for human risk assessment, whether currently toxicity testing methodologies are sufficient for fulfilling those needs, or whether treatment-induced tumorigenic responses in rodents are predictive of potential human risk. An alternative to the traditional bioassays are mechanism-based toxicology and molecular and cellular approaches, combined with comparative in vitro systems. These approaches might allow the rapid screen of chemicals for setting priorities for further studies to determine the dose-response relationship for chemical effects at low doses, to assess effects other than mutagenesis and/or tumorigenesis, or to establish qualitative and quantitative relationships of biomarkers to toxic effects. Until there is enough information on the predictive value of mechanism-based toxicology for risk assessment, this approach should be used in conjunction with and validated by the traditional in vivo long-term bioassays. Images Figure 1. Figure 2. Figure 3. Figure 4. Figure 5. Figure 6. Figure 7. A Figure 7. B Figure 8. A Figure 8. B Figure 9. Figure 10. Figure 11. Figure 12. Figure 13. Figure 14. Figure 15. Figure 16. Figure 17. Figure 18. Figure 19. Figure 20. Figure 21. Figure 22. Figure 23. Figure 24. Figure 25. Figure 26. PMID:8899375

How to Monitor the Breathing of Laboratory Rodents: A Review of the Current Methods.

PubMed

Grimaud, Julien; Murthy, Venkatesh N

2018-05-23

Accurately measuring respiration in laboratory rodents is essential for many fields of research, including olfactory neuroscience, social behavior, learning and memory, and respiratory physiology. However, choosing the right technique to monitor respiration can be tricky, given the many criteria to take into account: reliability, precision, and invasiveness, to name a few. This review aims to assist experimenters in choosing the technique that will best fit their needs, by surveying the available tools, discussing their strengths and weaknesses, and offering suggestions for future improvements.

A MATHEMATICAL MODEL FOR THE ANDROGENIC REGULATION OF THE PROSTATE IN INTACT AND CASTRATE ADULT MALE RATS

EPA Science Inventory

An abstract that provides understanding for a mathematical model by Barton and Anderson, for the dynamics of androgenic synthesis, transport, metabolism, and regulation of the rodent ventral prostate.

Ecological, Social and Biological Risk Factors for Continued Trypanosoma cruzi Transmission by Triatoma dimidiata in Guatemala

PubMed Central

Bustamante, Dulce M.; De Urioste-Stone, Sandra M.; Juárez, José G.; Pennington, Pamela M.

2014-01-01

Background Chagas disease transmission by Triatoma dimidiata persists in Guatemala and elsewhere in Central America under undefined ecological, biological and social (eco-bio-social) conditions. Methodology Eco-bio-social risk factors associated with persistent domiciliary infestation were identified by a cross-sectional survey and qualitative participatory methods. Quantitative and qualitative data were generated regarding Trypanosoma cruzi reservoirs and triatomine hosts. Blood meal analysis and infection of insects, dogs and rodents were determined. Based on these data, multimodel inference was used to identify risk factors for domestic infestation with the greatest relative importance (>0.75). Principal Findings Blood meal analysis showed that 64% of 36 bugs fed on chickens, 50% on humans, 17% on dogs; 24% of 34 bugs fed on Rattus rattus and 21% on Mus musculus. Seroprevalence among 80 dogs was 37%. Eight (17%) of 46 M. musculus and three (43%) of seven R. rattus from households with infected triatomines were infected with T. cruzi Distinct Typing Unit I. Results from interviews and participatory meetings indicated that vector control personnel and some householders perceived chickens roosting and laying eggs in the house as bug infestation risk factors. House construction practices were seen as a risk factor for bug and rodent infestation, with rodents being perceived as a pest by study participants. Multimodel inference showed that house infestation risk factors of high relative importance are dog density, mouse presence, interior wall plaster condition, dirt floor, tile roofing and coffee tree presence. Conclusions/Significance Persistent house infestation is closely related to eco-bio-social factors that maintain productive T. dimidiata habitats associated with dogs, chickens and rodents. Triatomine, dog and rodent infections indicate active T. cruzi transmission. Integrated vector control methods should include actions that consider the role of peridomestic animals in transmission and community memberś level of knowledge, attitudes and practices associated with the disease and transmission process. PMID:25170955

Acute Stress Decreases but Chronic Stress Increases Myocardial Sensitivity to Ischemic Injury in Rodents

PubMed Central

Eisenmann, Eric D.; Rorabaugh, Boyd R.; Zoladz, Phillip R.

2016-01-01

Cardiovascular disease (CVD) is the largest cause of mortality worldwide, and stress is a significant contributor to the development of CVD. The relationship between acute and chronic stress and CVD is well evidenced. Acute stress can lead to arrhythmias and ischemic injury. However, recent evidence in rodent models suggests that acute stress can decrease sensitivity to myocardial ischemia–reperfusion injury (IRI). Conversely, chronic stress is arrhythmogenic and increases sensitivity to myocardial IRI. Few studies have examined the impact of validated animal models of stress-related psychological disorders on the ischemic heart. This review examines the work that has been completed using rat models to study the effects of stress on myocardial sensitivity to ischemic injury. Utilization of animal models of stress-related psychological disorders is critical in the prevention and treatment of cardiovascular disorders in patients experiencing stress-related psychiatric conditions. PMID:27199778

Acute Stress Decreases but Chronic Stress Increases Myocardial Sensitivity to Ischemic Injury in Rodents.

PubMed

Eisenmann, Eric D; Rorabaugh, Boyd R; Zoladz, Phillip R

2016-01-01

Cardiovascular disease (CVD) is the largest cause of mortality worldwide, and stress is a significant contributor to the development of CVD. The relationship between acute and chronic stress and CVD is well evidenced. Acute stress can lead to arrhythmias and ischemic injury. However, recent evidence in rodent models suggests that acute stress can decrease sensitivity to myocardial ischemia-reperfusion injury (IRI). Conversely, chronic stress is arrhythmogenic and increases sensitivity to myocardial IRI. Few studies have examined the impact of validated animal models of stress-related psychological disorders on the ischemic heart. This review examines the work that has been completed using rat models to study the effects of stress on myocardial sensitivity to ischemic injury. Utilization of animal models of stress-related psychological disorders is critical in the prevention and treatment of cardiovascular disorders in patients experiencing stress-related psychiatric conditions.

Brine saturation technique for extraction of light filth from rubbed, ground, and whole sage: collaborative study.

PubMed

Freeman, C C

1985-01-01

A new approach to the isolation of light filth from the 3 commercial forms of sage was studied collaboratively. It incorporates a simple isopropanol defatting, followed by saturation of the product with brine by alternately heating and cooling, and subsequent trapping of filth from tap water with olive oil. This method circumvents the use of hazardous, expensive solvents and more time-consuming pretreatment procedures. Overall recoveries were 92.1% for rodent hair and 78.7% for insect fragments on clean, easy-to-read papers. An additional blending step was necessary to obtain satisfactory recovery of rodent hair fragments from whole sage. The method has been adopted official first action for light filth in rubbed and ground sage only.

Schizophrenia and Depression Co-Morbidity: What We have Learned from Animal Models

PubMed Central

Samsom, James N.; Wong, Albert H. C.

2015-01-01

Patients with schizophrenia are at an increased risk for the development of depression. Overlap in the symptoms and genetic risk factors between the two disorders suggests a common etiological mechanism may underlie the presentation of comorbid depression in schizophrenia. Understanding these shared mechanisms will be important in informing the development of new treatments. Rodent models are powerful tools for understanding gene function as it relates to behavior. Examining rodent models relevant to both schizophrenia and depression reveals a number of common mechanisms. Current models which demonstrate endophenotypes of both schizophrenia and depression are reviewed here, including models of CUB and SUSHI multiple domains 1, PDZ and LIM domain 5, glutamate Delta 1 receptor, diabetic db/db mice, neuropeptide Y, disrupted in schizophrenia 1, and its interacting partners, reelin, maternal immune activation, and social isolation. Neurotransmission, brain connectivity, the immune system, the environment, and metabolism emerge as potential common mechanisms linking these models and potentially explaining comorbid depression in schizophrenia. PMID:25762938

Bioactive compounds of fourth generation gamma-irradiated Typhoniumflagelliforme Lodd. mutants based on gas chromatography-mass spectrometry

NASA Astrophysics Data System (ADS)

Sianipar, N. F.; Purnamaningsih, R.; Rosaria

2016-08-01

Rodent tuber (Typhonium flagelliforme Lodd.) is an Indonesian anticancer medicinal plant. The natural genetic diversity of rodent tuber is low due to vegetative propagation. Plant's genetic diversity has to be increased for obtaining clones which contain a high amount of anticancer compounds. In vitro calli were irradiated with 6 Gy of gamma ray to produce in vitro mutant plantlets. Mutant plantlets were acclimated and propagated in a greenhouse. This research was aimed to identify the chemical compounds in the leaves and tubers ofthe fourth generation of rodent tuber's vegetative mutant clones (MV4) and control plantsby using GC- MS method. Leaves and tubers of MV4 each contained 2 and 5 anticancer compounds which quantities were higher compared to control plants. MV4 leaves contained 5 new anticancer compounds while its tubers contained 3 new anticancer compounds which were not found in control. The new anticancer compounds in leaves were hexadecanoic acid, stigmast-5-en-3-ol, ergost-5-en-3-ol, farnesol isomer a, and oleic acid while the new anticancer compounds in tubers were alpha tocopherol, ergost-5-en-3-ol, and beta-elemene. Rodent tuber mutant clones are very potential to be developed into anticancer drugs.

Infectivity to experimental rodents of Cryptosporidium parvum oocysts from Siberian chipmunks (Tamias sibiricus) originated in the People's Republic of China.

PubMed

Matsui, T; Fujino, T; Kajima, J; Tsuji, M

2000-05-01

We isolated Cryptosporidium parvum-type oocysts from naturally infected siberian chipmunks which originated in the People's Republic of China and examined the infectivity to rodents as experimental animals. The naturally infected chipmunks did not show any clinical symptoms. The oocysts were 4.8 x 4.2 microm on average in size. They were ovoid and morphologically similar to the C. parvum oocysts isolated from human and cattle. Experimental rodents were inoculated with 1.6 x 10(6) original oocysts each. SCID mice began to shed oocysts on day 7 and the OPG value was 10(5) from 50 days. The oocysts were found from ICR mice on days 13 and 16 by only sugar flotation method, however, any oocysts were not detected from the rats, guinea pigs and rabbits until 30 days. Two infected SCID mice were necropsied on days 100 and 102 and examined for coccidian organisms. Merozoites and oocysts were found in the low part of jejunum and ileum, however, no parasites were detected in the stomach. Consequently, it was considered that the present species was C. parvum and was probably genotype 2 from result of infectivity to rodents.

Rodents and Risk in the Mekong Delta of Vietnam: Seroprevalence of Selected Zoonotic Viruses in Rodents and Humans

PubMed Central

Van Cuong, Nguyen; Carrique-Mas, Juan; Vo Be, Hien; An, Nguyen Ngoc; Tue, Ngo Tri; Anh, Nguyet Lam; Anh, Pham Hong; Phuc, Nguyen The; Baker, Stephen; Voutilainen, Liina; Jääskeläinen, Anne; Huhtamo, Eili; Utriainen, Mira; Sironen, Tarja; Vaheri, Antti; Henttonen, Heikki; Vapalahti, Olli; Chaval, Yannick

2015-01-01

Abstract In the Mekong Delta in southern Vietnam, rats are commonly traded in wet markets and sold live for food consumption. We investigated seroprevalence to selected groups of rodent-borne viruses among human populations with high levels of animal exposure and among co-located rodent populations. The indirect fluorescence antibody test (IFAT) was used to determine seropositivity to representative reference strains of hantaviruses (Dobrava virus [DOBV], Seoul virus [SEOV]), cowpox virus, arenaviruses (lymphocytic choriomeningitis virus [LCMV]), flaviviruses (tick-borne encephalitis virus [TBEV]), and rodent parechoviruses (Ljungan virus), using sera from 245 humans living in Dong Thap Province and 275 rodents representing the five common rodent species sold in wet markets and present in peridomestic and farm settings. Combined seropositivity to DOBV and SEOV among the rodents and humans was 6.9% (19/275) and 3.7% (9/245), respectively; 1.1% (3/275) and 4.5% (11/245) to cowpox virus; 5.4% (15/275) and 47.3% (116/245) for TBEV; and exposure to Ljungan virus was 18.8% (46/245) in humans, but 0% in rodents. Very little seroreactivity was observed to LCMV in either rodents (1/275, 0.4%) or humans (2/245, 0.8%). Molecular screening of rodent liver tissues using consensus primers for flaviviruses did not yield any amplicons, whereas molecular screening of rodent lung tissues for hantavirus yielded one hantavirus sequence (SEOV). In summary, these results indicate low to moderate levels of endemic hantavirus circulation, possible circulation of a flavivirus in rodent reservoirs, and the first available data on human exposures to parechoviruses in Vietnam. Although the current evidence suggests only limited exposure of humans to known rodent-borne diseases, further research is warranted to assess public health implications of the rodent trade. PMID:25629782

Genetic structure and invasion history of the house mouse (Mus musculus domesticus) in Senegal, West Africa: a legacy of colonial and contemporary times.

PubMed

Lippens, C; Estoup, A; Hima, M K; Loiseau, A; Tatard, C; Dalecky, A; Bâ, K; Kane, M; Diallo, M; Sow, A; Niang, Y; Piry, S; Berthier, K; Leblois, R; Duplantier, J-M; Brouat, C

2017-08-01

Knowledge of the genetic make-up and demographic history of invasive populations is critical to understand invasion mechanisms. Commensal rodents are ideal models to study whether complex invasion histories are typical of introductions involving human activities. The house mouse Mus musculus domesticus is a major invasive synanthropic rodent originating from South-West Asia. It has been largely studied in Europe and on several remote islands, but the genetic structure and invasion history of this taxon have been little investigated in several continental areas, including West Africa. In this study, we focussed on invasive populations of M. m. domesticus in Senegal. In this focal area for European settlers, the distribution area and invasion spread of the house mouse is documented by decades of data on commensal rodent communities. Genetic variation at one mitochondrial locus and 16 nuclear microsatellite markers was analysed from individuals sampled in 36 sites distributed across the country. A combination of phylogeographic and population genetics methods showed that there was a single introduction event on the northern coast of Senegal, from an exogenous (probably West European) source, followed by a secondary introduction from northern Senegal into a coastal site further south. The geographic locations of these introduction sites were consistent with the colonial history of Senegal. Overall, the marked microsatellite genetic structure observed in Senegal, even between sites located close together, revealed a complex interplay of different demographic processes occurring during house mouse spatial expansion, including sequential founder effects and stratified dispersal due to human transport along major roads.

Identification of consensus biomarkers for predicting non-genotoxic hepatocarcinogens

PubMed Central

Huang, Shan-Han; Tung, Chun-Wei

2017-01-01

The assessment of non-genotoxic hepatocarcinogens (NGHCs) is currently relying on two-year rodent bioassays. Toxicogenomics biomarkers provide a potential alternative method for the prioritization of NGHCs that could be useful for risk assessment. However, previous studies using inconsistently classified chemicals as the training set and a single microarray dataset concluded no consensus biomarkers. In this study, 4 consensus biomarkers of A2m, Ca3, Cxcl1, and Cyp8b1 were identified from four large-scale microarray datasets of the one-day single maximum tolerated dose and a large set of chemicals without inconsistent classifications. Machine learning techniques were subsequently applied to develop prediction models for NGHCs. The final bagging decision tree models were constructed with an average AUC performance of 0.803 for an independent test. A set of 16 chemicals with controversial classifications were reclassified according to the consensus biomarkers. The developed prediction models and identified consensus biomarkers are expected to be potential alternative methods for prioritization of NGHCs for further experimental validation. PMID:28117354

Spinal cord electrophysiology II: extracellular suction electrode fabrication.

PubMed

Garudadri, Suresh; Gallarda, Benjamin; Pfaff, Samuel; Alaynick, William

2011-02-20

Development of neural circuitries and locomotion can be studied using neonatal rodent spinal cord central pattern generator (CPG) behavior. We demonstrate a method to fabricate suction electrodes that are used to examine CPG activity, or fictive locomotion, in dissected rodent spinal cords. The rodent spinal cords are placed in artificial cerebrospinal fluid and the ventral roots are drawn into the suction electrode. The electrode is constructed by modifying a commercially available suction electrode. A heavier silver wire is used instead of the standard wire given by the commercially available electrode. The glass tip on the commercial electrode is replaced with a plastic tip for increased durability. We prepare hand drawn electrodes and electrodes made from specific sizes of tubing, allowing consistency and reproducibility. Data is collected using an amplifier and neurogram acquisition software. Recordings are performed on an air table within a Faraday cage to prevent mechanical and electrical interference, respectively.

Spinal Cord Electrophysiology II: Extracellular Suction Electrode Fabrication

PubMed Central

Garudadri, Suresh; Gallarda, Benjamin; Pfaff, Samuel; Alaynick, William

2011-01-01

Development of neural circuitries and locomotion can be studied using neonatal rodent spinal cord central pattern generator (CPG) behavior. We demonstrate a method to fabricate suction electrodes that are used to examine CPG activity, or fictive locomotion, in dissected rodent spinal cords. The rodent spinal cords are placed in artificial cerebrospinal fluid and the ventral roots are drawn into the suction electrode. The electrode is constructed by modifying a commercially available suction electrode. A heavier silver wire is used instead of the standard wire given by the commercially available electrode. The glass tip on the commercial electrode is replaced with a plastic tip for increased durability. We prepare hand drawn electrodes and electrodes made from specific sizes of tubing, allowing consistency and reproducibility. Data is collected using an amplifier and neurogram acquisition software. Recordings are performed on an air table within a Faraday cage to prevent mechanical and electrical interference, respectively. PMID:21372792

Animal models for Ebola and Marburg virus infections

PubMed Central

Nakayama, Eri; Saijo, Masayuki

2013-01-01

Ebola and Marburg hemorrhagic fevers (EHF and MHF) are caused by the Filoviridae family, Ebolavirus and Marburgvirus (ebolavirus and marburgvirus), respectively. These severe diseases have high mortality rates in humans. Although EHF and MHF are endemic to sub-Saharan Africa. A novel filovirus, Lloviu virus, which is genetically distinct from ebolavirus and marburgvirus, was recently discovered in Spain where filoviral hemorrhagic fever had never been reported. The virulence of this virus has not been determined. Ebolavirus and marburgvirus are classified as biosafety level-4 (BSL-4) pathogens and Category A agents, for which the US government requires preparedness in case of bioterrorism. Therefore, preventive measures against these viral hemorrhagic fevers should be prepared, not only in disease-endemic regions, but also in disease-free countries. Diagnostics, vaccines, and therapeutics need to be developed, and therefore the establishment of animal models for EHF and MHF is invaluable. Several animal models have been developed for EHF and MHF using non-human primates (NHPs) and rodents, which are crucial to understand pathophysiology and to develop diagnostics, vaccines, and therapeutics. Rhesus and cynomolgus macaques are representative models of filovirus infection as they exhibit remarkably similar symptoms to those observed in humans. However, the NHP models have practical and ethical problems that limit their experimental use. Furthermore, there are no inbred and genetically manipulated strains of NHP. Rodent models such as mouse, guinea pig, and hamster, have also been developed. However, these rodent models require adaptation of the virus to produce lethal disease and do not mirror all symptoms of human filovirus infection. This review article provides an outline of the clinical features of EHF and MHF in animals, including humans, and discusses how the animal models have been developed to study pathophysiology, vaccines, and therapeutics. PMID:24046765

Animal models for Ebola and Marburg virus infections.

PubMed

Nakayama, Eri; Saijo, Masayuki

2013-09-05

Ebola and Marburg hemorrhagic fevers (EHF and MHF) are caused by the Filoviridae family, Ebolavirus and Marburgvirus (ebolavirus and marburgvirus), respectively. These severe diseases have high mortality rates in humans. Although EHF and MHF are endemic to sub-Saharan Africa. A novel filovirus, Lloviu virus, which is genetically distinct from ebolavirus and marburgvirus, was recently discovered in Spain where filoviral hemorrhagic fever had never been reported. The virulence of this virus has not been determined. Ebolavirus and marburgvirus are classified as biosafety level-4 (BSL-4) pathogens and Category A agents, for which the US government requires preparedness in case of bioterrorism. Therefore, preventive measures against these viral hemorrhagic fevers should be prepared, not only in disease-endemic regions, but also in disease-free countries. Diagnostics, vaccines, and therapeutics need to be developed, and therefore the establishment of animal models for EHF and MHF is invaluable. Several animal models have been developed for EHF and MHF using non-human primates (NHPs) and rodents, which are crucial to understand pathophysiology and to develop diagnostics, vaccines, and therapeutics. Rhesus and cynomolgus macaques are representative models of filovirus infection as they exhibit remarkably similar symptoms to those observed in humans. However, the NHP models have practical and ethical problems that limit their experimental use. Furthermore, there are no inbred and genetically manipulated strains of NHP. Rodent models such as mouse, guinea pig, and hamster, have also been developed. However, these rodent models require adaptation of the virus to produce lethal disease and do not mirror all symptoms of human filovirus infection. This review article provides an outline of the clinical features of EHF and MHF in animals, including humans, and discusses how the animal models have been developed to study pathophysiology, vaccines, and therapeutics.

Nutritional programming of gastrointestinal tract development. Is the pig a good model for man?

PubMed

Guilloteau, Paul; Zabielski, Romuald; Hammon, Harald M; Metges, Cornelia C

2010-06-01

The consequences of early-life nutritional programming in man and other mammalian species have been studied chiefly at the metabolic level. Very few studies, if any, have been performed in the gastrointestinal tract (GIT) as the target organ, but extensive GIT studies are needed since the GIT plays a key role in nutrient supply and has an impact on functions of the entire organism. The possible deleterious effects of nutritional programming at the metabolic level were discovered following epidemiological studies in human subjects, and confirmed in animal models. Investigating the impact of programming on GIT structure and function would need appropriate animal models due to ethical restrictions in the use of human subjects. The aim of the present review is to discuss the use of pigs as an animal model as a compromise between ethically acceptable animal studies and the requirement of data which can be interpolated to the human situation. In nutritional programming studies, rodents are the most frequently used model for man, but GIT development and digestive function in rodents are considerably different from those in man. In that aspect, the pig GIT is much closer to the human than that of rodents. The swine species is closely comparable with man in many nutritional and digestive aspects, and thus provides ample opportunity to be used in investigations on the consequences of nutritional programming for the GIT. In particular, the 'sow-piglets' dyad could be a useful tool to simulate the 'human mother-infant' dyad in studies which examine short-, middle- and long-term effects and is suggested as the reference model.

Intracranial glioblastoma models in preclinical neuro-oncology: neuropathological characterization and tumor progression

PubMed Central

Candolfi, Marianela; Curtin, James F.; Stephen Nichols, W.; Muhammad, AKM. G.; King, Gwendalyn D.; Elizabeth Pluhar, G.; McNiel, Elizabeth A.; Ohlfest, John R.; Freese, Andrew B.; Moore, Peter F.; Lerner, Jonathan; Lowenstein, Pedro R.

2008-01-01

Although rodent glioblastoma (GBM) models have been used for over 30 years, the extent to which they recapitulate the characteristics encountered in human GBMs remains controversial. We studied the histopathological features of dog GBM and human xenograft GBM models in immune-deficient mice (U251 and U87 GBM in nude Balb/c), and syngeneic GBMs in immune-competent rodents (GL26 cells in C57BL/6 mice, CNS-1 cells in Lewis rats). All GBMs studied exhibited neovascularization, pleomorphism, vimentin immunoreactivity, and infiltration of T-cells and macrophages. All the tumors showed necrosis and hemorrhages, except the U87 human xenograft, in which the most salient feature was its profuse neovascularization. The tumors differed in the expression of astrocytic intermediate filaments: human and dog GBMs, as well as U251 xenografts expressed glial fibrillary acidic protein (GFAP) and vimentin, while the U87 xenograft and the syngeneic rodent GBMs were GFAP− and vimentin+. Also, only dog GBMs exhibited endothelial proliferation, a key feature that was absent in the murine models. In all spontaneous and implanted GBMs we found histopathological features compatible with tumor invasion into the non-neoplastic brain parenchyma. Our data indicate that murine models of GBM appear to recapitulate several of the human GBM histopathological features and, considering their reproducibility and availability, they constitute a valuable in vivo system for preclinical studies. Importantly, our results indicate that dog GBM emerges as an attractive animal model for testing novel therapies in a spontaneous tumor in the context of a larger brain. PMID:17874037

The utility of animal models to evaluate novel anti-obesity agents

PubMed Central

Vickers, Steven P; Jackson, Helen C; Cheetham, Sharon C

2011-01-01

The global incidence of obesity continues to rise and is a major driver of morbidity and mortality through cardiovascular and cerebrovascular diseases. Animal models used in the discovery of novel treatments for obesity range from straightforward measures of food intake in lean rodents to long-term studies in animals exhibiting obesity due to the continuous access to diets high in fat. The utility of these animal models can be extended to determine, for example, that weight loss is due to fat loss and/or assess whether beneficial changes in key plasma parameters (e.g. insulin) are evident. In addition, behavioural models such as the behavioural satiety sequence can be used to confirm that a drug treatment has a selective effect on food intake. Typically, animal models have excellent predictive validity whereby drug-induced weight loss in rodents subsequently translates to weight loss in man. However, despite this, at the time of writing orlistat (Europe; USA) remains the only drug currently marketed for the treatment of obesity, with sibutramine having recently been withdrawn from sale globally due to the increased incidence of serious, non-fatal cardiovascular events. While the utility of rodent models in predicting clinical weight loss is detailed, the review also discusses whether animals can be used to predict adverse events such as those seen with recent anti-obesity drugs in the clinic. LINKED ARTICLES This article is part of a themed issue on Translational Neuropharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue-4 PMID:21265828

SPIO-labeled Yttrium Microspheres for MR Imaging Quantification of Transcatheter Intrahepatic Delivery in a Rodent Model

PubMed Central

Li, Weiguo; Zhang, Zhuoli; Gordon, Andrew C.; Chen, Jeane; Nicolai, Jodi; Lewandowski, Robert J.; Omary, Reed A.

2016-01-01

Purpose To investigate the qualitative and quantitative impacts of labeling yttrium microspheres with increasing amounts of superparamagnetic iron oxide (SPIO) material for magnetic resonance (MR) imaging in phantom and rodent models. Materials and Methods Animal model studies were approved by the institutional Animal Care and Use Committee. The r2* relaxivity for each of four microsphere SPIO compositions was determined from 32 phantoms constructed with agarose gel and in eight concentrations from each of the four compositions. Intrahepatic transcatheter infusion procedures were performed in rats by using each of the four compositions before MR imaging to visualize distributions within the liver. For quantitative studies, doses of 5, 10, 15, or 20 mg 2% SPIO-labeled yttrium microspheres were infused into 24 rats (six rats per group). MR imaging R2* measurements were used to quantify the dose delivered to each liver. Pearson correlation, analysis of variance, and intraclass correlation analyses were performed to compare MR imaging measurements in phantoms and animal models. Results Increased r2* relaxivity was observed with incremental increases of SPIO microsphere content. R2* measurements of the 2% SPIO–labeled yttrium microsphere concentration were well correlated with known phantom concentrations (R2 = 1.00, P < .001) over a broader linear range than observed for the other three compositions. Microspheres were heterogeneously distributed within each liver; increasing microsphere SPIO content produced marked signal voids. R2*-based measurements of 2% SPIO–labeled yttrium microsphere delivery were well correlated with infused dose (intraclass correlation coefficient, 0.98; P < .001). Conclusion MR imaging R2* measurements of yttrium microspheres labeled with 2% SPIO can quantitatively depict in vivo intrahepatic biodistribution in a rat model. © RSNA, 2015 Online supplemental material is available for this article. PMID:26313619

Tesevatinib ameliorates progression of polycystic kidney disease in rodent models of autosomal recessive polycystic kidney disease

PubMed Central

Sweeney, William E; Frost, Philip; Avner, Ellis D

2017-01-01

AIM To investigate the therapeutic potential of tesevatinib (TSV), a unique multi-kinase inhibitor currently in Phase II clinical trials for autosomal dominant polycystic kidney disease (ADPKD), in well-defined rodent models of autosomal recessive polycystic kidney disease (ARPKD). METHODS We administered TSV in daily doses of 7.5 and 15 mg/kg per day by I.P. to the well characterized bpk model of polycystic kidney disease starting at postnatal day (PN) 4 through PN21 to assess efficacy and toxicity in neonatal mice during postnatal development and still undergoing renal maturation. We administered TSV by oral gavage in the same doses to the orthologous PCK model (from PN30 to PN90) to assess efficacy and toxicity in animals where developmental processes are complete. The following parameters were assessed: Body weight, total kidney weight; kidney weight to body weight ratios; and morphometric determination of a cystic index and a measure of hepatic disease. Renal function was assessed by: Serum BUN; creatinine; and a 12 h urinary concentrating ability. Validation of reported targets including the level of angiogenesis and inhibition of angiogenesis (active VEGFR2/KDR) was assessed by Western analysis. RESULTS This study demonstrates that: (1) in vivo pharmacological inhibition of multiple kinase cascades with TSV reduced phosphorylation of key mediators of cystogenesis: EGFR, ErbB2, c-Src and KDR; and (2) this reduction of kinase activity resulted in significant reduction of renal and biliary disease in both bpk and PCK models of ARPKD. The amelioration of disease by TSV was not associated with any apparent toxicity. CONCLUSION The data supports the hypothesis that this multi-kinase inhibitor TSV may provide an effective clinical therapy for human ARPKD. PMID:28729967

Assays of homeopathic remedies in rodent behavioural and psychopathological models.

PubMed

Bellavite, Paolo; Magnani, Paolo; Marzotto, Marta; Conforti, Anita

2009-10-01

The first part of this paper reviews the effects of homeopathic remedies on several models of anxiety-like behaviours developed and described in rodents. The existing literature in this field comprises some fifteen exploratory studies, often published in non-indexed and non-peer-reviewed journals. Only a few results have been confirmed by multiple laboratories, and concern Ignatia, Gelsemium, Chamomilla (in homeopathic dilutions/potencies). Nevertheless, there are some interesting results pointing to the possible efficacy of other remedies, and confirming a statistically significant effect of high dilutions of neurotrophic molecules and antibodies. In the second part of this paper we report some recent results obtained in our laboratory, testing Aconitum, Nux vomica, Belladonna, Argentum nitricum, Tabacum (all 5CH potency) and Gelsemium (5, 7, 9 and 30CH potencies) on mice using ethological models of behaviour. The test was performed using coded drugs and controls in double blind (operations and calculations). After an initial screening that showed all the tested remedies (except for Belladonna) to have some effects on the behavioural parameters (light-dark test and open-field test), but with high experimental variability, we focused our study on Gelsemium, and carried out two complete series of experiments. The results showed that Gelsemium had several effects on the exploratory behaviour of mice, which in some models were highly statistically significant (p < 0.001), in all the dilutions/dynamizations used, but with complex differences according to the experimental conditions and test performed. Finally, some methodological issues of animal research in this field of homeopathy are discussed. The "Gelsemium model" - encompassing experimental studies in vitro and in vivo from different laboratories and with different methods, including significant effects of its major active principle gelsemine - may play a pivotal rule for investigations on other homeopathic remedies.

The Great Roundleaf Bat (Hipposideros armiger) as a Good Model for Cold-Induced Browning of Intra-Abdominal White Adipose Tissue

PubMed Central

Ke, Shanshan; Fang, Na; Irwin, David M.; Lei, Ming; Zhang, Junpeng; Shi, Huizhen; Zhang, Shuyi; Wang, Zhe

2014-01-01

Background Inducing beige fat from white adipose tissue (WAT) is considered to be a shortcut to weight loss and increasingly becoming a key area in research into treatments for obesity and related diseases. However, currently, animal models of beige fat are restricted to rodents, where subcutaneous adipose tissue (sWAT, benign WAT) is more liable to develop into the beige fat under specific activators than the intra-abdominal adipose tissue (aWAT, malignant WAT) that is the major source of obesity related diseases in humans. Methods Here we induced beige fat by cold exposure in two species of bats, the great roundleaf bat (Hipposideros armiger) and the rickett's big-footed bat (Myotis ricketti), and compared the molecular and morphological changes with those seen in the mouse. Expression of thermogenic genes (Ucp1 and Pgc1a) was measured by RT-qPCR and adipocyte morphology examined by HE staining at three adipose locations, sWAT, aWAT and iBAT (interscapular brown adipose tissue). Results Expression of Ucp1 and Pgc1a was significantly upregulated, by 729 and 23 fold, respectively, in aWAT of the great roundleaf bat after exposure to 10°C for 7 days. Adipocyte diameters of WATs became significantly reduced and the white adipocytes became brown-like in morphology. In mice, similar changes were found in the sWAT, but much lower amounts of changes in aWAT were seen. Interestingly, the rickett's big-footed bat did not show such a tendency in beige fat. Conclusions The great roundleaf bat is potentially a good animal model for human aWAT browning research. Combined with rodent models, this model should be helpful for finding therapies for reducing harmful aWAT in humans. PMID:25393240

Urban resident attitudes toward rodents, rodent control products, and environmental effects

EPA Science Inventory

Rodent control in urban areas can result in the inadvertent mortality of non-target species (e.g., bobcats). However, there is little detailed information about rodent control practices of urban residents. Our objective was to evaluate urban rodent control behaviors in two area...

Detection of Myelination Using a Novel Histological Probe

PubMed Central

Xiang, Zhongmin; Nesterov, Evgueni E.; Skoch, Jesse; Lin, Tong; Hyman, Bradley T.; Swager, Timothy M.; Bacskai, Brian J.; Reeves, Steven A.

2005-01-01

Current methods for myelin staining in tissue sections include both histological and immunohistochemical techniques. Fluorescence immunohistochemistry, which uses antibodies against myelin components such as myelin basic protein, is often used because of the convenience for multiple labeling. To facilitate studies on myelin, this paper describes a quick and easy method for direct myelin staining in rodent and human tissues using novel near-infrared myelin (NIM) dyes that are comparable to other well-characterized histochemical reagents. The near-infrared fluorescence spectra of these probes allow fluorescent staining of tissue sections in multiple channels using visible light fluorophores commonly used in immunocytochemistry. These dyes have been used successfully to detect normal myelin structure and myelin loss in a mouse model of demyelination disease. PMID:16046669

Anticoagulant rodenticides and wildlife: Introduction

USGS Publications Warehouse

van den Brink, Nico W.; Elliott, John E.; Shore, Richard F.; Rattner, Barnett A.; van den Brink, Nico W.; Elliott, John E.; Shore, Richard F.; Rattner, Barnett A.

2018-01-01

Rodents have interacted with people since the beginning of systematic food storage by humans in the early Neolithic era. Such interactions have had adverse outcomes such as threats to human health, spoiling and consumption of food sources, damage to human infrastructure and detrimental effects on indigenous island wildlife (through inadvertent anthropogenic assisted introductions). These socio/economic and environmental impacts illustrate the clear need to control populations of commensal rodents. Different methods have been applied historically but the main means of control in the last decades is through the application of rodenticides, mainly anticoagulant rodenticides (ARs) that inhibit blood clotting. The so-called First Generation Anticoagulant Rodenticides (FGARs) proved highly effective but rodents increasingly developed resistance. This led to a demand for more effective alternative compounds and paved the way to the development of Second Generation Anticoagulant Rodenticides (SGARs). These were more acutely toxic and persistent, making them more effective but also increasing the risks of exposure of non-target species and secondary poisoning of predatory species. SGARs often fail the environmental thresholds of different regulatory frameworks because of these negative side-effects, but their use is still permitted because of the overwhelming societal needs for rodent control and the lack of effective alternatives. This book provides a state-of-the-art overview of the scientific advancements in assessment of environmental exposure, effects and risks of currently used ARs. This is discussed in relation to the societal needs for rodent control, including risk mitigation and development of alternatives.

Genetic identification of Iberian rodent species using both mitochondrial and nuclear loci: application to noninvasive sampling.

PubMed

Barbosa, S; Pauperio, J; Searle, J B; Alves, P C

2013-01-01

Species identification through noninvasive sampling is increasingly used in animal conservation genetics, given that it obviates the need to handle free-living individuals. Noninvasive sampling is particularly valuable for elusive and small species such as rodents. Although rodents are not usually assumed to be the most obvious target for conservation, of the 21 species or near-species present in Iberia, three are considered endangered and declining, while several others are poorly studied. Here, we develop a genetic tool for identifying all rodent species in Iberia by noninvasive genetic sampling. To achieve this purpose, we selected one mitochondrial gene [cytochrome b (cyt-b)] and one nuclear gene [interphotoreceptor retinoid-binding protein (IRBP)], which we first sequenced using tissue samples. Both genes allow for the phylogenetic distinction of all species except the sibling species Microtus lusitanicus and Microtus duodecimcostatus. Overall, cyt-b showed higher resolution than IRBP, revealing a clear barcoding gap. To allow these markers to be applied to noninvasive samples, we selected a short highly diagnostic fragment from each gene, which we used to obtain sequences from faeces and bones from owl pellets. Amplification success for the cyt-b and IRBP fragment was 85% and 43% in faecal and 88% and 64% in owl-pellet DNA extractions, respectively. The method allows the unambiguous identification of the great majority of Iberian rodent species from noninvasive samples, with application in studies of distribution, spatial ecology and population dynamics, and for conservation. © 2012 Blackwell Publishing Ltd.

Rodent models of insomnia: a review of experimental procedures that induce sleep disturbances.

PubMed

Revel, Florent G; Gottowik, Juergen; Gatti, Sylvia; Wettstein, Joseph G; Moreau, Jean-Luc

2009-06-01

Insomnia, the most common sleep disorder, is characterized by persistent difficulty in falling or staying asleep despite adequate opportunity to sleep, leading to daytime fatigue and mental dysfunction. As sleep is a sophisticated physiological process generated by a network of neuronal systems that cannot be reproduced in-vitro, pre-clinical development of hypnotic drugs requires in-vivo investigations. Accordingly, this review critically evaluates current and putative rodent models of insomnia which could be used to screen novel hypnotics. Only few valid insomnia models are currently available, although many experimental conditions lead to disturbance of physiological sleep. We categorized these conditions as a function of the procedure used to induce perturbation of sleep, and we discuss their respective advantages and pitfalls with respect to validity, feasibility and translational value to human research.

The Role of Estrogens in Pancreatic Islet Physiopathology.

PubMed

Mauvais-Jarvis, Franck; Le May, Cedric; Tiano, Joseph P; Liu, Suhuan; Kilic-Berkmen, Gamze; Kim, Jun Ho

2017-01-01

In rodent models of insulin-deficient diabetes, 17β-estradiol (E2) protects pancreatic insulin-producing β-cells against oxidative stress, amyloid polypeptide toxicity, gluco-lipotoxicity, and apoptosis. Three estrogen receptors (ERs)-ERα, ERβ, and the G protein-coupled ER (GPER)-have been identified in rodent and human β-cells. This chapter describes recent advances in our understanding of the role of ERs in islet β-cell function, nutrient homeostasis, survival from pro-apoptotic stimuli, and proliferation. We discuss why and how ERs represent potential therapeutic targets for the maintenance of functional β-cell mass.

Using Modelling to Disentangle the Relative Contributions of Zoonotic and Anthroponotic Transmission: The Case of Lassa Fever

PubMed Central

Lo Iacono, Giovanni; Cunningham, Andrew A.; Fichet-Calvet, Elisabeth; Garry, Robert F.; Grant, Donald S.; Khan, Sheik Humarr; Leach, Melissa; Moses, Lina M.; Schieffelin, John S.; Shaffer, Jeffrey G.; Webb, Colleen T.; Wood, James L. N.

2015-01-01

Background Zoonotic infections, which transmit from animals to humans, form the majority of new human pathogens. Following zoonotic transmission, the pathogen may already have, or may acquire, the ability to transmit from human to human. With infections such as Lassa fever (LF), an often fatal, rodent-borne, hemorrhagic fever common in areas of West Africa, rodent-to-rodent, rodent-to-human, human-to-human and even human-to-rodent transmission patterns are possible. Indeed, large hospital-related outbreaks have been reported. Estimating the proportion of transmission due to human-to-human routes and related patterns (e.g. existence of super-spreaders), in these scenarios is challenging, but essential for planned interventions. Methodology/Principal Findings Here, we make use of an innovative modeling approach to analyze data from published outbreaks and the number of LF hospitalized patients to Kenema Government Hospital in Sierra Leone to estimate the likely contribution of human-to-human transmission. The analyses show that almost of the cases at KGH are secondary cases arising from human-to-human transmission. However, we found much of this transmission is associated with a disproportionally large impact of a few individuals (‘super-spreaders’), as we found only of human cases result in an effective reproduction number (i.e. the average number of secondary cases per infectious case) , with a maximum value up to . Conclusions/Significance This work explains the discrepancy between the sizes of reported LF outbreaks and a clinical perception that human-to-human transmission is low. Future assessment of risks of LF and infection control guidelines should take into account the potentially large impact of super-spreaders in human-to-human transmission. Our work highlights several neglected topics in LF research, the occurrence and nature of super-spreading events and aspects of social behavior in transmission and detection. PMID:25569707

Using modelling to disentangle the relative contributions of zoonotic and anthroponotic transmission: the case of lassa fever.

PubMed

Lo Iacono, Giovanni; Cunningham, Andrew A; Fichet-Calvet, Elisabeth; Garry, Robert F; Grant, Donald S; Khan, Sheik Humarr; Leach, Melissa; Moses, Lina M; Schieffelin, John S; Shaffer, Jeffrey G; Webb, Colleen T; Wood, James L N

2015-01-01

Zoonotic infections, which transmit from animals to humans, form the majority of new human pathogens. Following zoonotic transmission, the pathogen may already have, or may acquire, the ability to transmit from human to human. With infections such as Lassa fever (LF), an often fatal, rodent-borne, hemorrhagic fever common in areas of West Africa, rodent-to-rodent, rodent-to-human, human-to-human and even human-to-rodent transmission patterns are possible. Indeed, large hospital-related outbreaks have been reported. Estimating the proportion of transmission due to human-to-human routes and related patterns (e.g. existence of super-spreaders), in these scenarios is challenging, but essential for planned interventions. Here, we make use of an innovative modeling approach to analyze data from published outbreaks and the number of LF hospitalized patients to Kenema Government Hospital in Sierra Leone to estimate the likely contribution of human-to-human transmission. The analyses show that almost [Formula: see text] of the cases at KGH are secondary cases arising from human-to-human transmission. However, we found much of this transmission is associated with a disproportionally large impact of a few individuals ('super-spreaders'), as we found only [Formula: see text] of human cases result in an effective reproduction number (i.e. the average number of secondary cases per infectious case) [Formula: see text], with a maximum value up to [Formula: see text]. This work explains the discrepancy between the sizes of reported LF outbreaks and a clinical perception that human-to-human transmission is low. Future assessment of risks of LF and infection control guidelines should take into account the potentially large impact of super-spreaders in human-to-human transmission. Our work highlights several neglected topics in LF research, the occurrence and nature of super-spreading events and aspects of social behavior in transmission and detection.

Animal reservoir, natural and socioeconomic variations and the transmission of hemorrhagic fever with renal syndrome in Chenzhou, China, 2006-2010.

PubMed

Xiao, Hong; Tian, Huai-Yu; Gao, Li-Dong; Liu, Hai-Ning; Duan, Liang-Song; Basta, Nicole; Cazelles, Bernard; Li, Xiu-Jun; Lin, Xiao-Ling; Wu, Hong-Wei; Chen, Bi-Yun; Yang, Hui-Suo; Xu, Bing; Grenfell, Bryan

2014-01-01

China has the highest incidence of hemorrhagic fever with renal syndrome (HFRS) worldwide. Reported cases account for 90% of the total number of global cases. By 2010, approximately 1.4 million HFRS cases had been reported in China. This study aimed to explore the effect of the rodent reservoir, and natural and socioeconomic variables, on the transmission pattern of HFRS. Data on monthly HFRS cases were collected from 2006 to 2010. Dynamic rodent monitoring data, normalized difference vegetation index (NDVI) data, climate data, and socioeconomic data were also obtained. Principal component analysis was performed, and the time-lag relationships between the extracted principal components and HFRS cases were analyzed. Polynomial distributed lag (PDL) models were used to fit and forecast HFRS transmission. Four principal components were extracted. Component 1 (F1) represented rodent density, the NDVI, and monthly average temperature. Component 2 (F2) represented monthly average rainfall and monthly average relative humidity. Component 3 (F3) represented rodent density and monthly average relative humidity. The last component (F4) represented gross domestic product and the urbanization rate. F2, F3, and F4 were significantly correlated, with the monthly HFRS incidence with lags of 4 months (r = -0.289, P<0.05), 5 months (r = -0.523, P<0.001), and 0 months (r = -0.376, P<0.01), respectively. F1 was correlated with the monthly HFRS incidence, with a lag of 4 months (r = 0.179, P = 0.192). Multivariate PDL modeling revealed that the four principal components were significantly associated with the transmission of HFRS. The monthly trend in HFRS cases was significantly associated with the local rodent reservoir, climatic factors, the NDVI, and socioeconomic conditions present during the previous months. The findings of this study may facilitate the development of early warning systems for the control and prevention of HFRS and similar diseases.

Clonidine Reduces Norepinephrine and Improves Bone Marrow Function in a Rodent Model of Lung Contusion, Hemorrhagic Shock and Chronic Stress

PubMed Central

Alamo, Ines G.; Kannan, Kolenkode B.; Ramos, Harry; Loftus, Tyler J.; Efron, Philip A.; Mohr, Alicia M.

2016-01-01

Background Propranolol has been shown previously to restore bone marrow function and improve anemia after lung contusion/hemorrhagic shock. We hypothesized that daily clonidine administration would inhibit central sympathetic outflow and restore bone marrow function in our rodent model of lung contusion/hemorrhagic shock with chronic stress. Methods Male Sprague-Dawley rats underwent six days of restraint stress after lung contusion/hemorrhagic shock during which the animals received clonidine (75μg/kg) after the restraint stress. On post-injury day seven, we assessed urine norepinephrine, blood hemoglobin, plasma granulocyte colony stimulating factor (G-CSF), and peripheral blood mobilization of hematopoietic progenitor cells (HPC), as well as bone marrow cellularity and erythroid progenitor cell growth. Results The addition of clonidine to lung contusion/hemorrhagic shock with chronic restraint stress, significantly decreased urine norepinephrine levels, improved bone marrow cellularity, restored erythroid progenitor colony growth, and improved hemoglobin (14.1±0.6 vs. 10.8±0.6 g/dL). The addition of clonidine to lung contusion/hemorrhagic shock with chronic restraint stress significantly decreased HPC mobilization and restored G-CSF levels. Conclusions After lung contusion/hemorrhagic shock with chronic restraint stress, daily administration of clonidine restored bone marrow function and improved anemia. Alleviating chronic stress and decreasing norepinephrine is a key therapeutic target to improve bone marrow function after severe injury. PMID:27742030

Challenges in Modelling Hypoglycaemia-Associated Autonomic Failure: A Review of Human and Animal Studies

PubMed Central

Zhou, Xin-Fu

2016-01-01

Recurrent insulin-induced hypoglycaemia is a major limitation to insulin treatment in diabetes patients leading to a condition called hypoglycaemia-associated autonomic failure (HAAF). HAAF is characterised by reduced sympathoadrenal response to subsequent hypoglycaemia thereby predisposing the patients to severe hypoglycaemia that can lead to coma or even death. Despite several attempts being made, the mechanism of HAAF is yet to be clearly established. In order for the mechanism of HAAF to be elucidated, establishing a human/animal model of the phenomenon is the foremost requirement. Several research groups have attempted to reproduce the phenomenon in diabetic and nondiabetic humans and rodents and reported variable results. The success of the phenomenon is marked by a significant reduction in plasma adrenaline response to subsequent hypoglycaemic episode relative to that of the antecedent hypoglycaemic episode. A number of factors such as the insulin dosage, route of administration, fasting conditions, blood sampling methods and analyses, depth, duration, and number of antecedent hypoglycaemic episodes can impact the successful reproduction of the phenomenon and thus have to be carefully considered while developing the protocol. In this review, we have outlined the protocols followed by different research groups to reproduce the phenomenon in diabetic and nondiabetic humans and rodents including our own observations in rats and discussed the factors that have to be given careful consideration in reproducing the phenomenon successfully. PMID:27843452

Epigenetic mechanisms of dietary restriction induced aging in Drosophila.

PubMed

Lian, Ting; Gaur, Uma; Yang, Deying; Li, Diyan; Li, Ying; Yang, Mingyao

2015-12-01

Aging is a long-standing problem that people are always interested in. Thus, it is critical to understand the underlying molecular mechanisms in aging and explore the most efficient method to extend life expectancy. To achieve this goal, a wide range of systems including cells, rodent models, budding yeast, worms and flies have been employed for decades. In recent years, the effect of dietary restriction (DR) on lifespan is in the prime focus. Although we have confirmed that reduced insulin and/or insulin-like growth factor (IGF) and the target of rapamycin (TOR) signaling can increase Drosophila lifespan; the precise molecular mechanisms and nutritional response landscape of diet-mediated aging is ambiguous. Epigenetic events have been considered as the major contributors to lifespan extension with response to DR. The role of DNA methylation in aging is well acknowledged in mammals and rodents where it has been shown to impact aging by regulating the transcription, though the mechanism of regulation is not limited to only transcription. In Drosophila, the contribution of methylation during DR in aging is definitely less explored. In this review, we will update the advances in mechanisms of DR, with a particular focus on methylation as an upcoming target for aging studies and discuss Drosophila as a powerful model to understand mechanisms of aging with response to diet. Copyright © 2015 Elsevier Inc. All rights reserved.

Clinical and pathological manifestations of cardiovascular disease in rat models: the influence of acute ozone exposure

EPA Science Inventory

This paper shows that rat models of cardiovascular diseases have differential degrees of underlying pathologies at a young age. Rodent models of cardiovascular diseases (CVD) and metabolic disorders are used for examining susceptibility variations to environmental exposures. How...

Leveraging Small Aquarium Fishes to Advance Understanding of Environmentally Influenced Human Disorders and Diseases

EPA Science Inventory

Small aquarium fishes provide a model organism that recapitulates the development, physiology and specific disease processes present in humans without the many limitations of rodent-based models currently in use. Fish models offer advantages in cost, rapid life-cycles, and extern...

More than two decades of Apc modeling in rodents

PubMed Central

Zeineldin, Maged; Neufeld, Kristi L.

2013-01-01

Mutation of tumor suppressor gene Adenomatous polyposis coli (APC) is an initiating step in most colon cancers. This review summarizes Apc models in mice and rats, with particular concentration on those most recently developed, phenotypic variation among different models, and genotype/ phenotype correlations. PMID:23333833

Setting the main circadian clock of a diurnal mammal by hypocaloric feeding

PubMed Central

Mendoza, Jorge; Gourmelen, Sylviane; Dumont, Stephanie; Sage-Ciocca, Dominique; Pévet, Paul; Challet, Etienne

2012-01-01

Caloric restriction attenuates the onset of a number of pathologies related to ageing. In mammals, circadian rhythms, controlled by the hypothalamic suprachiasmatic (SCN) clock, are altered with ageing. Although light is the main synchronizer for the clock, a daily hypocaloric feeding (HF) may also modulate the SCN activity in nocturnal rodents. Here we report that a HF also affects behavioural, physiological and molecular circadian rhythms of the diurnal rodent Arvicanthis ansorgei. Under constant darkness HF, but not normocaloric feeding (NF), entrains circadian behaviour. Under a light–dark cycle, HF at midnight led to phase delays of the rhythms of locomotor activity and plasma corticosterone. Furthermore, Per2 and vasopressin gene oscillations in the SCN were phase delayed in HF Arvicanthis compared with animals fed ad libitum. Moreover, light-induced expression of Per genes in the SCN was modified in HF Arvicanthis, despite a non-significant effect on light-induced behavioural phase delays. Together, our data show that HF affects the circadian system of the diurnal rodent Arvicanthis ansorgei differentially from nocturnal rodents. The Arvicanthis model has relevance for the potential use of HF to manipulate circadian rhythms in diurnal species including humans. PMID:22570380

Ultrasonic vocalisation emitted by infant rodents: a tool for assessment of neurobehavioural development.

PubMed

Branchi, I; Santucci, D; Alleva, E

2001-11-01

Ultrasonic vocalisations (USVs) emitted by altricial rodent pups are whistle-like sounds with frequencies between 30 and 90 kHz. These signals play an important communicative role in mother-offspring interaction since they elicit in the dam a prompt response concerning caregiving behaviours. Both physical and social parameters modulate the USV emission in the infant rodent. Recently, a more detailed analysis of the ultrasonic vocalisation pattern, considering the spectrographic structure of sounds has allowed a deeper investigation of this behaviour. In order to investigate neurobehavioural development, the analysis of USVs presents several advantages, mainly: (i) USVs are one of the few responses produced by very young mice that can be quantitatively analysed and elicited by quantifiable stimuli; (ii) USV production follows a clear ontogenetic profile from birth to PND 14-15, thus allowing longitudinal neurobehavioural analysis during very early postnatal ontogeny. The study of this ethologically-ecologically relevant behaviour represent a valid model to evaluate possible alterations in the neurobehavioural development of perinatally treated or genetically modified infant rodents. Furthermore, the role played by several receptor agonists and antagonists in modulating USV rate makes this measure particularly important when investigating the effects of anxiogenic and anxiolytic compounds, and emotional behaviour in general.

Behavioral and physiological consequences of enrichment loss in rats

PubMed Central

Smith, Brittany L.; Lyons, Carey E; Correa, Fernanda Guilhaume; Benoit, Stephen C.; Myers, Brent; Solomon, Matia B.; Herman, James P.

2017-01-01

Significant loss produces the highest degree of stress and compromised well-being in humans. Current rodent models of stress involve the application of physically or psychologically aversive stimuli, but do not address the concept of loss. We developed a rodent model for significant loss, involving removal of long-term access to a rewarding enriched environment. Our results indicate that removal from environmental enrichment produces a profound behavioral and physiological phenotype with depression-like qualities, including helplessness behavior, hypothalamo-pituitary-adrenocortical axis dysregulation and overeating. Importantly, this enrichment removal phenotype was prevented by antidepressant treatment. Furthermore, the effects of enrichment removal do not occur following relief from chronic stress and are not duplicated by loss of exercise or social contact. PMID:28012292

Teratology studies in the mouse.

PubMed

Marsden, Edward; Leroy, Mariline

2013-01-01

The rat is the routine species of choice as the rodent model for regulatory safety testing of xenobiotics such as medicinal products, food additives, and other chemicals. However, the rat is not always suitable for pharmacological, toxicological, immunogenic, pharmacokinetic, or even practical reasons. Under such circumstances, the mouse offers an alternative for finding a suitable rodent model acceptable to the regulatory authorities. Since all essential routes of administration are possible, the short reproductive cycle and large litter size of the mouse make it a species well adapted for use in teratology studies. Given that good quality animals, including virgin mated females, can be acquired relatively easily and inexpensively, the mouse has been used in reproductive toxicity studies for decades and study protocols are well established.

Hantavirus Immunology of Rodent Reservoirs: Current Status and Future Directions

PubMed Central

Schountz, Tony; Prescott, Joseph

2014-01-01

Hantaviruses are hosted by rodents, insectivores and bats. Several rodent-borne hantaviruses cause two diseases that share many features in humans, hemorrhagic fever with renal syndrome in Eurasia or hantavirus cardiopulmonary syndrome in the Americas. It is thought that the immune response plays a significant contributory role in these diseases. However, in reservoir hosts that have been closely examined, little or no pathology occurs and infection is persistent despite evidence of adaptive immune responses. Because most hantavirus reservoirs are not model organisms, it is difficult to conduct meaningful experiments that might shed light on how the viruses evade sterilizing immune responses and why immunopathology does not occur. Despite these limitations, recent advances in instrumentation and bioinformatics will have a dramatic impact on understanding reservoir host responses to hantaviruses by employing a systems biology approach to identify important pathways that mediate virus/reservoir relationships. PMID:24638205

Hantavirus immunology of rodent reservoirs: current status and future directions.

PubMed

Schountz, Tony; Prescott, Joseph

2014-03-14

Hantaviruses are hosted by rodents, insectivores and bats. Several rodent-borne hantaviruses cause two diseases that share many features in humans, hemorrhagic fever with renal syndrome in Eurasia or hantavirus cardiopulmonary syndrome in the Americas. It is thought that the immune response plays a significant contributory role in these diseases. However, in reservoir hosts that have been closely examined, little or no pathology occurs and infection is persistent despite evidence of adaptive immune responses. Because most hantavirus reservoirs are not model organisms, it is difficult to conduct meaningful experiments that might shed light on how the viruses evade sterilizing immune responses and why immunopathology does not occur. Despite these limitations, recent advances in instrumentation and bioinformatics will have a dramatic impact on understanding reservoir host responses to hantaviruses by employing a systems biology approach to identify important pathways that mediate virus/reservoir relationships.

Antitumor Efficacy Testing in Rodents

PubMed Central

2008-01-01

The preclinical research and human clinical trials necessary for developing anticancer therapeutics are costly. One contributor to these costs is preclinical rodent efficacy studies, which, in addition to the costs associated with conducting them, often guide the selection of agents for clinical development. If inappropriate or inaccurate recommendations are made on the basis of these preclinical studies, then additional costs are incurred. In this commentary, I discuss the issues associated with preclinical rodent efficacy studies. These include the identification of proper preclinical efficacy models, the selection of appropriate experimental endpoints, and the correct statistical evaluation of the resulting data. I also describe important experimental design considerations, such as selecting the drug vehicle, optimizing the therapeutic treatment plan, properly powering the experiment by defining appropriate numbers of replicates in each treatment arm, and proper randomization. Improved preclinical selection criteria can aid in reducing unnecessary human studies, thus reducing the overall costs of anticancer drug development. PMID:18957675

Dendrimer-driven neurotrophin expression differs in temporal patterns between rodent and human stem cells.

PubMed

Shakhbazau, Antos; Shcharbin, Dzmitry; Seviaryn, Ihar; Goncharova, Natalya; Kosmacheva, Svetlana; Potapnev, Mihail; Bryszewska, Maria; Kumar, Ranjan; Biernaskie, Jeffrey; Midha, Rajiv

2012-05-07

This study reports the use of a nonviral expression system based on polyamidoamine dendrimers for time-restricted neurotrophin overproduction in mesenchymal stem cells and skin precursor-derived Schwann cells. The dendrimers were used to deliver plasmids for brain-derived neurotrophic factor (BDNF) or neurotrophin-3 (NT-3) expression in both rodent and human stem cells, and the timelines of expression were studied. We have found that, despite the fact that transfection efficiencies and protein expression levels were comparable, dendrimer-driven expression in human mesenchymal stem cells was characterized by a more rapid decline compared to rodent cells. Transient expression systems can be beneficial for some neurotrophins, which were earlier reported to cause unwanted side effects in virus-based long-term expression models. Nonviral neurotrophin expression is a biologically safe and accessible alternative to increase the therapeutic potential of autologous adult stem cells and stem cell-derived functional differentiated cells.

Perceptual Decision Making in Rodents, Monkeys, and Humans.

PubMed

Hanks, Timothy D; Summerfield, Christopher

2017-01-04

Perceptual decision making is the process by which animals detect, discriminate, and categorize information from the senses. Over the past two decades, understanding how perceptual decisions are made has become a central theme in the neurosciences. Exceptional progress has been made by recording from single neurons in the cortex of the macaque monkey and using computational models from mathematical psychology to relate these neural data to behavior. More recently, however, the range of available techniques and paradigms has dramatically broadened, and researchers have begun to harness new approaches to explore how rodents and humans make perceptual decisions. The results have illustrated some striking convergences with findings from the monkey, but also raised new questions and provided new theoretical insights. In this review, we summarize key findings, and highlight open challenges, for understanding perceptual decision making in rodents, monkeys, and humans. Copyright © 2017 Elsevier Inc. All rights reserved.

Environmental variability and the transmission of haemorrhagic fever with renal syndrome in Changsha, People's Republic of China.

PubMed

Xiao, H; Gao, L D; Li, X J; Lin, X L; Dai, X Y; Zhu, P J; Chen, B Y; Zhang, X X; Zhao, J; Tian, H Y

2013-09-01

The transmission of haemorrhagic fever with renal syndrome (HFRS) is influenced by climatic, reservoir and environmental variables. The epidemiology of the disease was studied over a 6-year period in Changsha. Variables relating to climate, environment, rodent host distribution and disease occurrence were collected monthly and analysed using a time-series adjusted Poisson regression model. It was found that the density of the rodent host and multivariate El Niño Southern Oscillation index had the greatest effect on the transmission of HFRS with lags of 2–6 months. However, a number of climatic and environmental factors played important roles in affecting the density and transmission potential of the rodent host population. It was concluded that the measurement of a number of these variables could be used in disease surveillance to give useful advance warning of potential disease epidemics.

Rodent wearable ultrasound system for wireless neural recording.

PubMed

Piech, David K; Kay, Joshua E; Boser, Bernhard E; Maharbiz, Michel M

2017-07-01

Advances in minimally-invasive, distributed biological interface nodes enable possibilities for networks of sensors and actuators to connect the brain with external devices. The recent development of the neural dust sensor mote has shown that utilizing ultrasound backscatter communication enables untethered sub-mm neural recording devices. These implanted sensor motes require a wearable external ultrasound interrogation device to enable in-vivo, freely-behaving neural interface experiments. However, minimizing the complexity and size of the implanted sensors shifts the power and processing burden to the external interrogator. In this paper, we present an ultrasound backscatter interrogator that supports real-time backscatter processing in a rodent-wearable, completely wireless device. We demonstrate a generic digital encoding scheme which is intended for transmitting neural information. The system integrates a front-end ultrasonic interface ASIC with off-the-shelf components to enable a highly compact ultrasound interrogation device intended for rodent neural interface experiments but applicable to other model systems.

A radiographic method to estimate lung volume and its use in small mammals.

PubMed

Canals, Mauricio; Olivares, Ricardo; Rosenmann, Mario

2005-01-01

In this paper we develop a method to estimate lung volume using chest x-rays of small mammals. We applied this method to assess the lung volume of several rodents. We showed that a good estimator of the lung volume is: V*L = 0.496 x VRX approximately equal to 1/2 x VRX, where VRX is a measurement obtained from the x-ray that represents the volume of a rectangular box containing the lungs and mediastinum organs. The proposed formula may be interpreted as the volume of an ellipsoid formed by both lungs joined at their bases. When that relationship was used to estimate lung volume, values similar to those expected from allometric relationship were found in four rodents. In two others, M. musculus and R. norvegicus, lung volume was similar to reported data, although values were lower than expected.

Zoonoses of rabbits and rodents.

PubMed

Hill, William Allen; Brown, Julie Paige

2011-09-01

Millions of households in the US own rabbits or rodents, including hamsters, guinea pigs, and gerbils. Activities such as hunting and camping also involve human interactions with wild rabbits and rodents. In many environments, feral rabbits and rodents live in close proximity to humans, domesticated animals, and other wildlife. Education of rodent and rabbit owners and individuals with occupational or recreational exposures to these species is paramount to reduce the prevalence of zoonoses associated with rabbit and rodent exposure.

Lassa serology in natural populations of rodents and horizontal transmission.

PubMed

Fichet-Calvet, Elisabeth; Becker-Ziaja, Beate; Koivogui, Lamine; Günther, Stephan

2014-09-01

Lassa virus causes hemorrhagic fever in West Africa. Previously, we demonstrated by PCR screening that only the multimammate mouse, Mastomys natalensis, hosts Lassa virus in Guinea. In the present study, we used the same specimen collection from 17 villages in Coastal, Upper, and Forest Guinea to investigate the Lassa virus serology in the rodent population. The aim was to determine the dynamics of antibody development in M. natalensis and to detect potential spillover infections in other rodent species. Immunoglobulin G (IgG) antibody screening was performed using the indirect immunofluorescence assay with the Guinean Lassa virus strain Bantou 289 as antigen. The overall seroprevalence was 8% (129/1551) with the following rodents testing positive: 109 M. natalensis, seven Mastomys erythroleucus, four Lemniscomys striatus, four Praomys daltoni, three Mus minutoides, and two Praomys rostratus. Nearly all of them (122/129) originated from Bantou, Tanganya, and Gbetaya, where Lassa virus is highly endemic in M. natalensis. The antibody seroprevalence in M. natalensis from this high-endemic area (27%; 108/396) depended on the village, habitat, host age, and host abundance. A main positive factor was age; the maximum seroprevalence reached 50% in older animals. Our data fit with a model implicating that most M. natalensis rodents become horizontally infected, clear the virus within a period significantly shorter than their life span, and develop antibodies. In addition, the detection of antibodies in other species trapped in the habitats of M. natalensis suggests spillover infections.

Rodent models in Down syndrome research: impact and future opportunities

PubMed Central

2017-01-01

ABSTRACT Down syndrome is caused by trisomy of chromosome 21. To date, a multiplicity of mouse models with Down-syndrome-related features has been developed to understand this complex human chromosomal disorder. These mouse models have been important for determining genotype-phenotype relationships and identification of dosage-sensitive genes involved in the pathophysiology of the condition, and in exploring the impact of the additional chromosome on the whole genome. Mouse models of Down syndrome have also been used to test therapeutic strategies. Here, we provide an overview of research in the last 15 years dedicated to the development and application of rodent models for Down syndrome. We also speculate on possible and probable future directions of research in this fast-moving field. As our understanding of the syndrome improves and genome engineering technologies evolve, it is necessary to coordinate efforts to make all Down syndrome models available to the community, to test therapeutics in models that replicate the whole trisomy and design new animal models to promote further discovery of potential therapeutic targets. PMID:28993310

Rodent models in Down syndrome research: impact and future opportunities.

PubMed

Herault, Yann; Delabar, Jean M; Fisher, Elizabeth M C; Tybulewicz, Victor L J; Yu, Eugene; Brault, Veronique

2017-10-01

Down syndrome is caused by trisomy of chromosome 21. To date, a multiplicity of mouse models with Down-syndrome-related features has been developed to understand this complex human chromosomal disorder. These mouse models have been important for determining genotype-phenotype relationships and identification of dosage-sensitive genes involved in the pathophysiology of the condition, and in exploring the impact of the additional chromosome on the whole genome. Mouse models of Down syndrome have also been used to test therapeutic strategies. Here, we provide an overview of research in the last 15 years dedicated to the development and application of rodent models for Down syndrome. We also speculate on possible and probable future directions of research in this fast-moving field. As our understanding of the syndrome improves and genome engineering technologies evolve, it is necessary to coordinate efforts to make all Down syndrome models available to the community, to test therapeutics in models that replicate the whole trisomy and design new animal models to promote further discovery of potential therapeutic targets. © 2017. Published by The Company of Biologists Ltd.

Relevance of Rodent Models of Depression in Clinical Practice: Can We Overcome the Obstacles in Translational Neuropsychiatry?

PubMed

Söderlund, Johan; Lindskog, Maria

2018-04-23

The diagnosis of a mental disorder generally depends on clinical observations and phenomenological symptoms reported by the patient. The definition of a given diagnosis is criteria based and relies on the ability to accurately interpret subjective symptoms and complex behavior. This type of diagnosis comprises a challenge to translate to reliable animal models, and these translational uncertainties hamper the development of new treatments. In this review, we will discuss how depressive-like behavior can be induced in rodents, and the relationship between these models and depression in humans. Specifically, we suggest similarities between triggers of depressive-like behavior in animal models and human conditions known to increase the risk of depression, for example exhaustion and bullying. Although we acknowledge the potential problems in comparing animal findings to human conditions, such comparisons are useful for understanding the complexity of depression, and we highlight the need to develop clinical diagnoses and animal models in parallel to overcome translational uncertainties.

An ex vivo rat eye model to aid development of high-resolution retina imaging devices for rodents

NASA Astrophysics Data System (ADS)

van Oterendorp, Christian; Martin, Keith R.; Zhong, Jiang Jian; Diaz-Santana, Luis

2010-09-01

High resolution in vivo retinal imaging in rodents is becoming increasingly important in eye research. Development of suitable imaging devices currently requires many lengthy animal procedures. We present an ex vivo rat model eye with fluorescently labelled retinal ganglion cells (RGC) and nerve fibre bundles that reduces the need for animal procedures while preserving key properties of the living rat eye. Optical aberrations and scattering of four model eyes and eight live rat eyes were quantified using a Shack-Hartmann sensor. Fluorescent images from RGCs were obtained using a prototype scanning laser ophthalmoscope. The wavefront aberration root mean square value without defocus did not significantly differ between model and living eyes. Higher order aberrations were slightly higher but RGC image quality was comparable to published in vivo work. Overall, the model allows a large reduction in number and duration of animal procedures required to develop new in vivo retinal imaging devices.

Intrinsic neurophysiological properties of hilar ectopic and normotopic dentate granule cells in human temporal lobe epilepsy and a rat model.

PubMed

Althaus, A L; Sagher, O; Parent, J M; Murphy, G G

2015-02-15

Hilar ectopic dentate granule cells (DGCs) are a salient feature of aberrant plasticity in human temporal lobe epilepsy (TLE) and most rodent models of the disease. Recent evidence from rodent TLE models suggests that hilar ectopic DGCs contribute to hyperexcitability within the epileptic hippocampal network. Here we investigate the intrinsic excitability of DGCs from humans with TLE and the rat pilocarpine TLE model with the objective of comparing the neurophysiology of hilar ectopic DGCs to their normotopic counterparts in the granule cell layer (GCL). We recorded from 36 GCL and 7 hilar DGCs from human TLE tissue. Compared with GCL DGCs, hilar DGCs in patient tissue exhibited lower action potential (AP) firing rates, more depolarized AP threshold, and differed in single AP waveform, consistent with an overall decrease in excitability. To evaluate the intrinsic neurophysiology of hilar ectopic DGCs, we made recordings from retrovirus-birthdated, adult-born DGCs 2-4 mo after pilocarpine-induced status epilepticus or sham treatment in rats. Hilar DGCs from epileptic rats exhibited higher AP firing rates than normotopic DGCs from epileptic or control animals. They also displayed more depolarized resting membrane potential and wider AP waveforms, indicating an overall increase in excitability. The contrasting findings between disease and disease model may reflect differences between the late-stage disease tissue available from human surgical specimens and the earlier disease stage examined in the rat TLE model. These data represent the first neurophysiological characterization of ectopic DGCs from human hippocampus and prospectively birthdated ectopic DGCs in a rodent TLE model. Copyright © 2015 the American Physiological Society.

Quantitative trait locus gene mapping: a new method for locating alcohol response genes.

PubMed

Crabbe, J C

1996-01-01

Alcoholism is a multigenic trait with important non-genetic determinants. Studies with genetic animal models of susceptibility to several of alcohol's effects suggest that several genes contributing modest effects on susceptibility (Quantitative Trait Loci, or QTLs) are important. A new technique of QTL gene mapping has allowed the identification of the location in mouse genome of several such QTLs. The method is described, and the locations of QTLs affecting the acute alcohol withdrawal reaction are described as an example of the method. Verification of these QTLs in ancillary studies is described and the strengths, limitations, and future directions to be pursued are discussed. QTL mapping is a promising method for identifying genes in rodents with the hope of directly extrapolating the results to the human genome. This review is based on a paper presented at the First International Congress of the Latin American Society for Biomedical Research on Alcoholism, Santiago, Chile, November 1994.

Pulmonary Complications Resulting from Genetic Cardiovascular Disease in Two Rat Models

EPA Science Inventory

Underlying cardiovascular disease (CVD) has been considered a risk factor for exacerbation of air pollution health effects. Therefore, rodent models of CVD are increasingly used to examine mechanisms of variation in susceptibility. Pulmonary complications and altered iron homeost...

THE SPONTANEOUSLY HYPERTENSIVE RAT: AN EXPERIMENTAL MODEL OF SULFUR DIOXIDE-INDUCED AIRWAYS DISEASE

EPA Science Inventory

Chronic obstructive pulmonary disease (COPD) is characterized by airway obstruction, inflammation and mucus hypersecretion; features that capture bronchitis, emphysema and often asthma. However, current rodent models do not reflect this human disease. Because genetically predisp...

The Effects of Fortetropin Supplementation on Body Composition, Strength, and Power in Humans and Mechanism of Action in a Rodent Model.

PubMed

Sharp, Matthew H; Lowery, Ryan P; Mobley, C Brooks; Fox, Carlton D; de Souza, Eduardo O; Shields, Kevin A; Healy, James C; Arick, Ned Q; Thompson, Richard M; Roberts, Michael D; Wilson, Jacob M

2016-01-01

The purpose of this study was to investigate the effects of Fortetropin on skeletal muscle growth and strength in resistance-trained individuals and to investigate the anabolic and catabolic signaling effects using human and rodent models. In the rodent model, male Wistar rats (250 g) were gavage fed with either 1.2 ml of tap water control (CTL) or 0.26 g Fortetropin for 8 days. Then rats participated in a unilateral plantarflexion exercise bout. Nonexercised and exercised limbs were harvested at 180 minutes following and analyzed for gene and protein expression relative to mammalian target of rapamycin (mTOR) and ubiquitin signaling. For the human model, 45 (of whom 37 completed the study), resistance-trained college-aged males were divided equally into 3 groups receiving a placebo macronutrient matched control, 6.6 or 19.8 g of Fortetropin supplementation during 12 weeks of resistance training. Lean mass, muscle thickness, and lower and upper body strength were measured before and after 12 weeks of training. The human study results indicated a Group × Time effect (p ≤ 0.05) for lean mass in which the 6.6 g (+1.7 kg) and 19.8 g (+1.68 kg) but not placebo (+0.6 kg) groups increased lean mass. Similarly, there was a Group × Time effect for muscle thickness (p ≤ 0.05), which increased in the experimental groups only. All groups increased equally in bench press and leg press strength. In the rodent model, a main effect for exercise (p ≤ 0.05) in which the control plus exercise but not Fortetropin plus exercise increased both ubiquitin monomer protein expression and polyubiquitination. mTOR signaling was elevated to a greater extent in the Fortetropin exercising conditions as indicated by greater phosphorylation status of 4EBP1, rp6, and p70S6K for both exercising conditions. Fortetropin supplementation increases lean body mass (LBM) and decreases markers of protein breakdown while simultaneously increasing mTOR signaling.

Screening and Characterization of Spontaneous Porcine Congenital Heart Defects for Gene Identification and Models of Human Disease

USDA-ARS?s Scientific Manuscript database

Background: Rodent models of human congenital birth defects have been instrumental for gene discovery and investigation of mechanisms of disease. However, these models are limited by their small size making practiced intervention or detailed anatomic evaluation difficult. Swine have similar anato...