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Sample records for altering phagocyte behavior

  1. Altered dynamics of Candida albicans phagocytosis by macrophages and PMNs when both phagocyte subsets are present.

    PubMed

    Rudkin, Fiona M; Bain, Judith M; Walls, Catriona; Lewis, Leanne E; Gow, Neil A R; Erwig, Lars P

    2013-10-29

    phagocyte subset, versus a mixed phagocyte population, on these individual stages. Through this approach, we identified that the rate of fungal cell engulfment and rate of phagocyte killing altered significantly when both macrophages and PMNs were incubated in coculture with C. albicans compared to the rate of either phagocyte subset incubated alone with the fungus. This research highlights the significance of studying pathogen-host cell interactions with a combination of phagocytes in order to gain a greater understanding of the interactions that occur between cells of the host immune system in response to fungal invasion.

  2. Altered Dynamics of Candida albicans Phagocytosis by Macrophages and PMNs When Both Phagocyte Subsets Are Present

    PubMed Central

    Rudkin, Fiona M.; Bain, Judith M.; Walls, Catriona; Lewis, Leanne E.; Gow, Neil A. R.; Erwig, Lars P.

    2013-01-01

    ABSTRACT An important first line of defense against Candida albicans infections is the killing of fungal cells by professional phagocytes of the innate immune system, such as polymorphonuclear cells (PMNs) and macrophages. In this study, we employed live-cell video microscopy coupled with dynamic image analysis tools to provide insights into the complexity of C. albicans phagocytosis when macrophages and PMNs were incubated with C. albicans alone and when both phagocyte subsets were present. When C. albicans cells were incubated with only one phagocyte subtype, PMNs had a lower overall phagocytic capacity than macrophages, despite engulfing fungal cells at a higher rate once fungal cells were bound to the phagocyte surface. PMNs were more susceptible to C. albicans-mediated killing than macrophages, irrespective of the number of C. albicans cells ingested. In contrast, when both phagocyte subsets were studied in coculture, the two cell types phagocytosed and cleared C. albicans at equal rates and were equally susceptible to killing by the fungus. The increase in macrophage susceptibility to C. albicans-mediated killing was a consequence of macrophages taking up a higher proportion of hyphal cells under these conditions. In the presence of both PMNs and macrophages, C. albicans yeast cells were predominantly cleared by PMNs, which migrated at a greater speed toward fungal cells and engulfed bound cells more rapidly. These observations demonstrate that the phagocytosis of fungal pathogens depends on, and is modified by, the specific phagocyte subsets present at the site of infection. PMID:24169578

  3. Methamphetamine Alters the Antimicrobial Efficacy of Phagocytic Cells during Methicillin-Resistant Staphylococcus aureus Skin Infection

    PubMed Central

    Mihu, Mircea Radu; Roman-Sosa, Jessica; Varshney, Avanish K.; Eugenin, Eliseo A.; Shah, Bhavikkumar P.; Ham Lee, Hiu; Nguyen, Long N.; Guimaraes, Allan J.; Fries, Bettina C.; Nosanchuk, Joshua D.

    2015-01-01

    ABSTRACT Methamphetamine (METH) is a major drug of abuse in the United States and worldwide. Furthermore, Staphylococcus aureus infections and METH use are coemerging public health problems. S. aureus is the single most important bacterial pathogen in infections among injection drug users, with skin and soft tissue infections (SSTI) being extremely common. Notably, the incidence of SSTI, especially in drug users, is difficult to estimate because such infections are often self-treated. Although there is substantial information on the behavioral and cognitive defects caused by METH in drug users, there is a dearth of knowledge regarding its impact on bacterial infections and immunity. Therefore, we hypothesized that METH exacerbates S. aureus skin infection. Using a murine model of METH administration and wound infection, we demonstrated that METH reduces wound healing and facilitates host-mediated collagen degradation by increased expression and production of matrix metalloproteinase-2 (MMP-2). Additionally, we found that METH induces S. aureus biofilm formation and leads to detrimental effects on the functions of human and murine phagocytic cells, enhancing susceptibility to S. aureus infection. Our findings provide empirical evidence of the adverse impact of METH use on the antimicrobial efficacy of the cells that comprise innate immunity, the initial host response to combat microbial infection. PMID:26507236

  4. Effect of Estragole on Leukocyte Behavior and Phagocytic Activity of Macrophages

    PubMed Central

    Wiirzler, Luiz Alexandre Marques; Silva-Filho, Saulo Euclides; Kummer, Raquel; Pedroso, Raissa Bocchi; Spironello, Ricardo Alexandre; Silva, Expedito Leite; Bersani-Amado, Ciomar Aparecida; Cuman, Roberto Kenji Nakamura

    2014-01-01

    Estragole, a chemical constituent of the essential oils of many aromatic plants, is used as flavoring in beverage and food industries. In vivo and in vitro experimental assays have shown that EST has sedative, anticonvulsant, antioxidant, antimicrobial, and anesthetic activity. In this work, we evaluate the effect of EST on leukocyte behavior and phagocytic activity of macrophages. In the peritonitis model, EST (500 and 750 mg/kg) decreased the infiltration of peritoneal exudate leukocytes. In vitro chemotaxis assay showed that EST (3, 10, 30, and 60 μg/mL) inhibited neutrophil migration toward fMLP. In the in vivo microcirculation assay, EST at doses of 250, 500, and 750 mg/kg significantly reduced the number of rolling and adherent leukocytes and at doses of 250 and 500 mg/kg decreased number of leukocyte migrated to perivascular tissue. The results showed that EST (3, 10, and 30 μg/mL) was able to stimulate the macrophages phagocytosis but only at concentration of 10 μg/mL promoted an increase in nitric oxide (NO) production. In conclusion, this study showed that EST had potential anti-inflammatory effects, likely by inhibiting leukocyte migration and by stimulating macrophages phagocytosis. PMID:25152763

  5. An observational study of phagocytes and Klebsiella pneumoniae relationships: different behaviors.

    PubMed

    Maisonneuve, Elodie; Cateau, Estelle; Delouche, Marion; Quellard, Nathalie; Rodier, Marie-Helene

    2017-01-10

    Klebsiella pneumoniae is a bacterium that can be in relation with free living amoebae like Acanthamoeba castellanii in natural environments such as soil and water. This pathogen, which is responsible for community-acquired pneumonia and for nosocomial infections, also has interactions with host defense mechanisms like macrophages. As it has been shown that A. castellanii shares some traits with macrophages, in particular the ability to phagocyte bacteria, we have studied the uptake and the fate of the bacteria after contact with the two phagocytic cells. In our conditions, K. pneumoniae growth was increased in coculture in presence of A. castellanii or Thp-1 macrophagic cells and bacterial development was also increased by A. castellanii supernatant. In addition, we showed that the presence of the bacteria had a negative effect on the macrophages whereas it does not affect amoeba viability. Using gentamicin, which kills bacteria outside cells, we showed that only macrophages were able to internalize K. pneumoniae. This result was confirmed by electron microscopy. We have consequently reported some differences in bacterial uptake and internalization between a free living amoeba and macrophagic cells, highlighting the fact that results obtained with this amoebal model should not be extrapolated to the relationships between K. pneumoniae and macrophages.

  6. The Malnutrition-Related Increase in Early Visceralization of Leishmania donovani Is Associated with a Reduced Number of Lymph Node Phagocytes and Altered Conduit System Flow

    PubMed Central

    Ibrahim, Marwa K.; Barnes, Jeffrey L.; Anstead, Gregory M.; Jimenez, Fabio; Travi, Bruno L.; Peniche, Alex G.; Osorio, E. Yaneth; Ahuja, Seema S.; Melby, Peter C.

    2013-01-01

    In a murine model of moderate childhood malnutrition we found that polynutrient deficiency led to a 4–5-fold increase in early visceralization of L. donovani (3 days post-infection) following cutaneous infection and a 16-fold decrease in lymph node barrier function (p<0.04 for all). To begin to understand the mechanistic basis for this malnutrition-related parasite dissemination we analyzed the cellularity, architecture, and function of the skin-draining lymph node. There was no difference in the localization of multiple cell populations in the lymph node of polynutrient deficient (PND) mice, but there was reduced cellularity with fewer CD11c+dendritic cells (DCs), fibroblastic reticular cells (FRCs), MOMA-2+ macrophages, and CD169+ subcapsular sinus macrophage (p<0.05 for all) compared to the well-nourished (WN) mice. The parasites were equally co-localized with DCs associated with the lymph node conduit network in the WN and PND mice, and were found in the high endothelial venule into which the conduits drain. When a fluorescent low molecular weight (10 kD) dextran was delivered in the skin, there was greater efflux of the marker from the lymph node conduit system to the spleens of PND mice (p<0.04), indicating that flow through the conduit system was altered. There was no evidence of disruption of the conduit or subcapsular sinus architecture, indicating that the movement of parasites into the subcortical conduit region was due to an active process and not from passive movement through a leaking barrier. These results indicate that the impaired capacity of the lymph node to act as a barrier to dissemination of L. donovani infection is associated with a reduced number of lymph node phagocytes, which most likely leads to reduced capture of parasites as they transit through the sinuses and conduit system. PMID:23967356

  7. Hypergravity-induced altered behavior in Drosophila

    NASA Astrophysics Data System (ADS)

    Hosamani, Ravikumar; Wan, Judy; Marcu, Oana; Bhattacharya, Sharmila

    2012-07-01

    Microgravity and mechanical stress are important factors of the spaceflight environment, and affect astronaut health and behavior. Structural, functional, and behavioral mechanisms of all cells and organisms are adapted to Earth's gravitational force, 1G, while altered gravity can pose challenges to their adaptability to this new environment. On ground, hypergravity paradigms have been used to predict and complement studies on microgravity. Even small changes that take place at a molecular and genetic level during altered gravity may result in changes in phenotypic behavior. Drosophila provides a robust and simple, yet very reliable model system to understand the complexity of hypergravity-induced altered behavior, due to availability of a plethora of genetic tools. Locomotor behavior is a sensitive parameter that reflects the array of molecular adaptive mechanisms recruited during exposure to altered gravity. Thus, understanding the genetic basis of this behavior in a hypergravity environment could potentially extend our understanding of mechanisms of adaptation in microgravity. In our laboratory we are trying to dissect out the cellular and molecular mechanisms underlying hypergravity-induced oxidative stress, and its potential consequences on behavioral alterations by using Drosophila as a model system. In the present study, we employed pan-neuronal and mushroom body specific knock-down adult flies by using Gal4/UAS system to express inverted repeat transgenes (RNAi) to monitor and quantify the hypergravity-induced behavior in Drosophila. We established that acute hypergravity (3G for 60 min) causes a significant and robust decrease in the locomotor behavior in adult Drosophila, and that this change is dependent on genes related to Parkinson's disease, such as DJ-1α , DJ-1β , and parkin. In addition, we also showed that anatomically the control of this behavior is significantly processed in the mushroom body region of the fly brain. This work links a molecular

  8. Can Molecular Hippocampal Alterations Explain Behavioral ...

    EPA Pesticide Factsheets

    Studies in both humans and animals have shown that prenatal stress can alter cognitive function and other neurological behaviors in adult offspring. One possible underlying mechanism for this may lie with alterations in hippocampal gene expression. The present study examined genotypical outcomes in adult male and female offspring of rats exposed to variable stress during pregnancy. Dams (n=15/treatment) were subjected to several non-chemical stressors including intermittent noise, light, crowding, restraint, and altered circadian lighting, from gestational day (GD) 13 to 20. Tail blood was drawn on GD 12, 16 and 20 to verify a stress response. Corticosterone levels were not different between the stressed and non-stressed dams on GD12 but was significantly increased in stressed dams on GD 16 and 20 compared to controls. Dams gave birth on GD22 (postnatal day or PND 0). Several behavioral tests were used to assess the cognitive and behavioral phenotype of the offspring from PND 49 through 86, including the Morris water maze and novel object recognition. Male and female stressed offspring showed reduced reversal learning on the Morris water maze and stressed females did not show a significant preference for the novel object (57 ± 8%) while control females did (71 ± 3%). This indicates altered cognition in prenatally stressed offspring. On PND 91-92, offspring were necropsied and hippocampal tissue was collected. Genotypic outcomes of prenatal stress w

  9. Phagocytic Clearance in Neurodegeneration

    PubMed Central

    Sokolowski, Jennifer D.; Mandell, James W.

    2011-01-01

    The cellular and molecular mechanisms of phagocytic clearance of apoptotic cells and debris have been intensely studied in invertebrate model organisms and in the mammalian immune system. This evolutionarily conserved process serves multiple purposes. Uncleared debris from dying cells or aggregated proteins can be toxic and may trigger exaggerated inflammatory responses. Even though apoptotic cell death and debris accumulation are key features of neurodegenerative diseases, relatively little attention has been paid to this important homeostatic function in the central nervous system (CNS). This review attempts to summarize our knowledge of phagocytic clearance in the CNS, with a focus on retinal degeneration, forms of which are caused by mutations in genes within known phagocytic pathways, and on Alzheimer's disease (AD). Interest in phagocytic clearance mechanisms in AD was stimulated by the discovery that immunization could promote phagocytic clearance of amyloid-β; however, much less is known about clearance of neuronal and synaptic corpses in AD and other neurodegenerative diseases. Because the regulation of phagocytic activity is intertwined with cytokine signaling, this review also addresses the relationships among CNS inflammation, glial responses, and phagocytic clearance. PMID:21435432

  10. Chloride flux in phagocytes.

    PubMed

    Wang, Guoshun

    2016-09-01

    Phagocytes, such as neutrophils and macrophages, engulf microbes into phagosomes and launch chemical attacks to kill and degrade them. Such a critical innate immune function necessitates ion participation. Chloride, the most abundant anion in the human body, is an indispensable constituent of the myeloperoxidase (MPO)-H2 O2 -halide system that produces the potent microbicide hypochlorous acid (HOCl). It also serves as a balancing ion to set membrane potentials, optimize cytosolic and phagosomal pH, and regulate phagosomal enzymatic activities. Deficient supply of this anion to or defective attainment of this anion by phagocytes is linked to innate immune defects. However, how phagocytes acquire chloride from their residing environment especially when they are deployed to epithelium-lined lumens, and how chloride is intracellularly transported to phagosomes remain largely unknown. This review article will provide an overview of chloride protein carriers, potential mechanisms for phagocytic chloride preservation and acquisition, intracellular chloride supply to phagosomes for oxidant production, and methods to measure chloride levels in phagocytes and their phagosomes.

  11. The mononuclear phagocyte system.

    PubMed

    Hume, David A

    2006-02-01

    The mononuclear phagocyte system (MPS) has been defined as a family of cells comprising bone marrow progenitors, blood monocytes and tissue macrophages. Macrophages are a major cell population in most of the tissues in the body, and their numbers increase further in inflammation, wounding and malignancy. Their trophic roles for other cell types in development and homeostasis are becoming increasingly evident. The receptor for macrophage colony-stimulating factor (CSF-1R) is expressed in a large proportion of cells considered to be mononuclear phagocytes, including antigen-presenting dendritic cells, which can be considered a specialized adaptive state rather than a separate lineage. The unity of the MPS is challenged by evidence that there is a separate embryonic phagocyte lineage, by the transdifferentiation and fusion of MPS cells with other cell types, and by evidence of local renewal of tissue macrophage populations as opposed to monocyte recruitment. The concept of the MPS may have partly outlived its usefulness.

  12. Algal toxins alter copepod feeding behavior.

    PubMed

    Hong, Jiarong; Talapatra, Siddharth; Katz, Joseph; Tester, Patricia A; Waggett, Rebecca J; Place, Allen R

    2012-01-01

    Using digital holographic cinematography, we quantify and compare the feeding behavior of free-swimming copepods, Acartia tonsa, on nutritional prey (Storeatula major) to that occurring during exposure to toxic and non-toxic strains of Karenia brevis and Karlodinium veneficum. These two harmful algal species produce polyketide toxins with different modes of action and potency. We distinguish between two different beating modes of the copepod's feeding appendages-a "sampling beating" that has short durations (<100 ms) and involves little fluid entrainment and a longer duration "grazing beating" that persists up to 1200 ms and generates feeding currents. The durations of both beating modes have log-normal distributions. Without prey, A. tonsa only samples the environment at low frequency. Upon introduction of non-toxic food, it increases its sampling time moderately and the grazing period substantially. On mono algal diets for either of the toxic dinoflagellates, sampling time fraction is high but the grazing is very limited. A. tonsa demonstrates aversion to both toxic algal species. In mixtures of S. major and the neurotoxin producing K. brevis, sampling and grazing diminish rapidly, presumably due to neurological effects of consuming brevetoxins while trying to feed on S. major. In contrast, on mixtures of cytotoxin producing K. veneficum, both behavioral modes persist, indicating that intake of karlotoxins does not immediately inhibit the copepod's grazing behavior. These findings add critical insight into how these algal toxins may influence the copepod's feeding behavior, and suggest how some harmful algal species may alter top-down control exerted by grazers like copepods.

  13. Algal Toxins Alter Copepod Feeding Behavior

    PubMed Central

    Hong, Jiarong; Talapatra, Siddharth; Katz, Joseph; Tester, Patricia A.; Waggett, Rebecca J.; Place, Allen R.

    2012-01-01

    Using digital holographic cinematography, we quantify and compare the feeding behavior of free-swimming copepods, Acartia tonsa, on nutritional prey (Storeatula major) to that occurring during exposure to toxic and non-toxic strains of Karenia brevis and Karlodinium veneficum. These two harmful algal species produce polyketide toxins with different modes of action and potency. We distinguish between two different beating modes of the copepod’s feeding appendages–a “sampling beating” that has short durations (<100 ms) and involves little fluid entrainment and a longer duration “grazing beating” that persists up to 1200 ms and generates feeding currents. The durations of both beating modes have log-normal distributions. Without prey, A. tonsa only samples the environment at low frequency. Upon introduction of non-toxic food, it increases its sampling time moderately and the grazing period substantially. On mono algal diets for either of the toxic dinoflagellates, sampling time fraction is high but the grazing is very limited. A. tonsa demonstrates aversion to both toxic algal species. In mixtures of S. major and the neurotoxin producing K. brevis, sampling and grazing diminish rapidly, presumably due to neurological effects of consuming brevetoxins while trying to feed on S. major. In contrast, on mixtures of cytotoxin producing K. veneficum, both behavioral modes persist, indicating that intake of karlotoxins does not immediately inhibit the copepod’s grazing behavior. These findings add critical insight into how these algal toxins may influence the copepod’s feeding behavior, and suggest how some harmful algal species may alter top-down control exerted by grazers like copepods. PMID:22629336

  14. A phagocyte dilemma…

    PubMed Central

    Thrasher, Adrian J; Segal, Anthony W

    2015-01-01

    The NADPH oxidase of professional phagocytes has an important role in host defense against certain microbes, including tuberculous mycobacteria. The identification of patients with rare inherited hypomorphic mutations in genes encoding components of this enzyme complex could produce new mechanistic insights. PMID:21321592

  15. Unravelling mononuclear phagocyte heterogeneity

    PubMed Central

    Geissmann, Frédéric; Gordon, Siamon; Hume, David A.; Mowat, Allan M.; Randolph, Gwendalyn J.

    2011-01-01

    When Ralph Steinman and Zanvil Cohn first described dendritic cells (DCs) in 1973 it took many years to convince the immunology community that these cells were truly distinct from macrophages. Almost four decades later, the DC is regarded as the key initiator of adaptive immune responses; however, distinguishing DCs from macrophages still leads to confusion and debate in the field. Here, Nature Reviews Immunology asks five experts to discuss the issue of heterogeneity in the mononuclear phagocyte system and to give their opinion on the importance of defining these cells for future research. PMID:20467425

  16. Plasmodium and mononuclear phagocytes.

    PubMed

    Mac-Daniel, Laura; Ménard, Robert

    2015-01-01

    Plasmodium, the causative agent of malaria, initially multiplies inside liver cells and then in successive cycles inside erythrocytes, causing the symptoms of the disease. In this review, we discuss interactions between the extracellular and intracellular forms of the Plasmodium parasite and innate immune cells in the mammalian host, with a special emphasis on mononuclear phagocytes. We overview here what is known about the innate immune cells that interact with parasites, mechanisms used by the parasite to evade them, and the protective or detrimental contribution of these interactions on parasite progression through its life cycle and pathology in the host.

  17. The phagocytes: neutrophils and monocytes.

    PubMed

    Dale, David C; Boxer, Laurence; Liles, W Conrad

    2008-08-15

    The production and deployment of phagocytes are central functions of the hematopoietic system. In the 1950s, radioisotopic studies demonstrated the high production rate and short lifespan of neutrophils and allowed researchers to follow the monocytes as they moved from the marrow through the blood to become tissue macrophages, histiocytes, and dendritic cells. Subsequently, the discovery of the colony-stimulating factors greatly improved understanding the regulation of phagocyte production. The discovery of the microbicidal myeloperoxidase-H2O2-halide system and the importance of NADPH oxidase to the generation of H2O2 also stimulated intense interest in phagocyte disorders. More recent research has focused on membrane receptors and the dynamics of the responses of phagocytes to external factors including immunoglobulins, complement proteins, cytokines, chemokines, integrins, and selectins. Phagocytes express toll-like receptors that aid in the clearance of a wide range of microbial pathogens and their products. Phagocytes are also important sources of pro- and anti-inflammatory cytokines, thus participating in host defenses through a variety of mechanisms. Over the last 50 years, many genetic and molecular disorders of phagocytes have been identified, leading to improved diagnosis and treatment of conditions which predispose patients to the risk of recurrent fevers and infectious diseases.

  18. How Menthol Alters Tobacco-Smoking Behavior: A Biological Perspective

    PubMed Central

    Wickham, R.J.

    2015-01-01

    Mentholated cigarettes gained popularity in the 1950s and were often marketed as “healthy” cigarettes, attributable to their pleasurable mint flavor and cooling sensation in the mouth, lungs, and throat. While it is clear that nicotine is the primary psychoactive component in tobacco cigarettes, recent work has suggested that menthol may also play a role in exacerbating smoking behavior, despite original health claims. Recent evidence highlights four distinct biological mechanisms that can alter smoking behavior: 1) menthol acts to reduce the initially aversive experiences associated with tobacco smoking; 2) menthol can serve as a highly reinforcing sensory cue when associated with nicotine and promote smoking behavior; 3) menthol's actions on nicotinic acetylcholine receptors may change the reinforcing value of nicotine; and 4) menthol can alter nicotine metabolism, thus increasing nicotine bioavailability. The purpose of this review is to highlight and evaluate potential biological mechanisms by which menthol can alter smoking behavior. PMID:26339211

  19. Immunity and behavior: antibodies alter emotion.

    PubMed

    Huerta, Patricio T; Kowal, Czeslawa; DeGiorgio, Lorraine A; Volpe, Bruce T; Diamond, Betty

    2006-01-17

    Systemic lupus erythematosus is an autoimmune disease in which most patients express Abs that bind double-stranded DNA. Recent work has shown that a subset of lupus Abs can crossreact with the NR2A and NR2B subunits of the NMDA receptor. This receptor is expressed in neurons throughout the brain but is at highest density within cells of the hippocampus, amygdala, and hypothalamus. The neurons in the CNS are normally protected from brain-reactive Abs by the blood-brain barrier (BBB); however, a breach in the barrier's integrity exposes neurons to potentially pathogenic Abs. Previously, we have shown that mice that are immunized with a peptide mimetope of DNA produce lupus-like Abs that crossreact with DNA and the NMDA receptor. Moreover, after abrogation of the BBB by treatment with lipopolysaccharide, the immunized mice display hippocampal neuron damage with ensuing memory impairment. Given that rises in epinephrine can increase cerebral blood flow and can cause leaks in the BBB, we decided to investigate whether epinephrine could act as a permissive agent for Ab-mediated neurotoxicity. Here, we show that peptide-immunized mice, given epinephrine to open the BBB, lose neurons in the lateral amygdala and develop a behavioral disorder characterized by a deficient response to fear-conditioning paradigms. Thus, the agent used to open the BBB determines which brain region is made vulnerable to neurotoxic Abs, and Abs that penetrate brain tissue can cause changes not only in cognitive competence, but also in emotional behavior.

  20. Parathion alters incubation behavior of laughing gulls

    USGS Publications Warehouse

    White, D.H.; Mitchell, C.A.; Hill, E.F.

    1983-01-01

    One member of each pair of incubating laughing gulls at 9 nests was trapped, orally dosed with either 6 mg/kg parathion in corn oil or corn oil alone, and marked about the neck with red dye. Each nest was marked with a numbered stake and the treatment was recorded. A pilot study with captive laughing gulls had determined the proper dosage of parathion that would significantly inhibit their brain AChE activity (about 50% of normal) without overt signs of poisoning. After dosing, birds were released and the nests were observed for 2 1/2 days from a blind on the nesting island. The activities of the birds at each marked nest were recorded at 10-minute intervals. Results indicated that on the day of treatment there was no difference (P greater than 0.05, Chi-square test) in the proportion of time spent on the nest between treated and control birds. However, birds dosed with 6 mg/kg parathion spent significantly less time incubating on days 2 and 3 than did birds receiving only corn oil. By noon on the third day, sharing of nest duties between pair members in the treated group had approached normal, indicating recovery from parathion intoxication. These findings suggest that sublethal exposure of nesting birds to an organophosphate (OP) insecticide, such as parathion, may result in decreased nest attentiveness, thereby making the clutch more susceptible to predation or egg failure. Behavioral changes caused by sublethal OP exposure could be especially detrimental in avian species where only one pair member incubates or where both members are exposed in species sharing nest duties.

  1. Teacher Evaluation in Foreign Language Education: Behavior Alteration Techniques.

    ERIC Educational Resources Information Center

    Garrott, Carl L.

    A study examined the relationship between French teachers' use of behavior alteration techniques in the classroom, and the perceptions of individuals evaluating the teacher (students, peers, administrators) on the quality of instructional performance. Junior and community college French students, language teachers, and administrators responded to…

  2. Phagocytic cell function in active brucellosis.

    PubMed Central

    Ocon, P; Reguera, J M; Morata, P; Juarez, C; Alonso, A; Colmenero, J D

    1994-01-01

    In this study, we analyzed phagocytic cell function in 51 patients with active brucellosis and its relationship with different clinical, serological, and evolutionary variables. A control group was made up of 30 blood donors of similar geographic extraction, age, and sex, with no previous history of brucellosis or known exposure ot the infection or specific antibodies. The investigations were carried out at the time of diagnosis, at the conclusion of treatment, and after 6 months of follow-up. Polymorphonuclear leukocyte adherence and nitroblue tetrazolium reduction in response to Brucella antigen were significantly increased in the patients at the time of diagnosis with respect to the control group. In contrast, chemotaxis in response to Brucella antigen and phagocytosis were significantly reduced in the patients with respect to the control group. The alterations in phagocytic cell function were greater in patients with bacteremia, with focal forms of the disease, or with a longer diagnostic delay. Most of these initial alterations tended to normalize with treatment, indicating their transient character. PMID:8112863

  3. Atomic Layer Deposition Coating of Carbon Nanotubes with Aluminum Oxide Alters Pro-Fibrogenic Cytokine Expression by Human Mononuclear Phagocytes In Vitro and Reduces Lung Fibrosis in Mice In Vivo

    PubMed Central

    Taylor, Alexia J.; McClure, Christina D.; Shipkowski, Kelly A.; Thompson, Elizabeth A.; Hussain, Salik; Garantziotis, Stavros; Parsons, Gregory N.; Bonner, James C.

    2014-01-01

    Background Multi-walled carbon nanotubes (MWCNTs) pose a possible human health risk for lung disease as a result of inhalation exposure. Mice exposed to MWCNTs develop pulmonary fibrosis. Lung macrophages engulf MWCNTs and produce pro-fibrogenic cytokines including interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and osteopontin (OPN). Atomic layer deposition (ALD) is a novel process used to enhance functional properties of MWCNTs, yet the consequence of ALD-modified MWCNTs on macrophage biology and fibrosis is unknown. Methods The purpose of this study was to determine whether ALD coating with aluminum oxide (Al2O3) would alter the fibrogenic response to MWCNTs and whether cytokine expression in human macrophage/monocytes exposed to MWCNTs in vitro would predict the severity of lung fibrosis in mice. Uncoated (U)-MWCNTs or ALD-coated (A)-MWCNTs were incubated with THP-1 macrophages or human peripheral blood mononuclear cells (PBMC) and cell supernatants assayed for cytokines by ELISA. C57BL6 mice were exposed to a single dose of A- or U-MWCNTs by oropharyngeal aspiration (4 mg/kg) followed by evaluation of histopathology, lung inflammatory cell counts, and cytokine levels at day 1 and 28 post-exposure. Results ALD coating of MWCNTs with Al2O3 enhanced IL-1β secretion by THP-1 and PBMC in vitro, yet reduced protein levels of IL-6, TNF-α, and OPN production by THP-1 cells. Moreover, Al2O3 nanoparticles, but not carbon black NPs, increased IL-1β but decreased OPN and IL-6 in THP-1 and PBMC. Mice exposed to U-MWCNT had increased levels of all four cytokines assayed and developed pulmonary fibrosis by 28 days, whereas ALD-coating significantly reduced fibrosis and cytokine levels at the mRNA or protein level. Conclusion These findings indicate that ALD thin film coating of MWCNTs with Al2O3 reduces fibrosis in mice and that in vitro phagocyte expression of IL-6, TNF-α, and OPN, but not IL-1β, predict MWCNT-induced fibrosis in the lungs of mice in vivo

  4. Atomic layer deposition coating of carbon nanotubes with aluminum oxide alters pro-fibrogenic cytokine expression by human mononuclear phagocytes in vitro and reduces lung fibrosis in mice in vivo.

    PubMed

    Taylor, Alexia J; McClure, Christina D; Shipkowski, Kelly A; Thompson, Elizabeth A; Hussain, Salik; Garantziotis, Stavros; Parsons, Gregory N; Bonner, James C

    2014-01-01

    Multi-walled carbon nanotubes (MWCNTs) pose a possible human health risk for lung disease as a result of inhalation exposure. Mice exposed to MWCNTs develop pulmonary fibrosis. Lung macrophages engulf MWCNTs and produce pro-fibrogenic cytokines including interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and osteopontin (OPN). Atomic layer deposition (ALD) is a novel process used to enhance functional properties of MWCNTs, yet the consequence of ALD-modified MWCNTs on macrophage biology and fibrosis is unknown. The purpose of this study was to determine whether ALD coating with aluminum oxide (Al2O3) would alter the fibrogenic response to MWCNTs and whether cytokine expression in human macrophage/monocytes exposed to MWCNTs in vitro would predict the severity of lung fibrosis in mice. Uncoated (U)-MWCNTs or ALD-coated (A)-MWCNTs were incubated with THP-1 macrophages or human peripheral blood mononuclear cells (PBMC) and cell supernatants assayed for cytokines by ELISA. C57BL6 mice were exposed to a single dose of A- or U-MWCNTs by oropharyngeal aspiration (4 mg/kg) followed by evaluation of histopathology, lung inflammatory cell counts, and cytokine levels at day 1 and 28 post-exposure. ALD coating of MWCNTs with Al2O3 enhanced IL-1β secretion by THP-1 and PBMC in vitro, yet reduced protein levels of IL-6, TNF-α, and OPN production by THP-1 cells. Moreover, Al2O3 nanoparticles, but not carbon black NPs, increased IL-1β but decreased OPN and IL-6 in THP-1 and PBMC. Mice exposed to U-MWCNT had increased levels of all four cytokines assayed and developed pulmonary fibrosis by 28 days, whereas ALD-coating significantly reduced fibrosis and cytokine levels at the mRNA or protein level. These findings indicate that ALD thin film coating of MWCNTs with Al2O3 reduces fibrosis in mice and that in vitro phagocyte expression of IL-6, TNF-α, and OPN, but not IL-1β, predict MWCNT-induced fibrosis in the lungs of mice in vivo.

  5. Alterations in Striatal Circuits Underlying Addiction-Like Behaviors.

    PubMed

    Kim, Hyun Jin; Lee, Joo Han; Yun, Kyunghwa; Kim, Joung-Hun

    2017-06-30

    Drug addiction is a severe psychiatric disorder characterized by the compulsive pursuit of drugs of abuse despite potential adverse consequences. Although several decades of studies have revealed that psychostimulant use can result in extensive alterations of neural circuits and physiology, no effective therapeutic strategies or medicines for drug addiction currently exist. Changes in neuronal connectivity and regulation occurring after repeated drug exposure contribute to addiction-like behaviors in animal models. Among the involved brain areas, including those of the reward system, the striatum is the major area of convergence for glutamate, GABA, and dopamine transmission, and this brain region potentially determines stereotyped behaviors. Although the physiological consequences of striatal neurons after drug exposure have been relatively well documented, it remains to be clarified how changes in striatal connectivity underlie and modulate the expression of addiction-like behaviors. Understanding how striatal circuits contribute to addiction-like behaviors may lead to the development of strategies that successfully attenuate drug-induced behavioral changes. In this review, we summarize the results of recent studies that have examined striatal circuitry and pathway-specific alterations leading to addiction-like behaviors to provide an updated framework for future investigations.

  6. Chronic alcohol alters rewarded behaviors and striatal plasticity.

    PubMed

    DePoy, Lauren; Daut, Rachel; Wright, Tara; Camp, Marguerite; Crowley, Nicole; Noronha, Bianca; Lovinger, David; Holmes, Andrew

    2015-03-01

    Chronic intermittent ethanol (CIE) alters neural functions and behaviors mediated by the dorsolateral striatum (DLS) and prefrontal cortex. Here, we examined the effects of prolonged (16-bout) CIE on DLS plasticity and DLS-mediated behaviors. Ex vivo electrophysiological recordings revealed loss in efficacy of DLS synaptically induced activation and absent long-term depression after CIE. CIE increased two-bottle choice drinking and impaired Pavlovian-to-instrumental transfer but not discriminated approach. These data suggest prolonged CIE impaired DLS plasticity, to produce associated changes in drinking and cue-controlled reward-seeking. Given recent evidence that less-prolonged CIE can promote certain dorsal striatal-mediated behaviors, CIE may drive chronicity-dependent adaptations in corticostriatal systems regulating behavior. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  7. Fishing indirectly structures macroalgal assemblages by altering herbivore behavior.

    PubMed

    Madin, Elizabeth M P; Gaines, Steven D; Madin, Joshua S; Warner, Robert R

    2010-12-01

    Fishing has clear direct effects on harvested species, but its cascading, indirect effects are less well understood. Fishing disproportionately removes larger, predatory fishes from marine food webs. Most studies of the consequent indirect effects focus on density-mediated interactions where predator removal alternately drives increases and decreases in abundances of successively lower trophic-level species. While prey may increase in number with fewer predators, they may also alter their behavior. When such behavioral responses impact the food resources of prey species, behaviorally mediated trophic cascades can dramatically shape landscapes. It remains unclear whether this pathway of change is typically triggered by ocean fishing. By coupling a simple foraging model with empirical observations from coral reefs, we provide a mechanistic basis for understanding and predicting how predator harvest can alter the landscape of risk for herbivores and consequently drive dramatic changes in primary producer distributions. These results broaden trophic cascade predictions for fisheries to include behavioral changes. They also provide a framework for detecting the presence and magnitude of behaviorally mediated cascades. This knowledge will help to reconcile the disparity between expected and observed patterns of fishing-induced cascades in the sea.

  8. Dynamics of behavioral organization and its alteration in major depression

    NASA Astrophysics Data System (ADS)

    Nakamura, Toru; Kiyono, Ken; Yoshiuchi, Kazuhiro; Nakahara, Rika; Struzik, Zbigniew R.; Yamamoto, Yoshiharu

    2007-07-01

    We describe the nature of human behavioral organization, specifically how resting and active periods are interwoven throughout daily life. Active period durations with physical activity counts successively above a predefined threshold follow a stretched exponential (gamma-type) cumulative distribution with characteristic time, both in healthy individuals and in patients with major depressive disorder. On the contrary, resting period durations below the threshold for both groups obey a scale free power law cumulative distribution over two decades, with significantly lower scaling exponents in the patients. We thus find underlying robust laws governing human behavioral organization, with a parameter altered in depression.

  9. Altered avoidance behavior of young black ducks fed cadmium

    USGS Publications Warehouse

    Heinz, G.H.; Haseltine, S.D.; Sileo, L.

    1983-01-01

    Pairs of adult black ducks (Anas rubripes) were fed a diet containing 0, 4 or 40 ppm cadmium as cadmium chloride. One-week-old ducklings that had been fed thc same dietary concentrations of cadmium as had their parents were tested for avoidance of a fright stimulus. Ducklings fed 4 ppm cadmium ran significantly farther from the stimulus than did controls or ducklings fed 40 ppm cadmium. Such an alteration in behavior could have harmful effects on wild birds.

  10. Methylglyoxal can mediate behavioral and neurochemical alterations in rat brain.

    PubMed

    Hansen, Fernanda; Pandolfo, Pablo; Galland, Fabiana; Torres, Felipe Vasconcelos; Dutra, Márcio Ferreira; Batassini, Cristiane; Guerra, Maria Cristina; Leite, Marina Concli; Gonçalves, Carlos-Alberto

    2016-10-01

    Diabetes is associated with loss of cognitive function and increased risk for Alzheimer's disease (AD). Advanced glycation end products (AGEs) are elevated in diabetes and AD and have been suggested to act as mediators of the cognitive decline observed in these pathologies. Methylglyoxal (MG) is an extremely reactive carbonyl compound that propagates glycation reactions and is, therefore, able to generate AGEs. Herein, we evaluated persistent behavioral and biochemical parameters to explore the hypothesis that elevated exogenous MG concentrations, induced by intracerebroventricular (ICV) infusion, lead to cognitive decline in Wistar rats. A high and sustained administration of MG (3μmol/μL; subdivided into 6days) was found to decrease the recognition index of rats, as evaluated by the object-recognition test. However, MG was unable to impair learning-memory processes, as shown by the habituation in the open field (OF) and Y-maze tasks. Moreover, a single high dose of MG induced persistent alterations in anxiety-related behavior, diminishing the anxiety-like parameters evaluated in the OF test. Importantly, MG did not alter locomotion behavior in the different tasks performed. Our biochemical findings support the hypothesis that MG induces persistent alterations in the hippocampus, but not in the cortex, related to glyoxalase 1 activity, AGEs content and glutamate uptake. Glial fibrillary acidic protein and S100B content, as well as S100B secretion (astroglial-related parameters of brain injury), were not altered by ICV MG administration. Taken together, our data suggest that MG interferes directly in brain function and that the time and the levels of exogenous MG determine the different features that can be seen in diabetic patients.

  11. Alterations in behavior resulting from persistent lymphocytic choriomeningitis virus infection.

    PubMed

    Hotchin, J; Seegal, R

    1978-01-01

    We have studied behavioral change in mice persistently infected as neonates with lymphocytic choriomeningitis virus. Open-field, electric shock startle, and locomotor behavior were measured on these persistently infected mice and normal controls when they were 2--6 months of age. The infected mice exhibited significantly greater latency to move in the open-field, were more sensitive to low current electric shock and were slightly less active when tested for 4 days in running wheels. Immunofluorescent examination of adult mouse brain 14 days after the initiation of persistent infection with cyclophosphamide (given 3 days after virus) demonstrated viral antigen in hippocampal and olfactory tissue. Behavioral results were interpreted in terms of direct effects of virus on the brain, perhaps altering certain critical neurophysiologic and neurochemical parameters. The possible relationship between limbic system pathology and human mental disorder is raised.

  12. Alterations of the Host Microbiome Affect Behavioral Responses to Cocaine

    PubMed Central

    Kiraly, Drew D.; Walker, Deena M.; Calipari, Erin S.; Labonte, Benoit; Issler, Orna; Pena, Catherine J.; Ribeiro, Efrain A.; Russo, Scott J.; Nestler, Eric J.

    2016-01-01

    Addiction to cocaine and other psychostimulants represents a major public health crisis. The development and persistence of addictive behaviors comes from a complex interaction of genes and environment - the precise mechanisms of which remain elusive. In recent years a surge of evidence has suggested that the gut microbiome can have tremendous impact on behavioral via the microbiota-gut-brain axis. In this study we characterized the influence of the gut microbiota on cocaine-mediated behaviors. Groups of mice were treated with a prolonged course of non-absorbable antibiotics via the drinking water, which resulted in a substantial reduction of gut bacteria. Animals with reduced gut bacteria showed an enhanced sensitivity to cocaine reward and enhanced sensitivity to the locomotor-sensitizing effects of repeated cocaine administration. These behavioral changes were correlated with adaptations in multiple transcripts encoding important synaptic proteins in the brain’s reward circuitry. This study represents the first evidence that alterations in the gut microbiota affect behavioral response to drugs of abuse. PMID:27752130

  13. Perinatal exposure to polychlorinated biphenyls alters social behaviors in rats

    PubMed Central

    Jolous-Jamshidi, Banafsheh; Cromwell, Howard C.; McFarland, Ashley M.; Meserve, Lee A.

    2014-01-01

    Perinatal exposure to polychlorinated biphenyls (PCBs) leads to significant alterations of neural and hormonal systems. These alterations have been shown to impair motor and sensory development. Less is known about the influence of PCB exposure on developing emotional and motivational systems involved in social interactions and social learning. The present study examined the impact of perinatal PCB exposure (mixture of congeners 47 and 77) on social recognition in juvenile animals, conspecific-directed investigation in adults and on neural and hormonal systems involved in social functions. We used a standard habituation–dishabituation paradigm to evaluate juvenile recognition and a social port paradigm to monitor adult social investigation. Areal measures of the periventricular nucleus (PVN) of the hypothalamus were obtained to provide correlations with related hormone and brain systems. PCB exposed rats were significantly impaired in social recognition as indicated by persistent conspecific-directed exploration by juvenile animals regardless of social experience. As adults, PCB exposure led to a dampening of the isolation-induced enhancement of social investigation. There was not a concomitant alteration of social investigation in pair-housed PCB exposed animals at this stage of development. Interestingly, PVN area was significantly decreased in juvenile animals exposed to PCB during the perinatal period. Shifts in hypothalamic regulation of hormones involved in social behavior and stress could be involved in the behavioral changes observed. Overall, the results suggest that PCB exposure impairs context or experience-dependent modulation of social approach and investigation. These types of social-context deficits are similar to behavioral deficits observed in social disorders such as autism and other pervasive developmental disorders. PMID:20813172

  14. Galantamine reverses scopolamine-induced behavioral alterations in Dugesia tigrina.

    PubMed

    Ramakrishnan, Latha; Amatya, Christina; DeSaer, Cassie J; Dalhoff, Zachary; Eggerichs, Michael R

    2014-09-01

    In planaria (Dugesia tigrina), scopolamine, a nonselective muscarinic receptor antagonist, induced distinct behaviors of attenuated motility and C-like hyperactivity. Planarian locomotor velocity (pLMV) displayed a dose-dependent negative correlation with scopolamine concentrations from 0.001 to 1.0 mM, and a further increase in scopolamine concentration to 2.25 mM did not further decrease pLMV. Planarian hyperactivity counts was dose-dependently increased following pretreatment with scopolamine concentrations from 0.001 to 0.5 mM and then decreased for scopolamine concentrations ≥ 1 mM. Planarian learning and memory investigated using classical Pavlovian conditioning experiments demonstrated that scopolamine (1 mM) negatively influenced associative learning indicated by a significant decrease in % positive behaviors from 86 % (control) to 14 % (1 mM scopolamine) and similarly altered memory retention, which is indicated by a decrease in % positive behaviors from 69 % (control) to 27 % (1 mM scopolamine). Galantamine demonstrated a complex behavior in planarian motility experiments since co-application of low concentrations of galantamine (0.001 and 0.01 mM) protected planaria against 1 mM scopolamine-induced motility impairments; however, pLMV was significantly decreased when planaria were tested in the presence of 0.1 mM galantamine alone. Effects of co-treatment of scopolamine and galantamine on memory retention in planaria via classical Pavlovian conditioning experiments showed that galantamine (0.01 mM) partially reversed scopolamine (1 mM)-induced memory deficits in planaria as the % positive behaviors increased from 27 to 63 %. The results demonstrate, for the first time in planaria, scopolamine's effects in causing learning and memory impairments and galantamine's ability in reversing scopolamine-induced memory impairments.

  15. Effect of Metasomatic Alteration on Frictional Behavior of Subduction Megathrusts

    NASA Astrophysics Data System (ADS)

    Hirauchi, K. I.; Yamamoto, Y.; Den Hartog, S. A. M.; Spiers, C. J.

    2014-12-01

    Along-strike variations in seismicity of subduction megathrusts can be attributed to the frictional properties of the fault-zone material, which is affected by the distribution of weak clays (smectite and illite) within sediments on the incoming plate. In addition, metasomatic alteration of the subducting sediments may result in significant changes in fault strength and slip stability of the megathrust. We examined an exhumed subduction thrust that separates serpentinite from tectonic mélange (argillite) of the Franciscan Complex, central California. The serpentinite represents a cataclastic shear zone, consisting of angular fragments in a fine-grained talc matrix. Talc schist also developed near the fault in beds up to 2 m thick. The argillite away from the fault displays a scaly fabric, composed of illite/muscovite and chlorite, while it is altered near the fault, characterized by the overgrowth of tremolite and minor chlorite along the previous foliation. We determined the frictional characteristics of these samples by performing rotary shear experiments at pore fluid pressures of 40-120 MPa, effective normal stresses (σneff) of 60-180 MPa, temperatures (T) of 20-400°C, and sliding velocities of 0.3-100 μm/s. The serpentinite was frictionally strong (friction coefficient, μ, 0.6) and exhibited velocity strengthening only at 150°C. The talc schist showed a low μ of 0.1-0.2, characterized by velocity-strengthening behavior at all experimental conditions tested. Argillite showed μ ranging from 0.4 to 0.6 with increasing T and σneff and a transition from velocity strengthening to velocity weakening behavior as T increased above 300°C. The tremolite schist had a weaker normal-stress dependence of μ than argillite, with μ of 0.4-0.5 and a velocity strengthening to velocity weakening transition occurring at 400°C. We propose that intense fluid-rock interactions took place during movement of the investigated fault. The serpentinite-argillite contact is

  16. Prenatal tactile stimulation attenuates drug-induced behavioral sensitization, modifies behavior, and alters brain architecture.

    PubMed

    Muhammad, Arif; Kolb, Bryan

    2011-07-11

    Based on the findings of postnatal tactile stimulation (TS), a favorable experience in rats, the present study examined the influence of prenatal TS on juvenile behavior, adult amphetamine (AMPH) sensitization, and structural alteration in the prefrontal cortex (PFC) and the striatum. Female rats received TS through a baby hair brush throughout pregnancy, and the pups born were tested for open field locomotion, elevated plus maze (EPM), novel object recognition (NOR), and play fighting behaviors. Development and persistence of drug-induced behavioral sensitization in adults were tested by repeated AMPH administration and a challenge, respectively. Structural plasticity in the brain was assessed from the prefrontal cortical thickness and striatum size from serial coronal sections. The results indicate that TS females showed enhanced exploration in the open field. TS decreased the frequency of playful attacks whereas the response to face or evade an attack was not affected. Anxiety-like behavior and cognitive performance were not influenced by TS. AMPH administration resulted in gradual increase in locomotor activity (i.e., behavioral sensitization) that persisted at least for 2 weeks. However, both male and female TS rats exhibited attenuated AMPH sensitization compared to sex-matched controls. Furthermore, the drug-associated alteration in the prefrontal cortical thickness and striatum size observed in controls were prevented by TS experience. In summary, TS during prenatal development modified juvenile behavior, attenuated drug-induced behavioral sensitization in adulthood, and reorganized brain regions implicated in drug addiction. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. Age-related Alterations in the Dynamic Behavior of Microglia

    PubMed Central

    Damani, Mausam R.; Zhao, Lian; Fontainhas, Aurora M.; Amaral, Juan; Fariss, Robert N.; Wong, Wai T.

    2010-01-01

    Summary Microglia, the primary resident immune cells of the CNS, exhibit dynamic behavior involving rapid process motility and cellular migration that is thought to underlie key functions of immune surveillance and tissue repair. Although age-related changes in microglial activation have been implicated in the pathogenesis of neurodegenerative diseases of aging, how dynamic behavior in microglia is influenced by aging is not fully understood. In this study, we employed live imaging of retinal microglia in situ to compare microglial morphology and behavioral dynamics in young and aged animals. We found that aged microglia in the resting state have significantly smaller and less branched dendritic arbors, and also slower process motilities, which likely compromise their ability to continuously survey and interact with their environment. We also found that dynamic microglial responses to injury were age-dependent. While young microglia responded to extracellular ATP, an injury-associated signal, by increasing their motility and becoming more ramified, aged microglia exhibited a contrary response, becoming less dynamic and ramified. In response to laser-induced focal tissue injury, aged microglia demonstrated slower acute responses with lower rates of process motility and cellular migration compared to young microglia. Interestingly, the longer term response of disaggregation from the injury site was retarded in aged microglia, indicating that senescent microglial responses, while slower to initiate, are more sustained. Together, these altered features of microglial behavior at rest and following injury reveal an age-dependent dysregulation of immune response in the CNS that may illuminate microglial contributions to age-related neuroinflammatory degeneration. PMID:21108733

  18. Adolescence as a vulnerable period to alter rodent behavior.

    PubMed

    Schneider, Miriam

    2013-10-01

    Adolescence and puberty are highly important periods for postnatal brain maturation. During adolescence, drastic changes of neuronal architecture and function occur that concomitantly lead to distinct behavioral alterations. Unsurprisingly in view of the multitude of ongoing neurodevelopmental processes in the adolescent brain, most adult neuropsychiatric disorders have their roots exactly during this time span. Adolescence and puberty are therefore crucial developmental periods in terms of understanding the causes and mechanisms of adult mental illness. Valid animal models for adolescent behavior and neurodevelopment might offer better insights into the underlying mechanisms and help to identify specific time windows with heightened susceptibility during development. In order to increase the translational value of such models, we urgently need to define the detailed timing of adolescence and puberty in laboratory rodents. The aim of the present review is to provide a more precise delineation of the time course of these developmental periods during postnatal life in rats and mice and to discuss the impact of adolescence and related neurodevelopmental processes on the heightened susceptibility for mental disorders.

  19. Attack of sea urchin eggs by dogfish phagocytes: Model of phagocyte-mediated cellular cytotoxicity

    PubMed Central

    Weissmann, Gerald; Finkelstein, Morris C.; Csernansky, John; Quigley, James P.; Quinn, Ruth S.; Techner, Lee; Troll, Walter; Dunham, Philip B.

    1978-01-01

    To test whether lysosomal degranulation of phagocytes is associated with antibody-dependent cytotoxicity, eggs of Arbacia punctulata were used as targets for blood phagocytes of Mustelus canis. Eggs were coated with heat-aggregated dogfish IgM and exposed to phagocytes, and cytolysis of eggs was observed by Nomarski optics. Phagocytes adhered, degranulated, and raised fertilization membranes resembling those induced by sperm or ionophore A23187. Lysis was then observed as damage radiating from the point of phagocyte-egg contact. By 4 hr, coated eggs exposed to phagocytes released 8.9, 12.3, and 7.4% of total catalase (EC 1.11.1.6), β-glucuronidase (EC 3.2.1.31), and superoxide dismutase (EC 1.15.1.1) into the medium. Cytotoxic enzyme release significantly exceeded that from uncoated eggs incubated with phagocytes or eggs alone (uncoated or coated). Because activated eggs release a neutral protease, it was considered possible that this enzyme might be responsible for autolysis of eggs. This possibility was excluded because (i) lysis of eggs was not inhibited by soybean trypsin inhibitor (SBTI) whereas the egg protease was sensitive to SBTI, and (ii) the major trypsin-like activity of phagocytes was not inhibited by SBTI. These experiments demonstrate that Ig-coated cells are first activated, and then killed, when exposed to degranulating phagocytes and suggest that enzymes from attacking phagocytes, and not target cells, are responsible for cell death. Images PMID:347448

  20. Reactive oxygen species in phagocytic leukocytes

    PubMed Central

    2008-01-01

    Phagocytic leukocytes consume oxygen and generate reactive oxygen species in response to appropriate stimuli. The phagocyte NADPH oxidase, a multiprotein complex, existing in the dissociated state in resting cells becomes assembled into the functional oxidase complex upon stimulation and then generates superoxide anions. Biochemical aspects of the NADPH oxidase are briefly discussed in this review; however, the major focus relates to the contributions of various modes of microscopy to our understanding of the NADPH oxidase and the cell biology of phagocytic leukocytes. PMID:18597105

  1. Involvement of the serotonergic system in orexin-induced behavioral alterations in rats.

    PubMed

    Matsuzaki, Ichiyo; Sakurai, Takeshi; Kunii, Kaiko; Nakamura, Toshiaki; Yanagisawa, Masashi; Goto, Katsutoshi

    2002-03-15

    We have demonstrated involvement of the serotonergic system in orexin-induced behavioral responses in rats. Orexin-A and -B (hypocretin-1 and -2) significantly increased total locomotor activity when administered centrally. They also induced behavioral alterations; increasing grooming, face washing and wet dog shaking in rats. Haloperidol inhibited orexin-induced hyperlocomotion and these behavioral alterations. Serotonin antagonists, ritanserin and metergoline, did not attenuate orexin-induced hyperlocomotion but partly inhibited orexin-induced behavioral alterations. These results suggest that the dopaminergic system might be involved in orexin-induced hyperlocomotion, while both the serotonergic system as well as the dopaminergic system might be involved in orexin-induced behavioral responses.

  2. Phagocyte function in juvenile periodontitis.

    PubMed Central

    Repo, H; Saxén, L; Jäättelä, M; Ristola, M; Leirisalo-Repo, M

    1990-01-01

    We studied the chemotaxis of peripheral blood polymorphonuclear leukocytes (PMNs) and monocytes and the production of tumor necrosis factor alpha by monocytes of patients with juvenile periodontitis (JP). As a group, the patients' PMNs showed significantly increased chemotaxis determined by counting the number of migrating cells within a 3-microns-pore-size filter. Determined as distance of migration within the filter, as chemotactic increment based on checkerboard analysis, as leukotactic index calculated on the basis of distance of migration and cell count at different depths within a 3-microns-pore-size filter, as distance of migration under agarose, and as the number of PMNs migrating across a 5-microns-pore-size filter, the chemotactic migration rates of PMNs of patients were similar to those of controls. Evaluation of the data on an individual basis suggested that in terms of PMN chemotaxis some patients were hyperresponsive and some were hyporesponsive. Chemotaxis, spontaneous migration, and the rates of lipopolysaccharide-induced tumor necrosis factor alpha production by JP monocytes were similar to those of control cells. Our results give credence to the view that there are minor aberrations in the functions of JP phagocytes, but the extent to which these aberrations are relevant to accumulation of PMNs at sites of infection and inflammation in vivo and possibly contribute to the pathogenesis of JP remains unclear. PMID:2318531

  3. Effect of Calcium on Superoxide Production by Phagocytic Vesicles from Rabbit Alveolar Macrophages

    PubMed Central

    Lew, P. Daniel; Stossel, Thomas P.

    1981-01-01

    Phagocytic vesicles from rabbit lung macrophages produced superoxide in the presence of NADH or NADPH. At 37°C, these vesicles generated 51±7.8 nmol O2−/min per mg protein in the presence of 0.5 mM NADPH. The apparent Km for NADPH and NADH (66 and 266 μM, respectively), the pH optimum for the reaction (6.9), and the cyanide insensitivity were similar to properties of plasma membrane-rich fractions of stimulated polymorphonuclear leukocytes studied by others. The activity of the phagocytic vesicles was trypsin sensitive. The specific superoxide-generating activity of macrophage phagocytic vesicles isolated from cells incubated up to 90 min with phagocytic particles remained constant. Calcium in micromolar concentrations inhibited the NADPH-dependent O2−-generating activity of phagocytic vesicles. In a physiological ionic medium (100 mM KCl, 2.5 mM MgCl2, 30 mM imidazole-HCl, pH 6.9), a maximal inhibition of O2− generation by phagocytic vesicles of 80% was observed at 40 μM free Ca2+. The half maximum inhibitory effect was at 0.7 μM Ca2+. Variations of the calcium concentration resulted in rapid and reversible alterations in O2−-forming activity. Preincubation of phagocytic vesicles in the presence of EGTA rendered their O2− generation rate in the presence of NADPH insensitive to alterations in the free calcium concentration. This desensitization by low EGTA concentrations (≤100 μM) was reversible by the addition of excess calcium, but desensitization by high EGTA concentrations (>1 mM) was not reversible by the addition of calcium either in the presence or absence of purified rabbit lung macrophage or bovine brain calmodulins. Furthermore, trifluoperazine, a drug that inhibits calmodulin-stimulated reactions, did not alter the activity or the calcium sensitivity of the superoxide-generating system of sensitive phagocytic vesicles. Peripheral plasma membrane vesicles (podosomes) prepared by gentle sonication of macrophages possessed on O2

  4. Manipulating the Behavior-Altering Effect of the Motivating Operation: Examination of the Influence on Challenging Behavior during Leisure Activities

    ERIC Educational Resources Information Center

    O'Reilly, Mark F.; Sigafoos, Jeff; Lancioni, Giulio; Rispoli, Mandy; Lang, Russell; Chan, Jeff; Machalicek, Wendy; Langthorne, Paul

    2008-01-01

    We examined the behavior-altering effect of the motivating operation on challenging behavior during leisure activities for three individuals with severe disabilities. Prior functional analyses indicated that challenging behavior was maintained by positive reinforcement in the form of attention or tangible items for all participants. During leisure…

  5. Pioglitazone restores phagocyte mitochondrial oxidants and bactericidal capacity in Chronic Granulomatous Disease

    PubMed Central

    Fernandez-Boyanapalli, Ruby F.; Frasch, S. Courtney; Thomas, Stacey M.; Malcolm, Kenneth C.; Nicks, Michael; Harbeck, Ronald J.; Jakubzick, Claudia V.; Nemenoff, Raphael; Henson, Peter M.; Holland, Steven M.; Bratton, Donna L.

    2015-01-01

    Background Deficient production of reactive oxygen species (ROS) by the phagocyte NADPH oxidase in Chronic Granulomatous Disease (CGD) results in susceptibility to certain pathogens secondary to impaired oxidative killing and mobilization of other phagocyte defenses. PPARγ agonists including pioglitazone (Pio), approved for Type 2 diabetes therapy, alter cellular metabolism and can heighten ROS production. It was hypothesized that Pio treatment of gp91phox−/− mice, a murine model of human CGD, would enhance phagocyte oxidant production and killing of S. aureus, a significant pathogen in this disorder. Objectives We sought to determine if Pio treatment of gp91phox−/− mice enhanced phagocyte oxidant production and host defense. Methods Wild type (WT) and gp91phox−/− mice were treated with the PPARγ agonist Pio, and phagocyte ROS and killing of S. aureus investigated. Results As demonstrated by three different ROS sensing probes, short-term treatment of gp91phox−/− mice with Pio enhanced stimulated ROS production in neutrophils and monocytes from blood and neutrophils and inflammatory macrophages recruited to tissues. Mitochondria were identified as the source of ROS (mtROS). Findings were replicated in human CGD monocytes following ex vivo Pio treatment. Importantly, while mtROS were deficient in gp91phox−/− phagocytes, their restoration with treatment significantly enabled killing of S. aureus both ex vivo and in vivo. Conclusions Together, the data support the hypothesis that signaling from the NADPH oxidase under normal circumstances governs phagocyte mtROS production, and that such signaling is lacking in the absence of a functioning phagocyte oxidase. PPARγ agonism appears to bypass the need for the NADPH oxidase for enhanced mtROS production and partially restores host defense in CGD. PMID:25498313

  6. Neutrophils and Macrophages: the Main Partners of Phagocyte Cell Systems

    PubMed Central

    Silva, Manuel T.; Correia-Neves, Margarida

    2012-01-01

    Biological cellular systems are groups of cells sharing a set of characteristics, mainly key function and origin. Phagocytes are crucial in the host defense against microbial infection. The previously proposed phagocyte cell systems including the most recent and presently prevailing one, the mononuclear phagocyte system (MPS), grouped mononuclear cells but excluded neutrophils, creating an unacceptable situation. As neutrophils are archetypical phagocytes that must be members of comprehensive phagocyte systems, Silva recently proposed the creation of a myeloid phagocyte system (MYPS) that adds neutrophils to the MPS. The phagocytes grouped in the MYPS include the leukocytes neutrophils, inflammatory monocytes, macrophages, and immature myeloid DCs. Here the justifications behind the inclusion of neutrophils in a phagocyte system is expanded and the MYPS are further characterized as a group of dedicated phagocytic cells that function in an interacting and cooperative way in the host defense against microbial infection. Neutrophils and macrophages are considered the main arms of this system. PMID:22783254

  7. AN ENVIRONMENTAL ANTIANDROGEN, VINCLOZOLIN, ALTERS THE ORGANIZATION OF PLAY BEHAVIOR

    EPA Science Inventory

    ABSTRACT

    During mammalian sexual differentiation, the androgens, testosterone and dihydrotestosterone are critical for the organization of the male phenotype. In rats, play behavior is sexually dimorphic. Administration of exogenous androgens during the perinatal period r...

  8. Brief neonatal handling alters sexually dimorphic behaviors in adult rats.

    PubMed

    Fujimoto, Tetsuya; Kubo, Kazuhiko; Nishikawa, Yasuo; Aou, Shuji

    2014-03-01

    Several effects of neonatal handling on brain and behavior have been reported. We investigated the effects of neonatal handling on behaviors that have been shown to be sexually dimorphic in rats using an open-field test. "Gender differences" were observed in locomotor activity, exploratory behavior and grooming in the handled group. However, clear gender differences in these behaviors were not observed in the non-handled group. Our findings show that brief daily handling sessions (~ 1 min) in the first 2 weeks of postnatal life increased locomotor activity and exploratory behavior, and that these effects were more pronounced in females. Moreover, many rats in the non-handling group exhibited an increase in defecation relative to the handling group during the 10-min observation period. This suggests that the non-handling group experienced more stress in response to the novel open-field arena, and that this resulted in the absence of gender differences. Notably, this anxiety-related response was attenuated by neonatal handling. Our study underscores the impact of brief neonatal handling on sexually dimorphic behaviors, and indicates that caution should be exercised in controlling for the effects of handling between experimental groups, particularly in neurotoxicological studies that evaluate gender differences.

  9. Mononuclear phagocyte subpopulations in the mouse kidney.

    PubMed

    George, James F; Lever, Jeremie M; Agarwal, Anupam

    2017-04-01

    Mononuclear phagocytes are the most common cells in the kidney associated with immunity and inflammation. Although the presence of these cells in the kidney has been known for decades, the study of mononuclear phagocytes in the context of kidney function and dysfunction is still at an early stage. The purpose of this review is to summarize the present knowledge regarding classification of these cells in the mouse kidney and to identify relevant questions that would further advance the field and potentially lead to new opportunities for treatment of acute kidney injury and other kidney diseases.

  10. Paternal environmental enrichment transgenerationally alters affective behavioral and neuroendocrine phenotypes.

    PubMed

    Yeshurun, Shlomo; Short, Annabel K; Bredy, Timothy W; Pang, Terence Y; Hannan, Anthony J

    2017-03-01

    Recent studies have demonstrated that paternal stress in rodents can result in modification of offspring behavior. Environmental enrichment, which enhances cognitive stimulation and physical activity, modifies various behaviors and reduces stress responses in adult rodents. We investigated the transgenerational influence of paternal environmental enrichment on offspring behavior and physiological stress response. Adult C57BL/6J male mice (F0) were exposed to either environmental enrichment or standard housing for four weeks and then pair-mated with naïve females. The F2 generation was generated using F1 male offspring. Male and female F1 and F2 offspring were tested for anxiety using the elevated-plus maze and large open field at 8 weeks of age. Depression-related behavior was assessed using the forced-swim test. Hypothalamic-pituitary-adrenal (HPA) axis function was determined by quantification of serum corticosterone and adrenocorticotropic hormone (ACTH) levels at baseline and after forced-swim stress. Paternal environmental enrichment was associated with increased body weights of male F1 and F2 offspring. There was no significant effect on F1 offspring anxiety and depression-related behaviors. There were no changes in anxiety-related behaviors in the F2 offspring, however these mice displayed a reduced latency to immobility in the forced-swim test. Furthermore, F2 females had significantly higher serum corticosterone levels post-stress, but not ACTH. These results show that paternal environmental enrichment exerts a sex-specific transgenerational impact on the behavioral and physiological response to stress. Our findings have implications for the modelling of psychiatric disorders in rodents.

  11. Can Molecular Hippocampal Alterations Explain Behavioral Differences in Prenatally Stressed Rats?

    EPA Science Inventory

    Studies in both humans and animals have shown that prenatal stress can alter cognitive function and other neurological behaviors in adult offspring. One possible underlying mechanism for this may lie with alterations in hippocampal gene expression. The present study examined geno...

  12. Vulnerability of conditional NCAM-deficient mice to develop stress-induced behavioral alterations.

    PubMed

    Bisaz, Reto; Sandi, Carmen

    2012-03-01

    Previous studies in rodents showed that chronic stress induces structural and functional alterations in several brain regions, including shrinkage of the hippocampus and the prefrontal cortex, which are accompanied by cognitive and emotional disturbances. Reduced expression of the neural cell adhesion molecule (NCAM) following chronic stress has been proposed to be crucially involved in neuronal retraction and behavioral alterations. Since NCAM gene polymorphisms and altered expression of alternatively spliced NCAM isoforms have been associated with bipolar depression and schizophrenia in humans, we hypothesized that reduced expression of NCAM renders individuals more vulnerable to the deleterious effects of stress on behavior. Here, we specifically questioned whether mice in which the NCAM gene is inactivated in the forebrain by cre-recombinase under the control of the calcium-calmodulin-dependent kinase II promoter (conditional NCAM-deficient mice), display increased vulnerability to stress. We assessed the evolving of depressive-like behaviors and spatial learning and memory impairments following a subchronic stress protocol (2 weeks) that does not result in behavioral dysfunction, nor in altered NCAM expression, in wild-type mice. Indeed, while no behavioral alterations were detected in wild-type littermates after subchronic stress, conditional NCAM-deficient mice showed increased immobility in the tail suspension test and deficits in reversal spatial learning in the water maze. These findings indicate that diminished NCAM expression might be a critical vulnerability factor for the development of behavioral alterations by stress and further support a functional involvement of NCAM in stress-induced cognitive and emotional disturbances.

  13. On the Behavior of Phosphorus During the Aqueous Alteration of CM2 Carbonaceous Chondrites

    NASA Technical Reports Server (NTRS)

    Brearley, Adrian J.; Chizmadia, Lysa J.

    2005-01-01

    During the earliest period of solar system formation, water played an important role in the evolution of primitive dust, both after accretion of planetesimals and possible before accretion within the protoplanetary disk. Many chondrites show evidence of variable degrees of aqueous alteration, the CM2 chondrites being among the most studied [1]. This group of chondrites is characterized by mineral assemblages of both primary and secondary alteration phases. Hence, these meteorites retain a particularly important record of the reactions that occurred between primary high temperature nebular phases and water. Studies of these chondrites can provide information on the conditions and environments of aqueous alteration and the mobility of elements during alteration. This latter question is at the core of a debate concerning the location of aqueous alteration, i.e. whether alteration occurred predominantly within a closed system after accretion (parent body alteration) or whether some degree of alteration occurred within the solar nebula or on ephemeral protoplanetary bodies prior to accretion. At the core of the parent body alteration model is the hypothesis that elemental exchange between different components, principally chondrules and matrix, must have occurred. chondrules and matrix, must have occurred. In this study, we focus on the behavior of the minor element, phosphorus. This study was stimulated by observations of the behavior of P during the earliest stages of alteration in glassy mesostasis in type II chondrules in CR chondrites and extends the preliminary observations of on Y791198 to other CM chondrites.

  14. The mononuclear phagocyte system and lymphocytes

    USDA-ARS?s Scientific Manuscript database

    This book chapter outlines the cellular processes that are activated and interact during host immune responses including: (a) phagocytosis and antigen presentation by cells of the mononuclear phagocyte system (monocytes, macrophages, and dendritic cells), and (b) cell-mediated and humoral immunity ...

  15. Phagocytes Get Close to Their Enemies.

    PubMed

    Dustin, Michael L; Davis, Simon J

    2016-01-25

    Phagocytosis is key for many organismal functions. In a recent issue of Cell, Freeman et al. (2016) demonstrate a feed-forward signaling mechanism wherein F-actin and integrin receptors drive contact formation between phagocytes and antibody-coated solid particles, signaling their engulfment. This mechanism translates nanoscale proximity effects into wider self-propagating signals.

  16. Norepinephrine Suppresses Wound Macrophage Phagocytic Efficiency Through Alpha- and Beta-Adrenoreceptor Dependent Pathways

    PubMed Central

    Gosain, Ankush; Muthu, Kuzhali; Gamelli, Richard L.; DiPietro, Luisa A.

    2007-01-01

    Background The systemic response to injury is characterized by massive release of norepinephrine (NE) into the circulation as a result of global sympathetic activation. We have recently demonstrated that NE modulates the recruitment of macrophages to the cutaneous wound. We hypothesized that NE suppresses wound macrophage phagocytic function through canonical adrenergic signaling pathways. Methods Murine wound macrophages were harvested at five days after injury and treated with physiologic and pharmacologic dose norepinephrine. Phagocytosis of green fluorescent protein-labeled E.coli was assayed by flow cytometry. The signaling pathways mediating NE modulation of wound macrophage phagocytosis were interrogated by pharmacologic manipulation of alpha- and beta-ARs, intracellular cAMP and PKA. Tissue specificity was determined by comparison of wound macrophages to splenic macrophages. Results Both physiologic and pharmacologic dose NE suppressed wound macrophage phagocytic efficiency. This effect was mediated by alpha- and beta-ARs in a dose-dependent fashion. Direct stimulation of cAMP suppressed phagocytic efficiency and blockade of PKA signaling prevented NE-mediated suppression of phagocytic efficiency. Splenic macrophage phagocytic efficiency was less than that of wound macrophages and was not altered by NE. Conclusions NE has a profound immunosuppressive effect on wound macrophage function that is tissue specific and appears to be mediated through adrenergic receptors and their canonical downstream signaling pathway. Attenuation of post-injury immunosuppression represents another potential mechanism by which beta-AR blockade may reduce morbidity and mortality following severe injury. PMID:17689682

  17. Effect of prenatal haloperidol exposure on behavioral alterations in rats.

    PubMed

    Singh, K P; Singh, Mandavi

    2002-01-01

    Pregnant Charles-Foster rats were exposed to haloperidol (HAL), a neuroleptic drug that binds to and blocks dopamine (DA) receptor subtypes at a dose of 2.5 mg/kg body weight (intraperitoneally) from Gestation Day (GD) 12 to 20. The animals from both treated as well as vehicle control groups were allowed to deliver on GD 21. The offspring culled at birth on the basis of sex and weight were subjected to behavioral tests at the age of 8 weeks. The HAL-treated rat offspring showed a significant increase in anxiogenic behavior on the open field, elevated plus-maze and elevated zero-maze tests when compared with the vehicle-treated (control) rat offspring of the same age group. These findings suggest that prenatal exposure to HAL during a critical period of brain development leaves a lasting imprint on the brain, resulting in abnormal anxiety states, possibly through dopaminergic neurotransmission mechanisms.

  18. Altering Leadership Thinking and Organizational Behavior Through Web Services

    DTIC Science & Technology

    2010-04-01

    result. The proliferation of Web 2.0 services is enabling information sharing among employees and leaders. Regrettably, this level of information...investigates the relationship between Web services, commonly called Web 2.0 , and the influence these services wield on organizational behavior. To support the...infrastructure for those who can use Web 2.0 and other IT services. The data were sorted by officer, noncommissioned officer, and enlisted ranks for the

  19. Handling newborn monkeys alters later exploratory, cognitive, and social behaviors.

    PubMed

    Simpson, Elizabeth A; Sclafani, Valentina; Paukner, Annika; Kaburu, Stefano S K; Suomi, Stephen J; Ferrari, Pier F

    2017-08-18

    Touch is one of the first senses to develop and one of the earliest modalities for infant-caregiver communication. While studies have explored the benefits of infant touch in terms of physical health and growth, the effects of social touch on infant behavior are relatively unexplored. Here, we investigated the influence of neonatal handling on a variety of domains, including memory, novelty seeking, and social interest, in infant monkeys (Macaca mulatta; n=48) from 2 to 12 weeks of age. Neonates were randomly assigned to receive extra holding, with or without accompanying face-to-face interactions. Extra-handled infants, compared to standard-reared infants, exhibited less stress-related behavior and more locomotion around a novel environment, faster approach of novel objects, better working memory, and less fear towards a novel social partner. In sum, infants who received more tactile stimulation in the neonatal period subsequently demonstrated more advanced motor, social, and cognitive skills-particularly in contexts involving exploration of novelty-in the first three months of life. These data suggest that social touch may support behavioral development, offering promising possibilities for designing future early interventions, particularly for infants who are at heightened risk for social disorders. Copyright © 2017. Published by Elsevier Ltd.

  20. Peripheral injury alters schooling behavior in squid, Doryteuthis pealeii.

    PubMed

    Oshima, Megumi; di Pauli von Treuheim, Theodor; Carroll, Julia; Hanlon, Roger T; Walters, Edgar T; Crook, Robyn J

    2016-07-01

    Animals with detectable injuries are at escalated threat of predation. The anti-predation tactic of schooling reduces individual predation risk overall, but it is not known how schooling behavior affects injured animals, or whether risks are reduced equally for injured animals versus other school members. In this laboratory study we examined the effects of minor fin injury on schooling decisions made by squid. Schooling behavior of groups of squid, in which one member was injured, was monitored over 24h. Injured squid were more likely to be members of a school shortly after injury (0.5-2h), but there were no differences compared with sham-injured squid at longer time points (6-24h). Overall, the presence of an injured conspecific increased the probability that a school would form, irrespective of whether the injured squid was a member of the school. When groups containing one injured squid were exposed to a predator cue, injured squid were more likely to join the school, but their position depended on whether the threat was a proximate visual cue or olfactory cue. We found no evidence that injured squid oriented themselves to conceal their injury from salient threats. Overall we conclude that nociceptive sensitization after injury changes grouping behaviors in ways that are likely to be adaptive.

  1. Preserved respiratory and phagocytic functions of phagocytes exposed to flat sheet plasmapheresis equipment.

    PubMed

    Jungi, T W; Aeschbacher, B; Nydegger, U E

    1987-09-01

    Monocytes and polymorphonuclear leukocytes (PMN) were tested for functional integrity after exposure to flat sheet plasmapheresis equipment. Purified PMN were tested for chemiluminescence activity in response to a variety of triggers of the respiratory burst. Monocytes were assessed for their capacity to ingest erythrocytes sensitized with varying amounts of IgG antibodies. Both assays were demonstrated to be sensitive hallmarks of functional modulation. However, no functional differences were noted between phagocytes from blood collected prior to pheresis and those exposed to flat sheet plasmapheresis cylinders. These data suggest that plasmapheresis with the Autopheresis C system does not influence the respiratory and phagocytic function of phagocytes returned back to the donor and implies that contact of phagocytes with artificial surfaces and/or their exposure to surface-activated plasma factors generated in the collection cylinder are minimal when using this plasmapheresis method.

  2. Manipulating the behavior-altering effect of the motivating operation: examination of the influence on challenging behavior during leisure activities.

    PubMed

    O'Reilly, Mark F; Sigafoos, Jeff; Lancioni, Giulio; Rispoli, Mandy; Lang, Russell; Chan, Jeff; Machalicek, Wendy; Langthorne, Paul

    2008-01-01

    We examined the behavior-altering effect of the motivating operation on challenging behavior during leisure activities for three individuals with severe disabilities. Prior functional analyses indicated that challenging behavior was maintained by positive reinforcement in the form of attention or tangible items for all participants. During leisure sessions, each participant played preferred games (cards, jigsaws) with two individuals without disabilities. The discriminative stimuli for challenging behavior were present during leisure sessions but challenging behavior was never reinforced. Immediately prior to leisure sessions, the participants received either access to the reinforcers that maintained challenging behavior or no access. Access versus no access to reinforcers for challenging behavior prior to leisure sessions was alternated in a multi-element design. Results demonstrated higher levels of challenging behavior during leisure sessions when the participants did not have access to the reinforcers prior to the sessions. Little challenging behavior occurred during leisure sessions when the participants had prior access to the reinforcers. Arguments for further examining the behavior-altering effects of the motivating operation in future applied research are presented.

  3. Perturbed mononuclear phagocyte system in severely burned and septic patients

    PubMed Central

    Xiu, Fangming; Jeschke, Marc G.

    2013-01-01

    Burn is one of the most common and devastating forms of trauma. Major burn injury disturbs the immune system, resulting in marked alterations in bone marrow hematopoiesis and a progressive suppression of the immune response, which are thought to contribute to increased susceptibility to secondary infections and the development of sepsis. Immunosuppression in severely burned and septic patients leads to high morbidity and mortality in these patients. Mononuclear Phagocytes System (MPS) is a critical component of the innate immune response and play key roles in burn immunity. These phagocytes are the first cellular responders to severe burn injury after acute disruption of the skin barrier. They are not only able to internalize and digest bacteria and dead cells and scavenge toxic compounds produced by metabolism, but also able to initiate an adaptive immune response. Severe burn and sepsis profoundly inhibit the functions of DC, monocyte and macrophage. Adoptive transfer of MPS or stem cells to severely burned and septic patients that aim to restore MPS function is promising. A better understanding of the roles played by MPS in the pathophysiology of severe burn and sepsis will guarantee a more rational and effective immunotherapy of severely burned and septic patients. PMID:23860581

  4. Fluoxetine alters adult freshwater mussel behavior and larval metamorphosis.

    PubMed

    Hazelton, Peter D; Cope, W Gregory; Mosher, Shad; Pandolfo, Tamara J; Belden, Jason B; Barnhart, M Christopher; Bringolf, Robert B

    2013-02-15

    We used acute and partial-lifecycle tests to examine the effects of the pharmaceutical fluoxetine on freshwater mussels (Unionida). In acute tests lasting 24-48 h, we determined median effective concentrations (EC50s) for fluoxetine with larval (glochidia viability) and juvenile (survival) life-stages of fatmucket (Lampsilis siliquoidea) and black sandshell (Ligumia recta). In a 28-d behavioral test we exposed brooding adult female wavy-rayed lampmussels (Lampsilis fasciola) to 0.37 and 29.3 μg/L fluoxetine to determine effects on adult behavior (foot protrusion, mantle lure display and glochidia parturition). We also assessed the effects of 24-h exposure of 1 and 100 μg/L fluoxetine on glochidia viability duration and metamorphosis success for the wavy-rayed lampmussel. Fluoxetine EC50s ranged from 62 μg/L for juveniles (96 h) to 293 μg/L for glochidia (24 h). In adults, statistically significant increases were observed in foot protrusion at 0.37 and 29.3 μg/L fluoxetine and lure display rates at 29.3 μg/L; glochidia parturition was not significantly affected at any test concentration. Twenty-four hour exposure of glochidia to fluoxetine did not affect viability duration, but likelihood of metamorphosis to the juvenile stage significantly increased with 1 and 100 μg/L treatments. Our results demonstrated effects of fluoxetine to unionid mussels at concentrations less than previously reported and approaching concentrations measured in surface waters. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Phagocytic activity of monocytes, their subpopulations and granulocytes during post-transplant adverse events after hematopoietic stem cell transplantation.

    PubMed

    Döring, Michaela; Cabanillas Stanchi, Karin Melanie; Erbacher, Annika; Haufe, Susanne; Schwarze, Carl Philipp; Handgretinger, Rupert; Hofbeck, Michael; Kerst, Gunter

    2015-05-01

    Phagocytosis of granulocytes and monocytes presents a major mechanism that contributes to the clearance of pathogens and cell debris. We analyzed the phagocytic activity of the peripheral blood cell monocytes, three monocyte subpopulations and granulocytes before and up to one year after hematopoietic stem cell transplantation, as well as during transplant-related adverse events. 25 pediatric patients and young adults (median age of 11.0 years) with hemato-oncological malignancies and non malignancies were enrolled in the prospective study. Ingestion of fluorescence-labeled Escherichia coli bacteria was used to assess the phagocytic activity of monocytes and their subpopulations and granulocytes by means of flow cytometry in the patient group as well as in a control group (n=36). During sepsis, a significant increase of phagocytic activity of monocytes (P=0.0003) and a significant decrease of the phagocytic activity of granulocytes (P=0.0003) and the CD14+ CD16++ monocyte subpopulation (P=0.0020) occurred. At the onset of a veno-occlusive disease, a significant increase of phagocytic activity in the CD14++ CD16+ monocyte subpopulation (P=0.001) and a significant decrease in the phagocytic activity of the CD14++ CD16- monocyte subpopulation (P=0.0048) were observed. In conclusion, the phagocytic activity of monocytes, their subpopulations and granulocytes might be a useful and easy determinable parameter that enables identification of post-transplant complications after hematopoietic stem cell transplantation. The alterations of phagocytic activity contribute to the altered immune response that accompanies adverse events after hematopoietic stem cell transplantation. Copyright © 2014 Elsevier GmbH. All rights reserved.

  6. Norepinephrine transporter heterozygous knockout mice exhibit altered transport and behavior.

    PubMed

    Fentress, H M; Klar, R; Krueger, J J; Sabb, T; Redmon, S N; Wallace, N M; Shirey-Rice, J K; Hahn, M K

    2013-11-01

    The norepinephrine (NE) transporter (NET) regulates synaptic NE availability for noradrenergic signaling in the brain and sympathetic nervous system. Although genetic variation leading to a loss of NET expression has been implicated in psychiatric and cardiovascular disorders, complete NET deficiency has not been found in people, limiting the utility of NET knockout mice as a model for genetically driven NET dysfunction. Here, we investigate NET expression in NET heterozygous knockout male mice (NET(+/-) ), demonstrating that they display an approximately 50% reduction in NET protein levels. Surprisingly, these mice display no significant deficit in NET activity assessed in hippocampal and cortical synaptosomes. We found that this compensation in NET activity was due to enhanced activity of surface-resident transporters, as opposed to surface recruitment of NET protein or compensation through other transport mechanisms, including serotonin, dopamine or organic cation transporters. We hypothesize that loss of NET protein in the NET(+/-) mouse establishes an activated state of existing surface NET proteins. The NET(+/-) mice exhibit increased anxiety in the open field and light-dark box and display deficits in reversal learning in the Morris water maze. These data suggest that recovery of near basal activity in NET(+/-) mice appears to be insufficient to limit anxiety responses or support cognitive performance that might involve noradrenergic neurotransmission. The NET(+/-) mice represent a unique model to study the loss and resultant compensatory changes in NET that may be relevant to behavior and physiology in human NET deficiency disorders.

  7. Norepinephrine Transporter Heterozygous Knockout Mice Exhibit Altered Transport and Behavior

    PubMed Central

    Fentress, HM; Klar, R; Krueger, JK; Sabb, T; Redmon, SN; Wallace, NM; Shirey-Rice, JK; Hahn, MK

    2013-01-01

    The norepinephrine (NE) transporter (NET) regulates synaptic NE availability for noradrenergic signaling in the brain and sympathetic nervous system. Although genetic variation leading to a loss of NET expression has been implicated in psychiatric and cardiovascular disorders, complete NET deficiency has not been found in people, limiting the utility of NET knockout mice as a model for genetically-driven NET dysfunction. Here, we investigate NET expression in NET heterozygous knockout male mice (NET+/−), demonstrating that they display an ~50% reduction in NET protein levels. Surprisingly, these mice display no significant deficit in NET activity, assessed in hippocampal and cortical synaptosomes. We found that this compensation in NET activity was due to enhanced activity of surface-resident transporters, as opposed to surface recruitment of NET protein or compensation through other transport mechanisms, including serotonin, dopamine or organic cation transporters. We hypothesize that loss of NET protein in the NET+/− mouse establishes an activated state of existing, surface NET proteins. NET+/− mice exhibit increased anxiety in the open field and light-dark box and display deficits in reversal learning in the Morris Water Maze. These data suggest recovery of near basal activity in NET+/− mice appears to be insufficient to limit anxiety responses or support cognitive performance that might involve noradrenergic neurotransmission. The NET+/− mice represent a unique model to study the loss and resultant compensatory changes in NET that may be relevant to behavior and physiology in human NET deficiency disorders. PMID:24102798

  8. Altered behavioral and metabolic circadian rhythms in mice with disrupted NAD+ oscillation

    PubMed Central

    Sahar, Saurabh; Nin, Veronica; Barbosa, Maria Thereza; Chini, Eduardo Nunes; Sassone-Corsi, Paolo

    2011-01-01

    The Intracellular levels of nicotinamide adenine dinucleotide (NAD+) are rhythmic and controlled by the circadian clock. However, whether NAD+ oscillation in turn contributes to circadian physiology is not fully understood. To address this question we analyzed mice mutated for the NAD+ hydrolase CD38. We found that rhythmicity of NAD+ was altered in the CD38-deficient mice. The high, chronic levels of NAD+ results in several anomalies in circadian behavior and metabolism. CD38-null mice display a shortened period length of locomotor activity and alteration in the rest-activity rhythm. Several clock genes and, interestingly, genes involved in amino acid metabolism were deregulated in CD38-null livers. Metabolomic analysis identified alterations in the circadian levels of several amino acids, specifically tryptophan levels were reduced in the CD38-null mice at a circadian time paralleling with elevated NAD+ levels. Thus, CD38 contributes to behavioral and metabolic circadian rhythms and altered NAD+ levels influence the circadian clock. PMID:21937766

  9. Caffeine triggers behavioral and neurochemical alterations in adolescent rats.

    PubMed

    Ardais, A P; Borges, M F; Rocha, A S; Sallaberry, C; Cunha, R A; Porciúncula, L O

    2014-06-13

    Caffeine is the psychostimulant most consumed worldwide but concerns arise about the growing intake of caffeine-containing drinks by adolescents since the effects of caffeine on cognitive functions and neurochemical aspects of late brain maturation during adolescence are poorly known. We now studied the behavioral impact in adolescent male rats of regular caffeine intake at low (0.1mg/mL), moderate (0.3mg/mL) and moderate/high (1.0mg/mL) doses only during their active period (from 7:00 P.M. to 7:00 A.M.). All tested doses of caffeine were devoid of effects on locomotor activity, but triggered anxiogenic effects. Caffeine (0.3 and 1mg/mL) improved the performance in the object recognition task, but the higher dose of caffeine (1.0mg/mL) decreased the habituation to an open-field arena, suggesting impaired non-associative memory. All tested doses of caffeine decreased the density of glial fibrillary acidic protein and synaptosomal-associated protein-25, but failed to modify neuron-specific nuclear protein immunoreactivity in the hippocampus and cerebral cortex. Caffeine (0.3-1mg/mL) increased the density of brain-derived neurotrophic factor (BDNF) and proBDNF density as well as adenosine A1 receptor density in the hippocampus, whereas the higher dose of caffeine (1mg/mL) increased the density of proBDNF and BDNF and decreased A1 receptor density in the cerebral cortex. These findings document an impact of caffeine consumption in adolescent rats with a dual impact on anxiety and recognition memory, associated with changes in BDNF levels and decreases of astrocytic and nerve terminal markers without overt neuronal damage in hippocampal and cortical regions. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. Prenatal chlorpyrifos exposure in rats causes persistent behavioral alterations.

    PubMed

    Levin, Edward D; Addy, Nii; Baruah, Avanti; Elias, Alana; Christopher, N Channelle; Seidler, Frederic J; Slotkin, Theodore A

    2002-01-01

    Use of chlorpyrifos (CPF) has been curtailed due to its developmental neurotoxicity. In rats, postnatal CPF administration produces lasting changes in cognitive performance, but less information is available about the effects of prenatal exposure. We administered CPF to pregnant rats on gestational days (GD) 17-20, a peak period of neurogenesis, using doses (1 or 5 mg/kg/day) below the threshold for fetal growth impairment. We then evaluated performance in the T-maze, Figure-8 apparatus and 16-arm radial maze, beginning in adolescence and continuing into adulthood. CPF elicited initial locomotor hyperactivity in the T-maze. Females showed slower habituation in the Fig. 8 maze; no effects were seen in males. In the radial-arm maze, females showed impaired choice accuracy for both working and reference memory and again, males were unaffected. Despite the deficits, all animals eventually learned the maze with continued training. At that point, we challenged them with the muscarinic antagonist, scopolamine, to determine the dependence of behavioral performance on cholinergic function. Whereas control females showed impairment with scopolamine, CPF-exposed females did not, implying that the delayed acquisition of the task had been accomplished through alternative mechanisms. The differences were specific to muscarinic circuits, as control and CPF groups responded similarly to the nicotinic antagonist, mecamylamine. Surprisingly, adverse effects of CPF were greater in the group receiving 1 mg/kg as compared to 5 mg/kg. Promotional effects of acetylcholine (ACh) on cell differentiation may thus help to offset CPF-induced developmental damage that occurs through other noncholinergic mechanisms. Our results indicate that late prenatal exposure to CPF induces long-term changes in cognitive performance that are distinctly gender-selective. Additional defects may be revealed by similar strategies that subject the animals to acute challenges, thus, uncovering the adaptive

  11. Signaling pathway for phagocyte priming upon encounter with apoptotic cells.

    PubMed

    Nonaka, Saori; Ando, Yuki; Kanetani, Takuto; Hoshi, Chiharu; Nakai, Yuji; Nainu, Firzan; Nagaosa, Kaz; Shiratsuchi, Akiko; Nakanishi, Yoshinobu

    2017-05-12

    The phagocytic elimination of cells undergoing apoptosis is an evolutionarily conserved innate immune mechanism for eliminating unnecessary cells. Previous studies showed an increase in the level of engulfment receptors in phagocytes after the phagocytosis of apoptotic cells, which leads to the enhancement of their phagocytic activity. However, precise mechanisms underlying this phenomenon require further clarification. We found that the pre-incubation of a Drosophila phagocyte cell line with the fragments of apoptotic cells enhanced the subsequent phagocytosis of apoptotic cells, accompanied by an augmented expression of the engulfment receptors Draper and integrin αPS3. The DNA-binding activity of the transcription repressor Tailless was transiently raised in those phagocytes, depending on two partially overlapping signal-transduction pathways for the induction of phagocytosis as well as the occurrence of engulfment. The RNAi knockdown of tailless in phagocytes abrogated the enhancement of both phagocytosis and engulfment receptor expression. Furthermore, the hemocyte-specific RNAi of tailless reduced apoptotic cell clearance in Drosophila embryos. Taken together, we propose the following mechanism for the activation of Drosophila phagocytes after an encounter with apoptotic cells: two partially overlapping signal-transduction pathways for phagocytosis are initiated; transcription repressor Tailless is activated; expression of engulfment receptors is stimulated; and phagocytic activity is enhanced. This phenomenon most likely ensures the phagocytic elimination of apoptotic cells by stimulated phagocytes and is thus considered as a mechanism to prime phagocytes in innate immunity. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Social isolation and chronic handling alter endocannabinoid signaling and behavioral reactivity to context in adult rats

    PubMed Central

    Sciolino, Natale R.; Bortolato, Marco; Eisenstein, Sarah A.; Fu, Jin; Oveisi, Fariba; Hohmann, Andrea G.; Piomelli, Daniele

    2010-01-01

    Social deprivation in early life disrupts emotionality and attentional processes in humans. Rearing rats in isolation reproduces some of these abnormalities, which are attenuated by daily handling. However, the neurochemical mechanisms underlying these responses remain poorly understood. We hypothesized that post-weaning social isolation alters the endocannabinoid system, a neuromodulatory system that controls emotional responding. We characterized behavioral consequences of social isolation and evaluated whether handling would reverse social isolation-induced alterations in behavioral reactivity to context and the endocannabinoid system. At weaning, pups were single or group housed and concomitantly handled or not handled daily until adulthood. Rats were tested in emotionality- and attentional-sensitive behavioral assays (open field, elevated plus maze, startle and prepulse inhibition). Cannabinoid receptor densities and endocannabinoid levels were quantified in a separate group of rats. Social isolation negatively altered behavioral responding. Socially-isolated rats that were handled showed less deficits in the open field, elevated plus maze, and prepulse inhibition tests. Social isolation produced site-specific alterations (supraoptic nucleus, ventrolateral thalamus, rostral striatum) in cannabinoid receptor densities compared to group rearing. Handling altered the endocannabinoid system in neural circuitry controlling emotional expression. Handling altered endocannabinoid content (prefrontal and piriform cortices, nucleus accumbens) and cannabinoid receptor densities (lateral globus pallidus, cingulate and piriform cortices, hippocampus) in a region-specific manner. Some effects of social isolation on the endocannabinoid system were moderated by handling. Isolates were unresponsive to handling-induced increases in cannabinoid receptor densities (caudal striatum, anterior thalamus), but were sensitive to handling-induced increases in endocannabinoid content

  13. Social isolation and chronic handling alter endocannabinoid signaling and behavioral reactivity to context in adult rats.

    PubMed

    Sciolino, N R; Bortolato, M; Eisenstein, S A; Fu, J; Oveisi, F; Hohmann, A G; Piomelli, D

    2010-06-30

    Social deprivation in early life disrupts emotionality and attentional processes in humans. Rearing rats in isolation reproduces some of these abnormalities, which are attenuated by daily handling. However, the neurochemical mechanisms underlying these responses remain poorly understood. We hypothesized that post-weaning social isolation alters the endocannabinoid system, a neuromodulatory system that controls emotional responding. We characterized behavioral consequences of social isolation and evaluated whether handling would reverse social isolation-induced alterations in behavioral reactivity to context and the endocannabinoid system. At weaning, pups were single or group housed and concomitantly handled or not handled daily until adulthood. Rats were tested in emotionality- and attentional-sensitive behavioral assays (open field, elevated plus maze, startle and prepulse inhibition). Cannabinoid receptor densities and endocannabinoid levels were quantified in a separate group of rats. Social isolation negatively altered behavioral responding. Socially-isolated rats that were handled showed less deficits in the open field, elevated plus maze, and prepulse inhibition tests. Social isolation produced site-specific alterations (supraoptic nucleus, ventrolateral thalamus, rostral striatum) in cannabinoid receptor densities compared to group rearing. Handling altered the endocannabinoid system in neural circuitry controlling emotional expression. Handling altered endocannabinoid content (prefrontal and piriform cortices, nucleus accumbens) and cannabinoid receptor densities (lateral globus pallidus, cingulate and piriform cortices, hippocampus) in a region-specific manner. Some effects of social isolation on the endocannabinoid system were moderated by handling. Isolates were unresponsive to handling-induced increases in cannabinoid receptor densities (caudal striatum, anterior thalamus), but were sensitive to handling-induced changes in endocannabinoid content

  14. Fragile phagocytes: FMRP positively regulates engulfment activity.

    PubMed

    Logan, Mary A

    2017-03-06

    Defective immune system function is implicated in autism spectrum disorders, including Fragile X syndrome. In this issue, O'Connor et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201607093) demonstrate that phagocytic activity of systemic immune cells is compromised in a Drosophila melanogaster model of Fragile X, highlighting intriguing new mechanistic connections between FMRP, innate immunity, and abnormal development.

  15. Role of oxygen in phagocyte microbicidal action.

    PubMed Central

    Allen, R C

    1994-01-01

    Immune information in the form of inflammatory mediators directs phagocyte locomotion and increases expression of opsonin receptors such that contact with an opsonized microbe results in receptor ligation and activation of microbicidal metabolism. Carbohydrate dehydrogenation and O2 consumption feed reactions that effectively lower the spin quantum number (S) of O2 from 1 to 1/2 and finally to 0. Oxidase-catalyzed univalent reduction of O2 (S = 1; triplet multiplicity) yields hydrodioxylic acid (HO2) and its conjugate base superoxide, O2- (S = 1/2; doublet multiplicity). Acid or enzymatic disproportionation of superoxide yields H2O2 (S = 0; singlet multiplicity). Haloperoxidase catalyzes H2O2-dependent oxidation of Cl- yielding HOCl (S = 0), and reaction of HOCl with H2O2 yields singlet molecular oxygen, 1O2 (S = 0; singlet multiplicity). The Wigner spin conservation rule restricts direct reaction of S = 1 O2 with S = 0 organic molecules. Lowering the S of O2 overcomes this spin restriction and allows microbicidal combustion. High exergonicity dioxygenation reactions yield electronically excited carbonyl products that relax by photon emission, i.e., phagocyte luminescence. Addition of high quantum yield substrates susceptible to spin allowed dioxygenation, i.e., chemiluminigenic substrates, greatly increases detection sensitivity and defines the nature of the oxygenating agent. Measurement of luminescence allows high sensitivity, real-time, and substrate-specific differential analysis of phagocyte dioxygenating activities. Under assay conditions where immune mediator and opsonin exposure are controlled, luminescence analysis of the initial phase of opsonin-stimulated oxygenation activity allows functional assessment of the opsonin receptor expression per circulating phagocyte and can be used to gauge the in vivo state of immune activation. PMID:7705297

  16. Alteration of eating behaviors in patients with Parkinson's disease: possibly overlooked?

    PubMed

    Miwa, Hideto; Kondo, Tomoyoshi

    2008-01-01

    Patients with Parkinson's disease (PD) occasionally show food cravings and/or compulsive eating that result in significant, undesired weight gain. Dopamine replacement therapy may be the cause of this type of eating disorder. We evaluated 60 consecutive patients to see if they had any alteration of eating patterns after starting levodopa. Among them, five (8.3%) patients exhibited characteristic alterations of food preference following the start of dopamine replacement therapy. One patient showed an undesirable weight gain. Of the five patients exhibiting food preference alterations, all showed increased preference to consume sweet snacks, although this alteration was not always associated with hyperphagia (eating too much). This type of dietary alteration was not related to a specific antiparkinsonian drug, and could be observed in patients undergoing dopamine agonist monotherapy. Alteration of eating behavior may not be uncommon in PD patients, and is possibly overlooked. Since dopamine is closely involved in acquisition of food preferences, dietary changes with/without compulsive eating may be a manifestation of an alteration of appetitive behaviors due to excessive dopaminergic neurotransmission.

  17. Multiple Administrations of Viral Nanoparticles Alter in Vivo Behavior-Insights from Intravital Microscopy.

    PubMed

    Shukla, Sourabh; Dorand, R Dixon; Myers, Jay T; Woods, Sarah E; Gulati, Neetu M; Stewart, Phoebe L; Commandeur, Ulrich; Huang, Alex Y; Steinmetz, Nicole F

    2016-05-09

    Multiple administrations of nanoparticle-based formulations are often a clinical requirement for drug delivery and diagnostic imaging applications. Steady pharmacokinetics of nanoparticles is desirable to achieve efficient therapeutic or diagnostic outcomes over such repeat administrations. While clearance through mononuclear phagocytic system is a key determinant of nanoparticle persistence in vivo, multiple administrations could potentially result in altered pharmacokinetics by evoking innate or adaptive immune responses. Plant viral nanoparticles (VNPs) represent an emerging class of programmable nanoparticle platform technologies that offer a highly organized proteinaceous architecture and multivalency for delivery of large payloads of drugs and molecular contrast agents. These very structural features also render them susceptible to immune recognition and subsequent accelerated systemic clearance that could potentially affect overall efficiency. While the biodistribution and pharmacokinetics of VNPs have been reported, the biological response following repeat administrations remains an understudied area of investigation. Here, we demonstrate that weekly administration of filamentous plant viruses results in the generation of increasing levels of circulating, carrier-specific IgM and IgG antibodies. Furthermore, PVX specific immunoglobulins from the serum of immunized animals quickly form aggregates when incubated with PVX in vitro. Such aggregates of VNP-immune complexes are also observed in the mouse vasculature in vivo following repeat injections when imaged in real time using intravital two-photon laser scanning microscopy (2P-LSM). The size of aggregates diminishes at later time points, coinciding with antibody class switching from IgM to IgG. Together, our results highlight the need for careful in vivo assessment of (viral) nanoparticle-based platform technologies, especially in studying their performance after repeat administration. We also demonstrate

  18. Protective effect of alprazolam against sleep deprivation-induced behavior alterations and oxidative damage in mice.

    PubMed

    Singh, Anant; Kumar, Anil

    2008-04-01

    Sleep deprivation is considered as a risk factor for various diseases. Sleep deprivation leads to behavioral, hormonal, neurochemical and biochemical alterations in the animals. The present study was designed to explore the possible involvement of GABAergic mechanism in protective effect of alprazolam against 72h sleep deprivation-induced behavior alterations and oxidative damage in mice. In the present study, sleep deprivation caused anxiety-like behavior, weight loss, impaired ambulatory movements and oxidative damage as indicated by increase in lipid peroxidation, nitrite level and depletion of reduced glutathione and catalase activity in sleep-deprived mice brain. Treatment with alprazolam (0.25 and 0.5 mg/kg, ip) significantly improved behavioral alterations. Biochemically, alprazolam treatment significantly restored depleted reduced glutathione, catalase activity, reversed raised lipid peroxidation and nitrite level. Combination of flumazenil (0.5 mg/kg) and picrotoxin (0.5 mg/kg) with lower dose of alprazolam (0.25mg/kg) significantly antagonized protective effect of alprazolam. However, combination of muscimol (0.05 mg/kg) with alprazolam (0.25 mg/kg, ip) potentiated protective effect of alprazolam. On the basis of these results, it might be suggested that alprazolam might produce protective effect by involving GABAergic system against sleep deprivation-induced behavior alterations and related oxidative damage.

  19. The effect of Eleutheroside E on behavioral alterations in murine sleep deprivation stress model.

    PubMed

    Huang, Lin-Zhang; Wei, Lei; Zhao, Hong-Fang; Huang, Bao-Kang; Rahman, Khalid; Qin, Lu-Ping

    2011-05-11

    Eleutheroside E (EE), a principal component of Eleutherococcus senticosus, has been reported to have anti-inflammatory and protective effects in ischemia heart etc. However, whether it can mitigate behavioral alterations induced by sleep deprivation, has not yet been elucidated. Numerous studies have demonstrated that memory deficits induced by sleep deprivation in experimental animals can be used as a model of behavioral alterations. The present study investigated the effect of EE, on cognitive performances and biochemical parameters of sleep-deprived mice. Animals were repeatedly treated with saline, 10 or 50mg/kg EE and sleep-deprived for 72 h by the multiple platform method. Briefly, groups of 5-6 mice were placed in water tanks (45 × 34 × 17 cm), containing 12 platforms (3 cm in diameter) each, surrounded by water up to 1cm beneath the surface or kept in their home cage. After sleep deprivation, mice showed significant behavioral impairment as evident by reduced latency entering into a dark chamber, locomotion and correctly rate in Y maze, and increased monoamines in hippocampus. However, repeated treatment with EE restored these behavioral and biochemical alterations in mice. In conclusion, the beneficial effect of EE may provide an effective and powerful strategy to alleviate behavioral alterations induced by sleep deprivation. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Maternal treatment with picrotoxin in late pregnancy improved female sexual behavior but did not alter male sexual behavior of offspring.

    PubMed

    Bernardi, Maria M; Scanzerla, Kayne K; Chamlian, Mayra; Teodorov, Elizabeth; Felicio, Luciano F

    2013-08-01

    Previous studies from our laboratory investigated the effects of picrotoxin (PT), a γ-aminobutyric acid receptor antagonist administered during several perinatal periods, on the sexual behavior of male and female rats. We observed that the time of perinatal exposure to PT is critical to determine either facilitation or impairment of sexual behavior. The present study evaluated the effects of prenatal administration of a single dose of PT on gestation day 18 of dams (the first critical period of male brain sexual differentiation) on sexual behavior of male and female offspring. Thus, female Wistar rats were mated with males and, on gestation day 18, received 0.6 mg/kg of PT or 0.9% saline solution subcutaneously. On postnatal day 1, the offspring were weighed and several measures of sexual development were assessed. The sexual behaviors and the general activity in the open field of adult male and ovariectomized, hormone-treated female rats were observed. On comparison with the control group, maternal PT treatment: (i) did not alter the maternal weight, pup weight, anogenital distance, or male and female general activity; (ii) increased female sexual behavior, that is, decreased the latencies to first mount, first lordosis, and tenth lordosis, and the percentage of females presenting lordosis; and (iii) did not alter male sexual behavior. It is suggested that prenatal PT exposure interfered with epigenetic mechanisms related to the development of sex differences in the brain, leading to the observed sexually dimorphic effects on sexual behavior.

  1. Alterations to Functional Analysis Methodology to Clarify the Functions of Low Rate, High Intensity Problem Behavior

    PubMed Central

    Davis, Barbara J; Kahng, SungWoo; Schmidt, Jonathan; Bowman, Lynn G; Boelter, Eric W

    2012-01-01

    Current research provides few suggestions for modifications to functional analysis procedures to accommodate low rate, high intensity problem behavior. This study examined the results of the extended duration functional analysis procedures of Kahng, Abt, and Schonbachler (2001) with six children admitted to an inpatient hospital for the treatment of severe problem behavior. Results of initial functional analyses (Iwata, Dorsey, Slifer, Bauman, & Richman, 1982/1994) were inconclusive for all children because of low levels of responding. The altered functional analyses, which changed multiple variables including the duration of the functional analysis (i.e., 6 or 7 hrs), yielded clear behavioral functions for all six participants. These results add additional support for the utility of an altered analysis of low rate, high intensity problem behavior when standard functional analyses do not yield differentiated results. PMID:23326628

  2. Alterations to functional analysis methodology to clarify the functions of low rate, high intensity problem behavior.

    PubMed

    Davis, Barbara J; Kahng, Sungwoo; Schmidt, Jonathan; Bowman, Lynn G; Boelter, Eric W

    2012-01-01

    Current research provides few suggestions for modifications to functional analysis procedures to accommodate low rate, high intensity problem behavior. This study examined the results of the extended duration functional analysis procedures of Kahng, Abt, and Schonbachler (2001) with six children admitted to an inpatient hospital for the treatment of severe problem behavior. Results of initial functional analyses (Iwata, Dorsey, Slifer, Bauman, & Richman, 1982/1994) were inconclusive for all children because of low levels of responding. The altered functional analyses, which changed multiple variables including the duration of the functional analysis (i.e., 6 or 7 hrs), yielded clear behavioral functions for all six participants. These results add additional support for the utility of an altered analysis of low rate, high intensity problem behavior when standard functional analyses do not yield differentiated results.

  3. Parasites alter freshwater communities in mesocosms by modifying invasive crayfish behavior.

    PubMed

    Reisinger, Lindsey S; Lodge, David M

    2016-06-01

    Parasites can alter communities by reducing densities of keystone hosts, but few studies have examined how trait-mediated indirect effects of parasites can alter ecological communities. We test how trematode parasites (Microphallus spp.) that affect invasive crayfish (Orconectes rusticus) behavior alter how crayfish impact lake littoral communities. O. rusticus drive community composition in north temperate lakes, and predatory fish can reduce crayfish activity and feeding. In laboratory studies, Microphallus parasites also alter O. rusticus behavior: infected O. rusticus eat fewer macroinvertebrates and are bolder near predatory fish than uninfected individuals. We used a 2 x 2 factorial experiment to test how predatory fish and parasites affect O. rusticus impacts in large mesocosms over 4 weeks. We predicted (1) that when predators were absent, infected crayfish would have lower impacts than uninfected crayfish on macrophytes and macroinvertebrates (as well as reduced growth and higher mortality). However, (2) when predators were present but unable to consume crayfish, infected crayfish would have greater impacts (as well as greater growth and lower mortality) than uninfected crayfish because of increased boldness. Because of its effect on crayfish feeding behavior, we also predicted (3) that infection would alter macrophyte and macroinvertebrate community composition. In contrast to our first hypothesis, we found that infected and uninfected crayfish had similar impacts on lower trophic levels when predators were absent. Across all treatments, infected crayfish were more likely to be outside shelters and had greater growth than uninfected crayfish, suggesting that the reduced feeding observed in short-term experiments does not occur over longer timescales. However, in support of the second hypothesis, when predatory fish were present, infected crayfish ate more macroinvertebrates than did uninfected crayfish, likely due to increased boldness. We also observed a

  4. Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry in mice.

    PubMed

    Bercik, Premysl; Verdu, Elena F; Foster, Jane A; Macri, Joseph; Potter, Murray; Huang, Xiaxing; Malinowski, Paul; Jackson, Wendy; Blennerhassett, Patricia; Neufeld, Karen A; Lu, Jun; Khan, Waliul I; Corthesy-Theulaz, Irene; Cherbut, Christine; Bergonzelli, Gabriela E; Collins, Stephen M

    2010-12-01

    Clinical and preclinical studies have associated gastrointestinal inflammation and infection with altered behavior. We investigated whether chronic gut inflammation alters behavior and brain biochemistry and examined underlying mechanisms. AKR mice were infected with the noninvasive parasite Trichuris muris and given etanercept, budesonide, or specific probiotics. Subdiaphragmatic vagotomy was performed in a subgroup of mice before infection. Gastrointestinal inflammation was assessed by histology and quantification of myeloperoxidase activity. Serum proteins were measured by proteomic analysis, circulating cytokines were measured by fluorescence activated cell sorting array, and serum tryptophan and kynurenine were measured by liquid chromatography. Behavior was assessed using light/dark preference and step-down tests. In situ hybridization was used to assess brain-derived neurotrophic factor (BDNF) expression in the brain. T muris caused mild to moderate colonic inflammation and anxiety-like behavior that was associated with decreased hippocampal BDNF messenger RNA (mRNA). Circulating tumor necrosis factor-α and interferon-γ, as well as the kynurenine and kynurenine/tryptophan ratio, were increased. Proteomic analysis showed altered levels of several proteins related to inflammation and neural function. Administration of etanercept, and to a lesser degree of budesonide, normalized behavior, reduced cytokine and kynurenine levels, but did not influence BDNF expression. The probiotic Bifidobacterium longum normalized behavior and BDNF mRNA but did not affect cytokine or kynurenine levels. Anxiety-like behavior was present in infected mice after vagotomy. Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry, which can be normalized by inflammation-dependent and -independent mechanisms, neither of which requires the integrity of the vagus nerve. Copyright © 2010 AGA Institute. Published by Elsevier Inc

  5. Disentangling structural brain alterations associated with violent behavior from those associated with substance use disorders.

    PubMed

    Schiffer, Boris; Müller, Bernhard W; Scherbaum, Norbert; Hodgins, Sheilagh; Forsting, Michael; Wiltfang, Jens; Gizewski, Elke R; Leygraf, Norbert

    2011-10-01

    Studies aimed at identifying structural brain alterations associated with persistent violent behavior or psychopathy have not adequately accounted for a lifetime history of substance misuse. Thus, alterations in gray matter (GM) volume that have been reported to be correlates of violent behavior and/or psychopathy may instead be related to lifelong substance use disorders (SUDs). To identify alterations in GM volume associated with violent behavior and those associated with lifelong SUDs. Cross-sectional study. Participants were recruited from penitentiaries, forensic hospitals, psychiatric outpatient services, and communities in Germany. Structural magnetic resonance imaging was performed at a university hospital. Four groups of men were compared: 12 men with SUDs who exhibited violent behavior (hereafter referred to as violent offenders), 12 violent offenders without SUDs, 13 men with SUDs who did not exhibit violent behavior (hereafter referred to as nonoffenders), and 14 nonoffenders without SUDs. Voxel-based morphometry was used to analyze high-resolution magnetic resonance imaging scans. Assessments of mental disorders, psychopathy (using the Psychopathy Checklist-Screening Version), aggressive behavior, and impulsivity were conducted by trained clinicians. Compared with nonoffenders, violent offenders presented with a larger GM volume in the amygdala bilaterally, the left nucleus accumbens, and the right caudate head and with less GM volume in the left insula. Men with SUDs exhibited a smaller GM volume in the orbitofrontal cortex, ventromedial prefrontal cortex, and premotor cortex than did men without SUDs. Regression analyses indicated that the alterations in GM volume that distinguished the violent offenders from nonoffenders were associated with psychopathy scores and scores for lifelong aggressive behavior. The GM volumes of the orbitofrontal cortex and prefrontal cortex that distinguished the men with SUDs from the men without SUDs were correlated

  6. Targeting oxidative stress attenuates malonic acid induced Huntington like behavioral and mitochondrial alterations in rats.

    PubMed

    Kalonia, Harikesh; Kumar, Puneet; Kumar, Anil

    2010-05-25

    Objective of the present study was to explore the possible role of oxidative stress in the malonic acid induced behavioral, biochemical and mitochondrial alterations in rats. In the present study, unilateral single injections of malonic acid at different doses (1.5, 3 and 6 micromol) were made into the ipsilateral striatum in rats. Behavioral parameters were accessed on 1st, 7th and 14th day post malonic acid administration. Oxidative stress parameters and mitochondrial enzyme functions were assessed on day 14 after behavioral observations. Ipsilateral striatal malonic acid (3 and 6 micromol) administration significantly reduced body weight, locomotor activity, motor coordination and caused oxidative damage (lipid peroxidation, nitrite, superoxide dismutase, catalase and glutathione) in the striatum as compared to sham treated animal. Mitochondrial enzyme complexes and MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolinium bromide) activity were significantly inhibited by malonic acid. Vitamin E treatment (50 and 100 mg/kg, p.o.) significantly reversed the various behavioral, biochemical and mitochondrial alterations in malonic acid treated animals. Our findings show that targeting oxidative stress by vitamin E in malonic acid model, results in amelioration of behavioral and mitochondrial alterations are linked to inhibition of oxidative damage. Based upon these finding present study hypothesize that protection exerted by vitamin E on behavioral, mitochondrial markers indicates the possible preservation of the functional status of the striatal neurons by targeting the deleterious actions of oxidative stress.

  7. Understory avifauna exhibits altered mobbing behavior in tropical forest degraded by selective logging.

    PubMed

    Hua, Fangyuan; Sieving, Kathryn E

    2016-11-01

    In understanding the impacts of selective logging on biodiversity, relatively little is known about the critical behavioral link between altered forest conditions and population persistence. Predator-mobbing is a widespread anti-predator behavior in birds that expresses a well-known trade-off influencing prey survival under predation risk. Here, we ask whether the predator-mobbing behavior of understory forest birds is altered by selective logging and associated forest structural changes in the highly endangered lowland rainforest of Sumatra. At four study sites spanning a gradient of logging-induced forest degradation, we used standardized mobbing and owl call playbacks with predator model presentation to elicit the predator-mobbing behavior of understory prey birds, compared birds' mobbing intensity across sites, and related variation in this intensity to forest vegetation structure. We found that selective logging altered birds' predator-mobbing intensity (measured by behavioral conspicuousness and propensity to approach the predator) as well as forest structure, and that vegetative changes to canopy and understory were correlated with contrasting responses by the two major bird foraging guilds, gleaning versus flycatching birds. We additionally discuss the implications of our findings for further hypothesis testing pertaining to the impacts of selective logging on the ecological processes underlying prey mobbing behavior, particularly with regards to predator-prey interactions and prey accruement of energy reserves.

  8. Alterations in the functional neural circuitry supporting flexible choice behavior in autism spectrum disorders

    PubMed Central

    D'Cruz, A-M; Mosconi, M W; Ragozzino, M E; Cook, E H; Sweeney, J A

    2016-01-01

    Restricted and repetitive behaviors, and a pronounced preference for behavioral and environmental consistency, are distinctive characteristics of autism spectrum disorder (ASD). Alterations in frontostriatal circuitry that supports flexible behavior might underlie this behavioral impairment. In an functional magnetic resonance imaging study of 17 individuals with ASD, and 23 age-, gender- and IQ-matched typically developing control participants, reversal learning tasks were used to assess behavioral flexibility as participants switched from one learned response choice to a different response choice when task contingencies changed. When choice outcome after reversal was uncertain, the ASD group demonstrated reduced activation in both frontal cortex and ventral striatum, in the absence of task performance differences. When the outcomes of novel responses were certain, there was no difference in brain activation between groups. Reduced activation in frontal cortex and ventral striatum suggest problems in decision-making and response planning, and in processing reinforcement cues, respectively. These processes, and their integration, are essential for flexible behavior. Alterations in these systems may therefore contribute to a rigid adherence to preferred behavioral patterns in individuals with an ASD. These findings provide an additional impetus for the use of reversal learning paradigms as a translational model for treatment development targeting the domain of restricted and repetitive behaviors in ASD. PMID:27727243

  9. Context–Specific Social Behavior is Altered by Orbitofrontal Cortex Lesions in Adult Rhesus Macaques

    PubMed Central

    Babineau, Brooke A.; Bliss-Moreau, Eliza; Machado, Christopher J.; Toscano, Jessica E.; Mason, William A.; Amaral, David G.

    2012-01-01

    Although the orbitofrontal cortex has been implicated in important aspects of social behavior, few studies have evaluated semi-naturalistic social behavior in nonhuman primates after discrete lesions of this cortical area. In the present report, we evaluated the behavior of adult rhesus monkeys during dyadic social interactions with novel animals following discrete lesions of the orbitofrontal cortex. In a constrained condition, in which animals could engage in only restricted social behaviors, there were no significant differences in social behavior between the lesion group and the sham-operated control group. When the experimental animals could freely interact with partner animals, however, lesioned animals differed from control animals in terms of social interest and fear-related behaviors. These alterations were contingent on the partner with which they interacted. The lesioned animals, when compared to the control animals, had a significantly greater propensity to approach some but not all of their social partners. They also grimaced more towards the partner animal that they did not approach. Behavioral alterations were more apparent during the initial interactions between animals. We discuss these findings in relation to the role of the orbitofrontal cortex in context dependent modulation of social behavior. PMID:21256192

  10. Neonatal handling alters the structure of maternal behavior and affects mother-pup bonding.

    PubMed

    Reis, A R; de Azevedo, M S; de Souza, M A; Lutz, M L; Alves, M B; Izquierdo, I; Cammarota, M; Silveira, P P; Lucion, A B

    2014-05-15

    During early life, a mother and her pups establish a very close relationship, and the olfactory learning of the nest odor is very important for the bond formation. The olfactory bulb (OB) is a structure that plays a fundamental role in the olfactory learning (OL) mechanism that also involves maternal behavior (licking and contact). We hypothesized that handling the pups would alter the structure of the maternal behavior, affect OL, and alter mother-pup relationships. Moreover, changes in the cyclic AMP-response element binding protein phosphorylation (CREB) and neurotrophic factors could be a part of the mechanism of these changes. This study aimed to analyze the effects of neonatal handling, 1 min per day from postpartum day 1 to 10 (PPD 1 to PPD 10), on the maternal behavior and pups' preference for the nest odor in a Y maze (PPD 11). We also tested CREB's phosphorylation and BDNF signaling in the OB of the pups (PPD 7) by Western blot analysis. The results showed that handling alters mother-pups interaction by decreasing mother-pups contact and changing the temporal pattern of all components of the maternal behavior especially the daily licking and nest-building. We found sex-dependent changes in the nest odor preference, CREB and BDNF levels in pups OB. Male pups were more affected by alterations in the licking pattern, and female pups were more affected by changes in the mother-pup contact (the time spent outside the nest and nursing).

  11. Adaptive Responses to Prochloraz Exposure That Alter Dose-Response and Time-Course Behaviors

    EPA Science Inventory

    Dose response and time-course (DRTC) are, along with exposure, the major determinants of health risk. Adaptive changes within exposed organisms in response to environmental stress are common, and alter DRTC behaviors to minimize the effects caused by stressors. In this project, ...

  12. Adaptive Responses to Prochloraz Exposure That Alter Dose-Response and Time-Course Behaviors

    EPA Science Inventory

    Dose response and time-course (DRTC) are, along with exposure, the major determinants of health risk. Adaptive changes within exposed organisms in response to environmental stress are common, and alter DRTC behaviors to minimize the effects caused by stressors. In this project, ...

  13. Can antibodies against flies alter malaria transmission in birds by changing vector behavior?

    PubMed

    Ghosh, Suma; Waite, Jessica L; Clayton, Dale H; Adler, Frederick R

    2014-10-07

    Transmission of insect-borne diseases is shaped by the interactions among parasites, vectors, and hosts. Any factor that alters movement of infected vectors from infected to uninfeced hosts will in turn alter pathogen spread. In this paper, we study one such pathogen-vector-host system, avian malaria in pigeons transmitted by fly ectoparasites, where both two-way and three-way interactions play a key role in shaping disease spread. Bird immune defenses against flies can decrease malaria prevalence by reducing fly residence time on infected birds or increase disease prevalence by enhancing fly movement and thus infection transmission. We develop a mathematical model that illustrates how these changes in vector behavior influence pathogen transmission and show that malaria prevalence is maximized at an intermediate level of defense avoidance by the flies. Understanding how host immune defenses indirectly alter disease transmission by influencing vector behavior has implications for reducing the transmission of human malaria and other vectored pathogens.

  14. Morphological changes and depressed phagocytic efficiency in Dictyostelium amoebae treated with toxic concentrations of cadmium

    SciTech Connect

    Cyr, R.J.; Bernstein, R.L.

    1984-10-01

    The morphology and phagocytic efficiency of Dictyostelium discoideum amoebae exposed to cadmium was investigated at two Cd concentrations: a low toxic concentration - 7 x 10/sup -5/ m, and a high toxic concentration - 2 x 10/sup -4/ m. Both concentrations inhibited growth completely; however, only in the culture containing a high toxic concentration of cadmium were severe ultrastructural anomalies observed, notably, nucleolar changes and autophagic vacuolar formation. Using biological indices it was concluded that the high concentration of cadmium was lethal and that morphological changes associated with this dose of cadmium may be secondary to cell death. In contrast, amoebae treated with a low toxic but nonlethal concentration of Cd showed an altered size distribution of cytoplasmic vacuoles and a decreased phagocytic efficiency. Cultures whose growth was completely inhibited with cobalt were also examined, as were untreated control cultures. By 24 hr Cd-treated amoebae showed a 20% decrease in the cytoplasmic mean-vacuolar diameter and a 69% decrease in phagocytic efficiency whereas Co and untreated controls showed no significant decrease in the cytoplasmic mean-vacuolar diameter. Phagocytic efficiency was only slightly diminished by Co. Changes in vacuolar profiles had been shown earlier to be related to membrane utilization in Dictyostelium amoebae. Cd at low toxic concentrations affects membrane function in Dictyostelium amoebae.

  15. Adhesins and Host Serum Factors Drive Yop Translocation by Yersinia into Professional Phagocytes during Animal Infection

    PubMed Central

    Maldonado-Arocho, Francisco J.; Green, Carlos; Fisher, Michael L.; Paczosa, Michelle K.; Mecsas, Joan

    2013-01-01

    Yersinia delivers Yops into numerous types of cultured cells, but predominantly into professional phagocytes and B cells during animal infection. The basis for this cellular tropism during animal infection is not understood. This work demonstrates that efficient and specific Yop translocation into phagocytes by Yersinia pseudotuberculosis (Yptb) is a multi-factorial process requiring several adhesins and host complement. When WT Yptb or a multiple adhesin mutant strain, ΔailΔinvΔyadA, colonized tissues to comparable levels, ΔailΔinvΔyadA translocated Yops into significantly fewer cells, demonstrating that these adhesins are critical for translocation into high numbers of cells. However, phagocytes were still selectively targeted for translocation, indicating that other bacterial and/or host factors contribute to this function. Complement depletion showed that complement-restricted infection by ΔailΔinvΔyadA but not WT, indicating that adhesins disarm complement in mice either by prevention of opsonophagocytosis or by suppressing production of pro-inflammatory cytokines. Furthermore, in the absence of the three adhesins and complement, the spectrum of cells targeted for translocation was significantly altered, indicating that Yersinia adhesins and complement direct Yop translocation into neutrophils during animal infection. In summary, these findings demonstrate that in infected tissues, Yersinia uses adhesins both to disarm complement-dependent killing and to efficiently translocate Yops into phagocytes. PMID:23818844

  16. Adhesins and host serum factors drive Yop translocation by yersinia into professional phagocytes during animal infection.

    PubMed

    Maldonado-Arocho, Francisco J; Green, Carlos; Fisher, Michael L; Paczosa, Michelle K; Mecsas, Joan

    2013-01-01

    Yersinia delivers Yops into numerous types of cultured cells, but predominantly into professional phagocytes and B cells during animal infection. The basis for this cellular tropism during animal infection is not understood. This work demonstrates that efficient and specific Yop translocation into phagocytes by Yersinia pseudotuberculosis (Yptb) is a multi-factorial process requiring several adhesins and host complement. When WT Yptb or a multiple adhesin mutant strain, ΔailΔinvΔyadA, colonized tissues to comparable levels, ΔailΔinvΔyadA translocated Yops into significantly fewer cells, demonstrating that these adhesins are critical for translocation into high numbers of cells. However, phagocytes were still selectively targeted for translocation, indicating that other bacterial and/or host factors contribute to this function. Complement depletion showed that complement-restricted infection by ΔailΔinvΔyadA but not WT, indicating that adhesins disarm complement in mice either by prevention of opsonophagocytosis or by suppressing production of pro-inflammatory cytokines. Furthermore, in the absence of the three adhesins and complement, the spectrum of cells targeted for translocation was significantly altered, indicating that Yersinia adhesins and complement direct Yop translocation into neutrophils during animal infection. In summary, these findings demonstrate that in infected tissues, Yersinia uses adhesins both to disarm complement-dependent killing and to efficiently translocate Yops into phagocytes.

  17. Fetal grafts alter chronic behavioral outcome after contusion damage to the adult rat spinal cord.

    PubMed

    Stokes, B T; Reier, P J

    1992-04-01

    In the present experiments, we have examined the capacity of intraspinal transplants to effect alterations in certain locomotor behaviors after spinal contusion injuries. An electromechanical impactor that was sensitive to tissue biomechanical characteristics was used to produce rapid (20 ms) compression injuries to the thoracic spinal cord (T8). Suspensions of fetal spinal tissue (14-day) were placed at 10 days postinjury into the intraspinal cavity created by these reproducible spinal injuries. In the pre- and postinjury period, a number of general and sensitive motor behaviors were used to characterize the immediate and long-term progress of hindlimb behavioral recovery over an extended period of time (73 days). Our data reveal that a lasting alteration in some motor behaviors can be achieved by suspension grafts. While little improvement in some generalized motor tasks (inclined plane analysis, grid walking) takes place, fetal transplants precipitate a rapid and enduring change in certain motivated fine motor behaviors (gait analysis). The base of support and stride length of the hindlimbs were improved by 7 days post-transplantation and the effect was stable over time. The angle of rotation was, however, not altered. The lasting effect in two gait parameters noted was accompanied by the presence of well-developed spinal grafts that often fused with the host spinal parenchyma. These results provide the first documentation of an influence of fetal transplants on motivated locomotor capacity in a well-characterized spinal injury model that mimics lesions seen in the contused adult human spinal cord.

  18. Puberty and gonadal hormones: role in adolescent-typical behavioral alterations.

    PubMed

    Varlinskaya, Elena I; Vetter-O'Hagen, Courtney S; Spear, Linda P

    2013-07-01

    This article is part of a Special Issue "Puberty and Adolescence". Adolescence is characterized by a variety of behavioral alterations, including elevations in novelty-seeking and experimentation with alcohol and other drugs of abuse. Some adolescent-typical neurobehavioral alterations may depend upon pubertal rises in gonadal hormones, whereas others may be unrelated to puberty. Using a variety of approaches, studies in laboratory animals have not revealed clear relationships between pubertal-related changes and adolescent- or adult-typical behaviors that are not strongly sexually dimorphic. Data reviewed suggest surprisingly modest influences of gonadal hormones on alcohol intake, alcohol preference and novelty-directed behaviors. Gonadectomy in males (but not females) increased ethanol intake in adulthood following surgery either pre-pubertally or in adulthood, with these increases in intake largely reversed by testosterone replacement in adulthood, supporting an activational role of androgens in moderating ethanol intake in males. In contrast, neither pre-pubertal nor adult gonadectomy influenced sensitivity to the social inhibitory or aversive effects of ethanol when indexed via conditioned taste aversions, although gonadectomy at either age altered the microstructure of social behavior of both males and females. Unexpectedly, the pre-pubertal surgical manipulation process itself was found to increase later ethanol intake, decrease sensitivity to ethanol's social inhibitory effects, attenuate novelty-directed behavior and lower social motivation, with gonadal hormones being necessary for these long-lasting effects of early surgical perturbations.

  19. Phagocytic, Opsonic and Immunoglobulin Studies in Newborns

    PubMed Central

    Miller, Michael E.; Stiehm, E. Richard

    1973-01-01

    Despite improved diagnositc and therapeutic measures, neonatal septicemia continues to be a major clinical problem. Improvement in the management of the septic neonate should result from application of the increasing information being learned of the neonatal host defense mechanisms. The earlier concept that the neonate was “immunologically null” can now be discarded. Evidence summarized in this review has established that the neonate can marshal an immune response to most antigens and infectious agents. A further major advance in recent years has been in understanding of the inflammatory response in the neonate, which includes such activities as chemotaxis, phagocytosis and bactericidal killing of ingested bacteria by phagocytes. PMID:4580226

  20. Mutagenesis and behavioral screening for altered circadian activity identifies the mouse mutant, Wheels.

    PubMed

    Pickard, G E; Sollars, P J; Rinchik, E M; Nolan, P M; Bucan, M

    1995-12-24

    The molecular processes underlying the generation of circadian behavior in mammals are virtually unknown. To identify genes that regulate or alter circadian activity rhythms, a mouse mutagenesis program was initiated in conjunction with behavioral screening for alterations in circadian period (tau), a fundamental property of the biological clock. Male mice of the inbred BALB/c strain, treated with the potent mutagen N-ethyl-N-nitrosourea were mated with wild-type hybrids. Wheel-running activity of approximately 300 male progeny was monitored for 6-10 weeks under constant dark (DD) conditions. The tau DD of a single mouse (#187) was longer than the population mean by more than three standard deviations (24.20 vs. 23.32 +/- 0.02 h; mean +/- S.E.M.; n = 277). In addition, mouse #187 exhibited other abnormal phenotypes, including hyperactive bi-directional circling/spinning activity and an abnormal response to light. Heterozygous progeny of the founder mouse, generated from outcrossings with wild-type C57BL/6J mice, displayed lengthened tau DD although approximately 20% of the animals showed no wheel-running activity despite being quite active. Under light:dark conditions, all animals displaying circling behavior that ran in the activity wheels exhibited robust wheel-running activity at lights-ON and these animals also showed enhanced wheel-running activity in constant light conditions. The genetic dissection of the complex behavior associated with this mutation was facilitated by the previously described genetic mapping of the mutant locus causing circling behavior, designated Wheels (Whl), to the subcentromeric portion of mouse chromosome 4. In this report, the same locus is shown to be responsible for the abnormal responses to light and presumably for the altered circadian behavior. Characterization of the gene altered in the novel Whl mutation will contribute to understanding the molecular elements involved in mammalian circadian regulation.

  1. Altering the function of commands presented to boys with oppositional and hyperactive behavior

    PubMed Central

    Danforth, Jeffrey S.

    2002-01-01

    Mentalistic and behavioral analyses of noncompliance among children with hyperactive behavior are contrasted. Then, a behavioral training program for 3 boys with behavior characteristic of attention deficit hyperactivity disorder and oppositional defiant disorder is described. The child-focused training was conducted in conjunction with parent training. In an effort to increase the rate of compliance, the child-training program was designed to alter the function of parent commands by teaching the boys to verbalize rules about parent commands and consequences in the context of observing parent—child role-plays. Training was conducted within a multiple baseline design across children. Direct observation of mother—child interactions, telephone interviews, and standardized rating scales showed that training resulted in clinically significant reductions in noncompliance and improved parenting behavior. A 6-month follow-up revealed stable outcomes. PMID:22477227

  2. [The role of phagocytic cells in periodontal disease].

    PubMed

    Matarasso, S; Cafiero, C; Bizzarri, L; Nicolò, M

    1991-04-01

    Having described the morphological and functional characteristics of phagocytic cells, the paper underlines that, in addition to the etiological responsibility of bacterial plaque, the main role in the onset and evolution of periodontitis is played by the host's response. Phagocytic response plays a fundamental role in the host's defence reaction and represents the first barrier to the penetration of bacteria into periodontal tissue. In addition to their defensive role, phagocytic cells may also be responsible for damage to periodontal tissue as a collateral effect of their phagocytic function, thus worsening the periodontal lesion.

  3. Behavioral alterations following blood-brain barrier disruption stimulated by focused ultrasound

    PubMed Central

    Yang, Feng-Yi; Huang, Sheng-Fang; Cheng, Irene Han-Juo

    2016-01-01

    The purpose of this study was to investigate the behavioral alterations and histological changes of the brain after FUS-induced BBB disruption (BBBD). Rats were behaviorally tested using the open field, hole-board, and grip strength tests from day 1 through day 32 after undergoing BBBD induced by FUS with either a mild or heavy parameter. In the open field test, we found an increase in center entries on day 1 and day 9 following heavy FUS treatment and a decrease in center entries at day 18 following mild FUS treatment. With regard to memory-related alterations, rats subjected to heavy FUS treatment exhibited longer latency to start exploring and to find the first baited hole. However, rats subjected to mild FUS treatment exhibited no significant differences in terms of memory performance or grip force. The obtained data suggest that heavy FUS treatment might induce hyperactivity, spatial memory impairment, and forelimb gripping deficits. Furthermore, while mild FUS treatment may have an impact on anxiety-related behaviors, the data suggested it had no impact on locomotor activity, memory, or grip force. Thus, the behavioral alterations following FUS-induced BBBD require further investigation before clinical application. PMID:27034007

  4. Helicobacter pylori infection inhibits phagocyte clearance of apoptotic gastric epithelial cells.

    PubMed

    Bimczok, Diane; Smythies, Lesley E; Waites, Ken B; Grams, Jayleen M; Stahl, Richard D; Mannon, Peter J; Peter, Shajan; Wilcox, C Mel; Harris, Paul R; Das, Soumita; Ernst, Peter B; Smith, Phillip D

    2013-06-15

    Increased apoptotic death of gastric epithelial cells is a hallmark of Helicobacter pylori infection, and altered epithelial cell turnover is an important contributor to gastric carcinogenesis. To address the fate of apoptotic gastric epithelial cells and their role in H. pylori mucosal disease, we investigated phagocyte clearance of apoptotic gastric epithelial cells in H. pylori infection. Human gastric mononuclear phagocytes were analyzed for their ability to take up apoptotic epithelial cells (AECs) in vivo using immunofluorescence analysis. We then used primary human gastric epithelial cells induced to undergo apoptosis by exposure to live H. pylori to study apoptotic cell uptake by autologous monocyte-derived macrophages. We show that HLA-DR(+) mononuclear phagocytes in human gastric mucosa contain cytokeratin-positive and TUNEL-positive AEC material, indicating that gastric phagocytes are involved in AEC clearance. We further show that H. pylori both increased apoptosis in primary gastric epithelial cells and decreased phagocytosis of the AECs by autologous monocyte-derived macrophages. Reduced macrophage clearance of apoptotic cells was mediated in part by H. pylori-induced macrophage TNF-α, which was expressed at higher levels in H. pylori-infected, compared with uninfected, gastric mucosa. Importantly, we show that H. pylori-infected gastric mucosa contained significantly higher numbers of AECs and higher levels of nonphagocytosed TUNEL-positive apoptotic material, consistent with a defect in apoptotic cell clearance. Thus, as shown in other autoimmune and chronic inflammatory diseases, insufficient phagocyte clearance may contribute to the chronic and self-perpetuating inflammation in human H. pylori infection.

  5. The effect of altering self-descriptive behavior on self-concept and classroom behavior.

    PubMed

    Lane, J; Muller, D

    1977-09-01

    This research examined the impact of operant reinforcement of positive self-descriptive behavior on the self-concepts and classroom behavior of 60 fifth-grade students. Three groups of 10 male and 10 female low self-concept students wrote a series of eight essays describing their school performance. The first group (P) received written reinforcement for positive self-descriptions of their school performance. The second group (G) received an equal number of reinforcements for general statements. The third group (C) received no reinforcement for written statements. Three areas of self-concept were measured with the Primary Self-Concept Inventory: personal-self, social-self, and intellectual-self. A frequency count was also made of nine classroom behaviors thought to be influenced by self-concept. The P group displayed increases in the frequency of positive self-descriptive statement and in intellectual self-concept but no changes in personal self-concept, social self-concept, or the nine classroom behaviors. The G and C groups showed no change in self-description, self-concept, or the nine classroom behaviors.

  6. Functional characterisation of phagocytes in the Pacific oyster Crassostrea gigas

    PubMed Central

    Jiang, Shuai; Jia, Zhihao; Zhang, Tao; Wang, Lingling; Qiu, Limei; Sun, Jinsheng

    2016-01-01

    Invertebrates lack canonical adaptive immunity and mainly rely on innate immune system to fight against pathogens. The phagocytes, which could engulf and kill microbial pathogens, are likely to be of great importance and have to undertake significant roles in invertebrate immune defense. In the present study, flow cytometry combined with histological and lectin staining was employed to characterise functional features of phagocytes in the Pacific oyster Crassostrea gigas. Based on the cell size and cellular contents, haemocytes were categorised into three cell types, i.e., granulocytes, semigranulocytes and agranulocytes. Agranulocytes with smaller cell volume and lower cytoplasmic-to-nuclear ratio did not show phagocytic activity, while semigranulocytes and agranulocytes exhibited larger cell volume, higher cytoplasmic-to-nuclear ratio and phagocytic activity. In addition, granulocytes with higher side scatter (SSC) exhibited higher phagocytic activity than that of semigranulocytes. When β-integrin and lectin-like receptors were blocked by RGD tripeptide and carbohydrates, respectively, the phagocytic activity of both granulocytes and semigranulocytes was significantly inhibited, indicating that β-integrin and certain lectin-like receptors were involved in phagocytosis towards microbes. Moreover, lipopolysaccharide but not peptidylglycan could enhance phagocytic activity of granulocytes and semigranulocytes towards Vibrio splendidus and Staphylococcus aureus. Lectin staining analysis revealed that Lycopersicon esculentum lectin (LEL), binding the epitope polylactosamine, was highly distributed on the extracellular cell surface of phagocytes, and could be utilized as a potential molecular marker to differentiate phagocytes from non-phagocytic haemocytes. The results, collectively, provide knowledge on the functional characters of oyster phagocytes, which would contribute to deep investigation of cell typing and cellular immunity in bivalves. PMID:27994957

  7. Microbiota alteration is associated with the development of stress-induced despair behavior.

    PubMed

    Marin, Ioana A; Goertz, Jennifer E; Ren, Tiantian; Rich, Stephen S; Onengut-Gumuscu, Suna; Farber, Emily; Wu, Martin; Overall, Christopher C; Kipnis, Jonathan; Gaultier, Alban

    2017-03-07

    Depressive disorders often run in families, which, in addition to the genetic component, may point to the microbiome as a causative agent. Here, we employed a combination of behavioral, molecular and computational techniques to test the role of the microbiota in mediating despair behavior. In chronically stressed mice displaying despair behavior, we found that the microbiota composition and the metabolic signature dramatically change. Specifically, we observed reduced Lactobacillus and increased circulating kynurenine levels as the most prominent changes in stressed mice. Restoring intestinal Lactobacillus levels was sufficient to improve the metabolic alterations and behavioral abnormalities. Mechanistically, we identified that Lactobacillus-derived reactive oxygen species may suppress host kynurenine metabolism, by inhibiting the expression of the metabolizing enzyme, IDO1, in the intestine. Moreover, maintaining elevated kynurenine levels during Lactobacillus supplementation diminished the treatment benefits. Collectively, our data provide a mechanistic scenario for how a microbiota player (Lactobacillus) may contribute to regulating metabolism and resilience during stress.

  8. Altered negative priming in older subjects: first evidence from behavioral and neural level

    PubMed Central

    Bauer, Eva; Gebhardt, Helge; Gruppe, Harald; Gallhofer, Bernd; Sammer, Gebhard

    2012-01-01

    The impact of aging on the negative priming (NP) effect has been subject of many studies using behavioral measures. Results are inconsistent and corresponding neural data do not exist. We were interested in, whether or not processing of NP is altered in older in comparison to young adults (YA) on behavioral and neural level. Eighteen young and eighteen older healthy adults performed a location-based NP paradigm during fMRI. YA behaviorally showed a NP effect and NP associated fronto-striatal activation, which is in accordance with the inhibitory model of NP. In older subjects no significant behavioral NP effect and no NP-related activation in predefined brain regions could be found. This is discussed in context of the “loss of efficiency” hypothesis. One possible source for the lack of NP-related activation is a reduction of gray matter (GM) volume in older subjects as shown using voxel based morphometry (VBM). PMID:23060774

  9. Microbiota alteration is associated with the development of stress-induced despair behavior

    PubMed Central

    Marin, Ioana A.; Goertz, Jennifer E.; Ren, Tiantian; Rich, Stephen S.; Onengut-Gumuscu, Suna; Farber, Emily; Wu, Martin; Overall, Christopher C.; Kipnis, Jonathan; Gaultier, Alban

    2017-01-01

    Depressive disorders often run in families, which, in addition to the genetic component, may point to the microbiome as a causative agent. Here, we employed a combination of behavioral, molecular and computational techniques to test the role of the microbiota in mediating despair behavior. In chronically stressed mice displaying despair behavior, we found that the microbiota composition and the metabolic signature dramatically change. Specifically, we observed reduced Lactobacillus and increased circulating kynurenine levels as the most prominent changes in stressed mice. Restoring intestinal Lactobacillus levels was sufficient to improve the metabolic alterations and behavioral abnormalities. Mechanistically, we identified that Lactobacillus-derived reactive oxygen species may suppress host kynurenine metabolism, by inhibiting the expression of the metabolizing enzyme, IDO1, in the intestine. Moreover, maintaining elevated kynurenine levels during Lactobacillus supplementation diminished the treatment benefits. Collectively, our data provide a mechanistic scenario for how a microbiota player (Lactobacillus) may contribute to regulating metabolism and resilience during stress. PMID:28266612

  10. Maternal separation altered behavior and neuronal spine density without influencing amphetamine sensitization.

    PubMed

    Muhammad, Arif; Kolb, Bryan

    2011-09-30

    We studied the long-term influence of maternal separation (MS) on periadolescent behavior, adult amphetamine (AMPH) sensitization, and structural plasticity in the corticolimbic regions in rats. Male and female pups, separated daily for 3h from the dam during postnatal day 3-21, were tested for periadolescent exploratory, emotional, cognitive, and social behaviors. The development and persistence of drug-induced behavioral sensitization were tested by repeated AMPH administration and a challenge, respectively. The spine density was examined in the nucleus accumbens (NAc), the medial prefrontal cortex (mPFC), and the orbital frontal cortex (OFC) from Golgi-Cox stained neurons. The results showed that MS enhanced anxiety-like behavior in males. MS abolished the sex difference in playful attacks observed in controls with resultant feminization of male play behavior. Furthermore, the probability of complete rotation defense to face an attack was decreased in females. AMPH administration resulted in the development of behavioral sensitization that persisted at least for two weeks. Sensitization was not influenced by MS. MS increased the spine density in the NAc, the mPFC, and the OFC. Repeated AMPH administration increased the spine density in the NAc and the mPFC, and decreased it in the OFC. MS blocked the drug-induced alteration in these regions. In sum, MS during development influenced periadolescent behavior in males, and structurally reorganized cortical and subcortical brain regions without affecting AMPH-induced behavioral sensitization. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Lysosomal and phagocytic activity is increased in astrocytes during disease progression in the SOD1 G93A mouse model of amyotrophic lateral sclerosis

    PubMed Central

    Baker, David J.; Blackburn, Daniel J.; Keatinge, Marcus; Sokhi, Dilraj; Viskaitis, Paulius; Heath, Paul R.; Ferraiuolo, Laura; Kirby, Janine; Shaw, Pamela J.

    2015-01-01

    Astrocytes are key players in the progression of amyotrophic lateral sclerosis (ALS). Previously, gene expression profiling of astrocytes from the pre-symptomatic stage of the SOD1G93A model of ALS has revealed reduced lactate metabolism and altered trophic support. Here, we have performed microarray analysis of symptomatic and late-stage disease astrocytes isolated by laser capture microdissection (LCM) from the lumbar spinal cord of the SOD1G93A mouse to complete the picture of astrocyte behavior throughout the disease course. Astrocytes at symptomatic and late-stage disease show a distinct up-regulation of transcripts defining a reactive phenotype, such as those involved in the lysosome and phagocytic pathways. Functional analysis of hexosaminidase B enzyme activity in the spinal cord and of astrocyte phagocytic ability has demonstrated a significant increase in lysosomal enzyme activity and phagocytic activity in SOD1G93A vs. littermate controls, validating the findings of the microarray study. In addition to the increased reactivity seen at both stages, astrocytes from late-stage disease showed decreased expression of many transcripts involved in cholesterol homeostasis. Staining for the master regulator of cholesterol synthesis, SREBP2, has revealed an increased localization to the cytoplasm of astrocytes and motor neurons in late-stage SOD1G93A spinal cord, indicating that down-regulation of transcripts may be due to an excess of cholesterol in the CNS during late-stage disease possibly due to phagocytosis of neuronal debris. Our data reveal that SOD1G93A astrocytes are characterized more by a loss of supportive function than a toxic phenotype during ALS disease progression and future studies should focus upon restorative therapies. PMID:26528138

  12. Dilute concentrations of a psychiatric drug alter behavior of fish from natural populations.

    PubMed

    Brodin, T; Fick, J; Jonsson, M; Klaminder, J

    2013-02-15

    Environmental pollution by pharmaceuticals is increasingly recognized as a major threat to aquatic ecosystems worldwide. A variety of pharmaceuticals enter waterways by way of treated wastewater effluents and remain biochemically active in aquatic systems. Several ecotoxicological studies have been done, but generally, little is known about the ecological effects of pharmaceuticals. Here we show that a benzodiazepine anxiolytic drug (oxazepam) alters behavior and feeding rate of wild European perch (Perca fluviatilis) at concentrations encountered in effluent-influenced surface waters. Individuals exposed to water with dilute drug concentrations (1.8 micrograms liter(-1)) exhibited increased activity, reduced sociality, and higher feeding rate. As such, our results show that anxiolytic drugs in surface waters alter animal behaviors that are known to have ecological and evolutionary consequences.

  13. Maternal high-fat diet alters anxiety behavior and glucocorticoid signaling in adolescent offspring.

    PubMed

    Sasaki, A; de Vega, W; Sivanathan, S; St-Cyr, S; McGowan, P O

    2014-07-11

    Maternal obesity and overconsumption of saturated fats during pregnancy have profound effects on offspring health, ranging from metabolic to behavioral disorders in later life. The influence of high-fat diet (HFD) exposure on the development of brain regions implicated in anxiety behavior is not well understood. We previously found that maternal HFD exposure is associated with an increase in anxiety behavior and alterations in the expression of several genes involved in inflammation via the glucocorticoid signaling pathway in adult rat offspring. During adolescence, the maturation of feedback systems mediating corticosteroid sensitivity is incomplete, and therefore distinct from adulthood. In this study, we examined the influence of maternal HFD on several measures of anxiety behavior and gene expression in adolescent offspring. We examined the expression of corticosteroid receptors and related inflammatory processes, as corticosteroid receptors are known to regulate circulating corticosterone levels during basal and stress conditions in addition to influencing inflammatory processes in the hippocampus and amygdala. We found that adolescent animals perinatally exposed to HFD generally showed decreased anxiety behavior accompanied by a selective alteration in the expression of the glucocorticoid receptor and several downstream inflammatory genes in the hippocampus and amygdala. These data suggest that adolescence constitutes an additional period when the effects of developmental programming may modify mental health trajectories. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  14. Cortical Structure Alterations and Social Behavior Impairment in p50-Deficient Mice.

    PubMed

    Bonini, Sara Anna; Mastinu, Andrea; Maccarinelli, Giuseppina; Mitola, Stefania; Premoli, Marika; La Rosa, Luca Rosario; Ferrari-Toninelli, Giulia; Grilli, Mariagrazia; Memo, Maurizio

    2016-06-01

    Alterations in genes that regulate neurodevelopment can lead to cortical malformations, resulting in malfunction during postnatal life. The NF-κB pathway has a key role during neurodevelopment by regulating the maintenance of the neural progenitor cell pool and inhibiting neuronal differentiation. In this study, we evaluated whether mice lacking the NF-κB p50 subunit (KO) present alterations in cortical structure and associated behavioral impairment. We found that, compared with wild type (WT), KO mice at postnatal day 2 present an increase in radial glial cells, an increase in Reelin protein expression levels, in addition to an increase of specific layer thickness. Moreover, adult KO mice display abnormal columnar organization in the somatosensory cortex, a specific decrease in somatostatin- and parvalbumin-expressing interneurons, altered neurite orientation, and a decrease in Synapsin I protein levels. Concerning behavior, KO mice, in addition to an increase in locomotor and exploratory activity, display impairment in social behaviors, with a reduction in social interaction. Finally, we found that risperidone treatment decreased hyperactivity of KO mice, but had no effect on defective social interaction. Altogether, these data add complexity to a growing body of data, suggesting a link between dysregulation of the NF-κB pathway and neurodevelopmental disorders pathogenesis.

  15. Cortical Structure Alterations and Social Behavior Impairment in p50-Deficient Mice

    PubMed Central

    Bonini, Sara Anna; Mastinu, Andrea; Maccarinelli, Giuseppina; Mitola, Stefania; Premoli, Marika; La Rosa, Luca Rosario; Ferrari-Toninelli, Giulia; Grilli, Mariagrazia; Memo, Maurizio

    2016-01-01

    Alterations in genes that regulate neurodevelopment can lead to cortical malformations, resulting in malfunction during postnatal life. The NF-κB pathway has a key role during neurodevelopment by regulating the maintenance of the neural progenitor cell pool and inhibiting neuronal differentiation. In this study, we evaluated whether mice lacking the NF-κB p50 subunit (KO) present alterations in cortical structure and associated behavioral impairment. We found that, compared with wild type (WT), KO mice at postnatal day 2 present an increase in radial glial cells, an increase in Reelin protein expression levels, in addition to an increase of specific layer thickness. Moreover, adult KO mice display abnormal columnar organization in the somatosensory cortex, a specific decrease in somatostatin- and parvalbumin-expressing interneurons, altered neurite orientation, and a decrease in Synapsin I protein levels. Concerning behavior, KO mice, in addition to an increase in locomotor and exploratory activity, display impairment in social behaviors, with a reduction in social interaction. Finally, we found that risperidone treatment decreased hyperactivity of KO mice, but had no effect on defective social interaction. Altogether, these data add complexity to a growing body of data, suggesting a link between dysregulation of the NF-κB pathway and neurodevelopmental disorders pathogenesis. PMID:26946128

  16. NLRP3 INFLAMMASOME ACTIVATION CONTRIBUTES TO LONG-TERM BEHAVIORAL ALTERATIONS IN MICE INJECTED WITH LIPOPOLYSACCHARIDE

    PubMed Central

    ZHU, WEI; CAO, FENG-SHENG; FENG, JUN; CHEN, HUA-WENG; WAN, JIE-RU; LU, QING; WANG, JIAN

    2017-01-01

    Lipopolysaccharide (LPS) might affect the central nervous system by causing neuroinflammation, which subsequently leads to brain damage and dysfunction. In this study, we evaluated the role of nod-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome activation in long-term behavioral alterations of 8-week-old male C57BL/6 mice injected intraperitoneally with LPS (5 mg/kg). At different time points after injection, we assessed locomotor function with a 24-point neurologic deficit scoring system and the rotarod test; assessed recognition memory with the novel object recognition test; and assessed emotional abnormality (anhedonia and behavioral despair) with the tail suspension test, forced swim test, and sucrose preference test. We also assessed protein expression of NLRP3, apoptosis-associated speck-like protein (ASC), and caspase-1 p10 in hippocampus by Western blotting; measured levels of interleukin (IL)-1β, IL-18, tumor necrosis factor α (TNFα), and IL-10 in hippocampus; measured TNFα and IL-1β in serum by ELISA; and evaluated microglial activity in hippocampus by Iba1 immunofluorescence. We found that LPS-injected mice displayed long-term depression-like behaviors and recognition memory deficit; elevated expression of NLRP3, ASC, and caspase-1 p10; increased levels of IL-1β, IL-18, and TNFα; decreased levels of IL-10; and increased microglial activation. These effects were blocked by the NLRP3 inflammasome inhibitor Ac-Tyr-Val-Ala-Asp-chloromethylketone. The results demonstrate proof of concept that NLRP3 inflammasome activation contributes to long-term behavioral alterations in LPS-exposed mice, probably through enhanced inflammation, and that NLRP3 inflammasome inhibition might alleviate peripheral and brain inflammation and thereby ameliorate long-term behavioral alterations in LPS-exposed mice. PMID:27923741

  17. Altered Sensory Code Drives Juvenile-to-Adult Behavioral Maturation in Caenorhabditis elegans

    PubMed Central

    Pantazis, Alexandros K.

    2016-01-01

    Abstract Adults perform better than juveniles in food-seeking tasks. Using the nematode Caenorhabditis elegans to probe the neural mechanisms underlying behavioral maturation, we found that adults and juveniles require different combinations of sensory neurons to generate age-specific food-seeking behavior. We first show that adults and juveniles differ in their response to and preference for food-associated odors, and we analyze genetic mutants to map the neuronal circuits required for those behavioral responses. We developed a novel device to trap juveniles and record their neuronal activity. Activity measurements revealed that adult and juvenile AWA sensory neurons respond to the addition of diacetyl stimulus, whereas AWB, ASK, and AWC sensory neurons encode its removal specifically in adults. Further, we show that reducing neurotransmission from the additional AWB, ASK, and AWC sensory neurons transforms odor preferences from an adult to a juvenile-like state. We also show that AWB and ASK neurons drive behavioral changes exclusively in adults, providing more evidence that age-specific circuits drive age-specific behavior. Collectively, our results show that an odor-evoked sensory code is modified during the juvenile-to-adult transition in animal development to drive age-appropriate behavior. We suggest that this altered sensory code specifically enables adults to extract additional stimulus features and generate robust behavior. PMID:28083560

  18. Homeostasis in the mononuclear phagocyte system.

    PubMed

    Jenkins, Stephen J; Hume, David A

    2014-08-01

    The mononuclear phagocyte system (MPS) is a family of functionally related cells including bone marrow precursors, blood monocytes, and tissue macrophages. We review the evidence that macrophages and dendritic cells (DCs) are separate lineages and functional entities, and examine whether the traditional view that monocytes are the immediate precursors of tissue macrophages needs to be refined based upon evidence that macrophages can extensively self-renew and can be seeded from yolk sac/foetal liver progenitors with little input from monocytes thereafter. We review the role of the growth factor colony-stimulating factor (CSF)1, and present a model consistent with the concept of the MPS in which local proliferation and monocyte recruitment are connected to ensure macrophages occupy their well-defined niche in most tissues.

  19. Transcriptional Regulation of Mononuclear Phagocyte Development

    PubMed Central

    Tussiwand, Roxane; Gautier, Emmanuel L.

    2015-01-01

    Mononuclear phagocytes (MP) are a quite unique subset of hematopoietic cells, which comprise dendritic cells (DC), monocytes as well as monocyte-derived and tissue-resident macrophages. These cells are extremely diverse with regard to their origin, their phenotype as well as their function. Developmentally, DC and monocytes are constantly replenished from a bone marrow hematopoietic progenitor. The ontogeny of macrophages is more complex and is temporally linked and specified by the organ where they reside, occurring early during embryonic or perinatal life. The functional heterogeneity of MPs is certainly a consequence of the tissue of residence and also reflects the diverse ontogeny of the subsets. In this review, we will highlight the developmental pathways of murine MP, with a particular emphasis on the transcriptional factors that regulate their development and function. Finally, we will discuss and point out open questions in the field. PMID:26539196

  20. Postpartum Behavioral Profiles in Wistar Rats Following Maternal Separation - Altered Exploration and Risk-Assessment Behavior in MS15 Dams.

    PubMed

    Daoura, Loudin; Hjalmarsson, My; Oreland, Sadia; Nylander, Ingrid; Roman, Erika

    2010-01-01

    The rodent maternal separation (MS) model is frequently used to investigate the impact of early environmental factors on adult neurobiology and behavior. The majority of MS studies assess effects in the offspring and few address the consequences of repeated pup removal in the dam. Such studies are of interest since alterations detected in offspring subjected to MS may, at least in part, be mediated by variations in maternal behavior and the amount of maternal care provided by the dam. The aim of this study was to investigate how daily short (15 min; MS15) and prolonged (360 min; MS360) periods of MS affects the dam by examining postpartum behavioral profiles using the multivariate concentric square field (MCSF) test. The dams were tested on postpartum days 24-25, i.e., just after the end of the separation period and weaning. The results reveal a lower exploratory drive and lower risk-assessment behavior in MS15 dams relative to MS360 or animal facility reared dams. The present results contrast some of the previously reported findings and provide new information about early post-weaning behavioral characteristics in a multivariate setting. Plausible explanations for the results are provided including a discussion how the present results fit into the maternal mediation hypothesis.

  1. Effects of fasting and immobilization stresses on the phagocytic capacity of rat polymorphonuclear phagocyte monolayers.

    PubMed

    Quindos, G; Ruiz de Gordoa, J C; Burgos, A; Ponton, J; Cisterna, R

    1986-01-01

    The effect of two different types of acute stress (immobilization and fasting) on the polymorphonuclear leukocyte phagocytic function has been studied in male and female rats. With this aim, a subgroup of rats was under immobilization and fasting, another under complete energy deprivation and a third one (controls), exposed to the normal activity of the animal room, for 15 hours. The stress induction was assessed by controlling weight variations and gastric ulcers generation. Both stressors induced weight loss but only immobilization resulted in the development of gastric ulcer in all the animals studied. Phagocytosis was increased in male rats stressed by fasting and in immobilized female rats. In the remaining subgroups polymorphonuclear leukocyte cells showed a phagocytic capacity within the range of control values. Only comparison of the males group stressed by fasting with the male group stressed by fasting and immobilization showed a significant depression in phagocytosis.

  2. Kinetics of MTT-formazan exocytosis in phagocytic and non-phagocytic cells.

    PubMed

    Molinari, Beatriz L; Tasat, Deborah R; Palmieri, Mónica A; Cabrini, Rómulo L

    2005-01-01

    MTT is taken up by cells by endocytosis and reduced to formazan in the endosomal/lysosomal compartment. Formazan is deposited intracellularly as blue granules and is later exocytosed as needle-like formazan crystals. The present study involves an analysis of the pattern of exocytosis of MTT in different cell types showing clearcut differences in the response that can be associated to their ability to phagocytose. To further assess the characteristics of the exocytic mechanism of MTT/formazan, different experimental conditions were assayed. When culture medium with decreasing serum concentration was used as a metabolic modulator no variations were observed in the proportion of cells with formazan crystals. Conversely, the markedly sensitivity of phagocytic cells to increasing concentrations of genistein constituted a remarkable difference with non-phagocytic cells. These results must be considered when the modulation of MTT exocytosis is used as a signal of the progress of human diseases.

  3. Effect of sub-lethal concentrations of endosulfan on phagocytic and hematological parameters in Nile tilapia (Oreochromis niloticus).

    PubMed

    Girón-Pérez, M I; Montes-López, M; García-Ramírez, L A; Romero-Bañuelos, C A; Robledo-Marenco, M L

    2008-03-01

    The effect of endosulfan (6,7,8,9,10,10-hexachloro-1,5,5a,6,9,9a-hexahydro-6,9-methano-2,4,3-benzodioxathiepin-3-oxide), an organochlorine pesticide, was evaluated on phagocytic (phagocytic index and percentage of active cells) and hematological parameters in Nile tilapia. Experimental data showed that an acute exposure to endosulfan (4.0 and 7.0 microg/L) induces a significant decrease in the phagocytic index and the percentage of active cells in peripherical blood of Nile tilapia. However, hemoglobin concentration (Hb), hematocrit (Hto), red blood cell count (RBC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) were not significantly altered in fish exposed to endosulfan compared with control group.

  4. Frustrated Phagocytic Spreading of J774A-1 Macrophages Ends in Myosin II-Dependent Contraction.

    PubMed

    Kovari, Daniel T; Wei, Wenbin; Chang, Patrick; Toro, Jan-Simon; Beach, Ruth Fogg; Chambers, Dwight; Porter, Karen; Koo, Doyeon; Curtis, Jennifer E

    2016-12-20

    Conventional studies of dynamic phagocytic behavior have been limited in terms of spatial and temporal resolution due to the inherent three-dimensionality and small features of phagocytosis. To overcome these issues, we use a series of frustrated phagocytosis assays to quantitatively characterize phagocytic spreading dynamics. Our investigation reveals that frustrated phagocytic spreading occurs in phases and is punctuated by a distinct period of contraction. The spreading duration and peak contact areas are independent of the surface opsonin density, although the opsonin density does affect the likelihood that a cell will spread. This reinforces the idea that phagocytosis dynamics are primarily dictated by cytoskeletal activity. Structured illumination microscopy reveals that F-actin is reorganized during the course of frustrated phagocytosis. F-actin in early stages is consistent with that observed in lamellipodial protrusions. During the contraction phase, it is bundled into fibers that surround the cell and is reminiscent of a contractile belt. Using traction force microscopy, we show that cells exert significant strain on the underlying substrate during the contraction phase but little strain during the spreading phase, demonstrating that phagocytes actively constrict during late-stage phagocytosis. We also find that late-stage contraction initiates after the cell surface area increases by 225%, which is consistent with the point at which cortical tension begins to rise. Moreover, reducing tension by exposing cells to hypertonic buffer shifts the onset of contraction to occur in larger contact areas. Together, these findings provide further evidence that tension plays a significant role in signaling late-stage phagocytic activity.

  5. Rat hippocampal alterations could underlie behavioral abnormalities induced by exposure to moderate noise levels.

    PubMed

    Uran, S L; Aon-Bertolino, M L; Caceres, L G; Capani, F; Guelman, L R

    2012-08-30

    Noise exposure is known to affect auditory structures in living organisms. However, it should not be ignored that many of the effects of noise are extra-auditory. Previous findings of our laboratory demonstrated that noise was able to induce behavioral alterations that are mainly related to the cerebellum (CE) and the hippocampus (HC). Therefore, the aim of this work was to reveal new data about the vulnerability of developing rat HC to moderate noise levels through the assessment of potential histological changes and hippocampal-related behavioral alterations. Male Wistar rats were exposed to noise (95-97 dB SPL, 2h daily) either for 1 day (acute noise exposure, ANE) or between postnatal days 15 and 30 (sub-acute noise exposure, SANE). Hippocampal histological evaluation as well as short (ST) and long term (LT) habituation and recognition memory assessments were performed. Results showed a mild disruption in the different hippocampal regions after ANE and SANE schemes, along with significant behavioral abnormalities. These data suggest that exposure of developing rats to noise levels of moderate intensity is able to trigger changes in the HC, an extra-auditory structure of the Central Nervous System (CNS), that could underlie the observed behavioral effects.

  6. Fitness consequences of altered feeding behavior in immune-challenged mosquitoes.

    PubMed

    Ohm, Johanna R; Teeple, Janet; Nelson, William A; Thomas, Matthew B; Read, Andrew F; Cator, Lauren J

    2016-02-29

    Malaria-infected mosquitoes have been reported to be more likely to take a blood meal when parasites are infectious than when non-infectious. This change in feeding behavior increases the likelihood of malaria transmission, and has been considered an example of parasite manipulation of host behavior. However, immune challenge with heat-killed Escherichia coli induces the same behavior, suggesting that altered feeding behavior may be driven by adaptive responses of hosts to cope with an immune response, rather than by parasite-specific factors. Here we tested the alternative hypothesis that down-regulated feeding behavior prior to infectiousness is a mosquito adaptation that increases fitness during infection. We measured the impact of immune challenge and blood feeding on the fitness of individual mosquitoes. After an initial blood meal, Anopheles stephensi Liston mosquitoes were experimentally challenged with heat-killed E. coli at a dose known to mimic the same temporal changes in mosquito feeding behavior as active malaria infection. We then tracked daily egg production and survivorship of females maintained on blood-feeding regimes that either mimicked down-regulated feeding behaviors observed during early malaria infection, or were fed on a four-day feeding cycle typically associated with uninfected mosquitoes. Restricting access to blood meals enhanced mosquito survival but lowered lifetime reproduction. Immune-challenge did not impact either fitness component. Combining fecundity and survival to estimate the population-scale intrinsic rate of increase (r), we found that, contrary to the mosquito adaptation hypothesis, mosquito fitness decreased if blood feeding was delayed following an immune challenge. Our data provide no support for the idea that malaria-induced suppression of blood feeding is an adaptation by mosquitoes to reduce the impact of immune challenge. Alternatively, the behavioral alterations may be neither host nor parasite adaptations, but

  7. Waterborne manganese exposure alters plasma, brain, and liver metabolites accompanied by changes in stereotypic behaviors

    PubMed Central

    Fordahl, Steve; Cooney, Paula; Qiu, Yunping; Xie, Guoxiang; Jia, Wei; Erikson, Keith M.

    2011-01-01

    Overexposure to waterborne manganese (Mn) is linked with cognitive impairment in children and neurochemical abnormalities in other experimental models. In order to characterize the threshold between Mn-exposure and altered neurochemistry, it is important to identify biomarkers that positively correspond with brain Mn-accumulation. The objective of this study was to identify Mn-induced alterations in plasma, liver, and brain metabolites using liquid/gas chromatography-time of flight-mass spectrometry metabolomic analyses; and to monitor corresponding Mn-induced behavior changes. Weanling Sprague-Dawley rats had access to deionized drinking water either Mn-free or containing 1g Mn/L for six weeks. Behaviors were monitored during the sixth week for a continuous 24h period while in a home cage environment using video surveillance. Mn-exposure significantly increased liver, plasma, and brain Mn concentrations compared to control, specifically targeting the globus pallidus (GP). Mn significantly altered 98 metabolites in the brain, liver, and plasma; notably shifting cholesterol and fatty acid metabolism in the brain (increased oleic and palmitic acid; 12.57 and 15.48 fold change (FC), respectively), and liver (increased oleic acid, 14.51 FC; decreased hydroxybutyric acid, −14.29 FC). Additionally, Mn-altered plasma metabolites homogentisic acid, chenodeoxycholic acid, and aspartic acid correlated significantly with GP and striatal Mn. Total distance traveled was significantly increased and positively correlated with Mn-exposure, while nocturnal stereotypic and exploratory behaviors were reduced with Mn-exposure and performed largely during the light cycle compared to unexposed rats. These data provide putative biomarkers for Mn-neurotoxicity and suggest that Mn disrupts the circadian cycle in rats. PMID:22056924

  8. Gender and estrous cycle influences on behavioral and neurochemical alterations in adult rats neonatally administered ketamine.

    PubMed

    Célia Moreira Borella, Vládia; Seeman, Mary V; Carneiro Cordeiro, Rafaela; Vieira dos Santos, Júnia; Romário Matos de Souza, Marcos; Nunes de Sousa Fernandes, Ethel; Santos Monte, Aline; Maria Mendes Vasconcelos, Silvânia; Quinn, John P; de Lucena, David F; Carvalho, André F; Macêdo, Danielle

    2016-05-01

    Neonatal N-methyl-D-aspartate (NMDA) receptor blockade in rodents triggers schizophrenia (SCZ)-like alterations during adult life. SCZ is influenced by gender in age of onset, premorbid functioning, and course. Estrogen, the hormone potentially driving the gender differences in SCZ, is known to present neuroprotective effects such as regulate oxidative pathways and the expression of brain-derived neurotrophic factor (BDNF). Thus, the aim of this study was to verify if differences in gender and/or estrous cycle phase during adulthood would influence the development of behavioral and neurochemical alterations in animals neonatally administered ketamine. The results showed that ketamine-treated male (KT-male) and female-in-diestrus (KTF-diestrus, the low estrogen phase) presented significant deficits in prepulse inhibition of the startle reflex and spatial working memory, two behavioral SCZ endophenotypes. On the contrary, female ketamine-treated rats during proestrus (KTF-proestrus, the high estradiol phase) had no behavioral alterations. This correlated with an oxidative imbalance in the hippocampus (HC) of both male and KTF-diestrus female rats, that is, decreased levels of GSH and increased levels of lipid peroxidation and nitrite. Similarly, BDNF was decreased in the KTF-diestrus rats while no alterations were observed in KTF-proestrus and male animals. The changes in the HC were in contrast to those in the prefrontal cortex in which only increased levels of nitrite in all groups studied were observed. Thus, there is a gender difference in the adult rat HC in response to ketamine neonatal administration, which is based on the estrous cycle. This is discussed in relation to neuropsychiatric conditions and in particular SCZ. © 2015 Wiley Periodicals, Inc.

  9. IL-4 Inhibits IL-1β-Induced Depressive-Like Behavior and Central Neurotransmitter Alterations.

    PubMed

    Park, Hyun-Jung; Shim, Hyun-Soo; An, Kyungeh; Starkweather, Angela; Kim, Kyung Soo; Shim, Insop

    2015-01-01

    It has been known that activation of the central innate immune system or exposure to stress can disrupt balance of anti-/proinflammatory cytokines. The aim of the present study was to investigate the role of pro- and anti-inflammatory cytokines in the modulation of depressive-like behaviors, the hormonal and neurotransmitter systems in rats. We investigated whether centrally administered IL-1β is associated with activation of CNS inflammatory pathways and behavioral changes and whether treatment with IL-4 could modulate IL-1β-induced depressive-like behaviors and central neurotransmitter systems. Infusion of IL-4 significantly decreased IL-1β-induced anhedonic responses and increased social exploration and total activity. Treatment with IL-4 markedly blocked IL-1β-induced increase in PGE2 and CORT levels. Also, IL-4 reduced IL-1β-induced 5-HT levels by inhibiting tryptophan hydroxylase (TPH) mRNA and activating serotonin transporter (SERT) in the hippocampus, and levels of NE were increased by activating tyrosine hydroxylase (TH) mRNA expression. These results demonstrate that IL-4 may locally contribute to the regulation of noradrenergic and serotonergic neurotransmission and may inhibit IL-1β-induced behavioral and immunological changes. The present results suggest that IL-4 modulates IL-1β-induced depressive behavior by inhibiting IL-1β-induced central glial activation and neurotransmitter alterations. IL-4 reduced central and systemic mediatory inflammatory activation, as well as reversing the IL-1β-induced alterations in neurotransmitter levels. The present findings contribute a biochemical pathway regulated by IL-4 that may have therapeutic utility for treatment of IL-1β-induced depressive behavior and neuroinflammation which warrants further study.

  10. IL-4 Inhibits IL-1β-Induced Depressive-Like Behavior and Central Neurotransmitter Alterations

    PubMed Central

    Park, Hyun-Jung; Shim, Hyun-Soo; An, Kyungeh; Starkweather, Angela; Kim, Kyung Soo; Shim, Insop

    2015-01-01

    It has been known that activation of the central innate immune system or exposure to stress can disrupt balance of anti-/proinflammatory cytokines. The aim of the present study was to investigate the role of pro- and anti-inflammatory cytokines in the modulation of depressive-like behaviors, the hormonal and neurotransmitter systems in rats. We investigated whether centrally administered IL-1β is associated with activation of CNS inflammatory pathways and behavioral changes and whether treatment with IL-4 could modulate IL-1β-induced depressive-like behaviors and central neurotransmitter systems. Infusion of IL-4 significantly decreased IL-1β-induced anhedonic responses and increased social exploration and total activity. Treatment with IL-4 markedly blocked IL-1β-induced increase in PGE2 and CORT levels. Also, IL-4 reduced IL-1β-induced 5-HT levels by inhibiting tryptophan hydroxylase (TPH) mRNA and activating serotonin transporter (SERT) in the hippocampus, and levels of NE were increased by activating tyrosine hydroxylase (TH) mRNA expression. These results demonstrate that IL-4 may locally contribute to the regulation of noradrenergic and serotonergic neurotransmission and may inhibit IL-1β-induced behavioral and immunological changes. The present results suggest that IL-4 modulates IL-1β-induced depressive behavior by inhibiting IL-1β-induced central glial activation and neurotransmitter alterations. IL-4 reduced central and systemic mediatory inflammatory activation, as well as reversing the IL-1β-induced alterations in neurotransmitter levels. The present findings contribute a biochemical pathway regulated by IL-4 that may have therapeutic utility for treatment of IL-1β-induced depressive behavior and neuroinflammation which warrants further study. PMID:26417153

  11. A genetic basis for altered sexual behavior in mutant female mice.

    PubMed

    Zakany, Jozsef; Duboule, Denis

    2012-09-25

    Although neural substrates of mammalian female mating behavior have been described, the association between complex courtship activity and specific underlying mechanisms remains elusive. We have isolated a mouse line that unexpectedly shows altered female social behavior with increased investigation of males and increased genital biting. We investigated adult individuals by behavioral observation and genetic and molecular neuroanatomy methods. We report exacerbated inverse pursuits and incapacitating bites directed at the genitals of stud males. This extreme deviation from wild-type female courtship segregates with a deletion of the Hoxd1 to Hoxd9 genomic region. This dominant Atypical female courtship allele (HoxD(Afc)) induces ectopic Hoxd10 gene expression in several regions in newborn forebrain transitorily and stably in a sparse subpopulation of cells in the cornu ammonis fields of adult hippocampus, which may thus lead to an abnormal modulation in the sexual behavior of mutant females. The resulting compulsive sexual solicitation behavior displayed by the most affected individuals suggests new avenues to study the genetic and molecular bases of normal and pathological mammalian affect and raises the potential involvement of the hippocampus in the control of female courtship behavior. The potential relevance to human 2q.31.1 microdeletion syndrome is discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Altered anxiety-related and abnormal social behaviors in rats exposed to early life seizures

    PubMed Central

    Castelhano, Adelisandra Silva Santos; Cassane, Gustavo dos Santos Teada; Scorza, Fulvio Alexandre; Cysneiros, Roberta Monterazzo

    2013-01-01

    Neonatal seizures are the most common manifestation of neurological dysfunction in the neonate. The prognosis of neonatal seizures is highly variable, and the controversy remains whether the severity, duration, or frequency of seizures may contribute to brain damage independently of its etiology. Animal data indicates that seizures during development are associated with a high probability of long-term adverse effects such as learning and memory impairment, behavioral changes and even epilepsy, which is strongly age dependent, as well as the severity, duration, and frequency of seizures. In preliminary studies, we demonstrated that adolescent male rats exposed to one-single neonatal status epilepticus (SE) episode showed social behavior impairment, and we proposed the model as relevant for studies of developmental disorders. Based on these facts, the goal of this study was to verify the existence of a persistent deficit and if the anxiety-related behavior could be associated with that impairment. To do so, male Wistar rats at 9 days postnatal were submitted to a single episode of SE by pilocarpine injection (380 mg/kg, i.p.) and control animals received saline (0.9%, 0.1 mL/10 g). It was possible to demonstrate that in adulthood, animals exposed to neonatal SE displayed low preference for social novelty, anxiety-related behavior, and increased stereotyped behavior in anxiogenic environment with no locomotor activity changes. On the balance, these data suggests that neonatal SE in rodents leads to altered anxiety-related and abnormal social behaviors. PMID:23675329

  13. Developmental exposure to methylmercury alters learning and induces depression-like behavior in male mice.

    PubMed

    Onishchenko, Natalia; Tamm, Christoffer; Vahter, Marie; Hökfelt, Tomas; Johnson, Jeffrey A; Johnson, Delinda A; Ceccatelli, Sandra

    2007-06-01

    To investigate the long-term effects of developmental exposure to methylmercury (MeHg), pregnant mice were exposed to at 0.5 mg MeHg/kg/day via drinking water from gestational day 7 until day 7 after delivery. The behavior of offspring was monitored at 5-15 and 26-36 weeks of age using an automated system (IntelliCage) designed for continuous long-term recording of the home cage behavior in social groups and complex analysis of basic activities and learning. In addition, spontaneous locomotion, motor coordination on the accelerating rotarod, spatial learning in Morris water maze, and depression-like behavior in forced swimming test were also studied. The analysis of behavior performed in the IntelliCage without social deprivation occurred to be more sensitive in detecting alterations in activity and learning paradigms. We found normal motor function but decreased exploratory activity in MeHg-exposed male mice, especially at young age. Learning disturbances observed in MeHg-exposed male animals suggest reference memory impairment. Interestingly, the forced swimming test revealed a predisposition to depressive-like behavior in the MeHg-exposed male offspring. This study provides novel evidence that the developmental exposure to MeHg can affect not only cognitive functions but also motivation-driven behaviors.

  14. Exogenous Androgen during Development Alters Adult Partner Preference and Mating Behavior in Gonadally Intact Male Rats

    PubMed Central

    Henley, C.L.; Nunez, A.A.; Clemens, L.G.

    2010-01-01

    In the rat, neonatal administration of testosterone propionate to a castrated male causes masculinization of behavior. However, if an intact male is treated neonatally with testosterone (hyper-androgen condition), male sexual behavior in adulthood is disrupted. There is a possibility that the hyper-androgen treatment is suppressing male sexual behavior by altering the male’s partner preference and thereby reducing his motivation to approach the female. If so, this would suggest that exposure to supra-physiological levels of androgen during development may result in the development of male-oriented partner preference in the male. To test this idea, male rats were treated either postnatally or prenatally with testosterone, and partner preference and sexual behavior were examined in adulthood. The principal finding of this study was that increased levels of testosterone during early postnatal life, but not prenatal, decreased male sexual behavior and increased the amount of time a male spent with a stimulus male, without affecting the amount of time spent with a stimulus female during partner preference tests. Thus, the reduction in male sexual behavior produced by early exposure to high levels of testosterone is not likely due to a reduction in the male’s motivation to approach a receptive female. PMID:20171967

  15. Neonatal isolation alters the estrous cycle interactions on the acute behavioral effects of cocaine.

    PubMed

    Kosten, Therese A; Sanchez, Hayde; Jatlow, Peter I; Kehoe, Priscilla

    2005-09-01

    We demonstrated that neonatal isolation (ISO) increases acquisition of cocaine self-administration and alters psychostimulant-induced ventral striatal dopamine and serotonin levels in female rats. Both dopamine and serotonin modulate the behavioral effects of cocaine and these effects can vary across estrous stages. We now test whether ISO modifies the manner in which estrous stage affects the acute behavioral responses to cocaine. Litters were assigned to ISO (1 h/day isolation; post-natal days 2-9) or non-handled (NH) conditions. In Experiment 1, the ability of cocaine (0.3-30 mg/kg; IP) to disrupt schedule-controlled responding for food was assessed in proestrus, estrus, and diestrus stages. Diestrus and proestrus NH females showed increased response rates at low cocaine doses and decreased rates at higher doses relative to baseline. In contrast, estrus NH females showed decreased responding across all doses. ISO eliminated this estrous stage distinction; only decreased responding to high cocaine doses were seen. Yet, estrous cyclicity during food restriction (Experiment 2) did not differ by group. To confirm this ISO effect, proestrus or estrus rats were administered cocaine (0, 5, 10 mg/kg; IP) and activity monitored in Experiment 3. Locomotor activity differed by estrous stage in NH but not ISO rats. Cocaine plasma levels (Experiment 4) at the time of peak behavioral activity did not differ by group or estrous stage. Results extend prior studies to show estrous stage alters the behavioral effects of cocaine. Neonatal isolation eliminates these effects perhaps reflecting alterations in accumbens monoamine levels or the effects of estrogen on this system.

  16. Invasive plant species alters consumer behavior by providing refuge from predation.

    PubMed

    Dutra, Humberto P; Barnett, Kirk; Reinhardt, Jason R; Marquis, Robert J; Orrock, John L

    2011-07-01

    Understanding the effects of invasive plants on native consumers is important because consumer-mediated indirect effects have the potential to alter the dynamics of coexistence in native communities. Invasive plants may promote changes in consumer pressure due to changes in protective cover (i.e., the architectural complexity of the invaded habitat) and in food availability (i.e., subsidies of fruits and seeds). No experimental studies have evaluated the relative interplay of these two effects. In a factorial experiment, we manipulated cover and food provided by the invasive shrub Amur honeysuckle (Lonicera maackii) to evaluate whether this plant alters the foraging activity of native mammals. Using tracking plates to quantify mammalian foraging activity, we found that removal of honeysuckle cover, rather than changes in the fruit resources it provides, reduced the activity of important seed consumers, mice in the genus Peromyscus. Two mesopredators, Procyon lotor and Didelphis virginiana, were also affected. Moreover, we found rodents used L. maackii for cover only on cloudless nights, indicating that the effect of honeysuckle was weather-dependent. Our work provides experimental evidence that this invasive plant species changes habitat characteristics, and in so doing alters the behavior of small- and medium-sized mammals. Changes in seed predator behavior may lead to cascading effects on the seeds that mice consume.

  17. Fluconazole alters the polysaccharide capsule of Cryptococcus gattii and leads to distinct behaviors in murine Cryptococcosis.

    PubMed

    Santos, Julliana Ribeiro Alves; Holanda, Rodrigo Assunção; Frases, Susana; Bravim, Mayara; Araujo, Glauber de S; Santos, Patrícia Campi; Costa, Marliete Carvalho; Ribeiro, Maira Juliana Andrade; Ferreira, Gabriella Freitas; Baltazar, Ludmila Matos; Miranda, Aline Silva; Oliveira, Danilo Bretas; Santos, Carolina Maria Araújo; Fontes, Alide Caroline Lima; Gouveia, Ludmila Ferreira; Resende-Stoianoff, Maria Aparecida; Abrahão, Jonatas Santos; Teixeira, Antônio Lúcio; Paixão, Tatiane Alves; Souza, Danielle G; Santos, Daniel Assis

    2014-01-01

    Cryptococcus gattii is an emergent human pathogen. Fluconazole is commonly used for treatment of cryptococcosis, but the emergence of less susceptible strains to this azole is a global problem and also the data regarding fluconazole-resistant cryptococcosis are scarce. We evaluate the influence of fluconazole on murine cryptococcosis and whether this azole alters the polysaccharide (PS) from cryptococcal cells. L27/01 strain of C. gattii was cultivated in high fluconazole concentrations and developed decreased drug susceptibility. This phenotype was named L27/01F, that was less virulent than L27/01 in mice. The physical, structural and electrophoretic properties of the PS capsule of L27/01F were altered by fluconazole. L27/01F presented lower antiphagocytic properties and reduced survival inside macrophages. The L27/01F did not affect the central nervous system, while the effect in brain caused by L27/01 strain began after only 12 hours. Mice infected with L27/01F presented lower production of the pro-inflammatory cytokines, with increased cellular recruitment in the lungs and severe pulmonary disease. The behavioral alterations were affected by L27/01, but no effects were detected after infection with L27/01F. Our results suggest that stress to fluconazole alters the capsule of C. gattii and influences the clinical manifestations of cryptococcosis.

  18. Fluconazole Alters the Polysaccharide Capsule of Cryptococcus gattii and Leads to Distinct Behaviors in Murine Cryptococcosis

    PubMed Central

    Santos, Julliana Ribeiro Alves; Holanda, Rodrigo Assunção; Frases, Susana; Bravim, Mayara; Araujo, Glauber de S.; Santos, Patrícia Campi; Costa, Marliete Carvalho; Ribeiro, Maira Juliana Andrade; Ferreira, Gabriella Freitas; Baltazar, Ludmila Matos; Miranda, Aline Silva; Oliveira, Danilo Bretas; Santos, Carolina Maria Araújo; Fontes, Alide Caroline Lima; Gouveia, Ludmila Ferreira; Resende-Stoianoff, Maria Aparecida; Abrahão, Jonatas Santos; Teixeira, Antônio Lúcio; Paixão, Tatiane Alves; Souza, Danielle G.; Santos, Daniel Assis

    2014-01-01

    Cryptococcus gattii is an emergent human pathogen. Fluconazole is commonly used for treatment of cryptococcosis, but the emergence of less susceptible strains to this azole is a global problem and also the data regarding fluconazole-resistant cryptococcosis are scarce. We evaluate the influence of fluconazole on murine cryptococcosis and whether this azole alters the polysaccharide (PS) from cryptococcal cells. L27/01 strain of C. gattii was cultivated in high fluconazole concentrations and developed decreased drug susceptibility. This phenotype was named L27/01F, that was less virulent than L27/01 in mice. The physical, structural and electrophoretic properties of the PS capsule of L27/01F were altered by fluconazole. L27/01F presented lower antiphagocytic properties and reduced survival inside macrophages. The L27/01F did not affect the central nervous system, while the effect in brain caused by L27/01 strain began after only 12 hours. Mice infected with L27/01F presented lower production of the pro-inflammatory cytokines, with increased cellular recruitment in the lungs and severe pulmonary disease. The behavioral alterations were affected by L27/01, but no effects were detected after infection with L27/01F. Our results suggest that stress to fluconazole alters the capsule of C. gattii and influences the clinical manifestations of cryptococcosis. PMID:25392951

  19. When two is better than one: macrophages and neutrophils work in concert in innate immunity as complementary and cooperative partners of a myeloid phagocyte system.

    PubMed

    Silva, Manuel T

    2010-01-01

    The antimicrobial effector activity of phagocytes is crucial in the host innate defense against infection, and the classic view is that the phagocytes operating against intracellular and extracellular microbial pathogens are,respectively, macrophages and neutrophils. As a result of the common origin of the two phagocytes, they share several functionalities, including avid phagocytosis,similar kinetic behavior under inflammatory/infectious conditions, and antimicrobial and immunomodulatory activities. However, consequent to specialization during their differentiation, macrophages and neutrophils acquire distinctive, complementary features that originate different levels of antimicrobial capacities and cytotoxicity and different tissue localization and lifespan.This review highlights data suggesting the perspective that the combination of overlapping and complementary characteristics of the two professional phagocytes promotes their cooperative participation as effectors and modulators in innate immunity against infection and as orchestrators of adaptive immunity. In the concerted activities operating in antimicrobial innate immunity, macrophages and neutrophils are not able to replace each other. The common and complementary developmental,kinetic, and functional properties of neutrophils and macrophages make them the effector arms of a myeloid phagocyte system that groups neutrophils with members of the old mononuclear phagocyte system. The use by mammals of a system with two dedicated phagocytic cells working cooperatively represents an advantageous innate immune attack strategy that allows the efficient and safe use of powerful but dangerous microbicidal molecules.This crucial strategy is a target of key virulence mechanisms of successful pathogens.

  20. Early life experience alters behavior during social defeat: focus on serotonergic systems.

    PubMed

    Gardner, K L; Thrivikraman, K V; Lightman, S L; Plotsky, P M; Lowry, C A

    2005-01-01

    Early life experience can have prolonged effects on neuroendocrine, autonomic, and behavioral responses to stress. The objective of this study was to investigate the effects of early life experience on behavior during social defeat, as well as on associated functional cellular responses in serotonergic and non-serotonergic neurons within the dorsal raphe nucleus, a structure which plays an important role in modulation of stress-related physiology and behavior. Male Long Evans rat pups were exposed to either normal animal facility rearing or 15 min or 180 min of maternal separation from postnatal days 2-14. As adults, these rats were exposed to a social defeat protocol. Differences in behavior were seen among the early life treatment groups during social defeat; rats exposed to 180 min of maternal separation from postnatal days 2-14 displayed more passive-submissive behaviors and less proactive coping behaviors. Analysis of the distribution of tryptophan hydroxylase and c-Fos-like immunoreactivity in control rats exposed to a novel cage and rats exposed to social defeat revealed that, independent of the early life experience, rats exposed to social defeat showed an increase in the number of c-Fos-like immunoreactive nuclei in serotonergic neurons in the middle and caudal parts of the dorsal dorsal raphe nucleus and caudal part of the ventral dorsal raphe nucleus, regions known to contain serotonergic neurons projecting to central autonomic and emotional motor control systems. This is the first study to show that the dorsomedial part of the mid-rostrocaudal dorsal raphe nucleus is engaged by a naturalistic stressor and supports the hypothesis that early life experience alters behavioral coping strategies during social conflict; furthermore, this study is consistent with the hypothesis that topographically organized subpopulations of serotonergic neurons principally within the mid-rostrocaudal and caudal part of the dorsal dorsal raphe nucleus modulate stress

  1. Invader danger: lizards faced with novel predators exhibit an altered behavioral response to stress.

    PubMed

    Trompeter, Whitney P; Langkilde, Tracy

    2011-07-01

    Animals respond to stressors by producing glucocorticoid stress hormones, such as corticosterone (CORT). CORT acts too slowly to trigger immediate behavioral responses to a threat, but can change longer-term behavior, facilitating an individual's survival to subsequent threats. To be adaptive, the nature of an animal's behavior following elevated CORT levels should be matched to the predominant threats that they face. Seeking refuge following a stressful encounter could be beneficial if the predominant predator is a visual hunter, but may prove detrimental when the predominant predator is able to enter these refuge sites. As a result, an individual's behavior when their CORT levels are high may differ among populations of a single species. Invasive species impose novel pressures on native populations, which may select for a shift in their behavior when CORT levels are high. We tested whether the presence of predatory invasive fire ants (Solenopsis invicta) at a site affects the behavioral response of native eastern fence lizards (Sceloporus undulatus) to elevated CORT levels. Lizards from an uninvaded site were more likely to hide when their CORT levels were experimentally elevated; a response that likely provides a survival advantage for lizards faced with native predatory threats (e.g. birds and snakes). Lizards from a fire ant invaded site showed the opposite response; spending more time moving and up on the basking log when their CORT levels were elevated. Use of the basking log likely reflects a refuge-seeking behavior, rather than thermoregulatory activity, as selected body temperatures were not affected by CORT. Fleeing off the ground may prove more effective than hiding for lizards that regularly encounter small, terrestrially-foraging fire ant predators. This study suggests that invasive species may alter the relationship between the physiological and behavioral stress response of native species.

  2. Phagocytes in cell suspensions of human colon mucosa.

    PubMed Central

    Beeken, W; Northwood, I; Beliveau, C; Gump, D

    1987-01-01

    Because little is known of the phagocytes of the human colon we enumerated these cells in mucosal suspensions and studied their phagocytic activity. Phagocyte rich suspensions were made by EDTA collagenase dissociation followed by elutriation centrifugation. Phagocytosis was evaluated by measuring cellular radioactivity after incubation of phagocytes with 3H-adenine labelled E coli ON2 and checked microscopically. Dissociation of normal mucosa from colorectal neoplasms yielded means of 1.9 X 10(6) eosinophils, 1.4 X 10(6) macrophages and 2 X 10(5) neutrophils per gram of mucosa. Visually normal mucosa of inflammatory states yielded 2.2 X 10(6) eosinophils, 2.3 X 10(6) macrophages and 7 X 10(5) neutrophils per gram of mucosa. Phagocyte rich suspensions of normal mucosa from tumour patients phagocytosed 21.8% of a pool of opsonised tritiated E coli ON2 and by microscopy 100% of mucosal neutrophils ingested bacteria, 83% of eosinophils were phagocytic, and 53% of macrophages contained bacteria. These results suggest that in the human colonic mucosa, the eosinophil is more abundant than the macrophage and the per cent of those cells exhibiting phagocytosis is intermediate between that of the macrophage and the neutrophil. Thus these three types of cells are actively phagocytic and share the potential for a major role in host defence against invasive enteric bacteria. PMID:3666566

  3. Environmental prenatal stress alters sexual dimorphism of maternal behavior in rats.

    PubMed

    Pérez-Laso, Carmen; Segovia, Santiago; Martín, José Luis R; Ortega, Esperanza; Gómez, Francisco; Del Cerro, M Cruz R

    2008-03-05

    The prenatal external environment can affect fetuses, altering the maternal behavior that they express when mature. In the present study, environmental prenatal stress (EPS) was applied to pregnant rats in their final week of gestation, and when their female offspring reached maturity, the long latency effect of the stress on those offspring was ascertained on their induced maternal behavior (MB), accessory olfactory bulb (AOB) morphology and plasma levels of ACTH and corticosterone (Cpd B). EPS reduced: the percentage of these virgins that showed induced MB, their retrieval of foster pups, the time spent crouching, and the quality of nest building; it also increased the incidence of their cannibalism of foster pups. The EPS-treated females presented a male-like pattern of induced MB. They showed increased plasma levels of ACTH and Cpd B and increased numbers of mitral cells in the AOB. These findings provide evidence that stress applied to the pregnant rat produces long-lasting behavioral, neuroanatomical and hormonal alterations in the female offspring that can be observed when they reach maturity.

  4. Alterations in adult behavioral responses to cocaine and dopamine transporters following juvenile exposure to methamphetamine.

    PubMed

    McFadden, Lisa; Yamamoto, Bryan K; Matuszewich, Leslie

    2011-01-20

    The present experiment assessed whether preadolescent exposure to methamphetamine would alter adult behavioral responses to cocaine and dopamine transporter immunoreactivity in the striatum of male and female rats. Juvenile rats were injected once daily with 0 or 2 mg/kg methamphetamine from postnatal days 21 to 35 and tested in adulthood. Male rats, but not female rats, exposed to methamphetamine showed an increase in responsiveness to cocaine in the open field and an increase in dopamine transporter immunoreactivity in the striatum. These findings suggest that early exposure to methamphetamine can lead to sex specific altered responses to psychostimulants in adulthood, which may contribute to later vulnerability to drug use. Copyright © 2010 Elsevier B.V. All rights reserved.

  5. Moderate prenatal alcohol exposure alters behavior and neuroglial parameters in adolescent rats.

    PubMed

    Brolese, Giovana; Lunardi, Paula; Broetto, Núbia; Engelke, Douglas S; Lírio, Franciane; Batassini, Cristiane; Tramontina, Ana Carolina; Gonçalves, Carlos-Alberto

    2014-08-01

    Alcohol consumption by women during gestation has become increasingly common. Although it is widely accepted that exposure to high doses of ethanol has long-lasting detrimental effects on brain development, the case for moderate doses is underappreciated, and benchmark studies have demonstrated structural and behavioral defects associated with moderate prenatal alcohol exposure in humans and animal models. This study aimed to investigate the influence of in utero exposure to moderate levels of ethanol throughout pregnancy on learning/memory, anxiety parameters and neuroglial parameters in adolescent offspring. Female rats were exposed to an experimental protocol throughout gestation up to weaning. After mating, the dams were divided into three groups and treated with only water (control), non-alcoholic beer (vehicle) or 10% (vv) beer solution (moderate prenatal alcohol exposure - MPAE). Adolescent male offspring were subjected to the plus-maze discriminative avoidance task to evaluate learning/memory and anxiety-like behavior. Hippocampi were dissected and slices were obtained for immunoquantification of GFAP, NeuN, S100B and the NMDA receptor. The MPAE group clearly presented anxiolytic-like behavior, even though they had learned how to avoid the aversive arm. S100B protein was increased in the cerebrospinal fluid (CSF) in the group treated with alcohol, and alterations in GFAP expression were also shown. This study indicates that moderate ethanol doses administered during pregnancy could induce anxiolytic-like effects, suggesting an increase in risk-taking behavior in adolescent male offspring. Furthermore, the data show the possibility that glial cells are involved in the altered behavior present after prenatal ethanol treatment.

  6. Functional genomics identifies negative regulatory nodes controlling phagocyte oxidative burst

    PubMed Central

    Graham, Daniel B.; Becker, Christine E.; Doan, Aivi; Goel, Gautam; Villablanca, Eduardo J.; Knights, Dan; Mok, Amanda; Ng, Aylwin C.Y.; Doench, John G.; Root, David E.; Clish, Clary B.; Xavier, Ramnik J.

    2015-01-01

    The phagocyte oxidative burst, mediated by Nox2 NADPH oxidase-derived reactive oxygen species, confers host defense against a broad spectrum of bacterial and fungal pathogens. Loss-of-function mutations that impair function of the Nox2 complex result in a life-threatening immunodeficiency, and genetic variants of Nox2 subunits have been implicated in pathogenesis of inflammatory bowel disease (IBD). Thus, alterations in the oxidative burst can profoundly impact host defense, yet little is known about regulatory mechanisms that fine-tune this response. Here we report the discovery of regulatory nodes controlling oxidative burst by functional screening of genes within loci linked to human inflammatory disease. Implementing a multi-omics approach, we define transcriptional, metabolic and ubiquitin-cycling nodes controlled by Rbpj, Pfkl and Rnf145, respectively. Furthermore, we implicate Rnf145 in proteostasis of the Nox2 complex by endoplasmic reticulum-associated degradation. Consequently, ablation of Rnf145 in murine macrophages enhances bacterial clearance, and rescues the oxidative burst defects associated with Ncf4 haploinsufficiency. PMID:26194095

  7. Fluoxetine alters behavioral consistency of aggression and courtship in male Siamese fighting fish, Betta splendens.

    PubMed

    Dzieweczynski, Teresa L; Hebert, Olivia L

    2012-08-20

    The detrimental effects of steroid-mimics are well known but investigations on non-steroid pharmaceuticals are less common. In addition, most behavioral studies do not examine the effects at multiple time points. This study examined the effects of fluoxetine, a selective serotonin reuptake inhibitor, on behavior when male Siamese fighting fish encounter female and male dummy conspecifics simultaneously. Thus, how chemical exposure impacts behavioral consistency and whether individuals differ in their sensitivity to exposure was assessed. Overall aggression was reduced after fluoxetine administration while courtship was unaffected. Fluoxetine affected behavioral consistency towards both the male and female, with individuals behaving less consistently to the male and more consistently to the female. In addition, males appeared to differ in their sensitivity to fluoxetine exposure as not all males reduced their aggression after administration. This has important implications for studying the effects of unintended pharmaceutical exposure. Exposure may have evolutionary implications as it may influence both territorial defense and mating success. In sum, these findings demonstrate that pharmaceutical exposure may alter more than just overall level of behavior and stress the importance of examining the effects of exposure on an individual level. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Effects of the essential oil from leaves of Alpinia zerumbet on behavioral alterations in mice.

    PubMed

    Murakami, Shio; Matsuura, Mariko; Satou, Tadaaki; Hayashi, Shinichiro; Koike, Kazuo

    2009-01-01

    In phytotherapy, the essential oil from the leaves of Alpinia zerumbet (Alpinia speciosa K. Schum.) (EOAZ) is used for neuropsychiatric symptoms, such as depression, stress and anxiety, and chronic problems that are associated with reproductive hormone imbalances in women. The chemical composition of EOAZ was analyzed by GC/MS, and the EOAZ properties inducing behavioral alterations in mice were examined by behavioral observations (BO) and an elevated plus-maze task (EPM), widely used as a method for assessing anxiolytic-like behaviors. Five major compounds, p-cymene (28.0 +/- 5.0%), 1,8-cineole (17.9 +/- 4.2%), terpinen-4-ol (11.9 +/- 6.3%), limonene (6.3 +/- 2.2%), and camphor (5.2 +/- 2.1%) were identified by retention indices, mass spectra and comparison with standards. Inhalational administration of EOAZ (8.7 ppm) induced unique jumping behaviors in mice. To further investigate the behavioral regulatory mechanisms of EOAZ, we administered an intraperitoneal injection of either 10 mg/kg 5-HTP or 10 mg/kg fluoxetine prior to the EOAZ inhalations. By 5-HTP or fluoxetine pretreatments, the jumping frequencies were significantly decreased. In EPM, EOAZ (0.087 and 8.7 ppm) obviously showed the anxiolytic-like activity in mice.

  9. Repeated ethanol exposure alters social behavior and oxidative stress parameters of zebrafish.

    PubMed

    Müller, Talise Ellwanger; Nunes, Stenio Zimermann; Silveira, Ariane; Loro, Vania Lucia; Rosemberg, Denis Broock

    2017-06-07

    Repeated ethanol (EtOH) consumption induces neurological disorders in humans and is considered an important public health problem. The physiological effects of EtOH are dose- and time-dependent, causing relevant changes in the social behavior. In addition, alcohol-induced oxidative stress has been proposed as a key mechanism involved in EtOH neurotoxicity. Here we investigate for the first time whether repeated EtOH exposure (REE) alters the social behavior of zebrafish and influences brain oxidation processes. Animals were exposed to water (control group) or 1% (v/v) EtOH (EtOH group) for 8 consecutive days (20min per day). EtOH was added directly to the tank water. At day 9, the social behavior and biochemical parameters were assessed. REE increased shoal cohesion by reducing inter-fish and farthest neighbor distances. SOD and CAT activities, as well as NPSH levels decreased in brain tissue. Moreover, REE increased lipid peroxidation suggesting oxidative damage. In summary, changes in oxidation processes may play a role in the CNS effects of EtOH, influencing the social behavior of zebrafish. Furthermore, in a translational neuroscience perspective, our data reinforces the utility of zebrafish to clarify the biochemical and behavioral effects of intermittent EtOH administration. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Adolescent social defeat alters neural, endocrine and behavioral responses to amphetamine in adult male rats

    PubMed Central

    Burke, Andrew R.; Renner, Kenneth J.; Forster, Gina L.; Watt, Michael J.

    2010-01-01

    The mesocorticolimbic dopamine system, which governs components of reward and goal-directed behaviors, undergoes final maturation during adolescence. Adolescent social stress contributes to adult behavioral dysfunction, and is linked to adult psychiatric and addiction disorders. Here, behavioral, corticosterone, and limbic dopamine responses to amphetamine were examined in adult male rats previously exposed to repeated social defeat stress during mid-adolescence. Amphetamine (2.5 mg/kg, ip) was administered after a novel environment test, with behavior observed in the same context for 90 min thereafter. Adult rats that had been defeated in adolescence showed increased locomotion in the novel environment, but reduced amphetamine-induced locomotion relative to non-defeated age matched controls. Monoamine and corticosterone responses to amphetamine were examined following a second amphetamine injection 3 days later. In previously defeated rats, corticosterone and medial prefrontal cortex dopamine responses to amphetamine were blunted while dopamine responses in the nucleus accumbens core were elevated. Our results suggest that experience of social defeat stress during adolescent development can contribute to altered behavioral and endocrine responses to amphetamine in adulthood. Furthermore, these effects are paralleled by changes in amphetamine-induced dopamine responses in corticolimbic systems implicated in addiction disorders. PMID:20603109

  11. Dynamical and phase behavior of a phospholipid membrane altered by an antimicrobial peptide at low concentration

    SciTech Connect

    Mamontov, Eugene; Tyagi, M.; Qian, Shuo; Rai, Durgesh K.; Urban, Volker S.; Sharma, V. K.

    2016-05-27

    Here we discuss that the mechanism of action of antimicrobial peptides is traditionally attributed to the formation of pores in the lipid cell membranes of pathogens, which requires a substantial peptide to lipid ratio. However, using incoherent neutron scattering, we show that even at a concentration too low for pore formation, an archetypal antimicrobial peptide, melittin, disrupts the regular phase behavior of the microscopic dynamics in a phospholipid membrane, dimyristoylphosphatidylcholine (DMPC). At the same time, another antimicrobial peptide, alamethicin, does not exert a similar effect on the DMPC microscopic dynamics. The melittin-altered lateral motion of DMPC at physiological temperature no longer resembles the fluid-phase behavior characteristic of functional membranes of the living cells. The disruptive effect demonstrated by melittin even at low concentrations reveals a new mechanism of antimicrobial action relevant in more realistic scenarios, when peptide concentration is not as high as would be required for pore formation, which may facilitate treatment with antimicrobial peptides.

  12. Dynamical and phase behavior of a phospholipid membrane altered by an antimicrobial peptide at low concentration

    SciTech Connect

    Mamontov, Eugene; Tyagi, M.; Qian, Shuo; Rai, Durgesh K.; Urban, Volker S.; Sharma, V. K.

    2016-05-27

    Here we discuss that the mechanism of action of antimicrobial peptides is traditionally attributed to the formation of pores in the lipid cell membranes of pathogens, which requires a substantial peptide to lipid ratio. However, using incoherent neutron scattering, we show that even at a concentration too low for pore formation, an archetypal antimicrobial peptide, melittin, disrupts the regular phase behavior of the microscopic dynamics in a phospholipid membrane, dimyristoylphosphatidylcholine (DMPC). At the same time, another antimicrobial peptide, alamethicin, does not exert a similar effect on the DMPC microscopic dynamics. The melittin-altered lateral motion of DMPC at physiological temperature no longer resembles the fluid-phase behavior characteristic of functional membranes of the living cells. The disruptive effect demonstrated by melittin even at low concentrations reveals a new mechanism of antimicrobial action relevant in more realistic scenarios, when peptide concentration is not as high as would be required for pore formation, which may facilitate treatment with antimicrobial peptides.

  13. THE IN VITRO DIFFERENTIATION OF MONONUCLEAR PHAGOCYTES

    PubMed Central

    Cohn, Zanvil A.; Hirsch, James G.; Fedorko, Martha E.

    1966-01-01

    The structure of unstimulated mouse peritoneal phagocytes has been examined by electron microscopy and compared to cells obtained from the inflamed peritoneum and from cultures maintained in vitro. The unstimulated cell resembles the blood monocyte and contains a moderate amount of rough surfaced endoplasmic reticulum, a small but well defined Golgi apparatus and a few, small, electron-opaque granules in the cytoplasm. During in vitro cultivation there are marked changes in cell ultrastructure. Most prominent is the formation of large electron-opaque granules, some of which have a complex matrix containing both electron-opaque and lucent vesicles. In addition, there is an increase in size of the Golgi apparatus with the appearance of new lamellae and tiny, smooth surfaced vesicles. With continued cultivation, large lipid droplets are found in apposition to the rough endoplasmic reticulum. The formation and size of electron-opaque granules as well as the enlargement of the Golgi region is stimulated by high concentrations of serum in the medium. Cells obtained from the peritoneal cavity of lipopolysaccharide stimulated animals demonstrated changes in ultrastructure similar to those seen in cells cultured in vitro. PMID:5931921

  14. Resistant Starch Alters the Microbiota-Gut Brain Axis: Implications for Dietary Modulation of Behavior.

    PubMed

    Lyte, Mark; Chapel, Ashley; Lyte, Joshua M; Ai, Yongfeng; Proctor, Alexandra; Jane, Jay-Lin; Phillips, Gregory J

    2016-01-01

    The increasing recognition that the gut microbiota plays a central role in behavior and cognition suggests that the manipulation of microbial taxa through diet may provide a means by which behavior may be altered in a reproducible and consistent manner in order to achieve a beneficial outcome for the host. Resistant starch continues to receive attention as a dietary intervention that can benefit the host through mechanisms that include altering the intestinal microbiota. Given the interest in dietary approaches to improve health, the aim of this study was to investigate whether the use of dietary resistant starch in mice to alter the gut microbiota also results in a change in behavior. Forty-eight 6 week-old male Swiss-Webster mice were randomly assigned to 3 treatment groups (n = 16 per group) and fed either a normal corn starch diet (NCS) or diets rich in resistant starches HA7 diet (HA7) or octenyl-succinate HA7 diet (OS-HA7) for 6 week and monitored for weight, behavior and fecal microbiota composition. Animals fed an HA7 diet displayed comparable weight gain over the feeding period to that recorded for NCS-fed animals while OS-HA7 displayed a lower weight gain as compared to either NCS or HA7 animals (ANOVA p = 0.0001; NCS:HA7 p = 0.244; HA7:OS-HA7 p<0.0001; NCS:OS-HA7 p<0.0001). Analysis of fecal microbiota using 16s rRNA gene taxonomic profiling revealed that each diet corresponded with a unique gut microbiota. The distribution of taxonomic classes was dynamic over the 6 week feeding period for each of the diets. At the end of the feeding periods, the distribution of taxa included statistically significant increases in members of the phylum Proteobacteria in OS-HA7 fed mice, while the Verrucomicrobia increased in HA7 fed mice over that of mice fed OS-HA7. At the class level, members of the class Bacilli decreased in the OS-HA7 fed group, and Actinobacteria, which includes the genus Bifidobacteria, was enriched in the HA7 fed group compared to the control

  15. Resistant Starch Alters the Microbiota-Gut Brain Axis: Implications for Dietary Modulation of Behavior

    PubMed Central

    Lyte, Mark; Chapel, Ashley; Lyte, Joshua M.; Ai, Yongfeng; Proctor, Alexandra; Jane, Jay-Lin; Phillips, Gregory J.

    2016-01-01

    The increasing recognition that the gut microbiota plays a central role in behavior and cognition suggests that the manipulation of microbial taxa through diet may provide a means by which behavior may be altered in a reproducible and consistent manner in order to achieve a beneficial outcome for the host. Resistant starch continues to receive attention as a dietary intervention that can benefit the host through mechanisms that include altering the intestinal microbiota. Given the interest in dietary approaches to improve health, the aim of this study was to investigate whether the use of dietary resistant starch in mice to alter the gut microbiota also results in a change in behavior. Forty-eight 6 week-old male Swiss-Webster mice were randomly assigned to 3 treatment groups (n = 16 per group) and fed either a normal corn starch diet (NCS) or diets rich in resistant starches HA7 diet (HA7) or octenyl-succinate HA7 diet (OS-HA7) for 6 week and monitored for weight, behavior and fecal microbiota composition. Animals fed an HA7 diet displayed comparable weight gain over the feeding period to that recorded for NCS-fed animals while OS-HA7 displayed a lower weight gain as compared to either NCS or HA7 animals (ANOVA p = 0.0001; NCS:HA7 p = 0.244; HA7:OS-HA7 p<0.0001; NCS:OS-HA7 p<0.0001). Analysis of fecal microbiota using 16s rRNA gene taxonomic profiling revealed that each diet corresponded with a unique gut microbiota. The distribution of taxonomic classes was dynamic over the 6 week feeding period for each of the diets. At the end of the feeding periods, the distribution of taxa included statistically significant increases in members of the phylum Proteobacteria in OS-HA7 fed mice, while the Verrucomicrobia increased in HA7 fed mice over that of mice fed OS-HA7. At the class level, members of the class Bacilli decreased in the OS-HA7 fed group, and Actinobacteria, which includes the genus Bifidobacteria, was enriched in the HA7 fed group compared to the control

  16. Alterations of molecular and behavioral responses to cocaine by selective inhibition of Elk-1 phosphorylation.

    PubMed

    Besnard, Antoine; Bouveyron, Nicolas; Kappes, Vincent; Pascoli, Vincent; Pagès, Christiane; Heck, Nicolas; Vanhoutte, Peter; Caboche, Jocelyne

    2011-10-05

    Activation of the extracellular signal-regulated kinase (ERK) signaling pathway in the striatum is crucial for molecular adaptations and long-term behavioral alterations induced by cocaine. In response to cocaine, ERK controls the phosphorylation levels of both mitogen and stress-activated protein kinase 1 (MSK-1), a nuclear kinase involved in histone H3 (Ser10) and cAMP response element binding protein phosphorylation, and Elk-1, a transcription factor involved in serum response element (SRE)-driven gene regulations. We recently characterized the phenotype of msk-1 knock-out mice in response to cocaine. Herein, we wanted to address the role of Elk-1 phosphorylation in cocaine-induced molecular, morphological, and behavioral responses. We used a cell-penetrating peptide, named TAT-DEF-Elk-1 (TDE), which corresponds to the DEF docking domain of Elk-1 toward ERK and inhibits Elk-1 phosphorylation induced by ERKs without modifying ERK or MSK-1 in vitro. The peptide was injected in vivo before cocaine administration in mice. Immunocytochemical, molecular, morphological, and behavioral studies were performed. The TDE inhibited Elk-1 and H3 (Ser10) phosphorylation induced by cocaine, sparing ERK and MSK-1 activation. Consequently, TDE altered cocaine-induced regulation of genes bearing SRE site(s) in their promoters, including c-fos, zif268, ΔFosB, and arc/arg3.1 (activity-regulated cytoskeleton-associated protein). In a chronic cocaine administration paradigm, TDE reversed cocaine-induced increase in dendritic spine density. Finally, the TDE delayed the establishment of cocaine-induced psychomotor sensitization and conditioned-place preference. We conclude that Elk-1 phosphorylation downstream from ERK is a key molecular event involved in long-term neuronal and behavioral adaptations to cocaine.

  17. Awake Intranasal Insulin Delivery Modifies Protein Complexes and Alters Memory, Anxiety, and Olfactory Behaviors

    PubMed Central

    Marks, D.R.; Tucker, K.; Cavallin, M.A.; Mast, T.G.; Fadool, D.A.

    2009-01-01

    The role of insulin pathways in olfaction is of significant interest with the widespread pathology of Diabetes mellitus and its associated metabolic and neuronal co-morbidities. The insulin receptor kinase (IR) is expressed at high levels in the olfactory bulb (OB), where it suppresses a dominant Shaker ion channel (Kv1.3) via tyrosine phosphorylation of critical N- and C-terminal residues. We optimized a seven day intranasal insulin delivery (IND) in awake mice to ascertain the biochemical and behavioral effects of insulin to this brain region, given that nasal sprays for insulin have been marketed notwithstanding our knowledge of the role of Kv1.3 in olfaction, metabolism, and axon targeting. IND evoked robust phosphorylation of Kv1.3, as well as increased channel protein-protein interactions with IR and post-synaptic density 95. IND-treated mice had an increased short- and long-term object memory recognition, increased anxiolytic behavior, and an increased odor-discrimination using an odor habituation protocol but only moderate change in odor threshold using a two-choice paradigm. Unlike Kv1.3 gene-targeted deletion that alters metabolism, adiposity, and axonal targeting to defined olfactory glomeruli, suppression of Kv1.3 via IND had no effect on body weight nor the size and number of M72 glomeruli or the route of its sensory axon projections. There was no evidence of altered expression of sensory neurons in the epithelium. In mice made pre-diabetic via diet-induced obesity, IND was no longer effective in increasing long-term object memory recognition nor increasing anxiolytic behavior, suggesting state dependency or a degree of insulin resistance related to these behaviors. PMID:19458242

  18. Differential behavioral and molecular alterations upon protracted abstinence from cocaine versus morphine, nicotine, THC and alcohol.

    PubMed

    Becker, Jérôme A J; Kieffer, Brigitte L; Le Merrer, Julie

    2016-04-28

    Unified theories of addiction are challenged by differing drug-seeking behaviors and neurobiological adaptations across drug classes, particularly for narcotics and psychostimulants. We previously showed that protracted abstinence to opiates leads to despair behavior and social withdrawal in mice, and we identified a transcriptional signature in the extended amygdala that was also present in animals abstinent from nicotine, Δ9-tetrahydrocannabinol (THC) and alcohol. Here we examined whether protracted abstinence to these four drugs would also share common behavioral features, and eventually differ from abstinence to the prototypic psychostimulant cocaine. We found similar reduced social recognition, increased motor stereotypies and increased anxiety with relevant c-fos response alterations in morphine, nicotine, THC and alcohol abstinent mice. Protracted abstinence to cocaine, however, led to strikingly distinct, mostly opposing adaptations at all levels, including behavioral responses, neuronal activation and gene expression. Together, these data further document the existence of common hallmarks for protracted abstinence to opiates, nicotine, THC and alcohol that develop within motivation/emotion brain circuits. In our model, however, these do not apply to cocaine, supporting the notion of unique mechanisms in psychostimulant abuse.

  19. Cellular immune responses and phagocytic activity of fishes exposed to pollution of volcano mud.

    PubMed

    Risjani, Yenny; Yunianta; Couteau, Jerome; Minier, Christophe

    2014-05-01

    Since May 29, 2006, a mud volcano in the Brantas Delta of the Sidoarjo district has emitted mud that has inundated nearby villages. Pollution in this area has been implicated in detrimental effects on fish health. In fishes, leukocyte and phagocytic cells play a vital role in body defenses. We report for the first time the effect of "LUSI" volcano mud on the immune systems of fish in the Brantas Delta. The aim of this study was to find biomarkers to allow the evaluation of the effects of volcanic mud and anthropogenic pollution on fish health in the Brantas Delta. The study took places at the Brantas Delta, which was polluted by volcano mud, and at reference sites in Karangkates and Pasuruan. Leukocyte numbers were determined using a Neubauer hemocytometer and a light microscope. Differential leukocyte counts were determined using blood smears stained with May Grunwald-Giemsa, providing neutrophil, lymphocyte and monocyte counts. Macrophages were taken from fish kidney, and their phagocytic activity was measured. In vitro analyses revealed that leukocyte and differential leukocyte counts (DLC) were higher in Channa striata and Chanos chanos caught from the polluted area. Macrophage numbers were higher in Oreochromis mossambicus than in the other species, indicating that this species is more sensitive to pollution. In areas close to volcanic mud eruption, all specimens had lower phagocytic activity. Our results show that immune cells were changed and phagocytic activity was reduced in the polluted area indicating cytotoxicity and alteration of the innate immune system in fishes exposed to LUSI volcano mud and anthropogenic pollution.

  20. Tebuconazole alters morphological, behavioral and neurochemical parameters in larvae and adult zebrafish (Danio rerio).

    PubMed

    Altenhofen, Stefani; Nabinger, Débora Dreher; Wiprich, Melissa Talita; Pereira, Talita Carneiro Brandão; Bogo, Maurício Reis; Bonan, Carla Denise

    2017-08-01

    In this study, we evaluated the effects of tebuconazole on morphology and exploratory larvae behavior and adult locomotion. Furthermore, we analyzed the effects of this fungicide on AChE activity and gene expression in zebrafish larvae and in the adult zebrafish brain. Tebuconazole (4 mg/L) increased the ocular distance in larvae and reduced the distance travelled, absolute turn angle, line crossing and time outside area in exposed larvae. Moreover, adult zebrafish that were exposed to this fungicide (4 and 6 mg/L) showed a decrease in distance travelled and mean speed when compared to the control group. However, tebuconazole did not alter the number of line crossings or time spent in the upper zone. Tebuconazole inhibited AChE activity at concentrations of 4 mg/L for larvae and 4 and 6 mg/L in the adult zebrafish brain. However, this fungicide did not alter AChE gene expression in the adult zebrafish brain but increased AChE mRNA transcript levels in larvae. These findings demonstrated that tebuconazole could modulate the cholinergic system by altering AChE activity and that this change may be associated with the reduced locomotion of these animals. Copyright © 2017. Published by Elsevier Ltd.

  1. Chronic social stress in puberty alters appetitive male sexual behavior and neural metabolic activity.

    PubMed

    Bastida, Christel C; Puga, Frank; Gonzalez-Lima, Francisco; Jennings, Kimberly J; Wommack, Joel C; Delville, Yvon

    2014-07-01

    Repeated social subjugation in early puberty lowers testosterone levels. We used hamsters to investigate the effects of social subjugation on male sexual behavior and metabolic activity within neural systems controlling social and motivational behaviors. Subjugated animals were exposed daily to aggressive adult males in early puberty for postnatal days 28 to 42, while control animals were placed in empty clean cages. On postnatal day 45, they were tested for male sexual behavior in the presence of receptive female. Alternatively, they were tested for mate choice after placement at the base of a Y-maze containing a sexually receptive female in one tip of the maze and an ovariectomized one on the other. Social subjugation did not affect the capacity to mate with receptive females. Although control animals were fast to approach females and preferred ovariectomized individuals, subjugated animals stayed away from them and showed no preference. Cytochrome oxidase activity was reduced within the preoptic area and ventral tegmental area in subjugated hamsters. In addition, the correlation of metabolic activity of these areas with the bed nucleus of the stria terminalis and anterior parietal cortex changed significantly from positive in controls to negative in subjugated animals. These data show that at mid-puberty, while male hamsters are capable of mating, their appetitive sexual behavior is not fully mature and this aspect of male sexual behavior is responsive to social subjugation. Furthermore, metabolic activity and coordination of activity in brain areas related to sexual behavior and motivation were altered by social subjugation. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Chicoric acid regulates behavioral and biochemical alterations induced by chronic stress in experimental Swiss albino mice.

    PubMed

    Kour, Kiranjeet; Bani, Sarang

    2011-09-01

    The present study was taken up to see the effect of chicoric acid (CA) on behavioral and biochemical alterations induced by chronic restraint stress in experimental Swiss albino mice. CA at 1mg/kg dose level exhibited considerable antidepressant activity as shown by significant decrease in immobility period in the Porsolt's swim stress-induced behavioral despair test and escape failures in Learned "helplessness test". The antidepressant activity shown by CA can be attributed to its modulating effect on nor-adrenaline (NA), dopamine (DA) and 5- hydroxy tryptamine (5-HT) as shown by their quantification in CA treated chronically stressed mice. Further, a significant antioxidant effect was exhibited by CA as shown by estimation of lipid peroxidation, glutathione (GSH) and glycogen in liver of chronically stressed mice. It also normalized altered values of serum glucose, triglycerides, aspartate aminotransferase (AST) alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in a dose dependent manner. The stress busting potential of CA was further confirmed by its regulating effect on raised plasma corticosterone levels and significant attenuation of the depleted ascorbic acid, cholesterol and corticosterone levels in adrenal glands. Thus, our results suggest that CA possesses considerable stress busting potential, and that anti-oxidation may be one of the mechanisms underlying its antistress action.

  3. An image processing framework for automated analysis of swimming behavior in tadpoles with vestibular alterations

    NASA Astrophysics Data System (ADS)

    Zarei, Kasra; Fritzsch, Bernd; Buchholz, James H. J.

    2017-03-01

    Micogravity, as experienced during prolonged space flight, presents a problem for space exploration. Animal models, specifically tadpoles, with altered connections of the vestibular ear allow the examination of the effects of microgravity and can be quantitatively monitored through tadpole swimming behavior. We describe an image analysis framework for performing automated quantification of tadpole swimming behavior. Speckle reducing anisotropic diffusion is used to smooth tadpole image signals by diffusing noise while retaining edges. A narrow band level set approach is used for sharp tracking of the tadpole body. The use of level set method for interface tracking provides an inherent advantage of using level set based image segmentation algorithm (active contouring). Active contour segmentation is followed by two-dimensional skeletonization, which allows the automated quantification of tadpole deflection angles, and subsequently tadpole escape (or C-start) response times. Evaluation of the image analysis methodology was performed by comparing the automated quantifications of deflection angles to manual assessments (obtained using a standard grading scheme), and produced a high correlation (r2 = 0.99) indicating high reliability and accuracy of the proposed method. The methods presented form an important element of objective quantification of the escape response of the tadpole vestibular system to mechanical and biochemical manipulations, and can ultimately contribute to a better understanding of the effects of altered gravity perception on humans.

  4. Alterations in the behavioral effects of LSD by motivational and neurohumoral variables.

    PubMed

    Joseph, J A; Appel, J B

    1976-07-01

    Forty naive male albino rats were trained to press a bar on a fixed-ratio (FR 32) schedule of water reinforcement. They were then divided into two groups, one of which (N = 20) received 5 min of extra water 12 hr before each experimental session; the other group (N = 20) received no extra water. Half of the animals in each group was given three daily doses (100 mg/kg) of the trytophan hydroxylase inhibitor p-chlorophenylalanine methyl ester (PCPA) while the remaining animals were given control injections of the PCPA vehicle. Ten days following the last administration of PCPA (or vehicle) all animals were given a low dose of LSD (20 mug/kg). Bar-pressing behavior was significantly disrupted only in those animals receiving both PCPA and extra water. Central (whold brain) concentrations of serotonin (5-HT) were significantly lower in all animals which had been treated with PCPA. These results, along with those previously reported, suggest that amount of deprivation can be an important determinant of both the ability of drugs to alter behavior and the dependence of such alterations upon underlying neuronal activity.

  5. Altered spontaneous neural activity in the occipital face area reflects behavioral deficits in developmental prosopagnosia.

    PubMed

    Zhao, Yuanfang; Li, Jingguang; Liu, Xiqin; Song, Yiying; Wang, Ruosi; Yang, Zetian; Liu, Jia

    2016-08-01

    Individuals with developmental prosopagnosia (DP) exhibit severe difficulties in recognizing faces and to a lesser extent, also exhibit difficulties in recognizing non-face objects. We used fMRI to investigate whether these behavioral deficits could be accounted for by altered spontaneous neural activity. Two aspects of spontaneous neural activity were measured: the intensity of neural activity in a voxel indexed by the fractional amplitude of spontaneous low-frequency fluctuations (fALFF), and the connectivity of a voxel to neighboring voxels indexed by regional homogeneity (ReHo). Compared with normal adults, both the fALFF and ReHo values within the right occipital face area (rOFA) were significantly reduced in DP subjects. Follow-up studies on the normal adults revealed that these two measures indicated further functional division of labor within the rOFA. The fALFF in the rOFA was positively correlated with behavioral performance in recognition of non-face objects, whereas ReHo in the rOFA was positively correlated with processing of faces. When considered together, the altered fALFF and ReHo within the same region (rOFA) may account for the comorbid deficits in both face and object recognition in DPs, whereas the functional division of labor in these two measures helps to explain the relative independency of deficits in face recognition and object recognition in DP. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Deletion of Rictor in catecholaminergic neurons alters locomotor activity and ingestive behavior.

    PubMed

    Kaska, Sophia; Brunk, Rebecca; Bali, Vedrana; Kechner, Megan; Mazei-Robison, Michelle S

    2017-05-01

    While the etiology of depression is not fully understood, increasing evidence from animal models suggests a role for the ventral tegmental area (VTA) in pathogenesis. In this paper, we investigate the potential role of VTA mechanistic target of rapamycin 2 (TORC2) signaling in mediating susceptibility to chronic social defeat stress (CSDS), a well-established mouse model of depression. Utilizing genetic and viral knockout of Rictor (rapamycin-insensitive companion of target of rapamycin), a requisite component of TORC2, we demonstrate that decreasing Rictor-dependent TORC2 signaling in catecholaminergic neurons, or within the VTA specifically, does not alter susceptibility to CSDS. Opiate abuse and mood disorders are often comorbid, and previous data demonstrate a role for VTA TORC2 in mediating opiate reward. Thus, we also investigated its potential role in mediating changes in opiate reward following CSDS. Catecholaminergic deletion of Rictor increases water, sucrose, and morphine intake but not preference in a two-bottle choice assay in stress-naïve mice, and these effects are maintained after stress. VTA-specific knockout of Rictor increases water and sucrose intake after physical CSDS, but does not alter consummatory behavior in the absence of stress. These findings suggest a novel role for TORC2 in mediating stress-induced changes in consummatory behaviors that may contribute to some aspects of mood disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Gestational exposure to perfluorooctanoic acid (PFOA): Alterations in motor related behaviors.

    PubMed

    Goulding, David R; White, Sally S; McBride, Sandra J; Fenton, Suzanne E; Harry, G Jean

    2017-01-01

    Perfluoroalkyl and polyfluoroalkyl substances are used in commercial applications and developmental exposure has been implicated in alterations in neurobehavioral functioning. While associations between developmental perfluorooctanoic acid (PFOA) exposure and human outcomes have been inconsistent, studies in experimental animals suggest alterations in motor related behaviors. To examine a dose-response pattern of neurobehavioral effects following gestational exposure to PFOA, pregnant CD-1 mice received PFOA (0, 0.1, 0.3, 1.0mg/kg/day) via oral gavage from gestational day 1-17 and the male offspring examined. Motor activity assessments on postnatal day (PND)18, 19, and 20 indicated a shift in the developmental pattern with an elevated activity level observed in the 1.0mg/kg/day dose group on PND18. In the adult, no alterations were observed in body weights, activity levels, diurnal pattern of running wheel activity, startle response, or pre-pulse startle inhibition. In response to a subcutaneous injection of saline or nicotine (80μg/kg), all animals displayed a transient increase in activity likely associated with handling with no differences observed across dose groups. Inhibition of motor activity over 18days of 400μg/kg nicotine injection was not significantly different across dose groups. Hyperactivity induced by 2mg/kg (+)-methamphetamine hydrochloride intraperitoneal injection was significantly lower in the 1.0mg/kg/day PFOA dose group as compared to controls. Taken together, these data suggest that the effects on motor-related behaviors with gestational PFOA exposure do not mimic those reported for acute postnatal exposure. Changes were not observed at dose levels under 1.0mg/kg/day PFOA. Further examination of pathways associated with methamphetamine-induced activity is warranted. Published by Elsevier B.V.

  8. Methylmercuric Chloride Induces Activation of Neuronal Stress Circuitry and Alters Exploratory Behavior in the Mouse

    PubMed Central

    Cooper, Joel F.

    2007-01-01

    Methylmercury (MeHg) is a well known neurotoxicant, responsible for neurological and cognitive alterations. However, there is very little information available on the effects of MeHg administration on activation of murine neuronal pathways involved in the stress response, and whether this is altered as a function of repeated exposure to MeHg. Moreover, interactions between MeHg and other psychogenic and inflammatory stressors have yet to be fully determined. Acute intraperitoneal (IP) exposure of male C57BL/6J mice to MeHg (2−8 mg/Kg) dose-dependently attenuated exploratory behavior in the open field in the presence and absence of a novel object. In addition, increased numbers of c-Fos immunoreactive cells appeared in response to acute IP and ICV MeHg within thalamic (PVA/PV), hypothalamic (PVN), central amygdaloid (CeC), septal and hippocampal (dentate gyrus) nuclei, medial bed nucleus (BSTm) and the locus coeruleus (Lc). The increase in c-Fos positive cells in response to acute IP and ICV MeHg did not appear to be influenced further by open field exposure. Repeated administration of MeHg led to an attenuation of most parameters of open field behavior altered by acute MeHg. However, increased c-Fos was significant in the CeC, Dg, supracapsular bed nucleus (BSTs), and Lc. Moreover, open field exposure after repeated treatments resulted in significant c-Fos responses in similar areas. Interestingly, 3 days after the final repeated MeHg dose (2 or 4 mg/kg) c-Fos increases to an immunogenic stressor (LPS) were not affected by MeHg pretreatment. These results demonstrate that systemic exposure to acute and repeated MeHg serves to activate the brain's stress circuitry, and furthermore appears to engage normal neuronal habituation processes. PMID:17764854

  9. Specifically targeted delivery of protein to phagocytic macrophages

    PubMed Central

    Yu, Min; Chen, Zeming; Guo, Wenjun; Wang, Jin; Feng, Yupeng; Kong, Xiuqi; Hong, Zhangyong

    2015-01-01

    Macrophages play important roles in the pathogenesis of various diseases, and are important potential therapeutic targets. Furthermore, macrophages are key antigen-presenting cells and important in vaccine design. In this study, we report on the novel formulation (bovine serum albumin [BSA]-loaded glucan particles [GMP-BSA]) based on β-glucan particles from cell walls of baker’s yeast for the targeted delivery of protein to macrophages. Using this formulation, chitosan, tripolyphosphate, and alginate were used to fabricate colloidal particles with the model protein BSA via electrostatic interactions, which were caged and incorporated BSA very tightly within the β-glucan particle shells. The prepared GMP-BSA exhibited good protein-release behavior and avoided protein leakage. The particles were also highly specific to phagocytic macrophages, such as Raw 264.7 cells, primary bone marrow-derived macrophages, and peritoneal exudate macrophages, whereas the particles were not taken up by nonphagocytic cells, including NIH3T3, AD293, HeLa, and Caco-2. We hypothesize that these tightly encapsulated protein-loaded glucan particles deliver various types of proteins to macrophages with notably high selectivity, and may have broad applications in targeted drug delivery or vaccine design against macrophages. PMID:25784802

  10. Chronic alcohol exposure alters behavioral and synaptic plasticity of the rodent prefrontal cortex.

    PubMed

    Kroener, Sven; Mulholland, Patrick J; New, Natasha N; Gass, Justin T; Becker, Howard C; Chandler, L Judson

    2012-01-01

    In the present study, we used a mouse model of chronic intermittent ethanol (CIE) exposure to examine how CIE alters the plasticity of the medial prefrontal cortex (mPFC). In acute slices obtained either immediately or 1-week after the last episode of alcohol exposure, voltage-clamp recording of excitatory post-synaptic currents (EPSCs) in mPFC layer V pyramidal neurons revealed that CIE exposure resulted in an increase in the NMDA/AMPA current ratio. This increase appeared to result from a selective increase in the NMDA component of the EPSC. Consistent with this, Western blot analysis of the postsynaptic density fraction showed that while there was no change in expression of the AMPA GluR1 subunit, NMDA NR1 and NRB subunits were significantly increased in CIE exposed mice when examined immediately after the last episode of alcohol exposure. Unexpectedly, this increase in NR1 and NR2B was no longer observed after 1-week of withdrawal in spite of a persistent increase in synaptic NMDA currents. Analysis of spines on the basal dendrites of layer V neurons revealed that while the total density of spines was not altered, there was a selective increase in the density of mushroom-type spines following CIE exposure. Examination of NMDA-receptor mediated spike-timing-dependent plasticity (STDP) showed that CIE exposure was associated with altered expression of long-term potentiation (LTP). Lastly, behavioral studies using an attentional set-shifting task that depends upon the mPFC for optimal performance revealed deficits in cognitive flexibility in CIE exposed mice when tested up to 1-week after the last episode of alcohol exposure. Taken together, these observations are consistent with those in human alcoholics showing protracted deficits in executive function, and suggest these deficits may be associated with alterations in synaptic plasticity in the mPFC.

  11. Chronic Alcohol Exposure Alters Behavioral and Synaptic Plasticity of the Rodent Prefrontal Cortex

    PubMed Central

    Kroener, Sven; Mulholland, Patrick J.; New, Natasha N.; Gass, Justin T.; Becker, Howard C.; Chandler, L. Judson

    2012-01-01

    In the present study, we used a mouse model of chronic intermittent ethanol (CIE) exposure to examine how CIE alters the plasticity of the medial prefrontal cortex (mPFC). In acute slices obtained either immediately or 1-week after the last episode of alcohol exposure, voltage-clamp recording of excitatory post-synaptic currents (EPSCs) in mPFC layer V pyramidal neurons revealed that CIE exposure resulted in an increase in the NMDA/AMPA current ratio. This increase appeared to result from a selective increase in the NMDA component of the EPSC. Consistent with this, Western blot analysis of the postsynaptic density fraction showed that while there was no change in expression of the AMPA GluR1 subunit, NMDA NR1 and NRB subunits were significantly increased in CIE exposed mice when examined immediately after the last episode of alcohol exposure. Unexpectedly, this increase in NR1 and NR2B was no longer observed after 1-week of withdrawal in spite of a persistent increase in synaptic NMDA currents. Analysis of spines on the basal dendrites of layer V neurons revealed that while the total density of spines was not altered, there was a selective increase in the density of mushroom-type spines following CIE exposure. Examination of NMDA-receptor mediated spike-timing-dependent plasticity (STDP) showed that CIE exposure was associated with altered expression of long-term potentiation (LTP). Lastly, behavioral studies using an attentional set-shifting task that depends upon the mPFC for optimal performance revealed deficits in cognitive flexibility in CIE exposed mice when tested up to 1-week after the last episode of alcohol exposure. Taken together, these observations are consistent with those in human alcoholics showing protracted deficits in executive function, and suggest these deficits may be associated with alterations in synaptic plasticity in the mPFC. PMID:22666364

  12. ApoE2 Exaggerates PTSD-Related Behavioral, Cognitive, and Neuroendocrine Alterations.

    PubMed

    Johnson, Lance A; Zuloaga, Damian G; Bidiman, Erin; Marzulla, Tessa; Weber, Sydney; Wahbeh, Helane; Raber, Jacob

    2015-09-01

    Apolipoprotein E (apoE) is an essential component of lipoprotein particles in both the brain and periphery, and exists in three isoforms in the human population: E2, E3, and E4. ApoE has numerous, well-established roles in neurobiology. Most notably, E4 is associated with earlier onset and increased risk of Alzheimer's disease (AD). Although possession of E2 is protective in the context of AD, E2 appears to confer an increased incidence and severity of posttraumatic stress disorder (PTSD). However, the biological processes underlying this link remain unclear. In this study, we began to elucidate these associations by examining the effects of apoE on PTSD severity in combat veterans, and on PTSD-like behavior in mice with human apoE. In a group of 92 veterans with PTSD, we observed significantly higher Clinician-Administered PTSD Scale and PTSD Checklist scores in E2+ individuals, as well as alterations in salivary cortisol levels. Furthermore, we measured behavioral and biological outcomes in mice expressing human apoE after a single stressful event as well as following a period of chronic variable stress, a model of combat-related trauma. Mice with E2 showed impairments in fear extinction, and behavioral, cognitive, and neuroendocrine alterations following trauma. To the best of our knowledge, these data constitute the first translational demonstration of PTSD severity in men and PTSD-like symptoms in mice with E2, and point to apoE as a novel biomarker of susceptibility, and potential therapeutic target, for PTSD.

  13. PPAR Agonists: II. Fenofibrate and Tesaglitazar Alter Behaviors Related to Voluntary Alcohol Consumption.

    PubMed

    Blednov, Yuri A; Black, Mendy; Benavidez, Jillian M; Stamatakis, Eleni E; Harris, R Adron

    2016-03-01

    In the accompanying article, we showed that activation of peroxisome proliferator-activated receptor alpha (PPARα) signaling by fenofibrate and tesaglitazar decreases ethanol (EtOH) consumption in mice. In this study, we determined the role of these PPAR agonists in EtOH-related behaviors and other actions that may be important in regulating EtOH consumption. The effects of fenofibrate (150 mg/kg) and tesaglitazar (1.5 mg/kg) were examined on the following responses in male and female C57BL/6J (B6) and B6 × 129S4 mice: preference for saccharin, EtOH-induced conditioned place preference (CPP), conditioned taste aversion (CTA), loss of righting reflex, and withdrawal, acoustic startle reflex, response to novelty, and EtOH clearance. Because the B6 inbred strain usually displays weak EtOH-induced CPP and weak EtOH-induced acute withdrawal, B6 × 129S4 mice were also studied. Fenofibrate and tesaglitazar decreased the novelty response and increased acute EtOH withdrawal severity, and fenofibrate increased EtOH-induced CTA. Two important factors for EtOH consumption (saccharin preference and EtOH-induced CPP) were not altered by fenofibrate or tesaglitazar. EtOH clearance was increased by both fenofibrate and tesaglitazar. Response to novelty, acute withdrawal, and EtOH clearance show sex differences and could contribute to the reduced EtOH consumption following fenofibrate administration. These studies indicate the complexity of EtOH-dependent and EtOH-independent behaviors that are altered by PPAR agonists and provide evidence for novel behavioral actions of these drugs that may contribute to PPAR-mediated effects on alcohol drinking. Copyright © 2016 by the Research Society on Alcoholism.

  14. Interactions between behaviorally relevant rhythms and synaptic plasticity alter coding in the piriform cortex

    PubMed Central

    Urban, Nathaniel N.

    2012-01-01

    Understanding how neural and behavioral timescales interact to influence cortical activity and stimulus coding is an important issue in sensory neuroscience. In air-breathing animals, voluntary changes in respiratory frequency alter the temporal patterning olfactory input. In the olfactory bulb, these behavioral timescales are reflected in the temporal properties of mitral/tufted (M/T) cell spike trains. As the odor information contained in these spike trains is relayed from the bulb to the cortex, interactions between presynaptic spike timing and short-term synaptic plasticity dictate how stimulus features are represented in cortical spike trains. Here we demonstrate how the timescales associated with respiratory frequency, spike timing and short-term synaptic plasticity interact to shape cortical responses. Specifically, we quantified the timescales of short-term synaptic facilitation and depression at excitatory synapses between bulbar M/T cells and cortical neurons in slices of mouse olfactory cortex. We then used these results to generate simulated M/T population synaptic currents that were injected into real cortical neurons. M/T population inputs were modulated at frequencies consistent with passive respiration or active sniffing. We show how the differential recruitment of short-term plasticity at breathing versus sniffing frequencies alters cortical spike responses. For inputs at sniffing frequencies, cortical neurons linearly encoded increases in presynaptic firing rates with increased phase locked, firing rates. In contrast, at passive breathing frequencies, cortical responses saturated with changes in presynaptic rate. Our results suggest that changes in respiratory behavior can gate the transfer of stimulus information between the olfactory bulb and cortex. PMID:22553016

  15. Limited Nesting Stress Alters Maternal Behavior and In Vivo Intestinal Permeability in Male Wistar Pup Rats

    PubMed Central

    Moussaoui, Nabila; Larauche, Muriel; Biraud, Mandy; Molet, Jenny; Million, Mulugeta; Mayer, Emeran; Taché, Yvette

    2016-01-01

    A few studies indicate that limited nesting stress (LNS) alters maternal behavior and the hypothalamic pituitary adrenal (HPA) axis of dams and offspring in male Sprague Dawley rats. In the present study, we evaluated the impact of LNS on maternal behavior in Wistar rats, and on the HPA axis, glycemia and in vivo intestinal permeability of male and female offspring. Intestinal permeability is known to be elevated during the first week postnatally and influenced by glucocorticoids. Dams and neonatal litters were subjected to LNS or normal nesting conditions (control) from days 2 to 10 postnatally. At day 10, blood was collected from pups for determination of glucose and plasma corticosterone by enzyme immunoassay and in vivo intestinal permeability by oral gavage of fluorescein isothiocyanate–dextran 4kDa. Dams exposed to LNS compared to control showed an increase in the percentage of time spent building a nest (118%), self-grooming (69%), and putting the pups back to the nest (167%). LNS male and female pups exhibited a reduction of body weight by 5% and 4%, adrenal weights/100g body weight by 17% and 18%, corticosterone plasma levels by 64% and 62% and blood glucose by 11% and 12% respectively compared to same sex control pups. In male LNS pups, intestinal permeability was increased by 2.7-fold while no change was observed in females compared to same sex control. There was no sex difference in any of the parameters in control pups except the body weight. These data indicate that Wistar dams subjected to LNS during the first postnatal week have an altered repertoire of maternal behaviors which affects the development of the HPA axis in both sexes and intestinal barrier function in male offspring. PMID:27149676

  16. ApoE2 Exaggerates PTSD-Related Behavioral, Cognitive, and Neuroendocrine Alterations

    PubMed Central

    Johnson, Lance A; Zuloaga, Damian G; Bidiman, Erin; Marzulla, Tessa; Weber, Sydney; Wahbeh, Helane; Raber, Jacob

    2015-01-01

    Apolipoprotein E (apoE) is an essential component of lipoprotein particles in both the brain and periphery, and exists in three isoforms in the human population: E2, E3, and E4. ApoE has numerous, well-established roles in neurobiology. Most notably, E4 is associated with earlier onset and increased risk of Alzheimer's disease (AD). Although possession of E2 is protective in the context of AD, E2 appears to confer an increased incidence and severity of posttraumatic stress disorder (PTSD). However, the biological processes underlying this link remain unclear. In this study, we began to elucidate these associations by examining the effects of apoE on PTSD severity in combat veterans, and on PTSD-like behavior in mice with human apoE. In a group of 92 veterans with PTSD, we observed significantly higher Clinician-Administered PTSD Scale and PTSD Checklist scores in E2+ individuals, as well as alterations in salivary cortisol levels. Furthermore, we measured behavioral and biological outcomes in mice expressing human apoE after a single stressful event as well as following a period of chronic variable stress, a model of combat-related trauma. Mice with E2 showed impairments in fear extinction, and behavioral, cognitive, and neuroendocrine alterations following trauma. To the best of our knowledge, these data constitute the first translational demonstration of PTSD severity in men and PTSD-like symptoms in mice with E2, and point to apoE as a novel biomarker of susceptibility, and potential therapeutic target, for PTSD. PMID:25857685

  17. Gestational exposure to yellow fever vaccine at different developmental stages induces behavioral alterations in the progeny.

    PubMed

    Marianno, P; Salles, M J S; Sonego, A B; Costa, G A; Galvão, T C; Lima, G Z; Moreira, E G

    2013-01-01

    The most effective method to prevent yellow fever and control the disease is a vaccine made with attenuated live virus. Due to the neurological tropism of the virus, preventive vaccination is not recommended for infants under 6 months and for pregnant women. However there is a paucity of data regarding the safety for pregnant women and there are no experimental studies investigating adverse effects to the offspring after maternal exposure to the vaccine. This study aimed to investigate, in mice, the effects of maternal exposure to the yellow fever vaccine at three different gestational ages on the physical and behavioral development of the offspring. Pregnant Swiss mice received a single subcutaneous injection of water for injection (control groups) or 2 log Plaque Forming Units (vaccine-treated groups) of the yellow fever vaccine on gestational days (GD) 5, 10 or 15. Neither maternal signs of toxicity nor alterations in physical development and reflex ontogeny of the offspring were observed in any of the groups. Data from behavioral evaluation indicated that yellow fever vaccine exposure induced motor hypoactivity in 22-day-old females independent of the day of exposure; and in 60-day-old male and female pups exposed at GD 10. Moreover, 22-day-old females also presented with a deficit in habituation memory. Altogether, these results indicate that in utero exposure to the yellow fever vaccine may induce behavioral alterations in the pups that may persist to adulthood in the absence of observed maternal toxicity or disruption of physical development milestones or reflex ontogeny. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Crickets in space: morphological, physiological and behavioral alterations induced by space flight and hypergravity

    NASA Astrophysics Data System (ADS)

    Horn, E.; Agricola, H.; Böser, S.; Förster, S.; Kämper, G.; Riewe, P.; Sebastian, C.

    "Crickets in Space" was a Neurolab experiment by which the balance between genetic programs and the gravitational environment for the development of a gravity sensitive neuronal system was studied. The model character of crickets was justified by their external gravity receptors, identified position-sensitive interneurons (PSI) and gravity-related compensatory head response, and by the specific relation of this behavior to neuronal arousal systems activated by locomotion. These advantages allowed to study the impact of modified gravity on cellular processes in a complex organism. Eggs, 1st, 4th and 6th stage larvae of Acheta domesticus were used. Post-flight experiments revealed a low susceptibility of the behavior to micro- and hypergravity while the physiology of the PSI was significantly affected. Immunocytological investigations revealed a stage-dependent sensitivity of thoracic GABAergic motoneurons to 3g-conditions concerning their soma sizes but not their topographical arrangement. The morphology of neuromuscular junctions was not affected by 3g-hypergravity. Peptidergic neurons from cerebral sensorimotor centers revealed no significant modifications by microgravity (μg). The contrary physiological and behavioral results indicate a facilitation of 1g-readaptation originating from accessory gravity, proprioceptive and visual sense organs. Absence of anatomical modifications point to an effective time window of μg- or 3g-expo-sure related to the period of neuronal proliferation. The analysis of basic mechanisms of how animals and man adapt to altered gravitational conditions will profit from a continuation of the project "Crickets in Space".

  19. Removal of GABAA Receptor γ2 Subunits from Parvalbumin Neurons Causes Wide-Ranging Behavioral Alterations

    PubMed Central

    Leppä, Elli; Linden, Anni-Maija; Vekovischeva, Olga Y.; Swinny, Jerome D.; Rantanen, Ville; Toppila, Esko; Höger, Harald; Sieghart, Werner; Wulff, Peer; Wisden, William; Korpi, Esa R.

    2011-01-01

    We investigated the behavioral significance of fast synaptic inhibition by αβγ2-type GABAA receptors on parvalbumin (Pv) cells. The GABAA receptor γ2 subunit gene was selectively inactivated in Pv-positive neurons by Cre/loxP recombination. The resulting Pv-Δγ2 mice were relatively healthy in the first postnatal weeks; but then as Cre started to be expressed, the mice progressively developed wide-ranging phenotypic alterations including low body weight, motor deficits and tremor, decreased anxiety levels, decreased pain sensitivity and deficient prepulse inhibition of the acoustic startle reflex and impaired spatial learning. Nevertheless, the deletion was not lethal, and mice did not show increased mortality even after one year. Autoradiography with t-butylbicyclophosphoro[35S]thionate suggested an increased amount of GABAA receptors with only α and β subunits in central nervous system regions that contained high levels of parvalbumin neurons. Using BAC-transgenesis, we reduced some of the Pv-Δγ2 phenotype by selectively re-expressing the wild-type γ2 subunit back into some Pv cells (reticular thalamic neurons and cerebellar Pv-positive neurons). This produced less severe impairments of motor skills and spatial learning compared with Pv-Δγ2 mice, but all other deficits remained. Our results reveal the widespread significance of fast GABAergic inhibition onto Pv-positive neurons for diverse behavioral modalities, such as motor coordination, sensorimotor integration, emotional behavior and nociception. PMID:21912668

  20. Ethanol exposure during gastrulation alters neuronal morphology and behavior in zebrafish.

    PubMed

    Shan, Shubham D; Boutin, Savanna; Ferdous, Jannatul; Ali, Declan W

    2015-01-01

    Ethanol (EtOH) exposure during development has been shown to lead to deficits in fine and gross motor control. In this study we used zebrafish embryos to determine the effects of EtOH treatment during gastrulation. We treated embryos in the gastrulation stage (5.25 hours post fertilization (hpf) to 10.75 hpf) with 10 mM, 50 mM or 100 mM EtOH and examined the effects on general animal morphology, the c-start reflex behavior, Mauthner cell (M-cell) morphology and motor neuron morphology. EtOH treated fish exhibited a minor but significant increase in gross morphological deformities compared with untreated fish. Behavioral studies showed that EtOH treatment resulted in an increase in the peak speed of the tail during the escape response. Furthermore, there was a marked increase in abnormally directed c-starts, with treated fish showing greater incidences of c-starts in inappropriate directions. Immunolabeling of the M-cells, which are born during gastrulation, revealed that they were significantly smaller in fish treated with 100 mM EtOH compared with controls. Immunolabeling of primary motor neurons using anti-znp1, showed no significant effect on axonal branching, whereas secondary motor axons had a greater number of branches in ethanol treated fish compared with controls. Together these findings indicate that ethanol exposure during gastrulation can lead to alterations in behavior, neuronal morphology and possibly function.

  1. Aniracetam Does Not Alter Cognitive and Affective Behavior in Adult C57BL/6J Mice

    PubMed Central

    Elston, Thomas W.; Pandian, Ashvini; Smith, Gregory D.; Holley, Andrew J.; Gao, Nanjing; Lugo, Joaquin N.

    2014-01-01

    There is a growing community of individuals who self-administer the nootropic aniracetam for its purported cognitive enhancing effects. Aniracetam is believed to be therapeutically useful for enhancing cognition, alleviating anxiety, and treating various neurodegenerative conditions. Physiologically, aniracetam enhances both glutamatergic neurotransmission and long-term potentiation. Previous studies of aniracetam have demonstrated the cognition-restoring effects of acute administration in different models of disease. No previous studies have explored the effects of aniracetam in healthy subjects. We investigated whether daily 50 mg/kg oral administration improves cognitive performance in naïve C57BL/6J mice in a variety of aspects of cognitive behavior. We measured spatial learning in the Morris water maze test; associative learning in the fear conditioning test; motor learning in the accelerating rotarod test; and odor discrimination. We also measured locomotion in the open field test, anxiety through the elevated plus maze test and by measuring time in the center of the open field test. We measured repetitive behavior through the marble burying test. We detected no significant differences between the naive, placebo, and experimental groups across all measures. Despite several studies demonstrating efficacy in impaired subjects, our findings suggest that aniracetam does not alter behavior in normal healthy mice. This study is timely in light of the growing community of healthy humans self-administering nootropic drugs. PMID:25099639

  2. Chemosensory cues affect amygdaloid neurogenesis and alter behaviors in the socially monogamous prairie vole.

    PubMed

    Liu, Y; Lieberwirth, C; Jia, X; Curtis, J T; Meredith, M; Wang, Z X

    2014-05-01

    The current study examined the effects of pheromonal exposure on adult neurogenesis and revealed the role of the olfactory pathways on adult neurogenesis and behavior in the socially monogamous prairie vole (Microtus ochrogaster). Subjects were injected with a cell proliferation marker [5-bromo-2'-deoxyuridine (BrdU)] and then exposed to their own soiled bedding or bedding soiled by a same- or opposite-sex conspecific. Exposure to opposite-sex bedding increased BrdU labeling in the amygdala (AMY), but not the dentate gyrus (DG), of female, but not male, voles, indicating a sex-, stimulus-, and brain region-specific effect. The removal of the main olfactory bulbs or lesioning of the vomeronasal organ (VNOX) in females reduced BrdU labeling in the AMY and DG, and inhibited the male bedding-induced BrdU labeling in the AMY, revealing the importance of an intact olfactory pathway for amygdaloid neurogenesis. VNOX increased anxiety-like behavior and altered social preference, but it did not affect social recognition memory in female voles. VNOX also reduced the percentage of BrdU-labeled cells that co-expressed the neuronal marker TuJ1 in the AMY, but not the DG. Together, our data indicate the importance of the olfactory pathway in mediating brain plasticity in the limbic system as well as its role in behavior.

  3. Exposition to tannery wastewater did not alter behavioral and biochemical parameters in Wistar rats.

    PubMed

    Moysés, Felipe dos Santos; Bertoldi, Karine; Spindler, Christiano; Sanches, Eduardo Farias; Elsner, Viviane Rostirola; Rodrigues, Marco Antonio Siqueira; Siqueira, Ionara Rodrigues

    2014-04-22

    There are scarce data on the neurotoxicity in mammalian induced by tannery wastewaters. Previously, the anxiogenic effect of tannery wastewater was demonstrated in mice, while wastewater submitted to photoelectrooxidation (PEO) process treatment did not affect the anxiety state. Considering that species may response differently to xenobiotics, the aim of the present work was to study the effects of exposure to tannery wastewaters (non-PEO or PEO-treated) on behavioral and neurochemical markers in another species of laboratory animals, specifically Wistar rats. Male Wistar rats were given free access to water bottles containing non-PEO or PEO-treated tannery wastewaters (0.1, 1 and 5% in drinking water). During the exposure, behavioral tests of anxiety (elevated plus-maze, neophobia, open field and light-dark box), depression (forced swimming) and memory (inhibitory avoidance, novel object and discriminative avoidance) were performed. On the 30th day, brain structures were dissected out to evaluate cellular oxidative state (hippocampus, cerebellum and striatum) and acetylcholinesterase activity (hippocampus and striatum). Exposure to tannery effluent with or without photoelectrochemical treatment did not alter any behavioral and neurochemical parameters evaluated. Our data indicate that Wistar rats may not be an adequate species for ecotoxicological studies involving tannery effluents and that POE treatment did not generate other toxic compounds.

  4. Insulin resistance in brain alters dopamine turnover and causes behavioral disorders

    PubMed Central

    Kleinridders, Andre; Cai, Weikang; Cappellucci, Laura; Ghazarian, Armen; Collins, William R.; Vienberg, Sara G.; Pothos, Emmanuel N.; Kahn, C. Ronald

    2015-01-01

    Diabetes and insulin resistance are associated with altered brain imaging, depression, and increased rates of age-related cognitive impairment. Here we demonstrate that mice with a brain-specific knockout of the insulin receptor (NIRKO mice) exhibit brain mitochondrial dysfunction with reduced mitochondrial oxidative activity, increased levels of reactive oxygen species, and increased levels of lipid and protein oxidation in the striatum and nucleus accumbens. NIRKO mice also exhibit increased levels of monoamine oxidase A and B (MAO A and B) leading to increased dopamine turnover in these areas. Studies in cultured neurons and glia cells indicate that these changes in MAO A and B are a direct consequence of loss of insulin signaling. As a result, NIRKO mice develop age-related anxiety and depressive-like behaviors that can be reversed by treatment with MAO inhibitors, as well as the tricyclic antidepressant imipramine, which inhibits MAO activity and reduces oxidative stress. Thus, insulin resistance in brain induces mitochondrial and dopaminergic dysfunction leading to anxiety and depressive-like behaviors, demonstrating a potential molecular link between central insulin resistance and behavioral disorders. PMID:25733901

  5. D1 and D2 dopamine receptor antagonists decrease behavioral bout duration, without altering the bout's repeated behavioral components, in a naturalistic model of repetitive and compulsive behavior.

    PubMed

    Hoffman, Kurt L; Rueda Morales, Rafael I

    2012-04-21

    Nest building behavior in the pregnant female rabbit (Oryctolagus cuniculus) is a model for compulsive behavior in Obsessive Compulsive Disorder (OCD). This behavior comprises a cycle of repeated, stereotyped components (collecting straw, entering nest box and depositing the straw there, returning to collect more straw), which itself is repeated 80+ times in a single bout that lasts approximately 50min. The bout, in turn, is repeated if necessary, according to the rabbit's perception of whether or not the nest is finished. We administered SCH23390 (5-100μg/kg; D1/D5 antagonist) or raclopride (0.05-1.0mg/kg; D2/D3 antagonist), subcutaneously to day 28 pregnant female rabbits, 30 or 60min before placing straw inside their home cage. At doses that minimally affected ambulatory behavior in open field (5-12.5μg/kg SCH23390, 0.5-1.0mg/kg raclopride), both antagonists dramatically reduced bout duration while not significantly affecting the initiation of straw carrying behavior, the sequential performance of the individual cycle components, maximum cycle frequency, or the total number of bouts performed. These results point to an important role for dopamine neurotransmission for the prolonged expression of a normal, repetitive and compulsive-like behavior. Moreover, the finding that dopamine receptor antagonists decrease the time spent engaged in repetitive behavior (without significantly altering the form of the repetitive behavior itself) suggests a possible explanation for why neuroleptics can be clinically effective for treating OCD. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. Manipulation of Autophagy in Phagocytes Facilitates Staphylococcus aureus Bloodstream Infection.

    PubMed

    O'Keeffe, Kate M; Wilk, Mieszko M; Leech, John M; Murphy, Alison G; Laabei, Maisem; Monk, Ian R; Massey, Ruth C; Lindsay, Jodi A; Foster, Timothy J; Geoghegan, Joan A; McLoughlin, Rachel M

    2015-09-01

    The capacity for intracellular survival within phagocytes is likely a critical factor facilitating the dissemination of Staphylococcus aureus in the host. To date, the majority of work on S. aureus-phagocyte interactions has focused on neutrophils and, to a lesser extent, macrophages, yet we understand little about the role played by dendritic cells (DCs) in the direct killing of this bacterium. Using bone marrow-derived DCs (BMDCs), we demonstrate for the first time that DCs can effectively kill S. aureus but that certain strains of S. aureus have the capacity to evade DC (and macrophage) killing by manipulation of autophagic pathways. Strains with high levels of Agr activity were capable of causing autophagosome accumulation, were not killed by BMDCs, and subsequently escaped from the phagocyte, exerting significant cytotoxic effects. Conversely, strains that exhibited low levels of Agr activity failed to accumulate autophagosomes and were killed by BMDCs. Inhibition of the autophagic pathway by treatment with 3-methyladenine restored the bactericidal effects of BMDCs. Using an in vivo model of systemic infection, we demonstrated that the ability of S. aureus strains to evade phagocytic cell killing and to survive temporarily within phagocytes correlated with persistence in the periphery and that this effect is critically Agr dependent. Taken together, our data suggest that strains of S. aureus exhibiting high levels of Agr activity are capable of blocking autophagic flux, leading to the accumulation of autophagosomes. Within these autophagosomes, the bacteria are protected from phagocytic killing, thus providing an intracellular survival niche within professional phagocytes, which ultimately facilitates dissemination.

  7. Altered behavioral development in Nrf2 knockout mice following early postnatal exposure to valproic acid

    PubMed Central

    Furnari, Melody A.; Saw, Constance Lay-Lay; Kong, Ah-Ng; Wagner, George C

    2015-01-01

    Early exposure to valproic acid results in autism-like neural and behavioral deficits in humans and other animals through oxidative stress-induced neural damage. In the present study, valproic acid was administered to genetically altered mice lacking the Nrf2 (nuclear factor-erythroid 2 related factor 2) gene on postnatal day 14 (P14). Nrf2 is a transcription factor that induces genes that protect against oxidative stress. It was found that valproic acid-treated Nrf2 knockout mice were less active in open field activity chambers, less successful on the rotorod, and had deficits in learning and memory in the Morris water maze compared to the valproic acid-treated wild type mice. Given these results, it appears that Nrf2 knockout mice were more sensitive to the neural damage caused by valproic acid administered during early development. PMID:25454122

  8. Reduction of GABAergic transmission and alterations in behavior after 6-OHDA treatment of rats.

    PubMed

    Podkletnova, I; Raevsky, V; Alho, H

    1996-07-20

    We studied the effects of neonatal administration of 6-hydroxydopamine (6-OHDA) upon gamma-aminobutyric acid (GABA) and noradrenergic neurotransmission in the developing rat brain. After 6-OHDA administration tyrosine hydroxylase (TH) immunolabelling revealed more than 70% loss of catecholaminergic terminals in cortex. Glutamic acid decarboxylase (GAD) immunolabelling showed that the intensity of staining and the density of labelled terminals were decreased by approximately 50% in the prefrontal cortex of 6-OHDA treated animals, but in visual and somatosensory zones there was no difference between lesioned and control cortex. The open field test revealed an altered development of the searching activity after neonatal 6-OHDA injections. A significant difference was found between 6-OHDA treated and control rats in searching, orienting and skills performance. Our results indicate that the behavioral changes observed in young rats after 6-OHDA treatment may be reflections not only of reduced catecholaminergic transmission but also of GABAergic disturbance, occurring in the frontal cortex.

  9. The use of messages in altering risky gambling behavior in college students: an experimental analogue study.

    PubMed

    Jardin, Bianca; Wulfert, Edelgard

    2009-01-01

    This study examined the effects of messages on altering risky gambling behavior in college students. While playing a chance-based computerized game with play money, three groups of participants either viewed occasional accurate messages that correctly described the contingencies of the game, neutral messages unrelated to the contingencies, or no messages. Participants in the accurate message condition spent overall less money gambling, played fewer trials in the final phase of the game when all trials resulted in losses, and were more likely to quit the game while they still had money remaining in the bank. The findings suggest that "reminders" about the random nature of games and the overall negative rate of return might lead to more responsible gaming.

  10. Altered behavioral development in Nrf2 knockout mice following early postnatal exposure to valproic acid.

    PubMed

    Furnari, Melody A; Saw, Constance Lay-Lay; Kong, Ah-Ng; Wagner, George C

    2014-10-01

    Early exposure to valproic acid results in autism-like neural and behavioral deficits in humans and other animals through oxidative stress-induced neural damage. In the present study, valproic acid was administered to genetically altered mice lacking the Nrf2 (nuclear factor-erythroid 2 related factor 2) gene on postnatal day 14 (P14). Nrf2 is a transcription factor that induces genes that protect against oxidative stress. It was found that valproic acid-treated Nrf2 knockout mice were less active in open field activity chambers, less successful on the rotorod, and had deficits in learning and memory in the Morris water maze compared to the valproic acid-treated wild type mice. Given these results, it appears that Nrf2 knockout mice were more sensitive to the neural damage caused by valproic acid administered during early development. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Gastric bypass surgery alters behavioral and neural taste functions for sweet taste in obese rats

    PubMed Central

    Kovacs, Peter; Ahmed, Tamer; Meirelles, Katia; Lynch, Christopher J.; Cooney, Robert N.

    2010-01-01

    Roux-en-Y gastric bypass surgery (GBS) is the most effective treatment for morbid obesity. GBS is a restrictive malabsorptive procedure, but many patients also report altered taste preferences. This study investigated the effects of GBS or a sham operation (SH) on body weight, glucose tolerance, and behavioral and neuronal taste functions in the obese Otsuka Long-Evans Tokushima Fatty (OLETF) rats lacking CCK-1 receptors and lean controls (LETO). OLETF-GBS rats lost body weight (−26%) and demonstrated improved glucose tolerance. They also expressed a reduction in 24-h two-bottle preference for sucrose (0.3 and 1.0 M) and decreased 10-s lick responses for sucrose (0.3 through 1.5 M) compared with OLETF-SH or LETO-GBS. A similar effect was noted for other sweet compounds but not for salty, sour, or bitter tastants. In lean rats, GBS did not alter responses to any stimulus tested. Extracellular recordings from 170 taste-responsive neurons of the pontine parabrachial nucleus revealed a rightward shift in concentration responses to oral sucrose in obese compared with lean rats (OLETF-SH vs. LETO-SH): overall increased response magnitudes (above 0.9 M), and maximum responses occurring at higher concentrations (+0.46 M). These effects were reversed by GBS, and neural responses in OLETF-GBS were statistically not different from those in any LETO groups. These findings confirm obesity-related alterations in taste functions and demonstrate the ability of GBS to alleviate these impairments. Furthermore, the beneficial effects of GBS appear to be independent of CCK-1 receptor signaling. An understanding of the underlying mechanisms for reduced preferences for sweet taste could help in developing less invasive treatments for obesity. PMID:20634436

  12. Loss of Protein Arginine Methyltransferase 8 Alters Synapse Composition and Function, Resulting in Behavioral Defects.

    PubMed

    Penney, Jay; Seo, Jinsoo; Kritskiy, Oleg; Elmsaouri, Sara; Gao, Fan; Pao, Ping-Chieh; Su, Susan C; Tsai, Li-Huei

    2017-09-06

    Diverse molecular mechanisms regulate synaptic composition and function in the mammalian nervous system. The multifunctional protein arginine methyltransferase 8 (PRMT8) possesses both methyltransferase and phospholipase activities. Here we examine the role of this neuron-specific protein in hippocampal plasticity and cognitive function. PRMT8 protein localizes to synaptic sites, and conditional whole-brain Prmt8 deletion results in altered levels of multiple synaptic proteins in the hippocampus, using both male and female mice. Interestingly, these altered protein levels are due to post-transcriptional mechanisms as the corresponding mRNA levels are unaffected. Strikingly, electrophysiological recordings from hippocampal slices of mice lacking PRMT8 reveal multiple defects in excitatory synaptic function and plasticity. Furthermore, behavioral analyses show that PRMT8 conditional knock-out mice exhibit impaired hippocampal-dependent fear learning. Together, these findings establish PRMT8 as an important component of the molecular machinery required for hippocampal neuronal function.SIGNIFICANCE STATEMENT Numerous molecular processes are critically required for normal brain function. Here we use mice lacking protein arginine methyltransferase 8 (PRMT8) in the brain to examine how loss of this protein affects the structure and function of neurons in the hippocampus. We find that PRMT8 localizes to the sites of communication between neurons. Hippocampal neurons from mice lacking PRMT8 have no detectable structural differences compared with controls; however, multiple aspects of their function are altered. Consistently, we find that mice lacking PRMT8 also exhibit reduced hippocampus-dependent memory. Together, our findings establish important roles for PRMT8 in regulating neuron function and cognition in the mammalian brain. Copyright © 2017 the authors 0270-6474/17/378655-12$15.00/0.

  13. Invasive plant architecture alters trophic interactions by changing predator abundance and behavior.

    PubMed

    Pearson, Dean E

    2009-03-01

    As primary producers, plants are known to influence higher trophic interactions by initiating food chains. However, as architects, plants may bypass consumers to directly affect predators with important but underappreciated trophic ramifications. Invasion of western North American grasslands by the perennial forb, spotted knapweed (Centaurea maculosa), has fundamentally altered the architecture of native grassland vegetation. Here, I use long-term monitoring, observational studies, and field experiments to document how changes in vegetation architecture have affected native web spider populations and predation rates. Native spiders that use vegetation as web substrates were collectively 38 times more abundant in C. maculosa-invaded grasslands than in uninvaded grasslands. This increase in spider abundance was accompanied by a large shift in web spider community structure, driven primarily by the strong response of Dictyna spiders to C. maculosa invasion. Dictyna densities were 46-74 times higher in C. maculosa-invaded than native grasslands, a pattern that persisted over 6 years of monitoring. C. maculosa also altered Dictyna web building behavior and foraging success. Dictyna webs on C. maculosa were 2.9-4.0 times larger and generated 2.0-2.3 times higher total prey captures than webs on Achillea millefolium, their primary native substrate. Dictyna webs on C. maculosa also captured 4.2 times more large prey items, which are crucial for reproduction. As a result, Dictyna were nearly twice as likely to reproduce on C. maculosa substrates compared to native substrates. The overall outcome of C. maculosa invasion and its transformative effects on vegetation architecture on Dictyna density and web building behavior were to increase Dictyna predation on invertebrate prey >/=89 fold. These results indicate that invasive plants that change the architecture of native vegetation can substantially impact native food webs via nontraditional plant --> predator --> consumer

  14. Examination of Poststroke Alteration in Motor Unit Firing Behavior Using High-Density Surface EMG Decomposition.

    PubMed

    Li, Xiaoyan; Holobar, Ales; Gazzoni, Marco; Merletti, Roberto; Rymer, William Zev; Zhou, Ping

    2015-05-01

    Recent advances in high-density surface electromyogram (EMG) decomposition have made it a feasible task to discriminate single motor unit activity from surface EMG interference patterns, thus providing a noninvasive approach for examination of motor unit control properties. In the current study, we applied high-density surface EMG recording and decomposition techniques to assess motor unit firing behavior alterations poststroke. Surface EMG signals were collected using a 64-channel 2-D electrode array from the paretic and contralateral first dorsal interosseous (FDI) muscles of nine hemiparetic stroke subjects at different isometric discrete contraction levels between 2 to 10 N with a 2 N increment step. Motor unit firing rates were extracted through decomposition of the high-density surface EMG signals and compared between paretic and contralateral muscles. Across the nine tested subjects, paretic FDI muscles showed decreased motor unit firing rates compared with contralateral muscles at different contraction levels. Regression analysis indicated a linear relation between the mean motor unit firing rate and the muscle contraction level for both paretic and contralateral muscles (p < 0.001), with the former demonstrating a lower increment rate (0.32 pulses per second (pps)/N) compared with the latter (0.67 pps/N). The coefficient of variation (averaged over the contraction levels) of the motor unit firing rates for the paretic muscles (0.21 ± 0.012) was significantly higher than for the contralateral muscles (0.17 ± 0.014) (p < 0.05). This study provides direct evidence of motor unit firing behavior alterations poststroke using surface EMG, which can be an important factor contributing to hemiparetic muscle weakness.

  15. Human papillomavirus causes an angiogenic switch in keratinocytes which is sufficient to alter endothelial cell behavior

    SciTech Connect

    Chen, W.; Li, F.; Mead, L.; White, H.; Walker, J.; Ingram, D.A.; Roman, A.

    2007-10-10

    One of the requirements for tumor growth is the ability to recruit a blood supply, a process known as angiogenesis. Angiogenesis begins early in the progression of cervical disease from mild to severe dysplasia and on to invasive cancer. We have previously reported that expression of human papillomavirus type 16 E6 and E7 (HPV16 E6E7) proteins in primary foreskin keratinocytes (HFKs) decreases expression of two inhibitors and increases expression of two angiogenic inducers [Toussaint-Smith, E., Donner, D.B., Roman, A., 2004. Expression of human papillomavirus type 16 E6 and E7 oncoproteins in primary foreskin keratinocytes is sufficient to alter the expression of angiogenic factors. Oncogene 23, 2988-2995]. Here we report that HPV-induced early changes in the keratinocyte phenotype are sufficient to alter endothelial cell behavior both in vitro and in vivo. Conditioned media from HPV16 E6E7 expressing HFKs as well as from human cervical keratinocytes containing the intact HPV16 were able to stimulate proliferation and migration of human microvascular endothelial cells. In addition, introduction of the conditioned media into immunocompetent mice using a Matrigel plug model resulted in a clear angiogenic response. These novel data support the hypothesis that HPV proteins contribute not only to the uncontrolled keratinocyte growth seen following HPV infection but also to the angiogenic response needed for tumor formation.

  16. Structural Brain Alterations Associated with Rapid Eye Movement Sleep Behavior Disorder in Parkinson’s Disease

    PubMed Central

    Boucetta, Soufiane; Salimi, Ali; Dadar, Mahsa; Jones, Barbara E.; Collins, D. Louis; Dang-Vu, Thien Thanh

    2016-01-01

    Characterized by dream-enactment motor manifestations arising from rapid eye movement (REM) sleep, REM sleep behavior disorder (RBD) is frequently encountered in Parkinson’s disease (PD). Yet the specific neurostructural changes associated with RBD in PD patients remain to be revealed by neuroimaging. Here we identified such neurostructural alterations by comparing large samples of magnetic resonance imaging (MRI) scans in 69 PD patients with probable RBD, 240 patients without RBD and 138 healthy controls, using deformation-based morphometry (p < 0.05 corrected for multiple comparisons). All data were extracted from the Parkinson’s Progression Markers Initiative. PD patients with probable RBD showed smaller volumes than patients without RBD and than healthy controls in the pontomesencephalic tegmentum, medullary reticular formation, hypothalamus, thalamus, putamen, amygdala and anterior cingulate cortex. These results demonstrate that RBD is associated with a prominent loss of volume in the pontomesencephalic tegmentum, where cholinergic, GABAergic and glutamatergic neurons are located and implicated in the promotion of REM sleep and muscle atonia. It is additionally associated with more widespread atrophy in other subcortical and cortical regions whose loss also likely contributes to the altered regulation of sleep-wake states and motor activity underlying RBD in PD patients. PMID:27245317

  17. Early life experience alters behavioral responses to sweet food and accumbal dopamine metabolism.

    PubMed

    Silveira, P P; Portella, A K; Assis, S A C N; Nieto, F B; Diehl, L A; Crema, L M; Peres, W; Costa, G; Scorza, C; Quillfeldt, J A; Lucion, A B; Dalmaz, C

    2010-02-01

    Neonatal handling in rats persistently alters behavioral parameters and responses to stress. Such animals eat more sweet food in adult life, without alterations in lab chow ingestion. Here, we show that neonatally handled rats display greater incentive salience to a sweet reward in a runway test; however they are less prone to conditioned place preference and show less positive hedonic reactions to sweet food. When injected with methylphenidate (a dopamine mimetic agent), non-handled rats increase their sweet food ingestion in the fasted state, while neonatally handled rats do not respond. We did not observe any differences regarding baseline general ambulatory activity between the groups. A lower dopamine metabolism in the nucleus accumbens was observed in handled animals, without differences in norepinephrine content. We suggest that early handling leads to a particular response to positive reinforcers such as palatable food, in a very peculiar fashion of higher ingestion but lower hedonic impact, as well as higher incentive salience, but diminished dopaminergic metabolism in the nucleus accumbens. Copyright 2009 ISDN. Published by Elsevier Ltd. All rights reserved.

  18. Metabolic and feeding behavior alterations provoked by prenatal exposure to aspartame.

    PubMed

    von Poser Toigo, E; Huffell, A P; Mota, C S; Bertolini, D; Pettenuzzo, L F; Dalmaz, C

    2015-04-01

    The use of artificial sweeteners has increased together with the epidemic growth of obesity. In addition to their widespread use in sodas, artificial sweeteners are added to nearly 6000 other products sold in the US, including baby foods, frozen dinners and even yogurts. It has been suggested that the use of nonnutritive sweeteners can lead to body weight gain and an altered metabolic profile. However, very few studies have evaluated the effects of maternal consumption of artificial non-caloric sweeteners on body weight, feeding behavior or the metabolism of offspring in adult life. In this study, we found that animals exposed to aspartame during the prenatal period presented a higher consumption of sweet foods during adulthood and a greater susceptibility to alterations in metabolic parameters, such as increased glucose, LDL and triglycerides. These effects were observed in both males and females, although they were more pronounced in males. Despite the preliminary nature of this study, and the need for further confirmation of these effects, our data suggest that the consumption of sweeteners during gestation may have deleterious long-term effects and should be used with caution. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. GABAergic modulation with classical benzodiazepines prevent stress-induced neuro-immune dysregulation and behavioral alterations

    PubMed Central

    Ramirez, Karol; Niraula, Anzela; Sheridan, John F.

    2015-01-01

    Objective Psychosocial stress is associated with altered immunity, anxiety, and depression. Repeated social defeat (RSD), a model of social stress, triggers egress of inflammatory myeloid progenitor cells (MPCs; CD11b+ /Ly6Chi) that traffic to the brain, promoting anxiety-like behavior. In parallel, RSD enhances neuroinflammatory signaling and long-lasting social avoidant behavior. Lorazepam and clonazepam are routinely prescribed anxiolytics that act by enhancing GABAergic activity in the brain. Besides binding to the central benzodiazepine binding site (CBBS) in the central nervous system (CNS), lorazepam binds to the translocator protein (TSPO) with high affinity causing immunomodulation. Clonazepam targets the CBBS and has low affinity for the TSPO. Here the aims were to determine if lorazepam and clonazepam would: 1) prevent stress-induced peripheral and central inflammatory responses, and 2) block anxiety and social avoidance behavior in mice subjected to RSD. Methods C57/BL6 mice were divided into experimental groups, and treated with either lorazepam (0.10mg/kg), clonazepam (0.25 mg/kg) or vehicle (0.9%NaCl). Behavioral data and tissues were collected the morning after the last cycle of RSD. Results Lorazepam and clonazepam were effective in attenuating mRNA expression of CRH in the hypothalamus and corticosterone in plasma in mice subjected to RSD. Both drugs blocked stress-induced levels of IL-6 in plasma. Lorazepam and clonazepam had different effects on stress-induced enhancement of myelopoiesis and inhibited trafficking of monocytes and granulocytes in circulation. Furthermore, lorazepam, but not clonazepam, inhibited splenomegaly and the production of pro-inflammatory cytokines in the spleen following RSD. Additionally, lorazepam and clonazepam, blocked stress-induced accumulation of macrophages (CD11b+/CD45high) in the CNS. In a similar manner, both lorazepam and clonazepam prevented neuroinflammatory signaling and reversed anxiety-like and

  20. GABAergic modulation with classical benzodiazepines prevent stress-induced neuro-immune dysregulation and behavioral alterations.

    PubMed

    Ramirez, Karol; Niraula, Anzela; Sheridan, John F

    2016-01-01

    Psychosocial stress is associated with altered immunity, anxiety, and depression. Repeated social defeat (RSD), a model of social stress, triggers egress of inflammatory myeloid progenitor cells (MPCs; CD11b(+)/Ly6C(hi)) that traffic to the brain, promoting anxiety-like behavior. In parallel, RSD enhances neuroinflammatory signaling and long-lasting social avoidant behavior. Lorazepam and clonazepam are routinely prescribed anxiolytics that act by enhancing GABAergic activity in the brain. Besides binding to the central benzodiazepine binding site (CBBS) in the central nervous system (CNS), lorazepam binds to the translocator protein (TSPO) with high affinity causing immunomodulation. Clonazepam targets the CBBS and has low affinity for the TSPO. Here the aims were to determine if lorazepam and clonazepam would: (1) prevent stress-induced peripheral and central inflammatory responses, and (2) block anxiety and social avoidance behavior in mice subjected to RSD. C57/BL6 mice were divided into experimental groups, and treated with either lorazepam (0.10mg/kg), clonazepam (0.25mg/kg) or vehicle (0.9% NaCl). Behavioral data and tissues were collected the morning after the last cycle of RSD. Lorazepam and clonazepam were effective in attenuating mRNA expression of CRH in the hypothalamus and corticosterone in plasma in mice subjected to RSD. Both drugs blocked stress-induced levels of IL-6 in plasma. Lorazepam and clonazepam had different effects on stress-induced enhancement of myelopoiesis and inhibited trafficking of monocytes and granulocytes in circulation. Furthermore, lorazepam, but not clonazepam, inhibited splenomegaly and the production of pro-inflammatory cytokines in the spleen following RSD. Additionally, lorazepam and clonazepam, blocked stress-induced accumulation of macrophages (CD11b(+)/CD45(high)) in the CNS. In a similar manner, both lorazepam and clonazepam prevented neuroinflammatory signaling and reversed anxiety-like and depressive-like behavior

  1. High-fat diet feeding alters olfactory-, social-, and reward-related behaviors of mice independent of obesity.

    PubMed

    Takase, Kenkichi; Tsuneoka, Yousuke; Oda, Satoko; Kuroda, Masaru; Funato, Hiromasa

    2016-04-01

    High-fat diet (HFD) consumption causes obesity, which is associated with well-known increased health risks. Moreover, obesity has been associated with altered sensorimotor and emotional behaviors of humans and mice. This study attempted to dissociate the influence of HFD-induced obesity on behaviors from the influence of HFD consumption itself. C57BL male mice were randomly allocated to a low-fat diet (LFD) group, an HFD-induced obesity (DIO) group, or a pair-fed HFD-feeding nonobese (HFD) group. A comprehensive behavioral test battery was performed on all three groups to assess sensorimotor functions, anxiety- and depression-like behaviors, reward-related behaviors, social behaviors, and learning/memory functions. Both the DIO and HFD groups exhibited disturbed olfaction, blunted ethanol preference, and enhanced social interactions. The DIO group exhibited blunted sucrose preference, shorter latency before falling off during the rotarod test, and a lower response to mechanical stimuli. The HFD-fed nonobese mice showed altered behaviors related to olfaction, social interactions, and rewards that were similar to those of the DIO mice. This finding suggests that HFD consumption alters a variety of behaviors independent of obesity. © 2016 The Obesity Society.

  2. Altered functional Connectivity in Lesional Peduncular Hallucinosis with REM Sleep Behavior Disorder

    PubMed Central

    Geddes, Maiya R.; Tie, Yanmei; Gabrieli, John D. E.; McGinnis, Scott M.; Golby, Alexandra J.; Whitfield-Gabrieli, Susan

    2016-01-01

    Brainstem lesions causing peduncular hallucinosis (PH) produce vivid visual hallucinations occasionally accompanied by sleep disorders. Overlapping brainstem regions modulate visual pathways and REM sleep functions via gating of thalamocortical networks. A 66-year-old man with paroxysmal atrial fibrillation developed abrupt-onset complex visual hallucinations with preserved insight and violent dream enactment behavior. Brain MRI showed restricted diffusion in the left rostrodorsal pons suggestive of an acute ischemic infarct. REM sleep behavior disorder (RBD) was diagnosed on polysomnography. We investigated the integrity of ponto-geniculate-occipital circuits with seed-based resting-state functional connectivity MRI (rs-fcMRI) in this patient compared to 46 controls. Rs-fcMRI revealed significantly reduced functional connectivity between the lesion and lateral geniculate nuclei (LGN), and between LGN and visual association cortex compared to controls. Conversely, functional connectivity between brainstem and visual association cortex, and between visual association cortex and PFC was significantly increased in the patient. Focal damage to the left rostrodorsal pons is sufficient to cause RBD and PH in humans, suggesting an overlapping mechanism in both syndromes. This lesion produced a pattern of altered functional connectivity consistent with disrupted visual cortex connectivity via de-afferentation of thalamocortical pathways. PMID:26656284

  3. Locomotor training alters the behavior of flexor reflexes during walking in human spinal cord injury.

    PubMed

    Smith, Andrew C; Mummidisetty, Chaithanya K; Rymer, William Zev; Knikou, Maria

    2014-11-01

    In humans, a chronic spinal cord injury (SCI) impairs the excitability of pathways mediating early flexor reflexes and increases the excitability of late, long-lasting flexor reflexes. We hypothesized that in individuals with SCI, locomotor training will alter the behavior of these spinally mediated reflexes. Nine individuals who had either chronic clinically motor complete or incomplete SCI received an average of 44 locomotor training sessions. Flexor reflexes, elicited via sural nerve stimulation of the right or left leg, were recorded from the ipsilateral tibialis anterior (TA) muscle before and after body weight support (BWS)-assisted treadmill training. The modulation pattern of the ipsilateral TA responses following innocuous stimulation of the right foot was also recorded in 10 healthy subjects while they stepped at 25% BWS to investigate whether body unloading during walking affects the behavior of these responses. Healthy subjects did not receive treadmill training. We observed a phase-dependent modulation of early TA flexor reflexes in healthy subjects with reduced body weight during walking. The early TA flexor reflexes were increased at heel contact, progressively decreased during the stance phase, and then increased throughout the swing phase. In individuals with SCI, locomotor training induced the reappearance of early TA flexor reflexes and changed the amplitude of late TA flexor reflexes during walking. Both early and late TA flexor reflexes were modulated in a phase-dependent pattern after training. These new findings support the adaptive capability of the injured nervous system to return to a prelesion excitability and integration state.

  4. Can a tablet device alter undergraduate science students' study behavior and use of technology?

    PubMed

    Morris, Neil P; Ramsay, Luke; Chauhan, Vikesh

    2012-06-01

    This article reports findings from a study investigating undergraduate biological sciences students' use of technology and computer devices for learning and the effect of providing students with a tablet device. A controlled study was conducted to collect quantitative and qualitative data on the impact of a tablet device on students' use of devices and technology for learning. Overall, we found that students made extensive use of the tablet device for learning, using it in preference to laptop computers to retrieve information, record lectures, and access learning resources. In line with other studies, we found that undergraduate students only use familiar Web 2.0 technologies and that the tablet device did not alter this behavior for the majority of tools. We conclude that undergraduate science students can make extensive use of a tablet device to enhance their learning opportunities without institutions changing their teaching methods or computer systems, but that institutional intervention may be needed to drive changes in student behavior toward the use of novel Web 2.0 technologies.

  5. HPA axis dysregulation and behavioral analysis of mouse mutants with altered GR or MR function

    PubMed Central

    Kolber, Benedict J.; Wieczorek, Lindsay; Muglia, Louis J.

    2009-01-01

    Corticosteroid receptors are critical for the maintenance of homeostasis after both psychological and physiological stress. To properly understand the different roles and interactions of the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) during stress, it is necessary to dissect the role of corticosteroid signaling at both the system and sub-system level. A variety of GR transgenic mouse lines have recently been used to characterize the role of GR in the CNS as a whole and particularly in the forebrain. We will describe both the behavioral and cellular/molecular implications of disrupting GR function in these animal models and describe the implications of this data for our understanding of normal endocrine function and stress adaptation. MRs in tight epithelia have a long established role in sodium homeostasis. Recently however, evidence has suggested that limbic MRs also play an important role in psychological stress. Just as with GR, targeted mutations in MR induce a variety of behavioral changes associated with stress adaptation. In this review, we will discuss the implications of this work on MR. Finally, we will discuss the possible interaction between MR and GR and how future work using double mutants (through conventional means or virus based gene alteration) will be needed to fully understand how signaling through these two steroid receptors provides the adaptive mechanisms to deal with a variety of stressors. PMID:18609295

  6. Dynamical and phase behavior of a phospholipid membrane altered by an antimicrobial peptide at low concentration

    DOE PAGES

    Mamontov, Eugene; Tyagi, M.; Qian, Shuo; ...

    2016-05-27

    Here we discuss that the mechanism of action of antimicrobial peptides is traditionally attributed to the formation of pores in the lipid cell membranes of pathogens, which requires a substantial peptide to lipid ratio. However, using incoherent neutron scattering, we show that even at a concentration too low for pore formation, an archetypal antimicrobial peptide, melittin, disrupts the regular phase behavior of the microscopic dynamics in a phospholipid membrane, dimyristoylphosphatidylcholine (DMPC). At the same time, another antimicrobial peptide, alamethicin, does not exert a similar effect on the DMPC microscopic dynamics. The melittin-altered lateral motion of DMPC at physiological temperature nomore » longer resembles the fluid-phase behavior characteristic of functional membranes of the living cells. The disruptive effect demonstrated by melittin even at low concentrations reveals a new mechanism of antimicrobial action relevant in more realistic scenarios, when peptide concentration is not as high as would be required for pore formation, which may facilitate treatment with antimicrobial peptides.« less

  7. Adolescent binge ethanol treatment alters adult brain regional volumes, cortical extracellular matrix protein and behavioral flexibility.

    PubMed

    Coleman, Leon Garland; Liu, Wen; Oguz, Ipek; Styner, Martin; Crews, Fulton T

    2014-01-01

    Adolescents binge drink more than any other age group, increasing risk of disrupting the development of the frontal cortex. We hypothesized that adolescent binge drinking would lead to persistent alterations in adulthood. In this study, we modeled adolescent weekend underage binge-drinking, using adolescent mice (post-natal days [P] 28-37). The adolescent intermittent binge ethanol (AIE) treatment includes 6 binge intragastric doses of ethanol in an intermittent pattern across adolescence. Assessments were conducted in adulthood following extended abstinence to determine if there were persistent changes in adults. Reversal learning, open field and other behavioral assessments as well as brain structure using magnetic imaging and immunohistochemistry were determined. We found that AIE did not impact adult Barnes Maze learning. However, AIE did cause reversal learning deficits in adults. AIE also caused structural changes in the adult brain. AIE was associated with adulthood volume enlargements in specific brain regions without changes in total brain volume. Enlarged regions included the orbitofrontal cortex (OFC, 4%), cerebellum (4.5%), thalamus (2%), internal capsule (10%) and genu of the corpus callosum (7%). The enlarged OFC volume in adults after AIE is consistent with previous imaging studies in human adolescents. AIE treatment was associated with significant increases in the expression of several extracellular matrix (ECM) proteins in the adult OFC including WFA (55%), Brevican (32%), Neurocan (105%), Tenacin-C (25%), and HABP (5%). These findings are consistent with AIE causing persistent changes in brain structure that could contribute to a lack of behavioral flexibility.

  8. Adolescent binge ethanol treatment alters adult brain regional volumes, cortical extracellular matrix protein and behavioral flexibility

    PubMed Central

    Coleman, Leon Garland; Liu, Wen; Oguz, Ipek; Styner, Martin; Crews, Fulton T.

    2014-01-01

    Adolescents binge drink more than any other age group, increasing risk of disrupting the development of the frontal cortex. We hypothesized that adolescent binge drinking would lead to persistent alterations in adulthood. In this study, we modeled adolescent weekend underage binge-drinking, using adolescent mice (post-natal days [P] 28–37). The adolescent intermittent binge ethanol (AIE) treatment includes 6 binge intragastric doses of ethanol in an intermittent pattern across adolescence. Assessments were conducted in adulthood following extended abstinence to determine if there were persistent changes in adults. Reversal learning, open field and other behavioral assessments as well as brain structure using magnetic imaging and immunohistochemistry were determined. We found AIE did not impact adult Barnes Maze learning. However, AIE did cause reversal learning deficits in adults. AIE also caused structural changes in the adult brain. AIE was associated with adulthood volume enlargements in specific brain regions without changes in total brain volume. Enlarged regions included the orbitofrontal cortex (OFC, 4%), cerebellum (4.5%), thalamus (2%), internal capsule (10%) and genu of the corpus callosum (7%). The enlarged OFC volume in adults after AIE is consistent with previous imaging studies in human adolescents. AIE treatment was associated with significant increases in the expression of several extracellular matrix (ECM) proteins in the adult OFC including WFA (55%), Brevican (32%), Neurocan (105%), Tenacin-C (25%), and HABP (5%). These findings are consistent with AIE causing persistent changes in brain structure that could contribute to a lack of behavioral flexibility. PMID:24275185

  9. 3. Impact of altered gravity on CNS development and behavior in male and female rats

    NASA Astrophysics Data System (ADS)

    Sajdel-Sulkowska, E. M.; Nguon, K.; Ladd, B.; Sulkowski, V. A.; Sulkowski, Z. L.; Baxter, M. G.

    The present study examined the effect of altered gravity on CNS development. Specifically, we compared neurodevelopment, behavior, cerebellar structure and protein expression in rat neonates exposed perinatally to hypergravity. Pregnant Sprague-Dawley rats were exposed to 1.5G-1.75G hypergravity on a 24-ft centrifuge starting on gestational day (G) 10, through giving birth on G22/G23, and nursing their offspring through postnatal day (P) 21. Cerebellar mass on P6 was decreased in 1.75G-exposed male pups by 27.5 percent; in 1.75G-exposed female pups it was decreased by 22.5 percent. The observed cerebellar changes were associated with alterations in neurodevelopment and motor behavior. Exposure to hypergravity impaired performance on the following neurocognitive tests: (1) righting time on P3 was more than doubled in 1.75G-exposed rats and the effect appeared more pronounced in female pups, (2) startle response on P10 was delayed in both male and female HG pups; HG pups were one-fifth as likely to respond to a clapping noise as SC pups, and (3) performance on a rotorod on P21 was decreased in HG pups; the duration of the stay on rotorod recorded for HG pups of both sexes was one tenth of the SC pups. Furthermore, Western blot analysis of selected cerebellar proteins suggested gender-specific changes in glial and neuronal proteins. On P6, GFAP expression was decreased by 59.2 percent in HG males, while no significant decrease was observed in female cerebella. Synaptophysin expression was decreased in HG male neonates by 29.9 percent and in HG female neonates by 20.7 percent as compared to its expression in SC cerebella. The results of this experiment suggest that perinatal exposure to hypergravity affects cerebellar development and behavior differently in male and female neonates. If one accepts that hypergravity is a good paradigm to study the effect of microgravity on the CNS, and since males and females were shown to respond differently to hypergravity, it can be

  10. Dynamic microglial alterations underlie stress-induced depressive-like behavior and suppressed neurogenesis.

    PubMed

    Kreisel, T; Frank, M G; Licht, T; Reshef, R; Ben-Menachem-Zidon, O; Baratta, M V; Maier, S F; Yirmiya, R

    2014-06-01

    The limited success in understanding the pathophysiology of major depression may result from excessive focus on the dysfunctioning of neurons, as compared with other types of brain cells. Therefore, we examined the role of dynamic alterations in microglia activation status in the development of chronic unpredictable stress (CUS)-induced depressive-like condition in rodents. We report that following an initial period (2-3 days) of stress-induced microglial proliferation and activation, some microglia underwent apoptosis, leading to reductions in their numbers within the hippocampus, but not in other brain regions, following 5 weeks of CUS exposure. At that time, microglia displayed reduced expression of activation markers as well as dystrophic morphology. Blockade of the initial stress-induced microglial activation by minocycline or by transgenic interleukin-1 receptor antagonist overexpression rescued the subsequent microglial apoptosis and decline, as well as the CUS-induced depressive-like behavior and suppressed neurogenesis. Similarly, the antidepressant drug imipramine blocked the initial stress-induced microglial activation as well as the CUS-induced microglial decline and depressive-like behavior. Treatment of CUS-exposed mice with either endotoxin, macrophage colony-stimulating factor or granulocyte-macrophage colony-stimulating factor, all of which stimulated hippocampal microglial proliferation, partially or completely reversed the depressive-like behavior and dramatically increased hippocampal neurogenesis, whereas treatment with imipramine or minocycline had minimal or no anti-depressive effects, respectively, in these mice. These findings provide direct causal evidence that disturbances in microglial functioning has an etiological role in chronic stress-induced depression, suggesting that microglia stimulators could serve as fast-acting anti-depressants in some forms of depressive and stress-related conditions.

  11. Venlafaxine reverses chronic fatigue-induced behavioral, biochemical and neurochemical alterations in mice.

    PubMed

    Dhir, Ashish; Kulkarni, S K

    2008-06-01

    A state of chronic fatigue was produced in mice by subjecting them to forced swim inside a rectangular jar of specific dimensions everyday for a 6 min session for 15 days. Immobility period was recorded on alternate days. The effect of venlafaxine, a dual reuptake inhibitor of serotonin and norepinephrine was evaluated in this murine model of chronic fatigue. Venlafaxine was administered daily and on the days of testing, it was injected 30 min before forced swim session. On the 16th day i.e. 24 h after the last dose of venlafaxine, various behavioral, biochemical and neurotransmitter estimations in the brain were carried out. There was a significant increase in immobility period in vehicle treated mice on successive days, the maximum immobility score reaching on the 7th day and sustained till 15th day. Behavioral parameters revealed hyperlocomotion, anxiety response, muscle incoordination, hyperalgesia and memory deficit. Biochemical analysis showed a significant increase in lipid peroxidation, nitrite and myeloperoxidase levels and a decrease in the reduced glutathione (GSH) levels in brain homogenates. Further, there was a decrease in adrenal ascorbic acid following chronic forced swim. The neurotransmitter estimations in the brain samples revealed a decrease in norepinephrine, serotonin and dopamine levels on chronic exposure to forced swim for 15 days. Daily treatment with venlafaxine (8 and 16 mg/kg, i.p.) for 15 days produced a significant reduction in immobility period and reversed various behavioral, biochemical and neurotransmitter alterations induced by chronic fatigue. Venlafaxine could be of therapeutic potential in the treatment of chronic fatigue.

  12. Environmental prenatal stress eliminates brain and maternal behavioral sex differences and alters hormone levels in female rats.

    PubMed

    Del Cerro, M C R; Ortega, E; Gómez, F; Segovia, S; Pérez-Laso, C

    2015-07-01

    Environmental prenatal stress (EPS) has effects on fetuses that are long-lasting, altering their hormone levels, brain morphology and behavior when they reach maturity. In previous research, we demonstrated that EPS affects the expression of induced maternal behavior (MB), the neuroendocrine system, and morphology of the sexually dimorphic accessory olfactory bulb (AOB) involved in reproductive behavior patterns. The bed nucleus of the accessory olfactory tract (BAOT) is another vomeronasal (VN) structure that plays an inhibitory role in rats in the expression of induced maternal behavior in female and male virgins. In the present study, we have ascertained whether the behavioral, neuroendocrine, and neuromorphological alterations of the AOB found after EPS also appear in the BAOT. After applying EPS to pregnant rats during the late gestational period, in their female offspring at maturity we tested induced maternal behavior, BAOT morphology and plasma levels of testosterone (T), estradiol (E2), progesterone (P), adrenocorticotropic hormone (ACTH) and corticosterone (Cpd B). EPS: a) affected the induction of MB, showed a male-like pattern of care for pups, b) elevated plasma levels of Cpd B and reduced E2 in comparison with the controls, and c) significantly increased the number of BAOT neurons compared to the control females and comparable to the control male group. These findings provide further evidence that stress applied to pregnant rats produces long-lasting behavioral, endocrine and neuroanatomical alterations in the female offspring that are evident when they become mature. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Functional significance of mononuclear phagocyte populations generated through adult hematopoiesis

    PubMed Central

    Gutknecht, Michael F.; Bouton, Amy H.

    2014-01-01

    Tissue homeostasis requires a complete repertoire of functional macrophages in peripheral tissues. Recent evidence indicates that many resident tissue macrophages are seeded during embryonic development and persist through adulthood as a consequence of localized proliferation. Mononuclear phagocytes are also produced during adult hematopoiesis; these cells are then recruited to sites throughout the body, where they function in tissue repair and remodeling, resolution of inflammation, maintenance of homeostasis, and disease progression. The focus of this review is on mononuclear phagocytes that comprise the nonresident monocyte/macrophage populations in the body. Key features of monocyte differentiation are presented, focusing primarily on the developmental hierarchy that is established through this process, the markers used to identify discrete cell populations, and novel, functional attributes of these cells. These features are then explored in the context of the tumor microenvironment, where mononuclear phagocytes exhibit extensive plasticity in phenotype and function. PMID:25225678

  14. Nanoparticles of barium induce apoptosis in human phagocytes

    PubMed Central

    Mores, Luana; França, Eduardo Luzia; Silva, Núbia Andrade; Suchara, Eliane Aparecida; Honorio-França, Adenilda Cristina

    2015-01-01

    Purpose Nutrients and immunological factors of breast milk are essential for newborn growth and the development of their immune system, but this secretion can contain organic and inorganic toxins such as barium. Colostrum contamination with barium is an important issue to investigate because this naturally occurring element is also associated with human activity and industrial pollution. The study evaluated the administration of barium nanoparticles to colostrum, assessing the viability and functional activity of colostral mononuclear phagocytes. Methods Colostrum was collected from 24 clinically healthy women (aged 18–35 years). Cell viability, superoxide release, intracellular Ca2+ release, and phagocyte apoptosis were analyzed in the samples. Results Treatment with barium lowered mononuclear phagocyte viability, increased superoxide release, and reduced intracellular calcium release. In addition, barium increased cell death by apoptosis. Conclusion These data suggest that nanoparticles of barium in colostrum are toxic to cells, showing the importance of avoiding exposure to this element. PMID:26451108

  15. The Role of Phagocytes and NETs in Dermatophytosis.

    PubMed

    Yoshikawa, Fábio Seiti Yamada; De Almeida, Sandro Rogério

    2017-02-01

    Innate immunity is the host first line of defense against pathogens. However, only in recent years, we are beginning to better understand the ways it operates. A key player is this branch of the immune response that are the phagocytes, as macrophages, dendritic cells and neutrophils. These cells act as sentinels, employing specialized receptors in the sensing of invaders and host injury, and readily responding to them by production of inflammatory mediators. They afford protection not only by ingesting and destroying pathogens, but also by providing a suitable biochemical environment that shapes the adaptive response. In this review, we aim to present a broad perspective about the role of phagocytes in dermatophytosis, focusing on the mechanisms possibly involved in protective and non-protective responses. A full understanding of how phagocytes fit in the pathogenesis of these infections may open the venue for the development of new and more effective therapeutic approaches.

  16. Phagocytic cells metabolize 25-hydroxyvitamin D3 in vitro.

    PubMed Central

    Cohen, M S; Gray, T K

    1984-01-01

    Phagocytic cells are widely distributed in tissues known to be important in the metabolism of vitamin D. Incubation of human polymorphonuclear leukocytes and monocytes and resident rat peritoneal macrophages with 3H-labeled 25-hydroxyvitamin D3 leads to the formation of three radioactive peaks. Peak I is most consistent with a lactone derivative of 25-hydroxyvitamin D3, and peak II has been identified as putative 24,25-dihydroxyvitamin D3. Peak III is a novel metabolite of 25-hydroxyvitamin D3 unlike any of the synthetic standards available in our laboratories. Human neutrophils converted more substrate than did the other phagocytes examined. The stimulation of neutrophils by opsonized zymosan or phorbol myristate acetate led to a 4-fold increase in synthesis of the metabolites. These results suggest that vitamin D metabolism by phagocytic cells may play a role in the microenvironmental events that surround bony metabolism and calcium homeostasis. PMID:6322179

  17. Comparison of fluorescence-based methods to determine nanoparticle uptake by phagocytes and non-phagocytic cells in vitro.

    PubMed

    Claudia, Meindl; Kristin, Öhlinger; Jennifer, Ober; Eva, Roblegg; Eleonore, Fröhlich

    2017-03-01

    At many portals of entry the relative uptake by phagocytes and non-phagocytic cells has a prominent effect on availability and biological action of nanoparticles (NPs). Cellular uptake can be determined for fluorescence-labeled NPs. The present study compares three methods (plate reader, flow cytometry and image analysis) in order to investigate the influence of particle size and functionalization and medium content on cellular uptake of fluorescence-labeled polystyrene particles and to study the respective method́s suitability for uptake studies. For comparison between the techniques, ratios of macrophage to alveolar epithelial cell uptakes were used. Presence of serum protein in the exposure solution decreased uptake of carboxyl-functionalized and non-functionalized particles; there was no clear effect for the amine-functionalized particles. The 200nm non- or carboxyl-functionalized NPs were taken up preferentially by phagocytes while for amine-functionalized particles preference was lowest. The presence of the serum slightly increased the preference for these particles. In conclusion, due to the possibility of calibration, plate reader measurements might present a better option than the other techniques to (semi)quantify differences between phagocytes and non-phagocytic cells for particles with different fluorescence. In order to obtain unbiased data the fluorescent labeling has to fulfill certain requirements.

  18. Comparison of fluorescence-based methods to determine nanoparticle uptake by phagocytes and non-phagocytic cells in vitro

    PubMed Central

    Claudia, Meindl; Kristin, Öhlinger; Jennifer, Ober; Eva, Roblegg; Eleonore, Fröhlich

    2017-01-01

    At many portals of entry the relative uptake by phagocytes and non-phagocytic cells has a prominent effect on availability and biological action of nanoparticles (NPs). Cellular uptake can be determined for fluorescence-labeled NPs. The present study compares three methods (plate reader, flow cytometry and image analysis) in order to investigate the influence of particle size and functionalization and medium content on cellular uptake of fluorescence–labeled polystyrene particles and to study the respective method’s suitability for uptake studies. For comparison between the techniques, ratios of macrophage to alveolar epithelial cell uptakes were used. Presence of serum protein in the exposure solution decreased uptake of carboxyl-functionalized and non-functionalized particles; there was no clear effect for the amine-functionalized particles. The 200 nm non- or carboxyl-functionalized NPs were taken up preferentially by phagocytes while for amine-functionalized particles preference was lowest. The presence of the serum slightly increased the preference for these particles. In conclusion, due to the possibility of calibration, plate reader measurements might present a better option than the other techniques to (semi)quantify differences between phagocytes and non-phagocytic cells for particles with different fluorescence. In order to obtain unbiased data the fluorescent labeling has to fulfill certain requirements. PMID:28065592

  19. Haemopoietic phagocytes in the early differentiating avian retina.

    PubMed Central

    Cuadros, M A; García-Martín, M; Martin, C; Ríos, A

    1991-01-01

    The existence of specialised phagocytic cells is described in regions of the retinal neuroepithelium undergoing intense cell death during early differentiation of the avian embryo retina (2.5-5 days of incubation). These results were obtained using routine techniques for light microscopy, acid phosphatase histochemistry and immunocytochemical staining with antibodies MB-1 and QH-1, both specific for quail endothelial cells and all blood cells except mature erythrocytes. Specialised phagocytes were distinguishable from neuroepithelial cells on the basis of morphological criteria: in the former, the nucleus was not oval in shape and was not oriented perpendicular to basement membrane neuroepithelium. The cytoplasm of the specialised phagocytes was often filled with dead cell fragments. In contrast to neuroepithelial cells, the specialised phagocytes showed acid phosphatase activity and were labelled with both MB-1 and QH-1 antibodies in normal quail embryos and chick----quail yolk sac chimeras. Moreover, some acid phosphatase positive and MB-1/QH-1 positive cells also appeared in the presumptive vitreous body, at the edges of the optic cup and in the surrounding mesenchyme. As the vitreal cells and the specialised phagocytes of the neural retina were immunolabelled in chick----quail yolk sac chimeras, we conclude that they are derived from haemopoietic cells in the yolk sac. Some images suggest that these cells enter the vitreous body from the surrounding mesenchyme and traverse the basement membrane of the neuroepithelium in the optic disc region to give rise to the specialised phagocytes of the retinal neuroepithelium. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 Fig. 15 Fig. 16 Fig. 17 Fig. 18 Fig. 19 Fig. 20 PMID:1769889

  20. Cannabinoids prevent the development of behavioral and endocrine alterations in a rat model of intense stress.

    PubMed

    Ganon-Elazar, Eti; Akirav, Irit

    2012-01-01

    Cannabinoids have recently emerged as a possible treatment of stress- and anxiety-related disorders such as post-traumatic stress disorder (PTSD). Here, we examined whether cannabinoid receptor activation could prevent the effects of traumatic stress on the development of behavioral and neuroendocrine measures in a rat model of PTSD, the single-prolonged stress (SPS) model. Rats were injected with the CB1/CB2 receptor agonist WIN55,212-2 (WIN) systemically or into the basolateral amygdala (BLA) at different time points following SPS exposure and were tested 1 week later for inhibitory avoidance (IA) conditioning and extinction, acoustic startle response (ASR), hypothalamic-pituitary-adrenal (HPA) axis function, and anxiety levels. Exposure to SPS enhanced conditioned avoidance and impaired extinction while enhancing ASR, negative feedback on the HPA axis, and anxiety. WIN (0.5 mg/kg) administered intraperitoneally 2 or 24 h (but not 48 h) after SPS prevented the trauma-induced alterations in IA conditioning and extinction, ASR potentiation, and HPA axis inhibition. WIN microinjected into the BLA (5 μg/side) prevented SPS-induced alterations in IA and ASR. These effects were blocked by intra-BLA co-administration of the CB1 receptor antagonist AM251 (0.3 ng/side), suggesting the involvement of CB1 receptors. These findings suggest that (i) there may be an optimal time window for intervention treatment with cannabinoids after exposure to a highly stressful event, (ii) some of the preventive effects induced by WIN are mediated by an activation of CB1 receptors in the BLA, and (iii) cannabinoids could serve as a pharmacological treatment of stress- and trauma-related disorders.

  1. Cannabinoids Prevent the Development of Behavioral and Endocrine Alterations in a Rat Model of Intense Stress

    PubMed Central

    Ganon-Elazar, Eti; Akirav, Irit

    2012-01-01

    Cannabinoids have recently emerged as a possible treatment of stress- and anxiety-related disorders such as post-traumatic stress disorder (PTSD). Here, we examined whether cannabinoid receptor activation could prevent the effects of traumatic stress on the development of behavioral and neuroendocrine measures in a rat model of PTSD, the single-prolonged stress (SPS) model. Rats were injected with the CB1/CB2 receptor agonist WIN55,212-2 (WIN) systemically or into the basolateral amygdala (BLA) at different time points following SPS exposure and were tested 1 week later for inhibitory avoidance (IA) conditioning and extinction, acoustic startle response (ASR), hypothalamic-pituitary-adrenal (HPA) axis function, and anxiety levels. Exposure to SPS enhanced conditioned avoidance and impaired extinction while enhancing ASR, negative feedback on the HPA axis, and anxiety. WIN (0.5 mg/kg) administered intraperitoneally 2 or 24 h (but not 48 h) after SPS prevented the trauma-induced alterations in IA conditioning and extinction, ASR potentiation, and HPA axis inhibition. WIN microinjected into the BLA (5 μg/side) prevented SPS-induced alterations in IA and ASR. These effects were blocked by intra-BLA co-administration of the CB1 receptor antagonist AM251 (0.3 ng/side), suggesting the involvement of CB1 receptors. These findings suggest that (i) there may be an optimal time window for intervention treatment with cannabinoids after exposure to a highly stressful event, (ii) some of the preventive effects induced by WIN are mediated by an activation of CB1 receptors in the BLA, and (iii) cannabinoids could serve as a pharmacological treatment of stress- and trauma-related disorders. PMID:21918506

  2. Altered hippocampal function before emotional trauma in rats susceptible to PTSD-like behaviors.

    PubMed

    Nalloor, Rebecca; Bunting, Kristopher M; Vazdarjanova, Almira

    2014-07-01

    Posttraumatic stress disorder (PTSD) is an anxiety disorder that occurs after experiencing a traumatic event. Susceptibility to PTSD exists, as only some trauma-exposed individuals develop this condition. Investigating susceptibilities in animal models can contribute to understanding the etiology of the disorder. We previously reported an animal model which allows reliable pre-classification of rats as susceptible (Sus) or resistant (Res) to developing a PTSD-like phenotype after a later trauma. Here we report that Sus, compared to Res, rats have altered hippocampal function, along the septo-temporal axis, prior to experiencing a traumatic event. In Experiment I, Res and Sus rats explored a novel box twice. Using a cellular imaging method for assessing plasticity-related immediate-early gene expression in large neuronal ensembles, Arc/Homer1a catFISH, we show that Sus rats have smaller vCA3 ensembles during the second exploration. This suppressed vCA3 activation in Sus rats was not due to a difference in exploratory behavior, or to a difference in Arc/Homer1a expression in the basolateral amygdala (BLA). BLA is a main source of inputs to vCA3, but both the ensemble size and overlap of BLA ensembles activated during the two explorations was similar to that of Res rats. Additionally, Sus rats had significant 'infidelity' in their dorsal hippocampal representations of the second event: a lower overlap, compared to Res rats, of Arc/Homer1a-expressing ensembles activated during the two explorations (the size of the ensembles were similar to those of Res rats). These differences were revealed only in conditions of relatively low stress, because they were not observed when Sus and Res rats experienced fear conditioning (Experiment II). Combined, the findings show that altered hippocampal function exists before experiencing emotional trauma in susceptible rats and suggest that this is a risk factor for PTSD.

  3. Autism-related Neuroligin-3 Mutation Alters Social Behavior and Spatial Learning

    PubMed Central

    Jaramillo, Thomas C.; Liu, Shunan; Pettersen, Ami; Birnbaum, Shari G; Powell, Craig M.

    2014-01-01

    LAY ABSTRACT Mutations in neuroligin genes have been identified in association with autism. This manuscript provides characterization of a specific mutation in the neuroligin-3 gene that has been associated with autism in two brothers. The resulting autism model has alterations in social and cognitive function reminiscent of autism in patients. This model will be useful to understand the role of neuroligin dysfunction as a rare cause of autism. SCIENTIFIC ABSTRACT Multiple candidate genes have been identified for autism spectrum disorders. While some of these genes reach genome-wide significance, others, such as the R451C point mutation in the synaptic cell adhesion molecule neuroligin-3, appear to be rare. Interestingly, two brothers with the same R451C point mutation in neuroligin-3 present clinically on seemingly disparate sides of the autism spectrum. These clinical findings suggest genetic background may play a role in modifying the penetrance of a particular autism-associated mutation. Animal models may contribute additional support for such mutations as functionally relevant and can provide mechanistic insights. Previously, in collaboration with the Südhof laboratory, we reported that mice with an R451C substitution in neuroligin-3 displayed social deficits and enhanced spatial learning. While some of these behavioral abnormalities have since been replicated independently in the Südhof laboratory, observations from the Crawley laboratory failed to replicate these findings in a similar neuroligin-3 mutant mouse model and suggested that genetic background may contribute to variation in observations across laboratories. Therefore we sought to replicate our findings in the neuroligin-3 R451C point mutant knockin mouse model (NL3R451C) in a different genetic background. We backcrossed our NL3R451C mouse line onto a 129S2/SvPasCrl genetic background and repeated a subset of our previous behavioral testing. NL3R451C mice on a 129S2/SvPasCrl displayed social

  4. Diet, age, and prior injury status differentially alter behavioral outcomes following concussion in rats.

    PubMed

    Mychasiuk, Richelle; Hehar, Harleen; van Waes, Linda; Esser, Michael J

    2015-01-01

    Mild traumatic brain injury (mTBI) or concussion affects a large portion of the population and although many of these individuals recover completely, a small subset of people experience lingering symptomology and poor outcomes. Little is known about the factors that affect individual susceptibility or resilience to poor outcomes after mTBI and there are currently no biomarkers to delineate mTBI diagnosis or prognosis. Based upon the growing literature associated with caloric intake and altered neurological aging and the ambiguous link between repetitive mTBI and progressive neurodegeneration, the current study was designed to examine the effect of a high fat diet (HFD), developmental age, and repetitive mTBI on behavioral outcomes following a mTBI. In addition, telomere length was examined before and after experimental mTBI. Sprague Dawley rats were maintained on a HFD or standard rat chow throughout life (including the prenatal period) and then experienced an mTBI/concussion at P30, P30 and P60, or only at P60. Behavioral outcomes were examined using a test battery that was administered between P61-P80 and included; beam-walking, open field, elevated plus maze, novel context mismatch, Morris water task, and forced swim task. Animals with a P30 mTBI often demonstrated lingering symptomology that was still present during testing at P80. Injuries at P30 and P60 rarely produced cumulative effects, and in some tests (i.e., beam walking), the first injury may have protected the brain from the second injury. Exposure to the high fat diet exacerbated many of the behavioral deficits associated with concussion. Finally, telomere length was shortened following mTBI and was influenced by the animal's dietary intake. Diet, age at the time of injury, and the number of prior concussion incidents differentially contribute to behavioral deficits and may help explain individual variations in susceptibility and resilience to poor outcomes following an mTBI. Copyright © 2014

  5. Enhancement of extinction learning attenuates ethanol-seeking behavior and alters plasticity in the prefrontal cortex.

    PubMed

    Gass, Justin T; Trantham-Davidson, Heather; Kassab, Amanda S; Glen, William B; Olive, M Foster; Chandler, L Judson

    2014-05-28

    Addiction is a chronic relapsing disorder in which relapse is often initiated by exposure to drug-related cues. The present study examined the effects of mGluR5 activation on extinction of ethanol-cue-maintained responding, relapse-like behavior, and neuronal plasticity. Rats were trained to self-administer ethanol and then exposed to extinction training during which they were administered either vehicle or the mGluR5 positive allosteric modulator 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl) or CDPPB. CDPPB treatment reduced active lever responding during extinction, decreased the total number of extinction sessions required to meet criteria, and attenuated cue-induced reinstatement of ethanol seeking. CDPPB facilitation of extinction was blocked by the local infusion of the mGluR5 antagonist 3-((2-methyl-4-thiazolyl)ethynyl) pyridine into the infralimbic (IfL) cortex, but had no effect when infused into the prelimbic (PrL) cortex. Analysis of dendritic spines revealed alterations in structural plasticity, whereas electrophysiological recordings demonstrated differential alterations in glutamatergic neurotransmission in the PrL and IfL cortex. Extinction was associated with increased amplitude of evoked synaptic PrL and IfL NMDA currents but reduced amplitude of PrL AMPA currents. Treatment with CDPPB prevented the extinction-induced enhancement of NMDA currents in PrL without affecting NMDA currents in the IfL. Whereas CDPPB treatment did not alter the amplitude of PrL or IfL AMPA currents, it did promote the expression of IfL calcium-permeable GluR2-lacking receptors in both abstinence- and extinction-trained rats, but had no effect in ethanol-naive rats. These results confirm changes in the PrL and IfL cortex in glutamatergic neurotransmission during extinction learning and demonstrate that manipulation of mGluR5 facilitates extinction of ethanol cues in association with neuronal plasticity.

  6. Enhancement of Extinction Learning Attenuates Ethanol-Seeking Behavior and Alters Plasticity in the Prefrontal Cortex

    PubMed Central

    Trantham-Davidson, Heather; Kassab, Amanda S.; Glen, William B.; Olive, M. Foster; Chandler, L. Judson

    2014-01-01

    Addiction is a chronic relapsing disorder in which relapse is often initiated by exposure to drug-related cues. The present study examined the effects of mGluR5 activation on extinction of ethanol-cue-maintained responding, relapse-like behavior, and neuronal plasticity. Rats were trained to self-administer ethanol and then exposed to extinction training during which they were administered either vehicle or the mGluR5 positive allosteric modulator 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl) or CDPPB. CDPPB treatment reduced active lever responding during extinction, decreased the total number of extinction sessions required to meet criteria, and attenuated cue-induced reinstatement of ethanol seeking. CDPPB facilitation of extinction was blocked by the local infusion of the mGluR5 antagonist 3-((2-methyl-4-thiazolyl)ethynyl) pyridine into the infralimbic (IfL) cortex, but had no effect when infused into the prelimbic (PrL) cortex. Analysis of dendritic spines revealed alterations in structural plasticity, whereas electrophysiological recordings demonstrated differential alterations in glutamatergic neurotransmission in the PrL and IfL cortex. Extinction was associated with increased amplitude of evoked synaptic PrL and IfL NMDA currents but reduced amplitude of PrL AMPA currents. Treatment with CDPPB prevented the extinction-induced enhancement of NMDA currents in PrL without affecting NMDA currents in the IfL. Whereas CDPPB treatment did not alter the amplitude of PrL or IfL AMPA currents, it did promote the expression of IfL calcium-permeable GluR2-lacking receptors in both abstinence- and extinction-trained rats, but had no effect in ethanol-naive rats. These results confirm changes in the PrL and IfL cortex in glutamatergic neurotransmission during extinction learning and demonstrate that manipulation of mGluR5 facilitates extinction of ethanol cues in association with neuronal plasticity. PMID:24872560

  7. Acute illness-induced behavioral alterations are similar to those observed during withdrawal from acute alcohol exposure

    PubMed Central

    Richey, Laura; Doremus-Fitzwater, Tamara L.; Buck, Hollin M.; Deak, Terrence

    2012-01-01

    Exposure to an immunogen results in a constellation of behavioral changes collectively referred to as “sickness behaviors,” with alterations in cytokine expression previously shown to contribute to this sickness response. Since behaviors observed during ethanol withdrawal are strikingly similar to sickness behaviors, we hypothesized that behavioral manifestations of ethanol withdrawal might be an expression of sickness behaviors induced by ethanol-related changes in peripheral and/or central cytokine expression. Accordingly, behaviors exhibited during a modified social investigation test were first characterized in male rats following an acute injection of lipopolysaccharide (LPS; 100 μg/kg). Subsequently, behavioral changes after either a high (4-g/kg; Experiment 2) or low dose (0.5 g/kg; Experiment 3) of ethanol were also examined in the same social investigation test, as well as in the forced-swim test (FST; Experiment 4). Results from these experiments demonstrated similar reductions in both exploration and social investigatory behavior during acute illness and ethanol withdrawal, while a seemingly paradoxical decrease in immobility was observed in the FST during acute ethanol withdrawal. In follow-up studies, neither indomethacin (Experiment 5) nor interleukin-1 receptor antagonist (Experiment 6) pre-exposure reversed the ethanol withdrawal-induced behavioral changes observed in this social investigation test. Taken together, these studies demonstrate that the behavioral sequelae of acute illness and ethanol withdrawal are similar in nature, while antagonist studies suggest that these behavioral alterations are not reversed by blockade of IL-1 receptors or inhibition of prostaglandin synthesis. Though a direct mechanistic link between cytokines and the expression of acute ethanol withdrawal-related behaviors has yet to be found, future studies examining the involvement of brain cytokines as potential mediators of ethanol effects are greatly needed. PMID

  8. Short and long term neuro-behavioral alterations in type 1 diabetes mellitus pediatric population

    PubMed Central

    Litmanovitch, Edna; Geva, Ronny; Rachmiel, Marianna

    2015-01-01

    Type 1 diabetes mellitus (T1DM) is one of the most prevalent chronic conditions affecting individuals under the age of 18 years, with increasing incidence worldwide, especially among very young age groups, younger than 5. There is still no cure for the disease, and therapeutic goals and guidelines are a challenge. Currently, despite T1DM intensive management and technological interventions in therapy, the majority of pediatric patients do not achieve glycemic control goals. This leads to a potential prognosis of long term diabetic complications, nephrological, cardiac, ophthalmological and neurological. Unfortunately, the neurological manifestations, including neurocognitive and behavioral complications, may present soon after disease onset, during childhood and adolescence. These manifestations may be prominent, but at times subtle, thus they are often not reported by patients or physicians as related to the diabetes. Furthermore, the metabolic mechanism for such manifestations has been inconsistent and difficult to interpret in practical clinical care, as reported in several reviews on the topic of brain and T1DM. However, new technological methods for brain assessment, as well as the introduction of continuous glucose monitoring, provide new insights and information regarding brain related manifestations and glycemic variability and control parameters, which may impact the clinical care of children and youth with T1DM. This paper provides a comprehensive review of the most recently reported behavioral, cognitive domains, sleep related, electrophysiological, and structural alterations in children and adolescences from a novel point of view. The review focuses on reported impairments based on duration of T1DM, its timeline, and modifiable disease related risk parameters. These findings are not without controversy, and limitations of data are presented in addition to recommendations for future research direction. PMID:25789107

  9. Plant vitrification solution 2 lowers water content and alters freezing behavior in shoot tips during cryoprotection.

    PubMed

    Volk, Gayle M; Walters, Christina

    2006-02-01

    Plant shoot tips do not survive exposure to liquid nitrogen temperatures without cryoprotective treatments. Some cryoprotectant solutions, such as plant vitrification solution 2 (PVS2), dehydrate cells and decrease lethal ice formation, but the extent of dehydration and the effect on water freezing properties are not known. We examined the effect of a PVS2 cryoprotection protocol on the water content and phase behavior of mint and garlic shoot tips using differential scanning calorimetry. The temperature and enthalpy of water melting transitions in unprotected and recovering shoot tips were comparable to dilute aqueous solutions. Exposure to PVS2 changed the behavior of water in shoot tips: enthalpy of melting transitions decreased to about 40 J g H2O(-1) (compared to 333 J g H2O(-1) for pure H2O), amount of unfrozen water increased to approximately 0.7 g H2O g dry mass(-1) (compared to approximately 0.4 g H2Og dry mass(-1) for unprotected shoot tips), and a glass transition (T(g)) at -115 degrees C was apparent. Evaporative drying at room temperature was slower in PVS2-treated shoot tips compared to shoot tips receiving no cryoprotection treatments. We quantified the extent that ethylene glycol and dimethyl sulfoxide components permeate into shoot tips and replace some of the water. Since T(g) in PVS2-treated shoot tips occurs at -115 degrees C, mechanisms other than glass formation prevent freezing at temperatures between 0 and -115 degrees C. Protection is likely a result of controlled dehydration or altered thermal properties of intracellular water. A comparison of thermodynamic measurements for cryoprotection solutions in diverse plant systems will identify efficacy among cryopreservation protocols.

  10. Neonatal exposure to sucralose does not alter biochemical markers of neuronal development or adult behavior.

    PubMed

    Viberg, Henrik; Fredriksson, Anders

    2011-01-01

    Sucralose, a high-intensity sweetener, has been approved as a general-purpose sweetener in all food since the late 1990s. Due to its good taste and physiochemical profile, its use has increased and sucralose is considered a way of managing health and an option to improve the quality of life in the diabetic population. Recently high concentrations of sucralose have been found in the environment. Other environmental pollutants have been shown to induce neurotoxic effects when administered during a period of rapid brain growth and development. This period of rapid brain growth and development is postnatal in mice and rats, spanning the first 3-4 wk of life, reaching its peak around postnatal day 10, whereas in humans, brain growth and development is perinatal. The proteins calcium/calmodulin-dependent protein kinase II, growth-associated protein-43, synaptophysin, and tau play important roles during brain growth and development. In the present study, mice were orally exposed to 5-125 mg of sucralose per kilogram of body weight per day during postnatal days 8-12. Twenty-four hours after last exposure, brains were analyzed for calcium/calmodulin-dependent protein kinase II, growth-associated protein-43, synaptophysin, and tau, and at the age of 2 mo the animals were tested for spontaneous behavior. The protein analysis showed no alterations in calcium/calmodulin-dependent protein kinase II, growth-associated protein-43, synaptophysin, or tau. Furthermore, there were no disturbances in adult behavior or habituation after neonatal sucralose exposure. The present study shows that repeated neonatal exposure to the artificial sweetener sucralose does not result in neurotoxicity, which supports that sucralose seems to be a safe alternative for people who want or need to reduce or substitute glucose in their diet. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Common behaviors alterations after extremely low-frequency electromagnetic field exposure in rat animal model.

    PubMed

    Mahdavi, Seyed Mohammad; Sahraei, Hedayat; Rezaei-Tavirani, Mostafa; Najafi Abedi, Akram

    2016-01-01

    Naturally, the presence of electromagnetic waves in our living environment affects all components of organisms, particularly humans and animals, as the large part of their body consists of water. In the present study, we tried to investigate the relation between exposure to the extremely low-frequency electromagnetic field (ELF-EMF) and common behaviors such as body weight, food and water intake, anorexia (poor appetite), plasma glucose concentration, movement, rearing and sniffing in rats. For this purpose, rats were exposed to 40  Hz ELF-EMF once a day for 21 days, then at days 1, 3, 7, 14 and 21 after exposure, any changes in the above-mentioned items were assessed in the exposed rats and compared to the non-exposed group as control. Body weight of irradiated rats significantly increased only a week after exposure and decreased after that. No significant change was observed in food and water intake of irradiated rats compared to the control, and the anorexia parameter in the group exposed to ELF-EMF was significantly decreased at one and two weeks after irradiation. A week after exposure, the level of glucose was significantly increased but at other days these changes were not significant. Movements, rearing and sniffing of rats at day 1 after exposure were significantly decreased and other days these changes did not follow any particular pattern. However, the result of this study demonstrated that exposure to ELF-EMF can alter the normal condition of animals and may represent a harmful impact on behavior.

  12. Artificial Outdoor Nighttime Lights Associate with Altered Sleep Behavior in the American General Population

    PubMed Central

    Ohayon, Maurice M.; Milesi, Cristina

    2016-01-01

    Study Objectives: Our study aims to explore the associations between outdoor nighttime lights (ONL) and sleep patterns in the human population. Methods: Cross-sectional telephone study of a representative sample of the general US population age 18 y or older. 19,136 noninstitutionalized individuals (participation rate: 83.2%) were interviewed by telephone. The Sleep-EVAL expert system administered questions on life and sleeping habits; health; sleep, mental and organic disorders (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision; International Classification of Sleep Disorders, Second Edition; International Classification of Diseases, 10th Edition). Individuals were geolocated by longitude and latitude. Outdoor nighttime light measurements were obtained from the Defense Meteorological Satellite Program's Operational Linescan System (DMSP/OLS), with nighttime passes taking place between 19:30 and 22:30 local time. Light data were correlated precisely to the geolocation of each participant of the general population sample. Results: Living in areas with greater ONL was associated with delayed bedtime (P < 0.0001) and wake up time (P < 0.0001), shorter sleep duration (P < 0.01), and increased daytime sleepiness (P < 0.0001). Living in areas with greater ONL also increased the dissatisfaction with sleep quantity and quality (P < 0.0001) and the likelihood of having a diagnostic profile congruent with a circadian rhythm disorder (P < 0.0001). Conclusions: Although they improve the overall safety of people and traffic, nighttime lights in our streets and cities are clearly linked with modifications in human sleep behaviors and also impinge on the daytime functioning of individuals living in areas with greater ONL. Citation: Ohayon MM, Milesi C. Artificial outdoor nighttime lights associate with altered sleep behavior in the american general population. SLEEP 2016;39(6):1311–1320. PMID:27091523

  13. Prenatal chlorpyrifos exposure alters motor behavior and ultrasonic vocalization in cd-1 mouse pups

    PubMed Central

    2009-01-01

    Background Chlorpyrifos (CPF) is a non-persistent organophosphate (OP) largely used as pesticide. Studies from animal models indicate that CPF is a developmental neurotoxicant able to target immature central nervous system at dose levels well below the threshold of systemic toxicity. So far, few data are available on the potential short- and long-term adverse effects in children deriving from low-level exposures during prenatal life and infancy. Methods Late gestational exposure [gestational day (GD) 14–17] to CPF at the dose of 6 mg/kg was evaluated in CD-1 mice during early development, by assessment of somatic and sensorimotor maturation [reflex-battery on postnatal days (PNDs) 3, 6, 9, 12 and 15] and ultrasound emission after isolation from the mother and siblings (PNDs 4, 7 and 10). Pups' motor skills were assessed in a spontaneous activity test on PND 12. Maternal behavior of lactating dams in the home cage and in response to presentation of a pup previously removed from the nest was scored on PND 4, to verify potential alterations in maternal care directly induced by CPF administration. Results As for the effects on the offspring, results indicated that on PND 10, CPF significantly decreased number and duration of ultrasonic calls while increasing latency to emit the first call after isolation. Prenatal CPF also reduced motor behavior on PND 12, while a tendency to hyporeflexia was observed in CPF pups by means of reflex-battery scoring. Dams administered during gestation with CPF showed baseline levels of maternal care comparable to those of controls, but higher levels of both pup-directed (licking) and explorative (wall rearing) responses. Conclusion Overall our results are consistent with previous epidemiological data on OP neurobehavioral toxicity, and also indicate ultrasonic vocalization as an early marker of CPF exposure during development in rodent studies, with potential translational value to human infants. PMID:19331648

  14. An Scn1a epilepsy mutation in Scn8a alters seizure susceptibility and behavior

    PubMed Central

    Makinson, Christopher D.; Dutt, Karoni; Lin, Frank; Papale, Ligia A.; Shankar, Anupama; Barela, Arthur J.; Liu, Robert; Goldin, Alan L.; Escayg, Andrew

    2015-01-01

    Understanding the role of SCN8A in epilepsy and behavior is critical in light of recently identified human SCN8A epilepsy mutations. We have previously demonstrated that Scn8amed and Scn8amed-jo mice carrying mutations in the Scn8a gene display increased resistance to flurothyl and kainic acid-induced seizures; however, they also exhibit spontaneous absence seizures. To further investigate the relationship between altered SCN8A function and epilepsy, we introduced the SCN1A-R1648H mutation, identified in a family with generalized epilepsy with febrile seizures plus (GEFS+), into the corresponding position (R1627H) of the mouse Scn8a gene. Heterozygous R1627H mice exhibited increased resistance to some forms of pharmacologically and electrically induced seizures and the mutant Scn8a allele ameliorated the phenotype of Scn1a-R1648H mutants. Hippocampal slices from heterozygous R1627H mice displayed decreased bursting behavior compared to wild-type littermates. Paradoxically, at the homozygous level, R1627H mice did not display increased seizure resistance and were susceptible to audiogenic seizures. We furthermore observed increased hippocampal pyramidal cell excitability in heterozygous and homozygous Scn8a-R1627H mutants, and decreased interneuron excitability in heterozygous Scn8a-R1627H mutants. These results expand the phenotypes associated with disruption of the Scn8a gene and demonstrate that an Scn8a mutation can both confer seizure protection and increase seizure susceptibility. PMID:26410685

  15. Alterations in the brain adenosine metabolism cause behavioral and neurological impairment in ADA-deficient mice and patients

    PubMed Central

    Sauer, Aisha V.; Hernandez, Raisa Jofra; Fumagalli, Francesca; Bianchi, Veronica; Poliani, Pietro L.; Dallatomasina, Chiara; Riboni, Elisa; Politi, Letterio S.; Tabucchi, Antonella; Carlucci, Filippo; Casiraghi, Miriam; Carriglio, Nicola; Cominelli, Manuela; Forcellini, Carlo Alberto; Barzaghi, Federica; Ferrua, Francesca; Minicucci, Fabio; Medaglini, Stefania; Leocani, Letizia; la Marca, Giancarlo; Notarangelo, Lucia D.; Azzari, Chiara; Comi, Giancarlo; Baldoli, Cristina; Canale, Sabrina; Sessa, Maria; D’Adamo, Patrizia; Aiuti, Alessandro

    2017-01-01

    Adenosine Deaminase (ADA) deficiency is an autosomal recessive variant of severe combined immunodeficiency (SCID) caused by systemic accumulation of ADA substrates. Neurological and behavioral abnormalities observed in ADA-SCID patients surviving after stem cell transplantation or gene therapy represent an unresolved enigma in the field. We found significant neurological and cognitive alterations in untreated ADA-SCID patients as well as in two groups of patients after short- and long-term enzyme replacement therapy with PEG-ADA. These included motor dysfunction, EEG alterations, sensorineural hypoacusia, white matter and ventricular alterations in MRI as well as a low mental development index or IQ. Ada-deficient mice were significantly less active and showed anxiety-like behavior. Molecular and metabolic analyses showed that this phenotype coincides with metabolic alterations and aberrant adenosine receptor signaling. PEG-ADA treatment corrected metabolic adenosine-based alterations, but not cellular and signaling defects, indicating an intrinsic nature of the neurological and behavioral phenotype in ADA deficiency. PMID:28074903

  16. Alterations in the brain adenosine metabolism cause behavioral and neurological impairment in ADA-deficient mice and patients.

    PubMed

    Sauer, Aisha V; Hernandez, Raisa Jofra; Fumagalli, Francesca; Bianchi, Veronica; Poliani, Pietro L; Dallatomasina, Chiara; Riboni, Elisa; Politi, Letterio S; Tabucchi, Antonella; Carlucci, Filippo; Casiraghi, Miriam; Carriglio, Nicola; Cominelli, Manuela; Forcellini, Carlo Alberto; Barzaghi, Federica; Ferrua, Francesca; Minicucci, Fabio; Medaglini, Stefania; Leocani, Letizia; la Marca, Giancarlo; Notarangelo, Lucia D; Azzari, Chiara; Comi, Giancarlo; Baldoli, Cristina; Canale, Sabrina; Sessa, Maria; D'Adamo, Patrizia; Aiuti, Alessandro

    2017-01-11

    Adenosine Deaminase (ADA) deficiency is an autosomal recessive variant of severe combined immunodeficiency (SCID) caused by systemic accumulation of ADA substrates. Neurological and behavioral abnormalities observed in ADA-SCID patients surviving after stem cell transplantation or gene therapy represent an unresolved enigma in the field. We found significant neurological and cognitive alterations in untreated ADA-SCID patients as well as in two groups of patients after short- and long-term enzyme replacement therapy with PEG-ADA. These included motor dysfunction, EEG alterations, sensorineural hypoacusia, white matter and ventricular alterations in MRI as well as a low mental development index or IQ. Ada-deficient mice were significantly less active and showed anxiety-like behavior. Molecular and metabolic analyses showed that this phenotype coincides with metabolic alterations and aberrant adenosine receptor signaling. PEG-ADA treatment corrected metabolic adenosine-based alterations, but not cellular and signaling defects, indicating an intrinsic nature of the neurological and behavioral phenotype in ADA deficiency.

  17. The Relationship between Instructor Misbehaviors and Student Antisocial Behavioral Alteration Techniques: The Roles of Instructor Attractiveness, Humor, and Relational Closeness

    ERIC Educational Resources Information Center

    Claus, Christopher J.; Booth-Butterfield, Melanie; Chory, Rebecca M.

    2012-01-01

    Using rhetorical/relational goal theory as a guiding frame, we examined relationships between instructor misbehaviors (i.e., indolence, incompetence, and offensiveness) and the likelihood of students communicating antisocial behavioral alteration techniques (BATs). More specifically, the study focused on whether students' perceptions of instructor…

  18. Reducing Transition Latency and Transition-Related Problem Behavior in Children by Altering the Motivating Operations for Task Disengagement

    ERIC Educational Resources Information Center

    Sullivan, William E.; Martens, Brian K.; Morley, Allison J.; Long, Stephanie J.

    2017-01-01

    Activity schedules, guided compliance, and differential reinforcement are often used to reduce transition-related problem behavior in children with autism. One potential way to increase the effectiveness of these procedures when transitioning children from preferred to nonpreferred activities is to alter the motivating operations for…

  19. The Relationship between Instructor Misbehaviors and Student Antisocial Behavioral Alteration Techniques: The Roles of Instructor Attractiveness, Humor, and Relational Closeness

    ERIC Educational Resources Information Center

    Claus, Christopher J.; Booth-Butterfield, Melanie; Chory, Rebecca M.

    2012-01-01

    Using rhetorical/relational goal theory as a guiding frame, we examined relationships between instructor misbehaviors (i.e., indolence, incompetence, and offensiveness) and the likelihood of students communicating antisocial behavioral alteration techniques (BATs). More specifically, the study focused on whether students' perceptions of instructor…

  20. Developmental Exposure to Aroclor 1254 Alters Migratory Behavior in Juvenile European Starlings (Sturnus vulgaris).

    PubMed

    Flahr, Leanne M; Michel, Nicole L; Zahara, Alexander R D; Jones, Paul D; Morrissey, Christy A

    2015-05-19

    Birds exposed to endocrine disrupting chemicals during development could be susceptible to neurological and other physiological changes affecting migratory behaviors. We investigated the effects of ecologically relevant levels of Aroclor 1254, a polychlorinated biphenyl (PCB) mixture, on moult, fattening, migratory activity, and orientation in juvenile European starlings (Sturnus vulgaris). Birds were orally administered 0 (control), 0.35 (low), 0.70 (intermediate), or 1.05 (high) μg Aroclor 1254/g-body weight by gavage from 1 through 18 days posthatch and later exposed in captivity to a photoperiod shift simulating an autumn migration. Migratory activity and orientation were examined using Emlen funnel trials. Across treatments, we found significant increases in mass, fat, and moulting and decreasing plasma thyroid hormones over time. We observed a significant increase in activity as photoperiod was shifted from 13L:11D (light:dark) to 12L:12D, demonstrating that migratory condition was induced in captivity. At 12L:12D, control birds oriented to 155.95° (South-Southeast), while high-dosed birds did not. High-dosed birds showed a delayed orientation to 197.48° (South-Southwest) under 10L:14D, concomitant with apparent delays in moult. These findings demonstrate how subtle contaminant-induced alterations during development could lead to longer-scale effects, including changes in migratory activity and orientation, which could potentially result in deleterious effects on fitness and survival.

  1. Alteration of the behavioral effects of nicotine by chronic caffeine exposure.

    PubMed

    Tanda, G; Goldberg, S R

    2000-05-01

    The prevalence of tobacco smoking and coffee drinking place nicotine and caffeine among the most used licit drugs in many societies and their consumption is often characterised by concurrent use. The pharmacological basis for any putative interaction between these drugs remains unclear. Some epidemiological reports support anecdotal evidence, which suggests that smokers consume caffeine to enhance the effects of nicotine. This paper reviews various aspects of the pharmacology of caffeine and nicotine, in humans and experimental animals, important for the understanding of the interactions between these drugs. In particular, recent experiments are reviewed in which chronic exposure to caffeine in the drinking water of rats facilitated acquisition of self-adminstration behavior, enhanced nicotine-induced increases in dopamine levels in the shell of the nucleus accumbens and altered the dopaminergic component of a nicotine discrimination. These studies provide evidence that the rewarding and subjective properties of nicotine can be changed by chronic caffeine exposure and indicate that caffeine exposure may be an important environmental factor in shaping and maintaining tobacco smoking.

  2. Alcohol during adolescence selectively alters immediate and long-term behavior and neurochemistry

    PubMed Central

    Maldonado-Devincci, Antoniette M.; Badanich, Kimberly A.; Kirstein, Cheryl L.

    2014-01-01

    Alcohol use increases across adolescence and is a concern in the United States. In humans, males and females consume different amounts of alcohol depending on the age of initiation and the long-term consequences of early ethanol consumption are not readily understood. The purpose of our work is to better understand the immediate and long-term impact of ethanol exposure during adolescence and the effects it can have on behavior and dopaminergic responsivity. We have assessed sex differences in voluntary ethanol consumption during adolescence and adulthood and the influence of binge ethanol exposure during adolescence. We have observed that males are sensitive to passive social influences that mediate voluntary ethanol consumption and early ethanol exposure induces long-term changes in responsivity to ethanol in adulthood. Exposure to moderate doses of ethanol during adolescence produced alterations in dopamine (DA) in the nucleus accumbens septi (NAcc) during adolescence and later in adulthood. Taken together, all of these data indicate the adolescent brain is sensitive to the impact of early ethanol exposure during this critical developmental period. PMID:20113874

  3. Arsenic moiety in gallium arsenide is responsible for neuronal apoptosis and behavioral alterations in rats.

    PubMed

    Flora, Swaran J S; Bhatt, Kapil; Mehta, Ashish

    2009-10-15

    Gallium arsenide (GaAs), an intermetallic semiconductor finds widespread applications in high frequency microwave and millimeter wave, and ultra fast supercomputers. Extensive use of GaAs has led to increased exposure to humans working in semiconductor industry. GaAs has the ability to dissociate into its constitutive moieties at physiological pH and might be responsible for the oxidative stress. The present study was aimed at evaluating, the principle moiety (Ga or As) in GaAs to cause neurological dysfunction based on its ability to cause apoptosis, in vivo and in vitro and if this neuronal dysfunction translated to neurobehavioral changes in chronically exposed rats. Result indicated that arsenic moiety in GaAs was mainly responsible for causing oxidative stress via increased reactive oxygen species (ROS) and nitric oxide (NO) generation, both in vitro and in vivo. Increased ROS further caused apoptosis via mitochondrial driven pathway. Effects of oxidative stress were also confirmed based on alterations in antioxidant enzymes, GPx, GST and SOD in rat brain. We noted that ROS induced oxidative stress caused changes in the brain neurotransmitter levels, Acetylcholinesterase and nitric oxide synthase, leading to loss of memory and learning in rats. The study demonstrates for the first time that the slow release of arsenic moiety from GaAs is mainly responsible for oxidative stress induced apoptosis in neuronal cells causing behavioral changes.

  4. Effect of wettability alteration on long-term behavior of fluids in subsurface

    SciTech Connect

    Bandara, Uditha C.; Palmer, Bruce J.; Tartakovsky, Alexandre M.

    2016-01-13

    Wettability is an important factor affecting fluid behavior in the subsurface, including oil, gas, and supercritical CO$_2$ in deep geological reservoirs. For example, CO$_2$ is generally assumed to behave as a non-wetting fluid, which favors safe storage. However, because of chemical heterogeneity of the reservoirs, mixed wettability conditions can exist. Furthermore, recent experiments suggest that with time, the wettability of super-critical CO$_2$ may change from non-wetting to partially-wetting due to changes in electrostatic interactions. These changes are caused by chemical reactions between dissolved CO$_2$ and its environment. To date, the effect of wettability alteration and mixed wettability on the long term fate of injected CO$_2$ has not well been studied. Here, we use the multiphase Pairwise Force Smoothed Particle Hydrodynamics (PF-SPH) Model to study complex pore-scale processes involved in geological CO$_2$ sequestration, including the effect of spatial and temporal wettability variations on long-term distribution of CO$_2$ in porous media. Results reveal that in the absence of dissolution of supercritical CO$_2$ and precipitation of carbonate minerals (mineral trapping), the amount of trapped supercritical CO$_2$ significantly decreases as the wettability of the porous media changes from brine-wet to partial-wet or CO$_2$-wet.

  5. Mutations in the circadian gene period alter behavioral and biochemical responses to ethanol in Drosophila.

    PubMed

    Liao, Jennifer; Seggio, Joseph A; Ahmad, S Tariq

    2016-04-01

    Clock genes, such as period, which maintain an organism's circadian rhythm, can have profound effects on metabolic activity, including ethanol metabolism. In turn, ethanol exposure has been shown in Drosophila and mammals to cause disruptions of the circadian rhythm. Previous studies from our labs have shown that larval ethanol exposure disrupted the free-running period and period expression of Drosophila. In addition, a recent study has shown that arrhythmic flies show no tolerance to ethanol exposure. As such, Drosophila period mutants, which have either a shorter than wild-type free-running period (perS) or a longer one (perL), may also exhibit altered responses to ethanol due to their intrinsic circadian differences. In this study, we tested the initial sensitivity and tolerance of ethanol exposure on Canton-S, perS, and perL, and then measured their Alcohol Dehydrogenase (ADH) and body ethanol levels. We showed that perL flies had slower sedation rate, longer recovery from ethanol sedation, and generated higher tolerance for sedation upon repeated ethanol exposure compared to Canton-S wild-type flies. Furthermore, perL flies had lower ADH activity and had a slower ethanol clearance compared to wild-type flies. The findings of this study suggest that period mutations influence ethanol induced behavior and ethanol metabolism in Drosophila and that flies with longer circadian periods are more sensitive to ethanol exposure. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Arsenic moiety in gallium arsenide is responsible for neuronal apoptosis and behavioral alterations in rats

    SciTech Connect

    Flora, Swaran J.S. Bhatt, Kapil; Mehta, Ashish

    2009-10-15

    Gallium arsenide (GaAs), an intermetallic semiconductor finds widespread applications in high frequency microwave and millimeter wave, and ultra fast supercomputers. Extensive use of GaAs has led to increased exposure to humans working in semiconductor industry. GaAs has the ability to dissociate into its constitutive moieties at physiological pH and might be responsible for the oxidative stress. The present study was aimed at evaluating, the principle moiety (Ga or As) in GaAs to cause neurological dysfunction based on its ability to cause apoptosis, in vivo and in vitro and if this neuronal dysfunction translated to neurobehavioral changes in chronically exposed rats. Result indicated that arsenic moiety in GaAs was mainly responsible for causing oxidative stress via increased reactive oxygen species (ROS) and nitric oxide (NO) generation, both in vitro and in vivo. Increased ROS further caused apoptosis via mitochondrial driven pathway. Effects of oxidative stress were also confirmed based on alterations in antioxidant enzymes, GPx, GST and SOD in rat brain. We noted that ROS induced oxidative stress caused changes in the brain neurotransmitter levels, Acetylcholinesterase and nitric oxide synthase, leading to loss of memory and learning in rats. The study demonstrates for the first time that the slow release of arsenic moiety from GaAs is mainly responsible for oxidative stress induced apoptosis in neuronal cells causing behavioral changes.

  7. Effect of wettability alteration on long-term behavior of fluids in subsurface

    NASA Astrophysics Data System (ADS)

    Bandara, Uditha C.; Palmer, Bruce J.; Tartakovsky, Alexandre M.

    2016-04-01

    Wettability is an important factor affecting fluid behavior in the subsurface, including oil, gas, and supercritical hbox {CO}_2 in deep geological reservoirs. For example, hbox {CO}_2 is generally assumed to behave as a non-wetting fluid, which favors safe storage. However, because of chemical heterogeneity of the reservoirs, mixed wettability conditions can exist. Furthermore, recent experiments suggest that with time, the wettability of super-critical hbox {CO}_2 may change from non-wetting to partially wetting due to changes in electrostatic interactions. These changes are caused by chemical reactions between dissolved hbox {CO}_2 and its environment. To date, the effect of wettability alteration and mixed wettability on the long-term fate of injected hbox {CO}_2 has not well been studied. Here, we use the multiphase pairwise force smoothed particle hydrodynamics model to study complex pore-scale processes involved in geological hbox {CO}_2 sequestration, including the effect of spatial and temporal wettability variations on long-term distribution of hbox {CO}_2 in porous media. Results reveal that in the absence of dissolution of supercritical hbox {CO}_2 and precipitation of carbonate minerals (mineral trapping), the amount of trapped supercritical hbox {CO}_2 significantly decreases as the wettability of the porous media changes from brine-wet to partial-wet or hbox {CO}_2-wet.

  8. Low dose effects of a Withania somnifera extract on altered marble burying behavior in stressed mice

    PubMed Central

    Dey, Amitabha; Chatterjee, Shyam Sunder; Kumar, Vikas

    2016-01-01

    Aim: Withania somnifera root (WSR) extracts are often used in traditionally known Indian systems of medicine for prevention and cure of psychosomatic disorders. The reported experiment was designed to test whether low daily oral doses of such extracts are also effective in suppressing marble burying behavior in stressed mice or not. Materials and Methods: Groups of mice treated with 10, 20, or 40 mg/kg daily oral doses of WSR were subjected to a foot shock stress-induced hyperthermia test on the 1st, 5th, 7th, and 10th day of the experiment. On the 11th and 12th treatment days, they were subjected to marble burying tests. Stress response suppressing effects of low dose WSR were estimated by its effects on body weight and basal core temperature of animals during the course of the experiment. Results: Alterations in bodyweight and basal core temperature triggered by repeated exposures to foot shock stress were absent even in the 10 mg/kg/day WSR treated group, whereas the effectiveness of the extract in foot shock stress-induced hyperthermia and marble burying tests increased with its increasing daily dose. Conclusion: Marble burying test in stressed mice is well suited for identifying bioactive constituents of W. somnifera like medicinal plants with adaptogenic, anxiolytic and antidepressant activities, or for quantifying pharmacological interactions between them. PMID:27366354

  9. Alcohol during adolescence selectively alters immediate and long-term behavior and neurochemistry.

    PubMed

    Maldonado-Devincci, Antoniette M; Badanich, Kimberly A; Kirstein, Cheryl L

    2010-02-01

    Alcohol use increases across adolescence and is a concern in the United States. In humans, males and females consume different amounts of alcohol depending on the age of initiation, and the long-term consequences of early ethanol consumption are not readily understood. The purpose of our work was to better understand the immediate and long-term impact of ethanol exposure during adolescence and the effects it can have on behavior and dopaminergic responsivity. We have assessed sex differences in voluntary ethanol consumption during adolescence and adulthood and the influence of binge ethanol exposure during adolescence. We have observed that males are sensitive to passive social influences that mediate voluntary ethanol consumption, and early ethanol exposure induces long-term changes in responsivity to ethanol in adulthood. Exposure to moderate doses of ethanol during adolescence produced alterations in dopamine in the nucleus accumbens septi during adolescence and later in adulthood. Taken together, all of these data indicate that the adolescent brain is sensitive to the impact of early ethanol exposure during this critical developmental period.

  10. Altered diurnal pattern of steroid hormones in relation to various behaviors, external factors and pathologies: A review.

    PubMed

    Collomp, K; Baillot, A; Forget, H; Coquerel, A; Rieth, N; Vibarel-Rebot, N

    2016-10-01

    The adrenal and gonadal stress steroids [i.e., cortisol, testosterone and dehydroepiandrosterone (DHEA)] have gathered considerable attention in the last few decades due to their very broad physiological and psychological actions. Their diurnal patterns have become a particular focus following new data implicating altered diurnal hormone patterns in various endocrine, behavioral and cardiovascular risk profiles. In this review of the current literature, we present a brief overview of the altered diurnal patterns of these hormones that may occur in relation to chronic stress, nutritional behaviors, physical exercise, drugs and sleep deprivation/shift. We also present data on the altered diurnal hormone patterns implicated in cardiometabolic and psychiatric/neurologic diseases, cancer and other complex pathologies. We consider the occasionally discrepant results of the studies, and summarize the current knowledge in this new field of interest, underlining the potential effects on both biological and psychological functioning, and assess the implications of these effects. Last, we conclude with some practical considerations and perspectives.

  11. Prenatal Alcohol Exposure and Chronic Mild Stress Differentially Alter Depressive- and Anxiety-Like Behaviors in Male and Female Offspring

    PubMed Central

    Hellemans, Kim G. C.; Verma, Pamela; Yoon, Esther; Yu, Wayne K.; Young, Allan H.; Weinberg, Joanne

    2016-01-01

    Background Fetal Alcohol Spectrum Disorder (FASD) is associated with numerous neuro behavioral alterations, as well as disabilities in a number of domains, including a high incidence of depression and anxiety disorders. Prenatal alcohol exposure (PAE) also alters hypothalamic-pituitary-adrenal (HPA) function, resulting in increased responsiveness to stressors and HPA dysregulation in adulthood. Interestingly, data suggest that pre-existing HPA abnormalities may be a major contributory factor to some forms of depression, particularly when an individual is exposed to stressors later in life. We tested the hypothesis that exposure to stressors in adulthood may unmask an increased vulnerability to depressive- and anxiety-like behaviors in PAE animals. Methods Male and female offspring from prenatal alcohol (PAE), pair-fed (PF), and ad libitumfed control (C) treatment groups were tested in adulthood. Animals were exposed to 10 consecutive days of chronic mild stress (CMS), and assessed in a battery of well-validated tasks sensitive to differences in depressive- and / or anxiety-like behaviors. Results We report here that the combination of PAE and CMS in adulthood increases depressive- and anxiety-like behaviors in a sexually dimorphic manner. PAE males showed impaired hedonic responsivity (sucrose contrast test), locomotor hyperactivity (open field), and alterations in affiliative and nonaffiliative social behaviors (social interaction test) compared to control males. By contrast, PAE and, to a lesser extent, PF, females showed greater levels of “behavioral despair” in the forced swim test, and PAE females showed altered behavior in the final 5 minutes of the social interaction test compared to control females. Conclusions These data support the possibility that stress may be a mediating or contributing factor in the psychopathologies reported in FASD populations. PMID:20102562

  12. Evaluation of Agaricus blazei in vivo for antigenotoxic, anticarcinogenic, phagocytic and immunomodulatory activities.

    PubMed

    Ishii, Priscila Lumi; Prado, Carolina Kato; Mauro, Mariana de Oliveira; Carreira, Clísia Mara; Mantovani, Mário Sérgio; Ribeiro, Lúcia Regina; Dichi, Jane Bandeira; Oliveira, Rodrigo Juliano

    2011-04-01

    The development of various types of cancer results from the interaction among endogenous, environmental and hormonal factors, where the most notable of these factors is diet. The aim of the present study was to determine the antigenotoxic, anticarcinogenic, phagocytic and immunomodulatory activities of Agaricus blazei. The test antigenotoxicity (Comet Assay) and anticarcinogenic (Test of Aberrant Crypt Foci) assess changes in DNA and/or intestinal mucosa that correlate to cancer development. Tests of phagocytosis in the spleen and differential count in blood cells allow the inference of modulation of the immune system as well as to propose a way of eliminating cells with DNA damage. Supplementation with the mushroom was carried out under pre-treatment, simultaneous treatment, post-treatment and pre-treatment+continuous conditions. Statistical analysis demonstrated that the mushroom did not have genotoxic activity but showed antigenotoxic activity. Supplementation caused an increase in the number of monocytes and in phagocytic activity, suggesting that supplementation increases a proliferation of monocytes, consequently increasing phagocytic capacity especially in the groups pre-treatment, simultaneous and pre-treatment+continuous. The data suggest that A. blazei could act as a functional food capable of promoting immunomodulation which can account for the destruction of cells with DNA alterations that correlate with the development of cancer, since this mushroom was demonstrated to have a preventive effect against pre-neoplastic colorectal lesions evaluated by the aberrant crypt foci assay. According to these results and the literature, it is believed that supplementation with A. blazei can be an efficient method for the prevention of cancer as well as possibly being an important coadjuvant treatment in chemotherapy.

  13. Bifidobacterium CECT 7765 modulates early stress-induced immune, neuroendocrine and behavioral alterations in mice.

    PubMed

    Moya-Pérez, A; Perez-Villalba, A; Benítez-Páez, A; Campillo, I; Sanz, Y

    2017-10-01

    could partly explain the restoration of immune, neuroendocrine and behavioral alterations caused by stress in early and later life. In summary, we show that B. pseudocatenulatum CECT 7765 is able to beneficially modulate the consequences of chronic stress on the HPA response produced by MS during infancy with long-lasting effects in adulthood, via modulation of the intestinal neurotransmitter and cytokine network with short and long-term consequences in brain biochemistry and behavior. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Probiotics Improve Inflammation-Associated Sickness Behavior by Altering Communication between the Peripheral Immune System and the Brain.

    PubMed

    D'Mello, Charlotte; Ronaghan, Natalie; Zaheer, Raza; Dicay, Michael; Le, Tai; MacNaughton, Wallace K; Surrette, Michael G; Swain, Mark G

    2015-07-29

    Patients with systemic inflammatory diseases (e.g., rheumatoid arthritis, inflammatory bowel disease, chronic liver disease) commonly develop debilitating symptoms (i.e., sickness behaviors) that arise from changes in brain function. The microbiota-gut-brain axis alters brain function and probiotic ingestion can influence behavior. However, how probiotics do this remains unclear. We have previously described a novel periphery-to-brain communication pathway in the setting of peripheral organ inflammation whereby monocytes are recruited to the brain in response to systemic TNF-α signaling, leading to microglial activation and subsequently driving sickness behavior development. Therefore, we investigated whether probiotic ingestion (i.e., probiotic mixture VSL#3) alters this periphery-to-brain communication pathway, thereby reducing subsequent sickness behavior development. Using a well characterized mouse model of liver inflammation, we now show that probiotic (VSL#3) treatment attenuates sickness behavior development in mice with liver inflammation without affecting disease severity, gut microbiota composition, or gut permeability. Attenuation of sickness behavior development was associated with reductions in microglial activation and cerebral monocyte infiltration. These events were paralleled by changes in markers of systemic immune activation, including decreased circulating TNF-α levels. Our observations highlight a novel pathway through which probiotics mediate cerebral changes and alter behavior. These findings allow for the potential development of novel therapeutic interventions targeted at the gut microbiome to treat inflammation-associated sickness behaviors in patients with systemic inflammatory diseases. This research shows that probiotics, when eaten, can improve the abnormal behaviors (including social withdrawal and immobility) that are commonly associated with inflammation. Probiotics are able to cause this effect within the body by changing how

  15. Cellular phagocytic studies in rheumatoid arthritis patients treated with levamisole.

    PubMed Central

    Wynne, K M; Dieppe, P A; Scott, J; Huskisson, E C

    1981-01-01

    A simple method is described which allows sequential monitoring of the endocytic activity of blood and synovial fluid cells from rheumatoid arthritis patients undergoing therapy with levamisole. Evidence of immediate (24 hours) and long-term (5-7 weeks) cellular phagocytic enhancement is presented. Images PMID:7259330

  16. Tumor Phagocytes Promote Breast Cancer Invasion and Metastasis

    DTIC Science & Technology

    2010-10-14

    cells. Finally, we also used CypHer 5E loading to confirm that epithelial cells have specific phagocytic activity. CypHer5E is a pH- sensitive cyanine ...with the Luminex technology and do not have any definitive data to report from these efforts. Cell culture media from epithelial cultures showed

  17. Adenylate Cyclase Toxin promotes bacterial internalisation into non phagocytic cells

    PubMed Central

    Martín, César; Etxaniz, Asier; Uribe, Kepa B.; Etxebarria, Aitor; González-Bullón, David; Arlucea, Jon; Goñi, Félix M.; Aréchaga, Juan; Ostolaza, Helena

    2015-01-01

    Bordetella pertussis causes whooping cough, a respiratory infectious disease that is the fifth largest cause of vaccine-preventable death in infants. Though historically considered an extracellular pathogen, this bacterium has been detected both in vitro and in vivo inside phagocytic and non-phagocytic cells. However the precise mechanism used by B. pertussis for cell entry, or the putative bacterial factors involved, are not fully elucidated. Here we find that adenylate cyclase toxin (ACT), one of the important toxins of B. pertussis, is sufficient to promote bacterial internalisation into non-phagocytic cells. After characterization of the entry route we show that uptake of “toxin-coated bacteria” proceeds via a clathrin-independent, caveolae-dependent entry pathway, allowing the internalised bacteria to survive within the cells. Intracellular bacteria were found inside non-acidic endosomes with high sphingomyelin and cholesterol content, or “free” in the cytosol of the invaded cells, suggesting that the ACT-induced bacterial uptake may not proceed through formation of late endolysosomes. Activation of Tyr kinases and toxin-induced Ca2+-influx are essential for the entry process. We hypothesize that B. pertussis might use ACT to activate the endocytic machinery of non-phagocytic cells and gain entry into these cells, in this way evading the host immune system. PMID:26346097

  18. Chemotactic and Phagocytic Activity of Blood Neutrophils in Allergic Asthma.

    PubMed

    Mosca, Tainá; Menezes, Maria C S; Silva, Ademir Veras; Stirbulov, Roberto; Forte, Wilma C N

    2015-01-01

    Allergic asthma is a chronic inflammatory airway disease, and has been considered a T helper-2-biased response. Studies suggest that neutrophils may be associated with exacerbation and asthma severity. We sought to evaluate the chemotactic activity and phagocytic capacity by peripheral blood neutrophils from individuals with controlled and uncontrolled allergic asthma, and compare the results with non-asthmatic controls groups. Blood neutrophils were isolated from 95 patients: 24 with controlled asthma, 24 uncontrolled asthma, 24 healthy subjects and 23 patients with IgE-mediated allergies other than asthma. The neutrophil chemotaxis, stimulated with LPS, autologous serum or homologous serum, was determined using Boyden chambers. The phagocytic capacity was assessed by ingestion of zimosan particles, and digestion phase was analyzed by NBT test. The phagocytic digestion phase and chemotaxis by neutrophils from asthmatic patients was higher than in non-asthmatic controls (p  < 0.05). Autologous serum-induced neutrophil chemotaxis in patients with uncontrolled asthma was greater (p  < 0.05) than in other study groups. The ingestion phase of phagocytosis showed similar values in asthmatics and non-asthmatics. We conclude that the blood neutrophil from controlled and uncontrolled asthmatic patients exhibit activation markers, particularly phagocytic digestion and chemotactic activities.

  19. Effect of temperature on phagocytic activity of neutrophils.

    PubMed

    Pramanik, Tapas; Thapa, Manoj; Saikia, Tolan Chandra

    2004-06-01

    The effect of temperature on phagocytic activity of neutrophils has been evaluated. Freshly collected heparinised blood samples from young healthy volunteers were incubated with heat killed Staphylococcus aureus at 37 degrees C, 38 degrees C, 39 degrees C and 40 degrees C for 20 minutes. Some of the neutrophils engulfed some heat killed bacteria. Then the blood smears were prepared and stained by Leishman's stain. Engulfed bacteria within the neutrophils stained intensely were observed and counted to find out the phagocytic index and avidity index of the neutrophils. It was found that phagocytic index increased significantly at 38 degrees C and 39 degrees C in comparison to that of at 37 degrees C but did not show significant increase when incubated at 40 degrees C. It seems that contractile elements responsible for the movement of the neutrophils through the formation of pseudopod is more activated at higher temperature (38 degrees C and 39 degrees C) in comparison to that of at normal body temperature (37 degrees C). Temperature higher than 39 degrees C may cause impairment in enzyme function responsible for assembly and disassembly of actin and myosin filaments in the cell causing decreased movement and decreased rate of formation of psudopod resulting in decreased phagocytic activity.

  20. Reaction Time is a Marker of Early Cognitive and Behavioral Alterations in Pure Cerebral Small Vessel Disease.

    PubMed

    Jouvent, Eric; Reyes, Sonia; De Guio, François; Chabriat, Hugues

    2015-01-01

    The assessment of early and subtle cognitive and behavioral effects of cerebral small vessel disease (SVD) requires specific and long-lasting evaluations performed by experienced neuropsychologists. Simpler tools would be helpful for daily clinical practice. To determine whether a simple reaction time task that lasts 5 minutes and can be performed without external supervision on any tablet or laptop can be used as a proxy of early cognitive and behavioral alterations in CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), a monogenic form of pure SVD related to NOTCH3 mutations. Twenty-two genetically confirmed patients with CADASIL having preserved global cognitive abilities and without disability (MMSE >24 and modified Rankin's scale ≤1) were compared to 29 age-and-gender matched controls to determine group differences according to: 1) conventional neuropsychological and behavioral testing; 2) a computerized battery evaluating reaction time, processing speed, and executive functions. In a second step, correlations between reaction time and cognitive and behavioral alterations detected using both conventional and computerized testing were tested in patients. Reaction time was significantly higher in patients than in controls (mean in patients: 283 ms - in controls: 254 ms, p = 0.03). In patients, reaction time was significantly associated with conventional and chronometric tests of executive functions, working memory, and apathy. Reaction time obtained using a very simple task may serve as a proxy of early cognitive and behavioral alterations in SVD and could be easily used in daily clinical practice.

  1. Increasing Maternal or Post-Weaning Folic Acid Alters Gene Expression and Moderately Changes Behavior in the Offspring

    PubMed Central

    Kuizon, Salomon; Buenaventura, Diego; Stapley, Nathan W.; Ruocco, Felicia; Begum, Umme; Guariglia, Sara R.; Brown, W. Ted; Junaid, Mohammed A.

    2014-01-01

    Background Studies have indicated that altered maternal micronutrients and vitamins influence the development of newborns and altered nutrient exposure throughout the lifetime may have potential health effects and increased susceptibility to chronic diseases. In recent years, folic acid (FA) exposure has significantly increased as a result of mandatory FA fortification and supplementation during pregnancy. Since FA modulates DNA methylation and affects gene expression, we investigated whether the amount of FA ingested during gestation alters gene expression in the newborn cerebral hemisphere, and if the increased exposure to FA during gestation and throughout the lifetime alters behavior in C57BL/6J mice. Methods Dams were fed FA either at 0.4 mg or 4 mg/kg diet throughout the pregnancy and the resulting pups were maintained on the diet throughout experimentation. Newborn pups brain cerebral hemispheres were used for microarray analysis. To confirm alteration of several genes, quantitative RT-PCR (qRT-PCR) and Western blot analyses were performed. In addition, various behavior assessments were conducted on neonatal and adult offspring. Results Results from microarray analysis suggest that the higher dose of FA supplementation during gestation alters the expression of a number of genes in the newborns’ cerebral hemispheres, including many involved in development. QRT-PCR confirmed alterations of nine genes including down-regulation of Cpn2, Htr4, Zfp353, Vgll2 and up-regulation of Xist, Nkx6-3, Leprel1, Nfix, Slc17a7. The alterations in the expression of Slc17a7 and Vgll2 were confirmed at the protein level. Pups exposed to the higher dose of FA exhibited increased ultrasonic vocalizations, greater anxiety-like behavior and hyperactivity. These findings suggest that although FA plays a significant role in mammalian cellular machinery, there may be a loss of benefit from higher amounts of FA. Unregulated high FA supplementation during pregnancy and throughout the

  2. Altered synaptic phospholipid signaling in PRG-1 deficient mice induces exploratory behavior and motor hyperactivity resembling psychiatric disorders.

    PubMed

    Schneider, Patrick; Petzold, Sandra; Sommer, Angela; Nitsch, Robert; Schwegler, Herbert; Vogt, Johannes; Roskoden, Thomas

    2017-08-24

    Plasticity related gene 1 (PRG-1) is a neuron specific membrane protein located at the postsynaptic density of glutamatergic synapses. PRG-1 modulates signaling pathways of phosphorylated lipid substrates such as lysophosphatidic acid (LPA). Deletion of PRG-1 increases presynaptic glutamate release probability leading to neuronal over-excitation. However, due to its cortical expression, PRG-1 deficiency leading to increased glutamatergic transmission is supposed to also affect motor pathways. We therefore analyzed the effects of PRG-1 function on exploratory and motor behavior using homozygous PRG-1 knockout (PRG-1(-/-)) mice and PRG-1/LPA2-receptor double knockout (PRG-1(-/-)/LPA2(-/-)) mice in two open field settings of different size and assessing motor behavior in the Rota Rod test. PRG-1(-/-) mice displayed significantly longer path lengths and higher running speed in both open field conditions. In addition, PRG-1(-/-) mice spent significantly longer time in the larger open field and displayed rearing and self-grooming behavior. Furthermore PRG-1(-/-) mice displayed stereotypical behavior resembling phenotypes of psychiatric disorders in the smaller sized open field arena. Altogether, this behavior is similar to the stereotypical behavior observed in animal models for psychiatric disease of autistic spectrum disorders which reflects a disrupted balance between glutamatergic and GABAergic synapses. These differences indicate an altered excitation/inhibition balance in neuronal circuits in PRG-1(-/-) mice as recently shown in the somatosensory cortex [38]. In contrast, PRG-1(-/-)/LPA2(-/-) did not show significant changes in behavior in the open field suggesting that these specific alterations were abolished when the LPA2-receptor was lacking. Our findings indicate that PRG-1 deficiency led to over-excitability caused by an altered LPA/LPA2-R signaling inducing a behavioral phenotype typically observed in animal models for psychiatric disorders. Copyright

  3. Altered nocifensive behavior in animal models of autism spectrum disorder: The role of the nicotinic cholinergic system.

    PubMed

    Wang, Li; Almeida, Luis E F; Nettleton, Margaret; Khaibullina, Alfia; Albani, Sarah; Kamimura, Sayuri; Nouraie, Mehdi; Quezado, Zenaide M N

    2016-12-01

    Caretakers and clinicians alike have long recognized that individuals with autism spectrum disorder (ASD) can have altered sensory processing, which can contribute to its core symptoms. However, the pathobiology of sensory alterations in ASD is poorly understood. Here we examined nocifensive behavior in ASD mouse models, the BTBR T(+)Itpr3(tf)/J (BTBR) and the fragile-X mental retardation-1 knockout (Fmr1-KO) mice. We also examined the effects of nicotine on nocifensive behavior given that nicotine, a nicotinic cholinergic receptor (nAChR) agonist that has antinociceptive effects, was shown to improve social deficits and decrease repetitive behaviors in BTBR mice. Compared to respective controls, both BTBR and Fmr1-KO had hyporesponsiveness to noxious thermal stimuli and electrical stimulation of C-sensory fibers, normal responsiveness to electrical stimulation of Aβ- and Aδ-fiber, and hyperresponsiveness to visceral pain after acetic acid intraperitoneal injection. In BTBR, nicotine at lower doses increased, whereas at higher doses, it decreased hotplate latency compared to vehicle. In a significantly different effect pattern, in control mice, nicotine had antinociceptive effects to noxious heat only at the high dose. Interestingly, these nocifensive behavior alterations and differential responses to nicotine antinociceptive effects in BTBR mice were associated with significant downregulation of α3, α4, α5, α7, β2, β3, and β4 nAChR subunits in several cerebral regions both, during embryonic development and adulthood. Taken together, these findings further implicate nAChRs in behaviors alterations in the BTBR model and lend support to the hypothesis that nAChRs may be a target for treatment of behavior deficits and sensory dysfunction in ASD.

  4. Phellinus baumii extract influences pathogenesis of Brucella abortus in phagocyte by disrupting the phagocytic and intracellular trafficking pathway.

    PubMed

    Lee, J J; Kim, D H; Kim, D G; Lee, H J; Min, W; Rhee, M H; Yun, B S; Kim, S

    2013-02-01

    To clarify the effects of Phellinus baumii ethanol extract (PBE) on Brucella abortus pathogenesis in phagocytes focusing on the phagocytic and intracellular trafficking pathway. The effects of PBE on Br. abortus infection in macrophages were evaluated through an adherence and infection assays and an analysis of LAMP-1 staining. The phosphorylation of ERK1/2 and the F-actin polymerization associated with PBE during Br. abortus uptake were detected by immunoblotting and FACS, respectively. The survival of Br. abortus in pure culture was remarkably reduced by PBE in a dose-dependent manner. PBE-treated cells showed significantly decreased uptake, intracellular replication and adherence of Br. abortus. The declines of ERK1/2 phosphorylation and F-actin polymerization following Br. abortus entry were apparent in PBE-treated cells compared with the control. Moreover, the co-localization of Br. abortus-containing phagosomes with LAMP-1 was elevated in PBE-treated cells compared with the control during intracellular trafficking. Phellinus baumii ethanol extract may possess the modulatory effect on pathogenesis of Br. abortus through disrupting the phagocytic and intracellular trafficking pathway in phagocyte. The potential modulation of PBE to Br. abortus pathogenesis could provide an alternative approach to control of brucellosis, contributing to attenuate Br. abortus manifestation in hosts. © 2012 The Society for Applied Microbiology.

  5. [Effect of general magnetotherapy on specific activity of blood phagocytes in patients with ischemic heart disease].

    PubMed

    Ishutin, I S; Klemenkov, S V; Lesovskaia, M I; Spiridonova, M S; Krotova, T K; Ishutin, E I; Tsyganova, O B

    2007-01-01

    In general magnetotherapy for patients with hyporeactive phagocytes (less than 67% from the level of normal chelicoluminescent response) the adequate level of magnetic induction is 1 mT, for patients with normoreactive phagocytes--0.5 mT and for patients with hyperreactive phagocytes (more than 133% from the level of normal chelicoluminescent response)--0.75 mT daily.

  6. Drosophila, Behavior & Gene Expression in Altered Gravity Conditions: Comparison between Space and Ground Facilities

    NASA Astrophysics Data System (ADS)

    Herranz, Raul; Lavan, David A.; Dijkstra, Camelia; Larkin, Oliver; Davey, Michael R.; van Loon, Jack J. W. A.; Medina, F. Javier; Marco, Roberto; Schiller, Peter

    2008-06-01

    Previous experiments in space (unmanned satellites, space shuttle and the International Space Station, ISS), have shown that adult Drosophila flies change their motile behaviour in microgravity. A consistent increase in motility in space was found in these experiments, but mature flies (two weeks old) showed less increase than recently hatched flies. In the case of relatively long exposure to microgravity, the aging of male flies measured upon return to Earth was increased, with flies dying earlier than the corresponding in-flight 1g centrifuge or ground controls. The older flies, which experienced a smaller increase in motility, did not show this acceleration in the aging process. More recently we have performed comparative experiments using ground simulation facilities. Preliminary experiments using a random positioning machine (RPM) indicate that the effects of this simulation approach on the behavior of Drosophila are of smaller magnitude than the corresponding exposure to real microgravity. Further experiments are in progress to confirm this effect. However, when exposed to magnetic levitation, flies exposed to simulated weightlessness increased markedly their motile behavior compared with 1g controls both inside and outside the magnet. This altered gravity-related increase in motility was also less pronounced in more mature flies. This motility effect at the levitation position reproduces the results in real microgravity indicating the interest for space science of this simulation approach. Similar experiments are being performed in the Larger Diameter Centrifuge (LDC) located in ESTEC (the Netherlands) and indicate that 6g, 12g and 20g are key points in the hypergravity response in flies. Our experiments have shown that developmental processes from embryo to adult proceeded normally in the magnet, the RPM and the LDC. In terms of gene expression, preliminary results indicate that the affected set of genes under hypergravity responds in general in an opposite

  7. Prenatal Exposure to Paint Thinner Alters Postnatal Development and Behavior in Mice

    PubMed Central

    Malloul, Hanaa; Mahdani, Ferdaousse M.; Bennis, Mohammed; Ba-M’hamed, Saadia

    2017-01-01

    prenatally treated offspring by 600 ppm of thinner. Based on these results, we can conclude that prenatally exposure to paint thinner causes a long-lasting developmental neurotoxicity and alters a wide range of behavioral functions in mice. This shows the risk that mothers who abuse thinner paint expose their offspring. PMID:28959195

  8. Relationship among Short and Long Term of Hypoinsulinemia-Hyperglycemia, Dermatophytosis, and Immunobiology of Mononuclear Phagocytes.

    PubMed

    Fraga-Silva, Thais F C; Marchetti, Camila M; Mimura, Luiza A N; Locachevic, Gisele A; Golim, Márjorie A; Venturini, James; Arruda, Maria S P

    2015-01-01

    Dermatophytes are fungi responsible for causing superficial infections. In patients with diabetes mellitus (DM), dermatophytosis is usually more severe and recurrent. In the present study, we aimed to investigate the influence of short and long term hypoinsulinemia-hyperglycemia (HH) during experimental infection by Trichophyton mentagrophytes as well as alterations in the mononuclear phagocytes. Our results showed two distinct profiles of fungal outcome and immune response. Short term HH induced a discrete impaired proinflammatory response by peritoneal adherent cells (PAC) and a delayed fungal clearance. Moreover, long term HH mice showed low and persistent fungal load and a marked reduction in the production of TNF-α by PAC. Furthermore, while the inoculation of TM in non-HH mice triggered high influx of Gr1(+) monocytes into the peripheral blood, long term HH mice showed low percentage of these cells. Thus, our results demonstrate that the time of exposure of HH interferes with the TM infection outcome as well as the immunobiology of mononuclear phagocytes, including fresh monocyte recruitment from bone marrow and PAC activity.

  9. Psychopathological alterations and neuroimaging findings with discriminant value in eating behavior disorders.

    PubMed

    Beato-Fernández, Luis; Rodríguez-Cano, Teresa; García-Vilches, Inmaculada

    2011-01-01

    The difficulties encountered in regards to defining the diagnosis of patients with an Eating Behavior Disorder (EBD) have favored the use of multidimensional models. This study has aimed to identify which psychopathological and neurobiological variables could have a discriminating capacity regarding the different EBD diagnostic subtypes. A total of 42 patients with an EBD diagnosis (11 Restrictive Anorexia (R-AN), 10 Purgative Anorexia (P-AN), 7 Non-purgative Bulimia (NP-BN), 14 Purgative Bulimia (P-BN)), according to DSM-IV criteria, were selected from those who came for treatment in the Ciudad Real General Hospital Eating Disorder Unit. Twelve healthy controls were also included. All of the subjects underwent a brain SPECT to measure regional cerebral blood flow (rCBF) in baseline situation (rest). A second one was performed after a visual neutral stimulus (sight of a calm sea) and another one after confronting them with their own corporal image, filmed two weeks before. A battery of questionnaires was administered to evaluate general and eating psychopathology. Patients with NP-BN showed less eating and general psychopathology. Furthermore, unlike patients with R-AN and P-BN, they did not experience an increase of the rCBF when confronted with their own body image. Discriminant variables were body dissatisfaction measured with the BSQ, BMI; BITE scores, ideal silhouette scores, and temporal right hyperactivation when they were shown their own body image. The subgroup of patients diagnosed with NP-BN showed less emotional alteration and less emotional response when they were shown their own body image than the rest of patients with EBD. These differences might have implications from the therapeutic, prognostic or even taxonomic viewpoint.

  10. Chronic Creatine Supplementation Alters Depression-like Behavior in Rodents in a Sex-Dependent Manner

    PubMed Central

    Allen, Patricia J; D'Anci, Kristen E; Kanarek, Robin B; Renshaw, Perry F

    2010-01-01

    Impairments in bioenergetic function, cellular resiliency, and structural plasticity are associated with the pathogenesis of mood disorders. Preliminary evidence suggests that creatine, an ergogenic compound known to promote cell survival and influence the production and usage of energy in the brain, can improve mood in treatment-resistant patients. This study examined the effects of chronic creatine supplementation using the forced swim test (FST), an animal model selectively sensitive to antidepressants with clinical efficacy in human beings. Thirty male (experiment 1) and 36 female (experiment 2) Sprague–Dawley rats were maintained on either chow alone or chow blended with either 2% w/w creatine monohydrate or 4% w/w creatine monohydrate for 5 weeks before the FST. Open field exploration and wire suspension tests were used to rule out general psychostimulant effects. Male rats maintained on 4% creatine displayed increased immobility in the FST as compared with controls with no differences by diet in the open field test, whereas female rats maintained on 4% creatine displayed decreased immobility in the FST and less anxiety in the open field test compared with controls. Open field and wire suspension tests confirmed that creatine supplementation did not produce differences in physical ability or motor function. The present findings suggest that creatine supplementation alters depression-like behavior in the FST in a sex-dependent manner in rodents, with female rats displaying an antidepressant-like response. Although the mechanisms of action are unclear, sex differences in creatine metabolism and the hormonal milieu are likely involved. PMID:19829292

  11. Polyunsaturated fatty acid supplementation during pregnancy alters neonatal behavior in sheep.

    PubMed

    Capper, Judith L; Wilkinson, Robert G; Mackenzie, Alexander M; Sinclair, Liam A

    2006-02-01

    The objectives of the study were to determine whether supplementation of pregnant ewes with long-chain (n-3) fatty acids present in fish oil, in combination with dietary vitamin E, would alter neonatal behavior in sheep. Twin- (n=36) and triplet- (n=12) bearing ewes were allocated at d 103 of gestation to 1 of 4 dietary treatments containing 1 of 2 fat sources [Megalac, a calcium soap of palm fatty acid distillate or a fish oil mixture, high in 20:5(n-3) and 22:6(n-3)] and 1 of 2 dietary vitamin E concentrations (50 or 500 mg/kg) in a 2 x 2 factorial design. Feeding fish oil increased gestation length by 2 d and increased the proportion of 22:6(n-3) within neonatal plasma by 5.1-fold and brain by 10%, whereas brain 20:5(n-3) was increased 5-fold. Supranutritional dietary vitamin E concentrations decreased the latency of lambs to stand in ewes fed fish oil but not Megalac, whereas latency to suckle was decreased from 43 to 34 min by fish oil supplementation. Supplementation with fish oil also substantially decreased the secretion rate (mL/h) of colostrum and the yield (g/h) of fat and protein. We conclude that supplementation of ewes with fish oil decreases the latency to suckle, increases gestation length and the 22:6(n-3):20:4(n-6) ratio in the neonatal brain, and may improve lamb survival rate. However, further work is required to determine how to mitigate the negative effects of fish oil on colostrum production.

  12. Dopamine D2 receptor over-expression alters behavior and physiology in Drd2-EGFP mice

    PubMed Central

    Kramer, Paul F.; Christensen, Christine H.; Hazelwood, Lisa A.; Dobi, Alice; Bock, Roland; Sibley, David R.; Mateo, Yolanda; Alvarez, Veronica A.

    2011-01-01

    BAC transgenic mice expressing the fluorescent reporter protein EGFP under the control of the D1 and D2 dopamine receptor promoters (Drd1-EGFP and Drd2-EGFP) have been widely used to study striatal function and have contributed to our understanding of the physiological and pathological function of the basal ganglia. These tools were produced and promptly made available to address questions in a cell-specific manner that has transformed the way we frame hypotheses in neuroscience. However, these mice have not been fully characterized until now. We found that Drd2-EGFP mice display a ~40% increase in membrane expression of the dopamine D2 receptor (D2R) and a two-fold increase in D2R mRNA levels in the striatum when compared to wild-type and Drd1-EGFP mice D2R over-expression was accompanied by behavioral hypersensitivity to D2R-like agonists, as well as enhanced electrophysiological responses to D2R activation in midbrain dopaminergic neurons. DA transients evoked by stimulation in the nucleus accumbens showed slower clearance in Drd2-EGFP mice and cocaine actions on DA clearance were impaired in these mice. Thus, it was not surprising to find that Drd2-EGFP mice were hyperactive when exposed to a novel environment and locomotion was suppressed by acute cocaine administration. All together, this study demonstrates that Drd2-EGFP mice over-express D2R and have altered dopaminergic signaling that fundamentally differentiates them from wild-type and Drd1-EGFP mice. PMID:21209197

  13. The Monomeric GTPase Rab35 Regulates Phagocytic Cup Formation and Phagosomal Maturation in Entamoeba histolytica.

    PubMed

    Verma, Kuldeep; Datta, Sunando

    2017-03-24

    One of the hallmarks of amoebic colitis is the detection of Entamoeba histolytica (Eh) trophozoites with ingested erythrocytes. Therefore, erythrophagocytosis is traditionally considered as one of the most important criteria to identify the pathogenic behavior of the amoebic trophozoites. Phagocytosis is an essential process for the proliferation and virulence of this parasite. Phagocytic cargo, upon internalization, follows a defined trafficking route to amoebic lysosomal degradation machinery. Here, we demonstrated the role of EhRab35 in the early and late phases of erythrophagocytosis by the amoeba. EhRab35 showed large vacuolar as well as punctate vesicular localization. The spatiotemporal dynamics of vacuolar EhRab35 and its exchange with soluble cytosolic pool were monitored by fluorescence recovery after photobleaching experiments. Using extensive microscopy and biochemical methods, we demonstrated that upon incubation with RBCs EhRab35 is recruited to the site of phagocytic cups as well as to the nascent phagosomes that harbor Gal/GalNAc lectin and actin. Overexpression of a dominant negative mutant of EhRab35 reduced phagocytic cup formation and thereby reduced RBC internalization, suggesting a potential role of the Rab GTPase in the cup formation. Furthermore, we also performed a phagosomal maturation assay and observed that the activated form of EhRab35 significantly increased the rate of RBC degradation. Interestingly, this mutant also significantly enhanced the number of acidic compartments in the trophozoites. Taken together, our results suggest that EhRab35 is involved in the initial stage of phagocytosis as well as in the phagolysosomal biogenesis in E. histolytica and thus contributes to the pathogenicity of the parasite. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Social Isolation Alters Social and Mating Behavior in the R451C Neuroligin Mouse Model of Autism

    PubMed Central

    Eastwood, A. F.; May, C.; Hill, T.; McLachlan, N. M.; Churilov, L.

    2017-01-01

    Autism spectrum disorder (ASD) is a neurodevelopmental disorder typified by impaired social communication and restrictive and repetitive behaviors. Mice serve as an ideal candidate organism for studying the neural mechanisms that subserve these symptoms. The Neuroligin-3 (NL3) mouse, expressing a R451C mutation discovered in two Swedish brothers with ASD, exhibits impaired social interactions and heightened aggressive behavior towards male mice. Social interactions with female mice have not been characterized and in the present study were assessed in male NL3R451C and WT mice. Mice were housed in social and isolation conditions to test for isolation-induced increases in social interaction. Tests were repeated to investigate potential differences in interaction in naïve and experienced mice. We identified heightened interest in mating and atypical aggressive behavior in NL3R451C mice. NL3R451C mice exhibited normal social interaction with WT females, indicating that abnormal aggressive behavior towards females is not due to altered motivation to engage. Social isolation rearing heightened interest in social behavior in all mice. Isolation housing selectively modulated the response to female pheromones in NL3R451C mice. This study is the first to show altered mating behavior in the NL3R451C mouse and has provided new insights into the aggressive phenotype in this model. PMID:28255463

  15. Experimental investigation of fatigue behavior of spur gear in altered tooth-sum gearing

    NASA Astrophysics Data System (ADS)

    Sachidananda, H. K.; Gonsalvis, Joseph; Prakash, H. R.

    2012-09-01

    This paper deals with the contact stress, power loss, and pitting of spur gear tooth in altered tooth-sum gearing for a tooth-sum of 100 teeth when altered by ±4% tooth-sum. Analytical and experimental methods were performed to investigate and compare the altered tooth-sum gearing against the standard tooth-sum gearing. The experiments were performed using a power recirculating type test rig. The tooth loads for the experimental investigations were determined considering the surface durability of gears. A clear picture of the surface damage was obtained using a scanning electron microphotograph. The negative alteration in the tooth-sum performed better than the positive alteration in a tooth-sum operating between specified center distances.

  16. Metabolic changes and DNA hypomethylation in cerebellum are associated with behavioral alterations in mice exposed to trichloroethylene postnatally

    SciTech Connect

    Blossom, Sarah J.; Cooney, Craig A.; Melnyk, Stepan B.; Rau, Jenny L.; Swearingen, Christopher J.; Wessinger, William D.

    2013-06-15

    Previous studies demonstrated that low-level postnatal and early life exposure to the environmental contaminant, trichloroethylene (TCE), in the drinking water of MRL +/+ mice altered glutathione redox homeostasis and increased biomarkers of oxidative stress indicating a more oxidized state. Plasma metabolites along the interrelated transmethylation pathway were also altered indicating impaired methylation capacity. Here we extend these findings to further characterize the impact of TCE exposure in mice exposed to water only or two doses of TCE in the drinking water (0, 2, and 28 mg/kg/day) postnatally from birth until 6 weeks of age on redox homeostasis and biomarkers of oxidative stress in the cerebellum. In addition, pathway intermediates involved in methyl metabolism and global DNA methylation patterns were examined in cerebellar tissue. Because the cerebellum is functionally important for coordinating motor activity, including exploratory and social approach behaviors, these parameters were evaluated in the present study. Mice exposed to 28 mg/kg/day TCE exhibited increased locomotor activity over time as compared with control mice. In the novel object exploration test, these mice were more likely to enter the zone with the novel object as compared to control mice. Similar results were obtained in a second test when an unfamiliar mouse was introduced into the testing arena. The results show for the first time that postnatal exposure to TCE causes key metabolic changes in the cerebellum that may contribute to global DNA methylation deficits and behavioral alterations in TCE-exposed mice. - Highlights: • We exposed male mice to low-level trichloroethylene from postnatal days 1 through 42. • This exposure altered redox potential and increased oxidative stress in cerebellum. • This exposure altered metabolites important in cellular methylation in cerebellum. • This exposure promoted DNA hypomethylation in cerebellum. • This exposure enhanced locomotor

  17. Study of neurometabolic and behavioral alterations in rodent model of mild traumatic brain injury: a pilot study.

    PubMed

    Singh, Kavita; Trivedi, Richa; Haridas, Seenu; Manda, Kailash; Khushu, Subash

    2016-12-01

    Mild traumatic brain injury (mTBI) is the most common form of TBI (70-90%) with consequences of anxiety-like behavioral alterations in approximately 23% of mTBI cases. This study aimed to assess whether mTBI-induced anxiety-like behavior is a consequence of neurometabolic alterations. mTBI was induced using a weight drop model to simulate mild human brain injury in rodents. Based on injury induction and dosage of anesthesia, four animal groups were included in this study: (i) injury with anesthesia (IA); (ii) sham1 (injury only, IO); (iii) sham2 (only anesthesia, OA); and (iv) control rats. After mTBI, proton magnetic resonance spectroscopy ((1) H-MRS) and neurobehavioral analysis were performed in these groups. At day 5, reduced taurine (Tau)/total creatine (tCr, creatine and phosphocreatine) levels in cortex were observed in the IA and IO groups relative to the control. These groups showed mTBI-induced anxiety-like behavior with normal cognition at day 5 post-injury. An anxiogenic effect of repeated dosage of anesthesia in OA rats was observed with normal Tau/tCr levels in rat cortex, which requires further examination. In conclusion, this mTBI model closely mimics human concussion injury with anxiety-like behavior and normal cognition. Reduced cortical Tau levels may provide a putative neurometabolic basis of anxiety-like behavior following mTBI.

  18. Exposure to seismic air gun signals causes physiological harm and alters behavior in the scallop Pecten fumatus.

    PubMed

    Day, Ryan D; McCauley, Robert D; Fitzgibbon, Quinn P; Hartmann, Klaas; Semmens, Jayson M

    2017-09-18

    Seismic surveys map the seabed using intense, low-frequency sound signals that penetrate kilometers into the Earth's crust. Little is known regarding how invertebrates, including economically and ecologically important bivalves, are affected by exposure to seismic signals. In a series of field-based experiments, we investigate the impact of exposure to seismic surveys on scallops, using measurements of physiological and behavioral parameters to determine whether exposure may cause mass mortality or result in other sublethal effects. Exposure to seismic signals was found to significantly increase mortality, particularly over a chronic (months postexposure) time scale, though not beyond naturally occurring rates of mortality. Exposure did not elicit energetically expensive behaviors, but scallops showed significant changes in behavioral patterns during exposure, through a reduction in classic behaviors and demonstration of a nonclassic "flinch" response to air gun signals. Furthermore, scallops showed persistent alterations in recessing reflex behavior following exposure, with the rate of recessing increasing with repeated exposure. Hemolymph (blood analog) physiology showed a compromised capacity for homeostasis and potential immunodeficiency, as a range of hemolymph biochemistry parameters were altered and the density of circulating hemocytes (blood cell analog) was significantly reduced, with effects observed over acute (hours to days) and chronic (months) scales. The size of the air gun had no effect, but repeated exposure intensified responses. We postulate that the observed impacts resulted from high seabed ground accelerations driven by the air gun signal. Given the scope of physiological disruption, we conclude that seismic exposure can harm scallops.

  19. Ameliorative potential of sodium cromoglycate and diethyldithiocarbamic acid in restraint stress-induced behavioral alterations in rats.

    PubMed

    Manchanda, Rajneet K; Jaggi, Amteshwar S; Singh, Nirmal

    2011-01-01

    The present study was designed to investigate the ameliorative effects of sodium cromoglycate and diethyldithiocarbamic acid in acute stress-induced behavioral alterations in rats subjected to restraint stress. The rats were placed in the restrainer (5.5 cm in diameter and 18 cm in length) for 3.5 h. Restraint stress-induced behavioral alterations were assessed using the hole-board, social interactions and open field tests. Restraint stress resulted in a decrease in the frequency of head dips, rearing in the hole board, line crossings and rearings in the open field, and an increase in avoidance behaviors in the social interaction tests. Sodium cromoglycate (25 mg/kg and 50 mg/kg, ip), a mast cell stabilizer, and diethyldithiocarbamic acid (75 mg/kg and 150 mg/kg, ip), a selective NF-κB inhibitor, were employed to modulate restraint stress-induced behavioral changes. The administration of sodium cromoglycate and diethyldithiocarbamic acid significantly attenuated the restraint stress-induced behavioral changes. The noted beneficial effects of sodium cromoglycate and diethyldithiocarbamic acid may possibly be attributed to mast cell stabilization and inhibition of NF-κB activity, respectively.

  20. Translational Rodent Paradigms to Investigate Neuromechanisms Underlying Behaviors Relevant to Amotivation and Altered Reward Processing in Schizophrenia

    PubMed Central

    Young, Jared W.; Markou, Athina

    2015-01-01

    Amotivation and reward-processing deficits have long been described in patients with schizophrenia and considered large contributors to patients’ inability to integrate well in society. No effective treatments exist for these symptoms, partly because the neuromechanisms mediating such symptoms are poorly understood. Here, we propose a translational neuroscientific approach that can be used to assess reward/motivational deficits related to the negative symptoms of schizophrenia using behavioral paradigms that can also be conducted in experimental animals. By designing and using objective laboratory behavioral tools that are parallel in their parameters in rodents and humans, the neuromechanisms underlying behaviors with relevance to these symptoms of schizophrenia can be investigated. We describe tasks that measure the motivation of rodents to expend physical and cognitive effort to gain rewards, as well as probabilistic learning tasks that assess both reward learning and feedback-based decision making. The latter tasks are relevant because of demonstrated links of performance deficits correlating with negative symptoms in patients with schizophrenia. These tasks utilize operant techniques in order to investigate neural circuits targeting a specific domain across species. These tasks therefore enable the development of insights into altered mechanisms leading to negative symptom-relevant behaviors in patients with schizophrenia. Such findings will then enable the development of targeted treatments for these altered neuromechanisms and behaviors seen in schizophrenia. PMID:26194891

  1. Sphingolipids as Regulators of the Phagocytic Response to Fungal Infections

    PubMed Central

    Bryan, Arielle M.; Del Poeta, Maurizio; Luberto, Chiara

    2015-01-01

    Fungal infections pose a significant risk for the increasing population of individuals who are immunocompromised. Phagocytes play an important role in immune defense against fungal pathogens, but the interactions between host and fungi are still not well understood. Sphingolipids have been shown to play an important role in many cell functions, including the function of phagocytes. In this review, we discuss major findings that relate to the importance of sphingolipids in macrophage and neutrophil function and the role of macrophages and neutrophils in the most common types of fungal infections, as well as studies that have linked these three concepts to show the importance of sphingolipid signaling in immune response to fungal infections. PMID:26688618

  2. Dancing cheek to cheek: Cryptococcus neoformans and phagocytes.

    PubMed

    Zhang, Mingshun; Sun, Donglei; Shi, Meiqing

    2015-01-01

    Meningoencephalitis caused by Cryptococcus neoformans (Cn) has become one of the leading causes of mortality in AIDS patients. Understanding the interactions between Cn and phagocytes is fundamental in exploring the pathogenicity of cryptococcal meningoencephalitis. Cn may be extracellular or contained in the monocytes, macrophages, neutrophils, dendritic cells and even endothelial cells. The internalized Cn may proliferate inside the host cells, or cause the lysis of host cells, or leave the host cells via non-lytic exocytosis, or even hijack the host cells (Trojan horse) for the brain dissemination, which are regulated by microbe factors and also immune molecules. Coexistence of protective and deleterious roles of phagocytes in the progression of cryptococcosis warrant further investigation.

  3. Flow Cytometric Analysis of Mononuclear Phagocytes in Nondiseased Human Lung and Lung-Draining Lymph Nodes

    PubMed Central

    Desch, A. Nicole; Gibbings, Sophie L.; Goyal, Rajni; Kolde, Raivo; Bednarek, Joe; Bruno, Tullia; Slansky, Jill E.; Jacobelli, Jordan; Mason, Robert; Ito, Yoko; Messier, Elise; Randolph, Gwendalyn J.; Prabagar, Miglena; Atif, Shaikh M.; Segura, Elodie; Xavier, Ramnik J.; Bratton, Donna L.; Janssen, William J.; Henson, Peter M.

    2016-01-01

    Rationale: The pulmonary mononuclear phagocyte system is a critical host defense mechanism composed of macrophages, monocytes, monocyte-derived cells, and dendritic cells. However, our current characterization of these cells is limited because it is derived largely from animal studies and analysis of human mononuclear phagocytes from blood and small tissue resections around tumors. Objectives: Phenotypic and morphologic characterization of mononuclear phagocytes that potentially access inhaled antigens in human lungs. Methods: We acquired and analyzed pulmonary mononuclear phagocytes from fully intact nondiseased human lungs (including the major blood vessels and draining lymph nodes) obtained en bloc from 72 individual donors. Differential labeling of hematopoietic cells via intrabronchial and intravenous administration of antibodies within the same lobe was used to identify extravascular tissue-resident mononuclear phagocytes and exclude cells within the vascular lumen. Multiparameter flow cytometry was used to identify mononuclear phagocyte populations among cells labeled by each route of antibody delivery. Measurements and Main Results: We performed a phenotypic analysis of pulmonary mononuclear phagocytes isolated from whole nondiseased human lungs and lung-draining lymph nodes. Five pulmonary mononuclear phagocytes were observed, including macrophages, monocyte-derived cells, and dendritic cells that were phenotypically distinct from cell populations found in blood. Conclusions: Different mononuclear phagocytes, particularly dendritic cells, were labeled by intravascular and intrabronchial antibody delivery, countering the notion that tissue and blood mononuclear phagocytes are equivalent systems. Phenotypic descriptions of the mononuclear phagocytes in nondiseased lungs provide a precedent for comparative studies in diseased lungs and potential targets for therapeutics. PMID:26551758

  4. URB597 reduces biochemical, behavioral and morphological alterations in two neurotoxic models in rats.

    PubMed

    Maya-López, Marisol; Ruiz-Contreras, Hipolito A; de Jesús Negrete-Ruíz, María; Martínez-Sánchez, Julián Elías; Benítez-Valenzuela, Juan; Colín-González, Ana Laura; Villeda-Hernández, Juana; Sánchez-Chapul, Laura; Parra-Cid, Carmen; Rangel-López, Edgar; Santamaría, Abel

    2017-04-01

    URB597 is a compound largely linked to the inhibition of fatty acid amide hydrolase (FAAH), an enzyme responsible for the metabolic degradation of the endocannabinoid anandamide (AEA). Despite this pharmacological property accounts for its modulatory profile demonstrated in some neurotoxic paradigms, the possible protective properties of this agent have been poorly investigated, and deserve exploration in different neurotoxic models. In this study, we explored the effects of URB597 on oxidative damage to lipids and other major endpoints of toxicity in two neurotoxic models in vivo in rats (the first one produced by the mitochondrial neurotoxin 3-nitropropionic acid [3-NP], and the other generated by the striatal injection of the pro-oxidant toxin 6-hydroxidopamine [6-OHDA]) in order to provide further supporting evidence of its modulatory profile. Male Wistar adult rats were treated for 5 or 7 consecutive days with URB597 (0.3mg/kg, i.p.) and simultaneously exposed to three injections of 3-NP (30mg/kg, i.p.) or a single intrastriatal infusion of 6-OHDA (0.02mg/2μl), respectively. Twenty four hours after all treatments were administered, lipid peroxidation was measured in the striatum of 3-NP-treated rats, and in the midbrain of 6-OHDA-treated rats. Motor skills and histological assessment in the striatum were also evaluated in 3-NP-treated rats 6 and 7days after the last drug administration, respectively; whereas apomorphine-induced circling behavior and tyrosine hydroxylase immunolocalization in the striatum and substantia nigra were investigated 21 and 22days after the last drug infusion, respectively. URB597 prevented the oxidative damage to lipids induced by 3-NP in the striatum, and this effect could account for the attenuation of motor deficits in this model. Attenuation of motor disturbances induced by URB597 in both models was associated with the morphological preservation of the striatum in the 3-NP model and the partial preservation of tyrosine

  5. Benefits of agomelatine in behavioral, neurochemical and blood brain barrier alterations in prenatal valproic acid induced autism spectrum disorder.

    PubMed

    Kumar, Hariom; Sharma, B M; Sharma, Bhupesh

    2015-12-01

    Valproic acid administration during gestational period causes behavior and biochemical deficits similar to those observed in humans with autism spectrum disorder. Although worldwide prevalence of autism spectrum disorder has been increased continuously, therapeutic agents to ameliorate the social impairment are very limited. The present study has been structured to investigate the therapeutic potential of melatonin receptor agonist, agomelatine in prenatal valproic acid (Pre-VPA) induced autism spectrum disorder in animals. Pre-VPA has produced reduction in social interaction (three chamber social behavior apparatus), spontaneous alteration (Y-Maze), exploratory activity (Hole board test), intestinal motility, serotonin levels (prefrontal cortex and ileum) and prefrontal cortex mitochondrial complex activity (complex I, II, IV). Furthermore, Pre-VPA has increased locomotor activity (actophotometer), anxiety, brain oxidative stress (thiobarbituric acid reactive species, glutathione, and catalase), nitrosative stress (nitrite/nitrate), inflammation (brain and ileum myeloperoxidase activity), calcium levels and blood brain barrier leakage in animals. Treatment with agomelatine has significantly attenuated Pre-VPA induced reduction in social interaction, spontaneous alteration, exploratory activity intestinal motility, serotonin levels and prefrontal cortex mitochondrial complex activity. Furthermore, agomelatine also attenuated Pre-VPA induced increase in locomotion, anxiety, brain oxidative stress, nitrosative stress, inflammation, calcium levels and blood brain barrier leakage. It is concluded that, Pre-VPA has induced autism spectrum disorder, which was attenuated by agomelatine. Agomelatine has shown ameliorative effect on behavioral, neurochemical and blood brain barrier alteration in Pre-VPA exposed animals. Thus melatonin receptor agonists may provide beneficial therapeutic strategy for managing autism spectrum disorder.

  6. Phagocyte-derived catecholamines enhance acute inflammatory injury.

    PubMed

    Flierl, Michael A; Rittirsch, Daniel; Nadeau, Brian A; Chen, Anthony J; Sarma, J Vidya; Zetoune, Firas S; McGuire, Stephanie R; List, Rachel P; Day, Danielle E; Hoesel, L Marco; Gao, Hongwei; Van Rooijen, Nico; Huber-Lang, Markus S; Neubig, Richard R; Ward, Peter A

    2007-10-11

    It is becoming increasingly clear that the autonomic nervous system and the immune system demonstrate cross-talk during inflammation by means of sympathetic and parasympathetic pathways. We investigated whether phagocytes are capable of de novo production of catecholamines, suggesting an autocrine/paracrine self-regulatory mechanism by catecholamines during inflammation, as has been described for lymphocytes. Here we show that exposure of phagocytes to lipopolysaccharide led to a release of catecholamines and an induction of catecholamine-generating and degrading enzymes, indicating the presence of the complete intracellular machinery for the generation, release and inactivation of catecholamines. To assess the importance of these findings in vivo, we chose two models of acute lung injury. Blockade of alpha2-adrenoreceptors or catecholamine-generating enzymes greatly suppressed lung inflammation, whereas the opposite was the case either for an alpha2-adrenoreceptor agonist or for inhibition of catecholamine-degrading enzymes. We were able to exclude T cells or sympathetic nerve endings as sources of the injury-modulating catecholamines. Our studies identify phagocytes as a new source of catecholamines, which enhance the inflammatory response.

  7. Fungal Invasion of Normally Non-Phagocytic Host Cells

    PubMed Central

    Filler, Scott G; Sheppard, Donald C

    2006-01-01

    Many fungi that cause invasive disease invade host epithelial cells during mucosal and respiratory infection, and subsequently invade endothelial cells during hematogenous infection. Most fungi invade these normally non-phagocytic host cells by inducing their own uptake. Candida albicans hyphae interact with endothelial cells in vitro by binding to N-cadherin on the endothelial cell surface. This binding induces rearrangement of endothelial cell microfilaments, which results in the endocytosis of the organism. The capsule of Cryptococcus neoformans is composed of glucuronoxylomannan, which binds specifically to brain endothelial cells, and appears to mediate both adherence and induction of endocytosis. The mechanisms by which other fungal pathogens induce their own uptake are largely unknown. Some angioinvasive fungi, such as Aspergillus species and the Zygomycetes, invade endothelial cells from the abluminal surface during the initiation of invasive disease, and subsequently invade the luminal surface of endothelial cells during hematogenous dissemination. Invasion of normally non-phagocytic host cells has different consequences, depending on the type of invading fungus. Aspergillus fumigatus blocks apoptosis of pulmonary epithelial cells, whereas Paracoccidioides brasiliensis induces apoptosis of epithelial cells. This review summarizes the mechanisms by which diverse fungal pathogens invade normally non-phagocytic host cells and discusses gaps in our knowledge that provide opportunities for future research. PMID:17196036

  8. Cooperation of Gastric Mononuclear Phagocytes with Helicobacter pylori during Colonization.

    PubMed

    Viladomiu, Monica; Bassaganya-Riera, Josep; Tubau-Juni, Nuria; Kronsteiner, Barbara; Leber, Andrew; Philipson, Casandra W; Zoccoli-Rodriguez, Victoria; Hontecillas, Raquel

    2017-03-06

    Helicobacter pylori, the dominant member of the human gastric microbiota, elicits immunoregulatory responses implicated in protective versus pathological outcomes. To evaluate the role of macrophages during infection, we employed a system with a shifted proinflammatory macrophage phenotype by deleting PPARγ in myeloid cells and found a 5- to 10-fold decrease in gastric bacterial loads. Higher levels of colonization in wild-type mice were associated with increased presence of mononuclear phagocytes and in particular with the accumulation of CD11b(+)F4/80(hi)CD64(+)CX3CR1(+) macrophages in the gastric lamina propria. Depletion of phagocytic cells by clodronate liposomes in wild-type mice resulted in a reduction of gastric H. pylori colonization compared with nontreated mice. PPARγ-deficient and macrophage-depleted mice presented decreased IL-10-mediated myeloid and T cell regulatory responses soon after infection. IL-10 neutralization during H. pylori infection led to increased IL-17-mediated responses and increased neutrophil accumulation at the gastric mucosa. In conclusion, we report the induction of IL-10-driven regulatory responses mediated by CD11b(+)F4/80(hi)CD64(+)CX3CR1(+) mononuclear phagocytes that contribute to maintaining high levels of H. pylori loads in the stomach by modulating effector T cell responses at the gastric mucosa.

  9. Degradation of biomaterials by phagocyte-derived oxidants.

    PubMed Central

    Sutherland, K; Mahoney, J R; Coury, A J; Eaton, J W

    1993-01-01

    Polymers used in implantable devices, although relatively unreactive, may degrade in vivo through unknown mechanisms. For example, polyetherurethane elastomers used as cardiac pacemaker lead insulation have developed surface defects after implantation. This phenomenon, termed "environmental stress cracking," requires intimate contact between polymer and host phagocytic cells, suggesting that phagocyte-generated oxidants might be involved. Indeed, brief exposure of polyetherurethane to activated human neutrophils, hypochlorous acid, or peroxynitrite produces modifications of the polymer similar to those found in vivo. Damage to the polymer appears to arise predominantly from oxidation of the urethane-aliphatic ester and aliphatic ether groups. There are substantial increases in the solid phase surface oxygen content of samples treated with hypochlorous acid, peroxynitrite or activated human neutrophils, resembling those observed in explanted polyetherurethane. Furthermore, both explanted and hypochlorous acid-treated polyetherurethane show marked reductions in polymer molecular weight. Interestingly, hypochlorous acid and peroxynitrite appear to attack polyetherurethane at different sites. Hypochlorous acid or activated neutrophils cause decreases in the urethane-aliphatic ester stretch peak relative to the aliphatic ether stretch peak (as determined by infrared spectroscopy) whereas peroxynitrite causes selective loss of the aliphatic ether. In vivo degradation may involve both hypohalous and nitric oxide-based oxidants because, after long-term implantation, both stretch peaks are diminished. These results suggest that in vivo destruction of implanted polyetherurethane involves attack by phagocyte-derived oxidants. Images PMID:8227352

  10. Fungal invasion of normally non-phagocytic host cells.

    PubMed

    Filler, Scott G; Sheppard, Donald C

    2006-12-01

    Many fungi that cause invasive disease invade host epithelial cells during mucosal and respiratory infection, and subsequently invade endothelial cells during hematogenous infection. Most fungi invade these normally non-phagocytic host cells by inducing their own uptake. Candida albicans hyphae interact with endothelial cells in vitro by binding to N-cadherin on the endothelial cell surface. This binding induces rearrangement of endothelial cell microfilaments, which results in the endocytosis of the organism. The capsule of Cryptococcus neoformans is composed of glucuronoxylomannan, which binds specifically to brain endothelial cells, and appears to mediate both adherence and induction of endocytosis. The mechanisms by which other fungal pathogens induce their own uptake are largely unknown. Some angioinvasive fungi, such as Aspergillus species and the Zygomycetes, invade endothelial cells from the abluminal surface during the initiation of invasive disease, and subsequently invade the luminal surface of endothelial cells during hematogenous dissemination. Invasion of normally non-phagocytic host cells has different consequences, depending on the type of invading fungus. Aspergillus fumigatus blocks apoptosis of pulmonary epithelial cells, whereas Paracoccidioides brasiliensis induces apoptosis of epithelial cells. This review summarizes the mechanisms by which diverse fungal pathogens invade normally non-phagocytic host cells and discusses gaps in our knowledge that provide opportunities for future research.

  11. Effects of polysaccharides from Silene vulgaris on phagocytes.

    PubMed

    Popov, S V; Popova, G Y; Ovodova, R G; Bushneva, O A; Ovodov, Y S

    1999-09-01

    The effects of the polysaccharides isolated from the intact plant (pectic polysaccharides P1, P2 and P3) and from the callus (acidic arabinogalactan C1 and pectin C2) of Silene vulgaris on phagocytic activity were studied in relation to an uptaking capacity and a myeloperoxidase activity of the peripheral human neutrophils and monocytes and rat peritoneal macrophages in vitro. Both intact plant and callus polysaccharides were shown to increase uptaking capacity of peripheral phagocytes. The callus acidic arabinogalactan C1 was only found to stimulate lysosomal activity of the peripheral phagocytes. Some polysaccharides studied were established to effect on peritoneal resident macrophages. Pectins P1, P3 and C2 failed to enhance myeloperoxidase activity of the macrophages in calcium-free solution, whereas the effect of callus arabinogalactan C1 was established to be independent of extracellular calcium. Polysaccharides studied failed to influence neither complement receptor CR3- nor scavenger receptor SR-mediated adhesion of the macrophages. The data obtained demonstrate that the intact S. vulgaris and its callus may be used as sources of immunoactive polysaccharides and that pectins and weakly acidic arabinogalactan seemed to stimulate macrophages through different mechanisms. Complement receptor type 3 and scavenger receptor failed to mediate the cell activation induced by plant polysaccharides.

  12. Embryonic intraventricular exposure to autism-specific maternal autoantibodies produces alterations in autistic-like stereotypical behaviors in offspring mice.

    PubMed

    Camacho, Jasmin; Jones, Karen; Miller, Elaine; Ariza, Jeanelle; Noctor, Stephen; de Water, Judy Van; Martínez-Cerdeño, Verónica

    2014-06-01

    Multiple studies have implicated a role of maternal autoantibodies reactive against fetal brain proteins specific to autism in the etiology of autism spectrum disorders (ASD). In the current study, we examined the impact of brain-reactive maternal autoantibodies of mothers of children with autism (MAU) on offspring behavior in mice compared to offspring exposed to non-reactive IgG of mothers of typically developing children (MTD). Embryonic offspring were exposed to a single intraventricular injection of MAU or MTD IgG on embryonic day 14. Offspring were allowed to mature to adulthood and were subsequently tested for sociability and stereotypic behaviors using a 3-chambered social approach task, marble burying task, and assessment of spontaneous grooming behaviors in response to a novel environment. Results indicate that MAU offspring display autistic-like stereotypical behavior in both marble burying and spontaneous grooming behaviors. Additionally, small alterations in social approach behavior were also observed in MAU offspring compared to MTD offspring. This report demonstrates for the first time the effects of a single, low dose intraventricular exposure of IgG derived from individual MAU samples on offspring behavior. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Mononuclear Phagocytes Are Dispensable for Cardiac Remodeling in Established Pressure-Overload Heart Failure

    PubMed Central

    Patel, Bindiya; Ismahil, Mohamed Ameen; Hamid, Tariq; Bansal, Shyam S.; Prabhu, Sumanth D.

    2017-01-01

    Background Although cardiac and splenic mononuclear phagocytes (MPs), i.e., monocytes, macrophages and dendritic cells (DCs), are key contributors to cardiac remodeling after myocardial infarction, their role in pressure-overload remodeling is unclear. We tested the hypothesis that these immune cells are required for the progression of remodeling in pressure-overload heart failure (HF), and that MP depletion would ameliorate remodeling. Methods and Results C57BL/6 mice were subjected to transverse aortic constriction (TAC) or sham operation, and assessed for alterations in MPs. As compared with sham, TAC mice exhibited expansion of circulating LyC6hi monocytes and pro-inflammatory CD206− cardiac macrophages early (1 w) after pressure-overload, prior to significant hypertrophy and systolic dysfunction, with subsequent resolution during chronic HF. In contrast, classical DCs were expanded in the heart in a biphasic manner, with peaks both early, analogous to macrophages, and late (8 w), during established HF. There was no significant expansion of circulating DCs, or Ly6C+ monocytes and DCs in the spleen. Periodic systemic MP depletion from 2 to 16 w after TAC in macrophage Fas-induced apoptosis (MaFIA) transgenic mice did not alter cardiac remodeling progression, nor did splenectomy in mice with established HF after TAC. Lastly, adoptive transfer of splenocytes from TAC HF mice into naïve recipients did not induce immediate or long-term cardiac dysfunction in recipient mice. Conclusions Mononuclear phagocytes populations expand in a phasic manner in the heart during pressure-overload. However, they are dispensable for the progression of remodeling and failure once significant hypertrophy is evident and blood monocytosis has normalized. PMID:28125666

  14. Mononuclear Phagocytes Are Dispensable for Cardiac Remodeling in Established Pressure-Overload Heart Failure.

    PubMed

    Patel, Bindiya; Ismahil, Mohamed Ameen; Hamid, Tariq; Bansal, Shyam S; Prabhu, Sumanth D

    2017-01-01

    Although cardiac and splenic mononuclear phagocytes (MPs), i.e., monocytes, macrophages and dendritic cells (DCs), are key contributors to cardiac remodeling after myocardial infarction, their role in pressure-overload remodeling is unclear. We tested the hypothesis that these immune cells are required for the progression of remodeling in pressure-overload heart failure (HF), and that MP depletion would ameliorate remodeling. C57BL/6 mice were subjected to transverse aortic constriction (TAC) or sham operation, and assessed for alterations in MPs. As compared with sham, TAC mice exhibited expansion of circulating LyC6hi monocytes and pro-inflammatory CD206- cardiac macrophages early (1 w) after pressure-overload, prior to significant hypertrophy and systolic dysfunction, with subsequent resolution during chronic HF. In contrast, classical DCs were expanded in the heart in a biphasic manner, with peaks both early, analogous to macrophages, and late (8 w), during established HF. There was no significant expansion of circulating DCs, or Ly6C+ monocytes and DCs in the spleen. Periodic systemic MP depletion from 2 to 16 w after TAC in macrophage Fas-induced apoptosis (MaFIA) transgenic mice did not alter cardiac remodeling progression, nor did splenectomy in mice with established HF after TAC. Lastly, adoptive transfer of splenocytes from TAC HF mice into naïve recipients did not induce immediate or long-term cardiac dysfunction in recipient mice. Mononuclear phagocytes populations expand in a phasic manner in the heart during pressure-overload. However, they are dispensable for the progression of remodeling and failure once significant hypertrophy is evident and blood monocytosis has normalized.

  15. Acute exposure to 17α-ethinylestradiol alters boldness behavioral syndrome in female Siamese fighting fish.

    PubMed

    Dzieweczynski, Teresa L; Campbell, Brennah A; Marks, Jodi M; Logan, Brittney

    2014-09-01

    The role of anthropogenic sources in generating, maintaining, and influencing behavioral syndromes has recently been identified as an important area of future research. Endocrine disrupting chemicals are prevalent and persistent in aquatic ecosystems worldwide. These chemicals are known to have marked effects on the morphology and behavior of exposed individuals and, as such, may serve as a potential influence on behavioral syndromes. However, both the effects of exposure on behaviors beyond courtship and aggression and how exposure might affect behavioral variation at the individual level are understudied. To address this question, we examined boldness behavior in female Siamese fighting fish in three different assays (Novel Environment, Empty Tank, Shoaling) both before and after they were exposed to the estrogen mimic, 17α-ethinylestradiol (EE2). EE2 influences courtship, aggression, and boldness in males of this species but its effects have not been examined in females, to our knowledge. Females were tested multiple times in each assay before and after exposure so that behavioral consistency could be examined. A behavioral syndrome for boldness and activity level occurred across the three assays. The reductions in boldness and loss of the behavioral syndrome that resulted from EE2 exposure were surprising and suggest that the effects of EE2 exposure on female behavior and physiology should be examined more frequently. This study is one of the first to examine the effects of EE2 in females as well as on correlated behaviors and emphasizes the importance of examining the effects of endocrine disrupting chemicals on individual behavioral variation and consistency. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Estrous phase alters social behavior in a polygynous but not a monogamous Peromyscus species.

    PubMed

    Karelina, Kate; Walton, James C; Weil, Zachary M; Norman, Greg J; Nelson, Randy J; Devries, A Courtney

    2010-07-01

    The social organization of rodent species determines behavioral patterns for both affiliative and agonistic encounters. The neuropeptide oxytocin has been implicated in the mediation of social behavior; however, variability in both neuropeptide expression and social behavior within a single species indicates an additional mediating factor. The purpose of the present comparative study was to investigate social behaviors in naïve mixed-sex pairs of monogamous Peromyscus californicus and polygynous Peromyscus leucopus. We identified substantial inter- and intra-specific variability in the expression of affiliative and agonistic behaviors. Although all P. californicus tested engaged in frequent and prolonged intervals of social contact and rarely engaged in aggressive behaviors, P. leucopus exhibited significant variability in both measures of social behaviors. The naturally occurring differences in social behavior displayed by P. leucopus vary across the estrous cycle, and correspond to hypothalamic oxytocin, as well as circulating oxytocin and glucocorticoid concentrations. These results provide evidence for a rhythm in social behavior across the estrous cycle in polygynous, but not monogamous, Peromyscus species. Copyright 2010 Elsevier Inc. All rights reserved.

  17. Acute Exposure to Fluoxetine Alters Aggressive Behavior of Zebrafish and Expression of Genes Involved in Serotonergic System Regulation

    PubMed Central

    Theodoridi, Antonia; Tsalafouta, Aleka; Pavlidis, Michail

    2017-01-01

    Zebrafish, Danio rerio, is an emerging model organism in stress and neurobehavioral studies. In nature, the species forms shoals, yet when kept in pairs it exhibits an agonistic and anxiety-like behavior that leads to the establishment of dominant-subordinate relationships. Fluoxetine, a selective serotonin reuptake inhibitor, is used as an anxiolytic tool to alter aggressive behavior in several vertebrates and as an antidepressant drug in humans. Pairs of male zebrafish were held overnight to develop dominant—subordinate behavior, either treated or non-treated for 2 h with fluoxetine (5 mg L−1), and allowed to interact once more for 1 h. Behavior was recorded both prior and after fluoxetine administration. At the end of the experiment, trunk and brain samples were also taken for cortisol determination and mRNA expression studies, respectively. Fluoxetine treatment significantly affected zebrafish behavior and the expression levels of several genes, by decreasing offensive aggression in dominants and by eliminating freezing in the subordinates. There was no statistically significant difference in whole-trunk cortisol concentrations between dominant and subordinate fish, while fluoxetine treatment resulted in higher (P = 0.004) cortisol concentrations in both groups. There were statistically significant differences between dominant and subordinate fish in brain mRNA expression levels of genes involved in stress axis (gr, mr), neural activity (bdnf, c-fos), and the serotonergic system (htr2b, slc6a4b). The significant decrease in the offensive and defensive aggression following fluoxetine treatment was concomitant with a reversed pattern in c-fos expression levels. Overall, an acute administration of a selective serotonin reuptake inhibitor alters aggressive behavior in male zebrafish in association with changes in the neuroendocrine mediators of coping styles. PMID:28487628

  18. Exposure to a low dose of bisphenol A during fetal life or in adulthood alters maternal behavior in mice.

    PubMed Central

    Palanza, Paola L; Howdeshell, Kembra L; Parmigiani, Stefano; vom Saal, Frederick S

    2002-01-01

    Maternal behavior in mammals is the result of a complex interaction between the lactating dam and her developing offspring. Slight perturbations of any of the components of the mother-infant interaction may result in alterations of the behavior of the mother and/or of the offspring. We studied the effects of exposure of female CD-1 mice to the estrogenic chemical bisphenol A (BPA) during fetal life and/or in adulthood during the last part of pregnancy on subsequent maternal behavior. Pregnant females were fed daily doses of corn oil (controls) or 10 microg/kg body weight BPA during gestation days 14-18. As adults, the prenatally treated female offspring were time-mated and again fed either corn oil (controls) or the same doses of BPA on gestation days 14-18, resulting in four treatment groups: controls, prenatal BPA exposure, adult BPA exposure, and both prenatal and adult BPA exposure. Maternal behavior was then observed on postnatal days 2-15 and reflex responses were examined in the offspring. Dams exposed to BPA either as fetuses or in adulthood spent less time nursing their pups and more time out of the nest compared with the control group. Females exposed to BPA both as fetuses and in adulthood did not significantly differ from controls. No alterations in postnatal reflex development were observed in the offspring of the females exposed to BPA. The changes seen in maternal behavior may be the result of a direct effect of BPA on the neuroendocrine substrates underlying the initiation of maternal behavior. PMID:12060838

  19. Dietary exposure to technical hexabromocyclododecane (HBCD) alters courtship, incubation and parental behaviors in American kestrels (Falco sparverius).

    PubMed

    Marteinson, Sarah C; Bird, David M; Letcher, Robert J; Sullivan, Katrina M; Ritchie, Ian J; Fernie, Kim J

    2012-11-01

    Hexabromocyclododecane (HBCD) is a high production volume brominated flame retardant that has been detected in the environment and wildlife at increasing concentrations. This study was designed to determine potential effects of dietary exposure to environmentally relevant levels of HBCD on behavior during reproduction in captive American kestrels. Twenty kestrel pairs were exposed to 0.51 μg technical HBCD g(-1) kestrel d(-1) from 4 weeks prior to pairing until chicks hatched (~75 d). Ten pairs of controls received the safflower oil vehicle only and were used for comparison. During the courtship period the chitter-calls were reduced in both sexes (p=0.038) and females performed fewer bonding displays (p=0.053). Both sexes showed a propensity to be less active than controls during courtship. The reduction in male courtship behavior was correlated with reduced courtship behaviors of females (p=0.008) as well as reduced egg mass (p=0.019). During incubation, nest temperatures of treatment pairs were lower at mid-incubation (p=0.038). HBCD-exposed males performed fewer key parental behaviors when rearing nestlings, including entering the nest-box, pair-bonding displays and food-retrievals. HBCD-exposed females appeared to compensate for the reduced parental behavior of their mates by performing these same behaviors more frequently than controls (p=0.004, p=0.027, p=0.025, respectively). This study demonstrates that HBCD affects breeding behavior in American kestrels throughout the reproductive season and behavioral alterations were linked to reproductive changes (egg size). This is the first study to report HBCD effects on reproductive behavior in any animal model.

  20. Post-weaning living with parents during juvenile period alters locomotor activity, social and parental behaviors in mandarin voles.

    PubMed

    Wu, Ruiyong; Song, Zhenzhen; Tai, Fadao; Wang, Lu; Kong, Lingzhe; Wang, Jianli

    2013-09-01

    Neonatal parental care plays an important role in the development of offspring behavior, but little is known about the effect of post-weaning contact between offspring and parents on locomotory, social and parental behavior. Here, we explore this concept using socially monogamous mandarin voles (Microtus mandarinus). Voles were assigned to live with parents and siblings from the same litter until 45d (natural dispersal time in the field) or to live with siblings from the same litter after weaning at 21d (normally weaned time, the control). At 70d of age, behaviors were recorded in open field and social interaction tests, and parental care toward their own offspring was measured. Results show that voles that live with parents post-weaning engaged in less locomotory activity and rearing behavior in the open field test, less sniffing of novel individuals and displayed more parental care, compared to voles that did not continue to live with their parents. These findings demonstrate that parent-offspring interaction post-weaning alters locomotory activity, social behavior and parental behavior of offspring at adulthood.

  1. Long-term Ovariectomy Alters Social and Anxious Behaviors in Semi-free Ranging Japanese Macaques

    PubMed Central

    Coleman, Kris; Robertson, Nicola D; Bethea, Cynthia L.

    2011-01-01

    Symptoms of anxiety and depression often occur in young women after complete hysterectomy and in older women during menopause. There are many variables that are hard to control in human population studies, but that are absent to a large extent in stable nonhuman primate troops. However, macaques exhibit depressive and anxious behaviors in response to similar situations as humans such as isolation, stress, instability or aggression. Therefore, we hypothesized that examination of behavior in ovariectomized individuals in a stable macaque troop organized along matriarchal lineages and in which individuals have social support from extended family, would reveal effects that were due to the withdrawal of ovarian steroids without many of the confounds of human society. We also tested the hypothesis that ovariectomy would elicit and increase anxious behavior in a stressful situation such as brief exposure to single caging. Japanese macaques (Macaca fuscata) were ovariectomized (Ovx) or tubal-ligated (intact controls) at 3 years of age and allowed to mature for 3 years in a stable troop of approximately 300 individuals. Behaviors were recorded in the outdoor corral in the third year followed by individual temperament tests in single cages. There was no obvious difference in anxiety-related behaviors such as scratching between Ovx and tubal-ligated animals in the corral. Nonetheless, compared to tubal-ligated animals, Ovx animals exhibited a significant decrease in (1) positive social behavior, (2) initiating dominance behavior (3) time receiving grooming, (4) locomoting, (5) mounting behavior, and in (6) consort behavior. However, Ovx females exhibited a significant increase in (1) consummatory behavior and (2) object play compared to tubal-ligated controls. In the individual temperament tests, Ovx individuals exhibited an increase in anxiety-related behaviors. There was no difference in adrenal weight/body weight suggesting that neither group was under chronic stress

  2. The amelioration of phagocytic ability in microglial cells by curcumin through the inhibition of EMF-induced pro-inflammatory responses

    PubMed Central

    2014-01-01

    Background Insufficient clearance by microglial cells, prevalent in several neurological conditions and diseases, is intricately intertwined with MFG-E8 expression and inflammatory responses. Electromagnetic field (EMF) exposure can elicit the pro-inflammatory activation and may also trigger an alteration of the clearance function in microglial cells. Curcumin has important roles in the anti-inflammatory and phagocytic process. Here, we evaluated the ability of curcumin to ameliorate the phagocytic ability of EMF-exposed microglial cells (N9 cells) and documented relative pathways. Methods N9 cells were pretreated with or without recombinant murine MFG-E8 (rmMFG-E8), curcumin and an antibody of toll-like receptor 4 (anti-TLR4), and subsequently treated with EMF or a sham exposure. Their phagocytic ability was evaluated using phosphatidylserine-containing fluorescent bioparticles. The pro-inflammatory activation of microglia was assessed via CD11b immunoreactivity and the production of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and nitric oxide (NO) via the enzyme-linked immunosorbent assay or the Griess test. We evaluated the ability of curcumin to ameliorate the phagocytic ability of EMF-exposed N9 cells, including checking the expression of MFG-E8, αvβ3 integrin, TLR4, nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) using Western blotting. Results EMF exposure dramatically enhanced the expression of CD11b and depressed the phagocytic ability of N9 cells. rmMFG-E8 could clearly ameliorate the phagocytic ability of N9 cells after EMF exposure. We also found that EMF exposure significantly increased the secretion of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β) and the production of NO; however, these increases were efficiently chilled by the addition of curcumin to the culture medium. This reduction led to the amelioration of the phagocytic ability of EMF-exposed N9 cells

  3. Chronic fluoxetine treatment induces anxiolytic responses and altered social behaviors in medaka, Oryzias latipes.

    PubMed

    Ansai, Satoshi; Hosokawa, Hiroshi; Maegawa, Shingo; Kinoshita, Masato

    2016-04-15

    Medaka (Oryzias latipes) is a small freshwater teleost that is an emerging model system for neurobehavioral research and toxicological testing. The selective serotonin reuptake inhibitor class of antidepressants such as fluoxetine is one of the widely prescribed drugs, but little is known about the effects of these drugs on medaka behaviors. To assess the behavioral effects of fluoxetine, we chronically administrated fluoxetine to medaka adult fish and analyzed the anxiety-related and social behaviors using five behavioral paradigms (diving, open-field, light-dark transition, mirror-biting, and social interaction) with an automated behavioral testing system. Fish chronically treated with fluoxetine exhibited anxiolytic responses such as an overall increased time spent in the top area in the diving test and an increased time spent in center area in the open-field test. Analysis of socially evoked behavior showed that chronic fluoxetine administration decreased the number of mirror biting times in the mirror-biting test and increased latency to first contact in the social interaction test. Additionally, chronic fluoxetine administration reduced the horizontal locomotor activity in the open-field test but not the vertical activity in the diving test. These investigations are mostly consistent with previous reports in the other teleost species and rodent models. These results indicate that behavioral assessment in medaka adult fish will become useful for screening of effects of pharmaceutical and toxicological compounds in animal behaviors.

  4. Group size alters postures, and maintenance, oral, locomotor and social behaviors of veal calves

    USDA-ARS?s Scientific Manuscript database

    The objective of this study was to evaluate the effect of group size on behavior of veal calves. Holstein-Friesian bull calves (n = 168; 44 ± 3 d of age), were randomly assigned to 1 of 3 treatments of group housing with 2, 4, or 8 calves per pen (1.82 m2 per calf for all groups). Behavior was obser...

  5. Metabolic changes and DNA hypomethylation in cerebellum are associated with behavioral alterations in mice exposed to trichloroethylene postnatally

    PubMed Central

    Blossom, Sarah J.; Cooney, Craig A.; Melnyk, Stepan B.; Rau, Jenny L.; Swearingen, Christopher J.; Wessinger, William D.

    2013-01-01

    Previous studies demonstrated that low-level postnatal and early life exposure to the environmental contaminant, trichloroethylene (TCE), in the drinking water of MRL+/+ mice altered glutathione redox homeostasis and increased biomarkers of oxidative stress indicating a more oxidized state. Plasma metabolites along the interrelated transmethylation pathway were also altered indicating impaired methylation capacity. Here we extend these findings to further characterize the impact of TCE exposure in mice exposed to water only or two doses of TCE in the drinking water (0, 2, and 28 mg/kg/day) postnatally from birth until 6 weeks of age on redox homeostasis and biomarkers of oxidative stress in the cerebellum. In addition, pathway intermediates involved in methyl metabolism and global DNA methylation patterns were examined in cerebellar tissue. Because the cerebellum is functionally important for coordinating motor activity, including exploratory and social approach behaviors, these parameters were evaluated in the present study. Mice exposed to 28 mg/kg/day TCE exhibited increased locomotor activity over time as compared with control mice. In the novel object exploration test, these mice were more likely to enter the zone with the novel object as compared to control mice Similar results were obtained in a second test when an unfamiliar mouse was introduced into the testing arena. The results show for the first time that postnatal exposure to TCE causes key metabolic changes in the cerebellum that may contribute to global DNA methylation deficits and behavioral alterations in TCE-exposed mice. PMID:23566951

  6. Binge cocaine administration in adolescent rats affects amygdalar gene expression patterns and alters anxiety-related behavior in adulthood

    PubMed Central

    Sillivan, Stephanie E.; Black, Yolanda D.; Naydenov, Alipi V.; Vassoler, Fair R.; Hanlin, Ryan P.; Konradi, Christine

    2011-01-01

    Background Administration of cocaine during adolescence alters neurotransmission and behavioral sensitization in adulthood, but its effect on the acquisition of fear memories and the development of emotion-based neuronal circuits is unknown. Methods We examined fear learning and anxiety-related behaviors in adult male rats that were subjected to binge cocaine treatment during adolescence. We furthermore conducted gene expression analyses of the amygdala 22 hours after the last cocaine injection to identify molecular patterns that might lead to altered emotional processing. Results Rats injected with cocaine during adolescence displayed less anxiety in adulthood than their vehicle-injected counterparts. In addition, cocaine-exposed animals were deficient in their ability to develop contextual fear responses. Cocaine administration caused transient gene expression changes in the Wnt signaling pathway, of axon guidance molecules, and of synaptic proteins, suggesting that cocaine perturbs dendritic structures and synapses in the amygdala. Phosphorylation of glycogen synthase kinase 3 beta, a kinase in the Wnt signaling pathway, was altered immediately following the binge cocaine paradigm and returned to normal levels 22 hours after the last cocaine injection. Conclusion Cocaine exposure during adolescence leads to molecular changes in the amygdala and decreases fear learning and fear responses in adulthood. PMID:21571252

  7. Knockdown of RhoA expression alters ovarian cancer biological behavior in vitro and in nude mice.

    PubMed

    Wang, Xiaoxia; Jiang, Wenyan; Kang, Jiali; Liu, Qicai; Nie, Miaoling

    2015-08-01

    RhoA regulates cell proliferation, migration, angiogenesis and gene expression. Altered RhoA activity contributes to cancer progression. The present study investigated the effects of RhoA knockdown on the regulation of ovarian cancer biological behavior in vitro and in nude mice. The expression of RhoA was knocked down using a lentivirus carrying RhoA short hairpin RNA (shRNA) in ovarian cancer cells and was confirmed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. The altered ovarian cancer biological behaviors were assayed by cell viability, terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling (TUNEL), migration, invasion, and nude mice tumorigenicity assays, while the altered gene expression was detected by RT-qPCR and western blot analysis. The results showed that lentivirus-carrying RhoA shRNA significantly suppressed RhoA expression in ovarian cancer cells, which suppressed tumor cell viability, migration, invasion and adhesion in vitro. RhoA silencing also inhibited the tumorigenicity of ovarian cancer cells in nude mice, which was characterized by the suppression of tumor xenograft formation and growth and induction of tumor cell apoptosis. The results of the present study demonstrated that knockdown of RhoA expression had a significant antitumor effect on ovarian cancer cells in vitro and in nude mice, suggesting that RhoA may be a target for the development of a novel therapeutic strategy in the control of ovarian cancer.

  8. Postnatal dietary choline supplementation alters behavior in a mouse model of Rett syndrome.

    PubMed

    Nag, Nupur; Berger-Sweeney, Joanne E

    2007-05-01

    Rett syndrome (RTT), a neurodevelopmental disorder primarily affecting females, is accompanied by behavioral and neuropathological abnormalities and decreases in brain cholinergic markers. Because the cholinergic system is associated with cognitive and motor functions, cholinergic deficits in RTT may underlie some of the behavioral abnormalities. In rodents, increased choline availability during development enhances transmission at cholinergic synapses and improves behavioral performance throughout life. We examined whether choline supplementation of nursing dams would attenuate deficits in Mecp2(1lox) offspring, a mouse model of RTT. Dams were given choline in drinking water, and pups nursed from birth to weaning. Offspring were assessed on development and behavior. In Mecp2(1lox) males, choline supplementation improved motor coordination and locomotor activity, whereas in females it enhanced grip strength. Choline supplementation did not improve response to fear conditioning. Postnatal choline supplementation attenuates some behavioral deficits in Mecp2(1lox) mice and should be explored further as a therapeutic agent in RTT.

  9. Training Mental Health Professionals to Assess and Manage Suicidal Behavior: Can Provider Confidence and Practice Behaviors Be Altered?

    ERIC Educational Resources Information Center

    Oordt, Mark S.; Jobes, David A.; Fonseca, Vincent P.; Schmidt, Steven M.

    2009-01-01

    Remarkably little systematic research has studied the effects of clinical suicidology training on changing practitioner attitudes and behaviors. In the current study we investigated whether training in an empirically-based assessment and treatment approach to suicidal patients administered through a continuing education workshop could meaningfully…

  10. Macrophage reprogramming: influence of latex beads with various functional groups on macrophage phenotype and phagocytic uptake in vitro.

    PubMed

    Akilbekova, Dana; Philiph, Rachel; Graham, Austin; Bratlie, Kaitlin M

    2015-01-01

    Macrophages play a crucial role in initiating immune responses with various functions ranging from wound healing to antimicrobial actions. The type of biomaterial is suggested to influence macrophage phenotype. Here, we show that exposing M1- and M2-activated macrophages to polystyrene latex beads bearing different functional groups can alter secretion profiles, providing a possible method for altering the course of the host response. Macrophages were stimulated with either lipopolysaccharide or interleukin (IL) 4 and cultured for 24 h with 10 different latex beads. Proinflammatory cytokines (tumor necrosis factor α, monocyte chemotactic protein 1) and nitrite served as markers for the M1 phenotype and proangiogenic cytokine (IL-10) and arginase activity for M2 cells. The ability of the macrophages to phagocytize Escherichia coli particles and water contact angles of the polymers were also assessed. Different patterns of cytokine expression and phagocytosis activity were induced by the various particles. Particles did not polarize the cells toward one specific phenotype versus another, but rather induced changes in both pro- and anti-inflammatory markers. Our results suggest a dependence of pro- and anti-inflammatory cytokines and phagocytic activities on material type and cytokine stimuli. These data also illustrate how biomaterials can be exploited to alter host responses for drug delivery and tissue engineering applications.

  11. Sleep Fragmentation Exacerbates Mechanical Hypersensitivity and Alters Subsequent Sleep-Wake Behavior in a Mouse Model of Musculoskeletal Sensitization

    PubMed Central

    Sutton, Blair C.; Opp, Mark R.

    2014-01-01

    Study Objectives: Sleep deprivation, or sleep disruption, enhances pain in human subjects. Chronic musculoskeletal pain is prevalent in our society, and constitutes a tremendous public health burden. Although preclinical models of neuropathic and inflammatory pain demonstrate effects on sleep, few studies focus on musculoskeletal pain. We reported elsewhere in this issue of SLEEP that musculoskeletal sensitization alters sleep of mice. In this study we hypothesize that sleep fragmentation during the development of musculoskeletal sensitization will exacerbate subsequent pain responses and alter sleep-wake behavior of mice. Design: This is a preclinical study using C57BL/6J mice to determine the effect on behavioral outcomes of sleep fragmentation combined with musculoskeletal sensitization. Methods: Musculoskeletal sensitization, a model of chronic muscle pain, was induced using two unilateral injections of acidified saline (pH 4.0) into the gastrocnemius muscle, spaced 5 days apart. Musculoskeletal sensitization manifests as mechanical hypersensitivity determined by von Frey filament testing at the hindpaws. Sleep fragmentation took place during the consecutive 12-h light periods of the 5 days between intramuscular injections. Electroencephalogram (EEG) and body temperature were recorded from some mice at baseline and for 3 weeks after musculoskeletal sensitization. Mechanical hypersensitivity was determined at preinjection baseline and on days 1, 3, 7, 14, and 21 after sensitization. Two additional experiments were conducted to determine the independent effects of sleep fragmentation or musculoskeletal sensitization on mechanical hypersensitivity. Results: Five days of sleep fragmentation alone did not induce mechanical hypersensitivity, whereas sleep fragmentation combined with musculoskeletal sensitization resulted in prolonged and exacerbated mechanical hypersensitivity. Sleep fragmentation combined with musculoskeletal sensitization had an effect on

  12. Diet-induced obesity progressively alters cognition, anxiety-like behavior and lipopolysaccharide-induced depressive-like behavior: focus on brain indoleamine 2,3-dioxygenase activation.

    PubMed

    André, Caroline; Dinel, Anne-Laure; Ferreira, Guillaume; Layé, Sophie; Castanon, Nathalie

    2014-10-01

    Obesity is associated with a high prevalence of mood symptoms and cognitive dysfunctions that emerges as significant risk factors for important health complications such as cardiovascular diseases and type 2 diabetes. It is therefore important to identify the dynamic of development and the pathophysiological mechanisms underlying these neuropsychiatric symptoms. Obesity is also associated with peripheral low-grade inflammation and increased susceptibility to immune-mediated diseases. Excessive production of proinflammatory cytokines and the resulting activation of the brain tryptophan catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) have been shown to promote neurobehavioral complications, particularly depression. In that context, questions arise about the impact of diet-induced obesity on the onset of neuropsychiatric alterations and the increased susceptibility to immune-mediated diseases displayed by obese patients, particularly through brain IDO activation. To answer these questions, we used C57Bl/6 mice exposed to standard diet or western diet (WD; consisting of palatable energy-dense food) since weaning and for 20 weeks. We then measured inflammatory and behavioral responses to a systemic immune challenge with lipopolysaccharide (LPS) in experimental conditions known to alter cognitive and emotional behaviors independently of any motor impairment. We first showed that in absence of LPS, 9 weeks of WD is sufficient to impair spatial recognition memory (in the Y-maze). On the other hand, 18 weeks of WD increased anxiety-like behavior (in the elevated plus-maze), but did not affect depressive-like behavior (in the tail-suspension and forced-swim tests). However, 20 weeks of WD altered LPS-induced depressive-like behavior compared to LPS-treated lean mice and exacerbated hippocampal and hypothalamic proinflammatory cytokine expression and brain IDO activation. Taken together, these results show that WD exposure alters cognition and anxiety in unstimulated

  13. [Alteration of Social Behaviors in Male Mice of CBA/Lac Strain under Agonistic Interactions].

    PubMed

    Kovalenko, I L; Kudryavtseva, N N

    2015-01-01

    Ability of people to communicate with each other is a necessary component of social behavior and normal development of individuals living in community. A pronounced impairment in communication may be the result of autism which is characterized by impaired socialization, low communication and restricted and/or repetitive behaviors. It is hypothesized that genes or rare mutations play a key role in the development of autism. However a multifold increase of the cases with autistic spectrum symptoms over the last years cannot be attributed exclusively to genetic mutations or heredity. Environmental contribution to the development of autistic symptoms has to be considered. The paper aimed to analyze the social behaviors of CBA/Lac mice with repeated experience of aggression or social defeats in daily agonistic interactions with accent on searches of associations with autistic symptoms in comparison with previously studied C57BL/6J animals. It has been shown that male mice of both strains with alternative social behaviors demonstrated the changes in social behaviors; however the expression of some form of behaviors was different. The data obtained to assert that long-term hostile social environment lead to development of disturbances in social behaviors, accompanying by autistic-like symptoms.

  14. Early Life Manipulations of the Nonapeptide System Alter Pair Maintenance Behaviors and Neural Activity in Adult Male Zebra Finches

    PubMed Central

    Baran, Nicole M.; Tomaszycki, Michelle L.; Adkins-Regan, Elizabeth

    2016-01-01

    Adult zebra finches (T. guttata) form socially monogamous pair bonds characterized by proximity, vocal communication, and contact behaviors. In this experiment, we tested whether manipulations of the nonapeptide hormone arginine vasotocin (AVT, avian homolog of vasopressin) and the V1a receptor (V1aR) early in life altered species-typical pairing behavior in adult zebra finches of both sexes. Although there was no effect of treatment on the tendency to pair in either sex, males in different treatments exhibited profoundly different profiles of pair maintenance behavior. Following a brief separation, AVT-treated males were highly affiliative with their female partner but sang very little compared to Controls. In contrast, males treated with a V1aR antagonist sang significantly less than Controls, but did not differ in affiliation. These effects on behavior in males were also reflected in changes in the expression of V1aR and immediate early gene activity in three brain regions known to be involved in pairing behavior in birds: the medial amygdala, medial bed nucleus of the stria terminalis, and the lateral septum. AVT males had higher V1aR expression in the medial amygdala than both Control and antagonist-treated males and immediate early gene activity of V1aR neurons in the medial amygdala was positively correlated with affiliation. Antagonist treated males showed decreased activity in the medial amygdala. In addition, there was a negative correlation between the activity of V1aR cells in the medial bed nucleus of the stria terminalis and singing. Treatment also affected the expression of V1aR and activity in the lateral septum, but this was not correlated with any behaviors measured. These results provide evidence that AVT and V1aR play developmental roles in specific pair maintenance behaviors and the neural substrate underlying these behaviors in a bird. PMID:27065824

  15. Dietary zinc status reversibly alters both the feeding behaviors of the rats and gene expression patterns in diencephalon.

    PubMed

    Okada, Shinji; Abuyama, Moe; Yamamoto, Ryo; Kondo, Takashi; Narukawa, Masataka; Misaka, Takumi

    2012-01-01

    Nutritional status influences feeding behaviors, food preferences, and taste sensations. For example, zinc-deficient rats have been reported to show reduced and cyclic food intake patterns with increased preferences for NaCl. Although some impairments of the central nervous and endocrine systems have been speculated to be involved in these phenomena, the effects of short-term zinc deficiency on the brain have not been well examined to date. In this study, we performed a comprehensive analysis of the gene expression patterns in the rat diencephalon, which is a portion of the brain that includes the hypothalamus and thalamus, after short-term zinc deficiency and also during zinc recovery. The rats showed reduced and cyclic food intake patterns with increased salt preferences after a 10-day dietary zinc deficiency. A comparative analysis of their diencephalons using cDNA microarrays revealed that approximately 1% of the genes expressed in the diencephalons showed significantly altered expression levels. On the other hand, a 6-day zinc supplementation following the deprivation allowed for the recovery to initial food intake behaviors and salt preferences. The expression levels of most of the genes that had been altered by exposure to zinc deficient conditions were also recovered. These results show that feeding behaviors, taste preferences and gene expression patterns in the diencephalon respond quickly to changing zinc levels. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.

  16. Prenatal stress alters the behavior and dendritic morphology of the medial orbitofrontal cortex in mouse offspring during lactation.

    PubMed

    Gutiérrez-Rojas, Cristian; Pascual, Rodrigo; Bustamante, Carlos

    2013-11-01

    Several preclinical and clinical studies have shown that prenatal stress alters neuronal dendritic development in the prefrontal cortex, together with behavioral disturbances (anxiety). Nevertheless, neither whether these alterations are present during the lactation period, nor whether such findings may reflect the onset of anxiety disorders observed in childhood and adulthood has been studied. The central aim of the present study was to determine the effects of prenatal stress on the neuronal development and behavior of mice offspring during lactation (postnatal days 14 and 21). We studied 24 CF-1 male mice, grouped as follows: (i) control P14 (n=6), (ii) stressed P14 (n=6), (iii) control P21 (n=6) and (iv) stressed P21 (n=6). On the corresponding days, animals were evaluated with the open field test and sacrificed. Their brains were then stained in Golgi-Cox solution for 30 days. The morphological analysis dealt with the study of 96 pyramidal neurons. The results showed, first, that prenatal stress resulted in a significant (i) decrease in the apical dendritic length of pyramidal neurons in the orbitofrontal cortex at postnatal day 14, (ii) increase in the apical dendritic length of pyramidal neurons in the orbitofrontal cortex at postnatal day 21, and (iii) reduction in exploratory behavior at postnatal day 14 and 21.

  17. Altered gene expression in hippocampus and depressive-like behavior in young adult female mice by early protein malnutrition.

    PubMed

    Belluscio, L M; Alberca, C D; Pregi, N; Cánepa, E T

    2016-11-01

    Perinatal development represents a critical period in the life of an individual. A common cause of poor development is that which comes from undernutrition or malnutrition. In particular, protein deprivation during development has been shown to have deep deleterious effects on brain's growth and plasticity. Early-life stress has also been linked with an increased risk to develop different psychopathologies later in life. We have previously shown that perinatal protein malnutrition in mice leads to the appearance of anxiety-related behaviors in the adulthood. We also found evidence that the female offspring was more susceptible to the development of depression-related behaviors. In the present work, we further investigated this behavior together with its molecular bases. We focused our study on the hippocampus, as it is a structure involved in coping with stressful situations. We found an increase in immobility time in the forced swimming test in perinatally malnourished females, and an alteration in the expression of genes related with neuroplasticity, early growth response 1, calcineurin and c-fos. We also found that perinatal malnutrition causes a reduction in the number of neurons in the hippocampus. This reduction, together with altered gene expression, could be related to the increment in immobility time observed in the forced swimming test. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  18. Influencing Eating Choices: Biological Food Cues in Advertising and Packaging Alter Trajectories of Decision Making and Behavior.

    PubMed

    Bailey, Rachel L

    2017-10-01

    From an ecological perception perspective (Gibson, 1977), the availability of perceptual information alters what behaviors are more and less likely at different times. This study examines how perceptual information delivered in food advertisements and packaging alters the time course of information processing and decision making. Participants categorized images of food that varied in information delivered in terms of color, glossiness, and texture (e.g., food cues) before and after being exposed to a set of advertisements that also varied in this way. In general, items with more direct cues enhanced appetitive motivational processes, especially if they were also advertised with direct food cues. Individuals also chose to eat products that were packaged with more available direct food cues compared to opaque packaging.

  19. Sevoflurane anesthesia alters exploratory and anxiety-like behavior in mice lacking the beta2 nicotinic acetylcholine receptor subunit.

    PubMed

    Wiklund, Andreas; Granon, Sylvie; Cloëz-Tayarani, Isabelle; Faure, Philippe; le Sourd, Anne-Marie; Sundman, Eva; Changeux, Jean-Pierre; Eriksson, Lars I

    2008-11-01

    Preexisting cognitive impairment and advanced age are factors that increase the risk of developing postoperative cognitive dysfunction. Because anesthetic agents interfere with cholinergic transmission and as impairment of cholinergic function is associated with cognitive decline, the authors studied how the volatile anesthetic sevoflurane affects exploratory and anxiety-like behavior in young and aged animals with a genetically modified cholinergic system. Young and aged wild-type and mutant mice lacking the beta2 subunit of the nicotinic cholinergic receptor (beta2KO) were anesthetized for 2 h with 2.6% sevoflurane in oxygen and compared with nonanesthetized controls. Locomotor activity and organization of movement in the open field model were assessed before and 24 h after anesthesia. Locomotor activity and anxiety-like behavior in the elevated plus maze were assessed 24 h after anesthesia. High- and low-affinity nicotinic receptor and cholinergic uptake site densities were evaluated in the hippocampus, amygdala, and forebrain regions using receptor autoradiography. Sevoflurane anesthesia significantly reduced locomotor activity, altered temporospatial organization of trajectories, and increased anxiety-like behavior in young beta2KO mice, whereas no such changes were observed in young wild-type mice. Aged wild-type and beta2KO mice displayed reactions that were similar, but not identical, to the reactions of young mice to sevoflurane anesthesia. However, behavioral changes were not associated with differences in nicotinic receptor or cholinergic uptake site densities. In conclusion, sevoflurane anesthesia altered exploratory and anxiety-like behavior in mice lacking the beta2 nicotinic acetylcholine receptor subunit.

  20. Modulation of fibronectin gene expression in human mononuclear phagocytes.

    PubMed Central

    Yamauchi, K; Martinet, Y; Crystal, R G

    1987-01-01

    Under some conditions, mononuclear phagocytes spontaneously synthesize and release fibronectin, an extracellular matrix glycoprotein with versatile effects on cell-matrix interactions. To gain insight into the processes that modulate the level of fibronectin secretion by these cells, we used monocytes, in vitro matured monocytes and alveolar macrophages as models to compare fibronectin mRNA levels and fibronectin secretion in a variety of circumstances. Using Northern analysis and dot-blot analysis with a 32P-labeled human fibronectin cDNA probe, we evaluated steady-state mRNA levels and a human fibronectin-specific ELISA was used to evaluate fibronectin secretion. In all cases the amounts of fibronectin secreted paralleled fibronectin mRNA levels. Specifically (a) when fibronectin mRNA was undetectable, as in the case of normal blood monocytes, no fibronectin was secreted, but whenever fibronectin mRNA was present, as in normal alveolar macrophages, fibronectin was secreted by the cells; (b) as monocytes matured into macrophages in vitro, the cells began to express fibronectin mRNA and the cells secreted fibronectin; (c) when alveolar macrophages were activated with surface stimuli such as lipopolysaccharide (LPS) or immune complexes, fibronectin mRNA levels decreased and in parallel, the cells secreted less fibronectin; (d) in idiopathic pulmonary fibrosis (IPF), alveolar macrophages contained severalfold more fibronectin mRNA transcripts that normal and the cells spontaneously secreted severalfold more fibronectin than normal; and (e) when IPF alveolar macrophages were placed in culture the fibronectin mRNA levels in the cells decreased with time, and concurrently the amounts of fibronectin produced per unit time continually decreased. The observation of a strict concordance of fibronectin mRNA levels and fibronectin release by mononuclear phagocytes suggests that, at least in many circumstances, fibronectin secretion by mononuclear phagocytes is controlled by

  1. Differential Rearing Alters Forced Swim Test Behavior, Fluoxetine Efficacy, and Post-Test Weight Gain in Male Rats.

    PubMed

    Arndt, David L; Peterson, Christy J; Cain, Mary E

    2015-01-01

    Environmental factors play a key role in the etiology of depression. The rodent forced swim test (FST) is commonly used as a preclinical model of depression, with increases in escape-directed behavior reflecting antidepressant effects, and increases in immobility reflecting behavioral despair. Environmental enrichment leads to serotonergic alterations in rats, but it is unknown whether these alterations may influence the efficacy of common antidepressants. Male Sprague-Dawley rats were reared in enriched (EC), standard (SC), or isolated (IC) conditions. Following the rearing period, fluoxetine (10 or 20 mg/kg, i.p.) was administered 23.5 hrs, 5 hrs, and 1 hr before locomotor and FST measures. Following locomotor testing and FST exposure, rats were weighed to assess fluoxetine-, FST-, and environmental condition-induced moderations in weight gain. Results revealed an antidepressant effect of environmental enrichment and a depressant effect of isolation. Regardless of significant fluoxetine effects on locomotor activity, fluoxetine generally decreased swimming and increased immobility in all three environmental conditions, with IC-fluoxetine (10 mg/kg) rats and EC-fluoxetine (20 mg/kg) rats swimming less than vehicle counterparts. Subchronic 20 mg/kg fluoxetine also induced significant weight loss, and differential rearing appeared to moderate weight gain following FST stress. These results suggest that differential rearing has the ability to alter FST behaviors, fluoxetine efficacy, and post-stressor well-being. Moreover, 20 mg/kg fluoxetine, administered subchronically, may lead to atypical effects of those commonly observed in the FST, highlighting the importance and impact of both environmental condition and dosing regimen in common animal models of depression.

  2. Differential Rearing Alters Forced Swim Test Behavior, Fluoxetine Efficacy, and Post-Test Weight Gain in Male Rats

    PubMed Central

    Arndt, David L.; Peterson, Christy J.; Cain, Mary E.

    2015-01-01

    Environmental factors play a key role in the etiology of depression. The rodent forced swim test (FST) is commonly used as a preclinical model of depression, with increases in escape-directed behavior reflecting antidepressant effects, and increases in immobility reflecting behavioral despair. Environmental enrichment leads to serotonergic alterations in rats, but it is unknown whether these alterations may influence the efficacy of common antidepressants. Male Sprague-Dawley rats were reared in enriched (EC), standard (SC), or isolated (IC) conditions. Following the rearing period, fluoxetine (10 or 20 mg/kg, i.p.) was administered 23.5 hrs, 5 hrs, and 1 hr before locomotor and FST measures. Following locomotor testing and FST exposure, rats were weighed to assess fluoxetine-, FST-, and environmental condition-induced moderations in weight gain. Results revealed an antidepressant effect of environmental enrichment and a depressant effect of isolation. Regardless of significant fluoxetine effects on locomotor activity, fluoxetine generally decreased swimming and increased immobility in all three environmental conditions, with IC-fluoxetine (10 mg/kg) rats and EC-fluoxetine (20 mg/kg) rats swimming less than vehicle counterparts. Subchronic 20 mg/kg fluoxetine also induced significant weight loss, and differential rearing appeared to moderate weight gain following FST stress. These results suggest that differential rearing has the ability to alter FST behaviors, fluoxetine efficacy, and post-stressor well-being. Moreover, 20 mg/kg fluoxetine, administered subchronically, may lead to atypical effects of those commonly observed in the FST, highlighting the importance and impact of both environmental condition and dosing regimen in common animal models of depression. PMID:26154768

  3. Role of Peroxide in Phagocytic Killing of Pneumococci

    PubMed Central

    Pitt, Jane; Bernheimer, Harriet P.

    1974-01-01

    Two mutants of a pneumococcus type I with diminished peroxide production were selected from a population of nitrosoguanidine-treated cells. White cells of normal patients killed the mutant pneumococci as well as the otherwise isogenic wild-type strain. In patients studied with chronic granulomatous disease, however, the peroxide-poor strain was killed far less well than the wild type. These studies indicate that the removal of a peroxide-generating system in the phagocytic vacuole specifically brings forth the killing defect in chronic granulomatous disease. PMID:4148725

  4. Differentiation and heterogeneity in the mononuclear phagocyte system.

    PubMed

    Hume, D A

    2008-11-01

    Cells of the mononuclear phagocyte system (MPS) are found in large numbers in every organ of the body, where they contribute to innate and acquired immunity and homeostasis. This review considers the locations of MPS cells, surface markers that distinguish subsets of monocytes and macrophages, the pathways of MPS differentiation, and the growth factors and transcription factors that guide them. Although the number of MPS sub-populations that can be defined is infinite, the features that unite the MPS remain compelling. Those features clearly include antigen-presenting dendritic cells within the MPS and argue against any basis for separating them from macrophages.

  5. Determining the phagocytic activity of clinical antibody samples.

    PubMed

    McAndrew, Elizabeth G; Dugast, Anne-Sophie; Licht, Anna F; Eusebio, Justin R; Alter, Galit; Ackerman, Margaret E

    2011-11-30

    Antibody-driven phagocytosis is induced via the engagement of Fc receptors on professional phagocytes, and can contribute to both clearance as well as pathology of disease. While the properties of the variable domains of antibodies have long been considered critical to in vivo function, the ability of antibodies to recruit innate immune cells via their Fc domains has become increasingly appreciated as a major factor in their efficacy, both in the setting of recombinant monoclonal antibody therapy, as well as in the course of natural infection or vaccination(1-3). Importantly, despite its nomenclature as a constant domain, the antibody Fc domain does not have constant function, and is strongly modulated by IgG subclass (IgG1-4) and glycosylation at Asparagine 297(4-6). Thus, this method to study functional differences of antigen-specific antibodies in clinical samples will facilitate correlation of the phagocytic potential of antibodies to disease state, susceptibility to infection, progression, or clinical outcome. Furthermore, this effector function is particularly important in light of the documented ability of antibodies to enhance infection by providing pathogens access into host cells via Fc receptor-driven phagocytosis(7). Additionally, there is some evidence that phagocytic uptake of immune complexes can impact the Th1/Th2 polarization of the immune response(8). Here, we describe an assay designed to detect differences in antibody-induced phagocytosis, which may be caused by differential IgG subclass, glycan structure at Asn297, as well as the ability to form immune complexes of antigen-specific antibodies in a high-throughput fashion. To this end, 1 μm fluorescent beads are coated with antigen, then incubated with clinical antibody samples, generating fluorescent antigen specific immune complexes. These antibody-opsonized beads are then incubated with a monocytic cell line expressing multiple FcγRs, including both inhibitory and activating. Assay output

  6. Hacker within! Ehrlichia chaffeensis Effector Driven Phagocyte Reprogramming Strategy

    PubMed Central

    Lina, Taslima T.; Farris, Tierra; Luo, Tian; Mitra, Shubhajit; Zhu, Bing; McBride, Jere W.

    2016-01-01

    Ehrlichia chaffeensis is a small, gram negative, obligately intracellular bacterium that preferentially infects mononuclear phagocytes. It is the etiologic agent of human monocytotropic ehrlichiosis (HME), an emerging life-threatening tick-borne zoonosis. Mechanisms by which E. chaffeensis establishes intracellular infection, and avoids host defenses are not well understood, but involve functionally relevant host-pathogen interactions associated with tandem and ankyrin repeat effector proteins. In this review, we discuss the recent advances in our understanding of the molecular and cellular mechanisms that underlie Ehrlichia host cellular reprogramming strategies that enable intracellular survival. PMID:27303657

  7. THE FATE OF DNA-CONTAINING PARTICLES PHAGOCYTIZED BY MAMMALIAN CELLS

    PubMed Central

    Bensch, Klaus; Gordon, Gerald; Miller, Leonard

    1964-01-01

    Particulate DNA protein coacervates were digested immediately after being phagocytized by L strain fibroblasts in suspension culture. Enlargement of the phagocytotic vacuoles occurred simultaneously with a loss of the electron opacity of the phagocytized particles. Cytochemical reactions positive for non-specific esterase, acid phosphatase, and nucleoside phosphatase in the phagocytotic vacuoles provided additional evidence for the probability of complete hydrolysis of the phagocytized nucleoprotein. PMID:14154484

  8. Functional defects in phagocytic cells following thermal injury. Application of flow cytometric analysis.

    PubMed Central

    Duque, R. E.; Phan, S. H.; Hudson, J. L.; Till, G. O.; Ward, P. A.

    1985-01-01

    Defective phagocytic cell function may partially account for the morbidity and mortality associated with thermal injury. In experimental thermal injury in the rat, small circulating blood volumes increase the difficulty in obtaining significant data. Furthermore, purification and or elicitation procedures have the potential for altering the cell surface characteristics and/or the functional response of the cell in question. We have examined the circulating neutrophils and pulmonary alveolar macrophages of anesthetized rats following a 16-20% body surface area scald injury to the shaved back. The circulating neutrophils of thermally injured rats were examined by flow cytometry following stimulation with phorbol myristate acetate (PMA) (100 ng/ml) in terms of the change in fluorescence intensity of the potentiometric cyanine dye, dipentyloxocarboxyanine and the formation of the oxidized product of 2',7'-dichlorofluorescin diacetate-loaded cells. The alveolar macrophages were examined after stimulation with PMA (100 ng/ml) in terms of the change in fluorescence intensity of the potentiometric dye, dipropylthiodicarbocyanine and the generation of superoxide production, as assessed by the superoxide dismutase inhibitable reduction of cytochrome c. Both cells exhibited a profound inhibition of cell function 4 hours after the insult, with partial return toward control values at later time points. Furthermore, the plasma of thermally injured rats, 4 hours after the burn was inhibitory to normal rat neutrophils. Fluorescent compounds suggestive of in vivo lipid peroxidation were maximally detectable at this time point. Further research is needed to establish the role of these products in the induction of phagocytic cell dysfunction. PMID:2981471

  9. The use of messages in altering risky gambling behavior in experienced gamblers.

    PubMed

    Jardin, Bianca F; Wulfert, Edelgard

    2012-03-01

    The present study was an experimental analogue that examined the relationship between gambling-related irrational beliefs and risky gambling behavior. Eighty high-frequency gamblers were randomly assigned to four conditions and played a chance-based computer game in a laboratory setting. Depending on the condition, during the game a pop-up screen repeatedly displayed either accurate or inaccurate messages concerning the game, neutral messages, or no messages. Consistent with a cognitive-behavioral model of gambling, accurate messages that correctly described the random contingencies governing the game decreased risky gambling behavior. Contrary to predictions, inaccurate messages designed to mimic gamblers' irrational beliefs about their abilities to influence chance events did not lead to more risky gambling behavior than exposure to neutral or no messages. Participants in the latter three conditions did not differ significantly from one another and all showed riskier gambling behavior than participants in the accurate message condition. The results suggest that harm minimization strategies that help individuals maintain a rational perspective while gambling may protect them from unreasonable risk-taking. PsycINFO Database Record (c) 2012 APA, all rights reserved.

  10. Maternal and developmental immune challenges alter behavior and learning ability of offspring.

    PubMed

    Grindstaff, Jennifer L; Hunsaker, Veronica R; Cox, Shelby N

    2012-08-01

    Stimulation of the offspring immune response during development is known to influence growth and behavioral phenotype. However, the potential for maternal antibodies to block the behavioral effects of immune activation during the neonatal period has not been assessed. We challenged female zebra finches (Taeniopygia guttata) prior to egg laying and then challenged offspring during the nestling and juvenile periods with one of two antigens (keyhole limpet hemocyanin (KLH) or lipopolysaccharide (LPS)). We then tested the effects of maternal and neonatal immune challenges on offspring growth rates and neophobia and learning ability of offspring during adulthood. Neonatal immune challenge depressed growth rates. Neophobia of adult offspring was influenced by a combination of maternal treatment, offspring treatment, and offspring sex. Males challenged with LPS during the nestling and juvenile periods had reduced learning performance in a novel foraging task; however, female learning was not impacted. Offspring challenged with the same antigen as mothers exhibited similar growth suppression and behavioral changes as offspring challenged with a novel antigen. Thus, developmental immune challenges have long-term effects on the growth and behavioral phenotype of offspring. We found limited evidence that matching of maternal and offspring challenges reduces the effects of immune challenge in the altricial zebra finch. This may be a result of rapid catabolism of maternal antibodies in altricial birds. Our results emphasize the need to address sex differences in the long-term effects of developmental immune challenge and suggest that neonatal immune activation may be one proximate mechanism underlying differences in adult behavior.

  11. Highly active modulators of indole signaling alter pathogenic behaviors in Gram-negative and Gram-positive bacteria.

    PubMed

    Minvielle, Marine J; Eguren, Kristen; Melander, Christian

    2013-12-16

    Indole is a universal signal that regulates various bacterial behaviors, such as biofilm formation and antibiotic resistance. To generate mechanistic probes of indole signaling and control indole-mediated pathogenic phenotypes in both Gram-positive and Gram-negative bacteria, we have investigated the use of desformylflustrabromine (dFBr) derivatives to generate highly active indole mimetics. We have developed non-microbicidal dFBr derivatives that are 27-2000 times more active than indole in modulating biofilm formation, motility, acid resistance, and antibiotic resistance. The activity of these analogues parallels indole, because they are dependent on temperature, the enzyme tryptophanase TnaA, and the transcriptional regulator SdiA. This investigation demonstrates that molecules based on the dFBr scaffold can alter pathogenic behaviors by mimicking indole-signaling pathways.

  12. Ifenprodil infusion in agranular insular cortex alters social behavior and vocalizations in rats exposed to moderate levels of ethanol during prenatal development.

    PubMed

    Bird, Clark W; Barto, Daniel; Magcalas, Christy M; Rodriguez, Carlos I; Donaldson, Tia; Davies, Suzy; Savage, Daniel D; Hamilton, Derek A

    2017-03-01

    Moderate exposure to alcohol during development leads to subtle neurobiological and behavioral effects classified under the umbrella term fetal alcohol spectrum disorders (FASDs). Alterations in social behaviors are a frequently observed consequence of maternal drinking, as children with FASDs display inappropriate aggressive behaviors and altered responses to social cues. Rodent models of FASDs mimic the behavioral alterations seen in humans, with rats exposed to ethanol during development displaying increased aggressive behaviors, decreased social investigation, and altered play behavior. Work from our laboratory has observed increased wrestling behavior in adult male rats following prenatal alcohol exposure (PAE), and increased expression of GluN2B-containing NMDA receptors in the agranular insular cortex (AIC). This study was undertaken to determine if ifenprodil, a GluN2B preferring negative allosteric modulator, has a significant effect on social behaviors in PAE rats. Using a voluntary ethanol exposure paradigm, rat dams were allowed to drink a saccharin-sweetened solution of either 0% or 5% ethanol throughout gestation. Offspring at 6-8 months of age were implanted with cannulae into AIC. Animals were isolated for 24h before ifenprodil or vehicle was infused into AIC, and after 15min they were recorded in a social interaction chamber. Ifenprodil treatment altered aspects of wrestling, social investigatory behaviors, and ultrasonic vocalizations in rats exposed to ethanol during development that were not observed in control animals. These data indicate that GluN2B-containing NMDA receptors in AIC play a role in social behaviors and may underlie alterations in behavior and vocalizations observed in PAE animals.

  13. Preschool-Aged Children with Iron Deficiency Anemia Show Altered Affect and Behavior1,2

    PubMed Central

    Lozoff, Betsy; Corapci, Feyza; Burden, Matthew J.; Kaciroti, Niko; Angulo-Barroso, Rosa; Sazawal, Sunil; Black, Maureen

    2012-01-01

    This study compared social looking and response to novelty in preschool-aged children (47–68 mo) with or without iron deficiency anemia (IDA). Iron status of the participants from a low-income community in New Delhi, India, was based on venous hemoglobin, mean corpuscular volume, and red cell distribution width. Children’s social looking toward adults, affect, and wary or hesitant behavior in response to novelty were assessed in a semistructured paradigm during an in-home play observation. Affect and behavior were compared as a function of iron status: IDA (n = 74) vs. nonanemic (n = 164). Compared with nonanemic preschoolers, preschoolers with IDA displayed less social looking toward their mothers, moved close to their mothers more quickly, and were slower to display positive affect and touch novel toys for the first time. These results indicate that IDA in the preschool period has affective and behavioral effects similar to those reported for IDA in infancy. PMID:17311960

  14. Altered behavior, physiology, and metabolism in fish exposed to polystyrene nanoparticles.

    PubMed

    Mattsson, Karin; Ekvall, Mikael T; Hansson, Lars-Anders; Linse, Sara; Malmendal, Anders; Cedervall, Tommy

    2015-01-06

    The use of nanoparticles in consumer products, for example, cosmetics, sunscreens, and electrical devices, has increased tremendously over the past decade despite insufficient knowledge about their effects on human health and ecosystem function. Moreover, the amount of plastic waste products that enter natural ecosystems, such as oceans and lakes, is increasing, and degradation of the disposed plastics produces smaller particles toward the nano scale. Therefore, it is of utmost importance to gain knowledge about how plastic nanoparticles enter and affect living organisms. Here we have administered 24 and 27 nm polystyrene nanoparticles to fish through an aquatic food chain, from algae through Daphnia, and studied the effects on behavior and metabolism. We found severe effects on feeding and shoaling behavior as well as metabolism of the fish; hence, we conclude that polystyrene nanoparticles have severe effects on both behavior and metabolism in fish and that commonly used nanosized particles may have considerable effects on natural systems and ecosystem services derived from them.

  15. Chronic social instability in adult female rats alters social behavior, maternal aggression and offspring development.

    PubMed

    Pittet, Florent; Babb, Jessica A; Carini, Lindsay; Nephew, Benjamin C

    2017-04-01

    We investigated the consequences of chronic social instability (CSI) during adulthood on social and maternal behavior in females and social behavior of their offspring in a rat model. CSI consisted of changing the social partners of adult females every 2-3 days for 28 days, 2 weeks prior to mating. Females exposed to CSI behaved less aggressively and more pro-socially towards unfamiliar female intruders. Maternal care was not affected by CSI in a standard testing environment, but maternal behavior of CSI females was less disrupted by a male intruder. CSI females were quicker to attack prey and did not differ from control females in their saccharin consumption indicating, respectively, no stress-induced sensory-motor or reward system impairments. Offspring of CSI females exhibited slower growth and expressed more anxiety in social encounters. This study demonstrates continued adult vulnerability to social challenges with an impact specific to social situations for mothers and offspring.

  16. Modeling acclimatization by hybrid systems: condition changes alter biological system behavior models.

    PubMed

    Assar, Rodrigo; Montecino, Martín A; Maass, Alejandro; Sherman, David J

    2014-07-01

    In order to describe the dynamic behavior of a complex biological system, it is useful to combine models integrating processes at different levels and with temporal dependencies. Such combinations are necessary for modeling acclimatization, a phenomenon where changes in environmental conditions can induce drastic changes in the behavior of a biological system. In this article we formalize the use of hybrid systems as a tool to model this kind of biological behavior. A modeling scheme called strong switches is proposed. It allows one to take into account both minor adjustments to the coefficients of a continuous model, and, more interestingly, large-scale changes to the structure of the model. We illustrate the proposed methodology with two applications: acclimatization in wine fermentation kinetics, and acclimatization of osteo-adipo differentiation system linking stimulus signals to bone mass. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. Interactions between Human Phagocytes and Candida albicans Biofilms Alone and in Combination with Antifungal Agents

    PubMed Central

    Katragkou, Aspasia; Kruhlak, Michael J.; Simitsopoulou, Maria; Chatzimoschou, Athanasios; Taparkou, Anna; Cotten, Catherine J.; Paliogianni, Fotini; Diza-Mataftsi, Eudoxia; Tsantali, Chaido; Walsh, Thomas J.; Roilides, Emmanuel

    2010-01-01

    Background Biofilm formation is an important component of vascular catheter infections caused by Candida albicans. Little is known about the interactions between human phagocytes and antifungal agents on Candida biofilms. Materials and Methods The interactions of C. albicans biofilms with human phagocytes alone and in combination with anidulafungin or voriconazole were investigated and compared with their corresponding planktonic counterparts using an in vitro biofilm model with clinical intravascular and green fluorescent protein (GFP) expressing strains. Phagocyte- and antifungal agent-mediated damages were determined by 2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]2H-tetrazolium-5-carboxanilide assay and structural effects visualized by confocal microscopy. Oxidative burst was evaluated by flow cytometric measurement of dihydrorhodamine (DHR)-123 oxidation and cytokine release measured by EIA. Results Phagocytes alone or in combination with antifungal agents induced less damage against biofilms as compared to planktonic cells. However, additive effects occurred between phagocytes and anidulafungin against Candida biofilms. Confocal microscopy demonstrated absence of phagocytosis within biofilms, but marked destruction caused by anidulafungin and phagocytes. Anidulafungin but not voriconazole elicited a TNF-α release from phagocytes compared with untreated biofilms. Conclusions Candida albicans within biofilms are more resistant to phagocytic host defenses but are susceptible to additive effects between phagocytes and an echinocandin. PMID:20415537

  18. Acute diclofenac treatment attenuates lipopolysaccharide-induced alterations to basic reward behavior and HPA axis activation in rats.

    PubMed

    De La Garza, Richard; Asnis, Gregory M; Fabrizio, Kevin R; Pedrosa, Erika

    2005-05-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) counteract stress hormone and pro-inflammatory cytokine activation, and are being considered as therapeutics for Alzheimer's and Parkinson's disease, and multiple sclerosis. Previous data from our laboratory revealed that repeated treatment with the NSAID diclofenac attenuated lipopolysaccharide (LPS)-induced alterations to reward behavior, implicating a role for NSAIDs in alleviating depressive-like behavior. To extend these findings, we sought to determine whether acute treatment with diclofenac would attenuate LPS-induced alterations to basic reward behavior, as well as neuroendocrine and neuroimmune function. Male, Wistar rats (n=8-9/grp) pressed a lever for sucrose pellet reward and after establishing a steady baseline were exposed to an injection of saline (1 ml/kg, SC) or diclofenac (2.5 mg/kg, SC) 30 min prior to a second injection of saline or LPS (20 microg/kg, IP). In saline pre-treated rats, LPS significantly reduced rate of sucrose pellet self-administration and total reinforcers obtained, suggestive of an anhedonia response. In addition, LPS increased corticosterone release, increased plasma intereleukin (IL)-1beta release, increased IL-1beta and IL-6 mRNA in hippocampus, increased corticotropin releasing hormone (CRH) mRNA in pituitary, and decreased CRH-1 mRNA in pituitary. Importantly, the behavioral and neuroendocrine effects, but not neuroimmune effects, produced by LPS were significantly attenuated in rats pre-treated with diclofenac. These new data provide a comprehensive assessment of the acute effects of diclofenac on LPS exposure in rats and confirm a role for NSAIDs in attenuating endotoxin-induced anhedonia. Of particular importance, the data reveal that the observed effects are mediated via the hypothalamic pituitary adrenal axis at the level of the pituitary or above.

  19. Food, stress, and reproduction: short-term fasting alters endocrine physiology and reproductive behavior in the zebra finch.

    PubMed

    Lynn, Sharon E; Stamplis, Teresa B; Barrington, William T; Weida, Nicholas; Hudak, Casey A

    2010-07-01

    Stress is thought to be a potent suppressor of reproduction. However, the vast majority of studies focus on the relationship between chronic stress and reproductive suppression, despite the fact that chronic stress is rare in the wild. We investigated the role of fasting in altering acute stress physiology, reproductive physiology, and reproductive behavior of male zebra finches (Taeniopygia guttata) with several goals in mind. First, we wanted to determine if acute fasting could stimulate an increase in plasma corticosterone and a decrease in corticosteroid binding globulin (CBG) and testosterone. We then investigated whether fasting could alter expression of undirected song and courtship behavior. After subjecting males to fasting periods ranging from 1 to 10h, we collected plasma to measure corticosterone, CBG, and testosterone. We found that plasma corticosterone was elevated, and testosterone was decreased after 4, 6, and 10h of fasting periods compared with samples collected from the same males during nonfasted (control) periods. CBG was lower than control levels only after 10h of fasting. We also found that, coincident with these endocrine changes, males sang less and courted females less vigorously following short-term fasting relative to control conditions. Our data demonstrate that acute fasting resulted in rapid changes in endocrine physiology consistent with hypothalamo-pituitary-adrenal axis activation and hypothalamo-pituitary-gonadal axis deactivation. Fasting also inhibited reproductive behavior. We suggest that zebra finches exhibit physiological and behavioral flexibility that makes them an excellent model system for studying interactions of acute stress and reproduction. Copyright 2010 Elsevier Inc. All rights reserved.

  20. Geochemical behavior of rare earth elements of the hydrothermal alterations within the Tepeoba porphyry Cu-Mo-Au deposits at Balikesir, NW Turkey

    NASA Astrophysics Data System (ADS)

    Doner, Zeynep; Abdelnasser, Amr; Kiran Yildirim, Demet; Kumral, Mustafa

    2016-04-01

    This work reports the geochemical characteristics and behavior of the rare earth elements (REE) of the hydrothermal alteration of the Tepeoba porphyry Cu-Mo-Au deposit located in the Anatolian tectonic belt at Biga peninsula (Locally Balikesir province), NW Turkey. The Cu-Mo-Au mineralization at this deposit hosted in the hornfels rocks and related to the silicic to intermediate intrusion of Eybek pluton. It locally formed with brecciated zones and quartz vein stockworks, as well as the brittle fracture zones associated with intense hydrothermal alteration. Three main alteration zones with gradual boundaries formed in the mine area in the hornfels rock that represents the host rock, along that contact the Eybek pluton; potassic, propylitic and phyllic alteration zones. The potassic alteration zone that formed at the center having high amount of Cu-sulfide minerals contains biotite, muscovite, and sericite with less amount of K-feldspar and associated with tourmalinization alteration. The propylitic alteration surrounds the potassic alteration having high amount of Mo and Au and contains chlorite, albite, epidote, calcite and pyrite. The phyllic alteration zone also surrounds the potassic alteration containing quartz, sericite and pyrite minerals. Based on the REE characteristics and content and when we correlate the Alteration index (AI) with the light REEs and heavy REEs of each alteration zone, it concluded that the light REEs decrease and heavy REEs increase during the alteration processes. The relationships between K2O index with Eu/Eu* and Sr/Sr* reveals a positive correlation in the potassic and phyllic alteration zones and a negative correlation in the propylitic alteration zone. This refers to the hydrothermal solution which is responsible for the studied porphyry deposits and associated potassic and phyllic alterations has a positive Eu and Sr anomaly as well as these elements were added to the altered rock from the hydrothermal solution. Keywords: Rare

  1. Conessine, an H3 receptor antagonist, alters behavioral and neurochemical effects of ethanol in mice.

    PubMed

    Morais-Silva, Gessynger; Ferreira-Santos, Mariane; Marin, Marcelo T

    2016-05-15

    Ethanol abuse potential is mainly due to its reinforcing properties, crucial in the transition from the recreational to pathological use. These properties are mediated by mesocorticolimbic and nigrostriatal dopaminergic pathways and neuroadaptations in these pathways seem to be responsible for addiction. Both pathways are modulated by other neurotransmitters systems, including neuronal histaminergic system. Among the histamine receptors, H3 receptor stands out due to its role in modulation of histamine and other neurotransmitters release. Thus, histaminergic system, through H3 receptors, may have an important role in ethanol addiction development. Aiming to understand these interactions, conessine, an H3 receptor antagonist, was given to mice subjected to the evaluation of ethanol-induced psychostimulation, ethanol CPP and quantification of norepinephrine, dopamine, serotonin and their metabolites in mesocorticolimbic and nigrostriatal pathways following acute ethanol treatment. Systemic conessine administration exacerbated ethanol effects on locomotor activity. Despite of conessine reinforcing effect on CPP, this drug did not alter acquisition of ethanol CPP. Ethanol treatment affects the serotoninergic neurotransmission in the ventral tegmental area, the dopaminergic neurotransmission in the pre-frontal cortex (PFC) and caudate-putamen nucleus (CPu) and the noradrenergic neurotransmission in the CPu. In the PFC, conessine blocked ethanol effects on dopaminergic and noradrenergic neurotransmission. The blockade of H3 receptors and ethanol seem to interact in the modulation of dopaminergic neurotransmission of nigrostriatal pathway, decreasing dopamine metabolites in substantia nigra. In conclusion, conessine was able to change psychostimulant effect of ethanol, without altering its reinforcing properties. This exacerbation of ethanol-induced psychostimulation would be related to alterations in dopaminergic neurotransmission in the nigrostriatal pathway.

  2. Neonatal exposure to bisphenol A alters estrogen-dependent mechanisms governing sexual behavior in the adult female rat.

    PubMed

    Monje, L; Varayoud, J; Muñoz-de-Toro, M; Luque, E H; Ramos, J G

    2009-12-01

    This study examines the effects of neonatal exposure to the endocrine disruptor bisphenol A (BPA) on the hypothalamic circuitry controlling the female sexual behaviors of adult rats. From postnatal day 1 (PND1) to PND7, pups were injected with corn oil (control) or BPA (BPA20: 20mg/kg-d; BPA.05: 0.05 mg/kg-d) and at PND85 the rats were bilaterally ovariectomized (OVX). At PND100, OVX-rats received estradiol alone or estradiol and progesterone to evaluate estrogen-dependent gene expression in the hypothalamus and sexual behavior. In BPA-exposed females, estrogen receptor alpha (ER alpha) expression was down-regulated in both the medial preoptic (MPN) and ventromedial nucleus (VMHvl), while repressor of estrogen receptor activity (REA) expression was up-regulated in the VMHvl. Interestingly, BPA-exposed females displayed significantly lower levels of proceptive behavior. Our results show that BPA permanently alters the hypothalamic estrogen-dependent mechanisms that govern sexual behavior in the adult female rat.

  3. Female Moth Calling and Flight Behavior Are Altered Hours Following Pheromone Autodetection: Possible Implications for Practical Management with Mating Disruption

    PubMed Central

    Stelinski, Lukasz; Holdcraft, Robert; Rodriguez-Saona, Cesar

    2014-01-01

    Female moths are known to detect their own sex pheromone—a phenomenon called “autodetection”. Autodetection has various effects on female moth behavior, including altering natural circadian rhythm of calling behavior, inducing flight, and in some cases causing aggregations of conspecifics. A proposed hypothesis for the possible evolutionary benefits of autodetection is its possible role as a spacing mechanism to reduce female-female competition. Here, we explore autodetection in two species of tortricids (Grapholita molesta (Busck) and Choristoneura rosaceana (Harris)). We find that females of both species not only “autodetect,” but that learning (change in behavior following experience) occurs, which affects behavior for at least 24 hours after pheromone pre-exposure. Specifically, female calling in both species is advanced at least 24 hours, but not 5 days, following pheromone pre-exposure. Also, the propensity of female moths to initiate flight and the duration of flights, as quantified by a laboratory flight mill, were advanced in pre-exposed females as compared with controls. Pheromone pre-exposure did not affect the proportion of mated moths when they were confined with males in small enclosures over 24 hours in laboratory assays. We discuss the possible implications of these results with respect to management of these known pest species with the use of pheromone-based mating disruption. PMID:26462694

  4. Long-term sex selective hormonal and behavior alterations in mice exposed to low doses of chlorpyrifos in utero.

    PubMed

    Haviland, Julia A; Butz, Daniel E; Porter, Warren P

    2010-01-01

    Chlorpyrifos, O,O-diethyl-O-(3,5,6-trichloro-2-pyridyl) phosphorothioate, is an organophosphate insecticide known to be present in human urine. In utero exposure to chlorpyrifos may cause long-term hormonal and behavior alterations. In this study mice were exposed to 0, 1 or 5mg/kg chlorpyrifos on gestational days 17-20. In utero exposed mice were then tested in a novel foraging behavior maze and assayed for thyroid hormones. Free Thyroxine Index increased significantly in females, but not males. Learning latency and reduced learning ability was evident during training sessions 5-9 in female mice exposed to 1 or 5mg/kg chlorpyrifos. No learning deficiencies were observed in male mice. No differences were seen in behavior when using a standard radial arm maze during the nine training sessions. These data suggest that mice are susceptible to neuro-endocrine reprogramming by chlorpyrifos, and demonstrate the efficacy of the novel foraging maze as an efficient behavior assay tool.

  5. Social Isolation Stress Induces Anxious-Depressive-Like Behavior and Alterations of Neuroplasticity-Related Genes in Adult Male Mice

    PubMed Central

    Ieraci, Alessandro; Mallei, Alessandra; Popoli, Maurizio

    2016-01-01

    Stress is a major risk factor in the onset of several neuropsychiatric disorders including anxiety and depression. Although several studies have shown that social isolation stress during postweaning period induces behavioral and brain molecular changes, the effects of social isolation on behavior during adulthood have been less characterized. Aim of this work was to investigate the relationship between the behavioral alterations and brain molecular changes induced by chronic social isolation stress in adult male mice. Plasma corticosterone levels and adrenal glands weight were also analyzed. Socially isolated (SI) mice showed higher locomotor activity, spent less time in the open field center, and displayed higher immobility time in the tail suspension test compared to group-housed (GH) mice. SI mice exhibited reduced plasma corticosterone levels and reduced difference between right and left adrenal glands. SI showed lower mRNA levels of the BDNF-7 splice variant, c-Fos, Arc, and Egr-1 in both hippocampus and prefrontal cortex compared to GH mice. Finally, SI mice exhibited selectively reduced mGluR1 and mGluR2 levels in the prefrontal cortex. Altogether, these results suggest that anxious- and depressive-like behavior induced by social isolation stress correlates with reduction of several neuroplasticity-related genes in the hippocampus and prefrontal cortex of adult male mice. PMID:26881124

  6. Repeated exposure of adult rats to transient oxidative stress induces various long-lasting alterations in cognitive and behavioral functions.

    PubMed

    Iguchi, Yoshio; Kosugi, Sakurako; Nishikawa, Hiromi; Lin, Ziqiao; Minabe, Yoshio; Toda, Shigenobu

    2014-01-01

    Exposure of neonates to oxidative stress may increase the risk of psychiatric disorders such as schizophrenia in adulthood. However, the effects of moderate oxidative stress on the adult brain are not completely understood. To address this issue, we systemically administrated 2-cyclohexen-1-one (CHX) to adult rats to transiently reduce glutathione levels. Repeated administration of CHX did not affect the acquisition or motivation of an appetitive instrumental behavior (lever pressing) rewarded by a food outcome under a progressive ratio schedule. In addition, response discrimination and reversal learning were not affected. However, acute CHX administration blunted the sensitivity of the instrumental performance to outcome devaluation, and this effect was prolonged in rats with a history of repeated CHX exposure, representing pro-depression-like phenotypes. On the other hand, repeated CHX administration reduced immobility in forced swimming tests and blunted acute cocaine-induced behaviors, implicating antidepressant-like effects. Multivariate analyses segregated a characteristic group of behavioral variables influenced by repeated CHX administration. Taken together, these findings suggest that repeated administration of CHX to adult rats did not cause a specific mental disorder, but it induced long-term alterations in behavioral and cognitive functions, possibly related to specific neural correlates.

  7. Traumatic Brain Injury in Young Rats Leads to Progressive Behavioral Deficits Coincident with Altered Tissue Properties in Adulthood

    PubMed Central

    Ajao, David O.; Pop, Viorela; Kamper, Joel E.; Adami, Arash; Rudobeck, Emil; Huang, Lei; Vlkolinsky, Roman; Hartman, Richard E.; Ashwal, Stephen; Obenaus, André

    2012-01-01

    Abstract Traumatic brain injury (TBI) affects many infants and children, and results in enduring motor and cognitive impairments with accompanying changes in white matter tracts, yet few experimental studies in rodent juvenile models of TBI (jTBI) have examined the timeline and nature of these deficits, histologically and functionally. We used a single controlled cortical impact (CCI) injury to the parietal cortex of rats at post-natal day (P) 17 to evaluate behavioral alterations, injury volume, and morphological and molecular changes in gray and white matter, with accompanying measures of electrophysiological function. At 60 days post-injury (dpi), we found that jTBI animals displayed behavioral deficits in foot-fault and rotarod tests, along with a left turn bias throughout their early developmental stages and into adulthood. In addition, anxiety-like behaviors on the zero maze emerged in jTBI animals at 60 dpi. The final lesion constituted only ∼3% of brain volume, and morphological tissue changes were evaluated using MRI, as well as immunohistochemistry for neuronal nuclei (NeuN), myelin basic protein (MBP), neurofilament-200 (NF200), and oligodendrocytes (CNPase). White matter morphological changes were associated with a global increase in MBP immunostaining and reduced compound action potential amplitudes at 60 dpi. These results suggest that brain injury early in life can induce long-term white matter dysfunction, occurring in parallel with the delayed development and persistence of behavioral deficits, thus modeling clinical and longitudinal TBI observations. PMID:22697253

  8. Social Isolation Stress Induces Anxious-Depressive-Like Behavior and Alterations of Neuroplasticity-Related Genes in Adult Male Mice.

    PubMed

    Ieraci, Alessandro; Mallei, Alessandra; Popoli, Maurizio

    2016-01-01

    Stress is a major risk factor in the onset of several neuropsychiatric disorders including anxiety and depression. Although several studies have shown that social isolation stress during postweaning period induces behavioral and brain molecular changes, the effects of social isolation on behavior during adulthood have been less characterized. Aim of this work was to investigate the relationship between the behavioral alterations and brain molecular changes induced by chronic social isolation stress in adult male mice. Plasma corticosterone levels and adrenal glands weight were also analyzed. Socially isolated (SI) mice showed higher locomotor activity, spent less time in the open field center, and displayed higher immobility time in the tail suspension test compared to group-housed (GH) mice. SI mice exhibited reduced plasma corticosterone levels and reduced difference between right and left adrenal glands. SI showed lower mRNA levels of the BDNF-7 splice variant, c-Fos, Arc, and Egr-1 in both hippocampus and prefrontal cortex compared to GH mice. Finally, SI mice exhibited selectively reduced mGluR1 and mGluR2 levels in the prefrontal cortex. Altogether, these results suggest that anxious- and depressive-like behavior induced by social isolation stress correlates with reduction of several neuroplasticity-related genes in the hippocampus and prefrontal cortex of adult male mice.

  9. Reduced Anxiety-Like Behavior and Altered Hippocampal Morphology in Female p75NTRexon IV−/− Mice

    PubMed Central

    Puschban, Zoe; Sah, Anupam; Grutsch, Isabella; Singewald, Nicolas; Dechant, Georg

    2016-01-01

    The presence of the p75 neurotrophin receptor (p75NTR) in adult basal forebrain cholinergic neurons, precursor cells in the subventricular cell layer and the subgranular cell layer of the hippocampus has been linked to alterations in learning as well as anxiety- and depression- related behaviors. In contrast to previous studies performed in a p75NTRexon III−/− model still expressing the short isoform of the p75NTR, we focused on locomotor and anxiety–associated behavior in p75NTRexon IV−/− mice lacking both p75NTR isoforms. Comparing p75NTRexon IV−/− and wildtype mice for both male and female animals showed an anxiolytic-like behavior as evidenced by increased central activities in the open field paradigm and flex field activity system as well as higher numbers of open arm entries in the elevated plus maze test in female p75NTR knockout mice. Morphometrical analyses of dorsal and ventral hippocampus revealed a reduction of width of the dentate gyrus and the granular cell layer in the dorsal but not ventral hippocampus in male and female p75NTRexon IV−/− mice. We conclude that germ-line deletion of p75NTR seems to differentially affect morphometry of dorsal and ventral dentate gyrus and that p75NTR may play a role in anxiety-like behavior, specifically in female mice. PMID:27313517

  10. Effect of nanohypericum (Hypericum perforatum gold nanoparticles) treatment on restraint stressinduced behavioral and biochemical alteration in male albino mice

    PubMed Central

    Prakash, D. Jaya; ArulKumar, S.; Sabesan, M.

    2010-01-01

    Backgorund: Hypericum perforatum extract (HPE), is known for its antidepressant effect. Methods: In the present study we investigated the effect of H. perforatum gold nanoparticles (Nanohypericum-HPGNPs) protective role against restraint stress-induced behavioral and biochemical alterations in mice. Animals were immobilized for a period of 6 hrs/day. HPE (200 mg/kg) and nanohypericum (20 mg/kg) were administered 30 minutes before the animals were subjected to acute immobilized stress. Behavioral test parameters for anxiety and spatial memory were assessed followed by biochemical parmeters (lipid peroxidation, super oxide dismutase, catalase, glutathione peroxidase, reduced glutathione, etc.) subsequently. Results: The behavior study showed severe anxiety and memory loss compared to unstressed animals. Biochemical analyses revealed an increase in lipid per oxidation, depletion of super oxide dismutase, reduced glutathione, catalase activity and glutathione per oxidase as compared to unstressed animal. Twenty one days of H. perforatum and nanohypericum treatment in a dose of 200 mg/kg and 20 mg/kg, respectively, significantly attenuated restraint stress-induced behavioral and oxidative damage. Conclusion: In conclusion nanohypericum prove the modest activity than the HPE. PMID:21713134

  11. Behavioral Phenotype of Fmr1 Knock-Out Mice during Active Phase in an Altered Light/Dark Cycle.

    PubMed

    Saré, R Michelle; Levine, Merlin; Smith, Carolyn Beebe

    2016-01-01

    Fragile X syndrome (FXS) is the most commonly inherited form of intellectual disability and is a disorder that is also highly associated with autism. FXS occurs as a result of an expanded CGG repeat sequence leading to transcriptional silencing. In an animal model of FXS in which Fmr1 is knocked out (Fmr1 KO), many physical, physiological, and behavioral characteristics of the human disease are recapitulated. Prior characterization of the mouse model was conducted during the day, the inactive phase of the circadian cycle. Circadian rhythms are an important contributor to behavior and may play a role in the study of disease phenotype. Moreover, changes in the parameters of circadian rhythm are known to occur in FXS animal models. We conducted an investigation of key behavioral phenotypes in Fmr1 KO mice during their active phase. We report that phase did not alter the Fmr1 KO phenotype in open field activity, anxiety, and learning and memory. There was a slight effect of phase on social behavior as measured by time in chamber, but not by time spent sniffing. Our data strengthen the existing data characterizing the phenotype of Fmr1 KO mice, indicating that it is independent of circadian phase.

  12. Prenatal Exposure to Maternal Obesity Alters Anxiety and Stress Coping Behaviors in Aged Mice.

    PubMed

    Balsevich, Georgia; Baumann, Valentin; Uribe, Andres; Chen, Alon; Schmidt, Mathias V

    2016-01-01

    There is growing evidence that maternal obesity and prenatal exposure to a high-fat diet program fetal development to regulate the physiology and behavior of the offspring in adulthood. Yet the extent to which the maternal dietary environment contributes to adult disease vulnerability remains unclear. In the current study we tested whether prenatal exposure to maternal obesity increases the offspring's vulnerability to stress-related psychiatric disorders. We used a mouse model of maternal diet-induced obesity to investigate whether maternal obesity affects the response to adult chronic stress exposure in young adult (3-month-old) and aged adult (12-month-old) offspring. Long-lasting, delayed impairments to anxiety-like behaviors and stress coping strategies resulted on account of prenatal exposure to maternal obesity. Although maternal obesity did not change the offspring's behavioral response to chronic stress per se, we demonstrate that the behavioral outcomes induced by prenatal exposure to maternal obesity parallel the deleterious effects of adult chronic stress exposure in aged male mice. We found that the glucocorticoid receptor (GR, Nr3c1) is upregulated in various hypothalamic nuclei on account of maternal obesity. In addition, gene expression of a known regulator of the GR, FKBP51, is increased specifically within the paraventricular nucleus. These findings indicate that maternal obesity parallels the deleterious effects of adult chronic stress exposure, and furthermore identifies GR/FKBP51 signaling as a novel candidate pathway regulated by maternal obesity. © 2015 S. Karger AG, Basel.

  13. Brief Report: Altered Social Behavior in Isolation-Reared "Fmr1" Knockout Mice

    ERIC Educational Resources Information Center

    Heitzer, Andrew M.; Roth, Alexandra K.; Nawrocki, Lauren; Wrenn, Craige C.; Valdovinos, Maria G.

    2013-01-01

    Social behavior abnormalities in Fragile X syndrome (FXS) are characterized by social withdrawal, anxiety, and deficits in social cognition. To assess these deficits, a model of FXS, the "Fmr1" knockout mouse ("Fmr1" KO), has been utilized. This mouse model has a null mutation in the fragile X mental retardation 1 gene ("Fmr1") and displays…

  14. Altering Misperception of Sleep in Insomnia: Behavioral Experiment Versus Verbal Feedback

    ERIC Educational Resources Information Center

    Tang, Nicole K. Y.; Harvey, Allison G.

    2006-01-01

    Forty-eight individuals with insomnia were asked to wear an actigraph and keep a sleep diary for 2 nights. On the following day, half were shown the discrepancy between the data recorded on the actigraph and their sleep diary via a behavioral experiment, whereas the other half were told of the discrepancy verbally. Participants were then asked to…

  15. Targeting the-Dopaminergic Nervous System: Altering Behavior in Larval Zebrafish

    EPA Science Inventory

    Zebrafish (Dania rerio) are becoming an important model system in studying the effects of environmental chemicals on behavior. In order to develop a rapid in vivo screen to prioritize toxic chemicals, we have begun assessing the acute locomotor effects of drugs that act on the do...

  16. The Use of Simultaneous Feedback to Alter Teaching Behaviors of University Instructors.

    ERIC Educational Resources Information Center

    Nyquist, Jody L.; Wulff, Donald H.

    1982-01-01

    Researchers used simultaneous feedback, a means of modifying behavior through verbal cues transmitted via a transistorized ear plug, to improve the teaching skills of university faculty engaged in the act of teaching. Faculty identified areas they wished to improve after viewing videotapes of their teaching. (Authors/PP)

  17. Host behavior alters spiny lobster-viral disease dynamics: a simulation study.

    PubMed

    Dolan, Thomas W; Butler, Mark J; Shields, Jeffrey D

    2014-08-01

    Social behavior confers numerous benefits to animals but also risks, among them an increase in the spread of pathogenic diseases. We examined the trade-off between risk of predation and disease transmission under different scenarios of host spatial structure and disease avoidance behavior using a spatially explicit, individual-based model of the host pathogen interaction between juvenile Caribbean spiny lobster (Panulirus argus) and Panulirus argus Virus 1 (PaV1). Spiny lobsters are normally social but modify their behavior to avoid diseased conspecifics, a potentially effective means of reducing transmission but one rarely observed in the wild. We found that without lobster avoidance of diseased conspecifics, viral outbreaks grew in intensity and duration in simulations until the virus was maintained continuously at unrealistically high levels. However, when we invoked disease avoidance at empirically observed levels, the intensity and duration of outbreaks was reduced and the disease extirpated within five years. Increased lobster (host) spatial aggregation mimicking that which occurs when sponge shelters for lobsters are diminished by harmful algal blooms, did not significantly increase PaV1 transmission or persistence in lobster populations. On the contrary, behavioral aversion of diseased conspecifics effectively reduced viral prevalence, even when shelters were limited, which reduced shelter availability for all lobsters but increased predation, especially of infected lobsters. Therefore, avoidance of diseased conspecifics selects against transmission by contact, promotes alternative modes of transmission, and results in a more resilient host-pathogen system.

  18. Brief Report: Altered Social Behavior in Isolation-Reared "Fmr1" Knockout Mice

    ERIC Educational Resources Information Center

    Heitzer, Andrew M.; Roth, Alexandra K.; Nawrocki, Lauren; Wrenn, Craige C.; Valdovinos, Maria G.

    2013-01-01

    Social behavior abnormalities in Fragile X syndrome (FXS) are characterized by social withdrawal, anxiety, and deficits in social cognition. To assess these deficits, a model of FXS, the "Fmr1" knockout mouse ("Fmr1" KO), has been utilized. This mouse model has a null mutation in the fragile X mental retardation 1 gene ("Fmr1") and displays…

  19. Diet induced alterations in gastrointestinal bacterial populations affect memory and learning behavior in mice

    USDA-ARS?s Scientific Manuscript database

    The ability of dietary manipulation to influence learning and behavior is well recognized. While the mechanism of action is almost exclusively interpreted as direct effects of dietary constituents on neural functioning within the central nervous system (CNS), the role of dietary modification on bact...

  20. Alterations in Error-Related Brain Activity and Post-Error Behavior over Time

    ERIC Educational Resources Information Center

    Themanson, Jason R.; Rosen, Peter J.; Pontifex, Matthew B.; Hillman, Charles H.; McAuley, Edward

    2012-01-01

    This study examines the relation between the error-related negativity (ERN) and post-error behavior over time in healthy young adults (N = 61). Event-related brain potentials were collected during two sessions of an identical flanker task. Results indicated changes in ERN and post-error accuracy were related across task sessions, with more…

  1. Heat Stress Alters Ruminal Fermentation and Digesta Characteristics, and Behavior in Lactating Dairy Cattle

    USDA-ARS?s Scientific Manuscript database

    In a study designed to assess the impact and interaction of nonfiber carbohydrates (NFC) and ruminally degradable protein (RDP) on ruminal characteristics and animal behavior, animals experienced heat stress in the first period (HS), and no/greatly reduced heat stress (NHS) in the second period, all...

  2. Altering Misperception of Sleep in Insomnia: Behavioral Experiment Versus Verbal Feedback

    ERIC Educational Resources Information Center

    Tang, Nicole K. Y.; Harvey, Allison G.

    2006-01-01

    Forty-eight individuals with insomnia were asked to wear an actigraph and keep a sleep diary for 2 nights. On the following day, half were shown the discrepancy between the data recorded on the actigraph and their sleep diary via a behavioral experiment, whereas the other half were told of the discrepancy verbally. Participants were then asked to…

  3. Targeting the-Dopaminergic Nervous System: Altering Behavior in Larval Zebrafish

    EPA Science Inventory

    Zebrafish (Dania rerio) are becoming an important model system in studying the effects of environmental chemicals on behavior. In order to develop a rapid in vivo screen to prioritize toxic chemicals, we have begun assessing the acute locomotor effects of drugs that act on the do...

  4. Mononuclear phagocyte system in kidney disease and repair.

    PubMed

    Alikhan, Maliha A; Ricardo, Sharon D

    2013-02-01

    The mononuclear phagocyte system is comprised of circulating monocytes, tissue macrophages and dendritic cells (DCs) that play key roles in tissue homeostasis, immune surveillance, and immune and non-immune-mediated tissue injury and repair. This review summarizes the various subsets within this system that exhibit significant functional and phenotypic diversity that can adapt to their surrounding microenvironments during inflammation and in response to colony-stimulating factor (CSF)-1. The current understanding of the co-ordination of monocyte infiltration into the homeostatic and diseased kidney through adhesion molecules, chemokines and chemokine receptors, and cytokines are described. Furthermore, the significant confusion and controversy associated with monocyte differentiation into renal macrophages and DCs following infiltration into the kidney, the considerable functional and phenotypic overlap between both tissue populations and their respective roles in immune and non-immune-mediated renal is also discussed. Understanding the factors that control the activation and recruitment of cells from the mononuclear phagocyte system during renal injury may offer an avenue for the development of new cellular and growth factor-based therapies in combination with existing therapies as an alternative treatment option for patients with renal disease.

  5. The effect of dialysate on peritoneal phagocyte oxidative metabolism.

    PubMed

    Topley, N; Alobaidi, H M; Davies, M; Coles, G A; Williams, J D; Lloyd, D

    1988-09-01

    The respiratory and oxidative responses of human peritoneal polymorphonuclear leukocytes (PMN) and peritoneal macrophages (PM phi) following exposure to unused continuous ambulatory peritoneal dialysis fluid (CAPD) and early dwell effluent were studied using an open oxygen (O2) electrode system and by measurement of oxygen radical-derived luminol-dependent chemiluminescence. Both cell types responded to stimulation by increasing O2 consumption and by generating chemiluminescence even at external O2 concentrations below 50 microM O2. Oxygen concentrations in the dialysate, as measured by blood gas analysis, were never lower than 118 +/- 8.3 microM O2 even during active peritonitis. Thus oxygen availability does not appear to be rate limiting for phagocyte oxidative metabolism in the peritoneal cavity. Preexposure of both inflammatory cell types to unused fluid or early dwell CAPD effluent significantly reduced both stimulated oxygen uptake and the subsequent ability of these cells to generate chemiluminescence without significantly affecting their viability. Further investigation of this down regulatory phenomenon using unused fluid and laboratory prepared dialysis fluid revealed that low pH (5.3) and high sodium lactate concentration in combination are directly responsible for the suppressive effect of unused fluid and early dwell effluent on cell function. These observations demonstrate that cellular host defense may be impaired early in the dialysis cycle as a result of lactate mediated "stunning" of resident phagocytes. The precise nature of the molecular species responsible for this suppressive effect remains to be identified.

  6. Ingestion of Giardia lamblia trophozoites by human mononuclear phagocytes.

    PubMed Central

    Hill, D R; Pearson, R D

    1987-01-01

    Mononuclear phagocytes may be important effector cells against Giardia lamblia. Human monocyte-derived macrophages were incubated with G. lamblia trophozoites in 13% heat-inactivated autologous serum. At a G. lamblia/macrophage ratio of 1:1, the number of trophozoites ingested per 100 macrophages ranged from 1 to 12 at 0.5 h and increased for all donors (n = 6) to 10 to 92 at 8 h. Ingestion was confirmed by electron microscopy. Increasing the parasite/phagocyte ratio to 5:1 increased the percentage of macrophages with adherent but not ingested trophozoites. Incubating Giardia cells and macrophages with 20% immune serum increased ingestion of parasites eightfold, indicating that anti-G. lamblia antibody can enhance ingestion. Both phase-contrast microscopy and electron microscopy documented trophozoite destruction within macrophages. Ingestion of parasites elicited an oxidative burst as measured by luminol-enhanced chemiluminescence. In vitro, Giardia trophozoites were killed by greater than or equal to 5 X 10(-5) M H2O2. Fusion of lysosomes with parasite-containing phagosomes was suggested by acridine orange-stained preparations. Human macrophages have the capacity to ingest Giardia trophozoites and to kill intracellular parasites, possibly by oxidative microbicidal mechanisms. Images PMID:3679547

  7. [Changes in the phagocytic cell functions elicited by surgical intervention].

    PubMed

    Imamura, Y

    1994-08-01

    To evaluate the feature of the phagocytic cell functions against surgical intervention, the author analyzed superoxide production and Mac-1 expression of peripheral polymorphonuclear leukocytes (PMN), cytokine production (IL-1 beta, TNF alpha) of peripheral monocyte (Mo) and peritoneal macrophage (M phi) in 35 surgical patients. The ability of PMNs in superoxide anion production and the level of Mac-1 expression on PMNs increased within 24 hr after operation. Those changes synchronized that of Mo to produce IL-1 and TNF increased after operation and peaked at 1 POD. And L-1 and TNF production of peritoneal M phi increased and peaked at 8 hr after operation. However, both IL-1 and TNF could not be detected in their sera of all patients. These findings disclosed that the surgical injury might induce in vivo activation of local M phi and circulating Mo, and priming of the PMN by activated M phi and due to their producing cytokines such as IL-1, TNF and G-CSF. It might be, therefore, concluded that these reactions of the phagocytic cells may be one of the host defense mechanisms against surgical injury.

  8. Extracellular traps and macrophages: new roles for the versatile phagocyte

    PubMed Central

    Boe, Devin M.; Curtis, Brenda J.; Chen, Michael M.; Ippolito, Jill A.; Kovacs, Elizabeth J.

    2015-01-01

    MΦ are multipurpose phagocytes with a large repertoire of well-characterized abilities and functions, including regulation of inflammation, wound healing, maintenance of tissue homeostasis, as well as serving as an integral component of the innate-immune defense against microbial pathogens. Working along with neutrophils and dendritic cells, the other myeloid-derived professional phagocytes, MΦ are one of the key effector cells initiating and directing the host reaction to pathogenic organisms and resolving subsequent responses once the threat has been cleared. ETs are a relatively novel strategy of host defense involving expulsion of nuclear material and embedded proteins from immune cells to immobilize and kill bacteria, fungi, and viruses. As research on ETs expands, it has begun to encompass many immune cell types in unexpected ways, including various types of MΦ, which are not only capable of generating METs in response to various stimuli, but recent preclinical data suggest that they are an important agent in clearing ETs and limiting ET-mediated inflammation and tissue damage. This review aims to summarize historical and recent findings of biologic research regarding ET formation and function and discuss the role of MΦ in ET physiology and associated pathologies. PMID:25877927

  9. Manipulation of the oxytocin system alters social behavior and attraction in pair-bonding primates, Callithrix penicillata

    PubMed Central

    Smith, Adam S.; Ågmo, Anders; Birnie, Andrew K.; French, Jeffrey A.

    2010-01-01

    The establishment and maintenance of stable, long-term male-female relationships, or pair bonds, are marked by high levels of mutual attraction, selective preference for the partner, and high rates of sociosexual behavior. Central oxytocin (OT) affects social preference and partner-directed social behavior in rodents, but the role of this neuropeptide has yet to be studied in heterosexual primate relationships. The present study evaluated whether the OT system plays a role in the dynamics of social behavior and partner preference during the first three weeks of cohabitation in male and female marmosets, Callithrix penicillata. OT activity was stimulated by intranasal administration of OT, and inhibited by oral administration of a non-peptide OT-receptor antagonist (L-368,899; Merck). Social behavior throughout the pairing varied as a function of OT treatment. Compared to controls, marmosets initiated huddling with their social partner more often after OT treatments but reduced proximity and huddling after OT antagonist treatments. OT antagonist treatment also eliminated food sharing between partners. During the 24-h preference test, all marmosets interacted more with an opposite-sex stranger than with the partner. By the third-week preference test, marmosets interacted with the partner and stranger equally with the exception that intranasal-OT treatments facilitated initial partner-seeking behavior over initial contact with the stranger. Our findings demonstrate that pharmacological manipulations of OT activity alter partner-directed social behavior during pair interactions, suggesting that central OT may facilitate the process of pair-bond formation and social relationships in marmoset monkeys. PMID:20025881

  10. Alterations in affective behavior during the time course of alcohol hangover.

    PubMed

    Karadayian, Analía G; Busso, María J; Feleder, Carlos; Cutrera, Rodolfo A

    2013-09-15

    Alcohol hangover is a temporary state described as the unpleasant next-day effects after binge-like drinking. Hangover begins when ethanol is absent in plasma and is characterized by physical and psychological symptoms. Affective behavior is impaired during the acute phase of alcohol intoxication; however, no reports indicate if similar effects are observed during withdrawal. The aim of this work was to study the time-extension and possible fluctuations in affective behavior during a hangover episode. Male Swiss mice were injected i.p. either with saline (control group) or with ethanol (3.8g/kg BW) (hangover group). Anxiety, fear-related behavior and despair phenotype were evaluated at a basal point (ZT0) and every 2h up to 20h after blood alcohol levels were close to zero (hangover onset). Also, anhedonia signs and pain perception disabilities were studied. Mice exhibited an increase in anxiety-like behavior during 4h and 14h after hangover onset when evaluated by the elevated-plus maze and open field test respectively (p<0.05). Fear-related behavior was detected in hangover animals by the increase of freezing and decrease of line crossings and rearing frequency during 16h after hangover onset (p<0.001). Depression signs were found in hangover mice during 14h (p<0.05). Hangover mice showed a significant decrease in pain perception when tested by tail immersion test at the beginning of hangover (p<0.05). Our findings demonstrate a time-extension between 14 and 16h for hangover affective impairments. This study shows the long lasting effects of hangover over the phase of ethanol intoxication.

  11. Altered Neural and Behavioral Dynamics in Huntington's Disease: An Entropy Conservation Approach

    PubMed Central

    Hong, S. Lee; Barton, Scott J.; Rebec, George V.

    2012-01-01

    Background Huntington's disease (HD) is an inherited condition that results in neurodegeneration of the striatum, the forebrain structure that processes cortical information for behavioral output. In the R6/2 transgenic mouse model of HD, striatal neurons exhibit aberrant firing patterns that are coupled with reduced flexibility in the motor system. The aim of this study was to test the patterns of unpredictability in brain and behavior in wild-type (WT) and R6/2 mice. Methodology/Principal Findings Striatal local field potentials (LFP) were recorded from 18 WT and 17 R6/2 mice (aged 8–11 weeks) while the mice were exploring a plus-shaped maze. We targeted LFP activity for up to 2 s before and 2 s after each choice-point entry. Approximate Entropy (ApEn) was calculated for LFPs and Shannon Entropy was used to measure the probability of arm choice, as well as the likelihood of making consecutive 90-degree turns in the maze. We found that although the total number of choice-point crossings and entropy of arm-choice probability was similar in both groups, R6/2 mice had more predictable behavioral responses (i.e., were less likely to make 90-degree turns and perform them in alternation with running straight down the same arm), while exhibiting more unpredictable striatal activity, as indicated by higher ApEn values. In both WT and R6/2 mice, however, behavioral unpredictability was negatively correlated with LFP ApEn. Conclusions/Significance HD results in a perseverative exploration of the environment, occurring in concert with more unpredictable brain activity. Our results support the entropy conservation hypothesis in which unpredictable behavioral patterns are coupled with more predictable brain activation patterns, suggesting that this may be a fundamental process unaffected by HD. PMID:22292068

  12. Parents' adulthood stress induces behavioral and hormonal alterations in male rat offspring.

    PubMed

    Niknazar, Somayeh; Nahavandi, Arezo; Najafi, Rezvan; Danialy, Samira; Zare Mehrjerdi, Fatemeh; Karimi, Mohsen

    2013-09-01

    Exposure to stress can influence hypothalamo-pituitary-adrenal (HPA) axis in mammals and impair their behavioral/hormonal development. Stress during fetal or early life may have wide range effects on the offspring phenotype in rodents. Since the role of parents' adulthood stress before mating is not fully understood yet, we investigated the effects of parents' adulthood stress on behavioral and hormonal parameters in 10- and 30-day-old male offspring. To induce stress in the adult male and female rats, a repeated forced swimming paradigm was employed daily over the course of 21 days. Then, they were categorized into four parental breeding groups: stressed parents (SP), stressed mother (SM), stressed father (SF) and non-stressed parents (NSP). Anxiety-like behavior was tested in adult rats and 30-day-old male pups, using the elevated plus maze (EPM). The level of serum corticosterone was measured by ELISA in all groups. Stressed adult rats showed enhanced serum corticosterone concentration and anxiety-like behavior. Serum corticosterone level of the 10- and 30-day-old pups of the SP, SM and SF groups was significantly higher than pups from the non-stressed group. Furthermore, 30-day-old pups of the SP, SM and SF groups had lower time spent in the open arms compared to the control group, but stress had no significant effects on the percent of entries into the open arms. In addition, serum corticosterone level in 30-day-old pups were raised by a stressed mother was markedly more than 10-day-old pups. These findings revealed that parents' adulthood stress have negative impacts on behavioral and hormonal responses of their male offspring. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Chronic cocaine or ethanol exposure during adolescence alters novelty-related behaviors in adulthood.

    PubMed

    Stansfield, Kirstie H; Kirstein, Cheryl L

    2007-04-01

    Adolescence is a time of high-risk behavior and increased exploration. This developmental period is marked by a greater probability to initiate drug use and is associated with an increased risk to develop addiction and adulthood dependency and drug use at this time is associated with an increased risk. Human adolescents are predisposed toward an increased likelihood of risk-taking behaviors [Zuckerman M. Sensation seeking and the endogenous deficit theory of drug abuse. NIDA Res Monogr 1986;74:59-70.], including drug use or initiation. In the present study, adolescent animals were exposed to twenty days of either saline (0.9% sodium chloride), cocaine (20 mg/kg) or ethanol (1 g/kg) i.p. followed by a fifteen-day washout period. All animals were tested as adults on several behavioral measures including locomotor activity induced by a novel environment, time spent in the center of an open field, novelty preference and novel object exploration. Animals exposed to cocaine during adolescence and tested as adults exhibited a greater locomotor response in a novel environment, spent less time in the center of the novel open field and spent less time with a novel object, results that are indicative of a stress or anxiogenic response to novelty or a novel situation. Adolescent animals chronically administered ethanol and tested as adults, unlike cocaine-exposed were not different from controls in a novel environment, indicated by locomotor activity or time spent with a novel object. However, ethanol-exposed animals approached the novel object more, suggesting that exposure to ethanol during development may result in less-inhibited behaviors during adulthood. The differences in adult behavioral responses after drug exposure during adolescence are likely due to differences in the mechanisms of action of the drugs and subsequent reward and/or stress responsivity. Future studies are needed to determine the neural substrates of these long lasting drug-induced changes.

  14. Microcystins Alter Chemotactic Behavior in Caenorhabditis elegans by Selectively Targeting the AWA Sensory Neuron

    PubMed Central

    Moore, Caroline E.; Lein, Pamela J.; Puschner, Birgit

    2014-01-01

    Harmful algal blooms expose humans and animals to microcystins (MCs) through contaminated drinking water. While hepatotoxicity following acute exposure to MCs is well documented, neurotoxicity after sub-lethal exposure is poorly understood. We developed a novel statistical approach using a generalized linear model and the quasibinomial family to analyze neurotoxic effects in adult Caenorhabditis elegans exposed to MC-LR or MC-LF for 24 h. Selective effects of toxin exposure on AWA versus AWC sensory neuron function were determined using a chemotaxis assay. With a non-monotonic response MCs altered AWA but not AWC function, and MC-LF was more potent than MC-LR. To probe a potential role for protein phosphatases (PPs) in MC neurotoxicity, we evaluated the chemotactic response in worms exposed to the PP1 inhibitor tautomycin or the PP2A inhibitor okadaic acid for 24 h. Okadaic acid impaired both AWA and AWC function, while tautomycin had no effect on function of either neuronal cell type at the concentrations tested. These findings suggest that MCs alter the AWA neuron at concentrations that do not cause AWC toxicity via mechanisms other than PP inhibition. PMID:24918360

  15. A literature review of surface alteration layer effects on waste glass behavior

    SciTech Connect

    Feng, X.; Cunnane, J.C.; Bates, J.K.

    1993-01-01

    When in contact with an aqueous solution, nuclear waste glass is subject to a chemical attack that results in progressive alteration. During tills alteration, constituent elements of the glass pass into the solution; elements initially in solution diffuse into, or are adsorbed onto, the solid; and new phases appear. This results in the formation of surface layers on the reacted glass. The glass corrosion and radionuclide release can be better understood by investigating these surface layer effects. In the past decade, there have been numerous studies regarding the effects of surface layers on glass reactions. This paper presents a systematic analysis and summary of the past knowledge regarding the effects of surface layers on glass-water interaction. This paper describes the major formation mechanisms of surface layers; reviews the role of surface layers in controlling mass transport and glass reaction affinity (through crystalline phases, an amorphous silica, a gel layer, or all the components in the glass); and discusses how the surface layers contribute to the retention of radionuclides during glass dissolution.

  16. A literature review of surface alteration layer effects on waste glass behavior

    SciTech Connect

    Feng, X.; Cunnane, J.C.; Bates, J.K.

    1993-05-01

    When in contact with an aqueous solution, nuclear waste glass is subject to a chemical attack that results in progressive alteration. During tills alteration, constituent elements of the glass pass into the solution; elements initially in solution diffuse into, or are adsorbed onto, the solid; and new phases appear. This results in the formation of surface layers on the reacted glass. The glass corrosion and radionuclide release can be better understood by investigating these surface layer effects. In the past decade, there have been numerous studies regarding the effects of surface layers on glass reactions. This paper presents a systematic analysis and summary of the past knowledge regarding the effects of surface layers on glass-water interaction. This paper describes the major formation mechanisms of surface layers; reviews the role of surface layers in controlling mass transport and glass reaction affinity (through crystalline phases, an amorphous silica, a gel layer, or all the components in the glass); and discusses how the surface layers contribute to the retention of radionuclides during glass dissolution.

  17. Altered behavioral and neural responsiveness to counterfactual gains in the elderly.

    PubMed

    Tobia, Michael J; Guo, Rong; Gläscher, Jan; Schwarze, Ulrike; Brassen, Stefanie; Büchel, Christian; Obermayer, Klaus; Sommer, Tobias

    2016-06-01

    Counterfactual information processing refers to the consideration of events that did not occur in comparison to those actually experienced, in order to determine optimal actions, and can be formulated as computational learning signals, referred to as fictive prediction errors. Decision making and the neural circuitry for counterfactual processing are altered in healthy elderly adults. This experiment investigated age differences in neural systems for decision making with knowledge of counterfactual outcomes. Two groups of healthy adult participants, young (N = 30; ages 19-30 years) and elderly (N = 19; ages 65-80 years), were scanned with fMRI during 240 trials of a strategic sequential investment task in which a particular strategy of differentially weighting counterfactual gains and losses during valuation is associated with more optimal performance. Elderly participants earned significantly less than young adults, differently weighted counterfactual consequences and exploited task knowledge, and exhibited altered activity in a fronto-striatal circuit while making choices, compared to young adults. The degree to which task knowledge was exploited was positively correlated with modulation of neural activity by expected value in the vmPFC for young adults, but not in the elderly. These findings demonstrate that elderly participants' poor task performance may be related to different counterfactual processing.

  18. Chronic Anabolic Androgenic Steroid Exposure Alters Corticotropin Releasing Factor Expression and Anxiety-Like Behaviors in the Female Mouse

    PubMed Central

    Costine, Beth A; Oberlander, Joseph G; Davis, Matthew C; Penatti, Carlos A A; Porter, Donna M; Leaton, Robert N; Henderson, Leslie P

    2010-01-01

    Summary In the past several decades, the therapeutic use of anabolic androgenic steroids (AAS) has been overshadowed by illicit use of these drugs by elite athletes and a growing number of adolescents to enhance performance and body image. As with adults, AAS use by adolescents is associated with a range of behavioral effects, including increased anxiety and altered responses to stress. It has been suggested that adolescents, especially adolescent females, may be particularly susceptible to the effects of these steroids, but few experiments in animal models have been performed to test this assertion. Here we show that chronic exposure of adolescent female mice to a mixture of three commonly abused AAS (testosterone cypionate, nandrolone decanoate and methandrostenolone; 7.5 mg/kg/day for 5 days) significantly enhanced anxiety-like behavior as assessed by the acoustic startle response (ASR), but did not augment the fear-potentiated startle response (FPS) or alter sensorimotor gating as assessed by prepulse inhibition of the acoustic startle response (PPI). AAS treatment also significantly increased the levels of corticotropin releasing factor (CRF) mRNA and somal-associated CRF immunoreactivity in the central amygdala (CeA), as well as neuropil-associated immunoreactivity in the dorsal aspect of the anterolateral division of the bed nucleus of the stria terminalis (dBnST). AAS treatment did not alter CRF receptor 1 or 2 mRNA in either the CeA or the dBnST; CRF immunoreactivity in the ventral BNST, the paraventricular nucleus (PVN) or the median eminence (ME); or peripheral levels of corticosterone. These results suggest that chronic AAS treatment of adolescent female mice may enhance generalized anxiety, but not sensorimotor gating or learned fear, via a mechanism that involves increased CRF-mediated signaling from CeA neurons projecting to the dBnST. PMID:20537804

  19. Chronic anabolic androgenic steroid exposure alters corticotropin releasing factor expression and anxiety-like behaviors in the female mouse.

    PubMed

    Costine, Beth A; Oberlander, Joseph G; Davis, Matthew C; Penatti, Carlos A A; Porter, Donna M; Leaton, Robert N; Henderson, Leslie P

    2010-11-01

    In the past several decades, the therapeutic use of anabolic androgenic steroids (AAS) has been overshadowed by illicit use of these drugs by elite athletes and a growing number of adolescents to enhance performance and body image. As with adults, AAS use by adolescents is associated with a range of behavioral effects, including increased anxiety and altered responses to stress. It has been suggested that adolescents, especially adolescent females, may be particularly susceptible to the effects of these steroids, but few experiments in animal models have been performed to test this assertion. Here we show that chronic exposure of adolescent female mice to a mixture of three commonly abused AAS (testosterone cypionate, nandrolone decanoate and methandrostenolone; 7.5 mg/kg/day for 5 days) significantly enhanced anxiety-like behavior as assessed by the acoustic startle response (ASR), but did not augment the fear-potentiated startle response (FPS) or alter sensorimotor gating as assessed by prepulse inhibition of the acoustic startle response (PPI). AAS treatment also significantly increased the levels of corticotropin releasing factor (CRF) mRNA and somal-associated CRF immunoreactivity in the central nucleus of the amygdala (CeA), as well as neuropil-associated immunoreactivity in the dorsal aspect of the anterolateral division of the bed nucleus of the stria terminalis (dBnST). AAS treatment did not alter CRF receptor 1 or 2 mRNA in either the CeA or the dBnST; CRF immunoreactivity in the ventral BnST, the paraventricular nucleus (PVN) or the median eminence (ME); or peripheral levels of corticosterone. These results suggest that chronic AAS treatment of adolescent female mice may enhance generalized anxiety, but not sensorimotor gating or learned fear, via a mechanism that involves increased CRF-mediated signaling from CeA neurons projecting to the dBnST.

  20. Adolescent binge drinking alters adult brain neurotransmitter gene expression, behavior, brain regional volumes, and neurochemistry in mice

    PubMed Central

    Coleman, Leon G.; He, Jun; Lee, Joohwi; Styner, Martin; Crews, Fulton T.

    2013-01-01

    Background Binge-drinking is common in human adolescents. The adolescent brain is undergoing structural maturation and has a unique sensitivity to alcohol neurotoxicity. Therefore, adolescent binge ethanol may have long-term effects on the adult brain that alter brain structure and behaviors that are relevant to alcohol use disorders. Methods In order to determine if adolescent ethanol binge drinking alters the adult brain, male C57BL/6 mice were treated with either water or ethanol during adolescence (5g/kg/day i.g., post-natal days P28-37) and assessed during adulthood (P60-P88). An array of neurotransmitter-specific genes, behavioral tests (i.e. reversal learning, prepulse inhibition, and open field), and post-mortem brain structure using MRI and immunohistochemistry, were employed to assess persistent alterations in adult brain. Results At P38, 24 hours after adolescent ethanol (AE) binge, many neurotransmitter genes, particularly cholinergic and dopaminergic, were reduced by ethanol treatment. Interestingly, dopamine receptor type 4 mRNA was reduced and confirmed using immunohistochemistry. Normal control maturation (P38-P88) resulted in decreased neurotransmitter mRNA, e.g. an average decrease of 56%. Following adolescent ethanol treatment, adults showed greater gene expression reductions than controls, averaging 73%. Adult spatial learning assessed in the Morris water maze was not changed by adolescent ethanol treatment, but reversal learning experiments revealed deficits. Assessment of adult brain region volumes using MRI indicated that the olfactory bulb and basal forebrain were smaller in adults following adolescent ethanol. Immunohistochemical analyses found reduced basal forebrain area and fewer basal forebrain cholinergic neurons. Conclusions Adolescent binge ethanol treatment reduces adult neurotransmitter gene expression, particularly cholinergic genes, reduces basal forebrain and olfactory bulb volumes, and causes a reduction in the density of basal

  1. Sleep fragmentation exacerbates mechanical hypersensitivity and alters subsequent sleep-wake behavior in a mouse model of musculoskeletal sensitization.

    PubMed

    Sutton, Blair C; Opp, Mark R

    2014-03-01

    Sleep deprivation, or sleep disruption, enhances pain in human subjects. Chronic musculoskeletal pain is prevalent in our society, and constitutes a tremendous public health burden. Although preclinical models of neuropathic and inflammatory pain demonstrate effects on sleep, few studies focus on musculoskeletal pain. We reported elsewhere in this issue of SLEEP that musculoskeletal sensitization alters sleep of mice. In this study we hypothesize that sleep fragmentation during the development of musculoskeletal sensitization will exacerbate subsequent pain responses and alter sleep-wake behavior of mice. This is a preclinical study using C57BL/6J mice to determine the effect on behavioral outcomes of sleep fragmentation combined with musculoskeletal sensitization. Musculoskeletal sensitization, a model of chronic muscle pain, was induced using two unilateral injections of acidified saline (pH 4.0) into the gastrocnemius muscle, spaced 5 days apart. Musculoskeletal sensitization manifests as mechanical hypersensitivity determined by von Frey filament testing at the hindpaws. Sleep fragmentation took place during the consecutive 12-h light periods of the 5 days between intramuscular injections. Electroencephalogram (EEG) and body temperature were recorded from some mice at baseline and for 3 weeks after musculoskeletal sensitization. Mechanical hypersensitivity was determined at preinjection baseline and on days 1, 3, 7, 14, and 21 after sensitization. Two additional experiments were conducted to determine the independent effects of sleep fragmentation or musculoskeletal sensitization on mechanical hypersensitivity. Five days of sleep fragmentation alone did not induce mechanical hypersensitivity, whereas sleep fragmentation combined with musculoskeletal sensitization resulted in prolonged and exacerbated mechanical hypersensitivity. Sleep fragmentation combined with musculoskeletal sensitization had an effect on subsequent sleep of mice as demonstrated by increased

  2. Persistent behavioral impairments and alterations of brain dopamine system after early postnatal administration of thimerosal in rats.

    PubMed

    Olczak, Mieszko; Duszczyk, Michalina; Mierzejewski, Pawel; Meyza, Ksenia; Majewska, Maria Dorota

    2011-09-30

    The neurotoxic organomercurial thimerosal (THIM), used for decades as vaccine preservative, is a suspected factor in the pathogenesis of some neurodevelopmental disorders. Previously we showed that neonatal administration of THIM at doses equivalent to those used in infant vaccines or higher, causes lasting alterations in the brain opioid system in rats. Here we investigated neonatal treatment with THIM (at doses 12, 240, 1440 and 3000 μg Hg/kg) on behaviors, which are characteristically altered in autism, such as locomotor activity, anxiety, social interactions, spatial learning, and on the brain dopaminergic system in Wistar rats of both sexes. Adult male and female rats, which were exposed to the entire range of THIM doses during the early postnatal life, manifested impairments of locomotor activity and increased anxiety/neophobia in the open field test. In animals of both sexes treated with the highest THIM dose, the frequency of prosocial interactions was reduced, while the frequency of asocial/antisocial interactions was increased in males, but decreased in females. Neonatal THIM treatment did not significantly affect spatial learning and memory. THIM-exposed rats also manifested reduced haloperidol-induced catalepsy, accompanied by a marked decline in the density of striatal D₂ receptors, measured by immunohistochemical staining, suggesting alterations to the brain dopaminergic system. Males were more sensitive than females to some neurodisruptive/neurotoxic actions of THIM. These data document that early postnatal THIM administration causes lasting neurobehavioral impairments and neurochemical alterations in the brain, dependent on dose and sex. If similar changes occur in THIM/mercurial-exposed children, they could contribute do neurodevelopmental disorders.

  3. Selective behavioral alterations on addition of a 4'-phenyl group to cocaine.

    PubMed

    Seale, T W; Niekrasz, I; Chang, F; Singh, S; Basmadjian, G P

    1996-01-31

    We synthesized a cocaine analog in which a phenyl group was added at the para-position of the benzene ring of cocaine. This substitution caused a modest reduction (four-fold compared with cocaine) in binding potency for the primate (Papio) dopamine transporter as judged by displacement of [3H]WIN 35,428 binding from caudate/putamen membranes. Behavioral effects of this structural modification in the mouse were complex and selective, comprising absence of stimulation of locomotor activity, enhanced inhibition of locomotion and reduced lethal potency. Convulsant potency was unaltered. Substituents at the 4'-position of cocaine are important in its actions. Simple changes in the chemical structure of this drug may produce complex and selective changes in its neurochemical and behavioral actions.

  4. Repeated threat (without direct harm) alters metabolic capacity in select regions that drive defensive behavior.

    PubMed

    Kim, D J; Lee, A S; Yttredahl, A A; Gómez-Rodríguez, R; Anderson, B J

    2017-06-14

    To understand the behavioral consequences of intermittent anticipatory stress resulting from threats without accompanying physiological challenges, we developed a semi-naturalistic rodent housing and foraging environment that can include threats that are unpredictable in timing. Behavior is automatically recorded while rats forage for food or water. Over three weeks, the threats have been shown to elicit risk assessment behaviors, increase defensive burying and increase adrenal gland weight. To identify brain regions activated by this manipulation, we measured cytochrome c oxidase (COX), which is tightly coupled to neural activity. Adolescent male Sprague-Dawley rats were randomly assigned to control (CT) or unpredictable threat/stress (ST) housing conditions consisting of two tub cages, one with food and another with water, separated by a tunnel. Over three weeks (P31-P52), the ST group received randomly timed (probability of 0.25), simultaneous presentations of ferret odor, an abrupt light, and sound at the center of the tunnel. The ST group had consistently fewer tunnel crossings than the CT group, but similar body weights. Group differences in COX activity were detected in regions implicated in the control of defensive burying. There was an increase in COX activity in the hypothalamic premammillary dorsal nucleus (PMD) and lateral septum (LS), whereas a decrease was observed in the periaqueductal gray (PAG) and CA3 region of the hippocampus. There were no significant differences in the anterior cingulate cortex, prefrontal cortex, striatum or motor cortex. The sites with changes in metabolic capacity are candidates for the sites of plasticity that may underlie the behavioral adaptations to intermittent threats. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  5. Relationship between dopamine deficit and the expression of depressive behavior resulted from alteration of serotonin system.

    PubMed

    Lee, Minkyung; Ryu, Young Hoon; Cho, Won Gil; Kang, Yeo Wool; Lee, Soo Jin; Jeon, Tae Joo; Lyoo, Chul Hyoung; Kim, Chul Hoon; Kim, Dong Goo; Lee, Kyochul; Choi, Tae Hyun; Choi, Jae Yong

    2015-09-01

    Depression frequently accompanies in Parkinson's disease (PD). Previous research suggested that dopamine (DA) and serotonin systems are closely linked with depression in PD. However, comprehensive studies about the relationship between these two neurotransmitter systems are limited. Therefore, the purpose of this study is to evaluate the effect of dopaminergic destruction on the serotonin system. The interconnection between motor and depression was also examined. Two PET scans were performed in the 6-hydroxydopamine (6-OHDA) lesioned and sham operated rats: [(18) F]FP-CIT for DA transporters and [(18) F]Mefway for serotonin 1A (5-HT(1A)) receptors. Here, 6-OHDA is a neurotoxin for dopaminergic neurons. Behavioral tests were used to evaluate the severity of symptoms: rotational number for motor impairment and immobility time, acquired from the forced swim test for depression. Region-of-interests were drawn in the striatum and cerebellum for the DA system and hippocampus and cerebellum for the 5-HT system. The cerebellum was chosen as a reference region. Nondisplaceable binding potential in the striatum and hippocampus were compared between 6-OHDA and sham groups. As a result, the degree of DA depletion was negatively correlated with rotational behavior (R(2)  = 0.79, P = 0.003). In 6-OHDA lesioned rats, binding values for 5-HT(1A) receptors was 22% lower than the sham operated group. This decrement of 5-HT(1A) receptor binding was also correlated with the severity of depression (R(2)  = 0.81, P = 0.006). Taken together, this research demonstrated that the destruction of dopaminergic system causes the reduction of the serotonergic system resulting in the expression of depressive behavior. The degree of dopaminergic dysfunction was positively correlated with the impairment of the serotonin system. Severity of motor symptoms was also closely related to depressive behavior.

  6. Antioxidant effect of melatonin on the functional activity of colostral phagocytes in diabetic women.

    PubMed

    Morceli, Gliciane; Honorio-França, Adenilda C; Fagundes, Danny L G; Calderon, Iracema M P; França, Eduardo L

    2013-01-01

    Melatonin is involved in a number of physiological and oxidative processes, including functional regulation in human milk. The present study investigated the mechanisms of action of melatonin and its effects on the functional activity of colostral phagocytes in diabetic women. Colostrum samples were collected from normoglycemic (N = 38) and diabetic (N = 38) women. We determined melatonin concentration, superoxide release, bactericidal activity and intracellular Ca(2+) release by colostral phagocytes treated or not with 8-(Diethylamino) octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8) and incubated with melatonin and its precursor (N-acetyl-serotonin-NAS), antagonist (luzindole) and agonist (chloromelatonin-CMLT). Melatonin concentration was higher in colostrum samples from hyperglycemic than normoglycemic mothers. Melatonin stimulated superoxide release by colostral phagocytes from normoglycemic but not hyperglycemic women. NAS increased superoxide, irrespective of glycemic status, whereas CMTL increased superoxide only in cells from the normoglycemic group. Phagocytic activity in colostrum increased significantly in the presence of melatonin, NAS and CMLT, irrespective of glycemic status. The bactericidal activity of colostral phagocytes against enterophatogenic Escherichia coli (EPEC) increased in the presence of melatonin or NAS in the normoglycemic group, but not in the hyperglycemic group. Luzindole blocked melatonin action on colostrum phagocytes. Phagocytes from the normoglycemic group treated with melatonin exhibited an increase in intracellular Ca(2+) release. Phagocytes treated with TMB-8 (intracellular Ca(2+) inhibitor) decreased superoxide, bactericidal activity and intracellular Ca(2+) release in both groups. The results obtained suggest an interactive effect of glucose metabolism and melatonin on colostral phagocytes. In colostral phagocytes from normoglycemic mothers, melatonin likely increases the ability of colostrum to protect against

  7. Antioxidant Effect of Melatonin on the Functional Activity of Colostral Phagocytes in Diabetic Women

    PubMed Central

    Fagundes, Danny L. G.; Calderon, Iracema M. P.; França, Eduardo L.

    2013-01-01

    Melatonin is involved in a number of physiological and oxidative processes, including functional regulation in human milk. The present study investigated the mechanisms of action of melatonin and its effects on the functional activity of colostral phagocytes in diabetic women. Colostrum samples were collected from normoglycemic (N = 38) and diabetic (N = 38) women. We determined melatonin concentration, superoxide release, bactericidal activity and intracellular Ca2+ release by colostral phagocytes treated or not with 8-(Diethylamino) octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8) and incubated with melatonin and its precursor (N-acetyl-serotonin-NAS), antagonist (luzindole) and agonist (chloromelatonin-CMLT). Melatonin concentration was higher in colostrum samples from hyperglycemic than normoglycemic mothers. Melatonin stimulated superoxide release by colostral phagocytes from normoglycemic but not hyperglycemic women. NAS increased superoxide, irrespective of glycemic status, whereas CMTL increased superoxide only in cells from the normoglycemic group. Phagocytic activity in colostrum increased significantly in the presence of melatonin, NAS and CMLT, irrespective of glycemic status. The bactericidal activity of colostral phagocytes against enterophatogenic Escherichia coli (EPEC) increased in the presence of melatonin or NAS in the normoglycemic group, but not in the hyperglycemic group. Luzindole blocked melatonin action on colostrum phagocytes. Phagocytes from the normoglycemic group treated with melatonin exhibited an increase in intracellular Ca2+ release. Phagocytes treated with TMB-8 (intracellular Ca2+ inhibitor) decreased superoxide, bactericidal activity and intracellular Ca2+ release in both groups. The results obtained suggest an interactive effect of glucose metabolism and melatonin on colostral phagocytes. In colostral phagocytes from normoglycemic mothers, melatonin likely increases the ability of colostrum to protect against EPEC

  8. Cortical spreading depolarization increases adult neurogenesis, and alters behavior and hippocampus-dependent memory in mice.

    PubMed

    Urbach, Anja; Baum, Eileen; Braun, Falko; Witte, Otto W

    2017-05-01

    Cortical spreading depolarizations are an epiphenomenon of human brain pathologies and associated with extensive but transient changes in ion homeostasis, metabolism, and blood flow. Previously, we have shown that cortical spreading depolarization have long-lasting consequences on the brains transcriptome and structure. In particular, we found that cortical spreading depolarization stimulate hippocampal cell proliferation resulting in a sustained increase in adult neurogenesis. Since the hippocampus is responsible for explicit memory and adult-born dentate granule neurons contribute to this function, cortical spreading depolarization might influence hippocampus-dependent cognition. To address this question, we induced cortical spreading depolarization in C57Bl/6 J mice by epidural application of 1.5 mol/L KCl and evaluated neurogenesis and behavior at two, four, or six weeks thereafter. Congruent with our previous findings in rats, we found that cortical spreading depolarization increases numbers of newborn dentate granule neurons. Moreover, exploratory behavior and object location memory were consistently enhanced. Reference memory in the water maze was virtually unaffected, whereas memory formation in the Barnes maze was impaired with a delay of two weeks and facilitated after four weeks. These data show that cortical spreading depolarization produces lasting changes in psychomotor behavior and complex, delay- and task-dependent changes in spatial memory, and suggest that cortical spreading depolarization-like events affect the emotional and cognitive outcomes of associated brain pathologies.

  9. Smart Home-Based Health Platform for Behavioral Monitoring and Alteration of Diabetes Patients

    PubMed Central

    Helal, Abdelsalam; Cook, Diane J.; Schmalz, Mark

    2009-01-01

    Background Researchers and medical practitioners have long sought the ability to continuously and automatically monitor patients beyond the confines of a doctor's office. We describe a smart home monitoring and analysis platform that facilitates the automatic gathering of rich databases of behavioral information in a manner that is transparent to the patient. Collected information will be automatically or manually analyzed and reported to the caregivers and may be interpreted for behavioral modification in the patient. Method Our health platform consists of five technology layers. The architecture is designed to be flexible, extensible, and transparent, to support plug-and-play operation of new devices and components, and to provide remote monitoring and programming opportunities. Results The smart home-based health platform technologies have been tested in two physical smart environments. Data that are collected in these implemented physical layers are processed and analyzed by our activity recognition and chewing classification algorithms. All of these components have yielded accurate analyses for subjects in the smart environment test beds. Conclusions This work represents an important first step in the field of smart environment-based health monitoring and assistance. The architecture can be used to monitor the activity, diet, and exercise compliance of diabetes patients and evaluate the effects of alternative medicine and behavior regimens. We believe these technologies are essential for providing accessible, low-cost health assistance in an individual's own home and for providing the best possible quality of life for individuals with diabetes. PMID:20046657

  10. Male-like behavioral patterns and physiological alterations induced by androgenic gland implantation in female crayfish.

    PubMed

    Barki, Assaf; Karplus, Ilan; Khalaila, Isam; Manor, Rivka; Sagi, Amir

    2003-06-01

    The androgenic gland (AG) has been shown to regulate male sexual differentiation and secondary male characteristics in Crustacea. This study presents for the first time in crustaceans evidence for masculinization effects of the AG on reproductive behavior, in addition to morpho-anatomical and physiological effects. AG implantation into immature female red claw crayfish Cherax quadricarinatus inhibited secondary vitellogenesis and development of the ovaries, as well as morphological traits that facilitate maternal egg brooding; it also caused the appearance of secondary male characteristics. However, primary male characteristics and a masculine reproductive system were not developed. In pair encounters, aggression was substantially lower in interactions between AG-implanted and intact females than in interactions within AG-implanted or intact pairs. Moreover, elements of mating behavior, i.e. male courtship displays and false copulations, were exhibited by AG-implanted females in several encounters with intact females. In addition to known morpho-anatomical and physiological effects of the AG in crustaceans, the present study suggests that the AG has novel effects on the neural network that generates social behavior.

  11. Smart home-based health platform for behavioral monitoring and alteration of diabetes patients.

    PubMed

    Helal, Abdelsalam; Cook, Diane J; Schmalz, Mark

    2009-01-01

    Researchers and medical practitioners have long sought the ability to continuously and automatically monitor patients beyond the confines of a doctor's office. We describe a smart home monitoring and analysis platform that facilitates the automatic gathering of rich databases of behavioral information in a manner that is transparent to the patient. Collected information will be automatically or manually analyzed and reported to the caregivers and may be interpreted for behavioral modification in the patient. Our health platform consists of five technology layers. The architecture is designed to be flexible, extensible, and transparent, to support plug-and-play operation of new devices and components, and to provide remote monitoring and programming opportunities. The smart home-based health platform technologies have been tested in two physical smart environments. Data that are collected in these implemented physical layers are processed and analyzed by our activity recognition and chewing classification algorithms. All of these components have yielded accurate analyses for subjects in the smart environment test beds. This work represents an important first step in the field of smart environment-based health monitoring and assistance. The architecture can be used to monitor the activity, diet, and exercise compliance of diabetes patients and evaluate the effects of alternative medicine and behavior regimens. We believe these technologies are essential for providing accessible, low-cost health assistance in an individual's own home and for providing the best possible quality of life for individuals with diabetes. © Diabetes Technology Society

  12. Loss of rostral brainstem cholinergic activity results in decreased ultrasonic vocalization behavior and altered sensorimotor gating.

    PubMed

    Machold, Robert P

    2013-11-01

    The parabigeminal (PBG), pedunculopontine (PPTg), and laterodorsal tegmental (LDTg) nuclei located in the rostral brainstem are the primary sources of the neurotransmitter acetylcholine (ACh) for the midbrain and thalamus, and as part of the ascending reticular activating system, these cholinergic signaling pathways regulate mouse behavioral responses to sensory stimuli. Here, I report that mice harboring a conditional deletion of ACh synthesis specifically within these nuclei (ChAT(En1 KO)) exhibit decreased ultrasonic vocalizations both as pups and adults, consistent with their previously reported hypoactivity when exploring the novel environment of the open field arena. Furthermore, in prepulse inhibition (PPI) tests, ChAT(En1 KO) animals exhibited increased sensorimotor gating in comparison to control littermates. These data suggest that ACh signaling arising from the rostral brainstem modulates animal behavior in part by tuning the levels of sensorimotor gating. Thus, the net effect of this cholinergic activity is to increase sensitivity to environmental stimuli, and loss of this pathway contributes to the hypoactivity in these mutants by raising the sensory threshold for eliciting exploratory behaviors. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Subchronic and mild social defeat stress alter mouse nest building behavior.

    PubMed

    Otabi, Hikari; Goto, Tatsuhiko; Okayama, Tsuyoshi; Kohari, Daisuke; Toyoda, Atsushi

    2016-01-01

    Behavioral and physiological evaluations of animal models of depression are essential to thoroughly understand the mechanisms of depression in humans. Various models have been developed and characterized, and the socially defeated mouse has been widely used for studying depression. Here, we developed and characterized a mouse model of social aversion using a subchronic and mild social defeat stress (sCSDS) paradigm. Compared to control mice, sCSDS mice showed significantly increased body weight gain, water intake, and social aversion to dominant mice on the social interaction test. We observed nest building behavior in sCSDS mice using the pressed cotton as a nest material. Although sCSDS mice eventually successfully built nests, the onset of nest building was severely delayed compared to control mice. The underlying mechanism of this significant delay in nest building by sCSDS mice is unclear. However, our results demonstrate that nest building evaluation is a simple and useful assay for understanding behavior in socially defeated mice and screening drugs such as antidepressants. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Bioconcentration of phenanthrene and metabolites in bile and behavioral alterations in the tropical estuarine guppy Poecilia vivipara.

    PubMed

    Torreiro-Melo, Anny Gabrielle A G; Silva, Juliana Scanoni; Bianchini, Adalto; Zanardi-Lamardo, Eliete; de Carvalho, Paulo Sérgio Martins

    2015-08-01

    Quantification of polycyclic aromatic hydrocarbon (PAH) metabolites in fish bile is widely used to evaluate levels of internal PAH contamination in fish, whereas behavioral effects are deemed important to address potential risks to fish populations. The estuarine guppy Poecilia vivipara was exposed for 96h to waterborne phenanthrene at concentrations of 10, 50, 200 and 500μgL(-1). Phenanthrene and metabolites in bile were analyzed by fixed fluorescence at 260/380nm (excitation/emission) wavelengths. Phenanthrene increased in the bile of exposed fish in a dose-dependent pattern, and log bile bioconcentration factors ranged from 4.3 to 3.9 at 10 and 500μgL(-1) phenanthrene, respectively, values that are similar to predicted bioconcentration factors based on phenanthrene Kow. Swimming resistance index was reduced to 81% of control values at 500μgL(-1). Alteration of swimming speed was non monotonic, with a significant speed increase relative to control fish in treatments 50 and 200μgL(-1) phenanthrene, respectively, followed by a speed decrease in fish exposed to 500μgL(-1). However, swimming trajectories of fish exposed to 50, 200 and 500μgL(-1) was altered by the development of a repetitive circular swimming behavior, in contrast to the controls that explored the entire experimental arena. This change in swimming patterns apparently explains the reduction in prey capture rates at 200μgL(-1) phenanthrene. This study provides important information enabling the use of the estuarine guppy P. vivipara to monitor PAH metabolites in bile and its bioconcentration, linking internal exposure with ecologically relevant behavioral effects in the species.

  15. Laurate Biosensors Image Brain Neurotransmitters In Vivo: Can an Antihypertensive Medication Alter Psychostimulant Behavior?

    PubMed Central

    Broderick, Patricia A.; Ho, Helen; Wat, Karyn; Murthy, Vivek

    2008-01-01

    Neuromolecular Imaging (NMI) with novel biosensors enables the selective detection of neurotransmitters in vivo within seconds, on line and in real time. Biosensors remain in place for continuing studies over a period of months. This biotechnological advance is based on conventional electrochemistry; the biosensors detect neurotransmitters by electron transfer. Simply stated, biosensors adsorb electrons from each neurotransmitter at specific oxidation potentials; the current derived from electron transfer is proportional to neurotransmitter concentration. Selective electron transfer properties of these biosensors permit the imaging of neurotransmitters, metabolites and precursors. The novel BRODERICK PROBE® biosensors we have developed, differ in formulation and detection capabilities from biosensors/electrodes used in conventional electrochemistry/voltammetry. In these studies, NMI, specifically, the BRODERICK PROBE® laurate biosensor images neurotransmitter signals within mesolimbic neuronal terminals, nucleus accumbens (NAc); dopamine (DA), serotonin (5-HT), homovanillic acid (HVA) and L-tryptophan (L-TP) are selectively imaged. Simultaneously, we use infrared photobeams to monitor open-field movement behaviors on line with NMI in the same animal subjects. The goals are to investigate integrated neurochemical and behavioral effects of cocaine and caffeine alone and co-administered and further, to use ketanserin to decipher receptor profiles for these psychostimulants, alone and co-administered. The rationale for selecting this medication is: ketanserin (a) is an antihypertensive and cocaine and caffeine produce hypertension and (b) acts at 5-HT2A/2C receptors, prevalent in NAc and implicated in hypertension and cocaine addiction. Key findings are: (a) the moderate dose of caffeine simultaneously potentiates cocaine's neurochemical and behavioral responses. (b) ketanserin simultaneously inhibits cocaine-increased DA and 5-HT release in NAc and open

  16. Broken or maladaptive? Altered trajectories in neuroinflammation and behavior after early life adversity

    PubMed Central

    Ganguly, Prabarna; Brenhouse, Heather C.

    2014-01-01

    Exposure to adversity and stress early in development yields vulnerability to mental illnesses throughout the lifespan. Growing evidence suggests that this vulnerability has mechanistic origins involving aberrant development of both neurocircuitry and neuro-immune activity. Here we review the current understanding of when and how stress exposure initiates neuroinflammatory events that interact with brain development. We first review how early life adversity has been associated with various psychopathologies, and how neuroinflammation plays a role in these pathologies. We then summarize data and resultant hypotheses describing how early life adversity may particularly alter neuro-immune development with psychiatric consequences. Finally, we review how sex differences contribute to individualistic vulnerabilities across the lifespan. We submit the importance of understanding how stress during early development might cause outright neural or glial damage, as well as experience-dependent plasticity that may insufficiently prepare an individual for sex-specific or life-stage specific challenges. PMID:25081071

  17. Fkbp52 heterozygosity alters behavioral, endocrine and neurogenetic parameters under basal and chronic stress conditions in mice.

    PubMed

    Hartmann, Jakob; Wagner, Klaus V; Dedic, Nina; Marinescu, Daria; Scharf, Sebastian H; Wang, Xiao-Dong; Deussing, Jan M; Hausch, Felix; Rein, Theo; Schmidt, Ulrike; Holsboer, Florian; Müller, Marianne B; Schmidt, Mathias V

    2012-12-01

    Aversive life events represent one of the main risk factors for the development of many psychiatric diseases, but the interplay between environmental factors and genetic predispositions is still poorly understood. One major finding in many depressed patients is an impaired regulation of the hypothalamic-pituitary-adrenal (HPA) axis. The negative feedback loop of the HPA axis is mediated via the glucocorticoid receptor (GR) and the mineralocorticoid receptor. The co-chaperones FK506-binding protein 51 (FKBP51) and FK506-binding protein 52 (FKBP52) are components of the heat shock protein 90-receptor-heterocomplex and are functionally divergent regulators of both receptors. Here, we characterized heterozygous Fkbp52 knockout (Fkbp52(+/-)) mice under basal or chronic social defeat stress (CSDS) conditions with regard to physiological, neuroendocrine, behavioral and mRNA expression alterations. Fkbp52(+/-) mice displayed symptoms of increased stress sensitivity in a subset of behavioral and neuroendocrine parameters. These included increased anxiety-related behavior in the elevated plus-maze and an enhanced neuroendocrine response to a forced swim test (FST), possibly mediated by reduced GR sensitivity. At the same time, Fkbp52(+/-) mice also demonstrated signs of stress resilience in other behavioral and neuroendocrine aspects, such as reduced basal corticosterone levels and more active stress-coping behavior in the FST following CSDS. These contrasting results are in line with previous reports showing that FKBP52 is not involved in all branches of GR signaling, but rather acts in a gene-specific manner to regulate GR transcriptional activation. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Rearrangement of the dendritic morphology in limbic regions and altered exploratory behavior in a rat model of autism spectrum disorder.

    PubMed

    Bringas, M E; Carvajal-Flores, F N; López-Ramírez, T A; Atzori, M; Flores, G

    2013-06-25

    Valproic acid (VPA) is a blocker of histone deacetylase widely used to treat epilepsy, bipolar disorders, and migraine; its administration during pregnancy increases the risk of autism spectrum disorder (ASD) in the child. Thus, prenatal VPA exposure has emerged as a rodent model of ASD. In the present study, we aimed to investigate the effect of prenatal administration of VPA (500mg/kg) at E12.5 on the exploratory behavior and locomotor activity in a novel environment, as well as on neuronal morphological rearrangement in the prefrontal cortex (PFC), in the hippocampus, in the nucleus accumbens (NAcc), and in the basolateral amygdala (BLA) at three different ages: immediately after weaning (postnatal day 21 [PD21]), prepubertal (PD35) and postpubertal (PD70) ages. Hyper-locomotion was observed in a novel environment in VPA animals at PD21 and PD70. Interestingly, exploratory behavior assessed by the hole board test at PD70 showed a reduced frequency but an increase in the duration of head-dippings in VPA-animals compared to vehicle-treated animals. In addition, the latency to the first head-dip was longer in prenatal VPA-treated animals at PD70. Quantitative morphological analysis of dendritic spine density revealed a reduced number of spines at PD70 in the PFC, dorsal hippocampus and BLA, with an increase in the dendritic spine density in NAcc and ventral hippocampus, in prenatal VPA-treated rats. In addition, at PD70 increases in neuronal arborization were observed in the NAcc, layer 3 of the PFC, and BLA, with retracted neuronal arborization in the ventral and dorsal hippocampus. Our results extend the list of altered behaviors (exploratory behavior) detected in this model of ASD, and indicate that the VPA behavioral phenotype is accompanied by previously undescribed morphological rearrangement in limbic regions.

  19. Time Course of Behavioral Alteration and mRNA Levels of Neurotrophic Factor Following Stress Exposure in Mouse.

    PubMed

    Hashikawa, Naoya; Ogawa, Takumi; Sakamoto, Yusuke; Ogawa, Mami; Matsuo, Yumi; Zamami, Yoshito; Hashikawa-Hobara, Narumi

    2015-08-01

    Stress is known to affect neurotrophic factor expression, which induces depression-like behavior. However, whether there are time-dependent changes in neurotrophic factor mRNA expression following stress remains unclear. In the present study, we tested whether chronic stress exposure induces long-term changes in depression-related behavior, serum corticosterone, and hippocampal proliferation as well as neurotrophic factor family mRNA levels, such as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3), and ciliary neurotrophic factor (CNTF), in the mouse hippocampus. The mRNA level of neurotrophic factors (BDNF, NGF, NT-3, and CNTF) was measured using the real-time PCR. The serum corticosterone level was evaluated by enzyme-linked immunosorbent assay, and, for each subject, the hippocampal proliferation was examined by 5-bromo-2-deoxyuridine immunostaining. Mice exhibited depression-like behavior in the forced-swim test (FST) and decreased BDNF mRNA and hippocampal proliferation in the middle of the stress exposure. After 15 days of stress exposure, we observed increased immobility in the FST, serum corticosterone levels, and BDNF mRNA levels and degenerated hippocampal proliferation, maintained for at least 2 weeks. Anhedonia-like behavior in the sucrose preference test and NGF mRNA levels were decreased following 15 days of stress. NGF mRNA levels were significantly higher 1 week after stress exposure. The current data demonstrate that chronic stress exposure induces prolonged BDNF and NGF mRNA changes and increases corticosterone levels and depression-like behavior in the FST, but does not alter other neurotrophic factors or performance in the sucrose preference test.

  20. Developmental fluoxetine exposure increases behavioral despair and alters epigenetic regulation of the hippocampal BDNF gene in adult female offspring.

    PubMed

    Boulle, Fabien; Pawluski, Jodi L; Homberg, Judith R; Machiels, Barbie; Kroeze, Yvet; Kumar, Neha; Steinbusch, Harry W M; Kenis, Gunter; van den Hove, Daniel L A

    2016-04-01

    A growing number of infants are exposed to selective serotonin reuptake inhibitor (SSRI) medications during the perinatal period. Perinatal exposure to SSRI medications alter neuroplasticity and increase depressive- and anxiety-related behaviors, particularly in male offspring as little work has been done in female offspring to date. The long-term effects of SSRI on development can also differ with previous exposure to prenatal stress, a model of maternal depression. Because of the limited work done on the role of developmental SSRI exposure on neurobehavioral outcomes in female offspring, the aim of the present study was to investigate how developmental fluoxetine exposure affects anxiety and depression-like behavior, as well as the regulation of hippocampal brain-derived neurotrophic factor (BDNF) signaling in the hippocampus of adult female offspring. To do this female Sprague-Dawley rat offspring were exposed to prenatal stress and fluoxetine via the dam, for a total of four groups of female offspring: 1) No Stress+Vehicle, 2) No Stress+Fluoxetine, 3) Prenatal Stress+Vehicle, and 4) Prenatal Stress+Fluoxetine. Primary results show that, in adult female offspring, developmental SSRI exposure significantly increases behavioral despair measures on the forced swim test, decreases hippocampal BDNF exon IV mRNA levels, and increases levels of the repressive histone 3 lysine 27 tri-methylated mark at the corresponding promoter. There was also a significant negative correlation between hippocampal BDNF exon IV mRNA levels and immobility in the forced swim test. No effects of prenatal stress or developmental fluoxetine exposure were seen on tests of anxiety-like behavior. This research provides important evidence for the long-term programming effects of early-life exposure to SSRIs on female offspring, particularily with regard to affect-related behaviors and their underlying molecular mechanisms.

  1. Bisphenol S (BPS) Alters Maternal Behavior and Brain in Mice Exposed During Pregnancy/Lactation and Their Daughters.

    PubMed

    Catanese, Mary C; Vandenberg, Laura N

    2017-03-01

    Estrogenic endocrine disrupting chemicals have been shown to disrupt maternal behavior in rodents. We investigated the effects of an emerging xenoestrogen, bisphenol S (BPS), on maternal behavior and brain in CD-1 mice exposed during pregnancy and lactation (F0 generation) and in female offspring exposed during gestation and perinatal development (F1 generation). We observed different effects in F0 and F1 dams for a number of components of maternal behavior, including time on the nest, time spent on nest building, latency to retrieve pups, and latency to retrieve the entire litter. We also characterized expression of estrogen receptor α in the medial preoptic area (MPOA) and quantified tyrosine hydroxylase immunoreactive cells in the ventral tegmental area, 2 brain regions critical for maternal care. BPS-treated females in the F0 generation had a statistically significant increase in estrogen receptor α expression in the caudal subregion of the central MPOA in a dose-dependent manner. In contrast, there were no statistically significant effects of BPS on the MPOA in F1 dams or the ventral tegmental area in either generation. This work demonstrates that BPS affects maternal behavior and brain with outcomes depending on generation, dose, and postpartum period. Many studies examining effects of endocrine disrupting chemicals view the mother as a means by which offspring can be exposed during critical periods of development. Here, we demonstrate that pregnancy and lactation are vulnerable periods for the mother. We also show that developmental BPS exposure alters maternal behavior later in adulthood. Both findings have potential public health implications. Copyright © 2017 by the Endocrine Society.

  2. Reduced expression of α5GABAA receptors elicits autism-like alterations in EEG patterns and sleep-wake behavior.

    PubMed

    Mesbah-Oskui, Lia; Penna, Antonello; Orser, Beverley A; Horner, Richard L

    2017-05-01

    A reduction in the activity of GABAA receptors, particularly α5 subunit-containing GABAA receptors (α5GABAARs), has been implicated in the etiology of Autism Spectrum Disorders (ASD). Genetically modified mice that lack α5GABAARs (Gabra5(-/-)) exhibit autism-like behaviors and both enhanced and impaired learning and memory, depending on the behavioral task. The aim of this study was to examine the electroencephalogram (EEG) activity and sleep-wake behaviors in Gabra5(-/-) mice and wild-type mice. In addition, since some individuals with ASD can exhibit elevated innate immune response, mice were treated with lipopolysaccharide (LPS; 125mg/kg intraperitoneal injection) or vehicle and EEG and sleep-wake patterns were assessed. The results showed that Gabra5(-/-) mice (n=3) exhibited elevated 0-2Hz EEG activity during all sleep-wake states (all p<0.04), decreased 8-12Hz EEG activity during REM sleep (p=0.04), and decreased sleep spindles under baseline conditions compared to wild-type controls (n=4) (all p≤0.03). Alterations in EEG activity and sleep-wake behavior were identified in Gabra5(-/-) mice following treatment with LPS, however these changes were similar to those in wild-type mice. Our findings support the hypothesis that reduced α5GABAAR activity contributes to an ASD phenotype. The results also suggest that Gabra5(-/-) mice may serve as an animal model for ASD, as assessed through EEG activity and sleep-wake behaviors. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Altered behavioral performance and live imaging of circuit-specific neural deficiencies in a zebrafish model for psychomotor retardation.

    PubMed

    Zada, David; Tovin, Adi; Lerer-Goldshtein, Tali; Vatine, Gad David; Appelbaum, Lior

    2014-09-01

    The mechanisms and treatment of psychomotor retardation, which includes motor and cognitive impairment, are indefinite. The Allan-Herndon-Dudley syndrome (AHDS) is an X-linked psychomotor retardation characterized by delayed development, severe intellectual disability, muscle hypotonia, and spastic paraplegia, in combination with disturbed thyroid hormone (TH) parameters. AHDS has been associated with mutations in the monocarboxylate transporter 8 (mct8/slc16a2) gene, which is a TH transporter. In order to determine the pathophysiological mechanisms of AHDS, MCT8 knockout mice were intensively studied. Although these mice faithfully replicated the abnormal serum TH levels, they failed to exhibit the neurological and behavioral symptoms of AHDS patients. Here, we generated an mct8 mutant (mct8-/-) zebrafish using zinc-finger nuclease (ZFN)-mediated targeted gene editing system. The elimination of MCT8 decreased the expression levels of TH receptors; however, it did not affect the expression of other TH-related genes. Similar to human patients, mct8-/- larvae exhibited neurological and behavioral deficiencies. High-throughput behavioral assays demonstrated that mct8-/- larvae exhibited reduced locomotor activity, altered response to external light and dark transitions and an increase in sleep time. These deficiencies in behavioral performance were associated with altered expression of myelin-related genes and neuron-specific deficiencies in circuit formation. Time-lapse imaging of single-axon arbors and synapses in live mct8-/- larvae revealed a reduction in filopodia dynamics and axon branching in sensory neurons and decreased synaptic density in motor neurons. These phenotypes enable assessment of the therapeutic potential of three TH analogs that can enter the cells in the absence of MCT8. The TH analogs restored the myelin and axon outgrowth deficiencies in mct8-/- larvae. These findings suggest a mechanism by which MCT8 regulates neural circuit assembly

  4. Altered Behavioral Performance and Live Imaging of Circuit-Specific Neural Deficiencies in a Zebrafish Model for Psychomotor Retardation

    PubMed Central

    Lerer-Goldshtein, Tali; Vatine, Gad David; Appelbaum, Lior

    2014-01-01

    The mechanisms and treatment of psychomotor retardation, which includes motor and cognitive impairment, are indefinite. The Allan-Herndon-Dudley syndrome (AHDS) is an X-linked psychomotor retardation characterized by delayed development, severe intellectual disability, muscle hypotonia, and spastic paraplegia, in combination with disturbed thyroid hormone (TH) parameters. AHDS has been associated with mutations in the monocarboxylate transporter 8 (mct8/slc16a2) gene, which is a TH transporter. In order to determine the pathophysiological mechanisms of AHDS, MCT8 knockout mice were intensively studied. Although these mice faithfully replicated the abnormal serum TH levels, they failed to exhibit the neurological and behavioral symptoms of AHDS patients. Here, we generated an mct8 mutant (mct8−/−) zebrafish using zinc-finger nuclease (ZFN)-mediated targeted gene editing system. The elimination of MCT8 decreased the expression levels of TH receptors; however, it did not affect the expression of other TH-related genes. Similar to human patients, mct8−/− larvae exhibited neurological and behavioral deficiencies. High-throughput behavioral assays demonstrated that mct8−/− larvae exhibited reduced locomotor activity, altered response to external light and dark transitions and an increase in sleep time. These deficiencies in behavioral performance were associated with altered expression of myelin-related genes and neuron-specific deficiencies in circuit formation. Time-lapse imaging of single-axon arbors and synapses in live mct8−/− larvae revealed a reduction in filopodia dynamics and axon branching in sensory neurons and decreased synaptic density in motor neurons. These phenotypes enable assessment of the therapeutic potential of three TH analogs that can enter the cells in the absence of MCT8. The TH analogs restored the myelin and axon outgrowth deficiencies in mct8−/− larvae. These findings suggest a mechanism by which MCT8 regulates neural

  5. Meals of differing caloric content do not alter physical activity behavior during a subsequent simulated recess period in children.

    PubMed

    Smith, Kelly J; Pohle-Krauza, Rachael; Uhas, Samantha; Barkley, Jacob E

    2016-01-01

    Research on adults and animals has demonstrated that chronic and acute overfeeding can alter physical activity behavior. However, there are no assessments of the acute effects of high-calorie (HC) meals on physical activity behavior in children. This is of importance as a typical school lunch is HC. If this type of meal negatively impacts subsequent physical activity behavior, the ability of post-lunch recess periods as a means to increase energy expenditure may be lessened. To assess the effect of two meals of differing caloric content, HC and low calorie (LC), on children's subsequent physical activity behavior. Nineteen healthy children (aged 6-10) completed two laboratory sessions where they were fed lunch with HC or LC content, but equivalent macronutrient distribution. Children had 15 min to consume as much of the meal as possible per session. Children consumed 659.5 ± 101.3 kcal in the HC condition and 291.8 ± 12.1 kcal in the LC condition. After the meal, children went to a gymnasium for 40 min. In the gymnasium children had free-choice access to obstacle courses, various sports equipment, and a table with sedentary activities. Children could play with any of the activities in any amount they wished for the entire activity session. Children's physical activity was monitored with accelerometers and that data was converted into caloric expenditure. Each child ate all meals and participated in the free-choice activity sessions with no other children present. Caloric expenditure during the free-choice activity sessions was not significantly different (p = 0.4) between the HC (89.2 ± 27.3 kcals) and LC (83.4 ± 34.9 kcals) conditions. However, caloric balance (kcals eaten-kcals expended) was 2.74-fold greater (p < 0.001) in the HC condition (Δ 570.3 ± 92.2 kcals) than the LC condition (Δ 208.4 ± 32.0 kcals). Children did not alter their physical activity behavior during a free-choice activity session after consuming a HC meal

  6. Hybrid nanoparticles improve targeting to inflammatory macrophages through phagocytic signals.

    PubMed

    Bagalkot, Vaishali; Badgeley, Marcus A; Kampfrath, Thomas; Deiuliis, Jeffrey A; Rajagopalan, Sanjay; Maiseyeu, Andrei

    2015-11-10

    Macrophages are innate immune cells with great phenotypic plasticity, which allows them to regulate an array of physiological processes such as host defense, tissue repair, and lipid/lipoprotein metabolism. In this proof-of-principle study, we report that macrophages of the M1 inflammatory phenotype can be selectively targeted by model hybrid lipid-latex (LiLa) nanoparticles bearing phagocytic signals. We demonstrate a simple and robust route to fabricate nanoparticles and then show their efficacy through imaging and drug delivery in inflammatory disease models of atherosclerosis and obesity. Self-assembled LiLa nanoparticles can be modified with a variety of hydrophobic entities such as drug cargos, signaling lipids, and imaging reporters resulting in sub-100nm nanoparticles with low polydispersities. The optimized theranostic LiLa formulation with gadolinium, fluorescein and "eat-me" phagocytic signals (Gd-FITC-LiLa) a) demonstrates high relaxivity that improves magnetic resonance imaging (MRI) sensitivity, b) encapsulates hydrophobic drugs at up to 60% by weight, and c) selectively targets inflammatory M1 macrophages concomitant with controlled release of the payload of anti-inflammatory drug. The mechanism and kinetics of the payload discharge appeared to be phospholipase A2 activity-dependent, as determined by means of intracellular Förster resonance energy transfer (FRET). In vivo, LiLa targets M1 macrophages in a mouse model of atherosclerosis, allowing noninvasive imaging of atherosclerotic plaque by MRI. In the context of obesity, LiLa particles were selectively deposited to M1 macrophages within inflamed adipose tissue, as demonstrated by single-photon intravital imaging in mice. Collectively, our results suggest that phagocytic signals can preferentially target inflammatory macrophages in experimental models of atherosclerosis and obesity, thus opening the possibility of future clinical applications that diagnose/treat these conditions. Tunable Li

  7. Hybrid nanoparticles improve targeting to inflammatory macrophages through phagocytic signals

    PubMed Central

    Bagalkot, Vaishali; Badgeley, Marcus A.; Kampfrath, Thomas; Deiuliis, Jeffrey A.; Rajagopalan, Sanjay; Maiseyeu, Andrei

    2016-01-01

    Macrophages are innate immune cells with great phenotypic plasticity, which allows them to regulate an array of physiological processes such as host defense, tissue repair, and lipid/lipoprotein metabolism. In this proof-of-principle study, we report that macrophages of the M1 inflammatory phenotype can be selectively targeted by model hybrid lipid–latex (LiLa) nanoparticles bearing phagocytic signals. We demonstrate a simple and robust route to fabricate nanoparticles and then show their efficacy through imaging and drug delivery in inflammatory disease models of atherosclerosis and obesity. Self-assembled LiLa nanoparticles can be modified with a variety of hydrophobic entities such as drug cargos, signaling lipids, and imaging reporters resulting in sub-100 nm nano-particles with low polydispersities. The optimized theranostic LiLa formulation with gadolinium, fluorescein and “eat-me” phagocytic signals (Gd-FITC-LiLa) a) demonstrates high relaxivity that improves magnetic resonance imaging (MRI) sensitivity, b) encapsulates hydrophobic drugs at up to 60% by weight, and c) selectively targets inflammatory M1 macrophages concomitant with controlled release of the payload of anti-inflammatory drug. The mechanism and kinetics of the payload discharge appeared to be phospholipase A2 activity-dependent, as determined by means of intracellular Förster resonance energy transfer (FRET). In vivo, LiLa targets M1 macrophages in a mouse model of atherosclerosis, allowing noninvasive imaging of atherosclerotic plaque by MRI. In the context of obesity, LiLa particles were selectively deposited to M1 macrophages within inflamed adipose tissue, as demonstrated by single-photon intravital imaging in mice. Collectively, our results suggest that phagocytic signals can preferentially target inflammatory macrophages in experimental models of atherosclerosis and obesity, thus opening the possibility of future clinical applications that diagnose/treat these conditions. Tunable

  8. Dengue Virus-1 Infection Did Not Alter the Behavioral Response of Aedes aegypti (Diptera: Culicidae) to DEET.

    PubMed

    Sugiharto, Victor A; Murphy, Jittawadee R; Turell, Michael J; Olsen, Cara H; Stewart, V Ann; Colacicco-Mayhugh, Michelle G; Grieco, John P; Achee, Nicole L

    2016-05-01

    No licensed vaccine or antiviral drug against dengue virus (DENV) is available; therefore, most of the effort to prevent this disease is focused on reducing vector-host interactions. One of the most widely accepted methods of blocking vector-human contact is to use insect repellents to interfere with mosquito host-seeking behavior. Some arboviruses can replicate in the nervous system of the vector, raising the concern that arboviral infection may alter the insect behavioral response toward chemical stimuli. Three different Aedes aegypti (L.) mosquito cohorts: DENV-1-injected, diluent-injected, and uninjected were subjected to behavioral tests using a high-throughput screening system with 2.5% DEET and 0.14% DEET on 1, 4, 7, 10, 14, and 17 d postinjection. All test cohorts exhibited significant contact irritant or escape responses when they were exposed to 2.5% or 0.14% DEET. However, we found no biologically relevant irritancy response change in DENV-1-infected Ae. aegypti mosquitoes when they were exposed to DEET. Further studies evaluating the effects of other arboviral infections on insect repellents activity are necessary in order to provide better recommendation on the prevention of vector-borne disease transmission.

  9. Transplantation of fecal microbiota from patients with irritable bowel syndrome alters gut function and behavior in recipient mice.

    PubMed

    De Palma, Giada; Lynch, Michael D J; Lu, Jun; Dang, Vi T; Deng, Yikang; Jury, Jennifer; Umeh, Genevieve; Miranda, Pedro M; Pigrau Pastor, Marc; Sidani, Sacha; Pinto-Sanchez, Maria Ines; Philip, Vivek; McLean, Peter G; Hagelsieb, Moreno-Gabriel; Surette, Michael G; Bergonzelli, Gabriela E; Verdu, Elena F; Britz-McKibbin, Philip; Neufeld, Josh D; Collins, Stephen M; Bercik, Premysl

    2017-03-01

    Irritable bowel syndrome (IBS) is a common disorder characterized by altered gut function and often is accompanied by comorbid anxiety. Although changes in the gut microbiota have been documented, their relevance to the clinical expression of IBS is unknown. To evaluate a functional role for commensal gut bacteria in IBS, we colonized germ-free mice with the fecal microbiota from healthy control individuals or IBS patients with diarrhea (IBS-D), with or without anxiety, and monitored gut function and behavior in the transplanted mice. Microbiota profiles in recipient mice clustered according to the microbiota profiles of the human donors. Mice receiving the IBS-D fecal microbiota showed a taxonomically similar microbial composition to that of mice receiving the healthy control fecal microbiota. However, IBS-D mice showed different serum metabolomic profiles. Mice receiving the IBS-D fecal microbiota, but not the healthy control fecal microbiota, exhibited faster gastrointestinal transit, intestinal barrier dysfunction, innate immune activation, and anxiety-like behavior. These results indicate the potential of the gut microbiota to contribute to both intestinal and behavioral manifestations of IBS-D and suggest the potential value of microbiota-directed therapies in IBS patients.

  10. Protective effect of alprazolam in acute immobilization stress-induced certain behavioral and biochemical alterations in mice.

    PubMed

    Goyal, Richa; Anil, Kumar

    2007-01-01

    Stress can be viewed as a cause of adverse circumstance that induces a wide range of biochemical and behavioral changes. Oxidative stress is a major contributor to the genesis of neurodegenerative and neuropsychiatric problems. In the present study, we investigated the protective effect of alprazolam in acute immobilization-induced various behavioral and biochemical alteration in mice. Mice were immobilized for a period of 6 h. Alprazolam (0.25 and 0.5 mg/kg, i.p.) was administered 30 min before subjecting the animals to acute stress and several behavioral (mirror chamber, actophotometer, tail flick test) and biochemical tests (malondialdehyde level, glutathione, catalase, nitrite and protein) were performed. Acute immobilization stress for a period of 6 h caused severe anxiety, analgesia and decreased locomotor activity in mice. Biochemical analyses revealed an increase in malondialdehyde, nitrite level and depleted glutathione and catalase activity in stressed brain. Pretreatment with alprazolam (0.25 and 0.5 mg/kg, i.p.) significantly reversed immobilization stress-induced anxiety, analgesia and impaired locomotor activity. Biochemically, alprazolam pretreatment decreased malondialdehyde, nitrite activity and restored reduced glutathione level and catalase activity. These results suggest that alprazolam has a neuroprotective effect and can be used in the treatment and management of stress and related disorders.

  11. Genetic disruption of ankyrin-G in adult mouse forebrain causes cortical synapse alteration and behavior reminiscent of bipolar disorder.

    PubMed

    Zhu, Shanshan; Cordner, Zachary A; Xiong, Jiali; Chiu, Chi-Tso; Artola, Arabiye; Zuo, Yanning; Nelson, Andrew D; Kim, Tae-Yeon; Zaika, Natalya; Woolums, Brian M; Hess, Evan J; Wang, Xiaofang; Chuang, De-Maw; Pletnikov, Mikhail M; Jenkins, Paul M; Tamashiro, Kellie L; Ross, Christopher A

    2017-09-11

    Genome-wide association studies have implicated the ANK3 locus in bipolar disorder, a major human psychotic illness. ANK3 encodes ankyrin-G, which organizes the neuronal axon initial segment (AIS). We generated a mouse model with conditional disruption of ANK3 in pyramidal neurons of the adult forebrain (Ank-G cKO). This resulted in the expected loss of pyramidal neuron AIS voltage-gated sodium and potassium channels. There was also dramatic loss of markers of afferent GABAergic cartridge synapses, resembling the cortical microcircuitry changes in brains from psychotic patients, and suggesting disinhibition. Expression of c-fos was increased in cortical pyramidal neurons, consistent with increased neuronal activity due to disinhibition. The mice showed robust behavioral phenotypes reminiscent of aspects of human mania, ameliorated by antimania drugs lithium and valproate. Repeated social defeat stress resulted in repeated episodes of dramatic behavioral changes from hyperactivity to "depression-like" behavior, suggestive of some aspects of human bipolar disorder. Overall, we suggest that this Ank-G cKO mouse model recapitulates some of the core features of human bipolar disorder and indicates that cortical microcircuitry alterations during adulthood may be involved in pathogenesis. The model may be useful for studying disease pathophysiology and for developing experimental therapeutics.

  12. Melanoma tumors alter proinflammatory cytokine production and monoamine brain function, and induce depressive-like behavior in male mice.

    PubMed

    Lebeña, Andrea; Vegas, Oscar; Gómez-Lázaro, Eneritz; Arregi, Amaia; Garmendia, Larraitz; Beitia, Garikoitz; Azpiroz, Arantza

    2014-10-01

    Depression is a commonly observed disorder among cancer patients; however, the mechanisms underlying the relationship between these disorders are not well known. We used an animal model to study the effects of tumor development on depressive-like behavior manifestation, proinflammatory cytokine expression, and central monoaminergic activity. Male OF1 mice were inoculated with B16F10 melanoma tumor cells and subjected to a 21-day behavioral evaluation comprising the novel palatable food (NPF) test and tail suspension test (TST). The mRNA expression levels of proinflammatory cytokines, interleukin (IL)-1β and IL-6, and tumor necrosis factor-alpha (TNF-α), were measured in the hypothalamus and hippocampus and the levels of IL-6 and TNF-α were measured in the blood plasma. We similarly determined the monoamine turnover in various brain areas. The tumors resulted in increasing the immobility in TST and the expression level of IL-6 in the hippocampus. These increases corresponded with a decrease in dopaminergic activity in the striatum and a decrease in serotonin turnover in the prefrontal cortex. Similarly, a high level of tumor development produced increases in the brain expression levels of IL-6 and TNF-α and plasma levels of IL-6. Our findings suggest that these alterations in inflammatory cytokines and monoaminergic system function might be responsible for the manifestation of depressive-like behaviors in tumor-bearing mice.

  13. Neonatal status epilepticus alters prefrontal-striatal circuitry and enhances methamphetamine-induced behavioral sensitization in adolescence.

    PubMed

    Lin, Tzu-Chao; Huang, Li-Tung; Huang, Ya-Ni; Chen, Gunng-Shinng; Wang, Jia-Yi

    2009-02-01

    Neonatal seizures may alter the developing neurocircuitry and cause behavioral abnormalities in adulthood. We found that rats previously subjected to lithium-pilocarpine (LiPC)-induced neonatal status epilepticus (NeoSE) exhibited enhanced behavioral sensitization to methamphetamine (MA) in adolescence. Neurochemically, dopamine (DA) and metabolites were markedly decreased in prefrontal cortex (PFC) and insignificantly changed in striatum by NeoSE, but were increased in both PFC and striatum by NeoSE+MA. Glutamate levels were increased in both PFC and striatum in the NeoSE+MA group. DA turnover, an index of utilization and activity, was increased by NeoSE but reversed by MA in PFC. Gene expression of the regulator of G-protein signaling 4 (RGS4) was downregulated in PFC and striatum by NeoSE and further suppressed by MA. These findings suggest NeoSE affects both dopaminergic and glutamatergic systems in the prefrontal-striatal circuitry that manifests as enhanced behavioral sensitization to MA in adolescence.

  14. Lack of thyroid hormone receptor alpha1 is associated with selective alterations in behavior and hippocampal circuits.

    PubMed

    Guadaño-Ferraz, A; Benavides-Piccione, R; Venero, C; Lancha, C; Vennström, B; Sandi, C; DeFelipe, J; Bernal, J

    2003-01-01

    Brain development and function are dependent on thyroid hormone (T3), which acts through nuclear hormone receptors. T3 receptors (TRs) are transcription factors that activate or suppress target gene expression in a hormone-dependent or -independent fashion. Two distinct genes, TRalpha and TRbeta, encode several receptor isoforms with specific functions defined in many tissues but not in the brain. Mutations in the TRbeta gene cause the syndrome of peripheral resistance to thyroid hormone; however, no alterations of the TRalpha gene have been described in humans. Here we demonstrate that mice lacking the TRalpha1 isoform display behavioral abnormalities of hippocampal origin, as shown by the open field and fear conditioning tests. In the open field test mutant mice revealed less exploratory behavior than wild-type mice. In the contextual fear conditioning test mutant mice showed a significantly higher freezing response than wild-type controls when tested 1 week after training. These findings correlated with fewer GABAergic terminals on the CA1 pyramidal neurons in the mutant mice. Our results indicate that TRalpha1 is involved in the regulation of hippocampal structure and function, and raise the possibility that deletions or mutations of this receptor isoform may lead to behavioral changes or even psychiatric syndromes in humans.

  15. Characterisation of the green turtle's leukocyte subpopulations by flow cytometry and evaluation of their phagocytic activity.

    PubMed

    Muñoz, F A; Franco-Noguez, S Y; Gonzalez-Ballesteros, E; Negrete-Philippe, A C; Flores-Romo, L

    2014-06-01

    Phagocytosis is a fundamental aspect of innate immunity that is conserved across many species making it a potentially useful health-assessment tool for wildlife. In non-mammalian vertebrates, heterophils, monocytes, macrophages, melanomacrophages, and thrombocytes all have phagocytic properties. Recently, B lymphocytes from fish, amphibians, and aquatic turtles have also showed phagocytic capacity. Phagocytes can be studied by flow cytometry; however, the use of this tool is complicated in reptiles partly because nucleated erythrocytes complicate the procedure. We separated green turtle leukocytes by density gradient centrifugation and identified subpopulations by flow cytometry and confocal microscopy. Additionally, we assessed their ability to phagocytize Fluorspheres and Ovoalbumin-Alexa. We found that heterophils and lymphocytes but not monocytes could be easily identified by flow cytometry. While heterophils from adults and juvenile turtles were equally able to phagocytize fluorspheres, adults had significantly more phagocytic ability for OVA-Alexa. Lymphocytes had a mild phagocytic activity with fluorospheres (27-38 %; 39-45 %) and OVA-Alexa (35-46 %; 14-22 %) in juvenile and adult green turtles, respectively. Confocal microscopy confirmed phagocytosis of fluorospheres in both heterophils and lymphocytes. This provides the first evidence that green turtle lymphocytes have phagocytic activity and that this assay could potentially be useful to measure one aspect of innate immunity in this species.

  16. Weight Reduction in Athletes May Adversely Affect the Phagocytic Function of Monocytes.

    ERIC Educational Resources Information Center

    Kono, Ichiro; And Others

    1988-01-01

    Study of the monocyte phagocytic function in nine competitive athletes before and after a two-week weight reduction (through calorie restriction) program revealed that their pre-program phagocytic activity was higher than in sedentary controls but decreased significantly after the program. This suggests calorie restriction may affect the human…

  17. Weight Reduction in Athletes May Adversely Affect the Phagocytic Function of Monocytes.

    ERIC Educational Resources Information Center

    Kono, Ichiro; And Others

    1988-01-01

    Study of the monocyte phagocytic function in nine competitive athletes before and after a two-week weight reduction (through calorie restriction) program revealed that their pre-program phagocytic activity was higher than in sedentary controls but decreased significantly after the program. This suggests calorie restriction may affect the human…

  18. Arsenic alters behavioral parameters and brain ectonucleotidases activities in zebrafish (Danio rerio).

    PubMed

    Baldissarelli, Luis Antonio; Capiotti, Katiucia Marques; Bogo, Mauricio Reis; Ghisleni, Gabriele; Bonan, Carla Denise

    2012-05-01

    Arsenic (As) exposure has been associated with serious chronic health risk to humans including cancer and neurological disturbances. However, there are limited studies about the mechanisms behind its toxicity. In this study, adult zebrafish were exposed to several concentrations of As (0.05, 5, and 15 mg As/L; Na(2)HAsO(4) as As(V)) during 96 h to evaluate the zebrafish locomotor activity, anxiety, and brain extracellular nucleotide hydrolysis. We showed that 5 mg/L As is able to promote significant decrease in the locomotor activity as evaluated by the number of line crossings. In addition, animals treated with 5mg/L As presented an increase in time spent in the lower zone of the tank test, suggesting an anxiogenic effect. Considering that behavioral parameters, such as anxiety and locomotion, might be modulated by the purinergic system, we also evaluated the ectonucleotidase activities in zebrafish brain after a 96-h As exposure. A significant decrease in ATP, ADP, and AMP hydrolysis was observed at 0.05, 5, and 15 mg/L when compared to control group. These findings demonstrated that As might affect behavioral parameters and the ectonucleotidase activities in zebrafish, suggesting this enzyme pathway is a target for neurotoxic effects induced by As. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Protective effect of curcumin (Curcuma longa), against aluminium toxicity: Possible behavioral and biochemical alterations in rats.

    PubMed

    Kumar, Anil; Dogra, Samrita; Prakash, Atish

    2009-12-28

    Aluminium is a potent neurotoxin and has been associated with Alzheimer's disease (AD) causality for decades. Prolonged aluminium exposure induces oxidative stress and increases amyloid beta levels in vivo. Current treatment modalities for AD provide only symptomatic relief thus necessitating the development of new drugs with fewer side effects. The aim of the study was to demonstrate the protective effect of chronic curcumin administration against aluminium-induced cognitive dysfunction and oxidative damage in rats. Aluminium chloride (100 mg/kg, p.o.) was administered to rats daily for 6 weeks. Rats were concomitantly treated with curcumin (per se; 30 and 60 mg/kg, p.o.) daily for a period of 6 weeks. On the 21st and 42nd day of the study behavioral studies to evaluate memory (Morris water maze and elevated plus maze task paradigms) and locomotion (photoactometer) were done. The rats were sacrificed on 43rd day following the last behavioral test and various biochemical tests were performed to assess the extent of oxidative damage. Chronic aluminium chloride administration resulted in poor retention of memory in Morris water maze, elevated plus maze task paradigms and caused marked oxidative damage. It also caused a significant increase in the acetylcholinesterase activity and aluminium concentration in aluminium treated rats. Chronic administration of curcumin significantly improved memory retention in both tasks, attenuated oxidative damage, acetylcholinesterase activity and aluminium concentration in aluminium treated rats (P<0.05). Curcumin has neuroprotective effects against aluminium-induced cognitive dysfunction and oxidative damage.

  20. Altered social behavior and sexual characteristics in mosquitofish (Gambusia holbrooki) living downstream of a paper mill.

    PubMed

    Toft, Gunnar; Baatrup, Erik; Guillette, Louis J

    2004-12-10

    Several environmental contaminants have been found in paper mill effluent including substances with androgenic properties. The presence of androgenic substances in paper mill effluent was also indicated in the present study which demonstrated masculinized anal fins of female mosquitofish from the paper mill effluent contaminated Fenholloway River. In addition, when compared to the nearby Econfina River, which does not receive paper mill effluent, fewer females from the contaminated river were pregnant, they were smaller and their estradiol concentration exhibited greater variation. Males from the Fenholloway River and the Econfina River had similar sperm counts, but the testes were larger and greater variation in testosterone concentration was observed in male fish from the Fenholloway River. In males and females from the Fenholloway River, liver weights were increased and computer-aided behavior analysis demonstrated a reduction in their social behavior when compared to reference fish. We conclude that a number of sexual characteristics were affected in mosquitofish living in the paper mill contaminated Fenholloway River, with possible adverse effects on the reproduction of this population.

  1. Tickling during adolescence alters fear-related and cognitive behaviors in rats after prolonged isolation.

    PubMed

    Hori, Miyo; Yamada, Kazuo; Ohnishi, Junji; Sakamoto, Shigeko; Furuie, Hiroki; Murakami, Kazuo; Ichitani, Yukio

    2014-05-28

    Social interactions during adolescence are important especially for neuronal development and behavior. We recently showed that positive emotions induced by repeated tickling could modulate fear-related behaviors and sympatho-adrenal stress responses. In the present study, we examined whether tickling during early to late adolescence stage could reverse stress vulnerability induced by socially isolated rearing. Ninety-five male Fischer rats were reared under different conditions from postnatal day (PND) 21 to 53: group-housed (three rats/cage), isolated-nontickled (one rat/cage) and isolated-tickled (received tickling stimulation for 5min a day). Auditory fear conditioning was then performed on the rats at PND 54. Isolated-tickled rats exhibited significantly lower freezing compared with group-housed rats in the first retention test performed 48h after conditioning and compared with isolated-nontickled rats in the second retention test performed 96h after conditioning. Moreover, group-housed and isolated-tickled rats tended to show a significant decrease in freezing responses in the second retention test; however, isolated-nontickled rats did not. In the Morris water maze task that was trained in adulthood (PND 88), but not in adolescence (PND 56), isolated-nontickled rats showed slower decrease of escape latency compared to group-housed rats; however, tickling treatment significantly improved this deficit. These results suggest that tickling stimulation can alleviate the detrimental effects of isolated rearing during adolescence on fear responses and spatial learning. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Positive reinforcement training as a technique to alter nonhuman primate behavior: quantitative assessments of effectiveness.

    PubMed

    Schapiro, Steven J; Bloomsmith, Mollie A; Laule, Gail E

    2003-01-01

    Many suggest that operant conditioning techniques can be applied successfully to improve the behavioral management of nonhuman primates in research settings. However, relatively little empirical data exist to support this claim. This article is a review of several studies that discussed applied positive reinforcement training techniques (PRT) on breeding/research colonies of rhesus macaques (Macaca mulatta) and chimpanzees (Pan troglodytes) at The University of Texas M. D. Anderson Cancer Center and measured their effectiveness. Empirical analyses quantified the amount of time required to train rhesus monkeys to come up, station, target, and stay. Additionally, a study found that time spent affiliating by female rhesus was changed as a function of training low affiliators to affiliate more and high affiliators to affiliate less. Another study successfully trained chimpanzees to feed without fighting and to come inside on command. PRT is an important behavioral management tool that can improve the care and welfare of primates in captivity. Published empirical findings are essential for managers to assess objectively the utility of positive reinforcement training techniques in enhancing captive management and research procedures.

  3. Trpc2-deficient lactating mice exhibit altered brain and behavioral responses to bedding stimuli.

    PubMed

    Hasen, Nina S; Gammie, Stephen C

    2011-03-01

    The trpc2 gene encodes an ion channel involved in pheromonal detection and is found in the vomeronasal organ. In tprc2(-/-) knockout (KO) mice, maternal aggression (offspring protection) is impaired and brain Fos expression in females in response to a male are reduced. Here we examine in lactating wild-type (WT) and KO mice behavioral and brain responses to different olfactory/pheromonal cues. Consistent with previous studies, KO dams exhibited decreased maternal aggression and nest building, but we also identified deficits in nighttime nursing and increases in pup weight. When exposed to the bedding tests, WT dams typically ignored clean bedding, but buried male-soiled bedding from unfamiliar males. In contrast, KO dams buried both clean and soiled bedding. Differences in brain Fos expression were found between WT and KO mice in response to either no bedding, clean bedding, or soiled bedding. In the accessory olfactory bulb, a site of pheromonal signal processing, KO mice showed suppressed Fos activation in the anterior mitral layer relative to WT mice in response to clean and soiled bedding. However, in the medial and basolateral amygdala, KO mice showed a robust Fos response to bedding, suggesting that regions of the amygdala canonically associated with pheromonal sensing can be active in the brains of KO mice, despite compromised signaling from the vomeronasal organ. Together, these results provide further insights into the complex ways by which pheromonal signaling regulates the brain and behavior of the maternal female.

  4. Trpc2-deficient lactating mice exhibit altered brain and behavioral responses to bedding stimuli

    PubMed Central

    Hasen, Nina S.; Gammie, Stephen C.

    2010-01-01

    The trpc2 gene encodes an ion channel involved in pheromonal detection and is found in the vomeronasal organ. In tprc2-/- knockout (KO) mice, maternal aggression (offspring protection) is impaired and brain Fos expression in females in response to a male are reduced. Here we examine in lactating wild-type (WT) and KO mice behavioral and brain responses to different olfactory/pheromonal cues. Consistent with previous studies, KO dams exhibited decreased maternal aggression and nest building, but we also identified deficits in nighttime nursing and increases in pup weight. When exposed to the bedding tests, WT dams typically ignored clean bedding, but buried male-soiled bedding from unfamiliar males. In contrast, KO dams buried both clean and soiled bedding. Differences in brain Fos expression were found between WT and KO mice in response to either no bedding, clean bedding, or soiled bedding. In the accessory olfactory bulb, a site of pheromonal signal processing, KO mice showed suppressed Fos activation in the anterior mitral layer relative to WT mice in response to clean and soiled bedding. However, in the medial and basolateral amygdala, KO mice showed a robust Fos response to bedding, suggesting that regions of the amygdala canonically associated with pheromonal sensing can be active in the brains of KO mice, despite compromised signaling from the vomeronasal organ. Together, these results provide further insights into the complex ways by which pheromonal signaling regulates the brain and behavior of the maternal female. PMID:21070815

  5. Orbitofrontal Dopamine Depletion Upregulates Caudate Dopamine and Alters Behavior via Changes in Reinforcement Sensitivity

    PubMed Central

    Cardinal, R. N.; Rygula, R.; Hong, Y. T.; Fryer, T. D.; Sawiak, S. J.; Ferrari, V.; Cockcroft, G.; Aigbirhio, F. I.; Robbins, T. W.; Roberts, A. C.

    2014-01-01

    Schizophrenia is associated with upregulation of dopamine (DA) release in the caudate nucleus. The caudate has dense connections with the orbitofrontal cortex (OFC) via the frontostriatal loops, and both areas exhibit pathophysiological change in schizophrenia. Despite evidence that abnormalities in dopaminergic neurotransmission and prefrontal cortex function co-occur in schizophrenia, the influence of OFC DA on caudate DA and reinforcement processing is poorly understood. To test the hypothesis that OFC dopaminergic dysfunction disrupts caudate dopamine function, we selectively depleted dopamine from the OFC of marmoset monkeys and measured striatal extracellular dopamine levels (using microdialysis) and dopamine D2/D3 receptor binding (using positron emission tomography), while modeling reinforcement-related behavior in a discrimination learning paradigm. OFC dopamine depletion caused an increase in tonic dopamine levels in the caudate nucleus and a corresponding reduction in D2/D3 receptor binding. Computational modeling of behavior showed that the lesion increased response exploration, reducing the tendency to persist with a recently chosen response side. This effect is akin to increased response switching previously seen in schizophrenia and was correlated with striatal but not OFC D2/D3 receptor binding. These results demonstrate that OFC dopamine depletion is sufficient to induce striatal hyperdopaminergia and changes in reinforcement learning relevant to schizophrenia. PMID:24872570

  6. Self-affirmation alters the brain’s response to health messages and subsequent behavior change

    PubMed Central

    Falk, Emily B.; O’Donnell, Matthew Brook; Cascio, Christopher N.; Tinney, Francis; Kang, Yoona; Lieberman, Matthew D.; Taylor, Shelley E.; An, Lawrence; Resnicow, Kenneth; Strecher, Victor J.

    2015-01-01

    Health communications can be an effective way to increase positive health behaviors and decrease negative health behaviors; however, those at highest risk are often most defensive and least open to such messages. For example, increasing physical activity among sedentary individuals affects a wide range of important mental and physical health outcomes, but has proven a challenging task. Affirming core values (i.e., self-affirmation) before message exposure is a psychological technique that can increase the effectiveness of a wide range of interventions in health and other domains; however, the neural mechanisms of affirmation’s effects have not been studied. We used functional magnetic resonance imaging (fMRI) to examine neural processes associated with affirmation effects during exposure to potentially threatening health messages. We focused on an a priori defined region of interest (ROI) in ventromedial prefrontal cortex (VMPFC), a brain region selected for its association with self-related processing and positive valuation. Consistent with our hypotheses, those in the self-affirmation condition produced more activity in VMPFC during exposure to health messages and went on to increase their objectively measured activity levels more. These findings suggest that affirmation of core values may exert its effects by allowing at-risk individuals to see the self-relevance and value in otherwise-threatening messages. PMID:25646442

  7. Colonization of Bacteria on the Surfaces of Cold-Sprayed Copper Coatings Alters Their Electrochemical Behaviors

    NASA Astrophysics Data System (ADS)

    Suo, Xinkun; Abdoli, Leila; Liu, Yi; Xia, Peng; Yang, Guanjun; Li, Hua

    2017-04-01

    Copper coatings were fabricated on stainless steel plates by cold spraying. Attachment and colonization of Bacillus sp. on their surfaces in artificial seawater were characterized, and their effects on anticorrosion performances of the coatings were examined. Attached bacteria were observed using field emission scanning electron microscopy. Electrochemical behaviors including potentiodynamic polarization and electrochemical impedance spectroscopy with/without bacterial attachment were evaluated using commercial electrochemical analysis station Modulab. Results show that Bacillus sp. opt to settle on low-lying spots of the coating surfaces in early stage, followed by recruitment and attachment of extracellular polymeric substances (EPS) secreted through metabolism of Bacillus sp. The bacteria survive with the protection of EPS. An attachment model is proposed to illustrate the bacterial behaviors on the surfaces of the coatings. Electrochemical data show that current density under Bacillus sp. environment decreases compared to that without the bacteria. Charge-transfer resistance increases markedly in bacteria-containing seawater, suggesting that corrosion resistance increases and corrosion rate decreases. The influencing mechanism of bacteria settlement on corrosion resistance of the cold-sprayed copper coatings was discussed and elucidated.

  8. Colonization of Bacteria on the Surfaces of Cold-Sprayed Copper Coatings Alters Their Electrochemical Behaviors

    NASA Astrophysics Data System (ADS)

    Suo, Xinkun; Abdoli, Leila; Liu, Yi; Xia, Peng; Yang, Guanjun; Li, Hua

    2017-02-01

    Copper coatings were fabricated on stainless steel plates by cold spraying. Attachment and colonization of Bacillus sp. on their surfaces in artificial seawater were characterized, and their effects on anticorrosion performances of the coatings were examined. Attached bacteria were observed using field emission scanning electron microscopy. Electrochemical behaviors including potentiodynamic polarization and electrochemical impedance spectroscopy with/without bacterial attachment were evaluated using commercial electrochemical analysis station Modulab. Results show that Bacillus sp. opt to settle on low-lying spots of the coating surfaces in early stage, followed by recruitment and attachment of extracellular polymeric substances (EPS) secreted through metabolism of Bacillus sp. The bacteria survive with the protection of EPS. An attachment model is proposed to illustrate the bacterial behaviors on the surfaces of the coatings. Electrochemical data show that current density under Bacillus sp. environment decreases compared to that without the bacteria. Charge-transfer resistance increases markedly in bacteria-containing seawater, suggesting that corrosion resistance increases and corrosion rate decreases. The influencing mechanism of bacteria settlement on corrosion resistance of the cold-sprayed copper coatings was discussed and elucidated.

  9. Self-affirmation alters the brain's response to health messages and subsequent behavior change.

    PubMed

    Falk, Emily B; O'Donnell, Matthew Brook; Cascio, Christopher N; Tinney, Francis; Kang, Yoona; Lieberman, Matthew D; Taylor, Shelley E; An, Lawrence; Resnicow, Kenneth; Strecher, Victor J

    2015-02-17

    Health communications can be an effective way to increase positive health behaviors and decrease negative health behaviors; however, those at highest risk are often most defensive and least open to such messages. For example, increasing physical activity among sedentary individuals affects a wide range of important mental and physical health outcomes, but has proven a challenging task. Affirming core values (i.e., self-affirmation) before message exposure is a psychological technique that can increase the effectiveness of a wide range of interventions in health and other domains; however, the neural mechanisms of affirmation's effects have not been studied. We used functional magnetic resonance imaging (fMRI) to examine neural processes associated with affirmation effects during exposure to potentially threatening health messages. We focused on an a priori defined region of interest (ROI) in ventromedial prefrontal cortex (VMPFC), a brain region selected for its association with self-related processing and positive valuation. Consistent with our hypotheses, those in the self-affirmation condition produced more activity in VMPFC during exposure to health messages and went on to increase their objectively measured activity levels more. These findings suggest that affirmation of core values may exert its effects by allowing at-risk individuals to see the self-relevance and value in otherwise-threatening messages.

  10. Meal time shift disturbs circadian rhythmicity along with metabolic and behavioral alterations in mice.

    PubMed

    Yoon, Ji-Ae; Han, Dong-Hee; Noh, Jong-Yun; Kim, Mi-Hee; Son, Gi Hoon; Kim, Kyungjin; Kim, Chang-Ju; Pak, Youngmi Kim; Cho, Sehyung

    2012-01-01

    In modern society, growing numbers of people are engaged in various forms of shift works or trans-meridian travels. Such circadian misalignment is known to disturb endogenous diurnal rhythms, which may lead to harmful physiological consequences including metabolic syndrome, obesity, cancer, cardiovascular disorders, and gastric disorders as well as other physical and mental disorders. However, the precise mechanism(s) underlying these changes are yet unclear. The present work, therefore examined the effects of 6 h advance or delay of usual meal time on diurnal rhythmicities in home cage activity (HCA), body temperature (BT), blood metabolic markers, glucose homeostasis, and expression of genes that are involved in cholesterol homeostasis by feeding young adult male mice in a time-restrictive manner. Delay of meal time caused locomotive hyperactivity in a significant portion (42%) of subjects, while 6 h advance caused a torpor-like symptom during the late scotophase. Accordingly, daily rhythms of blood glucose and triglyceride were differentially affected by time-restrictive feeding regimen with concurrent metabolic alterations. Along with these physiological changes, time-restrictive feeding also influenced the circadian expression patterns of low density lipoprotein receptor (LDLR) as well as most LDLR regulatory factors. Strikingly, chronic advance of meal time induced insulin resistance, while chronic delay significantly elevated blood glucose levels. Taken together, our findings indicate that persistent shifts in usual meal time impact the diurnal rhythms of carbohydrate and lipid metabolisms in addition to HCA and BT, thereby posing critical implications for the health and diseases of shift workers.

  11. Air pollution impairs cognition, provokes depressive-like behaviors and alters hippocampal cytokine expression and morphology.

    PubMed

    Fonken, L K; Xu, X; Weil, Z M; Chen, G; Sun, Q; Rajagopalan, S; Nelson, R J

    2011-10-01

    Particulate matter air pollution is a pervasive global risk factor implicated in the genesis of pulmonary and cardiovascular disease. Although the effects of prolonged exposure to air pollution are well characterized with respect to pulmonary and cardiovascular function, comparatively little is known about the impact of particulate matter on affective and cognitive processes. The central nervous system may be adversely affected by activation of reactive oxygen species and pro-inflammatory pathways that accompany particulate matter pollution. Thus, we investigated whether long-term exposure to ambient fine airborne particulate matter (<2.5 μm (PM(2.5))) affects cognition, affective responses, hippocampal inflammatory cytokines and neuronal morphology. Male mice were exposed to either PM(2.5) or filtered air (FA) for 10 months. PM(2.5) mice displayed more depressive-like responses and impairments in spatial learning and memory as compared with mice exposed to FA. Hippocampal pro-inflammatory cytokine expression was elevated among PM(2.5) mice. Apical dendritic spine density and dendritic branching were decreased in the hippocampal CA1 and CA3 regions, respectively, of PM(2.5) mice. Taken together, these data suggest that long-term exposure to particulate air pollution levels typical of exposure in major cities around the globe can alter affective responses and impair cognition.

  12. Central Thalamic Deep-Brain Stimulation Alters Striatal-Thalamic Connectivity in Cognitive Neural Behavior.

    PubMed

    Lin, Hui-Ching; Pan, Han-Chi; Lin, Sheng-Huang; Lo, Yu-Chun; Shen, Elise Ting-Hsin; Liao, Lun-De; Liao, Pei-Han; Chien, Yi-Wei; Liao, Kuei-Da; Jaw, Fu-Shan; Chu, Kai-Wen; Lai, Hsin-Yi; Chen, You-Yin

    2015-01-01

    Central thalamic deep brain stimulation (CT-DBS) has been proposed as an experimental therapeutic approach to produce consistent sustained regulation of forebrain arousal for several neurological diseases. We investigated local field potentials (LFPs) induced by CT-DBS from the thalamic central lateral nuclei (CL) and the striatum as potential biomarkers for the enhancement of lever-pressing skill learning. LFPs were simultaneously recorded from multiple sites in the CL, ventral striatum (Vstr), and dorsal striatum (Dstr). LFP oscillation power and functional connectivity were assessed and compared between the CT-DBS and sham control groups. The theta and alpha LFP oscillations were significantly increased in the CL and striatum in the CT-DBS group. Furthermore, interhemispheric coherences between bilateral CL and striatum were increased in the theta band. Additionally, enhancement of c-Fos activity, dopamine D2 receptor (Drd2), and α4-nicotinic acetylcholine receptor (α4-nAChR) occurred after CT-DBS treatment in the striatum and hippocampus. CT-DBS strengthened thalamic-striatal functional connectivity, which demonstrates that the inter-regional connectivity enhancement might contribute to synaptic plasticity in the striatum. Altered dopaminergic and cholinergic receptors resulted in modulation of striatal synaptic plasticity's ability to regulate downstream signaling cascades for higher brain functions of lever-pressing skill learning.

  13. Behavioral alterations and Fos protein immunoreactivity in brain regions of bile duct-ligated cirrhotic rats.

    PubMed

    Le Sueur-Maluf, Luciana; Viana, Milena B; Nagaoka, Márcia R; Amorim, Ana Laura B; Cardoso, Amanda N; Rodrigues, Bruna C; Mendes, Natália F; Bittencourt, Jackson C; Céspedes, Isabel C

    2015-03-01

    Hepatic encephalopathy (HE) encompasses a variety of neuropsychiatric symptoms, including anxiety and psychomotor dysfunction. Although HE is a frequent complication of liver cirrhosis, the neurobiological substrates responsible for its clinical manifestations are largely unclear. In the present study, male Wistar rats were bile duct-ligated (BDL), a procedure which induces liver cirrhosis, and on the 21st day after surgery tested in the elevated plus-maze (EPM) and in an open field for anxiety and locomotor activity measurements. Analysis of Fos protein immunoreactivity (Fos-ir) was used to better understand the neurobiological alterations present in BDL animals. Plasma levels of ammonia were quantified and histopathological analysis of the livers was performed. BDL rats showed a significant decrease in the percentage of entries and time spent in the open arms of the EPM, an anxiogenic effect. These animals also presented significant decreases in Fos-ir in the lateral septal nucleus and medial amygdalar nucleus. Their ammonia plasma levels were significantly higher when compared to the sham group and the diagnosis of cirrhosis was confirmed by histopathological analysis. These results indicate that the BDL model induces anxiogenic results, possibly related to changes in the activation of anxiety-mediating circuitries and to increases in ammonia plasma levels.

  14. Central Thalamic Deep-Brain Stimulation Alters Striatal-Thalamic Connectivity in Cognitive Neural Behavior

    PubMed Central

    Lin, Hui-Ching; Pan, Han-Chi; Lin, Sheng-Huang; Lo, Yu-Chun; Shen, Elise Ting-Hsin; Liao, Lun-De; Liao, Pei-Han; Chien, Yi-Wei; Liao, Kuei-Da; Jaw, Fu-Shan; Chu, Kai-Wen; Lai, Hsin-Yi; Chen, You-Yin

    2016-01-01

    Central thalamic deep brain stimulation (CT-DBS) has been proposed as an experimental therapeutic approach to produce consistent sustained regulation of forebrain arousal for several neurological diseases. We investigated local field potentials (LFPs) induced by CT-DBS from the thalamic central lateral nuclei (CL) and the striatum as potential biomarkers for the enhancement of lever-pressing skill learning. LFPs were simultaneously recorded from multiple sites in the CL, ventral striatum (Vstr), and dorsal striatum (Dstr). LFP oscillation power and functional connectivity were assessed and compared between the CT-DBS and sham control groups. The theta and alpha LFP oscillations were significantly increased in the CL and striatum in the CT-DBS group. Furthermore, interhemispheric coherences between bilateral CL and striatum were increased in the theta band. Additionally, enhancement of c-Fos activity, dopamine D2 receptor (Drd2), and α4-nicotinic acetylcholine receptor (α4-nAChR) occurred after CT-DBS treatment in the striatum and hippocampus. CT-DBS strengthened thalamic-striatal functional connectivity, which demonstrates that the inter-regional connectivity enhancement might contribute to synaptic plasticity in the striatum. Altered dopaminergic and cholinergic receptors resulted in modulation of striatal synaptic plasticity's ability to regulate downstream signaling cascades for higher brain functions of lever-pressing skill learning. PMID:26793069

  15. Aqueous exposure to the progestin, levonorgestrel, alters anal fin development and reproductive behavior in the eastern mosquitofish (Gambusia holbrooki).

    PubMed

    Frankel, Tyler E; Meyer, Michael T; Orlando, Edward F

    2016-08-01

    significant between the two treatments. LNG caused significant increases in the 4:6 anal fin ratio of males exposed to 100ng/L, with no effects observed in the 10ng/L treatment. In addition, the reproductive behavior of control males paired with female mosquitofish exposed to 100ng/L LNG was also altered, for these males spent more time exhibiting no reproductive behavior, had decreased attending behavior, and a lower number of gonopodial thrusts compared to control males paired to control female mosquitofish. Given the rapid effects on both anal fin morphology and behavior observed in this study, the mosquitofish is an excellent sentinel species for the detection of exposure to LNG and likely other 19-nortestosterone derived contraceptive progestins in the environment.

  16. Does Respondent Driven Sampling Alter the Social Network Composition and Health-Seeking Behaviors of Illicit Drug Users Followed Prospectively?

    PubMed Central

    Rudolph, Abby E.; Latkin, Carl; Crawford, Natalie D.; Jones, Kandice C.; Fuller, Crystal M.

    2011-01-01

    Respondent driven sampling (RDS) was originally developed to sample and provide peer education to injection drug users at risk for HIV. Based on the premise that drug users' social networks were maintained through sharing rituals, this peer-driven approach to disseminate educational information and reduce risk behaviors capitalizes and expands upon the norms that sustain these relationships. Compared with traditional outreach interventions, peer-driven interventions produce greater reductions in HIV risk behaviors and adoption of safer behaviors over time, however, control and intervention groups are not similarly recruited. As peer-recruitment may alter risk networks and individual risk behaviors over time, such comparison studies are unable to isolate the effect of a peer-delivered intervention. This analysis examines whether RDS recruitment (without an intervention) is associated with changes in health-seeking behaviors and network composition over 6 months. New York City drug users (N = 618) were recruited using targeted street outreach (TSO) and RDS (2006–2009). 329 non-injectors (RDS = 237; TSO = 92) completed baseline and 6-month surveys ascertaining demographic, drug use, and network characteristics. Chi-square and t-tests compared RDS- and TSO-recruited participants on changes in HIV testing and drug treatment utilization and in the proportion of drug using, sex, incarcerated and social support networks over the follow-up period. The sample was 66% male, 24% Hispanic, 69% black, 62% homeless, and the median age was 35. At baseline, the median network size was 3, 86% used crack, 70% used cocaine, 40% used heroin, and in the past 6 months 72% were tested for HIV and 46% were enrolled in drug treatment. There were no significant differences by recruitment strategy with respect to changes in health-seeking behaviors or network composition over 6 months. These findings suggest no association between RDS recruitment and changes in network

  17. Suppression of phagocytic and bactericidal functions of rat alveolar macrophages by the organic component of diesel exhaust particles.

    PubMed

    Yin, Xuejun J; Dong, Caroline C; Ma, Jane Y C; Roberts, Jenny R; Antonini, James M; Ma, Joseph K H

    2007-05-15

    Exposure to diesel exhaust particles (DEP) was shown to increase the susceptibility of the lung to bacterial infection in rats. In this study, the effects of DEP on alveolar macrophage (AM) phagocytic and bactericidal functions and cytokine secretion