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Sample records for albino male mice

  1. Reproductive toxic potential of panmasala in male Swiss albino mice.

    PubMed

    Kumari, A; Mojidra, Bn; Gautam, Ak; Verma, Y; Kumar, Sunil

    2011-09-01

    Some ingredients of panmasala have the ability to penetrate the blood-testis barrier but the reproductive toxic potential of panmasala has not been studied. This study is aimed to assess the possible damage caused by panmasala to male reproductive system in mice. Swiss albino male mice were randomly divided into 7 groups receiving either standard control diet or panmasala-containing diet. Three doses (0.5%, 1.5% and 3%) of panmasala plain (PMP) as well as panmasala with tobacco (PMT)-gutkha were given for a period of 6 months. Assessment of organ weight, sperm count and morphology, spermatid count, sperm production, testicular 17β-hydroxysteroid dehydrogenase (17β-HSD) activity and histology were conducted. A nonsignificant decrease in absolute and relative weight of testis and epididymis was observed. Spermatid count, sperm count and production were significantly decreased and 17β-HSD activity was found considerably declined at 3% of both PMP- and PMT-treated groups as compared to control. The histological observations revealed panmasala induced testicular damage. Abnormal morphology of sperm head shape was significantly elevated in higher doses of both types of panmasala-treated groups than control. The results suggests that panmasala has reproductive toxic potential and more alteration is seen with gutkha as compared to panmasala plain, indicating that similar effects might also be possible in humans. PMID:21343226

  2. Assessment of imidacloprid-induced mutagenic effects in somatic cells of Swiss albino male mice.

    PubMed

    Bagri, Preeti; Kumar, Vinod; Sikka, Anil K

    2016-10-01

    Pesticides are being used for plant protection to increase food protection and to reduce insect-borne diseases worldwide. Exposure to the pesticides may cause genotoxic effects on both the target and nontarget organisms, including man. Therefore, the mutagenicity evaluation of such pesticides has become a priority area of research. Imidacloprid (IMI), a neonicotinoid insecticide, is widely used in agriculture either alone or in combination with other insecticides. A combined approach employing micronucleus test (MNT) and chromosomal aberrations assay (CA) was utilized to assess the mutagenicity of imidacloprid in bone marrow of Swiss albino male mice. IMI suspension was prepared in 3% gum acacia and administered at doses of 5.5, 11 and 22 mg/kg body weight for 7, 14 and 28 days to mice. IMI treatment resulted in a dose and time-dependant increase in the frequencies of micronuclei per cell and chromosomal aberrations in bone marrow cells. A statistically significant increase in chromosomal aberrations and micronuclei/cell was found only after daily treatment of IMI at highest selected dose (22 mg/kg body weight) for longest selected time period (28 days) compared to the control group. Thus, daily exposure of imidacloprid at a dose level of 22 mg/kg body weight for 28 days caused mutagenic effects on the somatic cells of Swiss albino male mice. PMID:26823062

  3. Effect of imatinib on the biochemical parameters of the reproductive function in male Swiss albino mice

    PubMed Central

    Prasad, A.M.; Ramnarayan, K.; Nalini, K.; Bairy, K.L.

    2011-01-01

    Background: Treatment of cancers with cytotoxic agents such as tyrosine kinase inhibiting drugs often, but not always, result in transient to permanent testicular dysfunction. Germ cells are important targets of many chemicals. Most of the drugs are genotoxins and induce irreversible effect on genetic makeup. These mutagenic changes are proportionally related to carcinogenesis. This is alarmingly dangerous in youth and children, since these effects last longer, affecting fertility or forming basis for carcinogenesis. There is paucity of reports on planned studies of imatinib on the testicular function. Hence, the study was planned to assess the effects of imatinib on biochemical markers of testicular functions in male Swiss albino mice. Materials and Methods: Male Swiss albino mice were treated with imatinib and sacrificed at the end of first, second, fourth, fifth, seventh, and tenth week after the last exposure to imatinib. The testis were removed, weighed, and processed for biochemical analysis. Results: The intratesticular testosterone level was significantly (P<0.001) reduced in treated groups and severe effect was observed on week 4 and 5. The intratesticular lactate dehydrogenase (LDH) level was significantly increased by imatinib in all treated groups up to week 5. Conclusion: Imatinib does affect testosterone and LDH level significantly, but this effect is reversible once the drug is withdrawn. This finding may help the clinicians to plan and address the fertility-related issues in young patients of reproductive age who are being treated with imatinib for gastrointestinal tumors and chronic myeloid leukemia. PMID:21844991

  4. Effect of sorafenib on sperm count and sperm motility in male Swiss albino mice.

    PubMed

    Shetty, Surekha Devadasa; Bairy, Laxminarayana Kurady

    2015-01-01

    The issue of male germ line mutagenesis and the effects on developmental defects in the next generation has become increasingly high profile over recent years. Mutagenic substance affects germinal cells in the testis. Since the cells are undergoing different phases of cell division and maturation, it is an ideal system to study the effect of chemotherapeutic agents. There are lacunae in the literature on the effect of sorafenib on gonadal function. With background, a study was planned to evaluate the effects of sorafenib on sperm count and sperm motility in male Swiss albino mice. Male Swiss albino mice were used for the study. The animals were segregated into control, positive control (PC) and three treatment groups. PC received oral imatinib (100 mg/kg body weight) and treatment groups received 25, 50, and 100 mg/kg body weight of sorafenib orally for 7 consecutive days at intervals of 24 h between two administrations. The control group remained in the home cage for an equal duration of time to match their corresponding treatment groups. The animals were sacrificed at the end of 1(st), 2(nd), 4(th), 5(th), 7(th), and 10(th) weeks after the last exposure to drug, respectively. Sperm suspensions were prepared and introduced into a counting chamber. Total sperm count and motility were recorded. There was a significant decrease in sperm count and sperm motility by sorafenib which was comparable with the effect of PC imatinib. Sorafenib adversely affects sperm count and sperm motility which are reversible after discontinuation of treatment. PMID:26605157

  5. Effect of sorafenib on sperm count and sperm motility in male Swiss albino mice

    PubMed Central

    Shetty, Surekha Devadasa; Bairy, Laxminarayana Kurady

    2015-01-01

    The issue of male germ line mutagenesis and the effects on developmental defects in the next generation has become increasingly high profile over recent years. Mutagenic substance affects germinal cells in the testis. Since the cells are undergoing different phases of cell division and maturation, it is an ideal system to study the effect of chemotherapeutic agents. There are lacunae in the literature on the effect of sorafenib on gonadal function. With background, a study was planned to evaluate the effects of sorafenib on sperm count and sperm motility in male Swiss albino mice. Male Swiss albino mice were used for the study. The animals were segregated into control, positive control (PC) and three treatment groups. PC received oral imatinib (100 mg/kg body weight) and treatment groups received 25, 50, and 100 mg/kg body weight of sorafenib orally for 7 consecutive days at intervals of 24 h between two administrations. The control group remained in the home cage for an equal duration of time to match their corresponding treatment groups. The animals were sacrificed at the end of 1st, 2nd, 4th, 5th, 7th, and 10th weeks after the last exposure to drug, respectively. Sperm suspensions were prepared and introduced into a counting chamber. Total sperm count and motility were recorded. There was a significant decrease in sperm count and sperm motility by sorafenib which was comparable with the effect of PC imatinib. Sorafenib adversely affects sperm count and sperm motility which are reversible after discontinuation of treatment. PMID:26605157

  6. Effect of Olea oleaster and Juniperus procera leaves extracts on thioacetamide induced hepatic cirrhosis in male albino mice

    PubMed Central

    Al-Attar, Atef M.; Alrobai, Ali A.; Almalki, Daklallah A.

    2015-01-01

    The effect of Olea oleaster and Juniperus procera leaves extracts and their combination on thioacetamide (TAA)-induced hepatic cirrhosis were investigated in male albino mice. One hundred sixty mice were used in this study and were randomly distributed into eight groups of 20 each. Mice of group 1 served as controls. Mice of group 2 were treated with TAA. Mice of group 3 were exposed to TAA and supplemented with O. oleaster leaves extracts. Mice of group 4 were treated with TAA and supplemented with J. procera leaves extracts. Mice of group 5 were subjected to TAA and supplemented with O. oleaster and J. procera leaves extracts. Mice of groups 6, 7 and 8 were supplemented with O. oleaster, J. procera, and O. oleaster and J. procera leaves extracts respectively. Administration of TAA for six and twelve weeks resulted in a decline in body weight gain and increased the levels of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and total bilirubin. Histopathological evaluations of hepatic sections from mice treated with TAA showed severe alterations including increase of fibrogenesis processes with structural damage. Treatment of mice with these extracts showed a pronounced attenuation in TAA induced hepatic cirrhosis associated with physiological and histopathological alterations. Finally, this study suggests that the supplementation of these extracts may act as antioxidant agents and could be an excellent adjuvant support in the therapy of hepatic cirrhosis. PMID:27081362

  7. Effect of Olea oleaster and Juniperus procera leaves extracts on thioacetamide induced hepatic cirrhosis in male albino mice.

    PubMed

    Al-Attar, Atef M; Alrobai, Ali A; Almalki, Daklallah A

    2016-05-01

    The effect of Olea oleaster and Juniperus procera leaves extracts and their combination on thioacetamide (TAA)-induced hepatic cirrhosis were investigated in male albino mice. One hundred sixty mice were used in this study and were randomly distributed into eight groups of 20 each. Mice of group 1 served as controls. Mice of group 2 were treated with TAA. Mice of group 3 were exposed to TAA and supplemented with O. oleaster leaves extracts. Mice of group 4 were treated with TAA and supplemented with J. procera leaves extracts. Mice of group 5 were subjected to TAA and supplemented with O. oleaster and J. procera leaves extracts. Mice of groups 6, 7 and 8 were supplemented with O. oleaster, J. procera, and O. oleaster and J. procera leaves extracts respectively. Administration of TAA for six and twelve weeks resulted in a decline in body weight gain and increased the levels of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and total bilirubin. Histopathological evaluations of hepatic sections from mice treated with TAA showed severe alterations including increase of fibrogenesis processes with structural damage. Treatment of mice with these extracts showed a pronounced attenuation in TAA induced hepatic cirrhosis associated with physiological and histopathological alterations. Finally, this study suggests that the supplementation of these extracts may act as antioxidant agents and could be an excellent adjuvant support in the therapy of hepatic cirrhosis. PMID:27081362

  8. Oral supplementation of Ocimum basilicum has the potential to improves the locomotory, exploratory, anxiolytic behavior and learning in adult male albino mice.

    PubMed

    Zahra, K; Khan, M A; Iqbal, F

    2015-01-01

    The aim of this project was to determine the effect of 100 mg/ml solvent/kg body weight of Ocimum basilicum leaf extract on neuromuscular co-ordination, exploratory, locomotory and short-term memory formation in male albino mice. Five weeks old, male albino mice were used as the experimental animals in order to demonstrate the effect of O. basilicum's extract on learning and memory. Each male albino mouse was weighted and orally treated either with 100 mg/ml solvent/kg body weight of O. basilicum leaf extract or with commercially available saline solution (Otsuka, Pakistan) for 7 days. Behavioral observations were made by applying a series of neurological tests (Elevated plus maze, Light and dark box, Open field and Rota rod). Dose supplementation continued during neurological testing. It was observed that 100 mg/ml solvent/kg body weight of leaf extract improves neuromuscular co-ordination and male albino mouse performance in open field, light dark box and during novel object test when compared with control group. We concluded that 100 mg/ml solvent/kg body weight of leaf extract has the potential to improve neuromuscular co-ordination, exploratory behavior, object recognition ability and transfer latency in male albino mice and can be safely administrated orally. PMID:25082078

  9. Ameliorative Effects of Curcumin on Artesunate-Induced Subchronic Toxicity in Testis of Swiss Albino Male Mice

    PubMed Central

    Rajput, Dhrupadsinh K.; Patel, Pragnesh B.; Highland, Hyacinth N.

    2015-01-01

    India is one of the endemic areas where control of malaria has become a formidable task. Artesunate is the current antimalarial drug used to treat malaria, especially chloroquine resistant. The objective of the present study was to investigate the dose-dependent effect of oral administration of artesunate on the oxidative parameters in testes of adult male Swiss albino mice and ameliorative efficacy of curcumin, a widely used antioxidant. An oral dose of 150 mg/kg body weight (bwt; low dose) and 300 mg/kg bwt (high dose) of artesunate was administered for a period of 45 days to male mice, and ameliorative efficacy of curcumin was also assessed. The results revealed that artesunate caused significant alteration in oxidative parameters in dose-dependent manner. Administration of artesunate brought about significant decrease in activities of superoxide dismutase, glutathione, glutathione peroxidase, and glutathione reductase, whereas lipid peroxidation and glutathione-S-transferase activity were found to be significantly increased. The results obtained show that oxidative insult is incurred upon the intracellular antioxidant system of testis tissue by artesunate treatment. Further, administration of curcumin at the dose level of 80 mg/kg bwt along with both doses of artesunate attenuated adverse effects in male mice. PMID:26673878

  10. Cognitive and biochemical effects of monosodium glutamate and aspartame, administered individually and in combination in male albino mice.

    PubMed

    Abu-Taweel, Gasem M; A, Zyadah M; Ajarem, Jamaan S; Ahmad, Mohammad

    2014-01-01

    The present study was designed to investigate the in vivo effects of monosodium glutamate (MSG) and aspartame (ASM) individually and in combination on the cognitive behavior and biochemical parameters like neurotransmitters and oxidative stress indices in the brain tissue of mice. Forty male Swiss albino mice were randomly divided into four groups of ten each and were exposed to MSG and ASM through drinking water for one month. Group I was the control and was given normal tap water. Groups II and III received MSG (8 mg/kg) and ASM (32 mg/kg) respectively dissolved in tap water. Group IV received MSG and ASM together in the same doses. After the exposure period, the animals were subjected to cognitive behavioral tests in a shuttle box and a water maze. Thereafter, the animals were sacrificed and the neurotransmitters and oxidative stress indices were estimated in their forebrain tissue. Both MSG and ASM individually as well as in combination had significant disruptive effects on the cognitive responses, memory retention and learning capabilities of the mice in the order (MSG+ASM)>ASM>MSG. Furthermore, while MSG and ASM individually were unable to alter the brain neurotransmitters and the oxidative stress indices, their combination dose (MSG+ASM) decreased significantly the levels of neurotransmitters (dopamine and serotonin) and it also caused oxidative stress by increasing the lipid peroxides measured in the form of thiobarbituric acid-reactive substances (TBARS) and decreasing the level of total glutathione (GSH). Further studies are required to evaluate the synergistic effects of MSG and ASM on the neurotransmitters and oxidative stress indices and their involvement in cognitive dysfunctions. PMID:24556450

  11. Effect of aqueous extract of Tinospora cordifolia on functions of peritoneal macrophages isolated from CCl4 intoxicated male albino mice

    PubMed Central

    2011-01-01

    Background The current practice of ingesting phytochemicals for supporting the immune system or fighting infections is based on centuries-old tradition. Macrophages are involved at all the stages of an immune response. The present study focuses on the immunostimulant properties of Tinospora cordifolia extract that are exerted on circulating macrophages isolated from CCl4 (0.5 ml/kg body weight) intoxicated male albino mice. Methods Apart from damaging the liver system, carbon tetrachloride also inhibits macrophage functions thus, creating an immunocompromised state, as is evident from the present study. Such cell functions include cell morphology, adhesion property, phagocytosis, enzyme release (myeloperoxidase or MPO), nitric oxide (NO) release, intracellular survival of ingested bacteria and DNA fragmentation in peritoneal macrophages isolated from these immunocompromised mice. T. cordifolia extract was tested for acute toxicity at the given dose (150 mg/kg body weight) by lactate dehydrogenase (LDH) assay. Results The number of morphologically altered macrophages was increased in mice exposed to CCl4. Administration of CCl4 (i.p.) also reduced the phagocytosis, cell adhesion, MPO release, NO release properties of circulating macrophages of mice. The DNA fragmentation of peritoneal macrophages was observed to be higher in CCl4 intoxicated mice. The bacterial killing capacity of peritoneal macrophages was also adversely affected by CCl4. However oral administration of aqueous fraction of Tinospora cordifolia stem parts at a dose of 40 mg/kg body weight (in vivo) in CCl4 exposed mice ameliorated the effect of CCl4, as the percentage of morphologically altered macrophages, phagocytosis activity, cell adhesion, MPO release, NO release, DNA fragmentation and intracellular killing capacity of CCl4 intoxicated peritoneal macrophages came closer to those of the control group. No acute toxicity was identified in oral administration of the aqueous extract of Tinospora

  12. Influences of crude extract of tea leaves, Camellia sinensis, on streptozotocin diabetic male albino mice

    PubMed Central

    Al-Attar, Atef M.; Zari, Talal A.

    2010-01-01

    Natural remedies from medicinal plants are considered to be effective and safe alternative treatment for diabetes mellitus. The aim of the present study was to investigate the hypoglycemic activity of the crude tea leaves extract on streptozotocin (STZ)-induced diabetic mice. The average body weight of animals with diabetes and their percentage changes of body weight gain after 15 and 30 days were significantly lower than that of the normal control mice. In diabetic mice, supplementation with tea leaves extract decreased the loss of body weight. After 15 and 30 days, significant increases in the levels of serum glucose, triglycerides, cholesterol, creatinine, urea, uric acid, glutamic pyruvic acid transaminase (GPT) and glutamic oxaloacetic acid transaminase (GOT) were noted in STZ-diabetic mice fed with normal diet. Also, the values of total protein in this group were statistically declined after 15 and 30 days. The levels of serum glucose and GPT were significantly elevated after 15 and 30 days in diabetic mice supplemented with tea leaves extract. Moreover, the level of serum GOT was notably increased after 30 days. Insignificant alterations were observed in the levels of serum triglycerides, cholesterol, total protein, creatinine, urea and uric acid in diabetic mice supplemented with tea leaves extract. Thus, the present results have shown that tea leaves extract has the antihyperglycemic, antihyperlipidemic, and antihyperproteinemic effects and consequently may alleviate liver and kidney damage associated with STZ-induced diabetes in mice. PMID:23961092

  13. Honey bee is a potential antioxidant against cyclophosphamide-induced genotoxicity in albino male mice.

    PubMed

    Zoheir, Khairy Mohamed Abdallah; Harisa, Gamaleldin Ibrahim; Abo-Salem, Osama Mohamed; Ahmad, Sheikh Fayaz

    2015-05-01

    The protective effects of honey bee (HB) and pollen grains against cyclophosphamide (CPM) -induced cytotoxic and genotoxic effects in mice were investigated. This was achieved through study the effects of CPM and HB on oxidative status, chromosomal aberrations and gene expression of the tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), interleukin-1β (IL1β), interleukin 17A (IL-17A) and interferon-gamma (IFN-γ) in mice. In addition, the levels of reduced glutathione (GSH) and malondialdehyde were determined. The results of this study revealed that CPM decrease in GSH level and increase in malondialdehyde (MDA) level in the liver and kidney tissues. Moreover, CPM induced sperm abnormality, chromosomal aberrations and down regulated the expression of the studied cytokine genes. HB treatment in association with CPM ameliorates GSH, MDA, chromosomal aberrations and regulated the expression of IL-1-β, IL-17A, IL-6, TNF-α and IFN-γ. Thus, HB inhibits the cytotoxic and genotoxic risks associated with CPM treatment in mice. PMID:26004732

  14. Effect of carbon monoxide on Swiss albino mice

    NASA Technical Reports Server (NTRS)

    Hilado, C. J.; Cumming, H. J.

    1977-01-01

    Times to incapacitation and death and LC50 values were determined for male Swiss albino mice exposed to different concentrations of carbon monoxide in a 4.2 liter hemispherical chamber. These values are compared to values reported in the literature. The LC50 for a 30 minute exposure was 3570 ppm CO.

  15. Influence of environmental enrichment vs. time-of-day on behavioral repertoire of male albino Swiss mice.

    PubMed

    Loss, Cássio Morais; Binder, Luisa Bandeira; Muccini, Eduarda; Martins, Wagner Carbolin; de Oliveira, Paulo Alexandre; Vandresen-Filho, Samuel; Prediger, Rui Daniel; Tasca, Carla Inês; Zimmer, Eduardo R; Costa-Schmidt, Luiz Ernesto; de Oliveira, Diogo Losch; Viola, Giordano Gubert

    2015-11-01

    Environmental enrichment (EE) is a non-pharmacological manipulation that promotes diverse forms of benefits in the central nervous system of captive animals. It is thought that EE influences animal behavior in a specie-(strain)-specific manner. Since rodents in general present different behaviors during distinct periods of the day, in this study we aimed to investigate the influence of time-of-day on behavioral repertoire of Swiss mice that reared in EE. Forty male Swiss mice (21days old) were housed in standard (SC) or enriched conditions (EC) for 60days. Behavioral assessments were conducted during the light phase (in presence of light) or dark phase (in absence of light) in the following tasks: open field, object recognition and elevated plus maze. First, we observed that the locomotor and exploratory activities are distinct between SC and EC groups only during the light phase. Second, we observed that "self-protective behaviors" were increased in EC group only when mice were tested during the light phase. However, "less defensive behaviors" were not affected by both housing conditions and time-of-day. Third, we showed that the performance of EE animals in object recognition task was improved in both light and dark conditions. Our findings highlight that EE-induced alterations in exploratory and emotional behaviors are just evident during light conditions. However, EE-induced cognitive benefits are remarkable even during dark conditions, when exploratory and emotional behaviors were similar between groups. PMID:26247375

  16. Nano gold conjugation, anti-arthritic potential and toxicity studies of snake Naja kaouthia (Lesson, 1831) venom protein toxin NKCT1 in male albino rats and mice.

    PubMed

    Saha, Partha Pratim; Bhowmik, Tanmoy; Dasgupta, Anjan Kumar; Gomes, Antony

    2014-08-01

    Nanoscience and Nanotechnology have found their way in the fields of pharmacology and medicine. The conjugation of drug to nanoparticles combines the properties of both. In this study, gold nanoparticle (GNP) was conjugated with NKCT1, a cytotoxic protein toxin from Indian cobra venom for evaluation of anti-arthritic activity and toxicity in experimental animal models. GNP conjugated NKCT1 (GNP-NKCT1) synthesized by NaBH4 reduction method was stable at room temperature (25 +/- 2 degrees C), pH 7.2. Hydrodynamic size of GNP-NKCT1 was 68-122 nm. Arthritis was developed by Freund's complete adjuvant induction in male albino rats and treatment was done with NKCT1/GNP-NKCT1/standard drug. The paw/ankle swelling, urinary markers, serum markers and cytokines were changed significantly in arthritic control rats which were restored after GNP-NKCT1 treatment. Acute toxicity study revealed that GNP conjugation increased the minimum lethal dose value of NKCT1 and partially reduced the NKCT1 induced increase of the serum biochemical tissue injury markers. Histopathological study showed partial restoration of toxic effect in kidney tissue after GNP conjugation. Normal lymphocyte count in culture was in the order of GNP-NKCT1 > NKCT1 > Indomethacine treatment. The present study confirmed that GNP conjugation increased the antiarthritic activity and decreased toxicity profile of NKCT1. PMID:25141538

  17. Metabolic rate and thermal insulation in albino and hairless mice

    PubMed Central

    Mount, L. E.

    1971-01-01

    1. Rates of oxygen consumption of albino and hairless mice were measured in a metabolism chamber during periods of approximately 5 or 24 hr. Rectal temperature was measured before and after each period. The chamber temperatures used were 22, 30 and 32° C for both albino and hairless, and in addition 34 and 36° C for the hairless mice. 2. The mean age and body weight of the albino mice were 102 days and 34·6 g; the corresponding values for the hairless mice were 87 days and 32·8 g. 3. The mean minimum rates of oxygen consumption (ml./kg.min) were 31·0 for the albino and 38·8 for the hairless mouse; the corresponding estimated critical temperatures were in the ranges 30-32° C for the albino mouse and 32-34° C for the hairless mouse. 4. The mean values for core-ambient thermal insulation (° C.m2.hr/kcal) were 0·418 and 0·328 for the albino mouse, and 0·275 and 0·221 for the hairless mouse, at 22 and 30° C respectively in each case. PMID:5097602

  18. Antispermatogenic and androgenic activities of various extracts of Hibiscus rosa sinesis in albino mice.

    PubMed

    Reddy, C M; Murthy, D R; Patil, S B

    1997-11-01

    The benzene chloroform and alcoholic extracts of the flowers of H.r.sinensis were administered (i.p.) at two different dose levels of 125 and 250 mg/kg body weight to adult male albino mice for 20 days. The results have shown decrease in the spermatogenic elements of testis and epididymal sperm count. High content of testicular cholesterol may be due to lowered androgen synthesis. The increase in the weight of accessory reproductive organs indicates the androgenicity of the plant extract itself, which is proved in the present study by testing the benzene extract in immature mice. PMID:9567744

  19. Retinal compensatory changes after light damage in albino mice

    PubMed Central

    Montalbán-Soler, Luis; Alarcón-Martínez, Luis; Jiménez-López, Manuel; Salinas-Navarro, Manuel; Galindo-Romero, Caridad; Bezerra de Sá, Fabrízio; García-Ayuso, Diego; Avilés-Trigueros, Marcelino; Vidal-Sanz, Manuel; Agudo-Barriuso, Marta

    2012-01-01

    Purpose To investigate the anatomic and functional changes triggered by light exposure in the albino mouse retina and compare them with those observed in the albino rat. Methods BALB/c albino mice were exposed to 3,000 lx of white light during 24 h and their retinas analyzed from 1 to 180 days after light exposure (ALE). Left pupil mydriasis was induced with topical atropine. Retinal function was analyzed by electroretinographic (ERG) recording. To assess retinal degeneration, hematoxylin and eosin staining, the TdT-mediated dUTP nick-end labeling (TUNEL) technique, and quantitative immunohistofluorescence for synaptophysin and protein kinase Cα (PKCα) were used in cross sections. Intravenous injection of horseradish peroxidase and Fluoro-Gold™ tracing were used in whole-mounted retinas to study the retinal vasculature and the retinal ganglion cell (RGC) population, respectively. Results Light exposure caused apoptotic photoreceptor death in the central retina. This death was more severe in the dorsal than in the ventral retina, sparing the periphery. Neither retinal vascular leakage nor retinal ganglion cell death was observed ALE. The electroretinographic a-wave was permanently impaired, while the b-wave decreased but recovered gradually by 180 days ALE. The scotopic threshold responses, associated with the inner retinal function, diminished at first but recovered completely by 14 days ALE. This functional recovery was concomitant with the upregulation of protein kinase Cα and synaptophysin. Similar results were obtained in both eyes, irrespective of mydriasis. Conclusions In albino mice, light exposure induces substantial retinal damage, but the surviving photoreceptors, together with compensatory morphological/molecular changes, allow an important restoration of the retinal function. PMID:22509098

  20. Effect of lead acetate toxicity on experimental male albino rat

    PubMed Central

    Ibrahim, Nabil M; Eweis, Esam A; El-Beltagi, Hossam S; Abdel-Mobdy, Yasmin E

    2012-01-01

    Objective To evaluate the effect of different doses of lead acetate (1/20, 1/40 and 1/60 of LD50) on body weight gain, blood picture, plasma protein profile and the function of liver, kidney and thyroid gland. Methods Male albino rats were divided into four groups, the first group represented the health control animals, while the second, third and fourth groups were ingested orally with sub lethal doses of lead acetate (1/20, 1/40 and 1/60) of the oral LD50, respectively. One dose was ingested every two days during the experimental period (14 weeks) including the adaptation time. Blood was collected and used for all analysis. Results The results showed that, the ingestion of Pb2+ induced significant stimulation in glutamic-pyruvic transaminase (ALT) and glutamic-oxalacetic transaminease (AST) activity. Also, total soluble protein and albumin contents of plasma were significantly decreased, while the content of globulin was changed by the Pb2+ treatments. The cholinesterase activity was inhibited, but the activities of alkaline and acid phosphates and lactate dehydrogenase were stimulated, while plasma glucose level was elevated as a result of lead acetate intoxication. In case of blood picture, Pb2+ ingestion reduced the contents of hemoglobin and RBCs count of intoxicated rat's blood and the plasma levels of T3, T4 and blood WBCs count were decreased. Conclusions It can be concluded that lead acetate has harmful effect on experimental male albino rats. Therefore, the present work advises people to prevent exposure to the lead compound to avoid injurious hazard risk. PMID:23569832

  1. Effect of Atorvastatin on Memory in Albino Mice

    PubMed Central

    M.C., Das; Rao A.S.R., Srinivasa; Kadali, SLDV Ramana Murty

    2014-01-01

    Objective: The aim and objective of the present study was to evaluate the effect of atorvastatin on learning and memory in albino mice. Materials and Methods: Thirty Swiss albino mice were divided into 5groups (n=6). In group2, group4 and group5 hyperlipidemia was induced by high fat diet (HFD) orally for 28days. Atrorvastatin was given to group3, group4 and group5 orally for 14 d. Learning and memory was evaluated with Hebb Williams’s maze, Elevated plus maze, Y maze and Step through latency. Continuous data were analyzed by one way ANOVA followed by Scheffe multiple range test, discrete data were analyzed by Kruskal - Wallis test. The level of significance was 5% (p ≤ 0.05). Result and Conclusion: HFD treatment had shown significant increase in body weight, significant impairment in learning and memory (p < 0.05). Only atorvastatin treated group had shown better learning and memory in comparison to HFD group. Atorvastatin 10mg/kg and 20 mg/kg had reversed the HFD induced impairment of learning and memory but there was no significant difference between the doses (p > 0.05). PMID:25584244

  2. Dietary Yucca schidigera supplementation reduces arsenic-induced oxidative stress in Swiss albino mice.

    PubMed

    Ince, Sinan; Kucukkurt, Ismail; Turkmen, Ruhi; Demirel, Hasan Huseyin; Sever, Emine

    2013-11-01

    The aim of this study was to clarify the effects of dietary supplementation with Yucca schidigera (Ys) on lipid peroxidation (LPO), antioxidant activity, some biochemical parameters and histopathological changes in arsenic-exposed mice. Forty Swiss albino male mice were divided into five equal groups. Group I (control group) was given normal diet and tap water for 28 days. Group II (arsenic group) was given normal diet and 100 mg/L arsenic along with drinking water for 28 days. Groups III-V were given three different doses of Ys (50, 100 and 200 mg/kg) in supplemented diet and arsenic (100 mg/L) along with drinking water throughout the entire period of 28 days. The arsenic significantly increased serum biochemical parameters and malondialdehyde levels in blood and tissue. However, arsenic significantly decreased tissue glutathione concentration, erythrocyte superoxide dismutase and catalase activities. In contrast, dietary supplementation of Ys, in a dose-dependent manner, resulted in reversal of arsenic-induced oxidative stress, LPO and activities of antioxidant enzymes. Moreover, Ys also exhibited protective action against the arsenic-induced focal gliosis and hyperemi in brain, necrosis and degeneration in liver, degeneration and dilatation in Bowman's capsule of kidney and hyaline degeneration in heart tissue of mice. Consequently, our results demonstrate that Ys especially high-dose supplementation in diet decreases arsenic-induced oxidative stress and enhances the antioxidant defence mechanism and regenerate of tissues in Swiss albino mice. PMID:22609855

  3. Neuroprotective Effect of Lercanidipine- A Novel Calcium Channel Blocker in Albino Mice

    PubMed Central

    Adhimoolam, Mangaiarkkarasi; Perumal, Deepa Kameswari; Rajamohammed, Meher Ali

    2015-01-01

    Background The available conventional antiepileptics do not afford cure or prophylactic treatment and henceforth there is always a quest to explore new targets for management of convulsions. In this perspective, dihydropyridine calcium channel blockers have been investigated in various animal models of epilepsy. Lercanidipine, a newer dihydropyridine calcium antagonist, is a potential candidate with its favourable lipid profile and longer duration of action. Objective (1) To evaluate the anticonvulsant effect of lercanidipine alone and in combination with standard drug in adult male Swiss albino mice. (2) To evaluate the muscle relaxant and spontaneous locomotor activity of lercanidipine in adult male Swiss albino mice. Materials and Methods Adult male Swiss albino mice weighing 20-30g were used to study the anticonvulsant, muscle relaxant and spontaneous locomotor activity using electroconvulsometer, rotarod and actophotometer apparatus respectively. The mice were divided into six groups of six animals in each group. Group 1 and 2 served as control (vehicle treated) and standard group respectively. Standard drug used to evaluate anticonvulsant effect is phenytoin sodium 25 mg/kg I.P. whereas muscle relaxant activity and locomotor activity is diazepam 4 mg/kg I.P., Group 3 and 4 received lercanidipine 1 and 3 mg/kg I.P., respectively. Anticonvulsant models included group 5 and 6 and they were given combination of phenytoin sodium 12.5 mg/kg I.P., with lercanidipine 1 and 3 mg/kg i.p, respectively. Abolition or reduction of tonic hind limb extension was considered as index of anticonvulsant activity whereas the balancing time of the animals in rod was recorded to asses muscle relaxant activity. The locomotor activity was recorded for 5 minutes. The data were analysed with one-way Analysis of Variance followed by post-hoc ‘Dunnett t-test’. Results Lercanidipine given alone in a dose of 1 and 3 mg/kg had significantly reduced the tonic hind limb extension

  4. Analysis of anti-depressant potential of curcumin against depression induced male albino wistar rats.

    PubMed

    Chang, Xue-Run; Wang, Li; Li, Jing; Wu, Dian-Shui

    2016-07-01

    The present study investigated the antidepressant potential of curcumin in olfactory bulbectomy and forced swimming test models of depression in male albino rats under chronic treatment. The experimental animals were divided into four groups, and curcumin was administered for 45 days. Our results showed that the curcumin significantly reduced olfactory bulbectomy-induced behavioral abnormalities including deficits in step-down passive avoidance, increased activity in the open area and immobility time. Chronic administration of curcumin significantly reversed levels of 3, 4-dihydroxyphenylacetic acid, noradrenaline, serotonin and 5-hydroxyindoleacetic acid in the hippocampus region of male albino rats. Also, curcumin normalizes the levels of dopamine, noradrenaline, and 5-hydroxyindoleacetic acid in the frontal cortex of rats. Taking all these results together, it may suggest that curcumin is potent compound acting against the depression in the male albino rats. PMID:26972530

  5. Effects of dietary creatine supplementation for 8 weeks on neuromuscular coordination and learning in male albino mouse following neonatal hypoxic ischemic insult.

    PubMed

    Iqbal, Shahid; Ali, Muhammad; Akbar, Atif; Iqbal, Furhan

    2015-05-01

    Creatine monohydrate (Cr) is a dietary supplement known to improve cognitive functions and has positive therapeutic results under various clinical conditions. The aim of this study was to determine the effect of 2 % Cr supplementation on learning, memory formation, neuromuscular coordination, exploratory and locomotory in male albino mice following hypoxic ischemic insult. At postnatal day, 10 male albino mice pups were subjected to right common carotid artery ligation followed by 8 % hypoxia for 25 min. On postnatal day 20, male mice were separated from the litter and divided into two groups on the basis of special diet supplementation. One group was supplemented with 2 % Cr in diet while the other group was raised on ordinary rodent chow for 8 weeks. Behavioral observations were made during rota rod, open field and Morris water maze test for both treatments. It was observed that supplementation with 2 % Cr for 8 weeks following neonatal brain damage resulted in enhanced muscular strength, neuromuscular coordination and improved body weight. In Morris water maze test, it was observed that Cr supplementation significantly improved mean swimming speed and mice on 2 % Cr diet covered more distance but the spatial memory was not improved significantly following hypoxia ischemia encephalopathy (HIE). Open field parameters and percentage of infarct volume remained unaffected following Cr supplementation. We concluded that 2 % dietary Cr supplementation has a potential to improve the muscle strength and body weight in male albino mice following (HIE) and should be considered for the treatment of neurological ailments. PMID:25511980

  6. Effect of amlodipine, a calcium channel antagonist, on gonadal steroid of male Wistar albino rats

    PubMed Central

    Onwuka, FC; wuanyanwu, KC Patrick-I; Nnodu, CK; Erhabor, O

    2010-01-01

    This study was carried out to investigate the effect of prolonged intake of calcium-channel blocker amlodipine, an antihypertensive drug on gonadal steroid hormone (testosterone) of male albino rats. Three different concentrations of amlodipine (0.01, 0.02 and 0.03 mg/kg body weight) was administered orally to three different groups (B, C, and D) of experimental male Wistar albino rats (n = 8) for six weeks. Group A rats were fed normal diet without amlodipine (n = 8) served as the control. The administration of amlodipine significantly reduced testosterone level in the following order, group A (0.22 ± 0.01) > B (0.18 ± 0.01) > C (0.14 ± 0.01) > D (0.10 ± 0.01). The reduction in testosterone levels corresponded with an increase in the concentration of amlodipine administered to male Wistar albino rats. The observation in this study reveals that long-term treatment of male Wistar rats with calcium-channel blocker and antihypertensive (amlodipine) produces a significant reduction in the level of testosterone a hormone associated with decreased ability of men to enjoy sex and to develop good quality erections. There is the need for a large scale study to investigate the potential effect of long-term antihypertensive therapy with amlodipine on sexual dysfunction in men.

  7. The therapeutic effect of curcumin in male albino rats and its putative mechanisms on cerebral microvascular flow.

    PubMed

    Xia, Jie; Wang, Hui; Zhang, Qi-Mei; Zheng, Zheng; Han, Zhong-Mou

    2016-07-01

    The present study aimed to investigate the therapeutic effect of curcumin on hypertension and its putative mechanisms in the cerebral microcirculation. The surgical preparation was made to generate a cranial window for observation of the capillary network in the cerebral cortex region. Digital image processing, intravital videomicroscopy, and laser Doppler flow meter were used in this investigation. The number of open capillaries, arterial blood pressure, red cell velocity, microvascular diameter, circulating endothelial cells, relative blood flow and frequency were determined. Control rats showed severe dysfunction in the microcirculation with increased blood pressure. In curcumin treated mice, the blood pressure significantly reduced compared to their respective controls. Curcumin significantly increased blood velocity and LDF flow in hypertensive and normotensive rats. Curcumin significantly altered the circulating endothelial cells and open capillaries number in the male albino rats. Our results suggested that the curcumin exerts its therapeutic effect in male albino rats by regulating vasomotion function, increasing blood perfusion, releasing the peripheral resistance and opening efficiently capillaries. Taking all these data together, it is concluded that the curcumin might be useful in the regulation of the cerebral microcirculatory function and hypertension. PMID:27017961

  8. Patulin in apple juice and its risk assessments on albino mice.

    PubMed

    Al-Hazmi, Mansour A

    2014-07-01

    The contamination of apple juice with patulin mycotoxin is a major risk factor in food safety. This study focuses to assess the biochemical and histopathological effects of patulin in apple juice samples collected from different outlets retailing in Jeddah, Kingdom of Saudi Arabia. On the basis of the selected dose level, 152.5 ppb patulin/ml was administered daily orally for up to 6 weeks to male albino mice. The exposure to contaminated samples revealed significant elevation of all the studied blood parameters (alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activities as well as creatinine, urea and uric acid contents). On the other hand, and with regard to the accumulated neuronal toxicity of the tested dose level, the toxic signs were recorded as significant increase in the aggressive and locomotor behavioral changes. In addition, the brain areas monoamines concentration revealed variable increased changes. The potential maximal changes in norepinephrine, dopamine and serotonin5-hydroxytryptamine levels attained in cortex, hypothalamus, striatum, hippocampus, midbrain and pons and medulla were assessed. Moreover, the histological examination revealed degeneration and necrosis in liver tissues and degenerated glomeruli and hemorrhage between the tubules of the cortical region in kidney tissues. The study declared that patulin-contaminated (152.5 ppb) apple juice exhibited liver, kidney and neurotoxicological effects in 6 weeks orally administered mice. PMID:23012343

  9. Ultrasonic Songs of Male Mice

    PubMed Central

    2005-01-01

    Previously it was shown that male mice, when they encounter female mice or their pheromones, emit ultrasonic vocalizations with frequencies ranging over 30–110 kHz. Here, we show that these vocalizations have the characteristics of song, consisting of several different syllable types, whose temporal sequencing includes the utterance of repeated phrases. Individual males produce songs with characteristic syllabic and temporal structure. This study provides a quantitative initial description of male mouse songs, and opens the possibility of studying song production and perception in an established genetic model organism. PMID:16248680

  10. Development of dog mammary tumor xenograft in immunosuppressed Swiss albino mice.

    PubMed

    Rajmani, R S; Singh, Prafull Kumar; Kumar, Sanjay; Kumar, G Ravi; Sahoo, Aditya P; Santra, Lakshman; Saxena, Shikha; Singh, Lakshya Veer; Chaturvedi, Uttara; Saxena, Lovleen; Desai, G S; Gupta, Shishir Kumar; Kumar, Amit; Jadon, N S; Tiwari, Ashok K

    2014-10-01

    Development and study of dog mammary tumour xenograft in immunosuppressed Swiss Albino Mice adds a new dimension in cancer research as dog tumors have many similarities with human tumors regarding progression, histopathology, molecular mechanism, immune response and therapy. Failure of the immune system to recognize and eliminate cancer cells leads to cancer progression and the fight between immune cells and cancer cells has a great role in understanding the mechanism of cancer progression and elimination. Rejection and acceptance of tumour xenograft depends on efficiency of CD4+, CD8+ and NK cell populations. In the present investigation, dog mammary tumor xenograft in cyclosporine-A and gamma-irradiated, immunosuppressed Swiss Albino mice was developed and the immune cell status of graft accepted and rejected mice was assessed. It was observed that all the major immune cells (CD4+, CD8+ and NK cells) play an equal role in tumour rejection. PMID:25345242

  11. What makes male mice paternal?

    PubMed

    Elwood, R W

    1986-07-01

    Both copulation and postcopulatory cohabitation with pregnant females reduce infanticide and enhance paternal responsiveness in male CS1 mice. The effectiveness of copulation in this process, however, depends on the number of occasions that males have previously encountered infants. Infanticidal males which have been subordinated in brief encounters with other males are less likely to commit infanticide in subsequent tests than are those which became dominant to other males. Males which copulate and cohabit with a relatively large female are less likely to be infanticidal than are those with a relatively small female. These data suggest that males are subordinated after copulation by their mates and that this subordination is a factor in the reduction of infanticide and the initiation of paternal responsiveness. PMID:3729896

  12. Royal jelly modulates oxidative stress and tissue injury in gamma irradiated male Wister Albino rats

    PubMed Central

    Azab, Khaled Shaaban; Bashandy, Mohamed; Salem, Mahmoud; Ahmed, Osama; Tawfik, Zaki; Helal, Hamed

    2011-01-01

    Background: Royal jelly is a nutritive secretion produced by the worker bees, rich in proteins, carbohydrates, vitamins and minerals. Aim: The present study was designed to determine the possible protective effects of royal jelly against radiation induced oxidative stress, hematological, biochemical and histological alterations in male Wister albino rats. Materials and Methods: Male Wister albino rats were exposed to a fractionated dose of gamma radiation (2 Gy every 3 days up to 8 Gy total doses). Royal jelly was administrated (g/Kg/day) by gavages 14 days before exposure to the 1st radiation fraction and the treatment was continued for 15 days after the 1st irradiation fraction till the end of the experiment. The rats were sacrificed 3rd, equivalent to 3rd post 2nd irradiation fraction, and equivalent to 3rd day post last irradiation fraction. Results: In the present study, gamma- irradiation induced hematological, biochemical and histological effects in male Wister albino rats. In royal jelly treated irradiated group, there was a noticeable decrease recorded in thiobarbituric reactive substances concentration when compared to γ-irradiated group. Also, the serum nitric oxide concentration was significantly improved. The administration of royal jelly to irradiated rats according to the current experimental design significantly ameliorates the changes induced in serum lipid profile. Moreover, in royal jelly treated irradiated group, there was a noticeable amelioration recorded in all hematological parameters along the three experimental intervals. The microscopic examination of cardiac muscle of royal jelly treated irradiated rats demonstrated structural amelioration, improved nuclei and normal features of capillaries and veins in endomysium when compared to gamma-irradiated rats. Conclusion: It was suggested that the biochemical, hematological and histological amelioration observed in royal jelly (g/Kg/day) treated irradiated rats might be due to the antioxidant

  13. Effect of tulsi (Ocimum Sanctum Linn.) on sperm count and reproductive hormones in male albino rabbits.

    PubMed

    Sethi, Jyoti; Yadav, Mridul; Sood, Sushma; Dahiya, Kiran; Singh, Veena

    2010-10-01

    Fresh leaves of Ocimum Sanctum (OS) were used to study its effect on male reproductive function (sperm count and reproductive hormones) in male albino rabbits. Animals in the test group received supplementation of 2 g of fresh leaves of OS per rabbit for 30 days, while the control group was maintained on normal diet for the same duration. Sperm count and hormonal estimation [testosterone, follicle stimulating hormone (FSH), and luteinizing hormone (LH)] were done in serum samples of both groups and compared. A significant decrease was noted in the sperm count in test group rabbits. Serum testosterone levels showed marked increase while FSH and LH levels were significantly reduced in OS-treated rabbits. The results suggest the potential use of OS as an effective male contraceptive agent. PMID:21455446

  14. Effects of male social status on reproductive success and on behavior in mice (Mus musculus).

    PubMed

    D'Amato, F R

    1988-06-01

    Differences in reproduction as well as in behavior in the presence of females were evaluated according to dominant and subordinate male rank in albino mice, in the temporary absence of each male's antagonist. Dominant males reproduced more successfully than subordinate males. Subordinate males were generally inactive, except for displacement activities, during the first 15 min they were exposed to female partners. These findings suggest that mechanisms other than male-male interference or mating order may be operating or influencing behavior and reproductive results. PMID:3396312

  15. Haematological, biochemical and histopathological alterations induced by abamectin and Bacillus thuringiensis in male albino rats.

    PubMed

    Eissa, F I; Zidan, N A

    2010-03-01

    The renal- and hepato-toxicity induced by abamectin pesticide (Vertimec) and a commercial form of a bio-insecticide Bacillus thuringiensis (Agerin) in male albino rats were evaluated. Blood picture and blood glucose level were investigated. Male albino rats were administered dietary doses each equivalent to 1/10 or 1/100 of the LD50 values of each toxicant for 30 consecutive days. Abamectin was found to pose risks of renal- and hepato-toxicity in rats, since the biochemical parameters of liver function (i.e. aspartate aminotransferase activity, alanine aminotransferase activity, acid phosphatase activity, albumin, and total protein levels) and kidney function (uric acid and creatinine concentration) were severely affected. These effects were verified by histopathological examination of liver and kidney tissues. Likewise, some haematological indices (i.e. erythrocyte count, leukocyte count and haemoglobin concentration) were also influenced; in addition abamectin might cause hypoglycaemia. On the other hand, the above-mentioned lesions were less pronounced in the case of Bacillus thuringiensis -treated rats. PMID:20194097

  16. Biochemical and immunological changes on oral glutamate feeding in male albino rats

    NASA Astrophysics Data System (ADS)

    Kumar, D.; Bansal, Anju; Thomas, Pauline; Sairam, M.; Sharma, S. K.; Mongia, S. S.; Singh, R.; Selvamurthy, W.

    High altitude stress leads to lipid peroxidation and free radical formation which results in cell membrane damage in organs and tissues, and associated mountain diseases. This paper discusses the changes in biochemical parameters and antibody response on feeding glutamate to male albino Sprague Dawley rats under hypoxic stress. Exposure of rats to simulated hypoxia at 7576 m, for 6 h daily for 5 consecutive days, in an animal decompression chamber at 32+/-2° C resulted in an increase in plasma malondialdehyde level with a concomitant decrease in blood glutathione (reduced) level. Supplementation of glutamate orally at an optimal dose (27 mg/kg body weight) in male albino rats under hypoxia enhanced glutathione level and decreased malondialdehyde concentration significantly. Glutamate feeding improved total plasma protein and glucose levels under hypoxia. The activities of serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) and the urea level remained elevated on glutamate supplementation under hypoxia. Glutamate supplementation increased the humoral response against sheep red blood cells (antibody titre). These results indicate a possible utility of glutamate in the amelioration of hypoxia-induced oxidative stress.

  17. Contraceptive studies of isolated fractions of Cuminum cyminum in male albino rats.

    PubMed

    Saxena, Poonam; Gupta, Rajnish; Gupta, R S

    2015-01-01

    The contraceptive efficacy of Cuminum cyminum isolated fractions (CcFr) in male albino rats was investigated. Oral dose of CcFr at 50 mg/rat/day for 60 days revealed no significant changes in body weight, while marked abnormalities in spermatogenesis were observed with decreased counts (P ≤ 0.001) in round spermatids, preleptotene spermatocytes and secondary spermatocytes. Cross sectional surface area of Sertoli cells as well as number of mature Leydig cell were decreased significantly (P ≤ 0.001). Testicular as well as accessory sex organ biochemical parameters were significantly changed (P ≤ 0.001). Sperm motility, density and morphology were resulted in 100% negative fertility. Testosterone levels were declined significantly. In conclusion, Cuminum cyminum inhibited spermatogenesis in rats, indicating the possibility of developing an herbal male contraceptive. PMID:25675391

  18. Differential effects of retinal degeneration on sleep and wakefulness responses to short light-dark cycles in albino mice.

    PubMed

    Hsiao, F-C; Liao, Y-H; Tsai, L-L

    2013-09-17

    This study characterizes the different response patterns of sleep and wakefulness (W) to short light-dark (LD) cycles in albino mice and examines whether retinal degeneration resulting from prolonged bright light treatment and/or rd/rd mutation alters such response patterns. Eight young male Institute for Cancer Research (ICR) mice with normal eyes, seven young male rd/rd Friend Virus B type (FVB) mice, six young ICR and five young rd/rd FVB mice receiving 48-h bright light treatment, and five older rd/rd FVB mice were implanted with skull and muscle electrodes to record sleep and W. All the mice were maintained in 12-h-12-h LD cycles at baseline and received 2 days of short LD cycle treatment, which included 5-min-5-min LD cycles for a total of 24 cycles presented 4h after lights-on and again 4h after lights-off. All the five mouse groups maintained photo-entrainment of sleep and W rhythms at the baseline and showed a preference for paradoxical sleep (PS) occurrence in the 5-min dark period and non-rapid eye movement sleep (NREMS) in the 5-min light period and a brief alerting effect of light onset on experimental days. Retinal degeneration rising from bright light treatment and/or genetic mutation failed to eliminate or reduce the response of PS and NREMS to short LD cycles, although it enhanced the LD contrast of W, i.e., bright light treatment prolonged the alerting effect of light and the rd mutation increased the suppressing effect of the dark on W. These results suggest that sleep responses to short LD cycles and the brief alerting effect of light were independent of the photoreceptors in the outer retina. Furthermore, the residual photoreceptors in the outer retina and/or the photosensitive cells in the inner retina may actively modulate the effect of light and dark signals on W. PMID:23811394

  19. Distribution of melanopsin positive neurons in pigmented and albino mice: evidence for melanopsin interneurons in the mouse retina

    PubMed Central

    Valiente-Soriano, Francisco J.; García-Ayuso, Diego; Ortín-Martínez, Arturo; Jiménez-López, Manuel; Galindo-Romero, Caridad; Villegas-Pérez, Maria Paz; Agudo-Barriuso, Marta; Vugler, Anthony A.; Vidal-Sanz, Manuel

    2014-01-01

    Here we have studied the population of intrinsically photosensitive retinal ganglion cells (ipRGCs) in adult pigmented and albino mice. Our data show that although pigmented (C57Bl/6) and albino (Swiss) mice have a similar total number of ipRGCs, their distribution is slightly different: while in pigmented mice ipRGCs are more abundant in the temporal retina, in albinos the ipRGCs are more abundant in superior retina. In both strains, ipRGCs are located in the retinal periphery, in the areas of lower Brn3a+RGC density. Both strains also contain displaced ipRGCs (d-ipRGCs) in the inner nuclear layer (INL) that account for 14% of total ipRGCs in pigmented mice and 5% in albinos. Tracing from both superior colliculli shows that 98% (pigmented) and 97% (albino) of the total ipRGCs, become retrogradely labeled, while double immunodetection of melanopsin and Brn3a confirms that few ipRGCs express this transcription factor in mice. Rather surprisingly, application of a retrograde tracer to the optic nerve (ON) labels all ipRGCs, except for a sub-population of the d-ipRGCs (14% in pigmented and 28% in albino, respectively) and melanopsin positive cells residing in the ciliary marginal zone (CMZ) of the retina. In the CMZ, between 20% (pigmented) and 24% (albino) of the melanopsin positive cells are unlabeled by the tracer and we suggest that this may be because they fail to send an axon into the ON. As such, this study provides the first evidence for a population of melanopsin interneurons in the mammalian retina. PMID:25477787

  20. Impact of acute and chronic stress hormone on male albino rat brain

    PubMed Central

    Han, Li-Li; Chen, Ling; Dong, Zhi-Ling

    2015-01-01

    The present investigation aimed to evaluate the acute and chronic effect of stress (stress hormone) in male albino rat brain. Nor-epinephrine was used for the treatment and saline used for the control. Nor-epinephrine was dissolved in the saline and administered orally to the rats. Following nor-epinephrine administration, the brain was removed surgically at 6 h, 12 h and 45 days. Alanine tansaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) were significantly altered in the rats. Lipid peroxidation was measured as malondialdehyde (MDA), showed altered lipid peroxidation. Hematological markers such as packed cell volume (PCV), white blood cells (WBC), neutrophil, lymphocytes and hemoglobin were significantly altered compared to controls. Altered serum biochemical and hematological markers, lipid peroxidation and enzyme activities leads to adverse effect in the cellular metabolism and physiological activities of rats. PMID:26261571

  1. 6-gingerol ameliorates gentamicin induced renal cortex oxidative stress and apoptosis in adult male albino rats.

    PubMed

    Hegazy, Ahmed M S; Mosaed, Mohammed M; Elshafey, Saad H; Bayomy, Naglaa A

    2016-06-01

    Ginger or Zingiber officinale which is used in traditional medicine has been found to possess antioxidant effect that can control the generation of free radicals. Free radicals are the causes of renal cell degeneration that leads to renal failure in case of gentamicin induced toxicity. This study was done to evaluate the possible protective effects of 6-gingerol as natural antioxidant on gentamicin-induced renal cortical oxidative stress and apoptosis in adult male albino rats. Forty adult male albino rats were used in this study and were randomly divided into four groups, control group; 6-gingerol treated group; gentamicin treated group and protected group (given simultaneous 6-gingerol and gentamicin). At the end of the study, blood samples were drawn for biochemical study. Kidney sections were processed for histological, and immunohistochemical examination for caspase-3 to detect apoptosis and anti heat shock protein 47 (HSP47) to detect oxidative damage. Gentamicin treated rats revealed a highly significant increase in renal function tests, tubular dilatation with marked vacuolar degeneration and desquamation of cells, interstitial hemorrhage and cellular infiltration. Immunohistochemically, gentamicin treated rats showed a strong positive immunoreaction for caspase-3 and anti heat shock protein 47 (HSP47). Protected rats showed more or less normal biochemical, histological, and immunohistochemical pictures. In conclusion, co-administration of 6-gingerol during gentamicin 'therapy' has a significant reno-protective effect in a rat model of gentamicin-induced renal damage. It is recommended that administration of ginger with gentamicin might be beneficial in men who receive gentamicin to treat infections. PMID:27036327

  2. Neuropharmacological activities of Taxus wallichiana bark in Swiss albino mice

    PubMed Central

    Sharma, Hitender; Garg, Munish

    2015-01-01

    Aims: The bark of Taxus wallichiana is widely used for preparing a decoction and consumed as a tea by several tribal communities of the Indian subcontinent. The sedative, motor coordination, anxiolytic, and antidepressant effects of the hydroalcoholic extract of T. wallichiana bark and its ethylacetate fraction were evaluated in mice models of behavior analysis. Materials and Methods: The effects were evaluated on diazepam-induced sleeping time, elevated plus maze and light and dark box, and on the forced swimming test. General locomotor activity and motor coordination effects were evaluated in the actophotmeter and rota-rod tests respectively. Statistical Analysis: Results are expressed as mean ± standard error of the mean. Statistical analysis was performed using ANOVA, followed by post-hoc Dunnett's test. *P < 0.05, **P < 0.01, ***P < 0.001 were considered as significant. Results: Both the hydroalcoholic extract and ethylacetate fraction showed a marked decrease in latency of sleep onset, prolonged the diazepam-induced sleeping time, decreased spontaneous locomotor activity; whereas ethylacetate fraction produced anxiolytic and antidepressant activity. Conclusions: Both hydroalcoholic extract and its ethylacetate fraction of the bark of T. wallichiana have bioactive principles, which induce neuropharmacological changes. PMID:26069368

  3. Capsaicin provokes apoptosis and restricts benzo(a)pyrene induced lung tumorigenesis in Swiss albino mice.

    PubMed

    Anandakumar, P; Kamaraj, S; Jagan, S; Ramakrishnan, G; Devaki, T

    2013-10-01

    Capsaicin (CAP), a constituent of red chilli and red pepper is exposed to exert compelling anticarcinogenic effects. In the present study, we examined the anti-tumorigenic potential of CAP on benzo(a)pyrene-induced mice lung tumorigenesis by analyzing the markers of apoptosis. Intraperitoneal administration of CAP (10mg/kg body weight) to Swiss albino mice suppressed the development of lung carcinoma by amending the protein expressions of apoptotic regulators p53, Bcl-2, Bax and caspase-3. The apoptotic-inducing nature of CAP was further confirmed by DNA agarose gel electrophoresis, transmission electron microscopic study and ethidium bromide/acridine orange staining. The results obtained from the present study show that CAP inhibits the development of mice lung carcinogenesis through its ability to induce apoptosis. Our present findings provide the basis for further clinical exploration of CAP as an anti-carcinogenic compound against lung carcinogenesis. PMID:23747734

  4. Antispermatogenic Activity of the Benzothiazoline Ligand and Corresponding Organoantimony(V) Derivative in Male Albino Rats

    PubMed Central

    Sharma, Pankaj K.; Rehwani, H.; Rai, A. K.; Gupta, R. S.; Singh, Y. P.

    2006-01-01

    Triphenylantimony(V) derivative, Ph3Sb(OPri) [SC6H4N : C(CH3)CH2C(O)CH3], 1b, and the corresponding benzothiazoline ligand [1, 2], HNC6H4SC⎴(CH3)CH2C(O)CH3, 1a, have been tested for their effects on the reproductive system of male albino rats. The oral administration of both 1a and 1b at the dose level of 10 mg/rat/day produced significant reduction in the weights of testes, epididymides, seminal vesicles, and ventral prostate. Significant decrease in sperm motility as well as in sperm density resulted in 100% sterility. Significant (P < .01) alterations were also found in biochemical parameters of reproductive organs in treated male rats as compared to the control group. Production of preleptotene, pachytene, and secondary spermatocytes was decreased by 42%, 43%, 39%, and by 44%, 49%, 55% in the ligand, 1a, and organoantimony(V) derivative, 1b, treated rats, respectively. These results indicate that both compounds 1a and 1b are antispermatogenic in nature and on oral administration in male rats, and finally caused sterility. A comparison indicates that the organoantimony(V) derivative 1b is more effective pertaining to its antispermatogenic activity than the corresponding ligand 1a. PMID:17496999

  5. Effect of Tectona grandis Linn. seeds on hair growth activity of albino mice.

    PubMed

    Jaybhaye, Deepali; Varma, Sushikumar; Gagne, Nitin; Bonde, Vijay; Gite, Amol; Bhosle, Deepak

    2010-10-01

    The seeds of Tectona grandis Linn. are traditionally acclaimed as hair tonic in the Indian system of medicine. Studies were therefore undertaken in order to evaluate petroleum ether extract of T. grandis seeds for its effect on hair growth in albino mice. The 5% and 10% extracts incorporated into simple ointment base were applied topically on shaved denuded skin of albino mice. The time required for initiation of hair growth as well as completion of hair growth cycle was recorded. Minoxidil 2% solution was applied topically and served as positive control. The result of treatment with minoxidil 2% is 49% hair in anagenic phase. Hair growth initiation time was significantly reduced to half on treatment with the extracts compared to control animals. The treatment was successful in bringing a greater number of hair follicles (64% and 51%) in anagenic phase than standard minoxidil (49%). The results of treatment with 5% and 10% petroleum ether extracts were comparable to the positive control minoxidil. PMID:21455447

  6. Zinc sulphate and vitamin E alleviate reproductive toxicity caused by aluminium sulphate in male albino rats.

    PubMed

    Rawi, Sayed M; Seif Al Nassr, Fatma M

    2015-03-01

    This study was designed to investigate the reproductive toxicity of aluminium sulphate and the therapeutic effects of administration of zinc sulphate and vitamin E individually or in combination against the toxic effect caused by aluminium (Al) in male albino rats. The animals were divided into five groups: group 1 received distilled water and served as control; group 2 received only aluminium sulphate (50 mg/kg body weight (b.w.)); group 3 received aluminium sulphate (50 mg/kg b.w.) plus zinc sulphate (50 mg/kg b.w.); group 4 received aluminium sulphate (50 mg/kg b.w.) and vitamin E (15 mg/kg b.w.); group 5 received aluminium sulphate plus a combination of zinc sulphate and vitamin E in similar doses as above. Doses were administered orally once daily for 45 consecutive days. The results revealed that aluminium sulphate induced significant decrease in body weight gain and testis weight and significant increase in Al level in both serum and testes of male rats. Biochemical analysis showed significant decrease in serum total protein and phospholipids levels, while serum total lipid was significantly elevated post Al treatment. In addition, significant decrease in total protein, phospholipids and cholesterol levels in the testes of Al-treated rats was recorded. The data also showed significant decrease in the levels of serum testosterone, leutinizing hormone and follicle stimulating hormone and significant increase in the level of serum prolactin in Al-intoxicated rats. Moreover, histological examination showed that aluminium sulphate caused apparent alterations in the testicular structure of the treated animals. Treatment with zinc sulphate and vitamin E individually or in combination ameliorated the harmful effects of Al, which was proved histopathologically by the noticeable improvement in the testicular tissues. We can conclude that the tested dose of aluminium sulphate induced toxic effect on the reproductive system of male albino rats and the treatment with

  7. Multi walled carbon nano tubes induced hepatotoxicity in Swiss albino mice.

    PubMed

    Awasthi, Kumud Kant; John, P J; Awasthi, Anjali; Awasthi, Kamlendra

    2013-01-01

    In the present study, multi walled carbon nano tubes (MWCNTs) were synthesized using chemical vapour deposition (CVD) technique. Swiss albino mice were orally administered with single dose of 60 and 100 mg/kg body weight of purified and functionalized MWCNTs suspended in water. The mice were autopsied on 7, 14, 21 and 28 days post exposure. Liver was taken out and part of it fixed in Bouin's solution for histopathological examinations. The remaining part was immersed in cold saline, blotted dry, weighed quickly and homogenized in ice cold buffer. The activity of superoxide dismutase (SOD) and catalase (CAT) was immediately measured in the supernatant. The MWCNTs in liver led to pathological changes, including injury to macrophages, cellular swelling, unspecific inflammation, spot necrosis and blood coagulation. Estimation of SOD and CAT showed altered levels in the experimental groups as compared to controls. Therefore, MWCNTs from manufactured and combustion sources in the environment can have adverse effects on human health. PMID:23000350

  8. Generating Chimeric Mice by Using Embryos from Nonsuperovulated BALB/c Mice Compared with Superovulated BALB/c and Albino C57BL/6 Mice.

    PubMed

    Esmail, Michael Y; Qi, Peimin; Connor, Aurora Burds; Fox, James G; García, Alexis

    2016-01-01

    The reliable generation of high-percentage chimeras from gene-targeted C57BL/6 embryonic stem cells has proven challenging, despite optimization of cell culture and microinjection techniques. To improve the efficiency of this procedure, we compared the generation of chimeras by using 3 different inbred, albino host, embryo-generating protocols: BALB/cAnNTac (BALB/c) donor mice superovulated at 4 wk of age, 12-wk-old BALB/c donor mice without superovulation, and C57BL/6NTac-Tyr(tm1Arte) (albino B6) mice superovulated at 4 wk of age. Key parameters measured included the average number of injectable embryos per donor, the percentage of live pups born from the total number of embryos transferred to recipients, and the number of chimeric pups with high embryonic-stem-cell contribution by coat color. Although albino B6 donors produced significantly more injectable embryos than did BALB/c donors, 12-wk-old BALB/c donor produced high-percentage (at least 70%) chimeras more than 2.5 times as often as did albino B6 mice and 20 times more efficiently than did 4-wk-old BALB/c donors. These findings clearly suggest that 12-wk-old BALB/c mice be used as blastocyst donors to reduce the number of mice used to generate each chimera, reduce the production of low-percentage chimeras, and maximize the generation of high-percentage chimeras from C57BL/6 embryonic stem cells. PMID:27423145

  9. Neuroprotective effect of grape seed extract against cadmium toxicity in male albino rats.

    PubMed

    El-Tarras, Adel El-Sayed; Attia, Hossam Fouad; Soliman, Mohammed Mohamed; El Awady, Mohammed Abdelhamid; Amin, Adnan Abelghani

    2016-09-01

    Cadmium toxicity can disturb brain chemistry leading to depression, anxiety, and weakened immunity. Cadmium disturbs the neurotransmitter dopamine, resulting in low energy, lack of motivation, and depression, which are predisposing factors for violence. The purpose of this study was to evaluate the ameliorative effect of grape seed extract (GSE) on the brain of 40 male albino rats after exposure to cadmium chloride (Cd) toxicity. The rats were separated into either the control group, the Cd group, the GSE group, or the GSE and Cd mixture (treated) group. The cerebrum showed evidence of degeneration of some nerve fibers and cells. Fibrosis, vacuolations, and congestion in the blood vessels were demonstrated. Satelletosis was located in the capsular cells. Immunohistochemical expression of Bax was strongly positive in the Cd group and decreased in the treated group. These histopathological changes were decreased in the brain tissue of the treated group, but a few blood vessels still had evidence of congestion. Cadmium administration increased the level of MDA and decreased MAO-A, acetylcholinesterase, and glutathione reductase (GR), while the treatment with GSE affected the alterations in these parameters. In addition, cadmium downregulated the mRNA expression levels of GST and GPx, while GSE treatment normalized the transcript levels. The expression of both dopamine and 5-hydroxytryptamine transporter was downregulated in the rats administered cadmium and the addition of GSE normalized the expression of these aggression associated genes. PMID:27271977

  10. Diuretic activity of leaves of Plectranthus amboinicus (Lour) Spreng in male albino rats

    PubMed Central

    Patel, Roshan; Mahobia, Naveen K.; Gendle, Ravindra; Kaushik, Basant; Singh, Sudarshan K.

    2010-01-01

    The shade-dried powder of leaves of Plectranthus amboinicus (Lour) Spreng was subjected to successive extraction using the various solvents (petroleum ether, chloroform, ethanol and water) in increasing order of polarity. The preliminary phytochemical analyses were carried out for all the extracts. The analyses of the leaves revealed the presence of alkaloids, carbohydrates, glycosides, proteins, amino acids, flavonoids, quinine, tannins, phenolic compounds and terpenoids. Since the phytoconstituents present in the ethanolic and aqueous extracts were similar, both the extracts were selected for further study. The diuretic properties of ethanolic and aqueous extracts were evaluated by determination of urine volume and electrolyte concentration in male albino rats. Furosemide (10 mg/kg) was used as standard while normal saline (0.9%) was used as control. Both ethanolic and aqueous extracts (500 mg/kg) have shown significant increase in the volume of urine and urinary concentration of Na, K and Cl ions. Thus, from the is study it may be concluded that the leaves of P. amboinicus (Lour) Spreng possess diuretic activities. PMID:21808546

  11. Diuretic activity of leaves of Plectranthus amboinicus (Lour) Spreng in male albino rats.

    PubMed

    Patel, Roshan; Mahobia, Naveen K; Gendle, Ravindra; Kaushik, Basant; Singh, Sudarshan K

    2010-03-01

    The shade-dried powder of leaves of Plectranthus amboinicus (Lour) Spreng was subjected to successive extraction using the various solvents (petroleum ether, chloroform, ethanol and water) in increasing order of polarity. The preliminary phytochemical analyses were carried out for all the extracts. The analyses of the leaves revealed the presence of alkaloids, carbohydrates, glycosides, proteins, amino acids, flavonoids, quinine, tannins, phenolic compounds and terpenoids. Since the phytoconstituents present in the ethanolic and aqueous extracts were similar, both the extracts were selected for further study. The diuretic properties of ethanolic and aqueous extracts were evaluated by determination of urine volume and electrolyte concentration in male albino rats. Furosemide (10 mg/kg) was used as standard while normal saline (0.9%) was used as control. Both ethanolic and aqueous extracts (500 mg/kg) have shown significant increase in the volume of urine and urinary concentration of Na, K and Cl ions. Thus, from the is study it may be concluded that the leaves of P. amboinicus (Lour) Spreng possess diuretic activities. PMID:21808546

  12. Experimental transmission of Trypanosoma cruzi through the genitalia of albino mice.

    PubMed

    Herrera, L; Urdaneta-Morales, S

    2001-07-01

    Trypanosoma cruzi is usually transmitted by contact with the excreta of infected Triatominae; among non-vectorial infections, direct transmission through coitus has been proposed. We investigated this possibility by instilling, through the external meatus of the vagina and the penis of previously anesthetized NMRI albino mice, blood of mice infected with strains isolated from Didelphis marsupialis (opossum, strain CO57), Rattus rattus (rat, strain CO22) and human (strain EP). Some animals were allowed to copulate the same day of the instillation. In other experiments, the strains were inoculated in the scrotum. To determine the effect of immunosuppression, some mice were treated with cyclophosphamide 30 days post-instillation. Controls were instilled orally and ocularly. Vaginal instillation with strain CO22 produced systemic infection with tropism to the heart, skeletal muscle, skin, duodenum, pancreas, ovary and sternum. Scrotal inoculation with strain EP likewise invaded liver, spleen, lung, lymph nodes and urogenital organs; while strain CO57 invaded skeletal and cardiac muscle, pancreas, testis, and vas deferens. Penile infection with strain CO22 was detected by xenodiagnosis. Immunosuppression did not increase parasitemia of vaginally infected mice or controls. Mating did not produce infection. Our results show that contact of blood trypomastigotes of T. cruzi with genital mucosa can produce blood and tissue infections. These results are discussed in relation to reports of frequent experimental tropism of T. cruzi toward urogenital organs. PMID:11500777

  13. Antitumour effect of Diospyros cordifolia bark on Ehrlich ascites carcinoma-bearing Swiss albino mice.

    PubMed

    Das, Sudipta; Bhattacharya, Sanjib; Pramanik, Goutam; Haldar, Pallab Kanti

    2012-01-01

    Diospyros cordifolia Roxb. (Ebenaceae), commonly known as Indian ebony, is used traditionally for several medicinal purposes. In this study, the methanol extract of D. cordifolia bark (MEDC) was evaluated for its antitumour effect against Ehrlich ascites carcinoma (EAC)-bearing Swiss albino mice. Twenty-four hours after intraperitoneal inoculation of tumour (EAC) cells in mice, MEDC was administered intraperitoneally at 25 and 50 mg kg⁻¹ bodyweight for 9 consecutive days. On the 10th day, half of the mice were sacrificed to determine the tumour volume, viable and non-viable tumour cell counts, and rest were kept alive for the assessment of median survival time and increase in life span. Haematological profiles were also determined. MEDC exhibited a marked decrease in tumour growth parameters and increased the survival rate of EAC-bearing animals. MEDC normalised the haematological parameters as compared with the EAC control mice. Therefore, this study demonstrated that D. cordifolia bark possessed remarkable antitumour efficacy. PMID:21985607

  14. Vetiver oil (Java) attenuates cisplatin-induced oxidative stress, nephrotoxicity and myelosuppression in Swiss albino mice.

    PubMed

    Sinha, Sonali; Jothiramajayam, Manivannan; Ghosh, Manosij; Jana, Aditi; Chatterji, Urmi; Mukherjee, Anita

    2015-07-01

    Clinical efficacy of the widely used anticancer drug cisplatin is limited due to its adverse side effects in normal tissues mediated by oxidative stress. This study was aimed to investigate the protective effects of vetiver acetate oil, Java (VO) against cisplatin-induced toxicity in Swiss albino mice. The ameliorating potential was evaluated by orally priming the animals with VO at doses 5, 10 or 20 mg/kg bw for 7 days prior to cisplatin treatment. Acute toxicity in mice was induced by injecting cisplatin (3 mg/kg bw) intraperitoneally for 5 consecutive days. Significant attenuation of renal toxicity was confirmed by histopathological examination, lowered levels of serum blood urea nitrogen, creatinine and reduced DNA damage. VO also compensated deficits in the renal antioxidant system. VO intervention significantly inhibited DNA damage, clastogenic effects, and cell cycle arrest in the bone marrow cells of mice. Hematological parameters indicated attenuation of cisplatin-induced myelosuppression. Overall, this study provides for the first time that VO has a protective role in the abatement of cisplatin-induced toxicity in mice which may be attributed to its antioxidant activity. PMID:25910835

  15. Antiplasmodial Effect of Anthocleista vogelii on Albino Mice Experimentally Infected with Plasmodium berghei berghei (NK 65)

    PubMed Central

    Gboeloh, Lebari Barine; Okon, Okpok Eta; Udoh, Samuel Effiong

    2014-01-01

    The objective of the present study was to investigate the antiplasmodial effect of the ethanolic stem bark extract of Anthocleista vogelii at different doses in albino mice infected with Plasmodium berghei berghei (NK 65). Thirty-six mice were divided into six groups of six mice each. Five groups (B1–B3, D, and G) were infected with Plasmodium berghei berghei parasitized red blood cells. Groups D, H, and G served as the controls. Six days after infection, mice in groups B1, B2, and B3 were treated orally with 100, 200, and 400 mg/kg body weight of Anthocleista vogelii, respectively, for six executive days. Group D was treated with 5 mg/kg body weight of chloroquine while Group G was given distilled water. Group H was not infected and was not treated. It served as the normal control. The extracts exhibited significant (P < 0.05) dose-dependent chemosuppression of P. berghei. The extract exhibited average chemosuppressive effects of 48.5%, 78.5%, and 86.6% at dose levels of 100, 200, and 400 mg/kg body weight, respectively. Phytochemical screening of the plant extract revealed the presence of saponins, cardiac glycosides, flavonoids, terpenes, alkaloids, and steroid. The acute toxicity (LD50) of the plant was estimated to be 3162 mg/kg body weight. It showed that the stem bark of A. vogelii possesses antiplasmodial property. PMID:24900913

  16. Antitumor and antioxidant status of Terminalia catappa against Ehrlich ascites carcinoma in Swiss albino mice

    PubMed Central

    Pandya, Naitik B.; Tigari, Prakash; Dupadahalli, Kotresha; Kamurthy, Hemalatha; Nadendla, Rama Rao

    2013-01-01

    Objective: The present study was undertaken to evaluate the antitumor and antioxidant status of ethanol extract of Terminalia catappa leaves against Ehrlich ascites carcinoma (EAC) in Swiss albino mice. Materials and Methods: The leaves powder was extracted with Soxhlet apparatus and subjected to hot continuous percolation using ethanol (95% v/v). Tumor bearing animals was treated with 50 and 200 mg/kg of ethanol extract. EAC induced in mice by intraperitoneal injection of EAC cells 1 × 106 cells/mice. The study was assed using life span of EAC-bearing hosts, hematological parameters, volume of solid tumor mass and status of antioxidant enzymes such as lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) activities. Total phenolics and flavonoids contents from the leaves extract were also determined. Results: Total phenolics and flavonoids contents from the leaves extract were found 354.02 and 51.67 mg/g extract. Oral administration of ethanol extract of T. catappa (50 and 200 mg/kg) increased the life span (27.82% and 60.59%), increased peritoneal cell count (8.85 ± 0.20 and 10.37 ± 0.26) and significantly decreased solid tumor mass (1.16 ± 0.14 cm2) at 200 mg/kg as compared with EAC-tumor bearing mice (P < 0.01). Hematological profile including red blood cell count, white blood cell count, hemoglobin (11.91 ± 0.47 % g) and protein estimation were found to be nearly normal levels in extract-treated mice compared with tumor bearing control mice. Treatment with T. catappa significantly decreased levels of LPO and GSH, and increased levels of SOD and CAT activity (P < 0.01). Conclusion: T. catappa exhibited antitumor effect by modulating LPO and augmenting antioxidant defense systems in EAC bearing mice. The phenolic and flavonoid components in this extract may be responsible for antitumor activity. PMID:24130380

  17. Evaluation of radioprotective effects of Rajgira (Amaranthus paniculatus) extract in Swiss albino mice.

    PubMed

    Krishna, Anita; Kumar, Ashok

    2005-06-01

    The radioprotective efficacy of aqueous extract of Rajgira (Amaranthus paniculatus) leaves against whole body gamma radiation was studied in Swiss albino mice. The oral administration of Rajgira extract at 800 mg/kg body weight/day for 15 consecutive days before whole body exposure to radiation was found to be effective with the LD50/30 values of 6.33 and 8.62 Gy for irradiation alone and Rajgira+irradiation group, respectively, giving a dose reduction factor of 1.36. This effect of Rajgira accompanied the increased endogenous spleen colonies and the spleen weight without any side effect or toxicity, as well as the modulation of the radiation-induced decrease of reduced glutathione and the radiation-induced increase in lipid peroxidation assessed in the liver and the blood. PMID:15988142

  18. Anti-seizure activity of flower extracts of Nepeta bractaeta in Swiss albino mice

    PubMed Central

    Bhat, Jalal Uddin; Parray, Shabir Ahmad; Aslam, Mohammad; Ansari, Shahid; Nizami, Qudsia; Khanam, Razia; Siddiqui, Aisha; Ahmad, Mohd Aftab

    2012-01-01

    Epilepsy is a neurological disorder characterized by unprovoked, recurring seizures that disrupts the nervous system and can cause mental and physical dysfunction. Based on the ethno pharmacological information of the plant, the methanolic and aqueous extracts of the flowers of Nepeta bractaeta was evaluated for its antiepileptic activity. The methanolic and aqueous extracts of the flowers of Nepeta bracteata were observed for their antiepileptic activity by increased current Electroshock seizures (ICES) test and Pentylenetetrazole (PTZ) test using Swiss albino mice. Both the extracts showed significant activity in ICES and PTZ induced convulsions in comparison to control. In ICES model, NBAE at higher dose showed 16.7 % and NBME at higher dose showed 33.3 % protection against seizure and in PTZ model, NBME at higher dose showed 33.3 % protection against seizure. From the experiments performed, it can be said that Nepeta bractaeta does possess anticonvulsant property.

  19. Anti-seizure activity of flower extracts of Nepeta bractaeta in Swiss albino mice.

    PubMed

    Bhat, Jalal Uddin; Parray, Shabir Ahmad; Aslam, Mohammad; Ansari, Shahid; Nizami, Qudsia; Khanam, Razia; Siddiqui, Aisha; Ahmad, Mohd Aftab

    2012-01-01

    Epilepsy is a neurological disorder characterized by unprovoked, recurring seizures that disrupts the nervous system and can cause mental and physical dysfunction. Based on the ethno pharmacological information of the plant, the methanolic and aqueous extracts of the flowers of Nepeta bractaeta was evaluated for its antiepileptic activity. The methanolic and aqueous extracts of the flowers of Nepeta bracteata were observed for their antiepileptic activity by increased current Electroshock seizures (ICES) test and Pentylenetetrazole (PTZ) test using Swiss albino mice. Both the extracts showed significant activity in ICES and PTZ induced convulsions in comparison to control. In ICES model, NBAE at higher dose showed 16.7 % and NBME at higher dose showed 33.3 % protection against seizure and in PTZ model, NBME at higher dose showed 33.3 % protection against seizure. From the experiments performed, it can be said that Nepeta bractaeta does possess anticonvulsant property. PMID:27540346

  20. Anticonvulsant activity of methanolic and aqueous extracts of Melissa parviflora in experimentally induced Swiss albino mice

    PubMed Central

    Bhat, Jalal Uddin; Nizami, Qudsia; Asiaf, Asia; Parray, Shabir Ahmad; Ahmad, Shiekh Tanveer; Aslam, Mohammad; Khanam, Razia; Mujeeb, Mohammad; Umar, Sadiq; Siddiqi, Ayesha

    2012-01-01

    The aim of the present study was to evaluate the anticonvulsant effect of whole plant extracts of Melissa parviflora using MES and PTZ induced seizures models. The dried whole plant was subjected to extraction in methanol and water. The extracts were subjected to phytochemical tests and the carbohydrate, flavonols, coumarins, glycosides and steroid were found to be present. The methanolic and aqueous extracts of the plant of Melissa parviflora were observed for their anticonvulsant activity by Maximal Electroshock seizures (MES) test and Pentylenetetrazole (PTZ) test using Swiss albino mice. Both the extracts showed significant activity in MES and PTZ induced convulsions in comparison to control. From the literature surveys as well experiments performed, it can be said that Melissa parviflora does pose anticonvulsant property. PMID:27298604

  1. Evaluation of anti-depressant and anxiolytic activity of Rasayana Ghana Tablet (A compound Ayurvedic formulation) in albino mice

    PubMed Central

    Deole, Yogesh S.; Chavan, Sulakshan S.; Ashok, B. K.; Ravishankar, B.; Thakar, A. B.; Chandola, H. M.

    2011-01-01

    In recent years, many Ayurvedic formulations are being researched to provide an effective antidepressant and anxiolytic drug in the field of psycho-pharmacology. The present study was planned to evaluate the anti-depressant and anxiolytic activity of Rasayana Ghana Tablet comprising three herbs Guduchi (Tinospora cordifolia Miers), Aamalaki (Emblica officinalis Garten) (RGT) and Gokshura (Tribulus terrestris Linn). Swiss albino mice were divided into four groups of six animals each, comprising of both male and female in each group. Group I received water served as normal control (WC), group II received vehicle and served as vehicle control (VC), group III received Rasayana Ghana tablet and group IV received standard drug diazepam (2 mg/kg) for anxiolytic study in elevated plus maze and standard antidepressant imipramine (5 mg/kg) for anti-depressant activity in behavior despair test. Rasayana Ghana tablet along with ghee and honey as vehicle is found to be having antidepressant and anxiolytic activity in experimental animals. Thus, this formulation can be used in prevention and treatment of depression and anxiety. PMID:22529654

  2. Assessment of Immunotoxicity of Dextran Coated Ferrite Nanoparticles in Albino Mice

    PubMed Central

    Syama, Santhakumar; Gayathri, Viswanathan; Mohanan, Parayanthala Valappil

    2015-01-01

    In this study, dextran coated ferrite nanoparticles (DFNPs) of size <25 nm were synthesized, characterized, and evaluated for cytotoxicity, immunotoxicity, and oxidative stress by in vitro and in vivo methods. Cytotoxicity was performed in vitro using splenocytes with different concentrations of DFNPs. Gene expression of selected cytokines (IL-1, IL-10, and TNF β) secretion by splenocytes was evaluated. Also, 100 mg of DFNPs was injected intraperitoneally to 18 albino mice for immunological stimulations. Six animals each were sacrificed at the end of 7, 14, and 21 days. Spleen was subjected to immunotoxic response and liver was analyzed for antioxidant parameters (lipid peroxidation, reduced glutathione, glutathione peroxidase, superoxide dismutase, and glutathione reductase). The results indicated that DFNPs failed to induce any immunological reactions and no significant alternation in antioxidant defense mechanism. Also, mRNA expression of the cytokines revealed an increase in IL-10 expression and subsequent decreased expression of IL-1 and TNF β. Eventually, DNA sequencing of liver actin gene revealed base alteration in nonconserved regions (10–20 bases) of all the treated groups when compared to control samples. Hence, it can be concluded that the DFNPs were nontoxic at the cellular level and nonimmunotoxic when exposed intraperitoneally to mice. PMID:26576301

  3. Radiomodulatory influence of Rajgira (Amaranthus paniculatus) leaf extract in Swiss albino mice.

    PubMed

    Maharwal, J; Samarth, R M; Saini, M R

    2003-12-01

    Radiomodulatory effect of Rajgira leaf extract against 6, 8 and 10 Gy gamma radiation has been evaluated by 30 day survival of Swiss albino mice. Animals of control groups (untreated irradiated) showed diarrhoea, ruffled hairs, epilation, facial edema and consistent decrease in body weight. These signs were less severe/absent in experimental groups (Rajgira treated irradiated), and recovery in body weight was also early and faster. Thirty day survivability was 66 per cent in control group, exposed to 6 Gy, whereas no animal survived beyond 14 and 10 days after irradiation with 8 and 10 Gy gamma rays respectively. However, 100, 60 and 25 percent survivability was observed in experimental groups at 6, 8 and 10 Gy respectively. Regression analysis of survival data showed that the LD50/30 values were 6.33 and 8.62 Gy for control and experimental animals respectively. The dose reduction factor (DRF) was computed as 1.36. A significant decrease in GSH content and increase in LPO level was observed in control animals, whereas in Rajgira pretreated irradiated animals the level of GSH was recorded significantly higher but LPO level decreased significantly. The results from the present study suggest that Rajgira pretreatment provide protection against gamma irradiation in mice. PMID:14669247

  4. In vivo DNA damaging and apoptotic potential of silver nanoparticles in Swiss albino mice

    PubMed Central

    Al Gurabi, Mohammed A; Ali, Daoud; Alkahtani, Saad; Alarifi, Saud

    2015-01-01

    Nanoparticles can potentially cause adverse effects on organs, tissue, cell levels, and protein levels because of their physicochemical properties. Silver nanoparticles (AgNPs) are being used on a wide scale in world consumer markets; their potential hazards for humans remain largely unknown. This study aimed to investigate the intraperitoneal toxicity of AgNPs (26 mg per kg of body weight, 52 mg per kg of body weight, and 78 mg per kg of body weight) over 72 hours in Swiss albino mice. AgNPs induced a significant increase in serum liver injury markers including alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase. Induction of DNA damage was also studied in mice injected with AgNPs. Apoptosis (detected by using the terminal deoxynucleotidyl transferase deoxyuridine triphosphatase nick end labeling assay method) in liver tissue and DNA strand breaks (detected by using the comet assay method) in lymphocytes revealed that a concentration of 78 mg of AgNPs per kg body weight can cause significant apoptosis and DNA damage. The DNA damage and apoptosis raise the concern about the safety associated with application of the AgNPs. Significantly more alterations were induced in the hepatocytes of animals exposed to AgNP doses than in the control animals. The induced histological and apoptotic changes may be due to AgNP toxicity. Immunohistochemical and ultrastructural of AgNP. PMID:25674004

  5. Evaluation of antihyperglycemic and antinociceptive activity of Xanthium indicum stem extract in Swiss albino mice

    PubMed Central

    2013-01-01

    Background Xanthium indicum stem is used in folk medicine of Bangladesh to control sugar in diabetic patients and to alleviate pain. The objective of the study was to evaluate antihyperglycemic and antinociceptive activity of methanolic extract of Xanthium indicum stems (XISE) in mice. Methods Antihyperglycemic activity was measured by oral glucose tolerance tests in glucose-loaded Swiss albino mice. Antinociceptive activity was determined by observed decreases in abdominal constrictions in acetic acid-induced gastric pain model in mice. Results The methanol extract of stems showed dose-dependent and statistically significant antihyperglycemic activity at doses of 50, 100, 200 and 400 mg per kg body weight (p values, respectively, < than 0.01, 0.01, 0.005, and 0.01). Highest reduction in blood glucose level (31.2%) was observed with the highest dose (400 mg) of the extract. A standard antihyperglycemic drug, glibenclamide, reduced blood glucose levels by 46.2%, when administered at a dose of 10 mg per kg body weight. In antinociceptive activity tests, the extract when administered at the afore-mentioned four doses, reduced the number of abdominal constrictions in mice, respectively, by 41.7, 50.0, 54.2, and 61.0%. In comparison, a standard antinociceptive drug, aspirin, when administered at a dose of 200 mg per kg body weight, reduced the number of abdominal constrictions by 37.5%. Conclusion The experimental results obtained in the present study validate the use of X. indicum stems in folk medicines of Bangladesh to lower blood sugar in diabetic patients and to alleviate pain. PMID:24171758

  6. Evaluation of Antinociceptive Activity of Aqueous Extract of Bark of Psidium Guajava in Albino Rats and Albino Mice

    PubMed Central

    Jayasree, T.; Ubedulla, Shaikh; Dixit, Rohit; V S, Manohar; J, Shankar

    2014-01-01

    Background: Psidium guajava is commonly known as guava. Psidium guajava is a medium sized tree belonging to the family Myrtaceae found throughout the tropics. All the parts of the plant, the leaves, followed by the fruits, bark and the roots are used in traditional medicine. The traditional uses of the plant are Antidiarrheal, Antimicrobial Activity, Antimalarial/Antiparasitic Activity, Antitussive and antihyperglycaemic. Leaves are used as Anti-inflammatory, Analgesic and Antinociceptive effects. Aim: To evaluate the antinociceptive activity of aqueous extract of bark of Psidium guajava in albino rats with that of control and standard analgesic drugs aspirin and tramadol. Materials and Methods: Mechanical (Tail clip method) and thermal (Tail flick method using Analgesiometer), 0.6% solution of acetic acid writhing models of nociception were used to evaluate the extract antinociceptive activity. Six groups of animals, each consists of 10 animals, first one as control, second and third as standard drugs, Aspirin and Tramadol, fourth, fifth and sixth groups as text received the extract (100, 200, and 400 mg/ kg) orally 60 min prior to subjection to the respective test. Results: The results obtained demonstrated that aqueous extract of bark of Psidium guajava produced significant antinociceptive response in all the mechanical and thermal-induced nociception models. Conclusion: AEPG antinociceptive activity involves activation of the peripheral and central mechanisms. PMID:25386462

  7. Lethality, accumulation and toxicokinetics of aluminum in some tissues of male albino rats.

    PubMed

    Rawy, Sayed M; Morsy, Gamal M; Elshibani, Majda M

    2013-04-01

    In the present work, the lethality percentiles including median lethal doses (LD50), accumulation, distribution and toxicokinetics of aluminum in the liver, kidney, intestine, brain and serum of male albino rats, following a single oral administration were studied throughout 1, 3, 7, 14 and 28 days. The estimated LD50 at 24 h was 3.45 g Al/kg body weight (b.wt.). The utilized dose of Al was 1/50 LD50 (0.07 g Al/kg b.wt.). Aluminum residues, in Al-treated rats, were significantly decreased in response to the experimental periods and were negatively correlated with time. In addition, the hepatic, renal, intestinal, brain and serum Al contents were significantly higher than the corresponding controls at all experimental periods, except the brain that showed significant depletion when compared with its corresponding control after 28 days. Kinetically, the highest average of Al area under concentration - time curves (AUCtotal, μg/g day) and area under moment concentration - time curves (AUMCtotal, µg/g day(2)) recorded in the brain followed by kidney, serum, intestine and liver. The longest elimination half-life time (t 1/2, day) and the mean residence time (MRT, day) were recorded in the brain followed by the liver, kidney, serum and intestine. On the other hand, the slowest clearance rates (Cls, L/day) of Al, in order, were recorded in brain, kidney, serum, intestine and the liver. The elimination rate constant (Lz, day(-) (1)) of Al from the brain was less than that in the intestine and serum was less than that in the liver and kidney. The computed maximum concentrations (C max) of Al in the intestine > kidney > serum > brain > liver were recorded after 3, 3.8, 2.2, 5.4 and 3.8 days, respectively. The computed starting concentration (C 0, μg) of Al in serum was higher than its level in the intestine followed by the brain, kidney and liver. PMID:22317823

  8. Studies on fate and toxicity of nanoalumina in male albino rats: Lethality, bioaccumulation and genotoxicity.

    PubMed

    Morsy, Gamal M; El-Ala, Kawther S Abou; Ali, Atef A

    2016-02-01

    The purpose of this study is to follow-up the distribution, lethality percentile doses (LDs) and bioaccumulation of aluminium oxide nanoparticles (Al2O3-NPs, average diameter 9.83 ± 1.61 nm) in some tissues of male albino rats, and to evaluate its genotoxicity to the brain tissues, during acute and sublethal experiments. The LDs of Al2O3-NPs, including median lethal dose (LD50), were estimated after intraperitoneal injection. The computed LD50 at 24 and 48 h were 15.10 and 12.88 g/kg body weight (b.w.), respectively. For acute experiments, the bioaccumulation of aluminium (Al) in the brain, liver, kidneys, intestine and spleen was estimated after 48 h of injection with a single acute dose (3.9, 6.4 and 8.5 g/kg b.w.), while for sublethal experiments it was after 1, 3, 7, 14 and 28 days of injection with 1.3 g/kg b.w. once in 2 days. Multi-way analysis of variance affirmed that Al uptake, in acute experiments, was significantly affected by the injected doses, organs (brain, liver, kidneys, intestine and spleen) and their interactions, while for sublethal experiments an altogether effect based on time (1, 3, 7, 14, 28 days), doses (0 and 1.3 g), organs and their interactions was reported. In addition, Al accumulated in the brain, liver, kidney, intestine and spleen of rats administered with Al2O3-NPs were significantly higher than the corresponding controls, during acute and sublethal experiments. The uptake of Al by the spleen of rats injected with acute doses was greater than that accumulated by kidney>brain>intestine>liver, whereas the brain of rats injected with sublethal dose accumulated lesser amount of Al followed by the kidney

  9. Ameliorative Effects of Acacia Honey against Sodium Arsenite-Induced Oxidative Stress in Some Viscera of Male Wistar Albino Rats

    PubMed Central

    Aliyu, Muhammad; Ibrahim, Sani; Inuwa, Hajiya M.; Sallau, Abdullahi B.; Abbas, Olagunju; Aimola, Idowu A.; Habila, Nathan; Uche, Ndidi S.

    2013-01-01

    Cancer is a leading cause of death worldwide and its development is frequently associated with oxidative stress-induced by carcinogens such as arsenicals. Most foods are basically health-promoting or disease-preventing and a typical example of such type is honey. This study was undertaken to investigate the ameliorative effects of Acacia honey on sodium arsenite-induced oxidative stress in the heart, lung and kidney tissues of male Wistar rats. Male Wistar albino rats divided into four groups of five rats each were administered distilled water, Acacia honey (20%), sodium arsenite (5 mg/kg body weight), Acacia honey, and sodium arsenite daily for one week. They were sacrificed anesthetically using 60 mg/kg sodium pentothal. The tissues were used for the assessment of glutathione peroxidase, catalase, and superoxide dismutase activities, protein content and lipid peroxidation. Sodium arsenite significantly (P < 0.05) suppressed the glutathione peroxidase, catalase, superoxide dismutase activities with simultaneous induction of lipid peroxidation. Administration of Acacia honey significantly increased (P < 0.05) glutathione peroxidase, catalase, and superoxide dismutase activities with concomitant suppression of lipid peroxidation as evident by the decrease in malondialdehyde level. From the results obtained, Acacia honey mitigates sodium arsenite induced-oxidative stress in male Wistar albino rats, which suggest that it may attenuate oxidative stress implicated in chemical carcinogenesis. PMID:24368942

  10. Bioassay of Eucalyptus extracts for anticancer activity against Ehrlich ascites carcinoma (eac) cells in Swiss albino mice

    PubMed Central

    Islam, Farhadul; Khatun, Hasina; Ghosh, Soby; Ali, MM; Khanam, JA

    2012-01-01

    Objective To evaluate the antineoplastic activity of Eucalyptus extract (EuE) against Ehrlich ascites carcinoma (EAC) in Swiss albino mice. Methods Preliminary examination of four plant extracts (namely Eucalyptus, Costus, Azadirachta, Feronia) has been done by observing the reduction ability of number of EAC cells in previously inoculated Swiss albino mice. Among them as EuE showed maximum capability, the whole study has been conducted with EuE only. Important parameters viz. enhancement of life span, reduction of average tumor weight etc. have been studied. In addition the effects of EuE on hematological parameters in both normal and EAC inoculated mice have been measured. Effect of EuE on normal peritoneal cells has also been studied. Results : EuE reduced tumor burden remarkably. It reduced the tumor growth rate and enhanced the life span of EAC bearing mice noticeably. It reversed back the hematological parameters towards normal, reduced the trasplantability of EAC cells and enhanced the immunomodulatory effects in mice. The host toxic effect of EuE in mice is minimum and mostly reversible with time. All such data have been compared with those obtained by running parallel experiments with bleomycin at dose 0.3 mg/kg (i.p.). Conclusions The Eucalyptus extract may be considered as a potent anticancer agent for advanced researches. PMID:23569937

  11. Inhibition of Ehrlich ascites carcinoma by Manilkara zapota L. stem bark in Swiss albino mice

    PubMed Central

    Osman, M Abu; Rashid, M Mamunur; Aziz, M Abdul; Habib, M Rowshahul; karim, M Rezaul

    2011-01-01

    Objective To evaluate the antitumor activity of Manilkara zapota (M. zapota) L. stem bark against Ehrlich ascites carcinoma (EAC) in Swiss albino mice. Methods The in vivo antitumour activity of the ethyl acetate extract of stem bark of M. zapota L. (EASM) was evaluated at 50, 100 and 200 mg/kg bw against EAC using mean survival time. After administration of the extract of M. zapota, viable EAC cell count and body weight in the EAC tumour hosts were observed. The animal was also observed for improvement in the haematological parameters (e.g., heamoglobin content, red and white blood cells count and differential cell count) after EASM treatment. Results Intraperitoneal administration of EASM reduced viable EAC cells, increased the survival time, and restored altered haematological parameters. Significant efficacy was observed for EASM at 100 mg/kg dose (P<0.05). Conclusions It can be concluded that the ethyl acetate extract of stem bark of M. zapota L. possesses significant antitumour activity. PMID:23569811

  12. Clastogenic Effects of Glyphosate in Bone Marrow Cells of Swiss Albino Mice

    PubMed Central

    Prasad, Sahdeo; Srivastava, Smita; Singh, Madhulika; Shukla, Yogeshwer

    2009-01-01

    Glyphosate (N-(phosphonomethyl) glycine, C3H8NO5P), a herbicide, used to control unwanted annual and perennial plants all over the world. Nevertheless, occupational and environmental exposure to pesticides can pose a threat to nontarget species including human beings. Therefore, in the present study, genotoxic effects of the herbicide glyphosate were analyzed by measuring chromosomal aberrations (CAs) and micronuclei (MN) in bone marrow cells of Swiss albino mice. A single dose of glyphosate was given intraperitoneally (i.p) to the animals at a concentration of 25 and 50 mg/kg b.wt. Animals of positive control group were injected i.p. benzo(a)pyrene (100 mg/kg b.wt., once only), whereas, animals of control (vehicle) group were injected i.p. dimethyl sulfoxide (0.2 mL). Animals from all the groups were sacrificed at sampling times of 24, 48, and 72 hours and their bone marrow was analyzed for cytogenetic and chromosomal damage. Glyphosate treatment significantly increases CAs and MN induction at both treatments and time compared with the vehicle control (P < .05). The cytotoxic effects of glyphosate were also evident, as observed by significant decrease in mitotic index (MI). The present results indicate that glyphosate is clastogenic and cytotoxic to mouse bone marrow. PMID:20107585

  13. Tuftsin Augments Antitumor Efficacy of Liposomized Etoposide against Fibrosarcoma in Swiss Albino Mice

    PubMed Central

    Khan, Arif; Khan, Aijaz A; Dwivedi, Varun; Ahmad, Manzoor G; Hakeem, Seema; Owais, Mohammad

    2007-01-01

    Anticancer drugs are generally plagued by toxic manifestations at doses necessary for control of various forms of cancer. Incorporating such drugs into liposomes not only reduces toxicity but also enhances the therapeutic index. Some antioxidants and potent immunomodulators have also been shown to impart significant antitumor activity presumably by nonspecific activation of the host immune system. In the present study, we evaluated augmentation of the antitumor activity of etoposide (ETP) by the immunomodulator tuftsin in Swiss albino mice with fibrosarcoma. The efficacies of the free form of ETP, liposomized ETP (Lip-ETP), and tuftsin-bearing liposomized ETP (Tuft-Lip-ETP) formulations were evaluated on the basis of tumor regression, effect on expression level of p53wt and p53mut, and survival of the treated animals. Tuft-Lip-ETP, when administered at a dosage of 10 mg/kg body weight/day for five days, significantly reduced tumor volume, delayed tumor growth, and also up-regulated the expression of p53wt. In contrast, although Lip-ETP delayed tumor growth, it did not decrease tumor size. The results of the present study suggest that tuftsin incorporation in drug-loaded liposomes is a promising treatment strategy for various forms of cancers, including fibrosarcoma. PMID:17622310

  14. [Comparative efficacy of albendazole and mebendazole oily suspensions in albino mice with experimental larval alveococcosis].

    PubMed

    Kovalenko, F P; Kukhaleva, I V; Shkoliar, N A; Legon'kov, Iu A

    2013-01-01

    The comparative efficacy of albendazole and mebendazole oily suspensions (AOS and MOS) was studied in an experimental model of experimental larval alveococcosis in albino mice. The animals were intragastrically injected with the agents once daily for 40 days on day 35 after intraperitoneal inoculation with E. multilocularis acephalocysts. They were dissected 29 days after treatment termination (103 days following inoculation) and the rate of infestation and viability and the degree of maturity of developed alveococcosis larvocysts (AL) were determined. The AOS and MOS efficiency estimated by the mean mass of AL per animal was 83.3 and 98.1%, respectively; whereas the similar indicator calculated by one largest AL weight per animal found among all the animals in the compared groups was equal to 57.7 and 96.9%, respectively. Under the equal conditions of solubilization in vegetable oil, the biological activity and bioavailability of mebendazole were shown to increase to a much greater extent than those of albendazole. The findings suggest that the use of mebendazole is promising for designing new vegetable oil-based formulations of the agent. PMID:24003516

  15. [EFFICACY OF A NEW MEBENDAZOLE FORMULATION FOR EXPERIMENTAL ECHINOCOCCUS GRANULOSUS LARVAL INVASION IN ALBINO MICE].

    PubMed

    Kovalenko, F P; Kukhaleva, I V; Shkolyar, N A; Legonkov, Yu A; Musaev, G Kh; Bulanova, T E; Samochatova, E I

    2015-01-01

    The problem of echinococcosis has acquired special urgency in Russia in the last 10 years. The dramatically worse epidemiological situation of echinococcosis in the country is suggested by just frequent cases of cystic echinococcosis in the indigenous population of Moscow and its region, including children. Currently, albendazole that is less toxic than mebendazole remains the drug of choice, However, some authors note that E. granulosus larval cysts are moresusceptible to mebendazole than to albendazole. Both drugs mainly show parasitological activity and have no larvicidal effect particularly in larval alveococcosis. Analysis of the results of chemotherapy, with a group of benzimidazole carbamates for echinococcosis in 6 clinical centers from 5 European countries (Italy, Bulgaria, Romania, Greece, and Turkey) over the past 30 years showed that the evaluation of therapeutic effectiveness was overestimated; thus, 40% of all parasitic larval cysts that were considered dead became active again after, 2 years after the treatment. The original oil micronized mebendazole suspension tested by us in albino mice with late-stage larval cystic echinococcosis showed the properties of a highly effective and safe systemic larvicide that caused prompt death in the entire parasite population in the treated animals even in extreme hyperinvasion when the baseline parasite weight was greater than the host's one. PMID:26827585

  16. Improvement of sperm density in neem-oil induced infertile male albino rats by Ipomoea digitata Linn

    PubMed Central

    Mahajan, Ghanashyam Keshav; Mahajan, Raghunath Totaram; Mahajan, Arun Y.

    2015-01-01

    Aim: Investigation has been carried out to validate folkloric claim of the potential of Ipomoea digitata (ID) based on reproductive health status in experimentally induced male albino rats. Materials and Methods: Emulsified neem oil fed albino rats were orally administered root powder of ID suspended in water for the doses of 250 and 500 mg/kg body weight for 40 days. Change in organ weight, sperm density and motility, serum hormonal levels and histomorphological changes were evaluated. Results: Significant increase in the sperm density and the sperm motility (P < 0.01) along with increase in the testis, and epididymes weight in neem-oil induced infertile rats treated with ID at both dose levels. This effect is vis-à-vis to serum hormonal levels. Presence of β-sitosterol in the root of ID likely to enhance the process of spermatogenesis as it is evident from histomorphological studies. Conclusion: Results of the present investigation reveal that ID is a good candidate for the management of male infertility. PMID:26401398

  17. Evaluation of antinociceptive and antidiarrhoeal properties of Manilkara zapota leaves in Swiss albino mice.

    PubMed

    Ganguly, Amlan; Al Mahmud, Zobaer; Kumar Saha, Sajal; Abdur Rahman, S M

    2016-08-01

    Context Manilkara zapota (L.). P. Royen. (Sapotaceae) has been used in folk medicine to treat pain, diarrhoea, inflammation, arthralgia, and other disorders. Objective Screening of Manilkara zapota leaves ethanol extract and its different solvent soluble fractions for possible antinociceptive and antidiarrhoeal activities in Swiss albino mice. Materials and methods The extract and various fractions (200 and 400 mg/kg body weight; p.o.) were tested for peripheral and central antinociceptive activity by acetic acid-induced writhing and radiant heat tail-flick method, respectively; castor oil-induced diarrhoeal model was used to evaluate antidiarrhoeal activity at both doses. All the samples were administered once in a day and the duration of study was approximately 5 h. Results Ethanol extract (400 mg/kg), petroleum ether fraction (400 mg/kg), and ethyl acetate fraction (400 mg/kg) showed significant peripheral antinociceptive activity having 59.89, 58.24, and 46.7% (p < 0.001) of writhing inhibition, respectively, which is comparable with that of standard diclofenac (59.34% inhibition). The ethanol extract (400 mg/kg) and petroleum ether fraction (400 mg/kg) also showed promising central analgesic activity having 74.15 and 82.15% (p < 0.001) elongation of reaction time, respectively, at 90 min after administration of sample which is also similar to that obtained by morphine (85.84% elongation). In antidiarrhoeal activity screening, ethanol extract (200 and 400 mg/kg) showed significant inhibition of defecation by 53.57 and 60.71%, respectively (p < 0.001) compared with that of loperamide (71.42%). Discussion and conclusion The findings of the studies demonstrated antinociceptive and antidiarrhoeal activities of M. zapota leaves which could be the therapeutic option against pain and diarrhoeal disease. PMID:26799747

  18. Hair growth promoting activity of Eclipta alba in male albino rats.

    PubMed

    Roy, R K; Thakur, Mayank; Dixit, V K

    2008-08-01

    Alopecia is a dermatological disorder with psychosocial implications on patients with hair loss. Eclipta alba Hassk. is a well-known Ayurvedic herb with purported claims of hair growth promotion. In the reported work attempts were undertaken to evaluate petroleum ether and ethanol extract of E. alba Hassk. for their effect on promoting hair growth in albino rats. The extracts were incorporated into oleaginous cream (water in oil cream base) and applied topically on shaved denuded skin of albino rats. The time (in days) required for hair growth initiation as well as completion of hair growth cycle was recorded. Minoxidil 2% solution was applied topically and served as positive control for comparison. Hair growth initiation time was significantly reduced to half on treatment with the extracts, as compared to control animals. The time required for complete hair growth was also significantly reduced. Quantitative analysis of hair growth after treatment with petroleum ether extract (5%) exhibited greater number of hair follicles in anagenic phase (69 +/- 4) which were higher as compared to control (47 +/- 13). The result of treatment with 2 and 5% petroleum ether extracts were better than the positive control minoxidil 2% treatment. PMID:18478241

  19. Antilithiatic effect of Asparagus racemosus Willd on ethylene glycol-induced lithiasis in male albino Wistar rats.

    PubMed

    Christina, A J M; Ashok, K; Packialakshmi, M; Tobin, G C; Preethi, J; Murugesh, N

    2005-11-01

    The ethanolic extract of Asparagus racemosus Willd. was evaluated for its inhibitory potential on lithiasis (stone formation), induced by oral administration of 0.75% ethylene glycolated water to adult male albino Wistar rats for 28 days. The ionic chemistry of urine was altered by ethylene glycol, which elevated the urinary concentration of crucial ions viz. calcium, oxalate, and phosphate, thereby contributing to renal stone formation. The ethanolic extract, however, significantly (p < 0.05) reduced the elevated level of these ions in urine. Also, it elevated the urinary concentration of magnesium, which is considered as one of the inhibitors of crystallization. The high serum creatinine level observed in ethylene glycol-treated rats was also reduced, following treatment with the extract. The histopathological findings also showed signs of improvement after treatment with the extract. All these observations provided the basis for the conclusion that this plant extract inhibits stone formation induced by ethylene glycol treatment. PMID:16357948

  20. Comparison of the acute ultraviolet photoresponse in congenic albino hairless C57BL/6J mice relative to outbred SKH1 hairless mice.

    PubMed

    Konger, Raymond L; Derr-Yellin, Ethel; Hojati, Delaram; Lutz, Cathleen; Sundberg, John P

    2016-09-01

    Hairless albino Crl:SKH1-Hr(hr) mice are commonly utilized for studies in which hair or pigmentation would introduce an impediment to observational studies. Being an outbred strain, the SKH1 model suffers from key limitations that are not seen with congenic mouse strains. Inbred and congenic C57BL/6J mice are commonly utilized for modified genetic mouse models. We compare the acute UV-induced photoresponse between outbred SKH1 mice and an immune competent, hairless, albino C57BL/6J congenic mouse line [B6.Cg-Tyr(c-2J) Hr(hr) /J]. Histologically, B6.Cg-Tyr(c-2J) Hr(hr) /J skin is indistinguishable from that of SKH1 mice. The skin of both SKH1 and B6.Cg-Tyr(c-2J) Hr(hr) /J mice exhibited a reduction in hypodermal adipose tissue, the presence of utricles and dermal cystic structures, the presence of dermal granulomas and epidermal thickening. In response to a single 1500 J/m(2) ultraviolet B dose, the oedema and apoptotic responses were equivalent in both mouse strains. However, B6.Cg-Tyr(c-2J) Hr(hr) /J mice exhibited a more robust delayed sunburn reaction, with an increase in epidermal erosion, scab formation and myeloperoxidase activity relative to SKH1 mice. Compared with SKH1 mice, B6.Cg-Tyr(c-2J) Hr(hr) /J also exhibited an aberrant proliferative response to this single UV exposure. Epidermal Ki67 immunopositivity was significantly suppressed in B6.Cg-Tyr(c-2J) Hr(hr) /J mice at 24 h post-UV. A smaller non-significant reduction in Ki67 labelling was observed in SKH1 mice. Finally, at 72 h post-UV, SKH1 mice, but not B6.Cg-Tyr(c-2J) Hr(hr) /J mice, exhibited a significant increase in Ki67 immunolabelling relative to non-irradiated controls. Thus, B6.Cg-Tyr(c-2J) Hr(hr) /J mice are suitable for photobiology experiments. PMID:27095432

  1. Amelioration of lead-induced hepatotoxicity by Allium sativum extracts in Swiss albino mice

    PubMed Central

    Sharma, Arti; Sharma, Veena; Kansal, Leena

    2010-01-01

    Lead is a blue–gray and highly toxic divalent metal that occurs naturally in the earth's crust and is spread throughout the environment by various human activities. The efficacy of garlic (Allium sativum) to reduce hepatotoxicity induced by lead nitrate was evaluated experimentally in male mice. Oral treatment with lead nitrate at a dose of 50 mg/kg body weight daily for 40 days (1/45 of LD50) induced a significant increase in the levels of hepatic aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, acid phosphatase, cholesterol, lipid peroxidation, and lead nitrate. In parallel, hepatic protein levels in lead-exposed mice were significantly depleted. Lead nitrate exposure also produced detrimental effects on the redox status of the liver indicated by a significant decline in the levels of liver antioxidants such as superoxide dismutase, catalase, and glutathione. After exposure to lead nitrate (50 mg/kg body weight for 10 days), the animals received aqueous garlic extract (250 mg/kg body weight and 500 mg/kg body weight) and ethanolic garlic extract (100 mg/kg body weight and 250 mg/kg body weight), and partially restored the deranged parameters significantly. Histological examination of the liver also revealed pathophysiological changes in lead nitrate-exposed group and treatment with garlic improved liver histology. Our data suggest that garlic is a phytoantioxidant that can counteract the deleterious effects of lead nitrate. PMID:21483544

  2. Methyl parathion inhibits the nuclear maturation, decreases the cytoplasmic quality in oocytes and alters the developmental potential of embryos of Swiss albino mice

    SciTech Connect

    Nair, Ramya; Singh, Vikram Jeet; Salian, Sujith Raj; Kalthur, Sneha Guruprasad; D'Souza, Antony Sylvan; Shetty, Pallavi K.; Mutalik, Srinivas; Kalthur, Guruprasad; Adiga, Satish Kumar

    2014-09-15

    Methyl parathion (MP) is one of the most commonly used and extremely toxic organophosphorous group of pesticide. A large number of studies in the literature suggest that it has adverse effects on the male reproductive system. However, there is limited information about its toxicity to the female reproductive system. In the present study we report the toxic effects of methyl parathion on the female reproductive system using Swiss albino mice as the experimental model. The female mice were administered orally with 5, 10 and 20 mg/kg of MP. One week later, the mice were superovulated with pregnant mare serum gonadotrophin (PMSG) and human chorionic gonadotrophin (hCG) to study the quality of the oocytes, spindle organization, developmental potential of early embryos and the DNA integrity in blastocysts. MP exposure resulted in a non-significant decrease in the number of primordial follicles and increased DNA damage in granulosa cells. Though MP did not have any effect on the ovulation it had a significant inhibitory effect on the nuclear maturity of oocytes which was associated with spindle deformity. In addition, the oocytes had higher cytoplasmic abnormalities with depleted glutathione level. Even though it did not have any effect on the fertilization and blastocyst rate at lower doses, at 20 mg/kg MP it resulted in a significant decrease in blastocyst hatching, decrease in cell number and high DNA damage. While low body weight gain was observed in F1 generation from 5 mg/kg group, at higher dose, the body weight in F1 generation was marginally higher than control. Post-natal death in F1 generation was observed only in mice treated with 20 mg/kg MP. In conclusion, we report that MP has adverse effects on the oocyte quality, developmental potential of the embryo and reproductive outcome. - Highlights: • Methyl parathion induces severe cytoplasmic abnormalities in oocytes. • Inhibits nuclear maturation and spindle damage • Poor blastocyst quality and high DNA

  3. Histopathology effects of nickel nanoparticles on lungs, liver, and spleen tissues in male mice

    NASA Astrophysics Data System (ADS)

    Ajdari, Marziyeh; Ziaee Ghahnavieh, Marziyeh

    2014-09-01

    Because of the classification of the nickel compounds as carcinogenic substances, there is a need for in vivo tests to nickel nanoparticles (NiNPs) for observing their effects on health experimentally. Spherical NiNPs with 10 nm in diameter and 75 ppm concentration were applied for investigating their toxicities within male albino mice as an in vivo model. We randomly made sham group, control group, and 75 ppm group (with five animals in each group). Then, the nanoparticles were injected into mice intraperitonealy for 7 days and after that their lungs, liver, and spleen were removed for histopathological observations. At the end of the test, section microscopic observations of liver, spleen, and lung in sham and control groups showed normal tissues but these tissues underwent significant abnormal effects in 75 ppm group. NiNPs can cause undesirable effects in lungs, liver, and spleen tissues with same condition of this study.

  4. [THERAPEUTIC ACTIVITY OF MICRONIZED MEBENDAZOLE IN THE MUSCULAR PHASE OF EXPERIMENTAL TRICHINELLA SPIRALIS INVASION IN ALBINO MICE].

    PubMed

    Kukhaleva, I V; Kovalenko, F P; Shkolyar, N A; Legonkov, Yu A; Musaev, A Kh; Bulanova, T E; Samochatova, E I

    2015-01-01

    The incidence of trichinosis in Russia was 0.07 per 100,000 population in 2014, which was 2.9-fold higher than that in 2013. Two WHO recommended medications mebendazole and albendazole are now used to treat humari trichinosis. The drugs are active against only mature helminths and non-encysted muscle larvae. The original oil suspension of micronized mebendazole was.found to have 100% efficacy against trichinosis in albino mice in the late muscular phase (encysted larvae) of hyperinvasion after intensive therapy under lifetime diagnostic guidance during and after a treatment cycle. The lifetime diagnostic method used to evaluate the larvicidal activity of anti-trichinosis agents in animals with experimental trichinosis revealed the signs of viaility, established a trend for deatih of Trichinella larvae, and determined their destructive changes. PMID:26827586

  5. Modulatory effect of whey proteins in some cytokines involved in wound healing in male diabetic albino rats.

    PubMed

    Abdel-Salam, Bahaa Kenawy Abuel-Hussien

    2014-10-01

    The anti-inflammatory cytokines (interleukin (IL)-4 and IL-10) and the pro-inflammatory cytokines (IL-1β, IL-6, and tumor necroses factor-alpha (TNF-α)) have important functions in wound healing. Thus, the aim of this study was to determine whether dietary supplementation with whey protein could enhance normal inflammatory responses during wound healing in diabetic rats. In this study, male albino rats were divided into a wounded control group, a wounded diabetic group, and a wounded diabetic group supplemented with whey protein orally at a dose of 100 mg/kg body weight. Tested rats showed increasing wound closure in rats treated with whey protein. In addition, after 4 days of wound, modulation in IL-4, IL-10, IL-1β, IL-6, and TNF-α levels were detected. Statistical analysis of data showed significant difference between the whey-protein-treated group and either control or diabetic groups (P < 0.05). Dietary supplementation with whey protein enhances the normal inflammatory responses during wound healing in diabetic rats by modulating the levels of some anti-inflammatory and inflammatory cytokines. PMID:24760706

  6. Cognitive effects of acute restraint stress in male albino rats and the impact of pretreatment with quetiapine versus ghrelin.

    PubMed

    Amin, Shaimaa Nasr; Gamal, Sarah Mahmoud; Esmail, Reham Shehab El Nemr; Aziz, Tarek Mohamed Abdel; Rashed, Laila Ahmed

    2014-12-01

    Stress is any condition that seriously affects the balance of the organism physiologically and psychologically. Stress activates the hypothalamic-pituitary-adrenal (HPA) releasing glucocorticoid hormones that produce generalized effects on different body systems including the nervous system. This study aimed to investigate the effect of acute restraint stress (ARS) on cognitive performance by measuring spatial working memory in Y-maze, behavior (anxiety and exploratory behavior) in open field test, expression of synaptophysin and glial fibrillary acidic protein (GFAP) in the hippocampus by immunohistochemistry, dopaminergic receptors (D2) in the basal ganglia by gene expression and comparing the effect of ghrelin and quetiapine on the previous parameters. 36 adult male albino rats constituted the animal model of this work and have been divided into six groups: control group, control group exposed to ARS, quetiapine group, quetiapine group exposed to ARS, ghrelin group and ghrelin group exposed to ARS. We demonstrated more neuroprotective effect for quetiapine compared to ghrelin on stress response, anxiety behavior and working spatial memory impairment due to ARS. PMID:25391717

  7. Effects of Ocimum sanctum and Camellia sinensis on stress-induced anxiety and depression in male albino Rattus norvegicus

    PubMed Central

    Tabassum, Imrana; Siddiqui, Zeba N.; Rizvi, Shamim J.

    2010-01-01

    Objective: The aim of this study was to study the ameliorative effects of Ocimum sanctum and Camellia sinensis on stress-induced anxiety and depression. Materials and Methods: The study was carried out using male albino rats (200 ± 50 g). The effect of O. sanctum and C. sinensis was evaluated for anxiety and depression using elevated plus maze (EPM) test, open field test (OFT), forced swim test (FST), and tail suspension test (TST). Result: Restraint stress (3 h/day for six consecutive days) induced a significant reduction in both the percentage number of entries and time spent in open arms in EPM, and these changes were reversed with post-treatment of aqueous extract of O. sanctum and C. sinensis (100 mg/kg for 6 days). Restraint stress-induced (a) increased latency and (b) decreased ambulation and rearing were also reversed by O. sanctum and C. sinensis in OFT. A significant increase in immobility period was observed in FST and TST after restraint stress. O. sanctum and C. sinensis significantly reduced the immobility times of rats in FST and TST. Conclusion: O. sanctum and C. sinensis possess anxiolytic and antidepressant activities. PMID:21206619

  8. Effect of different doses of monosodium glutamate on the thyroid follicular cells of adult male albino rats: a histological study

    PubMed Central

    Khalaf, Hanaa A; Arafat, Eetmad A

    2015-01-01

    Monosodium glutamate (MSG) is a major flavor enhancer used as a food additive. The present study investigates the effects of different doses of MSG on the morphometric and histological changes of the thyroid gland. 28 male albino rats were used. The rats were divided into four groups: group I control, group II, III and IV treated with MSG (0.25 g/kg, 3 g/kg, 6 g/kg daily for one month) respectively. The thyroid glands were dissected out and prepared for light and electron microscopic examination. Light microscopic examination of thyroid gland of group II revealed increase in follicular epithelial height. Groups III & IV showed decrease in the follicular diameter and irregularity in the shape of some follicles with discontinuity of basement membrane. Follicular hyperplasia was detected in some follicles with appearance of multiple pyknotic nuclei in follicular and interfollicular cells and multiple exfoliated cells in the colloid. In addition, areas of loss of follicular pattern were appeared in group IV. Immunohistochemical examination of BCL2 immunoexpression of the thyroid glands of groups III & IV reveals weak positive reaction in the follicular cells cytoplasm. Ultrathin sections examination of groups III & IV revealed follicular cells with irregular hyperchromatic nuclei, marked dilatation of rER and increased lysosomes with areas of short or lost apical microvilli. In addition, vacuolation of mitochondria was detected in group IV. The results displayed that MSG even at low doses is capable of producing alterations in the body weights and thyroid tissue function and histology. PMID:26884820

  9. Simple generation of albino C57BL/6J mice with G291T mutation in the tyrosinase gene by the CRISPR/Cas9 system.

    PubMed

    Mizuno, Seiya; Dinh, Tra Thi Huong; Kato, Kanako; Mizuno-Iijima, Saori; Tanimoto, Yoko; Daitoku, Yoko; Hoshino, Yoshikazu; Ikawa, Masahito; Takahashi, Satoru; Sugiyama, Fumihiro; Yagami, Ken-ichi

    2014-08-01

    Single nucleotide mutations (SNMs) are associated with a variety of human diseases. The CRISPR/Cas9 genome-editing system is expected to be useful as a genetic modification method for production of SNM-induced mice. To investigate whether SNM-induced mice can be generated by zygote microinjection of CRISPR/Cas9 vector and single-stranded DNA (ssDNA) donor, we attempted to produce albino C57BL/6J mice carrying the Tyr gene SNM (G291T) from pigmented C57BL/6J zygotes. We first designed and constructed a CRISPR/Cas9 expression vector for the Tyr gene (px330-Tyr-M). DNA cleavage activity of px330-Tyr-M at the target site of the Tyr gene was confirmed by the EGxxFP system. We also designed an ssDNA donor for homology-directed repair (HDR)-mediated gene modification. The px330-Tyr-M vector and ssDNA donor were co-microinjected into the pronuclei of 224 one-cell-stage embryos derived from C57BL/6J mice. We obtained 60 neonates, 28 of which showed the ocular albinism and absence of coat pigmentation. Genomic sequencing analysis of the albino mice revealed that the target of SNM, G291T in the Tyr gene, occurred in 11 mice and one founder was homozygously mutated. The remaining albino founders without Tyr G291T mutation also possessed biallelic deletion and insertion mutants adjacent to the target site in the Tyr locus. Simple production of albino C57BL/6J mice was provided by C57BL/6J zygote microinjection with px330-Tyr-M DNA vector and mutant ssDNA (G291T in Tyr) donor. A combination of CRISPR/Cas9 vector and optional mutant ssDNA could be expected to efficiently produce novel SNM-induced mouse models for investigating human diseases. PMID:24879364

  10. Effects of 10-GHz microwaves on hematological parameters in Swiss albino mice and their modulation by Prunus avium.

    PubMed

    Sisodia, Rashmi; Rifat, Faiza; Sharma, Archana; Srivastava, Preeti; Sharma, K

    2013-01-01

    The objective of this study was to investigate the modulatory role of Prunus avium fruit extract (PAE) on several blood parameters after exposure to 10-GHz microwaves. Swiss albino mice from an inbred colony were selected and divided into 3 groups. Mice in group I served as the control; they were placed in a Plexiglas cage (without energizing the system) for 2 hours/day for 30 consecutive days. Group II mice were exposed to 10-GHz microwaves for 2 hours/day for 30 consecutive days. Mice in group III received PAE (500 mg/kg/body weight) orally once daily 1 hour before exposure to 10-GHz microwaves (2 hours/day) for 30 consecutive days. After 30 days of treatment, blood samples were collected from mice in all groups and analyzed. Hemoglobin, monocytes, packed cell volume, red blood cells, mean corpuscular hemoglobin concentration declined significantly (P ≤ 0.01), whereas white blood cells, lymphocytes, erythrocyte sedimentation rate, and mean corpuscular volume increased significantly (P ≤ 0.01) compared to the control group (group I). Cholesterol, alkaline phosphatase, and lipid peroxidation also increased significantly (P ≤ 0.01). Depletion in blood sugar, total protein, acid phosphatase, and glutathione levels was noted after microwave exposure compared with levels in the sham-exposed (control) mice. Histopathological alterations in blood cells also were seen. Signs of improvements in the hematological, biochemical, and histopathological parameters were recorded in group III, where PAE was supplemented before exposure. Exposure to microwaves influences hematological parameters, which could be ameliorated by the supplementation of PAE. PMID:24266407

  11. Anticancer and antimutagenic properties of Acacia nilotica (Linn.) on 7,12-dimethylbenz(a)anthracene-induced skin papillomagenesis in Swiss albino mice.

    PubMed

    Meena, Punar Dutt; Kaushik, Pallavi; Shukla, Shalini; Soni, Anil Kumar; Kumar, Manish; Kumar, Ashok

    2006-01-01

    We report the chemopreventive activity of Acacia nilotica (Linn.) gum, flower and leaf aqueous extracts, on 7,12-dimethylbenz(a)anthracene (DMBA) induced skin papillomagenesis in male Swiss albino mice. Animals were divided into following groups: Group I (Controls) given DMBA and croton oil, with no extract ; Group II (treatment) animals treated with Acacia nilotica gum (Group II-a) (800 mg/kg body weight), flowers (Group II-b) (800 mg/kg body weight), or leaves (Group II-c) (800 mg/kg body weight) during the peri- and post initiation periods of DMBA and croton oil application. A significant reduction in the values of tumor burden, tumor incidence and cumulative number of papillomas was observed in mice treated by oral gavage with the Acacia nilotica gum, flower and leaf extracts as compared with the control group. The latency period in treatment Group-II (b) and Group-II (c) was significantly increased as compared with the control group. A significant reduction in the frequency of micronuclei was also observed in mice treated by oral gavage with the aqueous extracts, along with significant decrease in total chromosomal aberrations in the form of chromatid breaks, chromosome breaks, centric rings, dicentrics, acentric fragments and exchange. Treatment with Acacia nilotica flower (Group II-B) and leaf (Group II-C) aqueous extracts by oral gavage for 15 days resulted in a highly significant decrease in the lipid peroxidation (LPO) level in the liver, but this was less evident with the gum (Group II-A) . Conversely, reduced glutathione (GSH) content was observed to be significantly elevated as compared with the control group with leaves (Group II-C) and flowers (Group II-B). The chemopreventive and antimutagenic activity of the leaf extract of Acacia nilotica was most significant followed by the flower extract and then by gum. PMID:17250441

  12. Effects of lithium chloride on testicular steroidogenic and gametogenic functions in mature male albino rats

    SciTech Connect

    Ghosh, D.; Chaudhuri, A.; Biswas, N.M.; Ghosh, P.K. )

    1990-01-01

    The present study was undertaken to evaluate the effects of lithium, on steroidogenic and gametogenic functions of testis in the rat. Adult male rats of Wistar strain were injected with lithium chloride at the dose of 0.1 mg, 0.2 mg, and 0.4 mg/100 g body weight/day for 21 days. All the treated animals along with the vehicle treated controls were sacrificed 24 hours after the last injections. Testicular steroidogenic activity was evaluated by measuring the activities of two steroidogenic key enzymes, {Delta}{sup 5}-3{beta} hydroxysteriod dehydrogenase ({Delta}{sup 5} -3{beta}-HSD) and 17{beta} hydroxysteroid dehydrogenase (17{beta} -HSD). Gametogenic capacity was determined by counting the number of germ cells at stage VII of seminiferous cycle. Plasma levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL) and testosterone (T) were measured by radioimmunoassay (RIA). Administration of lithium chloride at a dose of 0.1 mg/100g body wt. for 21 days led to insignificant changes of plasma FSH, LH, PRL and T along with unaltered activities of testicular {Delta}5 -3{beta}-HSD, 17 {beta}-HSD activities and gametogenesis.

  13. Histopathological evaluation of gastro protective effect of Berberis vulgaris (Zereshk) seeds against aspirin induced ulcer in albino mice.

    PubMed

    Majeed, Wafa; Aslam, Bilal; Javed, Ijaz; Khaliq, Tanweer; Muhammad, Faqir; Ali, Asghar; Raza, Ahmed

    2015-11-01

    The present study was carried out to investigate the antiulcer activity of Berberis vulgaris (Zereshk) seeds in albino mice. After acclimatization, animals were divided into six equal groups. Aspirin 150 mg/kg was used to induce gastric ulcer in all groups except normal control. Omeprazole 20mg/kg was used as synthetic anti ulcer drug in study. Three dose levels of B. vulgaris seed powder 300 mg/kg, 600 mg/kg and 900 mg/kg were used respectively orally. Histopathological analysis was carried out to evaluate the gastroprotective activity of B. vulgaris seed powder. Results of the study showed that in case of aspirin treated mice gastric luminal mucosa villi were decreased in height or were absent. In the glandular region there was connective tissue proliferation and also infiltration of cells. Similar infiltration of cells was present on muscularis mucosa. In esophageal region tumor cells were present. However three dose levels of B. vulgaris significantly reduced the tissue proliferation, infiltration of cells and sloughing induced by aspirin. Highest dose of B. vulgaris (900 mg/kg) showed similar results as synthetic antiulcer drug omeprazole. PMID:26639472

  14. Biosynthesis of silver nanoparticles from Premna serratifolia L. leaf and its anticancer activity in CCl4-induced hepato-cancerous Swiss albino mice

    NASA Astrophysics Data System (ADS)

    Arockia John Paul, J.; Karunai Selvi, B.; Karmegam, N.

    2015-11-01

    In this study, we report the biosynthesis of silver nanoparticles using the ethanolic leaf powder extract of Premna serratifolia L. and its anticancer activity in carbon tetra chloride (CCl4)-induced liver cancer in Swiss albino mice (Balb/c). The synthesized silver nanoparticles were characterized by SEM, FTIR and XRD analyses. The Debye-Scherrer equation was used to calculate particle size and the average size of silver nanoparticles synthesized from P. serratifolia leaf extract was 22.97 nm. The typical pattern revealed that the sample contained cubic structure of silver nanoparticles. FTIR analysis confirmed that the bioreduction of silver ions to silver nanoparticles is due to reduction by capping material of the plant extract. The silver nanoparticles of P. serratifolia leaf extract were effective in treating liver cancer in Swiss albino mice when compared with P. serratifolia leaf extract with isoleucine.

  15. A comparison of the phototumorigenic potential of 8-MOP and 5-MOP in hairless albino mice exposed to solar simulated radiation.

    PubMed

    Young, A R; Magnus, I A; Davies, A C; Smith, N P

    1983-05-01

    Hairless albino mice have been treated with topically applied 8-methoxypsoralen and 5-methoxypsoralen at two concentrations and exposed to solar simulated radiation. Both these compounds significantly increased the incidence of cutaneous tumours when compared with controls irradiated after treatment with vehicle. This effect was related to psoralen concentration and at the two concentrations investigated there was no significant difference between the compounds. PMID:6849820

  16. Antiproliferative and antioxidant potential of hesperetin against benzo(a)pyrene-induced lung carcinogenesis in Swiss albino mice.

    PubMed

    Bodduluru, Lakshmi Narendra; Kasala, Eshvendar Reddy; Barua, Chandana C; Karnam, Kalyani Chowdary; Dahiya, Vicky; Ellutla, Maheswara

    2015-12-01

    Lung cancer is the foremost cause of cancer mortality and is a growing economic burden worldwide. Chemoprevention, employing the use of natural, dietary or synthetic agents has become an appealing strategy to combat the increasing cases of cancers worldwide. The present study was designed to investigate the mechanism-based chemopreventive nature of hesperetin (HSP) against B[a]P induced lung carcinogenesis in Swiss albino mice. We analyzed the chemopreventive potential of HSP by estimating the status of lipid peroxidation (LPO), enzymic (SOD, CAT, GPx, GR, and GST), nonenzymic antioxidants (GSH, Vit C and Vit E), proinflammatory cytokine (TNF-α), western blotting (CYP1A1, PCNA, Nrf2 and NF-κB expression) and histopathology of lung tissues of control and experimental mice. Administration of B[a]P (50 mg/kg, p.o.) resulted in an increase in lung weight, LPO with concomitant decrease in body weight, enzymic (SOD, CAT, GPx, GR, and GST) and non-enzymic (GSH, Vit C and Vit E) antioxidants. Histological examination of lungs revealed severe alveolar and bronchiolar damages in B[a]P-induced mice. Further, elevated levels of TNF-α along with activated expression of NF-κB, PCNA and CYP1A1, and downregulation of Nrf2 was observed in B[a]P intoxicated animals. Pre- and post-treatment with HSP effectively suppressed B[a]P induced lung carcinoma and the associated preneoplastic lesions by alleviating LPO, modulating antioxidants and decreasing the expression of NF-κB, PCNA and CYP1A1. These findings demonstrate that HSP possesses a potential chemopreventive activity against B[a]P induced lung cancer and this is attributed to its free radical scavenging, antioxidant, anti-inflammatory and antiproliferative properties. PMID:26546711

  17. Effects of glycowithanolides on lipid peroxidation and lipofuscinogenesis in male reproductive organs of mice

    PubMed Central

    Walvekar, Madhuri; Shaikh, Nilofar; Sarvalkar, Priti

    2013-01-01

    Background: Glycowithanolides (Withaferin A), is one of the main withanolides active principle isolated from plant Withania somnifera and is claimed that it possess the aphrodisiac, sedative, rejuvenate and life prolonging properties. Objective: In the present investigation, antioxidant activity of active principles of Withania somnifera was tested against D-galactose induced oxidative stress in mouse testes, epididymis and seminal vesicle. Materials and Methods: For the present investigation Swiss male albino mice Mus musculus (Linn) were used. They were grouped in to control (I), D-galactose treated (II), protective (III) and curative groups (IV). Oxidative stress was induced in six month old mice by injecting a low dose of D-galactose. Antioxidant effect of plant extract was studied in testes, epididymis, and seminal vesicle of oxidative stressed mice on Lipid peroxidation (LPO) and fluorescence product. Results: In the present study, both total as well as mitochondrial lipid peroxidation and fluorescence product in testes, epididymis and seminal vesicle were increased in D-galactose induced mice. After the treatment of glycowithanolides there was significantly decrease in total as well as mitochondrial lipid peroxidation and fluorescence product in protective and curative groups. Conclusion: Our results indicate that Withania somnifera has a capability of preventing oxidative stress and also combating stress induced infertility. PMID:24639810

  18. The antioxidant effects of silver, gold, and zinc oxide nanoparticles on male mice in in vivo condition

    PubMed Central

    Negahdary, Masoud; Chelongar, Reyhaneh; Zadeh, Shahrzad Kabiri; Ajdary, Marziyeh

    2015-01-01

    Background: We studied the effects of different doses of gold nanoparticles (AuNPs), silver nanoparticles (AgNPs), and zinc oxide nanoparticles (ZnONPs) on oxidative stress markers including glutathione peroxidase (GPX) and catalase (CAT) on male mice. Materials and Methods: Male albino mice of Wistar strain (N = 60), weighing 17-32 g, were used for this study. The mice were randomly assigned to three classes such that in each class, there were four groups of which one was control and the other three groups were fed with ZnONPs and AgNPs at 500, 250, and 125 ppm concentration and AuNPs at 100, 50, and 25 ppm concentration for 15 days. The heart blood was taken to measure GPX and CAT enzyme activities at the end of the treatment. Results: In male mice treated with AgNPs, the GPX and CAT activities were significantly increased, while significant decreases were seen in the GPX and CAT activities in mice treated with ZnONPs (P < 0.05) and in mice treated with AuNPs (P < 0.05). Conclusion: The results of this study showed that AuNPs and ZnONPs caused decreased antioxidant enzyme activities, while nanosilver had the reverse effect and increased the antioxidant enzyme activities and caused decreased stress oxidative. PMID:25878994

  19. Studies on fate and toxicity of nanoalumina in male albino rats: Oxidative stress in the brain, liver and kidney.

    PubMed

    Morsy, Gamal M; Abou El-Ala, Kawther S; Ali, Atef A

    2016-02-01

    The present work aimed to evaluate the oxidative stress of nanoalumina (aluminium oxide nanoparticles, Al2O3-NPs) with a diameter <13 nm (9.83 ± 1.61 nm) as assessed by the perturbations in the enzymatic and non-enzymatic antioxidants as well as lipid peroxidation (LPO) in the brain, liver and kidney of male albino rats, after 2 days of single acute dose (3.9 or 6.4 or 8.5 g/kg) injection and a sublethal dose of 1.3 g/kg once in 2 days for a period of 28 days. According to two-way analysis of variance, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities as well as the levels of glutathione (GSH) and LPO were significantly affected by the injected doses, organs and their interactions. On the other hand, in sublethal experiments, these parameters were affected by the experimental periods, organs and their interactions. Regression analysis confirmed that the activities of SOD, CAT, GPx and GSH levels in the brain, liver and kidney were inversely proportional with the acute doses, the experimental periods, and aluminium accumulated in these tissues, whereas the levels of LPO exhibited a positive relationship. Correlation coefficient indicated that oxidative stress mainly depends on aluminium accumulated in the studied organs, followed by injected doses and the experimental periods. In comparison with the corresponding controls, the acute and sublethal doses of Al2O3-NPs caused significant inhibition of the brain, hepatic and renal SOD, CAT, GPx activities and a severe marked reduction in the concentrations of GSH that were associated with a significant elevation in the levels of malondialdehyde (an indicator of LPO). In conclusion, our data indicated that rats injected with nanoalumina suffered from the oxidative stresses that were dose and time dependent. In addition, Al2O3-NPs released into the biospheres could be potentiating a risk to the environment and causing hazard effects on living organisms, including mammals. PMID:24081632

  20. Studies on fate and toxicity of nanoalumina in male albino rats: Some haematological, biochemical and histological aspects.

    PubMed

    Morsy, Gamal M; El-Ala, Kawther S Abou; Ali, Atef A

    2016-04-01

    The work aimed to evaluate the nanoalumina toxicity on the histological architecture, some haematological and biochemical aspects in male albino rats, during acute and sublethal experiments. Rats, in acute experiments, were injected with a single-acute dose of 3.9 g or 6.4 g or 8.5 g of aluminium oxide (Al2O3) kg(-) (1), whereas those of sublethal were injected with 1.3 g of Al2O3 kg(-) (1)2 days(-) (1) One-way analysis of variance indicated that injected doses and the experimental periods were significantly affected by haemoglobin (Hb) content; haematocrit value (Hct); white blood cell (WBC) count; blood platelet (Plt) count; mean corpuscular volume (MCV); mean corpuscular Hb (MCH) and MCH concentration (MCHC). In acute experiments, Hct, WBC count, MCV and Plt were significantly higher than the corresponding controls, whereas Hb, MCH and MCHC markedly decreased. In comparison with the related controls after 1, 3 and 7 days post-injection, red blood cell count, Hb, Hct, WBC count, Plt and MCV were significantly increased, but begun to decrease after 14 or/and 28 days and were associated with a marked decrease in MCH and MCHC. In serum of rats injected with acute or sublethal dose, the concentrations of total protein (TP) and total lipid (TL) were significantly lesser than the corresponding controls, whereas the levels of urea, uric acid, creatinine and the activities of aspartate aminotransferase and alanine aminotransferase were markedly increased. The injected doses were directly proportional with all the studied biochemical parameter, except the TL and TP that exhibited a negative correlation. Histologically, the highest acute and sublethal doses of nanoalumina caused hepatic irregular disarray, necrosis to the hepatic and Kupffer cells that are associated with congested blood sinusoids. The renal tissues characterized by the appearance of inter-tubular congestion that is accompanied by the dilation of the vascular glomeruli that completely occupied Bowman

  1. Ganoderma lucidum total triterpenes attenuate DLA induced ascites and EAC induced solid tumours in Swiss albino mice.

    PubMed

    Smina, T P; Mathew, J; Janardhanan, K K

    2016-01-01

    G. lucidum total triterpenes were assessed for its apoptosis-inducing and anti-tumour activities. The ability of the total triterpenes to induce apoptosis was evaluated in Dalton's lymphoma ascites (DLA) and Ehrlich's ascites carcinoma (EAC) cell lines. Total triterpenes were found to be highly cytotoxic to DLA and EAC cell lines with IC50 values 5 ± 0.32 and 7.9 ± 0.2 µg/ml respectively. Total triterpenes induced apoptosis in both cell lines which is evident from the DNA fragmentation assay. Anti-tumour activity was accessed using DLA induced solid and EAC induced ascites tumour models in Swiss albino mice. Administration of 10, 50 and 100 mg/kg b. wt. total triterpenes showed 11.86, 27.27 and 40.57% increase in life span of animals in ascites tumour model. Treatment with 10, 50 and 100 mg/kg b. wt. total triterpenes exhibited 76.86, 85.01 and 91.03% inhibition in tumour volume and 67.96, 72.38 and 77.90% inhibition in tumour weight respectively in the solid tumour model. The study reveals the significant dose-dependent anti-tumour activity of total triterpenes in both models. Total triterpenes were more active against the solid tumour than the ascites tumour. The anti-oxidant potential and ability to induce cell-specific apoptosis could be contributing to its anti-tumour activities. PMID:27188870

  2. Antioxidative effect of Rajgira leaf extract in liver of Swiss albino mice after exposure to different doses of gamma radiation.

    PubMed

    Maharwal, J; Samarth, R M; Saini, M R

    2005-08-01

    The radioprotective effect of Rajgira leaf extract (800 mg/kg b.wt.) was studied in the liver of Swiss albino mice at various post-irradiation intervals between day 1 and 30 after its oral administration for 15 consecutive days prior to whole body gamma irradiation with 6, 8 and 10 Gy of gamma rays. In this study, abnormal and binucleated hepatocytes were counted in both the control and experimental sets because these hepatocytes are good indicators of radiation-induced damage. In the experimental (RLE + irradiation) sets, the percentage of abnormal and binucleated hepatocytes was lower compared with their respective control (irradiation alone) sets at each autopsy interval with all three radiation doses studied. The increase in the percentage of these hepatocytes was also found to be dose-dependent in the control as well as in the RLE treated (experimental) sets. Thus, Rajgira leaf extract (RLE) treatment given before irradiation protects mouse liver against radiation-induced lesions by increasing the GSH content and decreasing the LPO level. PMID:16177977

  3. Assessment of chromosomal aberration in the bone marrow cells of Swiss Albino mice treated by 4-methylimidazole.

    PubMed

    Norizadeh Tazehkand, Mostafa; Topaktas, Mehmet; Yilmaz, Mehmet Bertan

    2016-07-01

    4-Methylimidazole (4-MEI) is formed during the production of certain caramel coloring agents used in many food and drink products. It may also be formed during the cooking, roasting, or other processing of some foods and beverages. So it was unintentionally consumed in worldwide. This study was aimed to investigate the genotoxic and cytotoxic effects of 4-MEI using chromosome aberration (CA) and mitotic index (MI) in Swiss Albino mice. In this research, CA and MI of the mouse bone marrow cells were analyzed after treating the animals with 4-MEI (100, 130 and 160 mg/kg) for 12 h and 24 h treatment times. All data were analyzed using statistical methods. 4-MEI significantly increased the percentage of CAs at all concentrations for 12 h and at highest concentration for 24 h treatment periods. 4-MEI at highest concentration for 12 h and at all concentrations for 24 h decreased the MI in comparison with control. Genotoxic and cytotoxic effects of 4-MEI at 24 h treatment periods were concentration dependent. Consequently, it can be said that 4-MEI have genotoxic and cytotoxic effect in mouse. PMID:26634952

  4. The effect of mycotoxins found in some herbal plants on biochemical parameters in blood of female albino mice.

    PubMed

    Alwakeel, Suaad S

    2009-04-15

    In this study, twenty five samples ofwell-known herbs in Riyadh, Saudi Arabia were collected and analyzed for Total Fungi Count (TFC). Mycotoxins were extracted and screened using SMKY liquid medium. One hundred and thirty adult female albino mice were grouped into three wherein one group (n = 110) was fed with an aqueous extract from herbal plants. The second group (n = 15) was fed with an aqueous extract of the isolated fungal species. The third group comprised the control group which was given water only (n = 5). All mice were fed with mice breeding diet by Pillsbury, UK. After 5 weeks, mice were fasted and blood was withdrawn for biochemical analysis including alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyltransferase (GGT), serum creatinine and urea. Calligonum comosum with 2 x 10(5) cfu g(-1) fungus spore, grained mixed herbs (24 x 10(3) cfu g(-1)) and Salvia officinalis (23 x 10(3) cfu g(-1)) were the most contaminated samples. The genus Aspergillus was the most dominant genus recovered (142 isolates) followed by Penicillium (14 isolates) and these two genera were found in 85.0 and 11.0% of the samples analyzed. Aspergillus fumigatus, Aspergillus flavus and Aspergillus ochraceus were the most dominant and frequently isolated (47.3, 46.5 and 18.1%, respectively), followed by Aspergillus citrinum (11.0%). Aspergillus ochraceus had 21.7 microg kg(-1) of Aflatoxin B2 and 7.25 microg kg(-1) of ochratoxin A, whereas Aspergillus flavus had 7.45 microg kg(-1) of Aflatoxin B2 and Aspergillus fumigatus had 3.5 microg kg(-1) of Aflatoxin B2 and 3.8 microg kg(-1) of ochratoxin A. Mean creatinine, urea, ALT, AST and GGT were higher in mice fed or treated with herbal and fungal extracts group than the control group. This study confirms previous studies demonstrating the predominance of Aspergillus species in herbal and medicinal plants and its capability in the production of aflatoxin with induction of nephrotoxicity and hepatoxicity in

  5. Hypoglycemic Effect of Aqueous and Methanolic Extract of Artemisia afra on Alloxan Induced Diabetic Swiss Albino Mice.

    PubMed

    Issa, Idris Ahmed; Hussen Bule, Mohammed

    2015-01-01

    Diabetes mellitus is metabolic syndrome that causes disability, early death, and many other complications. Currently insulin and many synthetic drugs are used in diabetes treatment. However, these pharmaceutical drugs are too expensive particularly for sub-Saharan population in addition to their undesirable side effects. The present study was aimed to evaluate antidiabetic effect and toxicity level of Artemisia afra which was collected from its natural habitat in Bale Zone, around Goba town, 455 km southeast of Addis Ababa. Air dried aerial parts of Artemisia afra were separately extracted with both distilled water and 95% methanol. Oral acute toxicity test was conducted on healthy Swiss albino mice. Antidiabetic effect of the aqueous and methanolic extracts of Artemisia afra was separately evaluated on alloxan induced diabetic mice at doses of 500, 750, and 1000 mg/Kg body weight orally. The results indicate that mean lethal dose (LD50) for aqueous extract of Artemisia afra was 9833.4 mg/Kg. Blood glucose level was significantly decreased by 24% (p < 0.005) and 56.9% (p < 0.0004) in groups that received aqueous extract of Artemisia afra at dose of 500 mg/Kg and 750 mg/Kg, respectively. The methanolic extract of Artemisia afra also significantly lowered blood glucose by 49.8% (p < 0.0001) at doses of 1000 mg/kg on the 5th hr. Aqueous extract of Artemisia afra was regarded as nontoxic and safe since its LD50 was found above 5000 mg/Kg. Aqueous extract showed higher effect at relatively lower dose as compared to methanolic extract. The aqueous extract was screened positive for phytochemicals like flavonoids, polyphenols, and tannins that were reported to have antioxidant activity. PMID:26345313

  6. Hypoglycemic Effect of Aqueous and Methanolic Extract of Artemisia afra on Alloxan Induced Diabetic Swiss Albino Mice

    PubMed Central

    Issa, Idris Ahmed; Hussen Bule, Mohammed

    2015-01-01

    Diabetes mellitus is metabolic syndrome that causes disability, early death, and many other complications. Currently insulin and many synthetic drugs are used in diabetes treatment. However, these pharmaceutical drugs are too expensive particularly for sub-Saharan population in addition to their undesirable side effects. The present study was aimed to evaluate antidiabetic effect and toxicity level of Artemisia afra which was collected from its natural habitat in Bale Zone, around Goba town, 455 km southeast of Addis Ababa. Air dried aerial parts of Artemisia afra were separately extracted with both distilled water and 95% methanol. Oral acute toxicity test was conducted on healthy Swiss albino mice. Antidiabetic effect of the aqueous and methanolic extracts of Artemisia afra was separately evaluated on alloxan induced diabetic mice at doses of 500, 750, and 1000 mg/Kg body weight orally. The results indicate that mean lethal dose (LD50) for aqueous extract of Artemisia afra was 9833.4 mg/Kg. Blood glucose level was significantly decreased by 24% (p < 0.005) and 56.9% (p < 0.0004) in groups that received aqueous extract of Artemisia afra at dose of 500 mg/Kg and 750 mg/Kg, respectively. The methanolic extract of Artemisia afra also significantly lowered blood glucose by 49.8% (p < 0.0001) at doses of 1000 mg/kg on the 5th hr. Aqueous extract of Artemisia afra was regarded as nontoxic and safe since its LD50 was found above 5000 mg/Kg. Aqueous extract showed higher effect at relatively lower dose as compared to methanolic extract. The aqueous extract was screened positive for phytochemicals like flavonoids, polyphenols, and tannins that were reported to have antioxidant activity. PMID:26345313

  7. Attenuation of hepatotoxicity and oxidative stress in diabetes STZ-induced type 1 by biotin in Swiss albino mice

    PubMed Central

    Aldahmash, Badr Abdullah; El-Nagar, Doaa Mohamed; Ibrahim, Khalid Elfakki

    2015-01-01

    Diabetes mellitus is one of the major health problems. This study was designed to investigate the effect of biotin to regulate blood glucose level, reduced toxicity and oxidative stress in liver of diabetic mice STZ-induced type 1. Male mice were divided into three groups, the first one served as the control group, the second and the third groups received single ip dose of 150 mg/kg of STZ, the second group served as the untreated diabetic group, the third group received daily oral dose of 15 mg/kg of biotin, livers and liver index showed insignificant difference among groups. Blood glucose level showed a significant decrease in treated diabetic mice compared to untreated diabetic mice. Biochemical analysis showed a significant decrease in liver enzymes AST and ALT compared to the control group. Histopathological examination showed severe changes in untreated diabetic liver tissue manifested by dilated portal vein, leukocytic infiltration, fatty degeneration and moderate to severe histopathological score, whereas, treated diabetic mice with biotin showed reduction in hepatotoxicity represented by appearance of relative healthy hepatocytes and normal histopathological score. Immunohistochemistry of acrolein showed intense immunoreactions in liver section of untreated diabetic mice and faint immunoreactions in treated diabetic mice with biotin as evidence to oxidative stress reduction. PMID:26981014

  8. Squaraine PDT induces oxidative stress in skin tumor of swiss albino mice

    NASA Astrophysics Data System (ADS)

    Cibin, T. R.; Gayathri, Devi D.; Ramaiah, D.; Abraham, Annie

    2010-02-01

    Photodynamic Therapy (PDT) using a sensitizing drug is recognized as a promising medical technique for cancer treatment. It is a two step process that requires the administration of a photosensitizer followed by light exposure to treat a disease. Following light exposure the photosensitizer is excited to a higher energy state which generates free radicals and singlet oxygen. The present study was carried out to assess the oxidative damage induced by bis (3, 5-diiodo-2, 4, 6- trihydroxyphenyl) squaraine in skin tumor tissues of mice with/ without light treatment. Skin tumor was induced using 7, 12-Dimethyl Benz(a)anthracene and croton oil. The tumor bearing mice were given an intraperitoneal injection with the squaraine dye. After 24h, the tumor area of a few animals injected with the dye, were exposed to visible light from a 1000 W halogen lamp and others kept away from light. All the mice were sacrificed one week after the PDT treatment and the oxidative profile was analyzed (TBARS, SOD, catalase, GSH, GPx and GR) in tumor/ skin tissues. The dye induces oxidative stress in the tumor site only on illumination and the oxidative status of the tumor tissue was found to be unaltered in the absence of light. The results of the study clearly shows that the tumor destruction mediated by PDT using bis (3, 5-diiodo-2, 4, 6-trihydroxyphenyl) squaraine as a photosensitizer is due to the generation of reactive oxygen species, produced by the light induced changes in the dye.

  9. Baclofen prevents the elevated plus maze behavior and BDNF expression during naloxone precipitated morphine withdrawal in male and female mice.

    PubMed

    Pedrón, Valeria T; Varani, André P; Balerio, Graciela N

    2016-05-01

    In previous studies we have shown that baclofen, a selective GABAB receptor agonist, prevents the somatic expression and reestablishes the dopamine and μ-opioid receptors levels, modified during naloxone-precipitated morphine withdrawal syndrome in male and female mice. There are no previous reports regarding sex differences in the elevated plus maze (EPM) and the expression of BDNF in morphine-withdrawn mice. The present study analyses the behavioral and biochemical variations during morphine withdrawal in mice of both sexes, and whether these variations are prevented with baclofen. Swiss-Webster albino prepubertal mice received morphine (2 mg/kg, i.p.) twice daily, for 9 consecutive days. On the 10th day, one group of morphine-treated mice received naloxone (opioid receptor antagonist; 6 mg/kg, i.p.) 1 h after the last dose of morphine to precipitate withdrawal. A second group received baclofen (2 mg/kg, i.p.) before naloxone administration. The EPM behavior was measured during 15 min after naloxone injection. The expression of BDNF-positive cells was determined by immunohistochemistry. Withdrawn male mice showed a higher percentage of time spent and number of entries to the open arms compared to withdrawn female mice. Baclofen prevented this behavior in both sexes. BDNF expression decreased in the AcbC, BNST, CeC, and CA3 of the hippocampus while increased in the BLA of morphine withdrawn male. Baclofen pretreatment prevented the BDNF expression observed in morphine withdrawn male mice in all the brain areas studied except in the CeC. Baclofen prevention of the EPM behavior associated to morphine withdrawal could be partially related to changes in BDNF expression. PMID:26789010

  10. Adaptogenic Activity of Lyophilized Hydroethanol Extract of Pandanus odoratissimus in Swiss Albino Mice.

    PubMed

    Adkar, Prafulla P; Jadhav, Pranita P; Ambavade, Shirishkumar D; Bhaskar, V H; Shelke, Tushar

    2014-01-01

    Background. The leaves of Pandanus odoratissimus Linn have been widely used in Ayurveda to treat a variety of common and stress related disorders. In the present investigation, hydroethanol extract of leaves of Pandanus odoratissimus Linn (LEPO) were evaluated for antistress activity in normal and stress induced mice. Furthermore, the extract was studied for nootropic (adaptogenic) activity in mice and in vitro antioxidant potential to correlate with its adaptogenic and antistress activity. LEPO (100 and 200 mg/kg p.o) was evaluated against forced swimming endurance stress test, anoxia stress tolerance and immobilization stress and chronic cold resistant stress tests, and biomarkers (serum glucose, Corticosterone, WBC, RBC, and DLC count) to assess the antistress activity in mice. Withania somnifera (WS) (100 mg/kg p.o) was selected as reference standard. The parameters like anoxia stress tolerance time were recorded in anoxia stress and estimation of biochemical marker levels and determination of organs weight were carried out in immobilization stress models. Results. Concomitant treatment with LEPO 200 mg/kg significantly increased in anoxia stress tolerance time. Dose dependent significant reduction in serum glucose, corticosterone, and WBC, RBC, and DLC was observed in immobilisation stress model as compared to stressed group. LEOP 200 mg/kg and WS 100 mg/kg significantly reversed/inhibited the stress induced changes in these parameters. The results from the present study indicate that these values also express that dose dependent significant adaptogenic activity in stressed animals. Conclusion. The present study provides scientific support for the antistress (adaptogenic) and nootropic activities of lyophilized hydroethanol extract of Pandanus odoratissimus Linn and substantiate the traditional claims for the usage of Pandanus in stress induced disorders. PMID:27379263

  11. Evaluation of antitussive potential of Jussiaea suffruticosa linn. extract in albino mice.

    PubMed

    Murugesan, T; Ghosh, L; Mukherjee, P K; Pal, M; Saha, B P

    2000-11-01

    The antitussive activity of a methanol extract of Jussiaea suffruticosa Linn. (MEJS) (family Onagraceae) leaves has been evaluated for its potential on a cough induced by sulphur dioxide (SO(2)) gas model in mice. The extract (MEJS) showed significant antitussive activity in a dose dependent manner. The antitussive potential of MEJS was comparable to that of codeine phosphate (10 mg/kg), a standard drug. The extract (MEJS) at a dose level of 200 and 400 mg/kg, p.o. showed appreciable inhibition on the cough reflex by 48.52% and 59.8% respectively during 120 min of the experiment. PMID:11054846

  12. Anti-neoplastic activities of sepia officinalis ink and coelatura aegyptiaca extracts against Ehrlich ascites carcinoma in Swiss albino mice

    PubMed Central

    Soliman, Amel M; Fahmy, Sohair R; El-Abied, Salma A

    2015-01-01

    Objectives: With the development of sophisticated instruments for the isolation and elucidation of natural products structures from marine and freshwater organisms, major advances have been made in the discovery of aquatic derived therapeutics. Present investigations were carried out to evaluate cuttlefish (Sepia officinalis) ink extract (IE) and freshwater clam (Coelatura aegyptiaca) extract (CE) for their anticancer and antioxidant activities as compared to 5-flurouracil (5-Fu), in Ehrlich ascites carcinoma (EAC). Methods: Sixty female Swiss albino mice were divided into five groups (n = 12). All groups except group I received EAC cells (5 × 106 cells/mouse i.p.) and this was taken as the 0th day. Group I served as saline control (5 ml/kg 0.9% NaCl w/v p.o). Group II served as EAC control. Rats of groups III, IV and V received IE, CE (200 mg/kg body weight i.p.), and reference drug (5-Fu, 20 mg/kg body weight i.p.), respectively. Results: The reduction in tumor volume, packed cell volume, tumor cell counts and increase in median survival time and percentage increase in life span in treated animals were observed. There was a significant increase in RBC count; Hb content in treated animals and reduction in total WBC count. There was a significant decrease in AST, ALT, ALP and liver MDA levels and increase in GSH, SOD and NO levels were observed in all treated animals. Conclusion: Both IE and CE were effective in inhibiting the tumor growth in ascitic tumor models. The biochemical, antioxidants and histopathological studies were also supported their antitumor properties. PMID:26097537

  13. Toxicity and inflammatory response in Swiss albino mice after intraperitoneal and oral administration of polyurethane nanoparticles.

    PubMed

    Silva, Adny H; Locatelli, Claudriana; Filippin-Monteiro, Fabíola B; Martin, Philip; Liptrott, Neill J; Zanetti-Ramos, Betina G; Benetti, Luana C; Nazari, Evelize M; Albuquerque, Cláudia A C; Pasa, André A; Owen, Andrew; Creczynski-Pasa, Tânia B

    2016-03-30

    In this work in vivo experiments were conducted in order to characterize the biocompatibility of polyurethane nanoparticles (PU-NPs) after intraperitoneal (i.p.) and oral administration. Additionally, ex vivo assays were performed to assess human blood compatibility as well as in vitro assays to assess protein binding. Our results indicated that administration of three different concentrations of PU-NPs induced a significant increase in visceral fat accumulation after oral dosing. In addition, fat tissue of mice intraperitoneally treated with the highest concentration of nanoparticles showed diffuse mononuclear inflammatory infiltrate in the fat tissue. Histopathological assessment showed inflammatory infiltrate and hepatocyte vacuolization in the liver, inflammatory infiltration and vascular congestion in the lung and glomerular necrosis in the kidney. Hepatic enzymes related with liver function were significantly increased in both groups of mice treated with PU-NPs. The PU-NPs did not affect the human blood cells number as well as coagulation time but showed a susceptibility to bind in proteins commonly found in the blood stream. In addition, increased amounts of pro inflammatory cytokines in vivo, as well as ex vivo in human cells were observed. Further studies to establish the consequences of long-term exposure to PU-NPs are warranted. PMID:26820842

  14. Effect of helium-neon laser irradiation on hair follicle growth cycle of Swiss albino mice.

    PubMed

    Shukla, S; Sahu, K; Verma, Y; Rao, K D; Dube, A; Gupta, P K

    2010-01-01

    We report the results of a study carried out to investigate the effect of helium-neon (He-Ne) laser (632.8 nm) irradiation on the hair follicle growth cycle of testosterone-treated and untreated mice. Both histology and optical coherence tomography (OCT) were used for the measurement of hair follicle length and the relative percentage of hair follicles in different growth phases. A positive correlation (R = 0.96) was observed for the lengths of hair follicles measured by both methods. Further, the ratios of the lengths of hair follicles in the anagen and catagen phases obtained by both methods were nearly the same. However, the length of the hair follicles measured by both methods differed by a factor of 1.6, with histology showing smaller lengths. He-Ne laser irradiation (at approximately 1 J/cm(2)) of the skin of both the control and the testosterone-treated mice was observed to lead to a significant increase (p < 0.05) in % anagen, indicating stimulation of hair growth. The study also demonstrates that OCT can be used to monitor the hair follicle growth cycle, and thus hair follicle disorders or treatment efficacy during alopecia. PMID:20016249

  15. Why do female mice mate with multiple males?

    PubMed

    Thonhauser, Kerstin E; Raveh, Shirley; Hettyey, Attila; Beissmann, Helmut; Penn, Dustin J

    2013-01-01

    Females often show multi-male mating (MMM), but the adaptive functions are unclear. We tested whether female house mice (Mus musculus musculus) show MMM when they can choose their mates without male coercion. We released 32 females into separate enclosures where they could choose to mate with two neighboring males that were restricted to their own territories. We also tested whether females increase MMM when the available males appeared unable to exclude intruders from their territories. To manipulate territorial intrusion, we introduced scent-marked tiles from the neighboring males into males' territories, or we rearranged tiles within males' own territories as a control. Each female was tested in treatment and control conditions and we conducted paternity analyses on the 57 litters produced. We found that 46 % of litters were multiply sired, indicating that multiple paternity is common when females can choose their mates. Intrusion did not increase multiple paternity, though multiple paternity was significantly greater in the first trial when the males were virgins compared to the second trial. Since virgin male mice are highly infanticidal, this finding is consistent with the infanticide avoidance hypothesis. We also found that multiple paternity was higher when competing males showed small differences in their amount of scent marking, suggesting that females reduce MMM when they can detect differences in males' quality. Finally, multiple paternity was associated with increased litter size but only in the intrusion treatment, which suggests that the effect of multiple paternity on offspring number is dependent on male-male interactions. PMID:24273373

  16. Acute inhalation toxicity of smoke of fentanyl and its 1-substituted analogs in Swiss albino mice.

    PubMed

    Yadav, S K; Swami, D; Kumar, P; Meena, M K; Maurya, C K; Gupta, P K; Ganesan, K; Jain, A K; Bhattacharya, R

    2014-01-01

    Fentanyl (N-(1-phenethyl-4-piperidinyl)propionanilide) is a synthetic, potent narcotic analgesic agent. However, it is known to have several side effects, which led to synthesis and evaluation of its new analogs for the management of pain. We have earlier reported the comparative bioassay of fentanyl and its eight 1-substituted analogs (1-8) in mice. Three compounds, viz., N-(1-(2-phenoxyethyl)-4-piperidinyl)propionanilide (2), N-isopropyl-3-(4-(N-phenylpropionamido)piperidin-1-yl)propanamide (5), and N-t-butyl-3-(4-(N-phenylpropionamido)piperidin-1-yl)propanamide (6) were found to be more effective and less toxic compared to fentanyl. The present study reports the comparative acute inhalation toxicity of smoke of fentanyl and its three analogs, viz., 2, 5, and 6 in mice. Animals were exposed to different concentrations of smoke generated by heating the compounds. Exposure was performed in a head only all glass static exposure assembly for 15 min to determine the median lethal concentration (LC50). The breathing pattern and various respiratory parameters of the animals were also monitored online using a polygraph. Out of three compounds tested, analog 5 was found to be most toxic (LC50 = 2820 mg/m3) while 2 was least toxic (LC50 = >8000 mg/m3). All the compounds caused long lasting respiratory depression in a dose-dependent manner, which did not completely resolve even after discontinuation of exposure. Aerodynamic median diameter and geometric standard deviation of smoke particles was determined employing eight-stage Andersen sampler. The particles were found to be within the respirable range. The study, however, concludes that due to possible decomposition of the compounds by heating or its poor absorption by the alveolar surface, the present inhalation technique cannot be employed to generate smoke of fentanyl and its analogs for any medical or surreptitious use. PMID:25208041

  17. Behavioral characterization of non-copulating male mice.

    PubMed

    Portillo, W; Antonio-Cabrera, E; Camacho, F J; Díaz, N F; Paredes, R G

    2013-06-01

    Non-copulating (NC) males are those animals that do not mate in spite of repeated testing with sexually receptive females. They have been observed in several species including rats and mice. The present experiment was designed to perform a detailed behavioral characterization of NC male mice. Thus, we evaluated their sexual incentive motivation for a sexually receptive female or a sexually active male, olfactory preference for volatile and non-volatile odors from females or males, and olfactory discrimination between female and male volatile odors and food related odors (milk versus vinegar). We compared the activity of the accessory olfactory system (AOS) in copulating (C) and NC males in response to estrous bedding using the induction of Fos-immunoreactivity (Fos-IR) as a measure of neuronal activation. We also determined if estradiol or dopamine treatment could induce sexual behavior in NC males. Finally, we compared the testis weight and the number of penile spines in C, NC, and gonadectomized males. In the sexual incentive motivation test C males spend significantly more time in the female incentive zone than in the male incentive zone. On the other hand, NC males spend the same amount of time in both incentive zones. In tests of olfactory preference, NC males spent less time investigating estrous odors than C males. As well, NC males discriminate urine from conspecifics but they spend less time smelling these odors than C males. In addition, no increase in Fos expression is observed in NC males when they are exposed to odors from estrous females. Our data also suggest that the deficits observed in NC males are not due to lower circulating levels of gonadal hormones, because estradiol supplementation does not induce sexual behavior in these animals, and their testis weight and the number of penile spines are normal. The results suggest that NC males are not sexually motivated by the receptive females and their odors. PMID:23673371

  18. REPRODUCTIVE DEVELOPMENT IN MALE DEER MICE EXPOSED TO AGGRESSIVE BEHAVIOR

    EPA Science Inventory

    Male deer mice (Peromyscus maniculatus bairdii) were reared in a long photoperiod and housed individually from 3 weeks of age until they were killed 2, 4, or 6 weeks later. Males that were exposed to aggressive females for 2 min, three times per week, were of normal body weight a...

  19. Self-Exposure to the Male Pheromone ESP1 Enhances Male Aggressiveness in Mice.

    PubMed

    Hattori, Tatsuya; Osakada, Takuya; Matsumoto, Ayaka; Matsuo, Naoki; Haga-Yamanaka, Sachiko; Nishida, Takaya; Mori, Yuji; Mogi, Kazutaka; Touhara, Kazushige; Kikusui, Takefumi

    2016-05-01

    Exocrine gland-secreting peptide 1 (ESP1) released into male tear fluids is a male pheromone that stimulates sexually receptive behavior in female mice via the vomeronasal sensory system. ESP1 also induces c-Fos expression in male brain regions distinct from those in females. However, behavior in males following ESP1 exposure has not been examined. In the present study, we show that ESP1, in conjunction with unfamiliar male urine, enhances male aggression via the specific vomeronasal receptor V2Rp5. In addition, male mice that secrete ESP1 but lack V2Rp5 exhibit a lower level of aggressiveness than do mice that express V2Rp5. These results suggest that ESP1 not only acts as a male pheromone in both sexes but also serves as an auto-stimulatory factor that enhances male aggressiveness by self-exposure. Finally, re-activation of ESP1-induced c-Fos-positive neurons by using the designer receptor exclusively activated by designer drug (DREADD) approach resulted in enhancement of sexual and aggressive behaviors in female and male mice, respectively, indicating that sexually dimorphic activation in the brain is a neural basis for the sex-specific behavioral responses to ESP1. PMID:27151664

  20. An Experimental Study to Evaluate the Effect of Memantine in Animal Models of Anxiety in Swiss Albino Mice

    PubMed Central

    AK, Afzal Khan; Shivaramegowda, Rekha M

    2015-01-01

    Background Due to the adverse effects produced by the present conventional medicines for anxiety disorders, research for newer drugs is still desirable. From the literature it is evident that NMDA receptors play a key role in animal models of anxiety. Aim The present study is done to evaluate the antianxiety effect of memantine in swiss albino mice. Materials and Methods The experimental study was conducted from November 2014 to January 2015. Animals were divided into four groups. Twelve mice were randomly allotted in each group. Animals in the first group received normal saline as a control 10ml/kg, lorazepam 0.5mg/kg was administered to second group, memantine 3mg/kg as a test drug was given to the third group and memantine 3mg/kg + lorazepam 0.5mg/kg was administered to the fourth group. All the drugs were given for 7 consecutive days by intraperitoneal route. Results Results were analyzed by one-way ANOVA followed by Post-hoc Tukey’s test. On the 1st day, memantine treated group did not show statistical significant anxiolytic effect in both the behavioural paradigms when compared to control group. On the 8th day, the animals showed significant decrease p<0.001 in step down latency period in shock free zone (185.4±3.87 Vs 278.3±5.49), significant increase p<0.001 in step down errors (6.8±0.78 Vs 1.4±0.19) and significant increase p<0.001 in total time spent in shock zone (32.1±2.22 Vs 5.6±0.6). In open field test, on 8th day the animals treated with memantine when compared to control group, showed significant increase p<0.001 in number of squares crossed (112.7± 2.69 Vs 83.2±2.96), time spent in central square (11.5±1.26 Vs 3.4±0.65), no. of rearings (32.4±2.61 Vs 17±1.81) and significant decrease p<0.001 in freezing time (15.2±1.12 Vs 20.2±2.29). Memantine showed synergistic antianxiety effect when combined with lorazepam. Conclusion Memantine showed significant anxiolytic effect in open field and passive avoidance response tests which are

  1. Biochemical and histopathological responses of the Swiss albino mice treated with uranyl nitrate and its recovery.

    PubMed

    Sangeetha Vijayan, P; Rekha, P D; Dinesh, U; Arun, A B

    2016-06-01

    Uranium is a radioactive heavy metal ubiquitous in the natural environment. In its chemical form, it is known to induce nephrotoxicity both in human and in animals. Its toxicity is dose and time dependent, also varies with form of uranium. In the present study, we assessed the nephrotoxicity induced by a single dose of uranyl nitrate (UN) in mice at different time intervals and recovery from its toxicity. Two doses of 2 and 4 mg/kg body weight of uranyl nitrate was injected intraperitoneally and animals were sacrificed after 1, 3, 5, 14, and 28 d of administration. Histopathological and biochemical alterations of post-UN dosing in comparison to control were evaluated. Tubular damage to about 75% was observed after 3 d (4 mg/kg) and the biochemical parameters such as serum creatinine, urea, and blood urea nitrogen levels were also significantly increased. Progression of tubular damage was not found after 5 d. Dose-dependent recovery of uranyl nitrate-treated animals was observed after 14 and 28 d of dosing. The concentration of uranium retained in kidney correlates with biochemical and histopathological analysis. PMID:26984368

  2. Chemopreventive effects of cardamom (Elettaria cardamomum L.) on chemically induced skin carcinogenesis in Swiss albino mice.

    PubMed

    Qiblawi, Samir; Al-Hazimi, Awdah; Al-Mogbel, Mohammed; Hossain, Ashfaque; Bagchi, Debasis

    2012-06-01

    The chemopreventive potential of cardamom was evaluated on 7,12-dimethylbenz[a]anthracene-initiated and croton oil-promoted mouse skin papillomagenesis. A significant reduction in the values of tumor incidence, tumor burden, and tumor yield and the cumulative number of papillomas was observed in mice treated orally with 0.5 mg of cardamom powder in suspension continuously at pre-, peri-, and post-initiational stages of papillomagenesis compared with the control group. The average weight and diameter of tumors recorded were also comparatively lower in the cardamom-treated mouse group. Treatment of cardamom suspension by oral gavage for 15 days resulted in a significant decrease in the lipid peroxidation level of the liver (P < .01). In addition, the reduced glutathione level was significantly elevated in comparison with the control group (P < .05) following cardamom suspension treatment. Taken together, these findings indicate the potential of cardamom as a chemopreventive agent against two-stage skin cancer. PMID:22404574

  3. Effect of prenatal lead toxicity on surface ultrastructural features, elemental composition and infrared absorption characteristics of the skin of albino mice.

    PubMed

    Dey, S; Arjun, J; Das, M; Bhattacharjee, C R; Dkhar, P S

    2001-01-01

    The epidermis and dermis of albino mice born to females receiving oral sublethal doses of lead during pregnancy developed several abnormalities. These included perforations, tissue damage, cell deformity, and disordered organization of collagen bundles, as revealed by scanning electron microscopy. An increase in the concentrations of zinc, iron, magnesium, calcium and a decrease in that of copper was evident from atomic absorption spectroscopical analysis, when entire skin tissues were examined. Infrared spectroscopy revealed the occurrence of split bands in the spectra at 1,200-1,000 cm(-1), suggesting a reduction in the symmetry of the sulphate group (glycosaminoglycans) of skin probably caused by covalent bonding of it with lead. PMID:11545451

  4. Female mice ultrasonically interact with males during courtship displays.

    PubMed

    Neunuebel, Joshua P; Taylor, Adam L; Arthur, Ben J; Egnor, S E Roian

    2015-01-01

    During courtship males attract females with elaborate behaviors. In mice, these displays include ultrasonic vocalizations. Ultrasonic courtship vocalizations were previously attributed to the courting male, despite evidence that both sexes produce virtually indistinguishable vocalizations. Because of this similarity, and the difficulty of assigning vocalizations to individuals, the vocal contribution of each individual during courtship is unknown. To address this question, we developed a microphone array system to localize vocalizations from socially interacting, individual adult mice. With this system, we show that female mice vocally interact with males during courtship. Males and females jointly increased their vocalization rates during chases. Furthermore, a female's participation in these vocal interactions may function as a signal that indicates a state of increased receptivity. Our results reveal a novel form of vocal communication during mouse courtship, and lay the groundwork for a mechanistic dissection of communication during social behavior. PMID:26020291

  5. Female mice ultrasonically interact with males during courtship displays

    PubMed Central

    Neunuebel, Joshua P; Taylor, Adam L; Arthur, Ben J; Egnor, SE Roian

    2015-01-01

    During courtship males attract females with elaborate behaviors. In mice, these displays include ultrasonic vocalizations. Ultrasonic courtship vocalizations were previously attributed to the courting male, despite evidence that both sexes produce virtually indistinguishable vocalizations. Because of this similarity, and the difficulty of assigning vocalizations to individuals, the vocal contribution of each individual during courtship is unknown. To address this question, we developed a microphone array system to localize vocalizations from socially interacting, individual adult mice. With this system, we show that female mice vocally interact with males during courtship. Males and females jointly increased their vocalization rates during chases. Furthermore, a female's participation in these vocal interactions may function as a signal that indicates a state of increased receptivity. Our results reveal a novel form of vocal communication during mouse courtship, and lay the groundwork for a mechanistic dissection of communication during social behavior. DOI: http://dx.doi.org/10.7554/eLife.06203.001 PMID:26020291

  6. Synthesis and biological evaluation of some novel 1-substituted fentanyl analogs in Swiss albino mice

    PubMed Central

    Yadav, Shiv Kumar; Maurya, Chandra Kant; Gupta, Pradeep Kumar; Jain, Ajai Kumar; Ganesan, Kumaran

    2014-01-01

    Fentanyl [N-(1-phenethyl-4-piperidinyl)propionanilide] is a potent opioid analgesic agent, but a has narrow therapeutic index. We reported earlier on the synthesis and bioefficacy of fentanyl and its 1-substituted analogs (1–4) in mice. Here we report the synthesis and biological evaluation of four additional analogs, viz. N-isopropyl-3-(4-(N-phenylpropionamido)piperidin-1-yl)propanamide (5), N-t-butyl-3-(4-(N-phenylpropionamido)piperidin-1-yl)propanamide (6), isopropyl 2-[4-(N-phenylpropionamido)piperidin-1-yl]propionate (7) and t-butyl 2-[4-(N-phenylpropionamido)piperidin-1-yl]propionate (8). The median lethal dose (LD50) determined by intravenous, intraperitoneal and oral routes suggests these analogs to be comparatively less toxic than fentanyl. On the basis of observational assessment on spontaneous activities of the central, peripheral, and autonomic nervous systems, all the analogs were found to be similar to fentanyl. Naloxone hydrochloride abolished the neurotoxic effects of these analogs, thereby ascertaining their opioid receptor-mediated effects. All the analogs displayed significant analgesic effects, measured by formalin-induced hind paw licking and tail immersion tests at their respective median effective dose (ED50). They also exhibited 8–12 fold increase in therapeutic index over fentanyl. However, 5 and 6 alone produced lower ED50 (20.5 and 21.0 µg/kg, respectively) and higher potency ratio (1.37 and 1.33, respectively) compared to fentanyl. They could thus be considered for further studies on pain management. PMID:26109885

  7. Antioxidant activity of ethanolic extract of Tinospora cordifolia on N-nitrosodiethylamine (diethylnitrosamine) induced liver cancer in male Wister albino rats

    PubMed Central

    Jayaprakash, R.; Ramesh, V.; Sridhar, M. P.; Sasikala, C.

    2015-01-01

    Background: Cancer is a disease that evokes wide spread fear among people and is one of the leading causes of deaths in the world. Diethylnitrosamine (DEN) is a known carcinogen in rodent liver. DENs reported to undergo metabolic activation by cytochrome P450 enzymes to form reactive electrophiles that cause oxidative stress leading to cytotoxicity, mutagenicity and carcinogenicity. Objective: The present study was carried out to evaluate the antioxidant activity of ethanolic extract of Tinospora cordifolia (EETC) in N-nitrosodiethylamine (DEN) induced liver cancer in male Wister albino rats. Materials and Methods: The antioxidant activity was assessed by the levels of lipid peroxidation (LPO), enzymic and nonenzymic antioxidants. Result: A significant levels of LPO was increased as the enzymic and nonenzymic antioxidants values were decreased in liver cancer bearing animals. Conclusions: The administration of EETC to cancer bearing animals reverted the LPO levels, enzymic and nonenzymic antioxidants to near normal PMID:26015745

  8. Differential effects of alprazolam and clonazepam on the immune system and blood vessels of non-stressed and stressed adult male albino rats

    PubMed Central

    Elmesallamy, Ghada E.; Abass, Marwa A.; Ahmed Refat, Nahla A.G.; Atta, Amal H.

    2011-01-01

    Benzodiazepines belongs to one of the most commonly used anxiolytic and anticonvulsant drugs in the world. Full description of toxic effects on different organs is lacking for nearly all the current benzodiazepines. The aim of the current work was to study the immunologic and vascular changes induced by sub-chronic administration of alprazolam and clonazepam in non-stressed and stressed adult male albino rats. Forty-two adult male albino rats were divided into 6 groups (I): (Ia) Negative control rats, (Ib): Positive control rats received distilled water, (II): Stressed rats, (III): Non-stressed rats received daily oral dose of clonazepam (0.5 mg/kg), (IV): Stressed rats received daily oral dose of clonazepam (0.5 mg/kg), (V): Non-stressed rats received daily oral dose of alprazolam (0.3 mg/kg). (VI): Stressed rats received daily oral dose of alprazolam (0.3 mg/kg). At the end of the 4th week, total leukocyte count (WBCs) and differential count were determined, anti-sheep RBC antibody (Anti-SRBC) titer and interleukin-2 (IL-2) level were assessed, thymus glands, lymph nodes, spleens and abdominal aortae were submitted to histopathological examination. Alprazolam was found to induce a significant increase in neutrophil count and a significant decrease in lymphocytes, anti-SRBC titer and IL-2 level with severe depletion of the splenic, thymal and nodal lymphocytes, accompanied by congestion and eosinophilic vasculitis of all organs tested in comparison to clonazepam treated rats. Stress enhanced the toxic effects. It was concluded that the immune system and blood vessels can be adversely affected to a greater extent by short-term chronic administration of alprazolam than by clonazepam, and these toxic effects are aggravated by stress. PMID:22058654

  9. Lactobacillus rhamnosus GG supplementation during critical windows of gestation influences immune phenotype in Swiss albino mice offspring.

    PubMed

    Himaja, N; Hemalatha, R; Narendra Babu, K; Shujauddin, M

    2016-03-11

    Probiotic supplementation during critical windows of gestation might have a significant influence on the infant's immune phenotype. Swiss albino mice (F0 generation) aged 31 days were supplemented orally with probiotic Lactobacillus rhamnosus GG (LGG); and the supplementation was continued throughout mating, gestation and lactation. The pups (F1 generation) born to them were separated post weaning and received either the same probiotic supplementation as their mothers or were denied supplementation postnatally. Neutrophil phagocytic ability, splenocyte proliferation, immunoglobulins and cytokines were determined in both F0 and F1 pups. In addition, antibody response against hepatitis-B surface antigen (HBsAg) was determined in F1 pups. Probiotic supplementation had no effect on the neutrophil phagocytic ability and splenocyte proliferation index. The serum immunoglobulin G (IgG) and secretory IgA (s-IgA) among the probiotic supplemented group of F0 generation were significantly (P<0.05) higher compared to the controls. Similarly, the mean concentration of interleukin (IL)-10, IL-17 and interferon gamma (IFN-γ) among F0 probiotic group were significantly higher (P<0.05) compared to the control. Prenatal and postnatal probiotic supplementation in F1 pups led to similar results as F0 dams. Prenatal probiotic supplementation in F1 pups led to significantly (P<0.05) higher serum IgG (55.15±1.35 ng/ml) and intestinal s-IgA (77.9 ± 2.86 ng/mg protein) concentration when compared to the control. Similarly, IFN-γ concentration increased (P<0.05) with prenatal probiotic supplementation compared to the control. However, IL-10 and IL-17 concentrations of prenatal probiotic supplemented F1 pups were comparable to the control. As for the antibody response to HBsAg, prenatal probiotic supplementation led to enhanced HBsAg antibody response (471.4±3.97 U/ml) compared to the control. LGG affected the immune regulation and immune responses favourably in mothers and offspring

  10. Functional and morphological effects of laser-induced ocular hypertension in retinas of adult albino Swiss mice

    PubMed Central

    Salinas-Navarro, Manuel; Alarcón-Martínez, Luis; Valiente-Soriano, Francisco Javier; Ortín-Martínez, Arturo; Jiménez-López, Manuel; Avilés-Trigueros, Marcelino; Villegas-Pérez, María Paz; de la Villa, Pedro

    2009-01-01

    Purpose To investigate the effects of laser photocoagulation (LP)-induced ocular hypertension (OHT) on the survival and retrograde axonal transport of retinal ganglion cells (RGC), as well as on the function of retinal layers. Methods Adult albino Swiss mice (35–45 g) received laser photocoagulation of limbal and episcleral veins in the left eye. Mice were sacrificed at 8, 17, 35, and 63 days. Intraocular pressure (IOP) in both eyes was measured with a Tono-Lab before LP and at various days after LP. Flash electroretinogram (ERG) scotopic threshold response (STR) and a- and b-wave amplitudes were recorded before LP and at various times after LP. RGCs were labeled with 10% hydroxystilbamidine methanesulfonate (OHSt) applied to both superior colliculi before sacrifice and in some mice, with dextran tetramethylrhodamine (DTMR) applied to the ocular stump of the intraorbitally transected optic nerve. Retinas were immunostained for RT97 or Brn3a. Retinas were prepared as whole-mounts and photographed under a fluorescence microscope. Labeled RGCs were counted using image analysis software, and an isodensity contour plot was generated for each retina. Results IOP increased to twice its basal values by 24 h and was maintained until day 5, after which IOP gradually declined to reach basal values by 1 wk. Similar IOP increases were observed in all groups. The mean total number of OHSt+ RGCs was 13,428±6,295 (n=12), 10,456±14,301 (n=13), 12,622±14,174 (n=21), and 10,451±13,949 (n=13) for groups I, II, III, and IV, respectively; these values represented 28%, 23%, 26%, and 22% of the values found in their contralateral fellow retinas. The mean total population of Brn3a+ RGCs was 24,343±5,739 (n=12) and 10,219±8,887 (n=9), respectively, for groups I and III; these values represented 49% and 20%, respectively, of the values found in their fellow eyes. OHT retinas showed an absence of OHSt+ and DTMR+ RGCs in both focal wedge-shaped and diffuse regions of the retina. By 1

  11. Delineating the antigenotoxic and anticytotoxic potentials of 4-methylimidazole against ethyl methanesulfonate toxicity in bone marrow cell of swiss albino mice.

    PubMed

    Norizadeh Tazehkand, M; Topaktas, M; Yilmaz, M B; Hajipour, O; Valipour, E

    2016-01-01

    4-Methylimidazole (4-MEI) is mostly used in beverages and coloring food, dark beers and common brands of cola drinks, which may contain more than 100 μg of this compound per 12-ounce serving. This study was aimed to investigate the antigenotoxic and anticytotoxic effects of 4-MEI (100, 130 and 160 mg/kg) against ethyl methanesulfonate (240 mg/kg) using chromosome aberrations (CAs) and Mitotic index (MI) tests in bone marrow cells of Swiss Albino Mice at 12 h and 24 h treatment periods. So, the t-test was used for the statistical analysis.In this research, 4-MEI at all concentrations for 12 h treatment period reduced chromosomal aberrations and at 130 and 160 mg/kg concentrations for 24 h treatment period increased chromosomal aberrations induced by EMS (240 mg/kg), but th ese reductions and increases were not significant. Also, intraperitoneal injection of 4-MEI at doses of 100, 130 and 160 mg/kg combined with EMS (240 mg/kg) showed that the mitotic index was decreased at 100 and 130 mg/kg for 12h and 130 mg/kg for 24 h treatment periods, when compared to positive sample (EMS), but did not show any statistically difference from the EMS treated group. It can be concluded that 4-MEI might not be antigenotoxic and protective effects in bone marrow cells of Swiss Albino Mice, because 4-MEI could not reduce the chromosomal aberrations induced by EMS. PMID:27215965

  12. Vitamin E attenuates liver injury induced by exposure to lead, mercury, cadmium and copper in albino mice

    PubMed Central

    Al-Attar, Atef M.

    2011-01-01

    Water pollution is the contamination of water resources by harmful wastes or toxins. Both community and private sources of drinking water are susceptible to a myriad of chemical contaminants. Heavy metals pollution of surface water can create health risks. The present study was aimed to investigate the effect of vitamin E supplementation on male mice exposed to a mixture of some heavy metals (lead, mercury, cadmium and copper) in their drinking water for seven weeks. Significant increases of blood alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT) were detected in heavy metals-treated mice. Histopathologically, the liver sections from heavy metals-treated mice showed severe changes including disarrangement of hepatic strands, rupture in hepatocytes, advanced hepatocellular necrosis, dilation and congestion of blood vessels with hemorrhage, dense lymphocytic infiltration round the central vein and dark stained hepatocytic nuclei indicating cell pycnosis. Administration of vitamin E at a dose of 50 IU/kg body weight, five times weekly improved the observed biochemical and histopathological changes induced by these heavy metals intoxication. Hence, the results of this study suggest that vitamin E protects against these heavy metals-induced liver injury and the attenuating effect of vitamin E may be due to its antioxidant activity. PMID:23961152

  13. Antiplasmodial activity of eco-friendly synthesized palladium nanoparticles using Eclipta prostrata extract against Plasmodium berghei in Swiss albino mice.

    PubMed

    Rajakumar, Govindasamy; Rahuman, Abdul Abdul; Chung, Ill-Min; Kirthi, Arivarasan Vishnu; Marimuthu, Sampath; Anbarasan, Karunanithi

    2015-04-01

    Malaria is an infectious disease caused by the Plasmodium parasite that continues to be a health issue for humans. It is one of the most common pathogenic factors of morbidity and mortality. Palladium nanoparticles (Pd NPs) have been used as target antimicrobial compounds, as a catalyst to manufacture pharmaceuticals, degrade harmful environmental pollutants, and as sensors for the detection of various analyses. The aim of this study was to investigate the antiplasmodial activity of synthesized Pd NPs by using leaf aqueous extract of Eclipta prostrata against Plasmodium berghei in Swiss albino mice. The synthesized Pd NPs were characterized by X-ray diffraction (XRD), Fourier transform infrared (FTIR), Scanning electron microscopy (SEM) with Energy dispersive X-ray spectroscopy (EDX), and High-resolution transmission electron microscope (HRTEM) with the Selected area (electron) diffraction (SAED). The XRD peaks appeared at 35.61°, 44.27°, 56.40°, and 74.51°, which correspond to (111), (200), (220), and (311) planes for palladium, respectively. The FTIR spectra that were carried out to identify the potential biomolecule of synthesized Pd NPs showed the peaks at 3361, 1540, 1399, 1257, 1049, and 659 in the region of 4000-500 cm(-1). The SEM images showed aggregation of NPs with an average size of 63 ± 1.4. The HRTEM images of the precipitated solid phase obtained after termination of the reaction of E. prostrata aqueous leaf extract were in the range from 18 to 64 nm with an average size of 27 ± 1.3 nm. The in vivo antiplasmodial assay was carried out as per Peters' 4-day suppressive test, and the synthesized Pd NP-treated mice group showed reduction of parasitemia by 78.13% with an inhibitory concentration (IC)50 value of 16.44 mg/kg/body weight. The growth inhibition of E. prostrata aqueous leaf extract, palladium acetate, and synthesized Pd NPs showed the IC20, IC50, and IC90 values of 1.90, 10.29, and 64.11; 4.49, 9.84, and 23.04; and 4.34, 8

  14. Social dominance in male vasopressin 1b receptor knockout mice.

    PubMed

    Caldwell, Heather K; Dike, Obianuju E; Stevenson, Erica L; Storck, Kathryn; Young, W Scott

    2010-07-01

    We have previously reported that mice with a targeted disruption of their vasopressin 1b receptor gene, Avpr1b, have mild impairments in social recognition and reduced aggression. The reductions in aggression are limited to social forms of aggression, i.e., maternal and inter-male aggression, while predatory aggression remains unaffected. To further clarify the role of the Avpr1b in the regulation of social behavior we first examined anxiety-like and depression-like behaviors in Avpr1b knockout (Avpr1b -/-) mice. We then went on to test the ability of Avpr1b -/- mice to form dominance hierarchies. No major differences were found between Avpr1b -/- and wildtype mice in anxiety-like behaviors, as measured using an elevated plus maze and an open field test, or depression-like behaviors, as measured using a forced swim test. In the social dominance study we found that Avpr1b -/- mice are able to form dominance hierarchies, though in early hierarchy formation dominant Avpr1b -/- mice display significantly more mounting behavior on Day 1 of testing compared to wildtype controls. Further, non-socially dominant Avpr1b -/- mice spend less time engaged in attack behavior than wildtype controls. These findings suggest that while Avpr1b -/- mice may be able to form dominance hierarchies they appear to employ alternate strategies. PMID:20298692

  15. Sexual attractiveness of male chemicals and vocalizations in mice

    PubMed Central

    Asaba, Akari; Hattori, Tatsuya; Mogi, Kazutaka; Kikusui, Takefumi

    2014-01-01

    Male-female interaction is important for finding a suitable mating partner and for ensuring reproductive success. Male sexual signals such as pheromones transmit information and social and sexual status to females, and exert powerful effects on the mate preference and reproductive biology of females. Likewise, male vocalizations are attractive to females and enhance reproductive function in many animals. Interestingly, females' preference for male pheromones and vocalizations is associated with their genetic background, to avoid inbreeding. Moreover, based on acoustic cues, olfactory signals have significant effects on mate choice in mice, suggesting mate choice involves multisensory integration. In this review, we synopsize the effects of both olfactory and auditory cues on female behavior and neuroendocrine functions. We also discuss how these male signals are integrated and processed in the brain to regulate behavior and reproductive function. PMID:25140125

  16. Histopathological studies of acute and chronic effects of Calliandra portoricensis leaf extract on the stomach and pancreas of adult Swiss albino mice

    PubMed Central

    Ofusori, David A; Adejuwon, Adebomi O

    2011-01-01

    Objective To evaluate the consequence of oral administration of Calliandra portoricensis (C. portoricensis) leaf extract on the stomach and pancreas in Swiss albino mice. Methods Three groups of mice (B, C and D) were treated with 4 mg/kg of C. portoricensis extract. Group A was the control and received an equivalent volume of distilled water. Group B received C. portoricensis leaf extract for 7 days, Group C received C. portoricensis leaf extract for 14 days, and Group D received C. portoricensis leaf extract for 28 days. At different stages in the study, the mice were sacrificed and the stomach and pancreas were excised and fixed in 10% formol saline for histological analysis. Results The result showed a normal microstructural outline in groups B and C as compared with the control. However, animals in group D showed disorganization of the mucosa and discontinuation of epithelial lining of the stomach while the islets of Langerans in the pancreas were at various degree of degeneration as compared with the control mice. Conclusions The present finding suggests that chronic administration (28 days as seen in this study) of C. portoricensis leaf extract may inhibit the proper function of the stomach and pancreas. PMID:23569755

  17. Male sterility and enhanced radiation sensitivity in TLS(-/-) mice.

    PubMed

    Kuroda, M; Sok, J; Webb, L; Baechtold, H; Urano, F; Yin, Y; Chung, P; de Rooij, D G; Akhmedov, A; Ashley, T; Ron, D

    2000-02-01

    TLS (also known as FUS) is an RNA-binding protein that contributes the N-terminal half of fusion oncoproteins implicated in the development of human liposarcomas and leukemias. Here we report that male mice homozygous for an induced mutation in TLS are sterile with a marked increase in the number of unpaired and mispaired chromosomal axes in pre-meiotic spermatocytes. Nuclear extracts from TLS(-/-) testes lack an activity capable of promoting pairing between homologous DNA sequences in vitro, and TLS(-/-) mice and embryonic fibroblasts exhibit increased sensitivity to ionizing irradiation. These results are consistent with a role for TLS in homologous DNA pairing and recombination. PMID:10654943

  18. [Effects of a new derivative of 5-alkyl-3N-furanones on the colonization resistance of the intestine in albino mice].

    PubMed

    Tomnikov, A Iu; Shub, G M

    1990-05-01

    By its antagonistic function normal microflora provides the intestine with resistance to colonization with exogenic opportunistic and pathogenic microorganisms. The drug was effective in inducing a decrease in the intestine colonization resistance which in its turn leads to filling of free ecological niches with exogenic microflora. In this connection the suggestion that specification of a new chemical agent should include along with other criteria its effect on colonization resistance is valid. It was shown with the use of indicator microorganisms that when administered per os in doses of 40 and 80 mg/kg daily for 3 and 6 days, respectively, a new original compound 1929, a derivative of 5-alkyl-3H-furanones, with high antimicrobial activity induced no significant or more pronounced changes in the colonization resistance of the gastrointestinal tract of noninbred albino mice than furagin used as the reference drug. PMID:2200373

  19. Increased alcohol consumption in relaxin-3 deficient male mice.

    PubMed

    Shirahase, Takahira; Aoki, Miku; Watanabe, Ryuji; Watanabe, Yoshihisa; Tanaka, Masaki

    2016-01-26

    Relaxin-3 is a neuropeptide expressed in the brainstem, and predominantly localized in the gray matter of the midline dorsal pons termed the nucleus incertus. Relaxin-3-expressing neurons densely project axons rostrally to various forebrain regions including the septum, hippocampus, and lateral hypothalamus. Several relaxin-3 functions have been reported including food intake, stress responses, neuroendocrine function, emotion, and spatial memory. In addition, recently relaxin-3 and its receptor, RXFP3, were shown to regulate alcohol intake using an RXFP3 antagonist and RXFP3 gene knockout mice. In the present study, we investigated alcohol consumption in relaxin-3 knockout mice, and found that male but not female mice significantly drank more alcohol than wild-type mice in the two-bottle choice test. However, after chronic alcohol vapor exposure, wild-type and mutant mice did not show this difference in alcohol intake, although both genotypes exhibited increased alcohol consumption compared with non-alcohol-exposed control mice. There was no genotype difference in sucrose or quinine preference. These results suggest that the relaxin-3 neuronal system modestly affects alcohol preference and consumption. PMID:26687275

  20. Estimation of absorbed cadmium in tissues of male and female albino rats through different routes of administration.

    PubMed

    Nwokocha, C R; Nwokocha, M I; Owu, D U; Edidjana, E; Nwogbo, N; Ekpo, U; Ufearo, C S

    2011-06-01

    The resultant effects of cadmium exposure are seen in almost all the systems of the body, however, this study is designed to quantify its accumulation in tissues of animals exposed to cadmium. The rats were divided into two distinct groups of males and females, which were then divided into three groups, each for the monitoring of exposure. Group 1 served as control male and female and received normal rat chow and tap water. Group 2 males and females were treated with 5 mg/kg body weight of cadmium chloride (Cd) intraperitoneally for eight days while Group 3 males and females rats received 100 ppm of Cd in drinking water for 18 days. The concentrations of cadmium were analyzed in tissues (lung, stomach, kidney, heart, spleen, blood) by AAS. There were significant (P<0.05) increase in Cd (ppm) accumulation in males compared with females lungs (2.253 ± 1.47 vs 0.317 ± 0.001), stomach (0.187 ± 0.094 vs 0.045 ± 0.032) and blood (0.070 ± 0.001 vs 0.001±0.001) when Cd was administered intraperitoneally. Following oral administration, there were significant (P<0.05) difference in Cd (ppm) content between males and females (kidney (0.506 ± 0.074 vs 0.748 ± 0.147), stomach (0.045 ± 0.020 vs 0.001± 0.001) and blood (1.126 ± 0.001 vs 0.114 ± 0.001). Our results suggest that Cd accumulation in the various organs was sex and route of exposure-dependent in rats. PMID:22314995

  1. Amelioration Effect of Zinc and Iron Supplementation on Selected Oxidative Stress Enzymes in Liver and Kidney of Cadmium-Treated Male Albino Rat

    PubMed Central

    Jamakala, Obaiah; Rani, Usha A.

    2015-01-01

    Cadmium (Cd) is a highly toxic, nonessential heavy metal with many industrial uses that can contribute to a well-defined spectrum of diseases in animals as well as in humans. The present study examines the effect of zinc (Zn) and iron (Fe) supplementation on oxidative stress enzymes in Cd-treated rats. Wistar strain male albino rats were treated with cadmium chloride (CdCl2) at a dose of 1/10th LD50/48 h, that is, 22.5 mg/kg body weight for 7, 15, and 30 days (d) time intervals. The 15d Cd-treated rats were divided into three groups. The first group received Zn (12 mg/kg), second group Fe (40 mg/kg) alone, and third group supplemented with both Zn and Fe and observed for 7, 15, and 30d. After the specific time intervals, rats were decapitated and oxidative stress enzymes like catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione S-transferase (GST) were assayed in liver and kidney. Simultaneously lipid peroxidation (LPO) levels were also measured. A significant elevation in LPO levels with decreased activity levels of CAT, SOD, GPx, and GST were observed during Cd intoxication. With Zn and/or Fe supplementation, a significant reversal in the oxidative stress enzymes was observed. Our study reveals that combination of Zn and Fe supplementation is effective in detoxifying the Cd body burden from the test tissues. PMID:26862254

  2. Amelioration Effect of Zinc and Iron Supplementation on Selected Oxidative Stress Enzymes in Liver and Kidney of Cadmium-Treated Male Albino Rat.

    PubMed

    Jamakala, Obaiah; Rani, Usha A

    2015-01-01

    Cadmium (Cd) is a highly toxic, nonessential heavy metal with many industrial uses that can contribute to a well-defined spectrum of diseases in animals as well as in humans. The present study examines the effect of zinc (Zn) and iron (Fe) supplementation on oxidative stress enzymes in Cd-treated rats. Wistar strain male albino rats were treated with cadmium chloride (CdCl2) at a dose of 1/10(th) LD50/48 h, that is, 22.5 mg/kg body weight for 7, 15, and 30 days (d) time intervals. The 15d Cd-treated rats were divided into three groups. The first group received Zn (12 mg/kg), second group Fe (40 mg/kg) alone, and third group supplemented with both Zn and Fe and observed for 7, 15, and 30d. After the specific time intervals, rats were decapitated and oxidative stress enzymes like catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione S-transferase (GST) were assayed in liver and kidney. Simultaneously lipid peroxidation (LPO) levels were also measured. A significant elevation in LPO levels with decreased activity levels of CAT, SOD, GPx, and GST were observed during Cd intoxication. With Zn and/or Fe supplementation, a significant reversal in the oxidative stress enzymes was observed. Our study reveals that combination of Zn and Fe supplementation is effective in detoxifying the Cd body burden from the test tissues. PMID:26862254

  3. Repeated positive fighting experience in male inbred mice.

    PubMed

    Kudryavtseva, Natalia N; Smagin, Dmitry A; Kovalenko, Irina L; Vishnivetskaya, Galina B

    2014-11-01

    Repeated aggression is a frequent symptom of many psychiatric and neurological disorders, including obsessive-compulsive and attention deficit hyperactivity disorders, bipolar and post-traumatic stress disorders, epilepsy, autism, schizophrenia and drug abuse. However, repeated aggression is insufficiently studied because there is a lack of adequate models in animals. The sensory contact model (SCM), widely used to study the effects of chronic social defeat stress, can also be used to investigate the effects of repeated aggression. Mice with repeated positive fighting experience in daily agonistic interactions in this model develop pronounced aggressiveness, anxiety and impulsivity, disturbances in motivated and cognitive behaviors, and impairments of sociability; they also demonstrate hyperactivity, attention-deficit behavior, motor dysfunctions and repetitive stereotyped behaviors, such as jerks, rotations and head twitches. In this protocol, we describe how to apply the SCM to study repeated aggression in mice. Severe neuropathology develops in male mice after 20-21 d of agonistic interactions. PMID:25340443

  4. Effects of dimethoate in male mice reproductive parameters.

    PubMed

    Jallouli, Manel; Dhouib, Ines El Bini; Dhouib, Hanène; Gharbi, Najoua; El Fazaa, Saloua

    2015-12-01

    The aim of the current study was to investigate the ability of dimethoate (DMT) to induce reprotoxicity in male mice. The dose (20 mg/kg/day) was given orally for 30 days. A significant decrease in sperm count, motility and viability and a significant increase of morphologically abnormal spermatozoa percent in DMT treated mice was observed. Testicular Acetylcholinesterase (AChE) and Butyrylcholinesterase (BChE) activities were inhibited. Also, a significant increase in lipid peroxidation level and a significant decrease in the activities of antioxidant enzymes were observed in testis of DMT mice. In addition, gene expression of glutathione peroxidase 4 (GPx4) was quantified in RNA samples extracted from the testis by real-time reverse transcription-polymerase chain reaction (RT-PCR). Compared with control, mRNA expression of GPx4 was slightly decreased after DMT-exposure. PMID:26482405

  5. Sex chromosome recombination failure, apoptosis, and fertility in male mice.

    PubMed

    Faisal, Imrul; Kauppi, Liisa

    2016-06-01

    Lack of crossing-over in meiosis can trigger an apoptotic response at metaphase I by the spindle assembly checkpoint (SAC). In contrast to females, segregation of sex chromosomes in males poses a particular challenge as recombination and chiasma formation is restricted to the pseudoautosomal region, the small region of homology between X and Y chromosomes. Existing data indicate that low levels of crossover failure in male meiosis can be tolerated without compromising fertility, while high levels of X-Y dissociation (in ≥70 % of cells) result in widespread apoptosis and subsequent infertility, demonstrated earlier, e.g., in Spo11β-only mice. Here, we explore the threshold of X-Y recombination failure frequency that is compatible with fertility. We show that in Spo11β-only(mb) mice with a mixed genetic background, in contrast to Spo11β-only mice with a C57BL/6 background, X-Y pairing fails in ~50 % of cells but this still allows for sperm production without any overt impact on fertility. We also review data on apoptosis and fertility from other achiasmate mouse models and propose that the incidence of homolog dissociation that can be tolerated in vivo without compromising male fertility lies between 50 and 70 %. PMID:26440410

  6. Sin Nombre hantavirus decreases survival of male deer mice.

    PubMed

    Luis, Angela D; Douglass, Richard J; Hudson, Peter J; Mills, James N; Bjørnstad, Ottar N

    2012-06-01

    How pathogens affect their hosts is a key question in infectious disease ecology, and it can have important influences on the spread and persistence of the pathogen. Sin Nombre virus (SNV) is the etiological agent of hantavirus pulmonary syndrome (HPS) in humans. A better understanding of SNV in its reservoir host, the deer mouse, could lead to improved predictions of the circulation and persistence of the virus in the mouse reservoir, and could help identify the factors that lead to increased human risk of HPS. Using mark-recapture statistical modeling on longitudinal data collected over 15 years, we found a 13.4% decrease in the survival of male deer mice with antibodies to SNV compared to uninfected mice (both male and female). There was also an additive effect of breeding condition, with a 21.3% decrease in survival for infected mice in breeding condition compared to uninfected, non-breeding mice. The data identified that transmission was consistent with density-dependent transmission, implying that there may be a critical host density below which SNV cannot persist. The notion of a critical host density coupled with the previously overlooked disease-induced mortality reported here contribute to a better understanding of why SNV often goes extinct locally and only seems to persist at the metapopulation scale, and why human spillover is episodic and hard to predict. PMID:22218940

  7. Pain Reduces Sexual Motivation in Female But Not Male Mice

    PubMed Central

    Farmer, Melissa A.; Leja, Alison; Foxen-Craft, Emily; Chan, Lindsey; MacIntyre, Leigh C.; Niaki, Tina; Chen, Mengsha; Mapplebeck, Josiane C.S.; Tabry, Vanessa; Topham, Lucas; Sukosd, Melissa; Binik, Yitzchak M.; Pfaus, James G.

    2014-01-01

    Chronic pain is often associated with sexual dysfunction, suggesting that pain can reduce libido. We find that inflammatory pain reduces sexual motivation, measured via mounting behavior and/or proximity in a paced mating paradigm, in female but not male laboratory mice. Pain was produced by injection of inflammogens zymosan A (0.5 mg/ml) or λ-carrageenan (2%) into genital or nongenital (hind paw, tail, cheek) regions. Sexual behavior was significantly reduced in female mice experiencing pain (in all combinations); male mice similarly treated displayed unimpeded sexual motivation. Pain-induced reductions in female sexual behavior were observed in the absence of sex differences in pain-related behavior, and could be rescued by the analgesic, pregabalin, and the libido-enhancing drugs, apomorphine and melanotan-II. These findings suggest that the well known context sensitivity of the human female libido can be explained by evolutionary rather than sociocultural factors, as female mice can be similarly affected. PMID:24760835

  8. Protective effect of curcumin against experimentally induced aflatoxicosis on the renal cortex of adult male albino rats: a histological and immunohisochemical study

    PubMed Central

    El-Mahalaway, Abeer M

    2015-01-01

    Background: Aflatoxin contamination of foods is a worldwide problem. Chronic aflatoxin exposure is associated with kidney damage. Curcumin is a herbal agent, used in medicine with a wide range of beneficial therapeutic effects. Objective: to evaluate the effect of curcumin against experimentally induced aflatoxicosis on the renal cortex of adult male albino rats. Materials and methods: Forty adult male rats were included and they were divided equally into 4 groups (10 rats each): Group I (control group), group II (Curcumin group): The rats received curcumin (200 mg/kg b.w.) orally by gastric tube for 5 days/week, group III (Aflatoxin B1 group): The rats received aflatoxin B1 (250 μg/kg b.w./day) orally by gastric tube 5 days/week for 4 weeks, group IV (Aflatoxin B1 and Curcumin group): The rats received aflatoxin and curcumin orally by gastric tube 5 days/week for 4 weeks. Kidney specimens were prepared and sections were stained with hematoxylin and eosin, Masson’s trichrome, Periodic acid Schiff, immunohistochemical detection of desmin and Bcl2. Results: The tubules of group III showed degenerative and necrotic changes with disruption of basal lamina. There was a significant decrease Bcl2 expression in the tubules, but the glomeruli showed an enlargement with dilation of their capillaries lumina in some areas, while the other areas showed glomerular atrophy with obliteration of their capillaries lumina. There was a significant increase in desmin expression in the glomerular cells. The interstitium showed hemorrhage and cellular infiltration. Group IV showed improvement of the histological and immunohistochemical changes described before. Conclusion: Aflatoxin B1 has deleterious effects of on the histological structure of the rat’s renal cortex and curcumin minimized these effects as it has antioxidant, anti-inflammatory and antiapoptotic activities. We advise eating nutritious diets that contain sufficient amounts of curcumin and regulation must implement to

  9. Protective role of diet supplements Spirulina and Tamarind fruit pulp on kidney in sodium fluoride exposed Swiss albino mice: Histological and biochemical indices.

    PubMed

    Yadav, N; Sharma, Shweta; Sharma, K p; Pandey, A; Pareek, P; Sharma, Subhasini

    2016-01-01

    Fluoride toxicity through potable water, particularly ground water, is not uncommon in countries such as India, China, Iran, Iraq, Turkey, parts of Africa and Afghanistan. Kidney being the main organ involved in fluoride removal, it accumulates considerable amount of fluoride. Here, we report toxic effects of oral exposure of Swiss albino mice to fluoride (sub-acute: 190 mg/kg body wt. for 7 days; and sub-chronic: 94 mg/kg body wt. for 90 days) and recovery of sub-chronic fluoride exposed mice after 90 days of sodium fluoride (NaF) withdrawal. The role of diet supplements (Spirulina and tamarind fruit pulp @ 230 mg/kg body wt. independently as well as in combination) in amelioration of fluoride toxicity has also been screened. Compared with controls, feed intake decreased from 3-43%, body wt. 4-18%, and kidney wt. 5-12% in treated mice (except diet supplement groups of sub-chronic exposure) while their water intake increased from 4-43%. Histopathological changes in the cortical region of kidney in fluoride treated mice were as follows: dilation of bowman's capsule and thickening of its parietal and visceral layer; alterations in glomeruli size and their sclerotization; increase in bowman's space; proliferation of mesangial cells; reduction in podocyte counts; and dilation of proximal and distal tubules. Fluoride exposure altered tissue biochemistry (protein, acid phosphatase and alkaline phosphatase content) and increased urea (23-58%) and creatinine content (14-127%) in the serum. Sub-acute exposure was found more toxic. The diet modulation not only reduced fluoride toxicity but also led to better recovery of treated mice after withdrawal, especially in combination. PMID:26891552

  10. Effects of Hydro-alcoholic Extract of Anethum Graveolens Seed on Pentylenetetrazol-induced Seizure in Adult Male Mice

    PubMed Central

    Rostampour, Mohammad; Ghaffari, Arghavan; Salehi, Peyman; Saadat, Farshid

    2014-01-01

    Introduction Regarding chronic nature of epilepsy and its side effects and to access the effective treatment procedures, herbal medicine has received remarkable interest. The aim of this study was to determine the anticonvulsant effects of hydro-alcoholic extract of Anethum graveolens seed on pentylenetetrazol (PTZ) -induced seizure in male mice. Methods Fifty-six albino male mice were divided randomly into seven groups including the negative control (saline), positive control (Phenobarbital) and treatment groups using different doses of hydro-alcoholic extract of Anethum graveolens seed (50, 100, 300, 500 and 1000 mg/ kg). To provoke convulsion, PTZ was injected to all groups and initiation time of myoclonic and tonic-clonic seizures as well as surveillance after 24 h were measured. Results The results indicated that hydro-alcoholic extract of Anethum graveolens seed (AGS) delayed the initiation time of myoclonic and tonic-clonic seizures in comparison with saline group. The latency was considerable for myoclonic and tonic-clonic seizures at all above mentioned doses of AGS extract except for the lowest one. Moreover, the protective effect of AGS extract against mortality was statistically significant at all doses except for 50 mg/kg. Discussion As the hydro-alcoholic extract of AGS showed an appropriate response in experimental model of convulsion, it might be considered as an adjuvant therapy with other traditional antiepileptic medications. PMID:25337380

  11. Responses of Male C57BL/6N Mice to Observing the Euthanasia of Other Mice.

    PubMed

    Boivin, Gregory P; Bottomley, Michael A; Grobe, Nadja

    2016-01-01

    The AVMA Panel on Euthanasia recommends that sensitive animals should not be present during the euthanasia of others, especially of their own species, but does not provide guidelines on how to identify a sensitive species. To determine if mice are a sensitive species we reviewed literature on empathy in mice, and measured the cardiovascular and activity response of mice observing euthanasia of conspecifics. We studied male 16-wk-old C57BL/6N mice and found no increase in cardiovascular parameters or activity in the response of the mice to observing CO2 euthanasia. Mice observing decapitation had an increase in all values, but this was paralleled by a similar increase during mock decapitations in which no animals were handled or euthanized. We conclude that CO2 euthanasia of mice does not have an impact on other mice in the room, and that euthanasia by decapitation likely only has an effect due to the noise of the guillotine. We support the conceptual idea that mice are both a sensitive species and display empathy, but under the controlled circumstances of the euthanasia procedures used in this study there was no signaling of stress to witnessing inhabitants in the room. PMID:27423146

  12. Phenolic Profiling and Evaluation of Contraceptive Effect of the Ethanolic Extract of Salsola imbricata Forssk. in Male Albino Rats

    PubMed Central

    Shehab, Naglaa Gamil

    2014-01-01

    Reported researches dealing with either composition or bioactivity of Salsola imbricata are limited. This study was conducted aiming to investigate the phenolic composition of the plant and evaluate its efficacy as male contraceptive. Polyphenols, namely, phenolic acids and flavonoids, were qualitatively and quantitatively analysed by RP-HPLC in the hydrolysed methanol extract using two different wavelengths, 280 and 330 nm. The efficiency of different solvents in extracting the plant phenolics was assessed via spectrophotometric determination of the total phenolic and flavonoid contents. Acute toxicity study was carried out on the ethanolic extract to ascertain its safety prior to biological evaluation. The contraceptive effect was assessed, in male rats, by oral administration of the extract at two doses (250 and 500 mg/kg b. wt.), over a period of 65 days. HPLC analyses allowed the identification and quantification of a total of 13 and 8 components in the hydrolysed-methanol extract; the overall phenolic composition was dominated by quercitrin (12.692%) followed by coumaric acid (4.251%). Prolonged oral administration of the ethanolic extract caused slight reduction in the testis weight only. A significant decrease in the sperm count was observed (P < 0.01) in the two treated groups while significant decrease in the epididymal sperm motility was only observed in the high dose group. Morphological abnormalities were observed in sperms of treated animals. No distinct change in serum FSH, LH, and testosterone concentration was recorded. The histopathological findings supported to a high extent these results. The male contraceptive activity of Salsola imbricata could be ascribed to its phenolic components, especially quercitrin. PMID:25587346

  13. Ultrasonic Vocalizations of Male Mice Differ among Species and Females Show Assortative Preferences for Male Calls

    PubMed Central

    Musolf, Kerstin; Meindl, Stefanie; Larsen, Angela L.; Kalcounis-Rueppell, Matina C.; Penn, Dustin J.

    2015-01-01

    Male house mice (Mus musculus) emit ultrasonic vocalizations (USVs) during courtship, which attract females, and we aimed to test whether females use these vocalizations for species or subspecies recognition of potential mates. We recorded courtship USVs of males from different Mus species, Mus musculus subspecies, and populations (F1 offspring of wild-caught Mus musculus musculus, Mus musculus domesticus (and F1 hybrid crosses), and Mus spicilegus), and we conducted playback experiments to measure female preferences for male USVs. Male vocalizations contained at least seven distinct syllable types, whose frequency of occurrence varied among species, subspecies, and populations. Detailed analyses of multiple common syllable types indicated that Mus musculus and Mus spicilegus could be discriminated based on spectral and temporal characteristics of their vocalizations, and populations of Mus musculus were also distinctive regardless of the classification model used. Females were able to discriminate USVs from different species, and showed assortative preferences for conspecific males. We found no evidence that females discriminate USVs of males from a different subspecies or separate populations of the same species, even though our spectral analyses identified acoustic features that differ between species, subspecies, and populations of the same species. Our results provide the first comparison of USVs between Mus species or between Mus musculus subspecies, and the first evidence that male USVs potentially facilitate species recognition. PMID:26309246

  14. Evaluation of the protective role of vitamin C in imidacloprid-induced hepatotoxicity in male Albino rats

    PubMed Central

    Soujanya, S.; Lakshman, M.; Kumar, A. Anaad; Reddy, A. Gopala

    2013-01-01

    In the present study, the effects of oral administration of imidacloprid for 4 weeks on serum biochemical, oxidative stress, histopathological and ultrastructural alterations were assessed in the liver of male rats. This study also aimed to investigate whether vitamin C could protect against the imidacloprid-induced oxidative stress. Forty-eight male Sprague dawley rats were divided into four groups of 12 animals each. Group 1 served as the control, while groups 2 and 4 were administered with imidacloprid (80 mg/kg body weight) daily by oral gavage for 28 days. In addition to imidacloprid, group 4 also received vitamin C at 10 mg/kg daily by oral gavage for 28 days. Group 3 was maintained as the vitamin C control (dose as above). The serum biochemical assays revealed a significant (P < 0.05) increase in alanine transaminase and aspartate transaminase and decrease in total protein in group 2. The tissue biochemical profile revealed a significant (P < 0.05) reduction in reduced glutathione concentration in the liver of group 2 animals. Histologically, the liver showed marked dilation, congestion of central vein, portal vein and sinusoidal spaces, vacuolation/fatty change and degenerated hepatocytes. Ultra thin sections of the liver revealed swollen nuclei, varied size and shape of mitochondria, disrupted chromatin and rough endoplasmic reticulum. Co-treatment with vitamin C significantly (P < 0.05) reversed the imidacloprid-induced changes. PMID:23633837

  15. Effect of green tea (camellia sinensis l.) leaf extract on reproductive system of adult male albino rats

    PubMed Central

    Das, Shyamal Kanti; Karmakar, Soumendra Nath

    2015-01-01

    Green tea leaf extract (GTLE), used in this experiment has shown great influence on male reproductive system functionally as well as morphologically. The extract was prepared according to the method of Wei. H. et al. The extract was given to two different experimental animal groups with two different doses during 26 consecutive days. After treatment it was found that, the weight of the testis was markedly reduced instead of normal weight gain of all the animals. The sperm count and motility were reduced for the treated groups as compared with control animal group. The enzymes like SGPT and SGOT were as usual and other blood parameters like glucose and protein were also as usual comparing with controlled group. Testosterone level was reduced in the treated groups. FSH and LH levels were also altered accordingly in treated groups. Histological examination showed inhibition of spermatogenesis as evidenced by disintegration of seminiferous tubules of testis. Result of this study showed that GTLE has potent castrative effect on male reproductive system in dose dependent manner. PMID:27073594

  16. Inhibition of Hep G2 hepatic cancer cell growth and CCl₄ induced liver cytotoxicity in Swiss albino mice by Mahua extract.

    PubMed

    Ray, Sudipta; Murmu, Nabendu; Adhikari, Jyotirmay; Bhattacharyya, Sayantan; Adhikari, Sumanto; Banerjee, Samir

    2014-01-01

    Mahua flower extract may provide protective effects against hepatotoxicity. The effect of Mahua flower extract (ME) was investigated on Hep G2 cell line and carbon tetrachloride (CCl4)-induced liver damages in Swiss albino mice. To investigate its cytotoxic effect in liver cancer, Hep G2 cells were treated with different doses of ME, and cell proliferation as well as colony formation assays demonstrated dose-dependent cytotoxicity of ME towards Hep G2 cells in tissue culture. Further gene expression studies showed significant down-regulation of AKT1/2/3, p-AKT, and COX-2 proteins including up-regulation of active caspase-3 in ME treated Hep G2 cells. In in vivo experiments, the mice were pretreated with ME for 15 days. On the 16th day CCl4 was injected intraperitoneally and after 24 h all mice were sacrificed. The antioxidant enzyme activities were measured in liver homogenates. CCl4-induced hepatotoxicity was evidenced by significant increase in lipid peroxidation and decrease in activities of antioxidant enzymes such as GST, GSH, SOD, CAT, and GPx. Histological studies showed CCl4-induced centrilobular necrosis and formation of fatty vacuoles in cirrhotic mice liver. Treatment with ME at a dose of 2 mg and 4 mg/kg exhibited the potential to prevent significant liver toxicity. The expression of active caspase-3 protein was down-regulated in ME treated groups compared to CCl4 exposed animals. This study demonstrated ME mediated antioxidant activity and hepatoprotective effects; therefore it could be used in the future for treating hepatic disorders including liver cancer, especially in combination with chemotherapeutics. PMID:25404377

  17. Electron microscopic ultrastructural study on the toxicological effects of AgNPs on the liver, kidney and spleen tissues of albino mice.

    PubMed

    Ansari, Mohammad Azam; Shukla, Arun Kumar; Oves, Mohammad; Khan, Haris M

    2016-06-01

    The present study deals with the intraperitoneal administration of 500, 1000, 3000, and 5000mg/kg of AgNPs in albino mice for 28 days to evaluate the potential toxicological effects of AgNPs on blood biochemical parameters and to investigate the light and electron microscopic histopathological alterations on three major targets organs i.e., liver, kidney and spleen. The AgNPs was well tolerated and no mortality was observed even at the highest dose i.e., 5000mg/kg. Mice treated with 500 and 1000mg/kg AgNPs did not show significant behavioral, biochemical and ultrastructural pathological changes. Mice treated with 1000mg/kg AgNPs produces little ultrastructural alteration in liver, kidney and spleen. However, mice treated with 3000 and 5000mg/kg AgNPs revealed significant changes in biochemical parameters. Electron microscopic ultrastructural investigation of liver and kidney shows that the administration of 3000 and 5000mg/kg AgNPs revealed irregularity in the nuclear membrane, nuclear chromatin condensations, degenerated hepatocytes, swollen and pleomorphic mitochondria with distorted cristae, extensive dilation of rough endoplasmic reticulum, destructed cytoplasm, hypertrophied and fused podocytes and thickened basement membrane in the endothelial cells of the proximal tubules. The spleen sections at 3000 and 5000mg/kg AgNPs revealed megakaryocytes hyperplasia, lobulations, invaginations and folding of nuclei and nuclear membrane. The present research indicates that AgNPs were well tolerated at the lower doses, but significant alterations in liver, kidney and spleen were observed at the higher doses tested. It is, therefore, suggested that further studies are needed for the minimization of the observed side effects, especially at higher doses before AgNPs being applied in pharmaceutical application. PMID:27100208

  18. Corticosteroids Are Essential for Maintaining Cardiovascular Function in Male Mice.

    PubMed

    Cruz-Topete, Diana; Myers, Page H; Foley, Julie F; Willis, Monte S; Cidlowski, John A

    2016-07-01

    Activation of the hypothalamic-pituitary-adrenal axis results in the release of hormones from the adrenal glands, including glucocorticoids and mineralocorticoids. The physiological association between corticosteroids and cardiac disease is becoming increasingly recognized; however, the mechanisms underlying this association are not well understood. To determine the biological effects of corticosteroids on the heart, we investigated the impact of adrenalectomy in C57BL/6 male mice. Animals were adrenalectomized (ADX) at 1 month of age and maintained for 3-6 months after surgery to evaluate the effects of long-term adrenalectomy on cardiac function. Morphological evaluation suggested that ADX mice showed significantly enlarged hearts compared with age-matched intact controls. These changes in morphology correlated with deficits in left ventricular (LV) function and electrocardiogram (ECG) abnormalities in ADX mice. Correlating with these functional defects, gene expression analysis of ADX hearts revealed aberrant expression of a large cohort of genes associated with cardiac hypertrophy and arrhythmia. Combined corticosterone and aldosterone replacement treatment prevented the emergence of cardiac abnormalities in ADX mice, whereas corticosterone replacement prevented the effects of adrenalectomy on LV function but did not block the emergence of ECG alterations. Aldosterone replacement did not preserve the LV function but prevented ECG abnormalities. Together, the data indicate that adrenal glucocorticoids and mineralocorticoids either directly or indirectly have selective effects in the heart and their signaling pathways are essential in maintaining normal cardiac function. PMID:27219275

  19. Antioxidative and antidiabetic activities of watermelon (Citrullus lanatus) juice on oxidative stress in alloxan-induced diabetic male Wistar albino rats

    PubMed Central

    Oseni, O. A.; Odesanmi, O. E.; Oladele, F. C.

    2015-01-01

    Background: The nutritional and medicinal importance of watermelon has been emphasized and its diseases preventive and curative power must be evaluated. Hence, this study was designed to evaluate the antioxidative and antidiabetic potentials of watermelon. Materials and Methods: The in vivo assay was carried out on 15 male albino rats which were divided into groups of three stages. In stage I, all animals received normal feeds and water for 1-week after, which five animals were selected and sacrificed for biochemical analyses which form the nondiabetic control, group. The remaining animals were fasted for 24 h before injected intra-peritoneally with a freshly prepared solution of alloxan at a dosage of 35 mg/kg body weight. Five out of the 10 rats were sacrificed as diabetic group while last five animals were fed with water melon juice for a week after, which they were sacrificed to form the treated group animals. In all the groups, body weights, fasting blood sugar, total protein level in the blood, and other biochemical parameters such as reduced glutathione (GSH), glutathione peroxidase (GPx), malondialdehyde (MDA) concentration; catalase, and superoxide dismutase (SOD) % inhibition activities were determined. Results: The results of the biochemical analyses showed a significant increase in the concentration of blood glucose level after treatment with alloxan, which indicates that diabetic was induced. Hence, watermelon juice caused increased in weight, hypoglycemia; and increases in GSH, GPx, catalase, and SOD % inhibition activities with reduced MDA concentration after treatments. Conclusion: The watermelon juice resulted in the restoration of impaired conditions of the rats. PMID:26759513

  20. Histological Study on Effect of Mesenchymal Stem Cell Therapy on Experimental Renal Injury Induced by Ischemia/Reperfusion in Male Albino Rat

    PubMed Central

    Sadek, Eman Mostafa; Afifi, Noha Mohamed; Elfattah, Lamiaa Ibrahim Abd; Mohsen, Manal Ali Abd-El

    2013-01-01

    Background and Objectives Acute kidney injury (AKI) represents a major clinical problem with high mortality and limited treatment protocols. This study was planned to evaluate the therapeutic effectiveness of bone marrow - derived mesenchymal stem cells (BM-MSCs) in a rat model of ischemia/reperfusion (I/R) AKI. Methods and Results This study was carried out on thirty adult male albino rats. Animals were divided equally into three groups. Group I (control sham-operated group) (n=10), were subdivided equally into two subgroups; Ia and Ib. The experimental group (n=20) were all subjected to I/R injury by clamping both renal pedicles for 40 minutes. Half of the I/R animals did not receive MSC therapy (group II) [non-MSC treated group]. The other half of the I/R animals received single intravenous injection of PKH26 labelled BM-MSCs immediately after removal of the clamps and visual confirmation of reflow (group III) [MSC treated group]. Animals were sacrificed 24 hrs (subgroups IIa & IIIa) and 72 hrs (subgroups IIb & IIIb) after intervention. Serological measurements included serum urea and creatinine. Kidney specimens were processed for H&E, PAS and PCNA. Mean % of renal corpuscles with affected glomeruli, mean % of affected tubules, mean area % of PAS-positive reaction and mean area % of PCNA immunoreactivity were measured by histomorphometric studies and statistically compared. MSCs-treated group exhibited protection against renal injury serologically and histologically. Conclusions Results of the present study suggest a potential reno-protective capacity of MSCs which could be of considerable therapeutic promise for cell-based management of clinical AKI. PMID:24298374

  1. Effect of Potassium Bromate on the Liver of Adult Male Albino Rat and A Possible Protective Role of Vitamin C: Histological, Immunohistochemical, and Biochemical Study.

    PubMed

    Bayomy, Naglaa A; Soliman, Gehan M; Abdelaziz, Eman Z

    2016-09-01

    Potassium bromate (KBrO3 ) is a food additive which is used primarily as a maturing agent for flour. It is proved as a toxic agent with significant reduction in the activities of antioxidant capacity. The therapeutic efficacy of vitamin C as antioxidant may provide a possible solution to KBrO3 mediated oxidative damage. Twenty four adult male albino rats were used to evaluate the protective role of vitamin C against KBrO3 induced hepatotoxicity and divided into four groups; Group 1 (control), Group 2: received 30 mg/Kg/day vitamin C orally for 4 weeks, Group 3: received 20 mg/Kg/dose KBrO3 orally twice weekly for 4 weeks and Group 4: received both KBrO3 and vitamin C. Liver specimens were processed for histological study by light and electron microscopes and stained immunohistochemically to detect glial fibriller acidic protein (GFAP). Serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were estimated as well as the levels of malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD) activities in all dissected tissues were determined. KBrO3 induced histological alterations in the form of degeneration, cellular infiltration and significant increase in collagen deposition in portal tracts with a significant increase in immunoexpression of GFAP. Significant rise in serum levels of AST, ALT, and MDA in liver tissues were recorded. However, levels of GSH and SOD were significantly decreased. Most of these changes were improved by vitamin C treatment. In conclusion, vitamin C ameliorates the histological and biochemical alterations of the liver induced by KBrO3 . Anat Rec, 299:1256-1269, 2016. © 2016 Wiley Periodicals, Inc. PMID:27373450

  2. Effect of carbon monoxide and nitrogen dioxide on ICR mice

    NASA Technical Reports Server (NTRS)

    Hilado, C. J.; Cumming, H. J.

    1977-01-01

    Times to incapacitation and death and LC(50) values were determined for male ICR mice exposed to different concentration of carbon monoxide for 30 min and of nitrogen dioxide for 10 min in a 4.2 liter hemispherical chamber. The data indicate that ICR mice are more resistant to these two toxicants than Swiss albino mice. The carbon monoxide LC(50) for a 30-min exposure was about 8,000 ppm for ICR mice compared to 3,570 ppm for Swiss albino mice. The nitrogen dioxide LC(50) for a 10-min exposure was above 2,000 ppm for ICR mice compared to about 1,000 ppm for Swiss albino mice.

  3. Lipopolysaccharide Cross-Tolerance Delays Platelet-Activating Factor-Induced Sudden Death in Swiss Albino Mice: Involvement of Cyclooxygenase in Cross-Tolerance

    PubMed Central

    Jacob, Shancy Petsel; Lakshmikanth, Chikkamenahalli Lakshminarayana; Chaithra, Vyala Hanumanthareddy; Kumari, Titus Ruth Shantha; Chen, Chu-Huang; McIntyre, Thomas M.; Marathe, Gopal Kedihitlu

    2016-01-01

    Lipopolysaccharide (LPS) signaling through Toll-like receptor-4 (TLR-4) has been implicated in the pathogenesis of many infectious diseases. Some believe that TLR-mediated pathogenicity is due, in part, to the lipid pro-inflammatory mediator platelet-activating factor (PAF), but this has been questioned. To test the direct contribution of PAF in endotoxemia in murine models, we injected PAF intraperitoneally into Swiss albino mice in the presence and absence of LPS. PAF alone (5 μg/mouse) caused death within 15–20 min, but this could be prevented by pretreating mice with PAF-receptor (PAF-R) antagonists or PAF-acetylhydrolase (PAF-AH). A low dose of LPS (5 mg/kg body wt) did not impair PAF-induced death, whereas higher doses (10 or 20 mg/kg body wt) delayed death, probably via LPS cross-tolerance. Cross-tolerance occurred only when PAF was injected simultaneously with LPS or within 30 min of LPS injection. Tolerance does not appear to be due to an abundant soluble mediator. Histologic examination of lungs and liver and measurement of circulating TNF-α and IL-10 levels suggested that the inflammatory response is not diminished during cross-tolerance. Interestingly, aspirin, a non-specific cyclooxygenase (COX) inhibitor, partially blocked PAF-induced sudden death, whereas NS-398, a specific COX-2 inhibitor, completely protected mice from the lethal effects of PAF. Both COX inhibitors (at 20 mg/kg body wt) independently amplified the cross-tolerance exerted by higher dose of LPS, suggesting that COX-derived eicosanoids may be involved in these events. Thus, PAF does not seem to have a protective role in endotoxemia, but its effects are delayed by LPS in a COX-sensitive way. These findings are likely to shed light on basic aspects of the endotoxin cross-tolerance occurring in many disease conditions and may offer new opportunities for clinical intervention. PMID:27064683

  4. Efficacy of Spirulina platensis in improvement of the reproductive performance and easing teratogenicity in hyperglycemic albino mice

    PubMed Central

    Pankaj, Pranay Punj

    2015-01-01

    Objectives: The present study evaluates the therapeutic efficacy of cell suspension of Spirulina platensis (SP) on estrous cycle, fetal development and embryopathy in alloxan (AXN) induced hyperglycemic mice. Materials and Methods: Diabetes was induced by intra-peritoneal administration of AXN. Mice with blood glucose level above 200 mg/dl were divided into Group I (control), Group II (diabetic control), Group III (diabetic control mice fed with SP), and Group IV (control mice fed with SP). Litter counts, estrous cycles, percent survival of litter, and gestation length were recorded. Results: In hyperglycemic mice, a significant (P < 0.05) increase in duration of diestrus (14.48%), estrus (84.21%), and metestrus (164.15%) with concomitant decrease in proestrus phase by 26.13% was recorded when compared with control. Reduction in litter count and survival of litter was 68.67% and 88.38%, respectively, whereas gestation length increased to 14.51% day in diabetic mice, but recovery in these parameters was observed (P < 0.05) when subjected to SP treatment. SP resulted in increased fertility rate from 77.5% to 82.5% and dropped off resorption of the fetus to 33.73% while the survival rate of offspring of diabetic mice went up to 88.89% from 83.61%. Conclusions: These findings suggest that SP is effective in improving the reproductive performance and easing teratogenic effects in diabetic mice and hence warrants further detailed dose-dependent studies to understand its mechanism of action. PMID:26285837

  5. In Vivo Antiplasmodial and Analgesic Effect of Crude Ethanol Extract of Piper guineense Leaf Extract in Albino Mice

    PubMed Central

    Kabiru, A. Y.; Ibikunle, G. F.; Innalegwu, D. A.; Bola, B. M.; Madaki, F. M.

    2016-01-01

    Antiplasmodial and analgesic effects of crude ethanol extract of Piper guineense was investigated in mice. The antiplasmodial and analgesic efficacy of the extract was judged on its ability to reduce parasitemia and writhing, respectively, in mice. The antiplasmodial screening involved treating infected mice with 200, 400, and 600 mg/kg body weight of extract while the positive control group was given standard artesunate drug. The analgesic test was carried out by administering 1000, 1500, and 2000 mg/kg body weight of extract to three groups of healthy mice, respectively, after induction of pain with 0.75% acetic acid. The positive control group was given aspirin drug. Parasitemia was reduced by 28.36%, 43.28%, and 62.69% in a dose-dependent pattern in the curative test which was significantly different (P < 0.05) from 96.03% of the standard drug. The reduction of writhing by mice given the extract was also dose-dependent (36.29, 45.43, and 59.07%). Aspirin drug was however more effective (86.36%). The extract was safe at 2000 mg/kg body weight. Phytochemical screening revealed the presence of flavonoids, tannins, phlobatannins, terpenoids, and coumarins. Result obtained in this study demonstrated the efficacy of ethanol extract of Piper guineense as an antiplasmodial and analgesic agent. PMID:27446637

  6. Chronic unpredictable stress (CUS) enhances the carcinogenic potential of 7,12-dimethylbenz(a)anthracene (DMBA) and accelerates the onset of tumor development in Swiss albino mice.

    PubMed

    Suhail, Nida; Bilal, Nayeem; Hasan, Shirin; Ahmad, Ausaf; Ashraf, Ghulam Md; Banu, Naheed

    2015-11-01

    Social stressors evolving from individual and population interactions produce stress reactions in many organisms (including humans), influencing homeostasis, altering the activity of the immunological system, and thus leading to various pathological states including cancer and their progression. The present study sought to validate the effectiveness of chronic unpredictable stress (CUS) in cancer promotion and to assess oxidative stress outcomes in terms of various in vivo biochemical parameters, oxidative stress markers, DNA damage, and the development of skin tumors in Swiss albino mice. Animals were randomized into different groups based on their exposure to CUS alone, 7,12-dimethylbenz(a)anthracene (DMBA) alone (topical), and DMBA-12-O-tetradecanoylphorbol-13-acetate (TPA) (topical) and exposure to CUS prior to DMBA or DMBA-TPA treatments and sacrificed after 16 weeks of treatment. Prior exposure to CUS significantly increased the pro-oxidant effect of carcinogen, depicted by compromised levels of antioxidants in the circulation and skin, accompanied by enhanced lipid peroxidation, plasma corticosterone, and marker enzymes as compared to DMBA-alone or DMBA-TPA treatments. DNA damage results corroborated the above biochemical outcomes. Also, the development of skin tumors (in terms of their incidence, tumor yield, and tumor burden) in mice in the presence and absence of stress further strongly supported our above biochemical measurements. CUS may work as a promoter of carcinogenesis by enhancing the pro-oxidant potential of carcinogens. Further studies may be aimed at the development of interventions for disease prevention by identifying the relations between psychological factors and DNA damage. PMID:26272695

  7. Exploring the Potential Role of Chemopreventive Agent, Hesperetin Conjugated Pegylated Gold Nanoparticles in Diethylnitrosamine-Induced Hepatocellular Carcinoma in Male Wistar Albino Rats.

    PubMed

    Gokuladhas, Krishnan; Jayakumar, Subramaniyan; Rajan, Balan; Elamaran, Ramasamy; Pramila, Chengalvarayan Subramani; Gopikrishnan, Mani; Tamilarasi, Sasivarman; Devaki, Thiruvengadam

    2016-04-01

    Liver cancer is the fifth most common cancer and is still one of the leading causes of death world wide, due to food additives, alcohol, fungal toxins, air, toxic industrial chemicals, and water pollutants. Chemopreventive drugs play a potential role in liver cancer treatment. Obviously in the production of anticancer drugs, the factors like poor solubility, bioavailability, biocompatibility, limited chemical stability, large amount of dose etc., plays a major role. Against this backdrop, the idea of designing the chemopreventive nature of bio flavanoid hesperetin (HP) drug conjugated with pegylated gold nanoparticles to increasing the solubility, improve bioavailability and enhance the targeting capabilities of the drug during diethylnitrosamine (DEN) induced liver cancer in male wistar albino rats. The dose fixation studies and the toxicity of pure HP and HP conjugated gold nanoparticles (Au-mPEG(5000)-S-HP) were analysed. After concluded the dose fixation and toxicity studies the experimental design were segregated in six groups for the anticancer analysis of DEN induced HCC for 16 weeks. After the experimental period the body weight, relative liver weight, number of nodules and size of nodules, the levels of tumor markers like CEA, AFP and the level of lipid peroxidation, lipid hydroperoxides and the activities of antioxidant enzymes were assessed. The administration of DEN to rats resulted in increased relative liver weight and serum marker enzymes aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase, and gamma glutamyl transpeptidase. The levels of lipid peroxides elevated (in both serum and tissue) with subsequent decrease in the final body weight and tissue antioxidants like superoxide dismutase, catalase, reduced glutathione, glutathione peroxidise, and glutathione reductase. HP supplementation (20 mg/kg b.wt) significantly attenuated these alterations, thereby showing potent anticancer effect in liver cancer and the

  8. The neural circuits of mating and fighting in male mice.

    PubMed

    Hashikawa, Koichi; Hashikawa, Yoshiko; Falkner, Annegret; Lin, Dayu

    2016-06-01

    Tinbergen proposed that instinctive behaviors can be divided into appetitive and consummatory phases. During mating and aggression, the appetitive phase contains various actions to bring an animal to a social target and the consummatory phase allows stereotyped actions to take place. Here, we summarize recent advances in elucidating the neural circuits underlying the appetitive and consummatory phases of sexual and aggressive behaviors with a focus on male mice. We outline the role of the main olfactory inputs in the initiation of social approach; the engagement of the accessory olfactory system during social investigation, and the role of the hypothalamus and its downstream pathways in orchestrating social behaviors through a suite of motor actions. PMID:26849838

  9. The course of experimental staphylococcus infection in albino mice during action of certain factors of space flight

    NASA Technical Reports Server (NTRS)

    Prokhorov, V. Y.; Shilov, V. M.; Borman, E. A.

    1980-01-01

    A study was made of the effect of certain factors of space flight, acceleration and hypokinesia, on the course of experimental staphylococcus infection in mice. Combined action of hypokinesia and acceleration caused a marked depression of the phagocytic activity of leukocytes and formation of a considerable amount of alpha toxin.

  10. Sub-chronic toxicity of gold nanoparticles in male mice

    PubMed Central

    Ajdary, Marziyeh; Ghahnavieh, Marziyeh Ziaee; Naghsh, Nooshin

    2015-01-01

    Background: Gold nanoparticles have many industrial applications; moreover, they are photothermic agents for clinical treatment of cancer. This study was provided to investigate the effects associated with different doses of applied gold nanoparticles by injection and contact procedures on the alterations of the serum levels and certain factors in male mice. Materials and Methods: 72 male mice were randomly assigned into two protocols in terms of touching and injection. The injection protocol was included of five groups: Sham, control, 25, 50, and 100 ppm. They received gold nanoparticles at 25, 50, and 100 ppm concentrations administered in form of 0.3 ml/day for the period of 14 days and that of touching protocol were received 0.2 ml/day gold nanoparticles. Blood sample of which was taken to measure the serum level of creatine kinase phosphate, fasting blood, creatinine, albumin, blood urea nitrogen and eventually, the kidney was dissected for the intent of pathological analysis. Results: The serum level of creatine kinase phosphate and fasting blood sugar at middle dose was significantly different (P ≤ 0.05) in touching protocol. In both protocols, the serum level of creatinine in high and medium doses showed a significant difference (P < 0.05) associated with the treated group. In the touching method, in high and medium doses administered to the treated group, the alteration was significant (P ≤ 0.05). In the both protocols, the serum level of albumin in high and medium doses of the treated group showed significant difference (P < 0.05). Thus, the gold nanoparticles could result in undesirable effects upon kidney tissue. Conclusion: The result of this study indicated that the administration of gold nanoparticles by touching method was more effective on the serum levels of these factors than that of injection method. PMID:25878992

  11. Evaluation of lemon fruit extract as an antioxidant agent against histopathological changes induced by cyclophosphamide in the testes of albino mice

    PubMed Central

    Quita, Salwa Mohammed

    2016-01-01

    Introduction The aim of this study was to determine the protective effects of lemon fruit extracts (LFE) against histopathological changes induced in the testes of male mice treated with cyclophosphamide (CP). Methods Thirty male mice were divided evenly into six groups: 1) group 1: the controls, 2) group 2: treated with LFE (10 ml/kg b wt.), 3) group 3: treated with CP (10 mg/kg b wt.), 4) group 4: treated with CP (20 mg/kg b wt.), 5) group 5: treated with LFE (10 ml/kg) + CP (10 mg/kg), 6) group 6: treated with LFE (10 ml/kg) + CP (20 mg/kg). Results Histological examination of the testes of mice treated with CP revealed histopathological changes, such as atrophy, degeneration, incomplete spermatogenic series in most seminiferous tubules, and spermatogenic necrosis with pyknotic nuclei. Advanced degree of improvement was seen in testes of mice treated with LFE co-administered with CP. Most of the seminiferous tubules restored their normal structure and spermatogenic layers appeared semi-normal with complete spermatogenic series. Conclusion Lemon fruit extract in conjunction with drug treatment protects the testicular tissue against CP-induced testicular injury in mice. PMID:26955455

  12. Transplantation of male germ line stem cells restores fertility in infertile mice

    PubMed Central

    Ogawa, Takehiko; Dobrinski, Ina; Avarbock, Mary R.

    2016-01-01

    Azoospermia or oligozoospermia due to disruption of spermatogenesis are common causes of human male infertility. We used the technique of spermatogonial transplantation in two infertile mouse strains, Steel (Sl) and dominant white spotting (W), to determine if stem cells from an infertile male were capable of generating spermatogenesis. Transplantation of germ cells from infertile Sl/Sld mutant male mice to infertile W/Wv or Wv/W54 mutant male mice restored fertility to the recipient mice. Thus, transplantation of spermatogonial stem cells from an infertile donor to a permissive testicular environment can restore fertility and result in progeny with the genetic makeup of the infertile donor male. PMID:10613820

  13. COMPETITIVE ABILITY IN MALE HOUSE MICE (Mus musculus): GENETIC INFLUENCES

    PubMed Central

    Cunningham, Christopher B.; Ruff, James S.; Chase, Kevin; Potts, Wayne K.; Carrier, David R.

    2013-01-01

    Conspecifics of many animal species physically compete to gain reproductive resources and thus fitness. Despite the importance of competitive ability across the animal kingdom, specific traits that influence or underpin competitive ability are poorly characterized. Here, we investigate whether there are genetic influences on competitive ability within male house mice. Additionally, we examined if litter demographics (litter size and litter sex ratio) influence competitive ability. We phenotyped two generations for a male s ability to possess a reproductive resource--a prime nesting site--using semi-natural enclosures with mixed sex groupings. We used the animal model coupled with an extensive pedigree to estimate several genetic parameters. Competitive ability was found to be highly heritable, but only displayed a moderate genetic correlation to body mass. Interestingly, litter sex ratio had a weak negative influence on competitive ability. Litter size had no significant influence on competitive ability. Our study also highlights how much remians unknown about the proximal causes of competitive ability. PMID:23291957

  14. Effect of benzene extract of Hibiscus rosa sinensis on the estrous cycle and ovarian activity in albino mice.

    PubMed

    Murthy, D R; Reddy, C M; Patil, S B

    1997-07-01

    The benzene extract of Hibiscus rosa sinensis flowers was administered intraperitoneally at the dose levels of 125 and 250 mg/kg body weight to adult mice and resulted in an irregular estrous cycle with prolonged estrus and metestrus. An increase in the atretic follicles and the absence of corpora lutea indicate the antiovulatory effect of the extract. The extract also showed estrogenic activity in immature mice by early opening of the vagina, premature cornification of the vaginal epithelium and an increase in uterine weight. Therefore the antiovulatory effect may be due to an imbalance in the hormonal environment, as there may be an increase in the endogenous secretion of estrogen by atretic follicles, and also to the estrogenicity of the flower extract. PMID:9255415

  15. The in vivo genotoxicity of cisplatin, isoflurane and halothane evaluated by alkaline comet assay in Swiss albino mice.

    PubMed

    Brozovic, Gordana; Orsolic, Nada; Knezevic, Fabijan; Horvat Knezevic, Anica; Benkovic, Vesna; Sakic, Katarina; Borojevic, Nikola; Dikic, Domagoj

    2011-08-01

    The aim of this study was to evaluate the genotoxicity of repeated exposure to isoflurane or halothane and compare it with the genotoxicity of repeated exposure to cisplatin. We also determined the genotoxicity of combined treatment with inhalation anaesthetics and cisplatin on peripheral blood leucocytes (PBL), brain, liver and kidney cells of mice. The mice were divided into six groups as follows: control, cisplatin, isoflurane, cisplatin-isoflurane, halothane and cisplatin-halothane, and were exposed respectively for three consecutive days. The mice were treated with cisplatin or exposed to inhalation anaesthetic; the combined groups were exposed to inhalation anaesthetic after treatment with cisplatin. The alkaline comet assay was performed. All drugs had a strong genotoxicity (P<0.05 vs. control group) in all of the observed cells. Isoflurane caused stronger DNA damage on the PBL and kidney cells, in contrast to halothane, which had stronger genotoxicity on brain and liver cells. The combination of cisplatin and isoflurane induced lower genotoxicity on PBL than isoflurane alone (P<0.05). Halothane had the strongest effect on brain cells, but in the combined treatment with cisplatin, the effect decreased to the level of cisplatin alone. Halothane also induced the strongest DNA damage of the liver cells, while the combination with cisplatin increased its genotoxicity even more. The genotoxicity of cisplatin and isoflurane on kidney cells were nearly at the same level, but halothane caused a significantly lower effect. The combinations of inhalation anaesthetics with cisplatin had stronger effects on kidney cells than inhalation anaesthetics alone. The observed drugs and their combinations induced strong genotoxicity on all of the mentioned cells. PMID:21509577

  16. Analysis of bacopaside I in biomatrices using liquid chromatography-tandem mass spectrometry: Pharmacokinetics and brain distribution in Swiss-albino mice.

    PubMed

    Bhateria, Manisha; Ramakrishna, Rachumallu; Puttrevu, Santosh Kumar; Singh, Rajbir; Bhatta, Rabi Sankar

    2016-06-01

    Bacopaside I (BP-I) is the major pseudojujubogenin glycoside of Bacopa monniera (BM) extract which has been widely used as a nerve tonic to improve the memory and intellect of human beings from ancient times. A selective and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of BP-I in mouse plasma and brain homogenate has been developed and validated. All biosamples were processed by liquid-liquid extraction and chromatographed on C18- reversed phase column using mobile phase consisting of ammonium acetate (10mM, pH 4) - acetonitrile (10:90, v/v) at a flow rate of 0.5mL/min. The detection was performed in negative electrospray ionization mode and the precursor/product ion transitions of BP-I and internal standard (IS) hydrochlorothiazide were quantified in multiple reaction monitoring (MRM) using QTRAP-5500 MS/MS. The linearity was established over the concentration range of 0.5-2000ng/mL (r(2)>0.990), with lower limit of quantification (LLOQ) of 0.5ng/mL in both plasma and brain matrix. Within- and between-run precision and accuracy were well within the acceptable limits of variation. Consistent and reproducible recovery (>70%) was obtained with insignificant matrix effect for BP-I and IS. The method fulfilled US Food and Drug Administration (USFDA) guidelines for bioanalytical method validation in terms of selectivity, sensitivity, linearity, accuracy, precision, matrix effect, dilution integrity, carry-over effect and stability. Further, the method was successfully applied to execute the plasma pharmacokinetics and brain distribution of BP-I in Swiss-albino mice following intravenous administration at a dose of 5mg/kg. PMID:27017568

  17. Chemopreventive Effect of Cardamom (Elettaria cardamomum L.) Against Benzo(α)Pyrene-Induced Forestomach Papillomagenesis in Swiss Albino Mice.

    PubMed

    Qiblawi, Samir; Dhanarasu, Sasikumar; Faris, Mo'ez Al-Islam

    2015-01-01

    Prevention of cancer through dietary intervention has recently gained significant recognition. Cardamom (Elettaria cardamomum), a dietary phytoproduct, is a popular spice that is regularly used as a flavoring agent in various cuisines, and is much valued for its medicinal properties. In the present study, the cancer chemopreventive potential of cardamom was investigated against benzo(α)pyrene [B(α)P]-induced forestomach papillomagenesis in mice. Results showed that treatment with cardamom [(B(α)P + cardamom] reduced tumor incidence and multiplicity significantly (P<0.001) by 41.67% and 74.55%, respectively, compared to that of the B(α)P control group. Biochemical assays revealed a significant enhancement in the hepatic activities of glutathione-S-transferases (P<0.01), superoxide dismutase (P<0.01), glutathione peroxidase (P<0.001), and catalase (P<0.001) in mice treated with cardamom compared with the control. Furthermore, the nonenzymatic antioxidant glutathione was significantly (P<0.001) increased in the cardamom-treated group, whereas the lipid peroxidation level along with lactate dehydrogenase activity exhibited a significant (P<0.01) reduction with cardamom treatment compared to the control. These results suggest that cardamom has the potential to become a pivotal chemopreventive agent against forestomach cancer. PMID:26081028

  18. The preventive effect of linalool on acute and chronic UVB-mediated skin carcinogenesis in Swiss albino mice.

    PubMed

    Gunaseelan, Srithar; Balupillai, Agilan; Govindasamy, Kanimozhi; Muthusamy, Ganesan; Ramasamy, Karthikeyan; Shanmugam, Mohana; Prasad, N Rajendra

    2016-07-01

    In this study, we evaluated the role of linalool in acute ultraviolet-B (UVB; 280-320 nm) radiation-induced inflammation and chronic UVB-mediated photocarcinogenesis in mouse skin. Acute UVB-irradiation (180 mJ cm(-2)) causes hyperplasia, edema formation, lipid peroxidation, antioxidant depletion, and overexpression of cyclooxygenase-2 (COX-2) and ornithine decarboxylase (ODC) in mouse skin. Topical or intraperitoneal (i.p.) treatment of linalool prevented acute UVB-induced hyperplasia, edema formation, lipid peroxidation, and antioxidant depletion in mouse skin. Further, linalool treatment prevented UVB-induced overexpression of COX-2 and ODC in mouse skin. In the chronic study, mice were subjected to UVB-exposure thrice weekly for 30 weeks. Chronic UVB-exposure induced tumor incidence and expression of proliferative markers such as NF-κB, TNF-α, IL-6, COX-2, VEGF, TGF-β1, Bcl-2 and mutated p53 in mouse skin. Treatment with linalool before each UVB-exposure significantly prevented the expression of these proliferative markers and subsequently decreased the tumor incidence in mice skin. Histopathological studies confirmed the development of dysplasia and squamous cell carcinoma (SCC) in the chronic UVB-exposed mouse skin; and this was prevented by both topical and i.p. linalool treatment. Therefore, linalool may be considered as a photochemopreventive agent against UVB radiation induced skin carcinogenesis. PMID:27251985

  19. Inheritance of steroid-independent male sexual behavior in male offspring of B6D2F1 mice.

    PubMed

    McInnis, Christine M; Bonthuis, Paul J; Rissman, Emilie F; Park, Jin Ho

    2016-04-01

    The importance of gonadal steroids in modulating male sexual behavior is well established. Individual differences in male sexual behavior, independent of gonadal steroids, are prevalent across a wide range of species, including man. However, the genetic mechanisms underlying steroid-independent male sexual behavior are poorly understood. A high proportion of B6D2F1 hybrid male mice demonstrates steroid-independent male sexual behavior (identified as "maters"), providing a mouse model that opens up avenues of investigation into the mechanisms regulating male sexual behavior in the absence of gonadal hormones. Recent studies have revealed several proteins that play a significant factor in regulating steroid-independent male sexual behavior in B6D2F1 male mice, including amyloid precursor protein (APP), tau, and synaptophysin. The specific goals of our study were to determine whether steroid-independent male sexual behavior was a heritable trait by determining if it was dependent upon the behavioral phenotype of the B6D2F1 sire, and whether the differential expression of APP, tau, and synaptophysin in the medial preoptic area found in the B6D2F1 sires that did and did not mate after gonadectomy was similar to those found in their male offspring. After adult B6D2F1 male mice were bred with C57BL/6J female mice, they and their male offspring (BXB1) were orchidectomized and identified as either maters or "non-maters". A significant proportion of the BXB1 maters was sired only from B6D2F1 maters, indicating that the steroid-independent male sexual behavior behavioral phenotype of the B6D2F1 hybrid males, when crossed with C57BL/6J female mice, is inherited by their male offspring. Additionally, APP, tau, and synaptophysin were elevated in in the medial preoptic area in both the B6D2F1 and BXB1 maters relative to the B6D2F1 and BXB1 non-maters, respectively, suggesting a potential genetic mechanism for the inheritance of steroid-independent male sexual behavior. PMID

  20. Repeated administrations of carbon nanotubes in male mice cause reversible testis damage without affecting fertility

    NASA Astrophysics Data System (ADS)

    Bai, Yuhong; Zhang, Yi; Zhang, Jingping; Mu, Qingxin; Zhang, Weidong; Butch, Elizabeth R.; Snyder, Scott E.; Yan, Bing

    2010-09-01

    Soluble carbon nanotubes show promise as materials for in vivo delivery and imaging applications. Several reports have described the in vivo toxicity of carbon nanotubes, but their effects on male reproduction have not been examined. Here, we show that repeated intravenous injections of water-soluble multiwalled carbon nanotubes into male mice can cause reversible testis damage without affecting fertility. Nanotubes accumulated in the testes, generated oxidative stress and decreased the thickness of the seminiferous epithelium in the testis at day 15, but the damage was repaired at 60 and 90 days. The quantity, quality and integrity of the sperm and the levels of three major sex hormones were not significantly affected throughout the 90-day period. The fertility of treated male mice was unaffected; the pregnancy rate and delivery success of female mice that mated with the treated male mice did not differ from those that mated with untreated male mice.

  1. Probiotic use decreases intestinal inflammation and increases bone density in healthy male but not female mice.

    PubMed

    McCabe, Laura R; Irwin, Regina; Schaefer, Laura; Britton, Robert A

    2013-08-01

    Osteoporosis can result from intestinal inflammation, as is seen with inflammatory bowel disease. Probiotics, microorganisms that provide a health benefit to the host when ingested in adequate amounts, can have anti-inflammatory properties and are currently being examined to treat inflammatory bowel disease. Here, we examined if treating healthy male mice with Lactobacillus reuteri ATCC PTA 6475 (a candidate probiotic with anti-TNFα activity) could affect intestinal TNFα levels and enhance bone density. Adult male mice were given L. reuteri 6475 orally by gavage for 3×/week for 4 weeks. Examination of jejunal and ileal RNA profiles indicates that L. reuteri suppressed basal TNFα mRNA levels in the jejunum and ileum in male mice, but surprisingly not in female mice. Next, we examined bone responses. Micro-computed tomography demonstrated that L. reuteri 6475 treatment increased male trabecular bone parameters (mineral density, bone volume fraction, trabecular number, and trabecular thickness) in the distal femur metaphyseal region as well as in the lumbar vertebrae. Cortical bone parameters were unaffected. Dynamic and static histomorphometry and serum remodeling parameters indicate that L. reuteri ingestion increases osteoblast serum markers and dynamic measures of bone formation in male mice. In contrast to male mice, L. reuteri had no effect on bone parameters in female mice. Taken together our studies indicate that femoral and vertebral bone formation increases in response to oral probiotic use, leading to increased trabecular bone volume in male mice. PMID:23389860

  2. Immune responses in male mice with aggressive and submissive behavior patterns: strain differences.

    PubMed

    Devoino, L; Alperina, E; Kudryavtseva, N; Popova, N

    1993-03-01

    Immune responses in two strains of male mice with aggressive and submissive behavior patterns was studied. In aggressive CBA males immunized on the 10th day of agonistic confrontations with submissive partners, greater numbers of plaque-forming cells (PFC) and rosette-forming cells (RFC) were noted compared to control mice. Unlike the CBA strain, both PFC and RFC levels in aggressive C57BL males did not increase, but both PFC and RFC numbers decreased in submissive animals. PMID:8471801

  3. Toxic effects of citrinin on the male reproductive system in mice.

    PubMed

    Qingqing, Han; Linbo, Yu; Yunqian, Guo; Shuqiang, Liu

    2012-07-01

    This study investigated the effects of citrinin (CTN) on male mouse reproductive organs. Adult male mice were exposed to intraperitoneal injection of CTN at 0-6.25 mg/kg body weight daily for 7 days, and then mated with sexually mature untreated female mice. Reproductive organ relative weights, semen quality, serum testosterone concentrations and fertility of treated mice were assessed. CTN significantly increased relative weights of the testes, epididymis, seminal vesicle and preputial gland, increased the number of abnormal spermatozoa and decreased the number of live spermatozoa. A significantly lower pregnancy rate was observed when females were mated with CTN-exposed males. The histological results indicated that distance of testicular seminiferus tubule increased. The sperm count and serum testosterone concentrations were significantly reduced in a dose-dependent manner in mice treated with CTN. The results suggest that CTN has adverse effects on the reproductive system of adult male mice. PMID:21095108

  4. Dominant lethal mutation test in male mice exposed to 900MHz radiofrequency fields.

    PubMed

    Zhu, Shunxing; Zhang, Jie; Liu, Chun; He, Qina; Vijayalaxmi; Prihoda, Thomas J; Tong, Jian; Cao, Yi

    2015-10-01

    Adult male ICR mice were exposed to continuous wave 900MHz radiofrequency fields (RF) at 1.6mW/cm(2) power intensity (whole body average specific absorption rate of 0.731W/kg) for 4 hour/day for 15 days. At the end of exposure, each mouse was caged with 3 mature virgin female mice for mating. After 7 days, each male mouse was transferred to a fresh cage and mated with a second batch of 3 females. This process was repeated for a total of 4 consecutive weeks. Sham exposed male mice and those subjected to an acute 2Gy γ-irradiation (GR) were handled similarly and used as un-exposed and positive controls, respectively. All females were sacrificed on the 18th day of gestation and presumptive mating and, the contents in their uteri were examined. The overall observations during the 4 weeks of mating indicated that the un-exposed female mice mated to RF-exposed male mice showed no significant differences in the percentage of pregnancies, total implants, live implants and dead implants when compared with those mated with sham-exposed mice. In contrast, female mice mated with GR-exposed males showed a consistent pattern of significant differences in the above indices in each and all 4 weeks of mating. Thus, the data indicated an absence of mutagenic potential of RF exposure in the germ cells of male mice. PMID:26433262

  5. Brain serotonin signaling does not determine sexual preference in male mice.

    PubMed

    Angoa-Pérez, Mariana; Herrera-Mundo, Nieves; Kane, Michael J; Sykes, Catherine E; Anneken, John H; Francescutti, Dina M; Kuhn, Donald M

    2015-01-01

    It was reported recently that male mice lacking brain serotonin (5-HT) lose their preference for females (Liu et al., 2011, Nature, 472, 95-100), suggesting a role for 5-HT signaling in sexual preference. Regulation of sex preference by 5-HT lies outside of the well established roles in this behavior established for the vomeronasal organ (VNO) and the main olfactory epithelium (MOE). Presently, mice with a null mutation in the gene for tryptophan hydroxylase 2 (TPH2), which are depleted of brain 5-HT, were tested for sexual preference. When presented with inanimate (urine scents from male or estrous female) or animate (male or female mouse in estrus) sexual stimuli, TPH2-/- males show a clear preference for female over male stimuli. When a TPH2-/- male is offered the simultaneous choice between an estrous female and a male mouse, no sexual preference is expressed. However, when confounding behaviors that are seen among 3 mice in the same cage are controlled, TPH2-/- mice, like their TPH2+/+ counterparts, express a clear preference for female mice. Female TPH2-/- mice are preferred by males over TPH2+/+ females but this does not lead to increased pregnancy success. In fact, if one or both partners in a mating pair are TPH2-/- in genotype, pregnancy success rates are significantly decreased. Finally, expression of the VNO-specific cation channel TRPC2 and of CNGA2 in the MOE of TPH2-/- mice is normal, consistent with behavioral findings that sexual preference of TPH2-/- males for females is intact. In conclusion, 5-HT signaling in brain does not determine sexual preference in male mice. The use of pharmacological agents that are non-selective for the 5-HT neuronal system and that have serious adverse effects may have contributed historically to the stance that 5-HT regulates sexual behavior, including sex partner preference. PMID:25706994

  6. Aggression as Positive Reinforcement in Mice under Various Ratio- and Time-Based Reinforcement Schedules

    ERIC Educational Resources Information Center

    May, Michael E.; Kennedy, Craig H.

    2009-01-01

    There is evidence suggesting aggression may be a positive reinforcer in many species. However, only a few studies have examined the characteristics of aggression as a positive reinforcer in mice. Four types of reinforcement schedules were examined in the current experiment using male Swiss CFW albino mice in a resident-intruder model of aggression…

  7. Elimination of aggressive behavior in male mice lacking endothelial nitric oxide synthase.

    PubMed

    Demas, G E; Kriegsfeld, L J; Blackshaw, S; Huang, P; Gammie, S C; Nelson, R J; Snyder, S H

    1999-10-01

    Male mice with targeted deletion of the gene encoding the neuronal isoform of nitric oxide synthase (nNOS(-/-)) display increased aggressive behavior compared with wild-type (WT) mice. Specific pharmacological inhibition of nNOS with 7-nitroindazole also augments aggressive behavior. We report here that male mice with targeted deletion of the gene encoding endothelial NOS (eNOS(-/-)) display dramatic reductions in aggression. The effects are selective, because an extensive battery of behavioral tests reveals no other deficits. In the resident-intruder model of aggression, resident eNOS(-/-) males show virtually no aggression. Latency for aggression onset is 25-30 times longer in eNOS(-/-) males compared with WT males in the rare instances of aggressive behaviors. Similarly, a striking lack of aggression is noted in tests of aggression among groups of four mice monitored in neutral cages. Although eNOS(-/-) mice are hypertensive ( approximately 14 mmHg blood pressure elevation), hypertension does not appear responsible for the diminished aggression. Reduction of hypertension with hydralazine does not change the prevalence of aggression in eNOS(-/-) mice. Extensive examination of brains from eNOS(-/-) male mice reveals no obvious neural damage from chronic hypertension. In situ hybridization in WT animals reveals eNOS mRNA in the brain associated exclusively with blood vessels and no neuronal localizations. Accordingly, vascular eNOS in the brain appears capable of influencing behavior with considerable selectivity. PMID:10493775

  8. Social isolation prompts maternal behavior in sexually naïve male ddN mice.

    PubMed

    Orikasa, Chitose; Nagaoka, Kentaro; Katsumata, Harumi; Sato, Manami; Kondo, Yasuhiko; Minami, Shiro; Sakuma, Yasuo

    2015-11-01

    Maternal behavior in mice is considered to be sexually dimorphic; that is, females show maternal care for their offspring, whereas this behavior is rarely shown in males. Here, we examined how social isolation affects the interaction of adult male mice with pups. Three weeks of isolation during puberty (5-8 weeks old) induced retrieving and crouching when exposed to pups, while males with 1 week isolation (7-8 weeks old) also showed such maternal care, but were less responsive to pups. We also examined the effect of isolation during young adulthood (8-11 weeks old), and found an induction of maternal behavior comparable to that in younger male mice. This effect was blocked by exposure to chemosensory and auditory social signals derived from males in an attached compartment separated by doubled opaque barriers. These results demonstrate that social isolation in both puberty and postpuberty facilitates male maternal behavior in sexually naïve mice. The results also indicate that air-borne chemicals and/or sounds of male conspecifics, including ultrasonic vocalization and noise by their movement may be sufficient to interfere with the isolation effect on induction of maternal behavior in male mice. PMID:26166155

  9. Protective effect of Tribulus terrestris L. fruit aqueous extracton lipid profile and oxidative stress in isoproterenol induced myocardial necrosis in male albino Wistar rats.

    PubMed

    Sailaja, K V; Shivaranjani, V Leela; Poornima, H; Rahamathulla, S B Md; Devi, K Lakshmi

    2013-01-01

    The objective of the present study was to evaluate the possible protective effects of Tribulus terrestris fruit aqueous extract (TTFAEt) on lipid profile and oxidative stress in isoproterenol (ISO) induced myocardial necrosis in albino Wistar rats. Albino Wistar rats were divided into normal control, TTFAEt alone treated, ISO control and pretreated (TTFAEt+ISO) groups. The extract was administered at a dose of 50 mg/kg body weight for 40 days orally by gavage and ISO was administered at a dose of 85 mg/kg body weight for two consecutive days intraperitoneally at an interval of 24 h. ISO induced myocardial infarction (MI) was confirmed by disturbances in serum lipid profile, heart tissue lipid peroxidation and antioxidant enzyme levels. There was a significant increase in the levels of serum total cholesterol (32.60 %), triglycerides (41.30 %), very low density lipoproteins (81.81 %), low density lipoproteins (84%) and phospholipids (38.88 %) and a significant decrease in the levels of high density lipoproteins (33.33 %) in the ISO control group when compared to normal controls. Additionally, there is a significant decrease in the levels of heart tissue antioxidant enzymes such as superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase and depletion of reduced glutathione, which indicates enhanced lipid peroxidation(172 %). Pretreatment with extract significantly showed a protective effect against ISO altered lipid profile, lipid peroxidation and antioxidant enzyme levels. The present study showed therapeutic effect of TTFAEt on lipid profile and oxidative stress in isoproterenol (ISO) induced myocardial necrosis in experimental rats. PMID:26417233

  10. Female scent mobilizes leukocytes to airways in BALB/c male mice.

    PubMed

    Litvinova, Ekatherina A; Moshkin, Mikhail P; Gerlinskaya, Ludmila A; Nagatomi, Ryoichi; Zhang, Xiumin; Matsuo, Kaori; Shikano, Shuichi

    2009-09-01

    The scent of receptive females as a signal to reproduction stimulates male mice to olfactory search of a potential breeding partner. This searching behavior is coupled with infection risk due to bacterial contamination of the fecal and urine scent marks. We hypothesized that sniffing of female soiled bedding induced the migration of immuno-competent cells into airways as a possible adaptation to breeding-related infection. Using bronchoalveolar lavage in a study on mice, we found the number of leukocytes to be significantly higher in male mice that were provided new portions of soiled bedding daily from female cages, in comparison with male mice that were kept in isolation from female scent. The number of leukocytes in blood was equal in both groups. However, monocytes were fewer in number in male mice exposed to female scent than in male mice isolated from female mice. Scent-induced migration of leukocytes was accompanied by typical behavioral (increased sniffing activity and aggressiveness) and morphological (increase preputial glands and seminal vesicles) responses to olfactory sexual stimulus. PMID:21392301

  11. Effects of α-zearalanol on spermatogenesis and sex hormone levels of male mice

    PubMed Central

    Bo, Cunxiang; Zhao, Wei; Jia, Qiang; Yang, Zhifeng; Sai, Linlin; Zhang, Fang; Du, Zhongjun; Yu, Gongchang; Xie, Lin; Zhang, Zhenling

    2015-01-01

    Aims: To investigate the mechanisms of α-zearalanol (Zeranol)-induced male reproductive toxicity, the effects of Zeranol on spermatogenesis and sex hormone levels of male mice were studied. Methods: Forty healthy sexually mature male Kunming mice were randomly divided into four groups. The mice were mock-treated or treated with Zeranol 25, 50 or 100 mg/kg via oral gavage for 35 days. The epididymal sperms were counted and their morphology and motility were analyzed. The testicles were examined by light and electron microscopy. The levels of serum/testicular testosterone (T), serum follicle stimulating hormone (FSH) and serum luteinizing hormone (LH) were determined by radioimmunoassay. Results: Zeranol decreased the epididymal sperm count and sperm motility in a dose depend manner. While there were not significant differences in the sperm malformation rates between the Zeranol treated groups and the control group. Furthermore, Zeranol could decrease the weight and the organ coefficient of the seminal vesicles and the testicles and lead to significant pathological changes of the testicles. Zeranol could also decrease the levels of serum T, FSH, LH as well as the levels of testicular T of male mice. Conclusions: Zeranol induced reproductive toxicity in adult male mice. It could damage spermatogenesis via its direct effects on the testicles and interfere with sex hormone levels of male mice through its effects on the hypothalamic-pituitary-testicular axis. PMID:26884912

  12. Morphological Alterations in Gastrocnemius and Soleus Muscles in Male and Female Mice in a Fibromyalgia Model

    PubMed Central

    Oezel, Lisa; Schwarzbach, Hans; Ocker, Matthias; Thieme, Kati; Di Fazio, Pietro; Kinscherf, Ralf

    2016-01-01

    Background Fibromyalgia (FM) is a chronic musculoskeletal pain disorder, characterized by chronic widespread pain and bodily tenderness and is often accompanied by affective disturbances, however often with unknown etiology. According to recent reports, physical and psychological stress trigger FM. To develop new treatments for FM, experimental animal models for FM are needed to be development and characterized. Using a mouse model for FM including intermittent cold stress (ICS), we hypothesized that ICS leads to morphological alterations in skeletal muscles in mice. Methods Male and female ICS mice were kept under alternating temperature (4°C/room temperature [22°C]); mice constantly kept at room temperature served as control. After scarification, gastrocnemius and soleus muscles were removed and snap-frozen in liquid nitrogen–cooled isopentane or fixed for electron microscopy. Results In gastrocnemius/soleus muscles of male ICS mice, we found a 21.6% and 33.2% decrease of fiber cross sectional area (FCSA), which in soleus muscle concerns the loss of type IIa and IIx FCSA. This phenomenon was not seen in muscles of female ICS mice. However, this loss in male ICS mice was associated with an increase in gastrocnemius of the density of MIF+ (8.6%)-, MuRF+ (14.7%)-, Fbxo32+ (17.8%)-cells, a 12.1% loss of capillary contacts/muscle fiber as well as a 30.7% increase of damaged mitochondria in comparison with male control mice. Moreover, significant positive correlations exist among densities (n/mm2) of MIF+, MuRF+, Fbxo32+-cells in gastrocnemius/ soleus muscles of male ICS mice; these cell densities inversely correlate with FCSA especially in gastrocnemius muscle of male ICS mice. Conclusion The ICS-induced decrease of FCSA mainly concerns gastrocnemius muscle of male mice due to an increase of inflammatory and atrogenic cells. In soleus muscle of male ICS and soleus/gastrocnemius muscles of female ICS mice morphological alterations seem to occur not at all or

  13. Different immune cells mediate mechanical pain hypersensitivity in male and female mice

    PubMed Central

    Sorge, Robert E.; Mapplebeck, Josiane C.S.; Rosen, Sarah; Beggs, Simon; Taves, Sarah; Alexander, Jessica K.; Martin, Loren J.; Austin, Jean-Sebastien; Sotocinal, Susana G.; Chen, Di; Yang, Mu; Shi, Xiang Qun; Huang, Hao; Pillon, Nicolas J.; Bilan, Philip J.; Tu, Yu Shan; Klip, Amira; Ji, Ru-Rong; Zhang, Ji; Salter, Michael W.; Mogil, Jeffrey S.

    2016-01-01

    A large and rapidly increasing body of evidence indicates that microglia-neuron signaling is essential for chronic pain hypersensitivity. Here we show using multiple approaches that microglia are not required for mechanical pain hypersensitivity in female mice; female mice achieve similar levels of pain hypersensitivity using adaptive immune cells, likely T-lymphocytes. This sexual dimorphism suggests that male mice cannot be used as proxies for females in pain research. PMID:26120961

  14. Sexual experience affects reproductive behavior and preoptic androgen receptors in male mice

    PubMed Central

    Swaney, William T.; Dubose, Brittany N.; Curley, James P.; Champagne, Frances A.

    2012-01-01

    Reproductive behavior in male rodents is made up of anticipatory and consummatory elements which are regulated in the brain by sensory systems, reward circuits and hormone signaling. Gonadal steroids play a key role in the regulation of male sexual behavior via steroid receptors in the hypothalamus and preoptic area. Typical patterns of male reproductive behavior have been characterized, however these are not fixed but are modulated by adult experience. We assessed the effects of repeated sexual experience on male reproductive behavior of C57BL/6 mice; including measures of olfactory investigation of females, mounting, intromission and ejaculation. The effects of sexual experience on the number of cells expressing either androgen receptor (AR) or estrogen receptor alpha (ERα) in the primary brain nuclei regulating male sexual behavior was also measured. Sexually experienced male mice engaged in less sniffing of females before initiating sexual behavior and exhibited shorter latencies to mount and intromit, increased frequency of intromission, and increased duration of intromission relative to mounting. No changes in numbers of ERα-positive cells were observed, however sexually experienced males had increased numbers of AR-positive cells in the medial preoptic area (MPOA); the primary regulatory nucleus for male sexual behavior. These results indicate that sexual experience results in a qualitative change in male reproductive behavior in mice that is associated with increased testosterone sensitivity in the MPOA and that this nucleus may play a key integrative role in mediating the effects of sexual experience on male behavior. PMID:22266118

  15. Individuality and Transgenerational Inheritance of Social Dominance and Sex Pheromones in Isogenic Male Mice.

    PubMed

    Fang, Qi; Zhang, Yao-Hua; Shi, Yao-Long; Zhang, Jin-Hua; Zhang, Jian-Xu

    2016-06-01

    Phenotypic variation and its epigenetic regulations within the inbred isogenic mice have long intrigued biologists. Here, we used inbred C57BL/6 mice to examine the individual differences and the inheritance of social dominance and male pheromones, expecting to create a model for studying the underlying epigenetic mechanisms for the evolution of these traits. We used a repeated male-male contest paradigm to form stable dominance-submission relationships between paired males and make superior or inferior quality manifest. Females showed olfactory preferences for the urine of dominant males to that of subordinate opponents. Gas chromatography-mass spectrometer analysis revealed that dominance-related or superior quality related pheromones were actually exaggerated male pheromone components (e.g., E-β-farnesene, hexadecanol, and 1-hexadecanol acetate) of preputial gland origin. Although the socially naïve sons of both dominant and subordinate males elicited the same female attraction when reaching adulthood, the former could dominated over the latter during undergoing the male-male competition and then gained more attraction of females. Our results demonstrated that social dominance or superior quality and the related pheromones were heritable and could be expressed through the interaction between aggression-related epigenotypes and male-male contests. It suggested that the evolution of sexually selected traits could be epigenetically determined and promoted through female mate choice. The epigenetic mechanisms driving the individual differences in behavior and male pheromones deserve further studies. PMID:27283352

  16. Effects of different forms of environmental enrichment on behavioral, endocrinological, and immunological parameters in male mice.

    PubMed

    Marashi, Vera; Barnekow, Angelika; Ossendorf, Edith; Sachser, Norbert

    2003-02-01

    This study investigated effects of different forms of environmental enrichment on behavioral, endocrinological, and immunological parameters in male mice. For this purpose, animals of the inbred strain CS were kept in groups of four males under three different housing conditions: (A) nonstructured Makrolon type III laboratory cages ("standard-housing" = S); (B) equivalent laboratory cages that were enriched with a box and a scaffolding ("enriched-housing" = E); and (C) spacious terraria that were structured richly ("super-enriched-housing" = SE). Both forms of enrichment caused a sharp rise in aggressive behavior, though play behavior was increased in E and SE mice, too. Levels of sociopositive behaviors in S and SE mice were higher than those in E mice. Plasma corticosterone concentrations and adrenal tyrosine hydroxylase activities were significantly increased in male mice kept in both forms of enriched cages, indicating an activation of the pituitary-adrenocortical and the adrenomedullary systems. The behavioral and endocrinological differences were partly reflected by immunological parameters: SE mice had levels of IgG1 and ratios of IFN-gamma/IL-10 and IL-2/IL-10 significantly lower than those of S mice. Ratios of IgG2a/IgG1 were significantly higher in SE mice. The absolute percentages of CD8 cells in E-mice were significantly lower than those in S mice. Despite the elevated levels of stress hormones under both forms of enriched housing, the behavioral parameters also indicate positive effects of the enrichment, especially on SE animals. Obviously, an environmental enrichment is beneficial for male mice as long as the spatial conditions are generous enough to allow coping with the increased aggression brought about by the enrichment. PMID:12694638

  17. The effect of fat removal on glucose tolerance is depot specific in male and female mice.

    PubMed

    Shi, Haifei; Strader, April D; Woods, Stephen C; Seeley, Randy J

    2007-10-01

    Energy is stored predominately as lipid in white adipose tissue (WAT) in distinct anatomical locations, with each site exerting different effects on key biological processes, including glucose homeostasis. To determine the relative contributions of subcutaneous and visceral WAT on glucose homeostasis, comparable amounts of adipose tissue from abdominal subcutaneous inguinal WAT (IWAT), intra-abdominal retroperitoneal WAT (RWAT), male gonadal epididymal WAT (EWAT), or female gonadal parametrial WAT (PWAT) were removed. Gonadal fat removal in both male and female chow-fed lean mice resulted in lowered glucose levels across glucose tolerance tests. Female lean C57BL/6J mice as well as male and female lean FVBN mice significantly improved glucose tolerance, indicated by decreased areas under glucose clearance curves. For the C57BL/6J mice maintained on a high-fat butter-based diet, glucose homeostasis was improved only in female mice with PWAT removal. Removal of IWAT or RWAT did not affect glucose tolerance in either dietary condition. We conclude that WAT contribution to glucose homeostasis is depot specific, with male gonadal EWAT contributing to glucose homeostasis in the lean state, whereas female gonadal PWAT contributes to glucose homeostasis in both lean and obese mice. These data illustrate both critical differences among various WAT depots and how they influence glucose homeostasis and highlight important differences between males and females in glucose regulation. PMID:17652151

  18. Central adiponectin acutely improves glucose tolerance in male mice.

    PubMed

    Koch, Christiane E; Lowe, Chrishanthi; Legler, Karen; Benzler, Jonas; Boucsein, Alisa; Böttiger, Gregor; Grattan, David R; Williams, Lynda M; Tups, Alexander

    2014-05-01

    Adiponectin, an adipocyte-derived hormone, regulates glucose and lipid metabolism. It is also antiinflammatory. During obesity, adiponectin levels and sensitivity are reduced. Whereas the action of adiponectin in the periphery is well established the neuroendocrine role of adiponectin is largely unknown. To address this we analyzed the expression of adiponectin and the 2 adiponectin receptors (AdipoR1 and AdipoR2) in response to fasting and to diet-induced and genetic obesity. We also investigated the acute impact of adiponectin on central regulation of glucose homeostasis. Adiponectin (1 μg) was injected intracerebroventricularly (ICV), and glucose tolerance tests were performed in dietary and genetic obese mice. Finally, the influence of ICV adiponectin administration on central signaling cascades regulating glucose homeostasis and on markers of hypothalamic inflammation was assessed. Gene expression of adiponectin was down-regulated whereas AdipoR1 was up-regulated in the arcuate nucleus of fasted mice. High-fat (HF) feeding increased AdipoR1 and AdipoR2 gene expression in this region. In mice on a HF diet and in leptin-deficient mice acute ICV adiponectin improved glucose tolerance 60 minutes after injection, whereas normoglycemia in control mice was unaffected. ICV adiponectin increased pAKT, decreased phospho-AMP-activated protein kinase, and did not change phospho-signal transducer and activator of transcription 3 immunoreactivity. In HF-fed mice, ICV adiponectin reversed parameters of hypothalamic inflammation and insulin resistance as determined by the number of phospho-glycogen synthase kinase 3 β(Ser9) and phospho-c-Jun N-terminal kinase (Thr183/Tyr185) immunoreactive cells in the arcuate nucleus and ventromedial hypothalamus. This study demonstrates that the insulin-sensitizing properties of adiponectin are at least partially based on a neuroendocrine mechanism that involves centrally synthesized adiponectin. PMID:24564394

  19. Spectrographic analysis of the ultrasonic vocalisations of adult male and female BALB/c mice

    NASA Astrophysics Data System (ADS)

    Gourbal, Benjamin E. F.; Barthelemy, Mathieu; Petit, Gilles; Gabrion, Claude

    In this study, a spectrographic analysis was designed to improve the description of the shape, the modulations, the rate, length and frequencies of BALB/c mouse calls in different behavioural situations. Male and female calls emitted during investigation of cages with clean bedding, soiled with male or female bedding, and during same-sex encounters, were recorded and described. BALB/c male mice uttered different types of vocalisations both when investigating counterpart odour cues and when interacting with same-sex counterparts. BALB/c female mice vocalised solely during same-sex counterpart encounters and it appeared that calls were uttered mainly by the resident females. Male and female mice present a complex array of calls, which seem to be linked to particular behavioural situations. Further studies using this technology may help to improve our understanding of the role of vocal communication in natural rodent populations.

  20. Castration of male mice prevents the progression of established angiotensin II-induced abdominal aortic aneurysms

    PubMed Central

    Zhang, Xuan; Thatcher, Sean; Wu, Congqing; Daugherty, Alan; Cassis, Lisa A.

    2014-01-01

    Objective Male sex is a non-modifiable risk factor for abdominal aortic aneurysm (AAA) development. Similar to humans, male mice are more susceptible to angiotensin II (AngII)-induced AAAs than females. Previous studies demonstrated that castration of males markedly reduced the formation of AngII-induced AAAs. Progression of AAA size is associated with increased risk of aneurysm rupture. In this study, we hypothesized that castration of male mice would reduce the progression of established AngII-induced AAAs. Methods Male apolipoprotein E (ApoE)-/- mice were infused with AngII for 1 month to induce AAA formation. Aortic diameters were measured by ultrasound and mice were stratified into 2 groups that were either sham-operated or castrated. AngII infusions were continued for a further 2 months. Ultrasound was used to quantify lumen diameters, and excised aortas were processed for quantification of AAA size, volume, and tissue characteristics. Results Sham-operated mice exhibited progressive dilation of suprarenal aortic lumen diameters during continued AngII infusion. Castration significantly decreased aortic lumen diameters (study endpoint: 1.88 ± 0.05 mm vs 1.63 ± 0.04 mm; P<.05; sham-operated [n = 15] vs castration [n = 17], respectively). However, maximal external AAA diameters were not significantly different between sham-operated and castrated mice. The vascular volume/lumen volume ratio of excised AAAs imaged by ultrasound was significantly increased by castration (sham-operated, 4.8 ± 0.9; castration, 9.5 ± 2.0 %; n = 11/group; P<.05). Moreover, compared to thin walled AAAs of sham-operated mice, aneurysm sections from castrated mice exhibited increased smooth muscle -actin and collagen. Conclusions Removal of endogenous male hormones by castration selectively reduces aortic lumen expansion while not altering the external AAA dimensions. PMID:24439319

  1. Exogenous Testosterone, Aging, and Changes in Behavioral Response of Gonadally Intact Male Mice

    PubMed Central

    Onaolapo, Olakunle J.; Onaolapo, Adejoke Y.; Omololu, Tope A.; Oludimu, Adedunke T.; Segun-Busari, Toluwalase; Omoleke, Taofeeq

    2016-01-01

    This study tested the hypothesis that aging significantly affects the influence of exogenous testosterone on neurobehavior in gonadally intact male mice. Groups of prepubertal and aged male mice received daily vehicle or testosterone propionate (TP; 2.5 or 5.0 mg/kg intraperitoneal [i.p.]) for 21 days. Behaviors were assessed on days 1 and 21. Weight gain was significant in prepubertal mice. Locomotion and rearing increased in prepubertal mice after first dose and decreased after last dose of TP. Rearing was suppressed in aged mice throughout. Suppression of grooming occurred in both age groups at day 21. Significant increase in working memory in both age groups was seen in the radial-arm maze (at specific doses) and in prepubertal mice in the Y-maze. Elevated plus maze test showed mixed anxiolytic/anxiogenic effects. Aged mice had higher serum testosterone. In conclusion, age is an important determinant for the influence of exogenous testosterone on behavior in gonadally intact male mice. PMID:27158222

  2. Acute behavioral effects of nicotine in male and female HINT1 knockout mice.

    PubMed

    Jackson, K J; Wang, J B; Barbier, E; Chen, X; Damaj, M I

    2012-11-01

    Human genetic association and brain expression studies, and mouse behavioral and molecular studies implicate a role for the histidine triad nucleotide-binding protein 1 (HINT1) in schizophrenia, bipolar disorder, depression and anxiety. The high comorbidity between smoking and psychiatric disorders, schizophrenia in particular, is well established. Associations with schizophrenia and HINT1 are also sex specific, with effects more predominant in males; however, it is unknown if sex differences associated with the gene extend to other phenotypes. Thus, in this study, using a battery of behavioral tests, we elucidated the role of HINT1 in acute nicotine-mediated behaviors using male and female HINT1 wild-type (+/+) and knockout (-/-) mice. The results show that male HINT1 -/- mice were less sensitive to acute nicotine-induced antinociception in the tail-flick, but not hot-plate test. At low nicotine doses, male and female HINT1 -/- mice were less sensitive to nicotine-induced hypomotility, although the effect was more pronounced in females. Baseline differences in locomotor activity observed in male HINT1 +/+ and -/- mice were absent in females. Nicotine did not produce an anxiolytic effect in male HINT1 -/- mice, but rather an anxiogenic response. Diazepam also failed to induce an anxiolytic response in these mice, suggesting a general anxiety phenotype not specific to nicotine. Differences in anxiety-like behavior were not observed in female mice. These results further support a role for HINT1 in nicotine-mediated behaviors and suggest that alterations in the gene may have differential effects on phenotype in males and females. PMID:22827509

  3. Behavioral transition from attack to parenting in male mice: a crucial role of the vomeronasal system.

    PubMed

    Tachikawa, Kashiko S; Yoshihara, Yoshihiro; Kuroda, Kumi O

    2013-03-20

    Sexually naive male mice show robust aggressive behavior toward pups. However, the proportion of male mice exhibiting pup-directed aggression declines after cohabitation with a pregnant female for 2 weeks after mating. Subsequently, on becoming fathers, they show parental behavior toward pups, similar to maternal behavior by mothers. To elucidate the neural mechanisms underlying this behavioral transition, we examined brain regions differentially activated in sexually naive males and fathers after exposure to pups, using c-Fos expression as a neuronal activation marker. We found that, after pup exposure, subsets of neurons along the vomeronasal neural pathway-including the vomeronasal sensory neurons, the accessory olfactory bulb, the posterior medial amygdala, the medioposterior division of the bed nucleus of stria terminalis, and the anterior hypothalamic area-were more strongly activated in sexually naive males than in fathers. Notably, c-Fos induction was not observed in the vomeronasal sensory neurons of fathers after pup exposure. Surgical ablation of the vomeronasal organ in sexually naive males resulted in the abrogation of pup-directed aggression and simultaneous induction of parental behavior. These results suggest that chemical cues evoking pup-directed aggression are received by the vomeronasal sensory neurons and activate the vomeronasal neural pathway in sexually naive male mice but not in fathers. Thus, the downregulation of pup pheromone-induced activation of the vomeronasal system might be important for the behavioral transition from attack to parenting in male mice. PMID:23516278

  4. Evidence for an audience effect in mice: male social partners alter the male vocal response to female cues.

    PubMed

    Seagraves, Kelly M; Arthur, Ben J; Egnor, S E Roian

    2016-05-15

    Mice (Mus musculus) form large and dynamic social groups and emit ultrasonic vocalizations in a variety of social contexts. Surprisingly, these vocalizations have been studied almost exclusively in the context of cues from only one social partner, despite the observation that in many social species the presence of additional listeners changes the structure of communication signals. Here, we show that male vocal behavior elicited by female odor is affected by the presence of a male audience - with changes in vocalization count, acoustic structure and syllable complexity. We further show that single sensory cues are not sufficient to elicit this audience effect, indicating that multiple cues may be necessary for an audience to be apparent. Together, these experiments reveal that some features of mouse vocal behavior are only expressed in more complex social situations, and introduce a powerful new assay for measuring detection of the presence of social partners in mice. PMID:27207951

  5. [Perinatal clomiphene citrate treatment changes sexual orientations of male mice].

    PubMed

    He, Feng-Qin; Zhang, Heng-Rui

    2013-10-01

    Perinatal period and adolescence are critical for brain development, which is the biological basis of an individual's sexual orientation and sexual behavior. In this study, animals were divided into two groups and their sexual orientations were observed: one group experienced drug treatments during the perinatal period, and the other group was castrated at puberty. The results showed that estradiol treatment had no effect on mature male offspring's sexual orientations, but 9 days and 14 days of clomiphene citrate treatment significantly increased the chance of homosexuality and effeminized behavior. In addition, the sexual orientation of mature normal male offspring, which were castrated when they were 21 days old,was not significant different from the control animals. These findings suggest that the inhibition of perinatal estrogen activities could suppress individual male-typical responses, enhance female-typical responses and induce homosexual orientations. Moreover, the masculinizing effects of estrogen were more obvious during perinatal period than adolescence. PMID:24115661

  6. Male Germline Stem Cells: From Mice to Men

    PubMed Central

    Brinster, Ralph L.

    2016-01-01

    The production of functional male gametes is dependent on the continuous activity of germline stem cells. The availability of a transplantation assay system to unequivocally identify male germline stem cells has allowed their in vitro culture, cryopreservation, and genetic modification. Moreover, the system has enabled the identification of conditions and factors involved in stem cell self-renewal, the foundation of spermatogenesis, and the production of spermatozoa. The increased knowledge about these cells is also of great potential practical value, for example, for the possible cryopreservation of stem cells from boys undergoing treatment for cancer to safeguard their germ line. PMID:17446391

  7. Male mice song syntax depends on social contexts and influences female preferences

    PubMed Central

    Chabout, Jonathan; Sarkar, Abhra; Dunson, David B.; Jarvis, Erich D.

    2015-01-01

    In 2005, Holy and Guo advanced the idea that male mice produce ultrasonic vocalizations (USV) with some features similar to courtship songs of songbirds. Since then, studies showed that male mice emit USV songs in different contexts (sexual and other) and possess a multisyllabic repertoire. Debate still exists for and against plasticity in their vocalizations. But the use of a multisyllabic repertoire can increase potential flexibility and information, in how elements are organized and recombined, namely syntax. In many bird species, modulating song syntax has ethological relevance for sexual behavior and mate preferences. In this study we exposed adult male mice to different social contexts and developed a new approach of analyzing their USVs based on songbird syntax analysis. We found that male mice modify their syntax, including specific sequences, length of sequence, repertoire composition, and spectral features, according to stimulus and social context. Males emit longer and simpler syllables and sequences when singing to females, but more complex syllables and sequences in response to fresh female urine. Playback experiments show that the females prefer the complex songs over the simpler ones. We propose the complex songs are to lure females in, whereas the directed simpler sequences are used for direct courtship. These results suggest that although mice have a much more limited ability of song modification, they could still be used as animal models for understanding some vocal communication features that songbirds are used for. PMID:25883559

  8. Reduced vas deferens contraction and male infertility in mice lacking P2X1 receptors.

    PubMed

    Mulryan, K; Gitterman, D P; Lewis, C J; Vial, C; Leckie, B J; Cobb, A L; Brown, J E; Conley, E C; Buell, G; Pritchard, C A; Evans, R J

    2000-01-01

    P2X1 receptors for ATP are ligand-gated cation channels, present on many excitable cells including vas deferens smooth muscle cells. A substantial component of the contractile response of the vas deferens to sympathetic nerve stimulation, which propels sperm into the ejaculate, is mediated through P2X receptors. Here we show that male fertility is reduced by approximately 90% in mice with a targeted deletion of the P2X1 receptor gene. Male mice copulate normally--reduced fertility results from a reduction of sperm in the ejaculate and not from sperm dysfunction. Female mice and heterozygote mice are unaffected. In P2X1-receptor-deficient mice, contraction of the vas deferens to sympathetic nerve stimulation is reduced by up to 60% and responses to P2X receptor agonists are abolished. These results show that P2X1 receptors are essential for normal male reproductive function and suggest that the development of selective P2X1 receptor antagonists may provide an effective non-hormonal male contraceptive pill. Also, agents that potentiate the actions of ATP at P2X1 receptors may be useful in the treatment of male infertility. PMID:10638758

  9. Severe Brown Fat Lipoatrophy Aggravates Atherosclerotic Process in Male Mice.

    PubMed

    Gómez-Hernández, Almudena; Beneit, Nuria; Escribano, Óscar; Díaz-Castroverde, Sabela; García-Gómez, Gema; Fernández, Silvia; Benito, Manuel

    2016-09-01

    Obesity is one of the major risk factors for the development of cardiovascular diseases and is characterized by abnormal accumulation of adipose tissue, including perivascular adipose tissue (PVAT). However, brown adipose tissue (BAT) activation reduces visceral adiposity. To demonstrate that severe brown fat lipoatrophy might accelerate atherosclerotic process, we generated a new mouse model without insulin receptor (IR) in BAT and without apolipoprotein (Apo)E (BAT-specific IR knockout [BATIRKO];ApoE(-/-) mice) and assessed vascular and metabolic alterations associated to obesity. In addition, we analyzed the contribution of the adipose organ to vascular inflammation. Brown fat lipoatrophy induces visceral adiposity, mainly in gonadal depot (gonadal white adipose tissue [gWAT]), severe glucose intolerance, high postprandial glucose levels, and a severe defect in acute insulin secretion. BATIRKO;ApoE(-/-) mice showed greater hypertriglyceridemia than the obtained in ApoE(-/-) and hypercholesterolemia similar to ApoE(-/-) mice. BATIRKO;ApoE(-/-) mice, in addition to primary insulin resistance in BAT, also showed a significant decrease in insulin signaling in liver, gWAT, heart, aorta artery, and thoracic PVAT. More importantly, our results suggest that severe brown fat lipoatrophy aggravates the atherosclerotic process, characterized by a significant increase of lipid depots, atherosclerotic coverage, lesion size and complexity, increased macrophage infiltration, and proinflammatory markers expression. Finally, an increase of TNF-α and leptin as well as a decrease of adiponectin by BAT, gWAT, and thoracic PVAT might also be responsible of vascular damage. Our results suggest that severe brown lipoatrophy aggravates atherosclerotic process. Thus, BAT activation might protect against obesity and its associated metabolic alterations. PMID:27414981

  10. Urinary Retention, Incontinence, and Dysregulation of Muscarinic Receptors in Male Mice Lacking Mras.

    PubMed

    Ehrhardt, Annette; Wang, Bin; Yung, Andrew C; Wang, Yanni; Kozlowski, Piotr; van Breemen, Cornelis; Schrader, John W

    2015-01-01

    Here we show that male, but not female mice lacking expression of the GTPase M-Ras developed urinary retention with distention of the bladder that exacerbated with age but occurred in the absence of obvious anatomical outlet obstruction. There were changes in detrusor morphology in Mras-/- males: Smooth muscle tissue, which exhibited a compact organization in WT mice, appeared disorganized and became increasingly 'layered' with age in Mras-/- males, but was not fibrotic. Bladder tissue near the apex of bladders of Mras-/- males exhibited hypercontractility in response to the cholinergic agonist carbachol in in vitro, while responses in Mras-/- females were normal. In addition, spontaneous phasic contractions of detrusors from Mras-/- males were increased, and Mras-/- males exhibited urinary incontinence. We found that expression of the muscarinic M2 and M3 receptors that mediate the cholinergic contractile stimuli of the detrusor muscle was dysregulated in both Mras-/- males and females, although only males exhibited a urinary phenotype. Elevated expression of M2R in young males lacking M-Ras and failure to upregulate M3R with age resulted in significantly lower ratios of M3R/M2R expression that correlated with the bladder abnormalities. Our data suggests that M-Ras and M3R are functionally linked and that M-Ras is an important regulator of male bladder control in mice. Our observations also support the notion that bladder control is sexually dimorphic and is regulated through mechanisms that are largely independent of acetylcholine signaling in female mice. PMID:26516777

  11. Urinary Retention, Incontinence, and Dysregulation of Muscarinic Receptors in Male Mice Lacking Mras

    PubMed Central

    Ehrhardt, Annette; Wang, Bin; Yung, Andrew C.; Wang, Yanni; Kozlowski, Piotr; van Breemen, Cornelis; Schrader, John W.

    2015-01-01

    Here we show that male, but not female mice lacking expression of the GTPase M-Ras developed urinary retention with distention of the bladder that exacerbated with age but occurred in the absence of obvious anatomical outlet obstruction. There were changes in detrusor morphology in Mras-/- males: Smooth muscle tissue, which exhibited a compact organization in WT mice, appeared disorganized and became increasingly ‘layered’ with age in Mras-/- males, but was not fibrotic. Bladder tissue near the apex of bladders of Mras-/- males exhibited hypercontractility in response to the cholinergic agonist carbachol in in vitro, while responses in Mras-/- females were normal. In addition, spontaneous phasic contractions of detrusors from Mras-/- males were increased, and Mras-/- males exhibited urinary incontinence. We found that expression of the muscarinic M2 and M3 receptors that mediate the cholinergic contractile stimuli of the detrusor muscle was dysregulated in both Mras-/- males and females, although only males exhibited a urinary phenotype. Elevated expression of M2R in young males lacking M-Ras and failure to upregulate M3R with age resulted in significantly lower ratios of M3R/M2R expression that correlated with the bladder abnormalities. Our data suggests that M-Ras and M3R are functionally linked and that M-Ras is an important regulator of male bladder control in mice. Our observations also support the notion that bladder control is sexually dimorphic and is regulated through mechanisms that are largely independent of acetylcholine signaling in female mice. PMID:26516777

  12. Age and isolation influence steroids release and chemical signaling in male mice.

    PubMed

    Mucignat-Caretta, Carla; Cavaggioni, Andrea; Redaelli, Marco; Da Dalt, Laura; Zagotto, Giuseppe; Gabai, Gianfranco

    2014-05-01

    Social interactions in mice involve olfactory signals, which convey information about the emitter. In turn, the mouse social and physiological status may modify the release of chemical cues. In this study, the influences of age and social isolation on the endocrine response and the release of chemical signals were investigated in male CD1 mice, allocated into four groups: Young Isolated (from weaning till 60days; N=6), Adult Isolated (till 180days; N=6), Young Grouped (6 mice/cage; till 60days; N=18), Adult Grouped (6 mice/cage; till 180days; N=18). Mice were transferred in a clean cage to observe the micturition pattern and then sacrificed. Body and organs weights, serum testosterone, dehydroepiandrosterone, corticosterone and the ratio Major Urinary Protein/creatinine were measured. Urinary volatile molecules potentially involved in pheromonal communication were identified. Androgen secretion was greater in isolated mice (P<0.05), suggesting a greater reactivity of the Hypothalamic-Pituitary-Gonadal axis. Grouped mice presented a higher degree of adrenal activity, and young mice showed a higher serum corticosterone (P<0.05) suggesting a greater stimulation of the Hypothalamic-Pituitary-Adrenal axis. The micturition pattern typical of dominant male, consisting in voiding numerous droplets, was observed in Young Isolated mice only, which showed a higher protein/creatinine ratio (P<0.05). Urinary 2-s-butyl-thiazoline was higher in both Young and Adult Isolated mice (P<0.005). Young Isolated mice showed the most prominent difference in both micturition pattern and potentially active substance emission, while long term isolation resulted in a less extreme phenotype; therefore social isolation had a higher impact on young mice hormone and pheromone release. PMID:24525008

  13. Deficiency of angiotensinogen in hepatocytes markedly decreases blood pressure in lean and obese male mice.

    PubMed

    Yiannikouris, Frederique; Wang, Yu; Shoemaker, Robin; Larian, Nika; Thompson, Joel; English, Victoria L; Charnigo, Richard; Su, Wen; Gong, Ming; Cassis, Lisa A

    2015-10-01

    We recently demonstrated that adipocyte deficiency of angiotensinogen (AGT) ablated high-fat diet-induced elevations in plasma angiotensin II (Ang II) concentrations and obesity-hypertension in male mice. Hepatocytes are the predominant source of systemic AGT. Therefore, in this study, we defined the contribution of hepatocyte-derived AGT to obesity-induced elevations in plasma AGT concentrations and hypertension. Male Agt(fl/fl) mice expressing albumin-driven Cre recombinase were bred to female Agt(fl/fl) mice to generate Agt(fl/fl) or hepatocyte AGT-deficient male mice (Agt(Alb)). Mice were fed a low-fat or high-fat diet for 16 weeks. Hepatocyte AGT deficiency had no significant effect on body weight. Plasma AGT concentrations were increased in obese Agt(fl/fl) mice. Hepatocyte AGT deficiency markedly reduced plasma AGT and Ang II concentrations in lean and obese mice. Moreover, hepatocyte AGT deficiency reduced the content and release of AGT from adipose explants. Systolic blood pressure was markedly decreased in lean (by 18 mm Hg) and obese Agt(Alb) mice (by 54 mm Hg) compared with Agt(fl/fl) controls. To define mechanisms, we quantified effects of Ang II on mRNA abundance of megalin, an AGT uptake transporter, in 3T3-L1 adipocytes. Ang II stimulated adipocyte megalin mRNA abundance and decreased media AGT concentrations. These results demonstrate that hepatocytes are the predominant source of systemic AGT in both lean and obese mice. Moreover, reductions in plasma angiotensin concentrations in obese hepatocyte AGT-deficient mice may have limited megalin-dependent uptake of AGT into adipocytes for the production of Ang II in the development of obesity-hypertension. PMID:26303292

  14. Mice do not habituate to metabolism cage housing--a three week study of male BALB/c mice.

    PubMed

    Kalliokoski, Otto; Jacobsen, Kirsten R; Darusman, Huda S; Henriksen, Trine; Weimann, Allan; Poulsen, Henrik E; Hau, Jann; Abelson, Klas S P

    2013-01-01

    The metabolism cage is a barren, non-enriched, environment, combining a number of recognized environmental stressors. We investigated the ability of male BALB/c mice to acclimatize to this form of housing. For three weeks markers of acute and oxidative stress, as well as clinical signs of abnormality were monitored. Forced swim tests were conducted to determine whether the animals experienced behavioral despair and the serotonergic integrity was tested using an 8-OH-DPAT challenge. The metabolism cage housed mice excreted approximately tenfold higher amounts of corticosterone metabolites in feces throughout the study when compared to controls. Urinary biomarkers confirmed that these mice suffered from elevated levels of oxidative stress, and increased creatinine excretions indicated increased muscle catabolism. Changes in the core body temperature (stress-induced hyperthermia) and the fur state of the mice also indicated impaired well-being in the metabolism cage housed mice. However, monitoring body weight and feed intake was found misleading in assessing the wellbeing of mice over a longer time course, and the forced swim test was found poorly suited for studying chronic stress in mice in the present setup. In conclusion, the mice were found not to acclimatize to the metabolism cages whereby concern for animal welfare would dictate that mice should be housed in this way for as short periods as possible. The elevated degree of HPA axis activity, oxidative stress, and increased overall metabolism warrant caution when interpreting data obtained from metabolism cage housed mice, as their condition cannot be considered representative of a normal physiology. PMID:23505511

  15. Foxn1 gene knockout suppresses sexual attractiveness and pheromonal components of male urine in inbred mice.

    PubMed

    Zhang, Jian-Xu; Sun, Lixing; Zhang, Yao-Hua

    2010-01-01

    The immunocompetence handicap hypothesis (ICHH) posits that females prefer signals emitted by immunocompetent males over immunocompromised males and that these signals are honest. However, mechanisms of mate choice under an ICHH model may be impacted by levels of genetic variation (inbred animals vs. outbred animals). Here, we conducted 2-choice female preference experiments and chemical analyses of male urine in inbred BALB/c and outbred CD-1 mice, both of which have immunocompromised nude (nu) strains resulting from a Foxn1 gene knockout. We found that inbred BALB/c females but not outbred CD-1 females preferred the urine of healthy males over that of immunocompromised males despite measured differences in the qualities of their urine. There was a clear increase in female-attracting pheromones (such as farnesenes) in the preputial glands and urine metabolites in healthy BALB/c males but no such difference between CD-1 and CD-1 nu males. Therefore, CD-1 male urine failed to provide an honest mate-choice cue for females. Our results suggest that deleterious traits associated with male odor in mice might be jointly affected by the level of inbreeding and immunodeficiency caused by a single-gene knockout. PMID:20019156

  16. Effects of environmental enrichment on males of a docile inbred strain of mice.

    PubMed

    Marashi, Vera; Barnekow, Angelika; Sachser, Norbert

    2004-10-15

    Environmental enrichment is intended to improve the welfare of laboratory animals. However, regarding male mice, numerous studies indicate an increase in aggressive behavior due to cage structuring. On the one hand, this might be a problem concerning animal welfare. On the other hand, enrichment is though to hamper environmental standardization and to increase variability of data. Furthermore, increasing fights, arousal, and/or injury in enriched housed animals might superimpose other (positive) environmental effects on behavior and physiology. Therefore, the present study investigated effects of environmental enrichment on behavioral, endocrinological, and immunological parameters in male mice of the docile inbred strain ABG. From weaning until day 77+/-3 of life, animals were kept in stable sibling groups of four under three different housing conditions: (A) nonstructured Makrolon type III laboratory cages ("standard housing"=S); (B) equivalent laboratory cages that were enriched with a box and scaffolding ("enriched housing"=E); and (C) spacious terrariums that were structured richly ("super-enriched housing"=SE). No differences in agonistic behavior, levels of plasma corticosterone (CORT), and activities of adrenal tyrosine hydroxylase (TH) existed among S-, E-, and SE-housed ABG males. Play behavior and general activity increased significantly with increasing enrichment. Concerning immunological parameters, males of both forms of enriched housing showed significantly lower percentages of CD4 and CD8 cells compared to S-housed mice. However, regarding the ratio of CD4/CD8 cells, IL-2, IL-4, IL-10, IFN-gamma, IgG1, and IgG2a, no significant housing-dependent differences were found. Enrichment did neither hamper standardization nor negatively influence the variability of physiological parameters. In summary, using a docile strain of mice revealed the positive effects of environmental enrichment also on male mice. The lack of adverse effects on behavior

  17. Curcumin improves liver damage in male mice exposed to nicotine

    PubMed Central

    Salahshoor, Mohammadreza; Mohamadian, Sabah; Kakabaraei, Seyran; Roshankhah, Shiva; Jalili, Cyrus

    2015-01-01

    The color of turmeric (薑黃 jiāng huáng) is because of a substance called curcumin. It has different pharmacological effects, such as antioxidant and anti-inflammatory properties. Nicotine is a major pharmacologically active substance in cigarette smoke. It is mainly metabolized in the liver and causes devastating effects. This study was designed to evaluate the protective role of curcumin against nicotine on the liver in mice. Forty-eight mice were equally divided into eight groups; control (normal saline), nicotine (2.5 mg/kg), curcumin (10, 30, and 60 mg/kg) and curcumin plus nicotine-treated groups. Curcumin, nicotine, and curcumin plus nicotine (once a day) were intraperitoneally injected for 4 weeks. The liver weight and histology, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and serum nitric oxide levels have been studied. The results indicated that nicotine administration significantly decreased liver weight and increased the mean diameter of hepatocyte, central hepatic vein, liver enzymes level, and blood serum nitric oxide level compared with the saline group (p < 0.05). However, curcumin and curcumin plus nicotine administration substantially increased liver weight and decreased the mean diameter of hepatocyte, central hepatic vein, liver enzymes, and nitric oxide levels in all groups compared with the nicotine group (p < 0.05). Curcumin demonstrated its protective effect against nicotine-induced liver toxicity. PMID:27114942

  18. Curcumin improves liver damage in male mice exposed to nicotine.

    PubMed

    Salahshoor, Mohammadreza; Mohamadian, Sabah; Kakabaraei, Seyran; Roshankhah, Shiva; Jalili, Cyrus

    2016-04-01

    The color of turmeric ( jiāng huáng) is because of a substance called curcumin. It has different pharmacological effects, such as antioxidant and anti-inflammatory properties. Nicotine is a major pharmacologically active substance in cigarette smoke. It is mainly metabolized in the liver and causes devastating effects. This study was designed to evaluate the protective role of curcumin against nicotine on the liver in mice. Forty-eight mice were equally divided into eight groups; control (normal saline), nicotine (2.5 mg/kg), curcumin (10, 30, and 60 mg/kg) and curcumin plus nicotine-treated groups. Curcumin, nicotine, and curcumin plus nicotine (once a day) were intraperitoneally injected for 4 weeks. The liver weight and histology, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and serum nitric oxide levels have been studied. The results indicated that nicotine administration significantly decreased liver weight and increased the mean diameter of hepatocyte, central hepatic vein, liver enzymes level, and blood serum nitric oxide level compared with the saline group (p < 0.05). However, curcumin and curcumin plus nicotine administration substantially increased liver weight and decreased the mean diameter of hepatocyte, central hepatic vein, liver enzymes, and nitric oxide levels in all groups compared with the nicotine group (p < 0.05). Curcumin demonstrated its protective effect against nicotine-induced liver toxicity. PMID:27114942

  19. Attenuation of Cocaine-Induced Locomotor Activity in Male and Female Mice by Active Immunization

    PubMed Central

    Kosten, Therese A.; Shen, Xiaoyun Y.; Kinsey, Berma M.; Kosten, Thomas R.; Orson, Frank M.

    2014-01-01

    Background and objectives Immunotherapy for drug addiction is being investigated in several laboratories but most studies are conducted in animals of one sex. Yet, women show heightened immune responses and are more likely to develop autoimmune diseases than men. The purpose of this study was to compare the effects of an active anti-cocaine vaccine, succinyl-norcocaine conjugated to keyhole limpet hemocyanin, for its ability to elicit antibodies and alter cocaine-induced ambulatory activity in male versus female mice. Methods Male and female BALB/c mice were vaccinated (n=44) or served as non-vaccinated controls (n=34). Three weeks after initial vaccination, a booster was given. Ambulatory activity induced by cocaine (20 mg/kg) was assessed at 7-wk and plasma obtained at 8-wk to assess antibody levels. Results High antibody titers were produced in mice of both sexes. The vaccine reduced ambulatory activity cocaine-induced but this effect was greater in female compared to male mice. Discussion and conclusions The efficacy of this anti-cocaine vaccine is demonstrated in mice of both sexes but its functional consequences are greater in females than males. Scientific significance Results point to the importance of testing animals of both sexes in studies of immunotherapies for addiction. PMID:25251469

  20. Male Men1 heterozygous mice exhibit fasting hyperglycemia in the early stage of MEN1.

    PubMed

    Gao, Zhongxiuzi; Zhang, Li; Xie, Wenting; Wang, Siqi; Bao, Xiaorui; Guo, Yuli; Zhang, Houjian; Hu, Qingzhong; Chen, Yi; Wang, Zeen; Xue, Maoqiang; Jin, Guanghui

    2016-09-01

    Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant inherited syndrome characterized by multiple tumors in the parathyroid glands, endocrine pancreas and anterior pituitary. Recent clinical studies have revealed a strong association between MEN1 syndrome and the risk of developing diabetes mellitus; however, the underlying mechanisms remain unknown. In this study, heterozygous Men1 knockout (Men1(+/-)) mice were used as MEN1 models to investigate MEN1-associated glucose metabolic phenotypes and mechanisms. Heterozygous deficiency of Men1 in 12-month-old male mice induced fasting hyperglycemia, along with increased serum insulin levels. However, male Men1(+/-) mice did not show insulin resistance, as evidenced by Akt activation in hepatic tissues and an insulin tolerance test. Increased glucose levels following pyruvate challenge and expression of key gluconeogenic genes suggested increased hepatic glucose output in the male Men1(+/-) mice. This effect could be partly due to higher basal serum glucagon levels, which resulted from pancreatic islet cell proliferation induced by heterozygous loss of Men1 Taken together, our results indicate that fasted male Men1(+/-) mice, in the early stage of development of MEN1, display glucose metabolic disorders. These disorders are caused not by direct induction of insulin resistance, but via increased glucagon secretion and the consequent stimulation of hepatic glucose production. PMID:27432891

  1. Incidence of plutonium-induced bone cancer in neutered mice

    SciTech Connect

    Taylor, G.N.; Gardner, P.; Mays, C.W.; Wrenn, M.E.; Charrier, K.

    1981-03-01

    The incidence of bone cancer, after a single i.p. injection of monomeric /sup 239/Pu citrate, is significantly higher in female than in male mice. To evaluate the role of the gonads in this sex-related difference, male and female C57BL/Do (albino) mice were castrated at 40 days of age. Fifty days later, they were given injections of /sup 239/Pu. After castration, the frequency of bone sarcomas in the two sexes was approximately equal. This resulted from an increased incidence in the castrated males and a decreased incidence in the ovariectomized females as compared to the intact plutonium-treated mice.

  2. Spirulina maxima prevents fatty liver formation in CD-1 male and female mice with experimental diabetes.

    PubMed

    Rodríguez-Hernández, A; Blé-Castillo, J L; Juárez-Oropeza, M A; Díaz-Zagoya, J C

    2001-07-20

    The dietary administration of 5% Spirulina maxima (SM) during four weeks to diabetic mice, starting one week after a single dose of alloxan, 250 mg/Kg body weight, prevented fatty liver production in male and female animals. The main action of SM was on triacylglycerol levels in serum and liver. There was also a moderate hypoglycemia in male mice. The thiobarbituric acid reactive substances also decreased in serum and liver after SM administration. There was also a decrease in the percentage of HDL in diabetic mice that was reverted by the SM administration. The sum of LDL + VLDL percentages was also partially normalized in diabetic animals by the SM administration. An additional observation was the lower incidence of adherences between the liver and the intestine loops in the diabetic mice treated with SM compared with diabetic mice without SM. Male and female mice showed differences to diabetes susceptibility and response to SM, the female being more resistant to diabetes induction by alloxan and more responsive to the beneficial effects of SM. It is worth future work of SM on humans looking for better quality of life and longer survival of diabetic patients. PMID:11508645

  3. [Mutagenic effect of human adenovirus type I on the somatic and sex cells of male mice].

    PubMed

    Podol'skaia, S V

    1986-01-01

    Human adenovirus 1 was studied for its effect on the chromosomal apparatus both in bone marrow cells and male sex cells of mice. Chromosome aberrations were most early detected in spermatocytes of the 1st order mice infected with human adenovirus 1. In bone marrow cells of mice the highest level of chromosome aberrations was observed 30, 60, 90 days after the inoculation, which corresponds to a more frequent detection of the adenoviral antigen. The UV-irradiated-virus caused chromosome aberrations in the later periods after the inoculation which might be induced by the virus reactivation in a cell. PMID:3705168

  4. A Vasoactive Role for Endogenous Relaxin in Mesenteric Arteries of Male Mice

    PubMed Central

    Gooi, Jon H.; Tare, Marianne; Parry, Laura J.

    2014-01-01

    The peptide hormone relaxin has striking effects on the vascular system. Specifically, endogenous relaxin treatment reduces myogenic reactivity through nitric oxide (NO)-mediated vasorelaxation and increases arterial compliance in small resistance arteries. However, less is known about the vascular roles of endogenous relaxin, particularly in males. Therefore, we used male wild-type (Rln+/+) and relaxin knockout (Rln−/−) mice to test the hypothesis that passive wall properties and vascular reactivity in mesenteric arteries would be compromised in Rln−/− mice. Passive compliance was determined in arteries (n = 8–9) mounted on a pressure myograph and in Ca2+-free Krebs containing 2 mM EGTA. Passive volume compliance was significantly (P = 0.01) decreased in the mesenteric arteries of Rln−/− mice. Vascular reactivity was assessed using wire myography. In mesenteric arteries (n = 5) of Rln−/− mice, there was a significant (P<0.03) increase in sensitivity to the vasoconstrictors phenylephrine and thromboxane-mimetic U41669. This enhanced responsiveness to vasoconstrictors was abolished by endothelial denudation, and attributed to impaired NO and prostanoid pathways in Rln−/− mice. Sensitivity to the endothelial agonist acetylcholine was significantly (n = 7–9, P≤0.03) decreased, and this was abolished in the presence of the cyclooxygenase inhibitor, indomethacin (2 µM). This indicates that prostanoid vasoconstrictor pathways were upregulated in the mesenteric arteries of Rln−/− mice. In summary, we demonstrate endothelial dysfunction and impaired arterial wall remodeling in male mice deficient in relaxin. Thus, our results highlight a role for endogenous relaxin in the maintenance of normal mesenteric artery structure and function in males. PMID:25243460

  5. Overexpression of PRL7D1 in Leydig Cells Causes Male Reproductive Dysfunction in Mice.

    PubMed

    Liu, Yaping; Su, Xingyu; Hao, Jie; Chen, Maoxin; Liu, Weijia; Liao, Xiaogang; Li, Gang

    2016-01-01

    Prolactin family 7, subfamily d, member 1 (PRL7D1) is found in mouse placenta. Our recent work showed that PRL7D1 is also present in mouse testis Leydig cells, and the expression of PRL7D1 in the testis exhibits an age-related increase. In the present study, we generated transgenic mice with Leydig cell-specific PRL7D1 overexpression to explore its function during male reproduction. Prl7d1 male mice exhibited subfertility as reflected by reduced sperm counts and litter sizes. The testes from Prl7d1 transgenic mice appeared histologically normal, but the frequency of apoptotic germ cells was increased. Prl7d1 transgenic mice also had lower testosterone concentrations than wild-type mice. Mechanistic studies revealed that Prl7d1 transgenic mice have defects in the testicular expression of steroidogenic acute regulatory protein (STAR) and hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase cluster (HSD3B). Further studies revealed that PRL7D1 overexpression affected the expression of transferrin (TF) in Sertoli cells. These results suggest that PRL7D1 overexpression could lead to increased germ cell apoptosis and exert an inhibitory effect on testosterone production in Leydig cells by reducing the expression of certain steroidogenic-related genes. In addition, PRL7D1 appears to have important roles in the function of Sertoli cells, which, in turn, affects male fertility. We conclude that the expression level of PRL7D1 is associated with the reproductive function of male mice. PMID:26771609

  6. Overexpression of PRL7D1 in Leydig Cells Causes Male Reproductive Dysfunction in Mice

    PubMed Central

    Liu, Yaping; Su, Xingyu; Hao, Jie; Chen, Maoxin; Liu, Weijia; Liao, Xiaogang; Li, Gang

    2016-01-01

    Prolactin family 7, subfamily d, member 1 (PRL7D1) is found in mouse placenta. Our recent work showed that PRL7D1 is also present in mouse testis Leydig cells, and the expression of PRL7D1 in the testis exhibits an age-related increase. In the present study, we generated transgenic mice with Leydig cell-specific PRL7D1 overexpression to explore its function during male reproduction. Prl7d1 male mice exhibited subfertility as reflected by reduced sperm counts and litter sizes. The testes from Prl7d1 transgenic mice appeared histologically normal, but the frequency of apoptotic germ cells was increased. Prl7d1 transgenic mice also had lower testosterone concentrations than wild-type mice. Mechanistic studies revealed that Prl7d1 transgenic mice have defects in the testicular expression of steroidogenic acute regulatory protein (STAR) and hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase cluster (HSD3B). Further studies revealed that PRL7D1 overexpression affected the expression of transferrin (TF) in Sertoli cells. These results suggest that PRL7D1 overexpression could lead to increased germ cell apoptosis and exert an inhibitory effect on testosterone production in Leydig cells by reducing the expression of certain steroidogenic-related genes. In addition, PRL7D1 appears to have important roles in the function of Sertoli cells, which, in turn, affects male fertility. We conclude that the expression level of PRL7D1 is associated with the reproductive function of male mice. PMID:26771609

  7. Chronic stress does not further exacerbate the abnormal psychoneuroendocrine phenotype of Cbg-deficient male mice.

    PubMed

    de Medeiros, Gabriela F; Minni, Amandine M; Helbling, Jean-Christophe; Moisan, Marie-Pierre

    2016-08-01

    Chronic stress leads to a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis which can constitute a base for pathophysiological consequences. Using mice totally deficient in Corticosteroid binding globulin (CBG), we have previously demonstrated the important role of CBG in eliciting an adequate response to an acute stressor. Here, we have studied its role in chronic stress situations. We have submitted Cbg ko and wild-type (WT) male mice to two different chronic stress paradigms - the unpredictable chronic mild stress and the social defeat. Then, their impact on neuroendocrine function - through corticosterone and CBG measurement - and behavioral responses - via anxiety and despair-like behavioral tests - was evaluated. Both chronic stress paradigms increased the display of despair-like behavior in WT mice, while that from Cbg ko mice - which was already high - was not aggravated. We have also found that control and defeated (stressed) Cbg ko mice show no difference in the social interaction test, while defeated WT mice reduce their interaction time when compared to unstressed WT mice. Interestingly, the same pattern was observed for corticosterone levels, where both chronic stress paradigms lowered the corticosterone levels of WT mice, while those from Cbg ko mice remained low and unaltered. Plasma CBG binding capacity remained unaltered in WT mice regardless of the stress paradigm. Through the use of the Cbg ko mice, which only differs genetically from WT mice by the absence of CBG, we demonstrated that CBG is crucial in modulating the effects of stress on plasma corticosterone levels and consequently on behavior. In conclusion, individuals with CBG deficiency, whether genetically or environmentally-induced, are vulnerable to acute stress but do not have their abnormal psychoneuroendocrine phenotype further affected by chronic stress. PMID:27153522

  8. Mild pituitary phenotype in 3- and 12-month-old Aip-deficient male mice.

    PubMed

    Lecoq, Anne-Lise; Zizzari, Philippe; Hage, Mirella; Decourtye, Lyvianne; Adam, Clovis; Viengchareun, Say; Veldhuis, Johannes D; Geoffroy, Valérie; Lombès, Marc; Tolle, Virginie; Guillou, Anne; Karhu, Auli; Kappeler, Laurent; Chanson, Philippe; Kamenický, Peter

    2016-10-01

    Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene predispose humans to pituitary adenomas, particularly of the somatotroph lineage. Mice with global heterozygous inactivation of Aip (Aip(+/-)) also develop pituitary adenomas but differ from AIP-mutated patients by the high penetrance of pituitary disease. The endocrine phenotype of these mice is unknown. The aim of this study was to determine the endocrine phenotype of Aip(+/-) mice by assessing the somatic growth, ultradian pattern of GH secretion and IGF1 concentrations of longitudinally followed male mice at 3 and 12 months of age. As the early stages of pituitary tumorigenesis are controversial, we also studied the pituitary histology and somatotroph cell proliferation in these mice. Aip(+/-) mice did not develop gigantism but exhibited a leaner phenotype than wild-type mice. Analysis of GH pulsatility by deconvolution in 12-month-old Aip(+/-) mice showed a mild increase in total GH secretion, a conserved GH pulsatility pattern, but a normal IGF1 concentration. No pituitary adenomas were detected up to 12 months of age. An increased ex vivo response to GHRH of pituitary explants from 3-month-old Aip(+/-) mice, together with areas of enlarged acini identified on reticulin staining in the pituitary of some Aip(+/-) mice, was suggestive of somatotroph hyperplasia. Global heterozygous Aip deficiency in mice is accompanied by subtle increase in GH secretion, which does not result in gigantism. The absence of pituitary adenomas in 12-month-old Aip(+/-) mice in our experimental conditions demonstrates the important phenotypic variability of this congenic mouse model. PMID:27621108

  9. The SocioBox: A Novel Paradigm to Assess Complex Social Recognition in Male Mice

    PubMed Central

    Krueger-Burg, Dilja; Winkler, Daniela; Mitkovski, Mišo; Daher, Fernanda; Ronnenberg, Anja; Schlüter, Oliver M.; Dere, Ekrem; Ehrenreich, Hannelore

    2016-01-01

    Impairments in social skills are central to mental disease, and developing tools for their assessment in mouse models is essential. Here we present the SocioBox, a new behavioral paradigm to measure social recognition. Using this paradigm, we show that male wildtype mice of different strains can readily identify an unfamiliar mouse among 5 newly acquainted animals. In contrast, female mice exhibit lower locomotor activity during social exploration in the SocioBox compared to males and do not seem to discriminate between acquainted and unfamiliar mice, likely reflecting inherent differences in gender-specific territorial tasks. In addition to a simple quantification of social interaction time of mice grounded on predefined spatial zones (zone-based method), we developed a set of unbiased, data-driven analysis tools based on heat map representations and characterized by greater sensitivity. First proof-of-principle that the SocioBox allows diagnosis of social recognition deficits is provided using male PSD-95 heterozygous knockout mice, a mouse model related to psychiatric pathophysiology. PMID:27563287

  10. The SocioBox: A Novel Paradigm to Assess Complex Social Recognition in Male Mice.

    PubMed

    Krueger-Burg, Dilja; Winkler, Daniela; Mitkovski, Mišo; Daher, Fernanda; Ronnenberg, Anja; Schlüter, Oliver M; Dere, Ekrem; Ehrenreich, Hannelore

    2016-01-01

    Impairments in social skills are central to mental disease, and developing tools for their assessment in mouse models is essential. Here we present the SocioBox, a new behavioral paradigm to measure social recognition. Using this paradigm, we show that male wildtype mice of different strains can readily identify an unfamiliar mouse among 5 newly acquainted animals. In contrast, female mice exhibit lower locomotor activity during social exploration in the SocioBox compared to males and do not seem to discriminate between acquainted and unfamiliar mice, likely reflecting inherent differences in gender-specific territorial tasks. In addition to a simple quantification of social interaction time of mice grounded on predefined spatial zones (zone-based method), we developed a set of unbiased, data-driven analysis tools based on heat map representations and characterized by greater sensitivity. First proof-of-principle that the SocioBox allows diagnosis of social recognition deficits is provided using male PSD-95 heterozygous knockout mice, a mouse model related to psychiatric pathophysiology. PMID:27563287

  11. ANEUPLOIDIES AND MICRONUCLEI IN THE GERM CELLS OF MALE MICE OF ADVANCED AGE

    EPA Science Inventory

    The objective of this research was to determine whether the frequencies of chromosomally defective germ cells increased with age in male laboratory mice. wo types of chromosomal abnormalities were characterized: (1) testicular spermatid aneuploidy (TSA) as measured by a new metho...

  12. THE EFFECTS OF HYPERTHERMIA ON SPERMATOGENESIS, APOPTOSIS, GENE EXPRESSION AND FERTILITY IN ADULT MALE MICE

    EPA Science Inventory

    The effects of hyperthermia on spermatogenesis, apoptosis, gene expression and fertility in adult male mice
    John C. Rockett1, Faye L. Mapp1, J. Brian Garges1, J. Christopher Luft1, Chisato Mori2 and David J. Dix1.
    1Reproductive Toxicology Division, National Health and Envir...

  13. Soy protein isolate protects against ethanol mediated tumor progression in diethylnitrosamine treated male mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In this study, DEN-treated male mice were assigned to 3 groups: a 35% high fat ethanol liquid diet (EtOH) with casein as the protein source, the same EtOH liquid diet with soy protein isolate as the sole protein source (EtOH/soy) and a chow group. EtOH feeding continued for 16 wks. As expected, E...

  14. Adipocyte deficiency of angiotensinogen prevents obesity-induced hypertension in male mice.

    PubMed

    Yiannikouris, Frederique; Gupte, Manisha; Putnam, Kelly; Thatcher, Sean; Charnigo, Richard; Rateri, Debra L; Daugherty, Alan; Cassis, Lisa A

    2012-12-01

    Previous studies demonstrated that diet-induced obesity increased plasma angiotensin II concentrations and elevated systolic blood pressures in male mice. Adipocytes express angiotensinogen and secrete angiotensin peptides. We hypothesize that adipocyte-derived angiotensin II mediates obesity-induced increases in systolic blood pressure in male high fat-fed C57BL/6 mice. Systolic blood pressure was measured by radiotelemetry during week 16 of low-fat or high-fat feeding in Agt(fl/fl) and adipocyte angiotensinogen-deficient mice (Agt(aP2)). Adipocyte angiotensinogen deficiency had no effect on diet-induced obesity. Basal 24-hour systolic blood pressure was not different in low fat-fed Agt(fl/fl) compared with Agt(aP2) mice (124 ± 3 versus 128 ± 3 mm Hg, respectively). In Agt(fl/fl) mice, high-fat feeding significantly increased systolic blood pressure (24 hours; 134 ± 2 mm Hg; P<0.05). In contrast, high fat-fed Agt(aP2) mice did not exhibit an increase in systolic blood pressure (126 ± 2 mm Hg). Plasma angiotensin II concentrations were increased by high-fat feeding in Agt(fl/fl) mice (low fat, 32 ± 14; high fat, 219 ± 58 pg/mL; P<0.05). In contrast, high fat-fed Agt(aP2) mice did not exhibit elevated plasma angiotensin II concentrations (high fat, 18 ± 7 pg/mL). Similarly, adipose tissue concentrations of angiotensin II were significantly decreased in low fat- and high fat-fed Agt(aP2) mice compared with controls. In conclusion, adipocyte angiotensinogen deficiency prevented high fat-induced elevations in plasma angiotensin II concentrations and systolic blood pressure. These results suggest that adipose tissue serves as a major source of angiotensin II in the development of obesity hypertension. PMID:23108647

  15. Early life stress in male mice induces superoxide production and endothelial dysfunction in adulthood.

    PubMed

    Ho, Dao H; Burch, Mariah L; Musall, Benjamin; Musall, Jacqueline B; Hyndman, Kelly A; Pollock, Jennifer S

    2016-05-01

    Early life stress (ELS) is a risk for cardiovascular disease in adulthood although very little mechanistic insight is available. Because oxidative stress and endothelial dysfunction are major contributors to cardiovascular risk, we hypothesized that ELS induces endothelial dysfunction in adult male mice via increased superoxide production. Studies employed a mouse model of ELS, maternal separation with early weaning (MSEW), in which litters were separated from the dam for 4 h/day [postnatal days (PD) 2-5] and 8 h/day (PD6-16), and weaned at PD17. Control litters remained undisturbed until weaning at PD21. When compared with control mice, thoracic aortic rings from adult male MSEW mice displayed significant endothelial dysfunction that was reversed by the superoxide scavenger, polyethylene glycol-superoxide dismutase (PEG-SOD). PEG-SOD-inhibitable superoxide production by aortae from MSEW mice was significantly greater than observed in control aortae, although unaffected by nitric oxide synthase inhibition, suggesting that uncoupled nitric oxide synthase was not responsible for the accelerated superoxide production. Aortic SOD expression, plasma SOD activity, and total antioxidant activity were similar in MSEW and control mice, indicating unaltered antioxidant capacity in MSEW mice. Increased expression of the NADPH oxidase subunits, NOX2 and NOX4, was evident in the aortae of MSEW mice. Moreover, endothelial dysfunction and superoxide production in MSEW mice was reversed with the NADPH oxidase inhibitor, apocynin, indicating increased NADPH oxidase-dependent superoxide production and endothelial dysfunction. The finding that MSEW induces superoxide production and endothelial dysfunction in adult mice may provide a mechanistic link between ELS and adult cardiovascular disease risk. PMID:26921433

  16. Changes in estrogen receptor signaling alters the timekeeping system in male mice.

    PubMed

    Blattner, Margaret S; Mahoney, Megan M

    2015-11-01

    Circadian rhythms are modulated by steroid hormones; however, the mechanisms of this action are not fully understood, particularly in males. In females estradiol regulates activity level, pattern of expression, and free running period (tau). We tested the hypothesis that activity level and distribution in male mice includes both classical and "non-classical" actions of estrogens at the estrogen receptor subtype 1 (ESR1). We used transgenic mice with mutations in their estrogen response pathways: ESR1 knock-out (ERKO) mice lack the ability to respond to estrogens via ESR1. "Non-classical" estrogen receptor knock-in (NERKI) mice have an inserted ESR1 receptor with a mutation in the estrogen-response-element binding domain, allowing activation via non-genomic and second messenger pathways. Gonadectomized male NERKI, ERKO, and wildtype (WT) littermates were given oil, or low or high dose estradiol and daily activity parameters were quantified. Estradiol shortened the ratio of activity in the light relative to dark (LD ratio), shortened tau, advanced the time of activity onset, and altered responsiveness to light cues administered in the late subjective night, suggesting modulation by an ESR1-independent mechanism. Estradiol treatment in NERKI but not WT males altered the timing of activity onset, LD ratio, and the behavioral response to light cues. These results may represent disruptions in the balance of genomic/nongenomic or ESR1/ESR2 signaling pathways. We also found a significant genotype effect on total activity, LD ratio, tau, and activity duration. These data provide new information about the role of ESR1-dependent and independent signaling pathways on the timekeeping system in male mice. PMID:26241171

  17. Promotion of hepatic preneoplastic lesions in male B6C3F{sub 1} mice by unleaded gasoline

    SciTech Connect

    Standeven, A.M.; Wolf, D.C.; Goldsworthy, T.L.

    1995-07-01

    In previous studies, unleaded gasoline (UG) vapor was found to be a liver tumor promotor and hepatocarcinogen in female mice, but UG was not a hepatocarcinogen in male mice. However, UG vapor had similar transient mitogenic effects in nonlesioned liver of both male and female mice under the conditions of the cancer bioassay. We used an initiation-promotion protocol to determine whether UG vapor acts as a liver tumor promoter in male mice and to examine proliferative effects that may be critical to tumor development. Twelve-day-old male B6C3F{sub 1} mice were injected with N-nitrosodiethylamine (DEN; 5 mg/kg, intraperitoneally) or vehicle. Starting at 5-7 weeks of age, mice were exposed by inhalation 6 hr/day, 5 days/week for 16 weeks to 0 or 2046 ppm of PS-6 blend UG. UG treatment caused a significant 2.3-fold increase in the number of macroscopic hepatic masses in DEN-initiated mice, whereas no macroscopic masses were observed in noninitiated mice. To study hepatocyte proliferative effects of UG, we treated mice with 5-bromo-2`-deoxyuridine (BrdU) via osmotic pump for 3 days before necropsy and measured hepatocyte BruU labeling index (LI) in AHF and nonlesioned liver. UG did not significantly affect BrdU LI in nonlesioned liver. However, hepatocyte LI in AHF was about 30% higher in DEN/UG-treated mice relative to mice treated with DEN alone. These data show that UG vapor promotes AHF in male mice and that liver tumor promotion is associated with a selective increase in hepatocyte proliferation in AHF. UG acts as a liver tumor promoter in both male and female mice, and these findings contrast with the lack of hepatocarcinogenicity of UG in male mice in a cancer bioassy. 36 refs., 1 fig., 3 tabs.

  18. Low Incidence of Miscarriage Induced by the Scent of Male Littermates of Original Mates: Male Kinship Reduces the Bruce Effect in Female Mice, Mus musculus

    PubMed Central

    Wang, Yuting; Liu, Dingzhen

    2013-01-01

    The scent of a novel male can elicit pregnancy block in recently mated female mice (Mus musculus), a phenomenon known as the Bruce effect. Despite abundant literature on the Bruce effect in rodents, it remains unclear whether males related to a female’s original mate can induce the Bruce effect in out-bred, communally living mice. We investigated this question using Kunming (KM) male mice of varying genetic relatedness. Recently mated females were subjected to three treatments: exposure to the urine of the mate, urine of the mate’s male littermate, and urine of a male unrelated to the mate. It was found that the urine of male littermates of the females’ mates did not elicit more pregnancy block than that of the females’ mates. However, the urine of novel males caused a higher rate of female miscarriage than that of the females’ mates. By using a habituation-dishabituation paradigm, we found that unmated females could discriminate the urine scents of two male littermates from those of a novel male unrelated to the littermates. To understand how females use urinary cues to discriminate between males with different genetic relationships, we used gas chromatography coupled with mass spectrometry (GC-MS) to examine the volatile composition of urine from males with varying relatedness. It was found that KM male littermates shared similar volatile compositions in their urine. Our results suggest that male kinship reduces the Bruce effect in female KM mice, and provide additional evidence for mate choice being partly mediated by the Bruce effect in KM mice. PMID:23874716

  19. Low incidence of miscarriage induced by the scent of male littermates of original mates: male kinship reduces the bruce effect in female mice, Mus musculus.

    PubMed

    Wang, Yuting; Liu, Dingzhen

    2013-01-01

    The scent of a novel male can elicit pregnancy block in recently mated female mice (Mus musculus), a phenomenon known as the Bruce effect. Despite abundant literature on the Bruce effect in rodents, it remains unclear whether males related to a female's original mate can induce the Bruce effect in out-bred, communally living mice. We investigated this question using Kunming (KM) male mice of varying genetic relatedness. Recently mated females were subjected to three treatments: exposure to the urine of the mate, urine of the mate's male littermate, and urine of a male unrelated to the mate. It was found that the urine of male littermates of the females' mates did not elicit more pregnancy block than that of the females' mates. However, the urine of novel males caused a higher rate of female miscarriage than that of the females' mates. By using a habituation-dishabituation paradigm, we found that unmated females could discriminate the urine scents of two male littermates from those of a novel male unrelated to the littermates. To understand how females use urinary cues to discriminate between males with different genetic relationships, we used gas chromatography coupled with mass spectrometry (GC-MS) to examine the volatile composition of urine from males with varying relatedness. It was found that KM male littermates shared similar volatile compositions in their urine. Our results suggest that male kinship reduces the Bruce effect in female KM mice, and provide additional evidence for mate choice being partly mediated by the Bruce effect in KM mice. PMID:23874716

  20. Efficacy of Tramadol as a Sole Analgesic for Postoperative Pain in Male and Female Mice

    PubMed Central

    Wolfe, A Marissa; Kennedy, Lucy H; Na, Jane J; Nemzek-Hamlin, Jean A

    2015-01-01

    Tramadol is a centrally acting weak μ opioid agonist that has few of the adverse side effects common to other opioids. Little work has been done to establish an effective analgesic dose of tramadol specific for surgical laparotomy and visceral manipulation in mice. We used general appearance parameters to score positive indicators of pain including posture, coat condition, activity, breathing, and interactions with other mice, activity events (that is, the number of times each mouse stretched up in a 3-min period) used as an indicator of decreased pain, von Frey fibers, and plasma levels of corticosterone to determine whether tramadol at 20, 40, or 80 mg/kg prevented postoperative pain in male and female C57BL/6 mice. A ventral midline laparotomy with typhlectomy was used as a model of postoperative pain. In male mice, none of the markers differed between groups that received tramadol (regardless of dose) and the saline-treated controls. However, general appearance scores and plasma corticosterone levels were lower in female mice that received 80 mg/kg tramadol compared with saline. In summary, for severe postoperative pain after laparotomy and aseptic typhlectomy, tramadol was ineffective in male C57BL/6 mice at all doses tested. Although 80 mg/kg ameliorated postoperative pain in female C57BL/6 mice, this dose is very close to the threshold reported to cause toxic side effects, such as tremors and seizures. Therefore, we do not recommend the use of tramadol as a sole analgesic in this mouse model of postoperative pain. PMID:26224442

  1. Pituitary tumor transforming gene-null male mice exhibit impaired pancreatic beta cell proliferation and diabetes

    PubMed Central

    Wang, Zhiyong; Moro, Enrico; Kovacs, Kalman; Yu, Run; Melmed, Shlomo

    2003-01-01

    The mammalian securin, pituitary tumor transforming gene (PTTG), regulates sister chromatid separation during mitosis. Mice or cell lines deficient in PTTG expression, however, are surprisingly viable. Here we show that PTTG disruption in mice (PTTG−/−) severely impairs glucose homeostasis leading to diabetes during late adulthood, especially in males associated with nonautoimmune insulinopenia and reversed alpha/beta cell ratio. Islet beta cell mass in PTTG−/− mice was already diminished before development of frank diabetes and only increased minimally during growth. BrdUrd incorporation of islet cells in PTTG-null mice was ≈65% lower (P < 0.005) than in the WT pancreas, whereas apoptosis rates were similar. PTTG−/− beta cells had pleiotropic nuclei, suggesting defects in cell division. The results indicated that securin is indispensable for normal pancreatic beta cell proliferation. PMID:12626748

  2. High stress hormone levels accelerate the onset of memory deficits in male Huntington's disease mice.

    PubMed

    Mo, Christina; Pang, Terence Y; Ransome, Mark I; Hill, Rachel A; Renoir, Thibault; Hannan, Anthony J

    2014-09-01

    Huntington's disease (HD) is a neurodegenerative disorder caused by a tandem repeat mutation in the huntingtin gene. Lifestyle factors, such as lack of activity may contribute to the variability in the age of disease onset. Therefore, better understanding of environmental modifiers may uncover potential therapeutic approaches to delay disease onset and progression. Recent data suggest that HD patients and transgenic mouse models show a dysregulated stress response. In this present study, we elevated stress hormone levels through oral corticosterone (CORT) treatment and assessed its impact on the development of motor impairment and cognitive deficits using the R6/1 transgenic mouse model of HD. We found that CORT consumption did not alter rotarod performance of R6/1 HD or wild-type (WT) littermates. However, the onset of hippocampal-dependent Y-maze deficits was accelerated in male R6/1 mice by 5days of CORT treatment, whereas short term memory of WT and female R6/1 mice was unaffected. We then further investigated the male HD susceptibility to CORT by measuring TrkB activation, BDNF and glucocorticoid receptor expression as well as the level of cell proliferation in the hippocampus. CORT treatment increased the levels of phosphorylated TrkB in male R6/1 mice only. There were no effects of CORT on hippocampal BDNF protein or mRNA levels; nor on expression of the glucocorticoid receptors in any group. Hippocampal cell proliferation was decreased in male R6/1 mice and this was further reduced in CORT-drinking male R6/1 mice. Female mice (WT and R6/1) appeared to be protected from the impacts of CORT treatment in all our hippocampal measures. Overall, our data demonstrate that treatment with corticosterone is able to modulate the onset of HD symptomatology. We present the first evidence of a male-specific vulnerability to stress impacting on the development of short-term memory deficits in HD. More generally, we found that female mice were protected from the

  3. Steroid Tumor Environment in Male and Female Mice Model of Canine and Human Inflammatory Breast Cancer

    PubMed Central

    Caceres, Sara; Peña, Laura; Silvan, Gema; Illera, Maria J.; Woodward, Wendy A.; Reuben, James M.; Illera, Juan C.

    2016-01-01

    Canine inflammatory mammary cancer (IMC) shares clinical and histopathological characteristics with human inflammatory breast cancer (IBC) and has been proposed as a good model for studying the human disease. The aim of this study was to evaluate the capacity of female and male mice to reproduce IMC and IBC tumors and identify the hormonal tumor environment. To perform the study sixty 6–8-week-old male and female mice were inoculated subcutaneously with a suspension of 106IPC-366 and SUM149 cells. Tumors and serum were collected and used for hormonal analysis. Results revealed that IPC-366 reproduced tumors in 90% of males inoculated after 2 weeks compared with 100% of females that reproduced tumor at the same time. SUM149 reproduced tumors in 40% of males instead of 80% of females that reproduced tumors after 4 weeks. Both cell lines produce distant metastasis in lungs being higher than the metastatic rates in females. EIA analysis revealed that male tumors had higher T and SO4E1 concentrations compared to female tumors. Serum steroid levels were lower than those found in tumors. In conclusion, IBC and IMC male mouse model is useful as a tool for IBC research and those circulating estrogens and intratumoral hormonal levels are crucial in the development and progression of tumors. PMID:27195300

  4. Steroid Tumor Environment in Male and Female Mice Model of Canine and Human Inflammatory Breast Cancer.

    PubMed

    Caceres, Sara; Peña, Laura; Silvan, Gema; Illera, Maria J; Woodward, Wendy A; Reuben, James M; Illera, Juan C

    2016-01-01

    Canine inflammatory mammary cancer (IMC) shares clinical and histopathological characteristics with human inflammatory breast cancer (IBC) and has been proposed as a good model for studying the human disease. The aim of this study was to evaluate the capacity of female and male mice to reproduce IMC and IBC tumors and identify the hormonal tumor environment. To perform the study sixty 6-8-week-old male and female mice were inoculated subcutaneously with a suspension of 10(6)IPC-366 and SUM149 cells. Tumors and serum were collected and used for hormonal analysis. Results revealed that IPC-366 reproduced tumors in 90% of males inoculated after 2 weeks compared with 100% of females that reproduced tumor at the same time. SUM149 reproduced tumors in 40% of males instead of 80% of females that reproduced tumors after 4 weeks. Both cell lines produce distant metastasis in lungs being higher than the metastatic rates in females. EIA analysis revealed that male tumors had higher T and SO4E1 concentrations compared to female tumors. Serum steroid levels were lower than those found in tumors. In conclusion, IBC and IMC male mouse model is useful as a tool for IBC research and those circulating estrogens and intratumoral hormonal levels are crucial in the development and progression of tumors. PMID:27195300

  5. Toxic effects of sub-chronic exposure of male albino rats to emamectin benzoate and possible ameliorative role of Foeniculum vulgare essential oil.

    PubMed

    El-Sheikh, El-Sayed A; Galal, Azza A A

    2015-05-01

    Emamectin benzoate (EB) is an avermectin insecticide used extensively in pest control on vegetable and field crops. Few studies have been done for evaluating adverse effects of EB. In the current study, we evaluated the toxic effects of EB on male rats and the possible ameliorative role of fennel essential oil (FEO). Thirty two male rats were randomly divided into 4 equal groups. All groups were treated orally with distilled water (control group), 0.5mlFEOkg(-1) BW (FEO group), 2.5mgEBkg(-1) BW (EB group), and 0.5mlFEOkg(-1) BW+2.5mgEBkg(-1) BW (FEO+EB group) for 28 days. The obtained results showed that EB treatment resulted in a significant decrease in body weight, body weight gain, RBC count, Hb concentration, % PCV, MCV and MCHC. Moreover, EB significantly decreased total leukocyte, lymphocyte, monocyte and platelet count but significantly increased granulocyte count. EB markedly decreased total protein, albumin, globulin, IgG and IgM concentrations with a significant increase in TNF-α secretion. EB had a negative impact on the liver as it significantly increased ALT, ALP, and MDA, while decreasing SOD activity. Regarding to the histopathological examination, EB treatment induced coagulative necrosis and blood vessels congestion of the liver in treated rats. Furthermore, it resulted in depletion and necrosis of the white pulp of the spleen in treated rats. The co-administration of FEO with EB, however, improved the majority of parameters studied, suggesting that FEO is an important substance in decreasing toxic effects of EB. PMID:25935540

  6. Citrus limon extract: possible inhibitory mechanisms affecting testicular functions and fertility in male mice.

    PubMed

    Singh, Nidhi; Singh, Shio Kumar

    2016-01-01

    The effect of oral administration of 50% ethanolic leaf extract of Citrus limon (500 and 1,000 mg/kg body weight/day) for 35 days on fertility and various male reproductive endpoints was evaluated in Parkes strain of mice. Testicular indices such as histology, 3β- and 17β-HSD enzymes activity, immunoblot expression of StAR and P450scc, and germ cell apoptosis by TUNEL and CASP- 3 expression were assessed. Motility, viability, and number of spermatozoa in the cauda epididymidis, level of serum testosterone, fertility indices, and toxicological parameters were also evaluated. Histologically, testes in extract-treated mice showed nonuniform degenerative changes in the seminiferous tubules. Treatment had adverse effects on steroidogenic markers in the testis and induced germ cell apoptosis. Significant reductions were noted in epididymal sperm parameters and serum level of testosterone in Citrus-treated mice compared to controls. Fertility of the extract-treated males was also suppressed, but libido remained unaffected. By 56 days of treatment withdrawal, alterations induced in the above parameters returned to control levels suggesting that Citrus treatment causes reversible suppression of spermatogenesis and fertility in Parkes mice. Suppression of spermatogenesis may result from germ cell apoptosis because of decreased production of testosterone. The present work indicated that Citrus leaves can affect male reproduction. PMID:26787324

  7. Crocin Improves Damage Induced by Nicotine on A Number of Reproductive Parameters in Male Mice

    PubMed Central

    Salahshoor, Mohammad Reza; Khazaei, Mozafar; Jalili, Cyrus; Keivan, Mona

    2016-01-01

    Background Crocin, a carotenoid isolated from Crocus sativus L. (saffron), is a pharmacologically active component of saffron. Nicotine consumption can decrease fertility in males through induction of oxidative stress and DNA damage. The aim of this study is to determine the effects of crocin on reproductive parameter damages in male mice exposed to nicotine. Materials and Methods In this experimental study, we divided 48 mice into 8 groups (n=6 per group): control (normal saline), nicotine (2.5 mg/kg), crocin (12.5, 25 and 50 mg/kg) and crocin (12.5, 25 and 50 mg/kg)+nicotine (2.5 mg/kg). Mice received once daily intraperitoneal injections of crocin, nicotine and crocin+nicotine for 4 weeks. Sperm parameters (count, motility, and viability), testis weight, seminiferous tube diameters, testosterone, and serum nitric oxide levels were analyzed and compared. Results Nicotine administration significantly decreased testosterone level; sperm count, viability, and motility; testis weight and seminiferous tubule diameters compared to the control group (P<0.05). However, increasing the dose of crocin in the crocin and crocin+nicotine groups significantly boosted sperm motility and viability; seminiferous tubule diameters; testis weight; and testosterone levels in all groups compared to the nicotine group (P<0.05). Conclusion Crocin improves nicotine-induced adverse effects on reproductive parameters in male mice. PMID:27123203

  8. Behavioral deficits and cholinergic pathway abnormalities in male Sanfilippo B mice.

    PubMed

    Kan, Shih-Hsin; Le, Steven Q; Bui, Quang D; Benedict, Braeden; Cushman, Jesse; Sands, Mark S; Dickson, Patricia I

    2016-10-01

    Sanfilippo B syndrome is a progressive neurological disorder caused by inability to catabolize heparan sulfate glycosaminoglycans. We studied neurobehavior in male Sanfilippo B mice and heterozygous littermate controls from 16 to 20 weeks of age. Affected mice showed reduced anxiety, with a decrease in the number of stretch-attend postures during the elevated plus maze (p=0.001) and an increased tendency to linger in the center of an open field (p=0.032). Water maze testing showed impaired spatial learning, with reduced preference for the target quadrant (p=0.01). In radial arm maze testing, affected mice failed to achieve above-chance performance in a win-shift working memory task (t-test relative to 50% chance: p=0.289), relative to controls (p=0.037). We found a 12.4% reduction in mean acetylcholinesterase activity (p<0.001) and no difference in choline acetyltransferase activity or acetylcholine in whole brain of affected male animals compared to controls. Cholinergic pathways are affected in adult-onset dementias, including Alzheimer disease. Our results suggest that male Sanfilippo B mice display neurobehavioral deficits at a relatively early age, and that as in adult dementias, they may display deficits in cholinergic pathways. PMID:27340089

  9. β-Actin protein expression differs in the submandibular glands of male and female mice.

    PubMed

    Chen, Gang; Zou, Ye; Zhang, Xuan; Xu, Lingfei; Hu, Qiaoyun; Li, Ting; Yao, Chenjuan; Yu, Shali; Wang, Xiaoke; Wang, Chun

    2016-07-01

    β-actin, a cytoskeletal protein, is the most widely used housekeeping gene. Although housekeeping genes are expressed in all tissues, the β-actin gene is expressed in certain cell types because of differential binding of transcriptional factors to the regulatory elements of the gene. The expression and localization of β-actin protein in the submandibular glands (SMG) of mice were investigated in this study, using Western blot analysis and immunohistochemistry. In ICR and C57BL/6J mice, the levels of β-actin protein in the SMG of females are significantly higher than those in the SMG of males. β-actin protein is majorly distributed in acinar cells of SMG. There is no significant difference in the expression level of β-actin protein between females and castrated males. After castrated male ICR mice are treated with 10 mg/kg/day testosterone propionate (TP) for 3 weeks, the levels of β-actin protein in SMG decrease. The numbers of duct per unit area increase, whereas the numbers of acinus per unit area decrease after TP administration. These data suggest that β-actin protein is mainly distributed in acinar cells of SMG and results in a marked sexual dimorphism in mice. PMID:27079296

  10. Papain-induced experimental pulmonary emphysema in male and female mice.

    PubMed

    Machado, Mariana Nascimento; Figueirôa, Silviane Fernandes da Silva; Mazzoli-Rocha, Flavia; Valença, Samuel dos Santos; Zin, Walter Araújo

    2014-08-15

    In papain-induced models of emphysema, despite the existing extensive description of the cellular and molecular aspects therein involved, sexual hormones may play a complex and still not fully understood role. Hence, we aimed at exploring the putative gender-related differences in lung mechanics, histology and oxidative stress in papain-exposed mice. Thirty adult BALB/c mice received intratracheally either saline (50 μL) or papain (10 U/50 μL saline) once a week for 2 weeks. In males papain increased lung resistive and viscoelastic/inhomogeneous pressures, static elastance, and viscoelastic component of elastance, while females showed higher static elastance and resistive pressure only. Both genders presented similar higher parenchymal cellularity and mean alveolar diameter, and less collagen-elastic fiber content and body weight gain than their respective controls. Increased functional residual capacity was more prominent in males. Female papain-treated mice were more susceptible to oxidative stress. Thus, male and female papain-exposed mice respond differently, which should be carefully considered to avoid confounding results. PMID:24931736

  11. [Redistribution of immune defence in male mice exposed by female scent].

    PubMed

    Litvinova, E A; Garms, A I; Zaĭdman, A M; Korel', A V; Gerlinskaia, L A; Moshkin, M P

    2009-01-01

    Since scent marks of mice are harbored by parasites, their sniffing during olfactory search of the mating partner leads to increase of the infection risk. A hypothesis that sexual signals can induce, along with the reproductive behavior, non-specific immune defense against respiratory infections is tested in the present paper. It was found in the experiments on outbred ICR mice that the scent of soiled bedding from cages with mature females stimulated leukocyte intervention to the upper air-ways. Migration of the white blood cells to lung tissue was accompanied with a more prominent immune and endocrine responeses to intranasal application of the bacterial lipopolysacharide (LPS). In particular, LPS administration to male mice treated by female scent was resulted in much greater amount of leukocyte aggregations in the peribronchial areas than that was found in the males kept isolated from the female signals. The female scent also enhanced adrenocortical response to LPS administration, which was coincided with statistically significant increase of IL-1beta concentration in hypothalamus. So, chemical signals of the mature female induce travel of white blood cells to the upper air-waya in the scent treated male mice. It can increase resistance to respiratory infections, on the one hand, and aggravates stress response to inhalation of the bacterial compounds, on the other hand. PMID:19326854

  12. Enzalutamide Reduces the Bone Mass in the Axial But Not the Appendicular Skeleton in Male Mice.

    PubMed

    Wu, Jianyao; Movérare-Skrtic, Sofia; Börjesson, Anna E; Lagerquist, Marie K; Sjögren, Klara; Windahl, Sara H; Koskela, Antti; Grahnemo, Louise; Islander, Ulrika; Wilhelmson, Anna S; Tivesten, Åsa; Tuukkanen, Juha; Ohlsson, Claes

    2016-02-01

    Testosterone is a crucial regulator of the skeleton, but the role of the androgen receptor (AR) for the maintenance of the adult male skeleton is unclear. In the present study, the role of the AR for bone metabolism and skeletal growth after sexual maturation was evaluated by means of the drug enzalutamide, which is a new AR antagonist used in the treatment of prostate cancer patients. Nine-week-old male mice were treated with 10, 30, or 100 mg/kg·d of enzalutamide for 21 days or were surgically castrated and were compared with vehicle-treated gonadal intact mice. Although orchidectomy reduced the cortical bone thickness and trabecular bone volume fraction in the appendicular skeleton, these parameters were unaffected by enzalutamide. In contrast, both enzalutamide and orchidectomy reduced the bone mass in the axial skeleton as demonstrated by a reduced lumbar spine areal bone mineral density (P < .001) and trabecular bone volume fraction in L5 vertebrae (P < .001) compared with vehicle-treated gonadal intact mice. A compression test of the L5 vertebrae revealed that the mechanical strength in the axial skeleton was significantly reduced by enzalutamide (maximal load at failure -15.3% ± 3.5%; P < .01). The effects of enzalutamide in the axial skeleton were associated with a high bone turnover. In conclusion, enzalutamide reduces the bone mass in the axial but not the appendicular skeleton in male mice after sexual maturation. We propose that the effect of testosterone on the axial skeleton in male mice is mainly mediated via the AR. PMID:26587782

  13. Expression of group III metabotropic glutamate receptors in the reproductive system of male mice.

    PubMed

    Marciniak, Marcin; Chruścicka, Barbara; Lech, Tomasz; Burnat, Grzegorz; Pilc, Andrzej

    2016-03-01

    Although the presence of metabotropic glutamate (mGlu) receptors in the central nervous system is well documented, they have recently been found in peripheral and non-neuronal tissues. In the present study we investigated the expression of group III mGlu receptors in the reproductive system of male mice. Reverse transcription-polymerase chain reaction analysis revealed the presence of mGlu6, mGlu7 and mGlu8 (but not mGlu4) receptor transcripts in testes and epididymides from adult mice. In addition, expression of mGlu6 (Grm6) and mGlu8 receptor (Grm8) mRNA was detected in spermatozoa isolated from the vas deferens. The vas deferens was found to contain only mGlu7 receptor (Grm7) mRNA, which was particularly intense in 21-day-old male mice. In penile homogenates, only the mGlu7 receptor signal was detected. Genetic ablation of the mGlu7 receptor in males led to fertility disorders manifested by decreased insemination capability as well as deterioration of sperm parameters, particularly sperm motility, vitality, sperm membrane integrity and morphology, with a simultaneous increase in sperm concentration. These results indicate that constitutively expressed mGlu receptors in the male reproductive system may play an important role in ejaculation and/or erection processes, as well as in the formation and maturation of spermatozoa. PMID:25066043

  14. Altered social cognition in male BDNF heterozygous mice and following chronic methamphetamine exposure.

    PubMed

    Manning, Elizabeth E; van den Buuse, Maarten

    2016-05-15

    Growing clinical evidence suggests that persistent psychosis which occurs in methamphetamine users is closely related to schizophrenia. However, preclinical studies in animal models have focussed on psychosis-related behaviours following methamphetamine, and less work has been done to assess endophenotypes relevant to other deficits observed in schizophrenia. Altered social behaviour is a feature of both the negative symptoms and cognitive deficits in schizophrenia, and significantly impacts patient functioning. We recently found that brain-derived neurotrophic factor (BDNF) heterozygous mice show disrupted sensitization to methamphetamine, supporting other work suggesting an important role of this neurotrophin in the pathophysiology of psychosis and the neuronal response to stimulant drugs. In the current study, we assessed social and cognitive behaviours in methamphetamine-treated BDNF heterozygous mice and wildtype littermate controls. Following chronic methamphetamine exposure male wildtype mice showed a 50% reduction in social novelty preference. Vehicle-treated male BDNF heterozygous mice showed a similar impairment in social novelty preference, with a trend for no further disruption by methamphetamine exposure. Female mice were unaffected in this task, and no groups showed any changes in sociability or short-term spatial memory. These findings suggest that chronic methamphetamine alters behaviour relevant to disruption of social cognition in schizophrenia, supporting other studies which demonstrate a close resemblance between persistent methamphetamine psychosis and schizophrenia. Together these findings suggest that dynamic regulation of BDNF signalling is necessary to mediate the effects of methamphetamine on behaviours relevant to schizophrenia. PMID:26965573

  15. The Forkhead Transcription Factor, FOXP3: A Critical Role in Male Fertility in Mice1

    PubMed Central

    Jasurda, Jake S.; Jung, Deborah O.; Froeter, Erin D.; Schwartz, David B.; Hopkins, Torin D.; Farris, Corrie L.; McGee, Stacey; Narayan, Prema; Ellsworth, Buffy S.

    2013-01-01

    ABSTRACT Fertility is dependent on the hypothalamic-pituitary-gonadal axis. Each component of this axis is essential for normal reproductive function. Mice with a mutation in the forkhead transcription factor gene, Foxp3, exhibit autoimmunity and infertility. We have previously shown that Foxp3 mutant mice have significantly reduced expression of pituitary gonadotropins. To address the role of Foxp3 in gonadal function, we examined the gonadal phenotype of these mice. Foxp3 mutant mice have significantly reduced seminal vesicle and testis weights compared with Foxp3+/Y littermates. Spermatogenesis in Foxp3 mutant males is arrested prior to spermatid elongation. Activation of luteinizing hormone signaling in Foxp3 mutant mice by treatment with human chorionic gonadotropin significantly increases seminal vesicle and testis weights as well as testicular testosterone content and seminiferous tubule diameter. Interestingly, human chorionic gonadotropin treatments rescue spermatogenesis in Foxp3 mutant males, suggesting that their gonadal phenotype is due primarily to a loss of pituitary gonadotropin stimulation rather than an intrinsic gonadal defect. PMID:24258212

  16. [Effects of ethanol on metastasis of Lewis lung carcinoma in male mice with different social states].

    PubMed

    Il'nitskaia, S I; Nikolin, V P; Popova, N A; Avgustinovich, D F; Kaledin, V I; Kudriavtseva, N N

    2009-01-01

    The aim of this work was to study the effect of ethanol on experimental metastasis of Lewis lung carcinoma in male mice in positive or negative emotional states. Sensory contact model was used for generating animals with repeated experience of social victories or defeats. Tumor cells were injected into the tail vein after 20 days of agonistic interactions, and the number of metastases in the lung was calculated 16 days later. Group-housed mice were used as the controls. Mice of all experimental groups were chronically treated with ethanol (20%, 2 ml/kg of weight, i.p.) and saline during 7 days starting with the day of tumor cells injections. The experimental metastasis was shown to develop differently in mice with opposing social experience: saline-treated winners had significantly less metastases in the lung than the saline-treated losers. Chronic ethanol injections decreased the number of metastases in the losers, increased it in the winners and did not affect the controls. The results obtained indicate that effects if ethanol on Lewis lung carcinoma metastasis depend on psychoemotional status in male mice. PMID:19323446

  17. Vasoactive Intestinal Peptide Excites GnRH Neurons in Male and Female Mice.

    PubMed

    Piet, Richard; Dunckley, Henry; Lee, Kiho; Herbison, Allan E

    2016-09-01

    A variety of external and internal factors modulate the activity of GnRH neurons to control fertility in mammals. A direct, vasoactive intestinal peptide (VIP)-mediated input to GnRH neurons originating from the suprachiasmatic nucleus is thought to relay circadian information within this network. In the present study, we examined the effects of VIP on GnRH neuron activity in male and female mice at different stages of the estrous cycle. We carried out cell-attached recordings in slices from GnRH-green fluorescent protein mice and calcium imaging in slices from a mouse line expressing the genetically encoded calcium indicator GCaMP3 selectively in GnRH neurons. We show that 50%-80% of GnRH neurons increase their firing rate in response to bath-applied VIP (1nM-1000nM) in both male and female mice and that this is accompanied by a robust increase in intracellular calcium concentrations. This effect is mediated directly at the GnRH neuron likely through activation of high-affinity VIP receptors. Because suprachiasmatic nucleus-derived timing cues trigger the preovulatory surge only on the afternoon of proestrus in female mice, we examined the effects of VIP during the estrous cycle at different times of day. VIP responsiveness in GnRH neurons did not vary significantly in diestrous and proestrous mice before or around the time of the expected preovulatory surge. These results indicate that the majority of GnRH neurons in male and female mice express functional VIP receptors and that the effects of VIP on GnRH neurons do not alter across the estrous cycle. PMID:27501185

  18. Beta-Catenin Haplo Insufficient Male Mice Do Not Lose Bone in Response to Hindlimb Unloading

    PubMed Central

    Farr, Joshua; Cheng, An-Lin; Johnson, Mark L.; Bonewald, Lynda F.

    2016-01-01

    As the β-catenin pathway has been shown to be involved in mechanotransduction, we sought to determine if haploinsufficiency would affect skeletal response to unloading. It has previously been shown that deletion of both alleles of β-catenin in bone cells results in a fragile skeleton highly susceptible to fracture, but deletion of one allele using Dmp1-Cre (Ctnnb1+/loxP; Dmp1-Cre, cKO HET) has little effect on the 2 mo old skeleton. We found that under normal housing conditions, trabecular bone volume was significantly less in 5 mo old male cKO HET mice compared to controls (Ctrl/HET:Tb. BV/TV = 13.96±2.71/8.92±0.95%, Tb.N. = 4.88±0.51/3.95±0.44/mm, Tb. Sp. = 0.20±0.02/0.26±0.03mm, a 36%, 19% and 30% change respectively) but not in females suggesting an age and gender related effect. Before performing suspension experiments and to control for the environmental effects, animals with the same tail attachment and housing conditions, but not suspended (NS), were compared to normally housed (NH) animals. Attachment and housing resulted in weight loss in both genders and phenotypes. Cortical bone loss was observed in the cKO HET males (NH/NS, Ct BV/TV: 90.45±0.72/89.12±0.56%) and both diaphyseal (0.19±0.01/0.17±0.01mm) and metaphyseal (0.10±0.01/0.08±0.01mm) thickness, but not in female cKO HET mice suggesting that male cKO HET mice are susceptible to attachment and housing conditions. These results with transgenic mice emphasizes the importance of proper controls when attributing skeletal responses to unloading. With suspension, cKO HET male mice did not lose bone unlike female cKO HET mice that had greater trabecular bone loss than controls (Ctrl 9%:cKO HET 21% decrease Tb. N; Ctrl 12%:cKO HET 27% increase Tb. Sp.). Suspended and non-suspended mice lost weight compared to normally housed animals. Taken together, the data suggest a protective effect of β-catenin against the effects of stress in males and partial protection against unloading in females

  19. Spatiotemporal features of early neuronogenesis differ in wild-type and albino mouse retina

    NASA Technical Reports Server (NTRS)

    Rachel, Rivka A.; Dolen, Gul; Hayes, Nancy L.; Lu, Alice; Erskine, Lynda; Nowakowski, Richard S.; Mason, Carol A.

    2002-01-01

    In albino mammals, lack of pigment in the retinal pigment epithelium is associated with retinal defects, including poor visual acuity from a photoreceptor deficit in the central retina and poor depth perception from a decrease in ipsilaterally projecting retinal fibers. Possible contributors to these abnormalities are reported delays in neuronogenesis (Ilia and Jeffery, 1996) and retinal maturation (Webster and Rowe, 1991). To further determine possible perturbations in neuronogenesis and/or differentiation, we used cell-specific markers and refined birth dating methods to examine these events during retinal ganglion cell (RGC) genesis in albino and pigmented mice from embryonic day 11 (E11) to E18. Our data indicate that relative to pigmented mice, more ganglion cells are born in the early stages of neuronogenesis in the albino retina, although the initiation of RGC genesis in the albino is unchanged. The cellular organization of the albino retina is perturbed as early as E12. In addition, cell cycle kinetics and output along the nasotemporal axis differ in retinas of albino and pigmented mice, both absolutely, with the temporal aspect of the retina expanded in albino, and relative to the position of the optic nerve head. Finally, blocking melanin synthesis in pigmented eyecups in culture leads to an increase in RGC differentiation, consistent with a role for melanin formation in regulating RGC neuronogenesis. These results point to spatiotemporal defects in neuronal production in the albino retina, which could perturb expression of genes that specify cell fate, number, and/or projection phenotype.

  20. The Protective Effect of Aged Garlic Extract on Nonsteroidal Anti-Inflammatory Drug-Induced Gastric Inflammations in Male Albino Rats

    PubMed Central

    Badr, Gehan Moustafa; AL-Mulhim, Jawaher Abdulaziz

    2014-01-01

    Natural products have long gained wide acceptance among the public and scientific community in the gastrointestinal ulcerative field. The present study explore the potential effects of aged garlic extract (AGE) on indomethacin-(IN-) induced gastric inflammation in male rats. Animals were divided into six groups (n = 8) control group, IN-induced gastric inflammation group via oral single dose (30 mg/kg to fasted rats) two AGE orally administered groups (100 and 200 mg/kg for 30 consecutive days) two AGE orally administered groups to rats pretreated with IN at the same aforementioned doses. The results declared the more potent effect of the higher AGE dose (200 mg/kg) as compared to that of the 100 mg/kg dose in the gastroprotective effects reflected by significant gastric mucosal healing of damage and reduction in the total microbial induced due to indomethacin administration. In addition to the significant effect to normalize the significant increase in malondialdehyde (MDA), myeloperoxidase (MPO), tumor necrosis factor-α (TNF-α) values, and the significant decrease in the total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) values induced by indomethacin. The results support AGE antioxidant, anti-inflammatory, and antimicrobial potency reflected by the healing of the gastric tissue damage induced by indomethacin. PMID:24876878

  1. Corrective role of Eugenia jambolana on testicular impairment in streptozotocin-induced diabetic male albino rat: an approach through genomic and proteomic study.

    PubMed

    Ghosh, A; Jana, K; Ali, K M; De, D; Chatterjee, K; Ghosh, D

    2014-04-01

    The present study was conducted to explore the effect of ethyl acetate fraction of hydro-methanolic (40 : 60) extract of seed of Eugenia jambolana on testicular impairment in diabetic rats. In this respect, biomarkers of oxidative stress, genomics and proteomics in testicular tissue were assessed. Side by side, glycated haemoglobin, serum testosterone, activities of glutamate oxaloacetate transaminase and glutamate pyruvate transaminase in serum, epididymal sperm count including reproductive organosomatic indices were evaluated. Results indicate that a significant recovery (P < 0.05) in the levels of these parameters in fraction-treated diabetic group in comparison with diabetic control. A significant recovery was noted (P < 0.05) in the expression of Bax and Bcl-2 gene towards the control after the treatment of said fraction. Histological study also focused a significant recovery (P < 0.05) in the number of different generation of germ cells at stage VII of spermatogenesis in fraction-treated diabetic group. The said fraction treatment to diabetic rat can recover the activities of serum glutamate oxaloacetate transaminase and glutamate pyruvate transaminase significantly towards the control (P < 0.05). Finally, it may be concluded that ethyl acetate fraction of seed of E. jambolana has a promiseable remedial effect on diabetes-induced testicular dysfunctions in male rat without inducing any metabolic toxicity. PMID:23521341

  2. The protective effect of aged garlic extract on nonsteroidal anti-inflammatory drug-induced gastric inflammations in male albino rats.

    PubMed

    Badr, Gehan Moustafa; Al-Mulhim, Jawaher Abdulaziz

    2014-01-01

    Natural products have long gained wide acceptance among the public and scientific community in the gastrointestinal ulcerative field. The present study explore the potential effects of aged garlic extract (AGE) on indomethacin-(IN-) induced gastric inflammation in male rats. Animals were divided into six groups (n = 8) control group, IN-induced gastric inflammation group via oral single dose (30 mg/kg to fasted rats) two AGE orally administered groups (100 and 200 mg/kg for 30 consecutive days) two AGE orally administered groups to rats pretreated with IN at the same aforementioned doses. The results declared the more potent effect of the higher AGE dose (200 mg/kg) as compared to that of the 100 mg/kg dose in the gastroprotective effects reflected by significant gastric mucosal healing of damage and reduction in the total microbial induced due to indomethacin administration. In addition to the significant effect to normalize the significant increase in malondialdehyde (MDA), myeloperoxidase (MPO), tumor necrosis factor- α (TNF- α ) values, and the significant decrease in the total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) values induced by indomethacin. The results support AGE antioxidant, anti-inflammatory, and antimicrobial potency reflected by the healing of the gastric tissue damage induced by indomethacin. PMID:24876878

  3. COMPARATIVE G.I. ENZYME ACTIVITY AND ACTIVATION OF THE PROMUTAGEN 2,6-DINITROTOLUENE IN MALE CD-1 MICE AND MALE FISCHER 344 RATS

    EPA Science Inventory

    Comparative intestinal nitroreductase, azo reductase, B-glucuronidase, dechlorinase, and dehydrochlorinase activities in young male Fischer 344 rats and young male CD-l mice were measured in vitro while the comparative biotransformation of 2,6 dinitrotoluene to mutagenic metaboli...

  4. Chronic exposure to a predator or its scent does not inhibit male–male competition in male mice lacking brain serotonin

    PubMed Central

    Huo, Ying; Fang, Qi; Shi, Yao-Long; Zhang, Yao-Hua; Zhang, Jian-Xu

    2014-01-01

    Although it is well-known that defective signaling of the 5-HT system in the brain and stressful stimuli can cause psychological disorders, their combined effects on male–male aggression and sexual attractiveness remain unknown. Our research aimed at examining such effects using tryptophan hydroxylase 2 (Tph2) knockout male mice vs. a rat- or rat scent-based chronic stress model. Tph2+/+ and Tph2−/− male mice were placed individually into the rat home cage (rat), a cage containing soiled rat bedding (rat scent) or a cage containing fresh bedding (control) for 5 h every other day for 56 consecutive days. In Tph2+/+ male mice, rat-exposure decreased male–male aggression and sexual attractiveness of urine odor relative to either rat scent-exposure or control; and rat scent-exposure decreased aggression rather than sexual attractiveness of urine odor compared with control. However, such dose-dependent and long-lasting behavioral inhibitory effects vanished in Tph2−/− male mice. RT-PCR assay further revealed that putative regulatory genes, such as AR, ERα and GluR4 in the prefrontal cortex, and TrkB-Tc and 5-HTR1A in the hippocampus, were down-regulated at the mRNA level in either rat- or rat scent-exposed Tph2+/+ male mice, but partially in the Tph2−/− ones. Hence, we suggest that the dose-dependent and long-lasting inhibitory effects of chronic predator exposure on male–male aggression, sexual attractiveness of urine odor, and mRNA expression of central regulatory genes might be mediated through the 5-HT system in the brain of male mice. PMID:24782727

  5. Developmental exposure to Ethinylestradiol affects transgenerationally sexual behavior and neuroendocrine networks in male mice

    PubMed Central

    Derouiche, Lyes; Keller, Matthieu; Duittoz, Anne Hélène; Pillon, Delphine

    2015-01-01

    Reproductive behavior and physiology in adulthood are controlled by hypothalamic sexually dimorphic neuronal networks which are organized under hormonal control during development. These organizing effects may be disturbed by endocrine disrupting chemicals (EDCs). To determine whether developmental exposure to Ethinylestradiol (EE2) may alter reproductive parameters in adult male mice and their progeny, Swiss mice (F1 generation) were exposed from prenatal to peripubertal periods to EE2 (0.1–1 μg/kg/d). Sexual behavior and reproductive physiology were evaluated on F1 males and their F2, F3 and F4 progeny. EE2-exposed F1 males and their F2 to F4 progeny exhibited EE2 dose-dependent increased sexual behavior, with reduced latencies of first mount and intromission, and higher frequencies of intromissions with a receptive female. The EE2 1 μg/kg/d exposed animals and their progeny had more calbindin immunoreactive cells in the medial preoptic area, known to be involved in the control of male sexual behavior in rodents. Despite neuroanatomical modifications in the Gonadotropin-Releasing Hormone neuron population of F1 males exposed to both doses of EE2, no major deleterious effects on reproductive physiology were detected. Therefore EE2 exposure during development may induce a hypermasculinization of the brain, illustrating how widespread exposure of animals and humans to EDCs can impact health and behaviors. PMID:26640081

  6. Modulatory effects of Crataeva nurvala bark against testosterone and N-methyl-N-nitrosourea-induced oxidative damage in prostate of male albino rats

    PubMed Central

    Kumar, Dugganaboyana Guru; Deepa, Purandekkattil; Rathi, Muthaiyan A.; Meenakshi, Periasamy; Gopalakrishnan, Velliyur K.

    2012-01-01

    Background: Antioxidant properties of Crataeva nurvala bark contains a variety of the bioactive phytochemical constituents in medicinal plants which include flavonoids, phenolic compounds, tannins, anthracene derivatives, and essential oils. Components from Crataeva nurvala bark have been accounted to play an important role in scavenging free radicals generated by mutagens and carcinogens. Androgens are the key factors in either the initiation or progression of prostate cancer by inducing oxidative stress. In the present set of investigations, the antioxidative potential of Crataeva nurvala bark extract against androgen-mediated oxidative stress in male Wistar rats has been studied. Materials and Methods: Oxidative damage in prostate was induced in rats by the injection of testosterone (100 mg/kg body weight [bw]) for 3 days followed by injection of chemical carcinogen N-Methyl N-Nitroso Urea (50 mg/kg bw) for 1 week. The oxidative damage in prostate-induced rats were treated with the ethanolic extract of Crataeva nurvala bark (150 mg/kg bw) and testosterone injection (2 mg/ kg bw) was also continued through the experimental period of 4 months. The prostate tissue was dissected out for biochemical analysis of lipid peroxidation and enzymic-antioxidants viz. catalase, superoxide dismutase, glutathione peroxidase, glutathione-S-transferase, and glutathione reductase; the non-enzymic antioxidants viz. reduced glutathione, and Vitamin C. Results: The results revealed that testosterone administration induced the oxidative stress in rat prostate; however, in drug (150 mg/kg bw) supplemented groups, a significant protective effect of Crataeva nurvala bark against testosterone-induced oxidative injury was recorded. Conclusion: Hence, the study reveals that constituents present in Crataeva nurvala bark impart protection against androgen-induced oxidative injury in prostate. PMID:24082632

  7. Altered somatotroph feedback regulation improves metabolic efficiency and limits adipose deposition in male mice.

    PubMed

    Romero, Christopher J; Wolfe, Andrew; Law, Yi Ying; Costelloe, ChenChen Z; Miller, Ryan; Wondisford, Fredric; Radovick, Sally

    2016-04-01

    Several transgenic mouse models with disruption in the growth hormone (GH) axis support the role of GH in augmenting metabolic homeostasis. Specifically, interest has focused on GH's lipolytic properties and ability to affect adipose deposition. Furthermore, both GH and insulin growth factor 1 (IGF-1) may also play a direct or indirect role in adipose development. The somatotroph insulin-like growth factor-1 receptor knockout (SIGFRKO) mouse with only a modest increase in serum GH and IGF-1 demonstrates less adipose tissue than controls. In order to characterize the metabolic phenotype of SIGFRKO mice, histologic analysis of fat depots confirmed a smaller average diameter of adipocytes in the SIGFRKO mice compared to controls. These changes were accompanied by an increase in lipolytic gene expression in fat depots. Indirect calorimetry performed on 6-8week old male mice and again at 25weeks of age demonstrated that SIGFRKO mice, at both ages, had a higher VO2 and increased energy expenditure when compared with controls. The calculated respiratory exchange ratio (RER) was lower in the younger SIGFRKO mice compared to controls. No differences in food consumption or in either ambulatory or total activity were seen between SIGFRKO and control mice in either age group. These studies highlight the role of GH in adipose deposition and its influence on the expression of lipolytic genes resulting in an altered metabolic state, thus providing a mechanism for the decrease in weight gain seen in the SIGFRKO mouse model. PMID:26975547

  8. Administration of saccharin to neonatal mice influences body composition of adult males and reduces body weight of females.

    PubMed

    Parlee, Sebastian D; Simon, Becky R; Scheller, Erica L; Alejandro, Emilyn U; Learman, Brian S; Krishnan, Venkatesh; Bernal-Mizrachi, Ernesto; MacDougald, Ormond A

    2014-04-01

    Nutritional or pharmacological perturbations during perinatal growth can cause persistent effects on the function of white adipose tissue, altering susceptibility to obesity later in life. Previous studies have established that saccharin, a nonnutritive sweetener, inhibits lipolysis in mature adipocytes and stimulates adipogenesis. Thus, the current study tested whether neonatal exposure to saccharin via maternal lactation increased susceptibility of mice to diet-induced obesity. Saccharin decreased body weight of female mice beginning postnatal week 3. Decreased liver weights on week 14 corroborated this diminished body weight. Initially, saccharin also reduced male mouse body weight. By week 5, weights transiently rebounded above controls, and by week 14, male body weights did not differ. Body composition analysis revealed that saccharin increased lean and decreased fat mass of male mice, the latter due to decreased adipocyte size and epididymal, perirenal, and sc adipose weights. A mild improvement in glucose tolerance without a change in insulin sensitivity or secretion aligned with this leaner phenotype. Interestingly, microcomputed tomography analysis indicated that saccharin also increased cortical and trabecular bone mass of male mice and modified cortical bone alone in female mice. A modest increase in circulating testosterone may contribute to the leaner phenotype in male mice. Accordingly, the current study established a developmental period in which saccharin at high concentrations reduces adiposity and increases lean and bone mass in male mice while decreasing generalized growth in female mice. PMID:24456165

  9. Administration of Saccharin to Neonatal Mice Influences Body Composition of Adult Males and Reduces Body Weight of Females

    PubMed Central

    Parlee, Sebastian D.; Simon, Becky R.; Scheller, Erica L.; Alejandro, Emilyn U.; Learman, Brian S.; Krishnan, Venkatesh; Bernal-Mizrachi, Ernesto

    2014-01-01

    Nutritional or pharmacological perturbations during perinatal growth can cause persistent effects on the function of white adipose tissue, altering susceptibility to obesity later in life. Previous studies have established that saccharin, a nonnutritive sweetener, inhibits lipolysis in mature adipocytes and stimulates adipogenesis. Thus, the current study tested whether neonatal exposure to saccharin via maternal lactation increased susceptibility of mice to diet-induced obesity. Saccharin decreased body weight of female mice beginning postnatal week 3. Decreased liver weights on week 14 corroborated this diminished body weight. Initially, saccharin also reduced male mouse body weight. By week 5, weights transiently rebounded above controls, and by week 14, male body weights did not differ. Body composition analysis revealed that saccharin increased lean and decreased fat mass of male mice, the latter due to decreased adipocyte size and epididymal, perirenal, and sc adipose weights. A mild improvement in glucose tolerance without a change in insulin sensitivity or secretion aligned with this leaner phenotype. Interestingly, microcomputed tomography analysis indicated that saccharin also increased cortical and trabecular bone mass of male mice and modified cortical bone alone in female mice. A modest increase in circulating testosterone may contribute to the leaner phenotype in male mice. Accordingly, the current study established a developmental period in which saccharin at high concentrations reduces adiposity and increases lean and bone mass in male mice while decreasing generalized growth in female mice. PMID:24456165

  10. Dual role of betel leaf extract on thyroid function in male mice.

    PubMed

    Panda, S; Kar, A

    1998-12-01

    The effects of betel leaf extract (0.10, 0.40, 0.80 and 2.0 g kg-1 day-1 for 15 days) on the alterations in thyroid hormone concentrations. lipid peroxidation (LPO) and on the activities of superoxide dismutase (SOD) and catalase (CAT) were investigated in male Swiss mice. Administration of betel leaf extract exhibited a dual role, depending on the different doses. While the lowest dose decreased thyroxine (T4) and increased serum triiodothyronine (T3) concentrations, reverse effects were observed at two higher doses. Higher doses also increased LPO with a concomitant decrease in SOD and CAT activities. However, with the lowest dose most of these effects were reversed. These findings suggest that betel leaf can be both stimulatory and inhibitory to thyroid function, particularly for T3 generation and lipid peroxidation in male mice, depending on the amount consumed. PMID:9990660

  11. Postnatal Male Germ Cell Expression of Cre Recombinase in Tex101-iCre Transgenic Mice

    PubMed Central

    Lei, Zhenmin; Lin, Jing; Li, Xian; Li, Shengqiang; Zhou, Huaxin; Araki, Yoshihiko; Lan, Zi-Jian

    2010-01-01

    We have generated a transgenic mouse line which expresses improved Cre recombinase (iCre) under the control of the testis-expressed gene 101 (Tex101) promoter. This transgenic mouse line was named Tex101-iCre. Using the floxed ROSA reporter mice, we found that robust Cre recombinase activity was detected in postnatal testes with weak or no activity in other tissues. Within the testis, Cre recombinase was active in spermatogenic cells as early as the prospermatogonia stage at day 1 after birth. In 30- and 60-day-old mice, positive Cre recombinase activity was detected not only in prospermatogonia but also in spermatogenic cells at later stages of spermatogenesis. There was little or no Cre activity in interstitial cells. Breeding wild-type females with homozygous floxed fibroblast growth factor receptor 2 (Fgfr2) males carrying the Tex101-iCre transgene did not produce any progeny with the floxed Fgfr2 allele. All of the progeny inherited a recombined Fgfr2 allele, indicating that complete deletion of the floxed Fgfr2 allele can be achieved in the male germline by Tex101-iCre mice. Furthermore, FGFR2 protein was not detected in spermatocytes and spermatids of adult Fgfr2fl/fl;Tex101-iCre mice. Taken together, our results suggest that the Tex101-iCre mouse line allows the inactivation of a floxed gene in spermatogenic cells in adult mice, which will facilitate the functional characterization of genes in normal spermatogenesis and male fertility. PMID:20853429

  12. Effects of velvet antler polypeptide on sexual behavior and testosterone synthesis in aging male mice

    PubMed Central

    Zang, Zhi-Jun; Tang, Hong-Feng; Tuo, Ying; Xing, Wei-Jie; Ji, Su-Yun; Gao, Yong; Deng, Chun-Hua

    2016-01-01

    Twenty-four-month-old male C57BL/6 mice with low serum testosterone levels were used as a late-onset hypogonadism (LOH) animal model for examining the effects of velvet antler polypeptide (VAP) on sexual function and testosterone synthesis. These mice received VAP for 5 consecutive weeks by daily gavage at doses of 100, 200, or 300 mg kg−1 body weight per day (n = 10 mice per dose). Control animals (n = 10) received the same weight-based volume of vehicle. Sexual behavior and testosterone levels in serum and interstitial tissue of testis were measured after the last administration of VAP. Furthermore, to investigate the mechanisms of how VAP affects sexual behavior and testosterone synthesis in vivo, the expression of steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), and 3β-hydroxysteroid dehydrogenase (3β-HSD) in Leydig cells was also measured by immunofluorescence staining and quantitative real-time PCR. As a result, VAP produced a significant improvement in the sexual function of these aging male mice. Serum testosterone level and intratesticular testosterone (ITT) concentration also increased in the VAP-treated groups. The expression of StAR, P450scc, and 3β-HSD was also found to be enhanced in the VAP-treated groups compared with the control group. Our results suggested that VAP was effective in improving sexual function in aging male mice. The effect of velvet antler on sexual function was due to the increased expression of several rate-limiting enzymes of testosterone synthesis (StAR, P450scc, and 3β-HSD) and the following promotion of testosterone synthesis in vivo. PMID:26608944

  13. Effects of velvet antler polypeptide on sexual behavior and testosterone synthesis in aging male mice.

    PubMed

    Zang, Zhi-Jun; Tang, Hong-Feng; Tuo, Ying; Xing, Wei-Jie; Ji, Su-Yun; Gao, Yong; Deng, Chun-Hua

    2016-01-01

    Twenty-four-month-old male C57BL/6 mice with low serum testosterone levels were used as a late-onset hypogonadism (LOH) animal model for examining the effects of velvet antler polypeptide (VAP) on sexual function and testosterone synthesis. These mice received VAP for 5 consecutive weeks by daily gavage at doses of 100, 200, or 300 mg kg-1 body weight per day (n = 10 mice per dose). Control animals (n = 10) received the same weight-based volume of vehicle. Sexual behavior and testosterone levels in serum and interstitial tissue of testis were measured after the last administration of VAP. Furthermore, to investigate the mechanisms of how VAP affects sexual behavior and testosterone synthesis in vivo, the expression of steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), and 3β-hydroxysteroid dehydrogenase (3β-HSD) in Leydig cells was also measured by immunofluorescence staining and quantitative real-time PCR. As a result, VAP produced a significant improvement in the sexual function of these aging male mice. Serum testosterone level and intratesticular testosterone (ITT) concentration also increased in the VAP-treated groups. The expression of StAR, P450scc, and 3β-HSD was also found to be enhanced in the VAP-treated groups compared with the control group. Our results suggested that VAP was effective in improving sexual function in aging male mice. The effect of velvet antler on sexual function was due to the increased expression of several rate-limiting enzymes of testosterone synthesis (StAR, P450scc, and 3β-HSD) and the following promotion of testosterone synthesis in vivo. PMID:26608944

  14. Impaired 17,20-Lyase Activity in Male Mice Lacking Cytochrome b5 in Leydig Cells.

    PubMed

    Sondhi, Varun; Owen, Bryn M; Liu, Jiayan; Chomic, Robert; Kliewer, Steven A; Hughes, Beverly A; Arlt, Wiebke; Mangelsdorf, David J; Auchus, Richard J

    2016-04-01

    Androgen and estrogen biosynthesis in mammals requires the 17,20-lyase activity of cytochrome P450 17A1 (steroid 17-hydroxylase/17,20-lyase). Maximal 17,20-lyase activity in vitro requires the presence of cytochrome b5 (b5), and rare cases of b5 deficiency in human beings causes isolated 17,20-lyase deficiency. To study the consequences of conditional b5 removal from testicular Leydig cells in an animal model, we generated Cyb5(flox/flox):Sf1-Cre (LeyKO) mice. The LeyKO male mice had normal body weights, testis and sex organ weights, and fertility compared with littermates. Basal serum and urine steroid profiles of LeyKO males were not significantly different than littermates. In contrast, marked 17-hydroxyprogesterone accumulation (100-fold basal) and reduced testosterone synthesis (27% of littermates) were observed after human chorionic gonadotropin stimulation in LeyKO animals. Testis homogenates from LeyKO mice showed reduced 17,20-lyase activity and a 3-fold increased 17-hydroxylase to 17,20-lyase activity ratio, which were restored to normal upon addition of recombinant b5. We conclude that Leydig cell b5 is required for maximal androgen synthesis and to prevent 17-hydroxyprogesterone accumulation in the mouse testis; however, the b5-independent 17,20-lyase activity of mouse steroid 17-hydroxylase/17,20-lyase is sufficient for normal male genital development and fertility. LeyKO male mice are a good model for the biochemistry but not the physiology of isolated 17,20-lyase deficiency in human beings. PMID:26974035

  15. Impaired 17,20-Lyase Activity in Male Mice Lacking Cytochrome b5 in Leydig Cells

    PubMed Central

    Sondhi, Varun; Owen, Bryn M.; Liu, Jiayan; Chomic, Robert; Kliewer, Steven A.; Hughes, Beverly A.; Arlt, Wiebke; Mangelsdorf, David J.

    2016-01-01

    Androgen and estrogen biosynthesis in mammals requires the 17,20-lyase activity of cytochrome P450 17A1 (steroid 17-hydroxylase/17,20-lyase). Maximal 17,20-lyase activity in vitro requires the presence of cytochrome b5 (b5), and rare cases of b5 deficiency in human beings causes isolated 17,20-lyase deficiency. To study the consequences of conditional b5 removal from testicular Leydig cells in an animal model, we generated Cyb5flox/flox:Sf1-Cre (LeyKO) mice. The LeyKO male mice had normal body weights, testis and sex organ weights, and fertility compared with littermates. Basal serum and urine steroid profiles of LeyKO males were not significantly different than littermates. In contrast, marked 17-hydroxyprogesterone accumulation (100-fold basal) and reduced testosterone synthesis (27% of littermates) were observed after human chorionic gonadotropin stimulation in LeyKO animals. Testis homogenates from LeyKO mice showed reduced 17,20-lyase activity and a 3-fold increased 17-hydroxylase to 17,20-lyase activity ratio, which were restored to normal upon addition of recombinant b5. We conclude that Leydig cell b5 is required for maximal androgen synthesis and to prevent 17-hydroxyprogesterone accumulation in the mouse testis; however, the b5-independent 17,20-lyase activity of mouse steroid 17-hydroxylase/17,20-lyase is sufficient for normal male genital development and fertility. LeyKO male mice are a good model for the biochemistry but not the physiology of isolated 17,20-lyase deficiency in human beings. PMID:26974035

  16. Reversible antifertility effect of aqueous leaf extract of Allamanda cathartica L. in male laboratory mice.

    PubMed

    Singh, A; Singh, S K

    2008-12-01

    The efficacy of oral administration of aqueous leaf extract of Allamanda cathartica (150 mg kg(-1) body weight day(-1) for 14, 28 and 42 days) in inducing infertility and changes in various male reproductive endpoints was evaluated in Parkes strain mice. The effect of the treatment on organ weight, histopathology, sperm parameters, testosterone level, haematology, serum biochemistry and on fertility indices was assessed. Histologically, testes in extract-treated mice showed nonuniform degenerative changes in the seminiferous tubules as both affected and normal tubules were observed in the same sections. The treatment also had adverse effects on motility, viability, morphology and on number of spermatozoa in the cauda epididymidis. Serum levels of testosterone, alanine aminotransferase, aspartate aminotransferase and creatinine, haematological parameters and liver and kidney histoarchitecture were, however, not affected by the treatment. Fertility of the extract-treated males was also suppressed, although the libido remained unaffected. By 56 days of treatment withdrawal, however, the above parameters recovered to control levels. Our results thus suggest that A. cathartica treatment causes reversible suppression of fertility in male mice, without causing detectable toxic effects. PMID:19032682

  17. Behavioral and EEG changes in male 5xFAD mice.

    PubMed

    Schneider, F; Baldauf, K; Wetzel, W; Reymann, K G

    2014-08-01

    Transgenic animal models of Alzheimer's disease (AD) are widely used to investigate mechanisms of pathophysiology and cognitive dysfunctions. A model with a very early development of parenchymal plaque load at the age of 2months is the 5xFAD mouse (Tg6799, Oakley et al. 2006). These 5xFAD mice over-express both human amyloid precursor protein (APP) and human presenilin 1 (PS1). Mice from this line have a high APP expression correlating with a high burden and an accelerated accumulation of the 42 amino acid species of amyloid-β (Aβ). The aim of this study was the behavioral and functional investigations of 5xFAD males because in most studies females of this strain were characterized. In comparison to literature of transgenic 5xFAD females, transgenic 5xFAD males showed decreased anxiety in the elevated plus maze, reduced locomotion and exploration in the open field and disturbances in learning performance in the Morris water maze starting at 9months of age. Electroencephalogram (EEG) recordings on 6month old transgenic mice revealed a decrease of delta, theta, alpha, beta and gamma frequency bands whereas the subdelta frequency was increased. EEG recordings during sleep showed a reduction of rapid eye movement sleep in relation to the amount of total sleep. Thus, 5xFAD males develop early functional disturbances and subsequently behavioral deficits and therefore they are a good mouse model for studying Alzheimer's disease. PMID:24907698

  18. Aqueous fruit extract of Mimusops elengi causes reversible suppression of spermatogenesis and fertility in male mice.

    PubMed

    Singh, N; Singh, S K

    2016-09-01

    Antifertility efficacy of oral administration of aqueous fruit extract of Mimusops elengi (200, 400 and 600 mg kg(-1) body weight/day for 35 days) was evaluated in Parkes strain male mice. Various reproductive end points such as histopathology, sperm parameters, testosterone level, haematology, serum biochemistry and fertility indices were assessed; activities of 3β- and 17β-hydroxysteroid dehydrogenases, and immunoblot expressions of StAR and P450scc in the testis were also assessed. Histologically, testes in Mimusops-treated mice showed nonuniform and diverse degenerative changes in the seminiferous tubules; both affected and normal tubules were observed in the same sections of testis. The treatment had adverse effects on testicular hydroxysteroid dehydrogenases and StAR and P450scc, serum level of testosterone and on motility, viability and number of spermatozoa in cauda epididymis. However, serum levels of alanine aminotransferase, aspartate aminotransferase and creatinine, and haematological parameters were not affected by the treatment. Also, libido was not affected in treated males, but their fertility was markedly suppressed. By 56 days of treatment withdrawal, the alterations caused in the above parameters recovered to control levels, suggesting that Mimusops treatment causes reversible suppression of spermatogenesis and fertility in Parkes mice. Further, there were no detectable signs of toxicity in treated males. PMID:27489141

  19. Soy content of basal diets determines the effects of supplemental selenium in male mice.

    PubMed

    Quiner, Trevor E; Nakken, Heather L; Mason, Brock A; Lephart, Edwin D; Hancock, Chad R; Christensen, Merrill J

    2011-12-01

    The effects of supplemental Se in rodent models may depend upon composition of the basal diet to which it is added. Wild-type male littermates of Transgenic Adenocarcinoma of Mouse Prostate mice were fed until 18 wk of age 1 of 2 Se-adequate stock diets high in soy (HS) or low in phytoestrogens (LP) or the same diets supplemented with 3.0 mg Se/kg diet as seleno-methylselenocysteine. Body and abdominal fat pad weights were lower (P < 0.01) in mice fed the HS diet. Supplemental Se reduced fat pad weights in mice receiving the LP diet but increased body and fat pad weights in mice consuming the HS formulation (P-interaction < 0.005). Serum free triiodothyronine concentrations were unaffected by supplemental Se in mice fed the LP diet but were decreased by Se supplementation of mice given the HS feed (P-interaction < 0.02). Free thyroxine concentrations were higher in mice consuming the HS diet regardless of Se intake (P < 0.001). Hepatic mRNA for iodothyronine deiodinase I was lower (P < 0.001) in mice fed the HS diet. Supplementation of Se increased this mRNA (P < 0.001) in both diet groups. Results from this study show a significant interaction between the composition of basal diets and the effects of supplemental Se with respect to body composition. These findings have important implications for future studies in rodent models of the effects of supplemental Se on heart disease, cancer, diabetes, and other conditions related to body weight and composition. PMID:22031663

  20. Elevated systolic blood pressure in male GH transgenic mice is age dependent.

    PubMed

    Jara, Adam; Benner, Chance M; Sim, Don; Liu, Xingbo; List, Edward O; Householder, Lara A; Berryman, Darlene E; Kopchick, John J

    2014-03-01

    Acromegaly is associated with an increased incidence of cardiovascular disease. Transgenic mice expressing bovine GH (bGH) gene have previously been used to examine the effects of chronic GH stimulation on cardiovascular function. Results concerning systolic blood pressure (SBP) in bGH mice are conflicting. We hypothesized that these discrepancies may be the result of the various ages of the mice used in previous studies. In the current study, SBP was assessed monthly in male bGH mice from 3-12 months of age. Factors known to alter blood pressure were assessed during this time and included: levels of brain natriuretic peptide (BNP) and glucose homeostasis markers, and renal levels of angiotensin-converting enzyme 2 and endothelial nitric oxide synthase. Beginning at 6 months of age bGH had increased SBP compared with wild-type controls, which remained elevated through 12 months of age. Despite having increased blood pressure and cardiac BNP mRNA, bGH mice had decreased circulating levels of BNP. Additionally, bGH mice had an age-dependent decline in insulin levels. For example, they were hyperinsulinemic at 3 months, but by 11 months of age were hypoinsulinemic relative to wild-type controls. This decrease in insulin was accompanied by improved glucose tolerance at 11 months. Finally, both angiotensin-converting enzyme 2 and endothelial nitric oxide synthase expression were severely depressed in kidneys of 11-month-old bGH mice. These results indicate that elevated SBP in bGH mice is dependent on age, independent of insulin resistance, and related to alterations in both the natriuretic peptide and renin-angiotensin systems. PMID:24424040

  1. Effect of dihydrotestosterone on gastrointestinal tract of male Alzheimer's disease transgenic mice.

    PubMed

    Karri, Sritulasi; Acosta-Martinez, Veronica; Coimbatore, Gopalakrishnan

    2010-05-01

    The cause of Alzheimer's disease (AD) is still unknown. While research contributions identifying brain as locus of the disease is growing, evidence of severely impaired gastrointestinal (GI) functions with ageing too is accumulating, there is an equal dearth of information on GI tract in AD condition. The aim of this study was to assess the molecular, histological, morphological and microflora alterations of GI tract in male Alzheimer's transgenic mice. The present study also investigates the effect of dihydrotestosterone (DHT) treatment (1 mg/kg) on AD mice. Histoarchitecture data revealed a significant decrease in the villi number, muscular layer thickness, villi length, width, crypt length, enterocyte length and nuclei length. A shift in colon feces microbial community composition was observed by fatty acid methyl ester analysis. Amyloid precursor protein (APP) expression levels in intestine significantly increased in AD mice revealing its toxicity. DHT treatment attenuated the effect caused by AD on GI morphometrics, APP expression and colon micro flora population. These results for the first time reveal the quantitative and qualitative characteristics of GI tract in male Alzheimer's disease transgenic mice. PMID:20795362

  2. Reproductive toxicity in male mice after exposure to high molybdenum and low copper concentrations.

    PubMed

    Wang, Hong-Wei; Zhou, Bian-Hua; Zhang, Sen; Guo, Hong-Wei; Zhang, Ji-Liang; Zhao, Jing; Tian, Er-Jie

    2016-09-01

    To evaluate the effects of dietary high molybdenum (HMo) and low copper (LCu) concentrations on reproductive toxicity of male mice, 80 mice were divided into 4 groups of 20. These groups were fed with the following: (1) normal control (NC) diet (NC group); (2) NC and HMo diets (HMo group); (3) LCu diet (LCu group); and (4) HMo and LCu diets (HMoLCu group). On the 50th and 100th day, superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC) were analyzed to determine oxidative stress states. Morphological changes in testicular tissue were evaluated with hematoxylin and eosin staining and ultrastructural changes were monitored by transmission electron microscopy. The results showed that administration of HMo, LCu, and HMoLCu not only decreased sperm density and motility but also increased the rate of teratosperm occurrence. A significant increase in MDA content and a decrease in SOD, GSH-Px, and T-AOC contents were observed in LCu, HMo, and HMoLCu groups. Testicular tissues and cells of mice were damaged by HMo and the damages were more serious in the case of Cu deficiency. Exposure to HMo adversely affected the reproductive system of male mice, and dietary LCu plays key roles in HMo-induced reproductive toxicity. PMID:25691499

  3. Chronic exposure to ethanol in male mice may be associated with hearing loss in offspring

    PubMed Central

    Liang, Fei; Diao, Lei; Jiang, Nan; Zhang, Jin; Wang, Hui-Jun; Zhou, Wen-Hao; Huang, Guo-Ying; Ma, Duan

    2015-01-01

    Although paternal ethanol (EtOH) abuse has been shown to affect the growth and behavior of offspring, the exact molecular and mechanistic basis remains largely unclear. Methylation alterations in imprinted genes may be related to well-documented teratogenic effects of ethanol. Here we show that chronic paternal ethanol exposure increases the susceptibility to abnormal behavior in offspring through male game epigenetic alteration. In our study, different doses of ethanol (0, 1.1, 3.3 g kg−1) were administered intra-gastrically to male mice and decreased sperm motility was found in the highest ethanol-exposed group compared with the controls. Data also showed a dose-dependent increase in deaf mice of the paternally ethanol-exposed groups. The methylation of H19, Peg3, Ndn and Snrpn was assessed in paternal spermatozoa and in the cerebral cortices of deaf mice. EtOH affected methylation of Peg3 (CpG 3, 7 and 9) in paternal spermatozoa and in the cerebral cortices of deaf mice, but the level of mRNA expression did not change, suggesting that other gene regulation may be involved in these processes. Overall, chronic paternal ethanol exposure could alter the methylation of imprinted genes in sire spermatozoa that could also be passed on to offspring, giving rise to developmental disorders. Our results provide possible epigenetic evidence for a paternal ethanol exposure contribution to Fetal Alcohol Syndrome (FAS). PMID:26262775

  4. Effects of fetal exposure to gamma rays on aggressive behavior in adult male mice.

    PubMed

    Minamisawa, T; Hirokaga, K; Sasaki, S; Noda, Y

    1992-09-01

    Aggressive behavior (AB) in first generation (F1) hybrid male C57BL/6xC3H mice irradiated on the 14th day of gestation was studied at 100-135 days of age. Gravid female mice were irradiated with 1.0 or 2.0 Gy of gamma rays to the whole body. The AB of pairs of mice were recorded with a capacitance-induction motility monitor and on videotape. Recordings were continued for 90 min, starting at 2:00 PM. Vigorous wrestling, boxing and biting were regarded as AB. Data recorded at 15-min intervals were stored on micro-computer discs. The body weight for the irradiated group was significantly lower than that for the control group. The number of instances of AB was significantly higher in the irradiated group. The AB of the 2.0 Gy group was significantly more intensive than that of the control group. No difference in the duration of AB was found for the 2 irradiated and the control groups. Results demonstrate that male mice irradiated prenatally show increased aggressiveness. PMID:1464856

  5. Chronic exposure to ethanol in male mice may be associated with hearing loss in offspring.

    PubMed

    Liang, Fei; Diao, Lei; Jiang, Nan; Zhang, Jin; Wang, Hui-Jun; Zhou, Wen-Hao; Huang, Guo-Ying; Ma, Duan

    2015-01-01

    Although paternal ethanol (EtOH) abuse has been shown to affect the growth and behavior of offspring, the exact molecular and mechanistic basis remains largely unclear. Methylation alterations in imprinted genes may be related to well-documented teratogenic effects of ethanol. Here we show that chronic paternal ethanol exposure increases the susceptibility to abnormal behavior in offspring through male game epigenetic alteration. In our study, different doses of ethanol (0, 1.1, 3.3 g kg-1 ) were administered intra-gastrically to male mice and decreased sperm motility was found in the highest ethanol-exposed group compared with the controls. Data also showed a dose-dependent increase in deaf mice of the paternally ethanol-exposed groups. The methylation of H19, Peg3, Ndn and Snrpn was assessed in paternal spermatozoa and in the cerebral cortices of deaf mice. EtOH affected methylation of Peg3 (CpG 3, 7 and 9) in paternal spermatozoa and in the cerebral cortices of deaf mice, but the level of mRNA expression did not change, suggesting that other gene regulation may be involved in these processes. Overall, chronic paternal ethanol exposure could alter the methylation of imprinted genes in sire spermatozoa that could also be passed on to offspring, giving rise to developmental disorders. Our results provide possible epigenetic evidence for a paternal ethanol exposure contribution to Fetal Alcohol Syndrome (FAS). PMID:26262775

  6. Cross-Fostering of Male Mice Subtly Affects Female Olfactory Preferences

    PubMed Central

    Liu, Ying-Juan; Zhang, Yao-Hua; Li, Lai-Fu; Du, Rui-Qing; Zhang, Jin-Hua; Zhang, Jian-Xu

    2016-01-01

    The maternal environment has been shown to influence female olfactory preferences through early chemosensory experience. However, little is known about the influence of the maternal environment on chemosignals. In this study, we used two inbred mouse strains, C57BL/6 (C57) and BALB/c (BALB), and explored whether adoption could alter male chemosignals and thus influence female olfactory preferences. In Experiment 1, C57 pups were placed with BALB dams. Adult BALB females then served as the subjects in binary choice tests between paired male urine odours (BALB vs. C57, BALB vs. adopted C57 and C57 vs. adopted C57). In Experiment 2, BALB pups were placed with C57 dams, and C57 females served as the subjects in binary choice tests between paired male urine odours (C57 vs. BALB, C57 vs. adopted BALB, and BALB vs. adopted BALB). In both experiments, we found that females preferred the urine of males from different genetic backgrounds, suggesting that female olfactory preferences may be driven by genetic compatibility. Cross-fostering had subtle effects on female olfactory preferences. Although the females showed no preference between the urine odours of adopted and non-adopted males of the other strain, the BALB females preferred the urine odour of BALB males to that of adopted C57 males, whereas the C57 females showed no preference between the urine odour of C57 and adopted BALB males. Using gas chromatography-mass spectrometry (GC-MS) and stepwise discriminant analysis, we found that the ratios of volatile chemicals from urine and preputial gland secretions were altered in the fostered male mice; these changes may have resulted in the behavioural changes observed in the females. Overall, the results suggest that female mice prefer urine odours from males with different genetic backgrounds; this preference may be driven by genetic compatibility. The early maternal environment influences the chemosignals of males and thus may influence the olfactory preferences of

  7. Female, but not male, mice show delayed cutaneous wound healing following aspirin administration.

    PubMed

    dos Santos, Jeanine S; Monte-Alto-Costa, Andréa

    2013-02-01

    Cyclo-oxygenase (COX) is an enzyme that participates in the wound healing process. Aspirin, a non-steroidal anti-inflammatory drug, simultaneously inhibits the aromatase activity of COX-1 and COX-2 isoforms, which is needed for prostaglandin synthesis. The aim of the present study was to determine whether aspirin, and thus COX inhibition, distinctly affects cutaneous wound healing in female and male mice. Female and male BALB/c mice were treated with aspirin (25 mg/kg per day) for 16 days until they were killed. The control group received vehicle (saline) only. A full-thickness excisional lesion was made on the back, 2 days after aspirin administration started, and macroscopic, histological and biochemical parameters were evaluated. Sections were stained and immunostained for microscopic analysis. Myeloperoxidase (MPO) activity, hydroxyproline quantity and the protein expression of von Willebrand factor (vWF) and vascular endothelial growth factor (VEGF) were also determined. Female control and aspirin-treated groups exhibited delayed wound closure and re-epithelization compared with the male control and aspirin-treated groups, respectively. The female control group exhibited reduced MPO activity and a decreased number of macrophage inhibitory factor-positive cells compared with the male control group. In the female aspirin-treated group, MPO activity and the number of F4/80-positive macrophages was higher than in the control group. Collagen was reduced only in the female aspirin-treated group. The expression of vWF and VEGF protein was increased in the female aspirin-treated group. In conclusion, aspirin administration impaired the wound healing process in BALB/c female, but not male, mice. PMID:23240590

  8. Early deprivation induces competitive subordinance in C57BL/6 male mice.

    PubMed

    Benner, Seico; Endo, Toshihiro; Endo, Nozomi; Kakeyama, Masaki; Tohyama, Chiharu

    2014-10-01

    Rodent models have been widely used to investigate the impact of early life stress on adult health and behavior. However, the social dimension has rarely been incorporated into the analysis due to methodological limitations. This study characterized the effects of neonatal social isolation (early deprivation, ED) on adult C57BL/6 mouse behavior in a social context using our recently developed behavioral test protocols for group-housed mice. During the first two postnatal weeks, half of the pups per dam were separated from their dam and littermates for 3h per day (ED group). Post weaning, ED and control pups were electronically tagged and co-housed. At 12weeks, the mixed cohorts were transferred to IntelliCages, equipped with computer-controlled operant chambers. Access to the chambers was used as an index to analyze novel object response, behavioral flexibility, and competitive dominance with minimal experimenter intervention. In general, ED had greater effects on males; ED males exhibited reduced body weight, increased novelty response, and were subordinate to control littermates when competing for reward access. Male ED mice also demonstrated mildly impaired reversal learning. Analyzing gene expression changes in brain regions controlling emotion, stress, spatial memory, and executive function revealed reduced BDNF and c-Fos in hippocampal CA1, enhanced c-Fos in the basolateral amygdala, reduced Map2 while enhanced HSD11β2 in prefrontal cortex of ED males. In male mice, it was suggested that neonatal social isolation results in sustained changes in social behavior with altered function of limbic and frontal cortices. PMID:25089814

  9. Removal of growth hormone receptor (GHR) in muscle of male mice replicates some of the health benefits seen in global GHR−/− mice

    PubMed Central

    List, Edward O.; Berryman, Darlene E.; Ikeno, Yuji; Hubbard, Gene B.; Funk, Kevin; Comisford, Ross; Young, Jonathan A.; Stout, Michael B.; Tchkonia, Tamar; Masternak, Michal M.; Bartke, Andrzej; Kirkland, James L.; Miller, Richard A.; Kopchick, John J.

    2015-01-01

    Global disruption of the GH receptor in mice (GHR−/−) produces a large and reproducible extension in lifespan. Since lack of GH action in muscle resulting in improved glucose homeostasis is potentially a mechanism by which GHR−/− mice are long-lived, and since no information on muscle-specific GHR disruption in females is available, we generated and characterized a line of muscle-specific GHR disrupted (MuGHRKO) mice. As expected, male MuGHRKO mice had improved fasting blood glucose, insulin, c-peptide, and glucose tolerance. In contrast, female MuGHRKO mice exhibited normal glucose, insulin, and glucose tolerance. Body weight was mildly but significantly altered in opposite directions in males (decreased) and females (increased) compared to controls. Grip strength and treadmill endurance were unchanged with advanced age in both sexes, suggesting that the direct action of GH on muscle has minimal effect on age-related musculoskeletal frailty. Longevity was unchanged in both sexes at Ohio University and significantly increased for males at University of Michigan. These data suggest that removal of GHR in muscle of male MuGHRKO mice replicates some of the health benefits seen in global GHR−/− mice including improvements to glucose homeostasis and smaller body weight in males, which may explain the trends observed in lifespan. PMID:26233957

  10. Phase-Specific Vocalizations of Male Mice at the Initial Encounter during the Courtship Sequence.

    PubMed

    Matsumoto, Yui K; Okanoya, Kazuo

    2016-01-01

    Mice produce ultrasonic vocalizations featuring a variety of syllables. Vocalizations are observed during social interactions. In particular, males produce numerous syllables during courtship. Previous studies have shown that vocalizations change according to sexual behavior, suggesting that males vary their vocalizations depending on the phase of the courtship sequence. To examine this process, we recorded large sets of mouse vocalizations during male-female interactions and acoustically categorized these sounds into 12 vocal types. We found that males emitted predominantly short syllables during the first minute of interaction, more long syllables in the later phases, and mainly harmonic sounds during mounting. These context- and time-dependent changes in vocalization indicate that vocal communication during courtship in mice consists of at least three stages and imply that each vocalization type has a specific role in a phase of the courtship sequence. Our findings suggest that recording for a sufficiently long time and taking the phase of courtship into consideration could provide more insights into the role of vocalization in mouse courtship behavior in future study. PMID:26841117

  11. Female puberty acceleration by male odour in mice: neural pathway and behavioural consequences.

    PubMed

    Jouhanneau, Mélanie; Szymanski, Laura A; Keller, Matthieu

    2014-08-01

    In female mice, exposure to male chemosignals results in early puberty onset characterized by advanced vaginal opening and higher uterine weight. Evidence suggests that the male chemosignals responsible for acceleration of female puberty are androgen-dependent, but not all of the compounds that contribute to puberty acceleration have been identified. The male chemosignals are primarily detected and processed by the vomeronasal system including the vomeronasal organ, the accessory olfactory bulb and the medial amygdala. By contrast, the mechanism by which this olfactory information is integrated in the hypothalamus is poorly understood. In this context, the recent identification of the neuropeptide kisspeptin as a gatekeeper of puberty onset may provide a good candidate neuropeptide system for the transmission of chemosensory information to the gonadotrope axis. PMID:25109972

  12. Pair bonding prevents reinforcing effects of testosterone in male California mice in an unfamiliar environment.

    PubMed

    Zhao, Xin; Marler, Catherine A

    2014-08-01

    Testosterone (T) can be released by stimuli such as social interactions, and thereby influence future social behaviours. Because the reinforcing effects of T can induce preferences for specific environmental locations, T has the potential to alter behaviour through space use. In a monogamous species, this T pulse may contribute differently to space use in sexually naive (SN) and pair-bonded (PB) males: SN males may be more likely to explore new areas to set up a territory than PB males, which are more likely to defend an existing, established territory. In this study, we test for variation in T-driven space use by examining variation in the formation of conditioned place preferences (CPPs) in SN and PB male California mice. In the three-chambered CPP apparatus, subcutaneous administrations of physiological levels of T were used to repeatedly condition SN and PB males to a side chamber, which is an unfamiliar/neutral environment. The final tests revealed that T-induced CPPs in the side chamber are developed in SN, but not PB males. This study fills a gap in our knowledge about plasticity in the rewarding nature of T pulses, based on past social experience. PMID:24943373

  13. EPHRIN-A5 REGULATES INTER-MALE AGGRESSION IN MICE

    PubMed Central

    Sheleg, Michal; Yochum, Carrie L.; Richardson, Jason R.; Wagner, George C.; Zhou, Renping

    2015-01-01

    The Eph family of receptor tyrosine kinases play key roles in both the patterning of the developing nervous system and neural plasticity in the mature brain. To determine functions of ephrin-A5, a GPI-linked ligand to the Eph receptors, in animal behavior regulations, we examined effects of its inactivation on male mouse aggression. When tested in the resident-intruder paradigm for offensive aggression, ephrin-A5-mutant animals (ephrin-A5−/−) exhibited severe reduction in conspecific aggression compared to wild-type controls. On the contrary, defensive aggression in the form of target biting was higher in ephrin-A5−/− mice, indicating that the mutant mice are capable of attacking behavior. In addition, given the critical role of olfaction in aggressive behavior, we examined the ability of the ephrin-A5−/− mice to smell and found no differences between the mutant and control animals. Testosterone levels in the mutant mice were also found to be within the normal range. Taken together, our data reveal a new role of ephrin-A5 in the regulation of aggressive behavior in mice. PMID:25746458

  14. Ephrin-A5 regulates inter-male aggression in mice.

    PubMed

    Sheleg, Michal; Yochum, Carrie L; Richardson, Jason R; Wagner, George C; Zhou, Renping

    2015-06-01

    The Eph family of receptor tyrosine kinases play key roles in both the patterning of the developing nervous system and neural plasticity in the mature brain. To determine functions of ephrin-A5, a GPI-linked ligand to the Eph receptors, in animal behavior regulations, we examined effects of its inactivation on male mouse aggression. When tested in the resident-intruder paradigm for offensive aggression, ephrin-A5-mutant animals (ephrin-A5(-/-)) exhibited severe reduction in conspecific aggression compared to wild-type controls. On the contrary, defensive aggression in the form of target biting was higher in ephrin-A5(-/-) mice, indicating that the mutant mice are capable of attacking behavior. In addition, given the critical role of olfaction in aggressive behavior, we examined the ability of the ephrin-A5(-/-) mice to smell and found no differences between the mutant and control animals. Testosterone levels in the mutant mice were also found to be within the normal range. Taken together, our data reveal a new role of ephrin-A5 in the regulation of aggressive behavior in mice. PMID:25746458

  15. Melanin-concentrating hormone is necessary for olanzapine-inhibited locomotor activity in male mice.

    PubMed

    Chee, Melissa J S; Douris, Nicholas; Forrow, Avery B; Monnard, Arnaud; Lu, Shuangyu; Flaherty, Stephen E; Adams, Andrew C; Maratos-Flier, Eleftheria

    2015-10-01

    Olanzapine (OLZ), an atypical antipsychotic, can be effective in treating patients with restricting type anorexia nervosa who exercise excessively. Clinical improvements include weight gain and reduced pathological hyperactivity. However the neuronal populations and mechanisms underlying OLZ actions are not known. We studied the effects of OLZ on hyperactivity using male mice lacking the hypothalamic neuropeptide melanin-concentrating hormone (MCHKO) that are lean and hyperactive. We compared the in vivo effects of systemic or intra-accumbens nucleus (Acb) OLZ administration on locomotor activity in WT and MCHKO littermates. Acute systemic OLZ treatment in WT mice significantly reduced locomotor activity, an effect that is substantially attenuated in MCHKO mice. Furthermore, OLZ infusion directly into the Acb of WT mice reduced locomotor activity, but not in MCHKO mice. To identify contributing neuronal mechanisms, we assessed the effect of OLZ treatment on Acb synaptic transmission ex vivo and in vitro. Intraperitoneal OLZ treatment reduced Acb GABAergic activity in WT but not MCHKO neurons. This effect was also seen in vitro by applying OLZ to acute brain slices. OLZ reduced the frequency and amplitude of GABAergic activity that was more robust in WT than MCHKO Acb. These findings indicate that OLZ reduced Acb GABAergic transmission and that MCH is necessary for the hypolocomotor effects of OLZ. PMID:26092201

  16. Additive Effects of Nicotine and High-Fat Diet on Hepatic Steatosis in Male Mice

    PubMed Central

    Friedman, Theodore C.; Sinha-Hikim, Indrani; Parveen, Meher; Najjar, Sonia M.; Liu, Yanjun; Mangubat, Michael; Shin, Chang-Sung; Lyzlov, Alexei; Ivey, Rasheed; Shaheen, Magda; French, Samuel W.

    2012-01-01

    Smoking is a major risk factor for diabetes and cardiovascular disease and may contribute to nonalcoholic fatty liver disease. We hypothesize that in the presence of nicotine, high-fat diet (HFD) causes more severe hepatic steatosis in obese mice. Adult C57BL6 male mice were fed a normal chow diet or HFD and received twice daily injections of nicotine (0.75 mg/kg body weight, ip) or saline for 10 wk. Light microscopic image analysis revealed significantly higher lipid accumulation in livers from mice on HFD plus nicotine (190 ± 19 μm2), compared with mice on HFD alone (28 ± 1.2 μm2). A significant reduction in the percent volume of endoplasmic reticulum (67.8%) and glycogen (49.2%) was also noted in hepatocytes from mice on HFD plus nicotine, compared with mice on HFD alone. The additive effects of nicotine on the severity of HFD-induced hepatic steatosis was associated with significantly greater oxidative stress, increased hepatic triglyceride levels, higher incidence of hepatocellular apoptosis, inactivation (dephosphorylation) of AMP-activated protein kinase, and activation of its downstream target acetyl-coenzyme A-carboxylase. Treatment with acipimox, an inhibitor of lipolysis, significantly reduced nicotine plus HFD-induced hepatic lipid accumulation. We conclude that: 1) greater oxidative stress coupled with inactivation of AMP-activated protein kinase mediate the additive effects of nicotine and HFD on hepatic steatosis in obese mice and 2) increased lipolysis is an important contributor to hepatic steatosis. We surmise that nicotine exposure is likely to exacerbate the metabolic abnormalities induced by high-fat intake in obese patients. PMID:23093702

  17. Animal models of physiologic markers of male reproduction: genetically defined infertile mice

    SciTech Connect

    Chubb, C.

    1987-10-01

    The present report focuses on novel animal models of male infertility: genetically defined mice bearing single-gene mutations that induce infertility. The primary goal of the investigations was to identify the reproductive defects in these mutant mice. The phenotypic effects of the gene mutations were deciphered by comparing the mutant mice to their normal siblings. Initially testicular steroidogenesis and spermatogenesis were investigated. The physiologic markers for testicular steroidogenesis were steroid secretion by testes perifused in vitro, seminal vesicle weight, and Leydig cell histology. Spermatogenesis was evaluated by the enumeration of homogenization-resistant sperm/spermatids in testes and by morphometric analyses of germ cells in the seminiferous epithelium. If testicular function appeared normal, the authors investigated the sexual behavior of the mice. The parameters of male sexual behavior that were quantified included mount patency, mount frequency, intromission latency, thrusts per intromission, ejaculation latency, and ejaculation duration. Females of pairs breeding under normal circumstances were monitored for the presence of vaginal plugs and pregnancies. The patency of the ejaculatory process was determined by quantifying sperm in the female reproductive tract after sexual behavior tests. Sperm function was studied by quantitatively determining sperm motility during videomicroscopic observation. Also, the ability of epididymal sperm to function within the uterine environment was analyzed by determining sperm capacity to initiate pregnancy after artificial insemination. Together, the experimental results permitted the grouping of the gene mutations into three general categories. They propose that the same biological markers used in the reported studies can be implemented in the assessment of the impact that environmental toxins may have on male reproduction.

  18. Animal models of physiologic markers of male reproduction: genetically defined infertile mice.

    PubMed Central

    Chubb, C

    1987-01-01

    The present report focuses on novel animal models of male infertility: genetically defined mice bearing single-gene mutations that induce infertility. The primary goal of our investigations was to identify the reproductive defects in these mutant mice. The phenotypic effects of the gene mutations were deciphered by comparing the mutant mice to their normal siblings. Initially testicular steroidogenesis and spermatogenesis were investigated. The physiologic markers for testicular steroidogenesis were steroid secretion by testes perifused in vitro, seminal vesicle weight, and Leydig cell histology. Spermatogenesis was evaluated by the enumeration of homogenization-resistant sperm/spermatids in testes and by morphometric analyses of germ cells in the seminiferous epithelium. If testicular function appeared normal, we investigated the sexual behavior of the mice. The parameters of male sexual behavior that were quantified included mount patency, mount frequency, intromission latency, thrusts per intromission, ejaculation latency, and ejaculation duration. Females of pairs breeding under normal circumstances were monitored for the presence of vaginal plugs and pregnancies. The patency of the ejaculatory process was determined by quantifying sperm in the female reproductive tract after sexual behavior tests. Sperm function was studied by quantitatively determining sperm motility during videomicroscopic observation. Also, the ability of epididymal sperm to function within the uterine environment was analyzed by determining sperm capacity to initiate pregnancy after artificial insemination. Together, the experimental results permitted the grouping of the gene mutations into three general categories. We propose that the same biological markers used in the reported studies can be implemented in the assessment of the impact that environmental toxins may have on male reproduction. PMID:3319549

  19. Immune alterations in male and female mice after 2-deoxy-D-glucose administration

    NASA Technical Reports Server (NTRS)

    Dreau, D.; Morton, D. S.; Foster, M.; Swiggett, J. P.; Sonnenfeld, G.

    1997-01-01

    Administration of 2-deoxy-D-glucose (2-DG) induces acute cellular glucoprivation. In the current study, we examined differences in immune parameters after 2-DG administration in both sexes. Male and female BDF1 mice were injected three times, 48 h apart, either with a saline solution (control group) or with 2-DG in saline (500 mg/kg). Two hours after the last injection, blood and spleens were collected. Plasma levels of interleukin-1beta, and interferon-gamma levels were measured. Additionally, the levels of the specific leukocyte antigens CD3, CD4, CD8, T cell receptor (TCR) alpha/beta, I-Ad, and H-2Ld/H-2Db were evaluated by flow cytometry on both blood and spleen cells. The blastogenic response of leukocytes from both tissues to mitogens was assessed. Levels of glucose, corticosterone, testosterone, progesterone, 17beta-estradiol, follicle-stimulating hormone, and luteinizing hormone were also determined. Increases in the percentage of cells bearing TCR alpha/beta and I-Ad in the blood and H-2Ld/H-2Db in the spleen were observed in the 2-DG-treated group for both sexes. In contrast, higher corticosterone and IL-1beta plasma concentrations, as well as higher percentages of splenocytes bearing TCR alpha/beta and I-Ad, and lower mitogen-induced proliferation of mature T splenocytes (79%) were observed in female but not in male mice injected with 2-DG compared with those injected with saline (p < 0.05). Taken together, these results suggest that female mice are more sensitive than male mice to immune alterations induced by 2-DG administration.

  20. Comparison of Neurological Function in Males and Females from Two Substrains of C57BL/6 Mice

    PubMed Central

    Ashworth, Amy; Bardgett, Mark E.; Fowler, Jocelyn; Garber, Helen; Griffith, Molly; Curran, Christine Perdan

    2016-01-01

    The C57BL/6 (B6) mouse is the background strain most frequently used for genetically-modified mice. Previous studies have found significant behavioral and genetic differences between the B6J (The Jackson Laboratory) and B6N substrains (National Institutes of Health); however, most studies employed only male mice. We performed a comprehensive battery of motor function and learning and memory tests on male and female mice from both substrains. The B6N male mice had greater improvement in the rotarod test. In contrast, B6J female mice had longer latencies to falling from the rotarod. In the Morris water maze (MWM), B6J males had significantly shorter latencies to finding the hidden platform. However, B6N females had significantly shorter path lengths in the reversal and shifted-reduced phases. In open field locomotor activity, B6J males had higher activity levels, whereas B6N females took longer to habituate. In the fear conditioning test, B6N males had a significantly longer time freezing in the new context compared with B6J males, but no significant differences were found in contextual or cued tests. In summary, our findings demonstrate the importance of testing both males and females in neurobehavioral studies. Both factors (sex and substrain) must be taken into account when designing developmental neurotoxicology studies. PMID:27081652

  1. Prolyl Endopeptidase (PREP) is Associated With Male Reproductive Functions and Gamete Physiology in Mice.

    PubMed

    Dotolo, Raffaele; Kim, Jung Dae; Pariante, Paolo; Minucci, Sergio; Diano, Sabrina

    2016-03-01

    Prolyl endopeptidase (PREP) is a serine protease which has been implicated in many biological processes, such as the maturation and degradation of peptide hormones and neuropeptides, learning and memory, cell proliferation and differentiation, and glucose metabolism. A small number of reports have also suggested PREP participation in both male and female reproduction-associated processes. In the present work, we examined PREP distribution in male germ cells and studied the effects of its knockdown (Prep(gt/gt)) on testis and sperm in adult mice. The protein is expressed and localized in elongating spermatids and luminal spermatozoa of wild type (wt) mice, as well as Sertoli, Leydig, and peritubular cells. PREP is also expressed in the head and midpiece of epididymal spermatozoa, whereas the remaining tail region shows a weaker signal. Furthermore, testis weight, histology of seminiferous tubules, and epididymal sperm parameters were assessed in wt and Prep(gt/gt) mice: wild type testes have larger average tubule and lumen diameter; in addition, lumenal composition of seminiferous tubules is dissimilar between wt and Prep(gt/gt), as the percentage of spermiated tubules is much higher in wt. Finally, total sperm count, sperm motility, and normal morphology are also higher in wt than in Prep(gt/gt). These results show for the first time that the expression of PREP could be necessary for a correct reproductive function, and suggest that the enzyme may play a role in mouse spermatogenesis and sperm physiology. PMID:26332268

  2. Partial Müllerian Duct Retention in Smad4 Conditional Mutant Male Mice

    PubMed Central

    Petit, Fabrice G.; Deng, Chuxia; Jamin, Soazik P.

    2016-01-01

    Müllerian duct regression is a complex process which involves the AMH signalling pathway. We have previously demonstrated that besides AMH and its specific type II receptor (AMHRII), BMPR-IA and Smad5 are two essential factors implicated in this mechanism. Mothers against decapentaplegic homolog 4 (Smad4) is a transcription factor and the common Smad (co-Smad) involved in transforming growth factor beta (TGF-β) signalling pathway superfamily. Since Smad4 null mutants die early during gastrulation, we have inactivated Smad4 in the Müllerian duct mesenchyme. Specific inactivation of Smad4 in the urogenital ridge leads to the partial persistence of the Müllerian duct in adult male mice. Careful examination of the urogenital tract reveals that the Müllerian duct retention is randomly distributed either on one side or both sides. Histological analysis shows a uterus-like structure, which is confirmed by the expression of estrogen receptor α. As previously described in a β-catenin conditional mutant mouse model, β-catenin contributes to Müllerian duct regression. In our mutant male embryos, it appears that β-catenin expression is locally reduced along the urogenital ridge as compared to control mice. Moreover, the expression pattern is similar to those observed in control female mice. This study shows that reduced Smad4 expression disrupts the Wnt/β-catenin signalling leading to the partial persistence of Müllerian duct. PMID:27194944

  3. Mfsd14a (Hiat1) gene disruption causes globozoospermia and infertility in male mice.

    PubMed

    Doran, Joanne; Walters, Cara; Kyle, Victoria; Wooding, Peter; Hammett-Burke, Rebecca; Colledge, William Henry

    2016-07-01

    The Mfsd14a gene, previously called Hiat1, encodes a transmembrane protein of unknown function with homology to the solute carrier protein family. To study the function of the MFSD14A protein, mutant mice (Mus musculus, strain 129S6Sv/Ev) were generated with the Mfsd14a gene disrupted with a LacZ reporter gene. Homozygous mutant mice are viable and healthy, but males are sterile due to a 100-fold reduction in the number of spermatozoa in the vas deferens. Male mice have adequate levels of testosterone and show normal copulatory behaviour. The few spermatozoa that are formed show rounded head defects similar to those found in humans with globozoospermia. Spermatogenesis proceeds normally up to the round spermatid stage, but the subsequent structural changes associated with spermiogenesis are severely disrupted with failure of acrosome formation, sperm head condensation and mitochondrial localization to the mid-piece of the sperm. Staining for β-galactosidase activity as a surrogate for Mfsd14a expression indicates expression in Sertoli cells, suggesting that MFSD14A may transport a solute from the bloodstream that is required for spermiogenesis. PMID:27107036

  4. The orphan nuclear receptor small heterodimer partner mediates male infertility induced by diethylstilbestrol in mice

    PubMed Central

    Volle, David H.; Decourteix, Mélanie; Garo, Erwan; McNeilly, Judy; Fenichel, Patrick; Auwerx, Johan; McNeilly, Alan S.; Schoonjans, Kristina; Benahmed, Mohamed

    2009-01-01

    Studies in rodents have shown that male sexual function can be disrupted by fetal or neonatal administration of compounds that alter endocrine homeostasis, such as the synthetic nonsteroidal estrogen diethylstilbestrol (DES). Although the molecular basis for this effect remains unknown, estrogen receptors likely play a critical role in mediating DES-induced infertility. Recently, we showed that the orphan nuclear receptor small heterodimer partner (Nr0b2), which is both a target gene and a transcriptional repressor of estrogen receptors, controls testicular function by regulating germ cell entry into meiosis and testosterone synthesis. We therefore hypothesized that some of the harmful effects of DES on testes could be mediated through Nr0b2. Here, we present data demonstrating that Nr0b2 deficiency protected mice against the negative effects of DES on testis development and function. During postnatal development, Nr0b2-null mice were resistant to DES-mediated inhibition of germ cell differentiation, which may be the result of interference by Nr0b2 with retinoid signals that control meiosis. Adult Nr0b2-null male mice were also protected against the effects of DES; however, we suggest that this phenomenon was due to the removal of the repressive effects of Nr0b2 on steroidogenesis. Together, these data demonstrate that Nr0b2 plays a critical role in the pathophysiological changes induced by DES in the mouse testis. PMID:19884658

  5. Influence of chronic exposure to uranium on male reproduction in mice

    SciTech Connect

    Llobet, J.M.; Sirvent, J.J.; Ortega, A.; Domingo, J.L. )

    1991-05-01

    Relatively few data are available concerning the reproductive and developmental toxicity of uranium. The present study was designed to evaluate the reproductive effects of this metal in male Swiss mice. The animals were treated with uranyl acetate dihydrate at doses of 0, 10, 20, 40, and 80 mg/kg/day given in the drinking water for 64 days. To evaluate the fertility of the uranium-treated males, mice were mated with untreated females for 4 days. There was a significant but non-dose-related decrease in the pregnancy rate of these animals. Body weights were significantly depressed only in the 80 mg/kg/day group. Testicular function/spermatogenesis was not affected by uranium at any dose, as evidenced by normal testes and epididymis weights and normal spermatogenesis, whereas interstitial alterations and vacuolization of Leydig cells were seen at 80 mg/kg/day. The results of this investigation indicate that uranium does not cause any adverse effect on testicular function in mice at the concentrations usually ingested in the diet and drinking water, with a safety factor of more than 1000. However, although spermatogenesis was not affected by uranium administration, uranium produces a significant decrease in the pregnancy rate at 10, 20, 40, or 80 mg/kg/day.

  6. Potential O-acyl-substituted (-)-Epicatechin gallate prodrugs as inhibitors of DMBA/TPA-induced squamous cell carcinoma of skin in Swiss albino mice.

    PubMed

    Vyas, Sandeep; Manon, Benu; Vir Singh, Tej; Dev Sharma, Pritam; Sharma, Manu

    2011-04-01

    (-)-Epicatechin-3-gallate (1) is one of the principal catechins of green tea and exhibits cancer-preventive activities in various animal models. However, this compound is unstable in neutral or alkaline medium and, therefore, has a poor bioavailability. To improve its stability, O-acyl derivatives of 1 were prepared by isolating the partially purified tea catechin fraction from green tea extract and treating it with a variety of acylating agents. The resulting derivatives, compounds 2-6, were screened for their antitumor potential against 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced squamous cell carcinogenesis of skin in mice. The results showed that the antitumor activity decreased with the increase in size of the chain length of the acyl groups, i.e., from compound 2, derivative with an Ac group, to compound 6, possessing a valeryl group. Moreover, the C(4) derivative with a branched acyl chain, 5, had a lower activity than the linear C(4) derivative 4. This reduction in the inhibitory activity may be due to the steric hindrance by the two Me groups. Moreover, significant increases in the protein levels analyzed by ELISA of c-Jun, p65, and p53 were observed in the skin of DMBA/TPA treated mice, whereas mice treated with 2 and DMBA/TPA had a similar expression of these transcription factors than the control mice. The prodrug potential of the O-acyl derivatives 2-6 showed that they were adequately stable to be absorbed intact from the intestine, more stable at gastric pH, and suitable for oral administration. PMID:21480506

  7. Protective Effect of Parsley Juice (Petroselinum crispum, Apiaceae) against Cadmium Deleterious Changes in the Developed Albino Mice Newborns (Mus musculus) Brain.

    PubMed

    Allam, Ahmed A; Maodaa, Salah N; Abo-Eleneen, Rasha; Ajarem, Jamaan

    2016-01-01

    Parsley was used as a probe of the current experiment to prevent the behavioral, morphological and biochemical changes in the newborn brain following the administration of cadmium (Cd) to the pregnant mice. The nonanesthetized pregnant mice were given daily parsley juice (Petroselinum crispum) at doses of 20 mg/kg and 10 mg/kg. Pregnant mothers were given Cd at a dose of 30 mg/kg divided into 3 equal times. The newborns have been divided into 6 groups: Group A, mothers did not take treatment; Groups B and C, mothers were treated with low and high dose of parsley, respectively; Group D, mothers were treated only with Cd (perinatal intoxication); Groups E and F, mothers were treated with Cd doses and protected by low and high doses of parsley, respectively. Light microscopy showed that Cd-induced neuronal degeneration by chromatolysis and pyknosis in the brain regions. The low dose of parsley 10 g/kg/day exhibited significant effects in neutralizing and reducing the deleterious changes due to Cd exposure during pregnancy on the behavioral activities, neurotransmitters, oxidative stress, and brain neurons morphology of the mice newborns. PMID:26966507

  8. Protective Effect of Parsley Juice (Petroselinum crispum, Apiaceae) against Cadmium Deleterious Changes in the Developed Albino Mice Newborns (Mus musculus) Brain

    PubMed Central

    Allam, Ahmed A.; Maodaa, Salah N.; Abo-Eleneen, Rasha; Ajarem, Jamaan

    2016-01-01

    Parsley was used as a probe of the current experiment to prevent the behavioral, morphological and biochemical changes in the newborn brain following the administration of cadmium (Cd) to the pregnant mice. The nonanesthetized pregnant mice were given daily parsley juice (Petroselinum crispum) at doses of 20 mg/kg and 10 mg/kg. Pregnant mothers were given Cd at a dose of 30 mg/kg divided into 3 equal times. The newborns have been divided into 6 groups: Group A, mothers did not take treatment; Groups B and C, mothers were treated with low and high dose of parsley, respectively; Group D, mothers were treated only with Cd (perinatal intoxication); Groups E and F, mothers were treated with Cd doses and protected by low and high doses of parsley, respectively. Light microscopy showed that Cd-induced neuronal degeneration by chromatolysis and pyknosis in the brain regions. The low dose of parsley 10 g/kg/day exhibited significant effects in neutralizing and reducing the deleterious changes due to Cd exposure during pregnancy on the behavioral activities, neurotransmitters, oxidative stress, and brain neurons morphology of the mice newborns. PMID:26966507

  9. Phase-Specific Vocalizations of Male Mice at the Initial Encounter during the Courtship Sequence

    PubMed Central

    Matsumoto, Yui K.; Okanoya, Kazuo

    2016-01-01

    Mice produce ultrasonic vocalizations featuring a variety of syllables. Vocalizations are observed during social interactions. In particular, males produce numerous syllables during courtship. Previous studies have shown that vocalizations change according to sexual behavior, suggesting that males vary their vocalizations depending on the phase of the courtship sequence. To examine this process, we recorded large sets of mouse vocalizations during male–female interactions and acoustically categorized these sounds into 12 vocal types. We found that males emitted predominantly short syllables during the first minute of interaction, more long syllables in the later phases, and mainly harmonic sounds during mounting. These context- and time-dependent changes in vocalization indicate that vocal communication during courtship in mice consists of at least three stages and imply that each vocalization type has a specific role in a phase of the courtship sequence. Our findings suggest that recording for a sufficiently long time and taking the phase of courtship into consideration could provide more insights into the role of vocalization in mouse courtship behavior in future study. PMID:26841117

  10. Male-Specific Cardiac Dysfunction in CTP:Phosphoethanolamine Cytidylyltransferase (Pcyt2)-Deficient Mice

    PubMed Central

    Basu, Poulami; Alibhai, Faisal J.; Tsimakouridze, Elena V.; Singh, Ratnesh K.; Paglialunga, Sabina; Holloway, Graham P.; Martino, Tami A.

    2015-01-01

    Phosphatidylethanolamine (PE) is the most abundant inner membrane phospholipid. PE synthesis from ethanolamine and diacylglycerol is regulated primarily by CTP:phosphoethanolamine cytidylyltransferase (Pcyt2). Pcyt2+/− mice have reduced PE synthesis and, as a consequence, perturbed glucose and fatty acid metabolism, which gradually leads to the development of hyperlipidemia, obesity, and insulin resistance. Glucose and fatty acid uptake and the corresponding transporters Glut4 and Cd36 are similarly impaired in male and female Pcyt2+/− hearts. These mice also have similarly reduced phosphatidylinositol 3-kinase (PI3K)/Akt1 signaling and increased reactive oxygen species (ROS) production in the heart. However, only Pcyt2+/− males develop hypertension and cardiac hypertrophy. Pcyt2+/− males have upregulated heart AceI expression, heart phospholipids enriched in arachidonic acid and other n-6 polyunsaturated fatty acids, and dramatically increased ROS production in the aorta. In contrast, Pcyt2+/− females have unmodified heart phospholipids but have reduced heart triglyceride levels and altered expression of the structural genes Acta (low) and Myh7 (high). These changes together protect Pcyt2+/− females from cardiac dysfunction under conditions of reduced glucose and fatty acid uptake and heart insulin resistance. Our data identify Pcyt2 and membrane PE biogenesis as important determinants of gender-specific differences in cardiac lipids and heart function. PMID:25986609

  11. Female house mice avoid fertilization by t haplotype incompatible males in a mate choice experiment.

    PubMed

    Manser, A; König, B; Lindholm, A K

    2015-01-01

    The t haplotype in house mice is a well-known selfish genetic element with detrimental, nonadditive fitness consequences to its carriers: recessive lethal mutations cause t/t homozygotes to perish in utero. Given the severe genetic incompatibility imposed by the t haplotype, we predict females to avoid fertilization by t haplotype incompatible males. Indeed, some of the strongest evidence for compatibility mate choice is related to the t haplotype in house mice. However, all previous evidence for compatibility mate choice in this system is based on olfactory preference. It is so far unknown how general these preferences are and whether they are relevant in an actual mating context. Here, we assess female compatibility mate choice related to t haplotypes in a setting that--for the first time--allowed females to directly interact and mate with males. This approach enabled us to analyse female behaviour during the testing period, and the resulting paternity success and fitness consequences of a given choice. We show that genetic incompatibilities arising from the t haplotype had severe indirect fitness consequences and t females avoided fertilization by t incompatible males. The results are inconclusive whether this avoidance of t fertilization by t females was caused by pre- or post-copulatory processes. PMID:25494878

  12. Quaternary ammonium disinfectants cause subfertility in mice by targeting both male and female reproductive processes.

    PubMed

    Melin, Vanessa E; Melin, Travis E; Dessify, Brian J; Nguyen, Christina T; Shea, Caroline S; Hrubec, Terry C

    2016-01-01

    Alkyl dimethyl benzyl ammonium chloride (ADBAC) and didecyl dimethyl ammonium chloride (DDAC) are common ingredients in household bathroom and kitchen cleaning sprays. ADBAC+DDAC cause reproductive toxicity in mice. The aim of the present study was to investigate gender-specific reproductive effects from ADBAC+DDAC. Female reproduction was assessed through ovulation, oocyte implantation, and estrus cycling. Male reproductive function was assessed by sperm concentration, motility, and viability. Numbers of corpora lutea were not different after 2 weeks, but decreased after 8 weeks of ADBAC+DDAC exposure. Dams exposed for 5 weeks to ADBAC+DDAC spent significantly less time in estrus. ADBAC+DDAC exposed males exhibited declines in both sperm concentration and motility, but not sperm viability. Subfertility in mice from ADBAC+DDAC exposure is, therefore, mediated through reproductive disturbances in both females and males. While the effect of ADBAC+DDAC exposure on human health is unclear, widespread exposure necessitates further consideration of their potential reproductive toxicity. PMID:26582257

  13. Female house mice avoid fertilization by t haplotype incompatible males in a mate choice experiment

    PubMed Central

    Manser, A; König, B; Lindholm, A K

    2015-01-01

    The t haplotype in house mice is a well-known selfish genetic element with detrimental, nonadditive fitness consequences to its carriers: recessive lethal mutations cause t/t homozygotes to perish in utero. Given the severe genetic incompatibility imposed by the t haplotype, we predict females to avoid fertilization by t haplotype incompatible males. Indeed, some of the strongest evidence for compatibility mate choice is related to the t haplotype in house mice. However, all previous evidence for compatibility mate choice in this system is based on olfactory preference. It is so far unknown how general these preferences are and whether they are relevant in an actual mating context. Here, we assess female compatibility mate choice related to t haplotypes in a setting that – for the first time – allowed females to directly interact and mate with males. This approach enabled us to analyse female behaviour during the testing period, and the resulting paternity success and fitness consequences of a given choice. We show that genetic incompatibilities arising from the t haplotype had severe indirect fitness consequences and t females avoided fertilization by t incompatible males. The results are inconclusive whether this avoidance of t fertilization by t females was caused by pre- or post-copulatory processes. PMID:25494878

  14. Acrylonitrile is a multisite carcinogen in male and female B6C3F1 mice.

    PubMed

    Ghanayem, Burhan I; Nyska, Abraham; Haseman, Joseph K; Bucher, John R

    2002-07-01

    Acrylonitrile is a heavily produced unsaturated nitrile, which is used in the production of synthetic fibers, plastics, resins, and rubber. Acrylonitrile is a multisite carcinogen in rats after exposure via gavage, drinking water, or inhalation. No carcinogenicity studies of acrylonitrile in a second animal species were available. The current studies were designed to assess the carcinogenicity of acrylonitrile in B6C3F1 mice of both sexes. Acrylonitrile was administered by gavage at 0, 2.5, 10, or 20 mg/kg/day, 5 days per week, for 2 years. Urinary thiocyanate and N-acetyl-S-(2-cyanoethyl)-L-cysteine were measured as markers of exposure to acrylonitrile. In general, there were dose-related increases in urinary thiocyanate and N-acetyl-S-(2-cyanoethyl)-L-cysteine concentrations in all dosed groups of mice and at all time points. Survival was significantly (p < 0.001) reduced in the top dose (20 mg/kg) group of male and female mice relative to controls. The incidence of forestomach papillomas and carcinomas was increased in mice of both sexes in association with an increase in forestomach epithelial hyperplasia. The incidence of Harderian gland adenomas and carcinomas was also markedly increased in the acrylonitrile-dosed groups. In female mice, the incidence of benign or malignant granulosa cell tumors (combined) in the ovary in the 10 mg/kg dose group was greater than that in the vehicle control group, but because of a lack of dose response, this was considered an equivocal finding. In addition, the incidences of atrophy and cysts in the ovary of the 10 and 20 mg/kg dose groups were significantly increased. The incidences of alveolar/bronchiolar adenoma or carcinoma (combined) were significantly increased in female mice treated with acrylonitrile at 10 mg/kg/day for 2 years. This was also considered an equivocal result. In conclusion, these studies demonstrated that acrylonitrile causes multiple carcinogenic effects after gavage administration to male and female B6

  15. Excessive Growth Hormone Expression in Male GH Transgenic Mice Adversely Alters Bone Architecture and Mechanical Strength

    PubMed Central

    Lim, S. V.; Marenzana, M.; Hopkinson, M.; List, E. O.; Kopchick, J. J.; Pereira, M.; Javaheri, B.; Roux, J. P.; Chavassieux, P.; Korbonits, M.

    2015-01-01

    Patients with acromegaly have a higher prevalence of vertebral fractures despite normal bone mineral density (BMD), suggesting that GH overexpression has adverse effects on skeletal architecture and strength. We used giant bovine GH (bGH) transgenic mice to analyze the effects of high serum GH levels on BMD, architecture, and mechanical strength. Five-month-old hemizygous male bGH mice were compared with age- and sex-matched nontransgenic littermates controls (NT; n=16/group). Bone architecture and BMD were analyzed in tibia and lumbar vertebrae using microcomputed tomography. Femora were tested to failure using three-point bending and bone cellular activity determined by bone histomorphometry. bGH transgenic mice displayed significant increases in body weight and bone lengths. bGH tibia showed decreases in trabecular bone volume fraction, thickness, and number compared with NT ones, whereas trabecular pattern factor and structure model index were significantly increased, indicating deterioration in bone structure. Although cortical tissue perimeter was increased in transgenic mice, cortical thickness was reduced. bGH mice showed similar trabecular BMD but reduced trabecular thickness in lumbar vertebra relative to controls. Cortical BMD and thickness were significantly reduced in bGH lumbar vertebra. Mechanical testing of femora confirmed that bGH femora have decreased intrinsic mechanical properties compared with NT ones. Bone turnover is increased in favor of bone resorption in bGH tibia and vertebra compared with controls, and serum PTH levels is also enhanced in bGH mice. These data collectively suggest that high serum GH levels negatively affect bone architecture and quality at multiple skeletal sites. PMID:25646711

  16. Pretreatment of male BALB/c mice with beta-ionone potentiates thioacetamide-induced hepatotoxicity.

    PubMed

    Jeong, T C; Gu, H K; Park, J I; Yun, H I; Kim, H C; Ha, C S; Roh, J K

    1999-03-01

    A possible role of metabolic activation by cytochrome P450 (P450) in thioacetamide-induced hepatotoxicity was investigated in male BALB/c mice. The mice were pretreated with the P450 inducer, beta-ionone, subcutaneously at 600 mg/kg, 72 and 48 h prior to an intraperitoneal administration of either 100 or 200 mg/kg of thioacetamide. The elevated activities of serum alanine aminotransferase and serum aspartate aminotransferase by thioacetamide were greatly potentiated by the pretreatment with beta-ionone. Moreover, the potentiation of thioacetamide-induced hepatotoxicity was also observed in the histopathological examination of livers. The hepatic necrosis by thioacetamide was potentiated when mice were pretreated with beta-ionone. In liver microsomes, the activities of P450 2B-specific pentoxyresorufin O-depentylase and benzyloxyresorufin O-debenzylase were significantly induced by the treatment with beta-ionone. Beta-ionone also induced other P450-associated monooxygenases. Because the pretreatment with beta-ionone was not hepatotoxic at the dose inducing P450s. our present results suggest that beta-ionone may be a useful model inducer of P450 enzyme(s) in studying toxic mechanism of certain chemicals which require metabolic activation by P450s in mice. PMID:10092055

  17. The role of ghrelin signalling for sexual behaviour in male mice.

    PubMed

    Egecioglu, Emil; Prieto-Garcia, Luna; Studer, Erik; Westberg, Lars; Jerlhag, Elisabet

    2016-03-01

    Ghrelin, a gut-brain signal, is well known to regulate energy homeostasis, food intake and appetite foremost via hypothalamic ghrelin receptors (GHS-R1A). In addition, ghrelin activates the reward systems in the brain, namely the mesolimbic dopamine system, and regulates thereby the rewarding properties of addictive drugs as well as of palatable foods. Given that the mesolimbic dopamine system mandates the reinforcing properties of addictive drugs and natural rewards, such as sexual behaviour, we hypothesize that ghrelin plays an important role for male sexual behaviour, a subject for the present studies. Herein we show that ghrelin treatment increases, whereas pharmacological suppression (using the GHSR-1A antagonist JMV2959) or genetic deletion of the GHS-R1A in male mice decreases the sexual motivation for as well as sexual behaviour with female mice in oestrus. Pre-treatment with L-dopa (a dopamine precursor) prior to treatment with JMV2959 significantly increased the preference for female mouse compared with vehicle treatment. On the contrary, treatment with 5-hydroxythyptohan (a precursor for serotonin) prior to treatment with JMV2959 decreased the sexual motivation compared to vehicle. In separate experiments, we show that ghrelin and GHS-R1A antagonism do not affect the time spent over female bedding as measured in the androgen-dependent bedding test. Collectively, these data show that the hunger hormone ghrelin and its receptor are required for normal sexual behaviour in male mice and that the effects of the ghrelin signalling system on sexual behaviour involve dopamine neurotransmission. PMID:25475101

  18. Dearth and Delayed Maturation of Testicular Germ Cells in Fanconi Anemia E Mutant Male Mice

    PubMed Central

    Fu, Chun; Begum, Khurshida; Jordan, Philip W.; He, Yan; Overbeek, Paul A.

    2016-01-01

    After using a self-inactivating lentivirus for non-targeted insertional mutagenesis in mice, we identified a transgenic family with a recessive mutation that resulted in reduced fertility in homozygous transgenic mice. The lentiviral integration site was amplified by inverse PCR. Sequencing revealed that integration had occurred in intron 8 of the mouse Fance gene, which encodes the Fanconi anemia E (Fance) protein. Fanconi anemia (FA) proteins play pivotal roles in cellular responses to DNA damage and Fance acts as a molecular bridge between the FA core complex and Fancd2. To investigate the reduced fertility in the mutant males, we analyzed postnatal development of testicular germ cells. At one week after birth, most tubules in the mutant testes contained few or no germ cells. Over the next 2–3 weeks, germ cells accumulated in a limited number of tubules, so that some tubules contained germ cells around the full periphery of the tubule. Once sufficient numbers of germ cells had accumulated, they began to undergo the later stages of spermatogenesis. Immunoassays revealed that the Fancd2 protein accumulated around the periphery of the nucleus in normal developing spermatocytes, but we did not detect a similar localization of Fancd2 in the Fance mutant testes. Our assays indicate that although Fance mutant males are germ cell deficient at birth, the extant germ cells can proliferate and, if they reach a threshold density, can differentiate into mature sperm. Analogous to previous studies of FA genes in mice, our results show that the Fance protein plays an important, but not absolutely essential, role in the initial developmental expansion of the male germ line. PMID:27486799

  19. Increased bile acids in enterohepatic circulation by short-term calorie restriction in male mice

    SciTech Connect

    Fu, Zidong Donna; Klaassen, Curtis D.

    2013-12-15

    Previous studies showed glucose and insulin signaling can regulate bile acid (BA) metabolism during fasting or feeding. However, limited knowledge is available on the effect of calorie restriction (CR), a well-known anti-aging intervention, on BA homeostasis. To address this, the present study utilized a “dose–response” model of CR, where male C57BL/6 mice were fed 0, 15, 30, or 40% CR diets for one month, followed by BA profiling in various compartments of the enterohepatic circulation by UPLC-MS/MS technique. This study showed that 40% CR increased the BA pool size (162%) as well as total BAs in serum, gallbladder, and small intestinal contents. In addition, CR “dose-dependently” increased the concentrations of tauro-cholic acid (TCA) and many secondary BAs (produced by intestinal bacteria) in serum, such as tauro-deoxycholic acid (TDCA), DCA, lithocholic acid, ω-muricholic acid (ωMCA), and hyodeoxycholic acid. Notably, 40% CR increased TDCA by over 1000% (serum, liver, and gallbladder). Interestingly, 40% CR increased the proportion of 12α-hydroxylated BAs (CA and DCA), which correlated with improved glucose tolerance and lipid parameters. The CR-induced increase in BAs correlated with increased expression of BA-synthetic (Cyp7a1) and conjugating enzymes (BAL), and the ileal BA-binding protein (Ibabp). These results suggest that CR increases BAs in male mice possibly through orchestrated increases in BA synthesis and conjugation in liver as well as intracellular transport in ileum. - Highlights: • Dose response effects of short-term CR on BA homeostasis in male mice. • CR increased the BA pool size and many individual BAs. • CR altered BA composition (increased proportion of 12α-hydroxylated BAs). • Increased mRNAs of BA enzymes in liver (Cyp7a1 and BAL) and ileal BA binding protein.

  20. Rare earths exposure and male infertility: the injury mechanism study of rare earths on male mice and human sperm.

    PubMed

    Chen, Jun; Xiao, Heng-Jun; Qi, Tao; Chen, Di-Ling; Long, He-Ming; Liu, Song-Hao

    2015-02-01

    The weight; testis/body coefficient; levels of LDH, SDH, SODH, G-6PD, and testosterone; cell cycle; and cell apoptosis of the male mice were influenced after being treated with 200 mg/[kg/day] of rare earths suspension for 3 weeks. The "Raman fingerprints" of the human sperm DNA exposed to 0.040 mg/ml CeCl3 were very different from those of the untreated; the Raman bands at 789 cm(-1) (backbone phosphodiester), PO4 backbone at 1,094 cm(-1), methylene deformation mode at 1,221 cm(-1), methylene deformation mode at 1,485 cm(-1), and amide II at 1,612 cm(-1), of which intensities and shifts were changed, might be the diagnostic biomarkers or potential therapeutic targets. The injury mechanism might be that the rare earths influence the oxidative stress and blood testosterone barrier, tangle the big biomolecule concurrently, which might cause the testicular cells and vascular system disorder and/or dysfunction, and at the same time change the physical and chemical properties of the sperm directly. PMID:25167826

  1. Dose-Dependent Adverse Effects of Salinomycin on Male Reproductive Organs and Fertility in Mice

    PubMed Central

    Ojo, Olajumoke Omolara; Bhadauria, Smrati; Rath, Srikanta Kumar

    2013-01-01

    Salinomycin is used as an antibiotic in animal husbandry. Its implication in cancer therapy has recently been proposed. Present study evaluated the toxic effects of Salinomycin on male reproductive system of mice. Doses of 1, 3 or 5 mg/kg of Salinomycin were administered daily for 28 days. Half of the mice were sacrificed after 24 h of the last treatment and other half were sacrificed 28 days after withdrawal of treatment. Effects of SAL on body and reproductive organ weights were studied. Histoarchitecture of testis and epididymis was evaluated along with ultrastructural changes in Leydig cells. Serum and testicular testosterone and luteinizing hormones were estimated. Superoxide dismutase, reduced glutathione, lipid peroxidation, catalase and lactate dehydrogenase activities were measured. Spermatozoa count, morphology, motility and fertility were evaluated. Expression patterns of steroidogenic acute regulatory protein (StAR) and cytochrome P450 side chain cleavage proteins (CYP11A1) were assessed by Western blotting. Salinomycin treatment was lethal to few mice and retarded body growth in others with decreased weight of testes and seminal vesicles in a dose dependent manner. Seminiferous tubules in testes were disrupted and the epithelium of epididymis showed frequent occurrence of vacuolization and necrosis. Leydig cells showed hypertrophied cytoplasm with shrunken nuclei, condensed mitochondria, proliferated endoplasmic reticulum and increased number of lipid droplets. Salinomycin decreased motility and spermatozoa count with increased number of abnormal spermatozoa leading to infertility. The testosterone and luteinizing hormone levels were decreased in testis but increased in serum at higher doses. Depletion of superoxide dismutase and reduced glutathione with increased lipid peroxidation in both testis and epididymis indicated generation of oxidative stress. Suppressed expression of StAR and CYP11A1 proteins indicates inhibition of steroidogenesis

  2. Bisphenol A Impairs Hepatic Glucose Sensing in C57BL/6 Male Mice

    PubMed Central

    Perreault, Leigh; McCurdy, Carrie; Kerege, Anna A.; Houck, Julie; Færch, Kristine; Bergman, Bryan C.

    2013-01-01

    Aims/Hypothesis Glucose sensing (eg. glucokinase activity) becomes impaired in the development of type 2 diabetes, the etiology of which is unclear. Estrogen can stimulate glucokinase activity, whereas the pervasive environmental pollutant bisphenol A (BPA) can inhibit estrogen action, hence we aimed to determine the effect of BPA on glucokinase activity directly. Methods To evaluate a potential acute effect on hepatic glucokinase activity, BPA in water (n = 5) vs. water alone (n = 5) was administered at the EPA’s purported “safe dose” (50 µg/kg) by gavage to lean 6-month old male C57BL/6 mice. Two hours later, animals were euthanized and hepatic glucokinase activity measured over glucose levels from 1–20 mmol/l in liver homogenate. To determine the effect of chronic BPA exposure on hepatic glucokinase activity, lean 6-month old male C57BL/6 mice were provided with water (n = 15) or water with 1.75 mM BPA (∼50 µg/kg/day; n = 14) for 2 weeks. Following the 2-week exposure, animals were euthanized and glucokinase activity measured as above. Results Hepatic glucokinase activity was signficantly suppressed after 2 hours in animals given an oral BPA bolus compared to those who received only water (p = 0.002–0.029 at glucose 5–20 mmol/l; overall treatment effect p<0.001). Exposure to BPA over 2 weeks also suppressed hepatic glucokinase activity in exposed vs. unexposed mice (overall treatment effect, p = 0.003). In both experiments, the Hill coefficient was higher and Vmax lower in mice treated with BPA. Conclusions/Interpretation Both acute and chronic exposure to BPA significantly impair hepatic glucokinase activity and function. These findings identify a potential mechanism for how BPA may increase risk for diabetes. PMID:23922885

  3. Comparative hepatotoxicity and clastogenicity of sodium arsenite and three petroleum products in experimental Swiss Albino Mice: the modulatory effects of Aloe vera gel.

    PubMed

    Gbadegesin, Michael A; Odunola, Oyeronke A; Akinwumi, Kazeem A; Osifeso, Olabode O

    2009-10-01

    Petroleum products (PPs) consist of complex chemical mixtures, mainly hydrocarbons. Their composition varies considerably with source and use. Inappropriate manual handling and use of PPs, in countries like Nigeria, results in excessive skin contact with the possibility of hazard to health. There has been inadequate evidence to classify diesel, kerosene and hydraulic oil as human carcinogens and there is limited evidence for their toxicity and carcinogenicity in experimental animals. We compared the hepatotoxicity and clastogenicity of diesel, petrol or hydraulic oil with that of sodium arsenite (Na(2)AsO(2)) in mice. Our findings showed that these PPs are capable of inducing gamma-glutamyl transferase (gammaGT) activity in the serum and liver to levels comparable with that induced by Na(2)AsO(2). Mice treated with individual PPs have elevated mean liver and serum gammaGT at levels that are significantly different from the values observed for the negative control group. Also, the individual PPs alone have micronuclei formation induction activity similar to Na(2)AsO(2). We found that treatment with Aloe vera gel before the PPs significantly reduced mean liver and serum gammaGT, and the mean number of micronuclei scored when compared with groups administered each of the PPs alone, supporting the presence of hepatoprotective components in Aloe vera. PMID:19583991

  4. CYP7B1 Enzyme Deletion Impairs Reproductive Behaviors in Male Mice

    PubMed Central

    Oyola, Mario G.; Zuloaga, Damian G.; Carbone, David; Malysz, Anna M.; Acevedo-Rodriguez, Alexandra; Handa, Robert J.

    2015-01-01

    In addition to androgenic properties mediated via androgen receptors, dihydrotestosterone (DHT) also regulates estrogenic functions via an alternate pathway. These estrogenic functions of DHT are mediated by its metabolite 5α-androstane-3β, 17β-diol (3β-diol) binding to estrogen receptor β (ERβ). CYP7B1 enzyme converts 3β-diol to inactive 6α- or 7α-triols and plays an important role as a regulator of estrogenic functions mediated by 3β-diol. Using a mutant mouse carrying a null mutation for the CYP7B1 gene (CYP7B1KO), we examined the contribution of CYP7B1 on physiology and behavior. Male, gonadectomized (GDX) CYP7B1KO and their wild type (WT) littermates were assessed for their behavioral phenotype, anxiety-related behavioral measures, and hypothalamic pituitary adrenal axis reactivity. No significant effects of genotype were evident in anxiety-like behaviors in open field (OFA), light-dark (L/D) exploration, and elevated plus maze (EPM). T significantly reduced open arm time on the EPM while not affecting L/D exploratory and OFA behaviors in CYP7B1KO and WT littermates. T also attenuated the corticosterone response to EPM in both genotypes. In GDX animals, T was able to reinstate male-specific reproductive behaviors (latencies and number of mounts, intromission, and ejaculations) in the WT but not in the CYP7B1KO mice. The male reproductive behavior defect in CYP7B1KO seems to be due to their inability to distinguish olfactory cues from a behavioral estrus female. CYP7B1KO mice also showed a reduction in androgen receptor mRNA expression in the olfactory bulb. Our findings suggest a novel role for the CYP7B1 enzyme in the regulation of male reproductive behaviors. PMID:25849728

  5. Central oxytocin regulates social familiarity and scent marking behavior that involves amicable odor signals between male mice.

    PubMed

    Arakawa, Hiroyuki; Blanchard, D Caroline; Blanchard, Robert J

    2015-07-01

    The effect of oxytocin on social behavior and odor communication was investigated in male C57BL/6J mice. In three-male colonies, in visible burrow systems, icv oxytocin (OT) infusion before colony formation substantially increased huddling together over the initial 8 h of grouping, accompanied by decreased expression of a number of social approaches associated with conspecific aggression and defense. OT antagonist infusion had little impact on expression of social approaches but decreased time engaging in social components including huddle over the initial 8 h. These results demonstrate a linkage of social familiarity to OT availability in the brain. In a scent marking paradigm central infusion of OT reduced territorial marking towards male conspecifics, and this in turn reduced the scent marking of untreated stimulus males to OT-infused subjects. Infusion of an OT antagonist into stimulus mice who were confronted with OT-infused subjects prevented the reduction/suppression of scent marking that was normally seen following exposure of social odors released from OT-injected mice. Odor of pair-housed mice also induced a suppression of territorial scent marking in odor recipients, but OT antagonist administration into pair-housed mice blocked this suppressive effect of odor cue. These results indicate that central OT modulates release as well as detection of amicable signals facilitating/maintaining familiar relationships and suppressing territorial behavior between male mice. Overall, these findings suggest that OT plays a significant role in regulating social familiarity via changing qualities of conspecific odor cues. PMID:26066721

  6. Floor Space Needs for Laboratory Mice: C56BL/6 Males in Solid-bottom Cages with Bedding.

    PubMed

    Fullwood, Steven; Hicks, Tiffanie A.; Brown, Jack C.; Norman, Reid L.; McGlone, John J.

    1998-12-01

    Measures of performance, mortality, adrenal weights, plasma glucocorticoid concentration, and selected immune measures were collected in an attempt to define space needs of laboratory mice. Six replications of 3 C57BL/6 male mice per cage were examined while housed on bedding at 5, 10, 15, or 20 in(2) (32.2, 64.5, 96.8, or 129 cm(2)) per mouse. Body weights were not influenced by treatment; however, mice in smaller spaces (5 in(2) per mouse) consumed or wasted more feed and water than mice given greater space allowances. Mice given the least amount of space (5 in(2) per mouse) had greater lymphocyte proliferation in response to the T-cell mitogen PHA than mice given more space. Mice provided 10 in(2) per mouse had greater natural killer cytotoxicity than mice given greater or less space. Mouse mortality was greater as more space was provided. In contrast, adrenal weights and plasma glucocorticoid concentrations were progressively greater with lower space allowances. The National Research Council 1996 recommendation of 15 in(2) per mouse, for this strain and sex of mice, would result in greater mortality and reduced activity of some immune measures. Socially housed male C57BL/6 mice will benefit from less space than recommended by the National Research Council in 1996. PMID:11406686

  7. Psoralen and Isopsoralen Ameliorate Sex Hormone Deficiency-Induced Osteoporosis in Female and Male Mice

    PubMed Central

    Yuan, Xiaomei; Bi, Yanan; Yan, Zeman; Pu, Weiling; Li, Yuhong; Zhou, Kun

    2016-01-01

    Osteoporosis is a systemic skeletal disease, which is characterized by a systemic destruction of bone mass and microarchitecture. With life standard improved, the treatment of osteoporosis attracted more attention. The aim of this study is to verify the osteoprotective effect of psoralen and isopsoralen in females and males. Female and male mice were divided into 7 groups in this study: control group (sham-operation), model group (by ovariectomy or orchidectomy), positive control group (females given estradiol valerate; males given alendronate sodium), psoralen groups (10 mg/kg and 20 mg/kg), and isopsoralen groups (10 mg/kg and 20 mg/kg). After administration of psoralen and isopsoralen for 8 weeks, osteoporosis was ameliorated with increasing bone strength and improving trabecular bone microstructure as indicated by CT scan and pathology. Serum alkaline phosphatase (ALP), tartrate resistant acid phosphatase (TRACP), osteocalcin (OC), and C-terminal cross-linking telopeptides of type I collagen (CTX-1) were examined. Decreased TRACP and increased ALP/TRACP suggested restoring from bone destruction. These results suggest that psoralen and isopsoralen may be used as good natural compounds for the treatment of osteoporosis in males, as well as females. PMID:27239473

  8. Social isolation increases cell proliferation in male and cell survival in female California mice (Peromyscus californicus).

    PubMed

    Ruscio, Michael G; Bradley King, S; Haun, Harold L

    2015-11-01

    Social environment has direct effects on an animal's behavior, physiology and neurobiology. In particular, adult neurogenesis is notably affected by a variety of social manipulations, including social isolation. We hypothesized that social isolation should have particularly acute effects on neurogenesis in a highly social (monogamous and bi-parental) species such as Peromyscus californicus, the California mouse. Adult male and female P. californicus mice were housed in isolation or in same-sex pairs for 4 or 24 days. At the end of each period, either cell proliferation or cell survival was quantified with BrdU label and neuronal markers (either TuJ1 or NeuN). After 4 days, isolated males had greater cellular proliferation in the dentate gyrus of the hippocampus (DG) than pair housed males. After 24 days, isolate females demonstrated greater cell survival in the DG than paired females. Males demonstrated a similar, but non-significant pattern. No differences in cellular proliferation or cell survival were found in the subventricular zone (SVZ), or medial amygdala (MeA). These results add to the evidence which demonstrates that neurogenic responses to environmental conditions are not identical across species. These data may be critical in understanding the functional significance of neurogenesis as it relates to the interactions between social systems, social environment and the display of social behaviors. PMID:26342752

  9. Basal Bone Phenotype and Increased Anabolic Responses to Intermittent Parathyroid Hormone in Healthy Male COX-2 Knockout Mice

    PubMed Central

    Xu, Manshan; Choudhary, Shilpa; Voznesensky, Olga; Gao, Qi; Adams, Douglas; Diaz-Doran, Vilmaris; Wu, Qian; Goltzman, David; Raisz, Lawrence G.; Pilbeam, Carol C.

    2011-01-01

    Cyclooxygenase-2 (COX-2) knockout (KO) mice in inbred strains can have renal dysfunction with secondary hyperparathyroidism (HPTH), making direct effects of COX-2 KO on bone difficult to assess. COX-2 KO mice in an outbred CD-1 background did not have renal dysfunction but still had two-fold elevated PTH compared to wild type (WT) mice. Compared to WT mice, KO mice had increased serum markers of bone turnover, decreased femoral bone mineral density (BMD) and cortical bone thickness, but no differences in trabecular bone volume by μCT or dynamic histomorphometry. Because PTH is a potent inducer of COX-2 and prostaglandin (PG) production, we examined effects of COX-2 KO on bone responses after three weeks of intermittent PTH. Intermittent PTH increased femoral BMD and cortical bone area more in KO mice than in WT mice and increased trabecular bone volume in the distal femur in both WT and KO mice. Although not statistically significant, PTH-stimulated increases in trabecular bone tended to be greater in KO mice than in WT mice. PTH increased serum markers of bone formation and resorption more in KO than in WT mice but increased the ratio of osteoblastic surface to osteoclastic surface only in KO mice. PTH also increased femoral mineral apposition rates and bone formation rates in KO mice more than in WT mice. Acute mRNA responses to PTH of genes that might mediate some anabolic and catabolic effects of PTH tended to be greater in KO than WT mice. We conclude that (1) the basal bone phenotype in male COX-2 KO mice might reflect HPTH, COX-2 deficiency or both, and (2) increased responses to intermittent PTH in COX-2 KO mice, despite the presence of chronic HPTH, suggest that absence of COX-2 increased sensitivity to PTH. It is possible that manipulation of endogenous PGs could have important clinical implications for anabolic therapy with PTH. PMID:20471507

  10. Cholestasis induced by model organic anions protects from acetaminophen hepatotoxicity in male CD-1 mice.

    PubMed

    Silva, Vanessa M; Hennig, Gayle E; Manautou, José E

    2006-01-25

    Administration of the non-metabolizable organic anion indocyanine green (ICG) prior to a toxic dose of acetaminophen (4-acetamidophenol; APAP) reduces liver injury 24h after dosing. ICG also produces a dose-dependent decrease in bile flow in mice and rats. Studies in bile duct-cannulated rats suggest that cholestasis can play a role in this protection. This study was conducted to determine if the ability of model organic anions to produce cholestasis is relevant to the protection against APAP hepatotoxicity afforded by ICG. In these studies, overnight fasted male CD-1 mice were dosed (i.v.) with the cholestatic dyes bromcresol green (BCG, 30 micromol/kg) and rose bengal (RB, 60 micromol/kg) immediately prior APAP administration (500 mg/kg, i.p.). Other groups of mice received the non-cholestatic dyes dibromosulphthalein (DBSP, 150 micromol/kg) and amaranth (AM, 300 micromol/kg) prior to APAP. Controls were given vehicle only. Hepatocellular necrosis was evident at 24 h in control mice receiving APAP. Pretreatment with the cholestatic dyes BCG and RB decreased the severity of hepatocellular necrosis induced by APAP. However, administration of the non-cholestatic dyes DBSP and AM did not alter APAP-induced liver damage. Glutathione replenishment was not altered by pretreatment with any of these dyes. Furthermore, ICG protected mice against carbon tetrachloride (CCl4) hepatotoxicity. Since CCl4 undergoes minimal biliary excretion and does not compete for biliary transport function, this finding supports the notion that cholestasis itself rather than competition for canalicular transporters is central to the hepatoprotection by ICG and other cholephilic dyes. PMID:16140478

  11. Hspa4l-Deficient Mice Display Increased Incidence of Male Infertility and Hydronephrosis Development▿

    PubMed Central

    Held, Torsten ; Paprotta, Ilona; Khulan, Janchiv; Hemmerlein, Bernhardt; Binder, Lutz; Wolf, Stephan; Schubert, Stephanie; Meinhardt, Andreas; Engel, Wolfgang; Adham, Ibrahim M.

    2006-01-01

    The Hspa4l gene, also known as Apg1 or Osp94, belongs to the HSP110 heat shock gene family, which includes three genes encoding highly conserved proteins. This study shows that Hspa4l is expressed ubiquitously and predominantly in the testis. The protein is highly expressed in spermatogenic cells, from late pachytene spermatocytes to postmeiotic spermatids. In the kidney, the protein is restricted to cortical segments of distal tubules. To study the physiological role of this gene in vivo, we generated mice deficient in Hspa4l by gene targeting. Hspa4l-deficient mice were born at expected ratios and appeared healthy. However, approximately 42% of Hspa4l−/− male mice suffered from fertility defects. Whereas the seminiferous tubules of Hspa4l−/− testes contained all stages of germ cells, the number of mature sperm in the epididymis and sperm motility were drastically reduced. The reduction of the sperm count was due to the elimination of a significant number of developing germ cells via apoptosis. No defects in fertility were observed in female mutants. In addition, 12% of null mutant mice developed hydronephrosis. Concentrations of plasma and urine electrolytes in Hspa4l−/− mice were similar to wild-type values, suggesting that the renal function was not impaired. However, Hspa4l−/− animals were preferentially susceptible to osmotic stress. These results provide evidence that Hspa4l is required for normal spermatogenesis and suggest that Hspa4l plays a role in osmotolerance. PMID:16923965

  12. Nordihydroguaiaretic acid and aspirin increase lifespan of genetically heterogeneous male mice.

    PubMed

    Strong, Randy; Miller, Richard A; Astle, Clinton M; Floyd, Robert A; Flurkey, Kevin; Hensley, Kenneth L; Javors, Martin A; Leeuwenburgh, Christiaan; Nelson, James F; Ongini, Ennio; Nadon, Nancy L; Warner, Huber R; Harrison, David E

    2008-10-01

    The National Institute on Aging's Interventions Testing Program was established to evaluate agents that are purported to increase lifespan and delay the appearance of age-related disease in genetically heterogeneous mice. Up to five compounds are added to the study each year and each compound is tested at three test sites (The Jackson Laboratory, University of Michigan, and University of Texas Health Science Center at San Antonio). Mice in the first cohort were exposed to one of four agents: aspirin, nitroflurbiprofen, 4-OH-alpha-phenyl-N-tert-butyl nitrone, or nordihydroguaiaretic acid (NDGA). Sample size was sufficient to detect a 10% difference in lifespan in either sex,with 80% power, using data from two of the three sites. Pooling data from all three sites, a log-rank test showed that both NDGA (p=0.0006) and aspirin (p=0.01) led to increased lifespan of male mice. Comparison of the proportion of live mice at the age of 90% mortality was used as a surrogate for measurement of maximum lifespan;neither NDGA (p=0.12) nor aspirin (p=0.16) had a significant effect in this test. Measures of blood levels of NDGA or aspirin and its salicylic acid metabolite suggest that the observed lack of effects of NDGA or aspirin on life span in females could be related to gender differences in drug disposition or metabolism. Further studies are warranted to find whether NDGA or aspirin, over a range of doses,might prove to postpone death and various age-related outcomes reproducibly in mice. PMID:18631321

  13. Modification of female and male social behaviors in estrogen receptor beta knockout mice by neonatal maternal separation

    PubMed Central

    Tsuda, Mumeko C.; Yamaguchi, Naoko; Nakata, Mariko; Ogawa, Sonoko

    2014-01-01

    Maternal separation (MS) is an animal model mimicking the effects of early life stress on the development of emotional and social behaviors. Recent studies revealed that MS stress increased social anxiety levels in female mice and reduced peri-pubertal aggression in male mice. Estrogen receptor (ER) β plays a pivotal role in the regulation of stress responses and anxiety-related and social behaviors. Behavioral studies using ERβ knockout (βERKO) mice reported increased social investigation and decreased social anxiety in βERKO females, and elevated aggression levels in βERKO males compared to wild-type (WT) mice. In the present study, using βERKO and WT mice, we examined whether ERβ contributes to MS effects on anxiety and social behaviors. βERKO and WT mice were separated from their dam daily (4 h) from postnatal day 1–14 and control groups were left undisturbed. First, MS and ERβ gene deletion individually increased anxiety-related behaviors in the open field test, but only in female mice. Anxiety levels were not further modified in βERKO female mice subjected to MS stress. Second, βERKO female mice showed higher levels of social investigation compared with WT in the social investigation test and long-term social preference test. However, MS greatly reduced social investigation duration and elevated number of stretched approaches in WT and βERKO females in the social investigation test, suggesting elevated levels of social anxiety in both genotypes. Third, peri-pubertal and adult βERKO male mice were more aggressive than WT mice as indicated by heightened aggression duration. On the other hand, MS significantly decreased aggression duration in both genotypes, but only in peri-pubertal male mice. Altogether, these results suggest that βERKO mice are sensitive to the adverse effects of MS stress on subsequent female and male social behaviors, which could then have overrode the ERβ effects on female social anxiety and male aggression. PMID:25228857

  14. Inhibitory effects of H2-receptor antagonists on cytochrome P450 in male ICR mice.

    PubMed

    Kim, D H; Kim, E J; Han, S S; Roh, J K; Jeong, T C; Park, J H

    1995-08-01

    1. The present study was undertaken to examine the effects of H2-receptor antagonists including newly developed mifentidine derivatives, IY-80843 and IY-80845, on cytochrome P450(P450) in vitro and in vivo. 2. Initially, 3-methylcholanthrene-, phenobarbital-, ethanol- and dexamethasone-induced liver microsomes were prepared from male ICR mice to study in vitro effects of above chemicals on ethoxyresorufin O-deethylase(EROD), pentoxyresorufin O-dealkylase(PROD), p-nitrophenol hydroxylase and erythromycin N-demethylase(ERDM) activities, respectively. It was found that histamine, cimetidine and famotidine were not inhibitory to four enzyme activities. Meanwhile, mifentidine slightly inhibited EROD and PROD activities and its derivatives IY-80843 and IY-80845 strongly inhibited PROD, EROD and ERDM activities. 3. Prolongation of hexobarbital-induced sleeping time was determined in male ICR mice to confirm in vitro inhibitory effects of mifentidine and its derivatives in vivo. It was observed that cimetidine, mifentidine, IY-80843 and IY-80845 caused dose-dependent increases in the sleeping time, indicating the inhibition of P450 responsible for hexobarbital metabolism. 4. It was concluded that mifentidine and its derivatives are P450 inhibitors and that our newly synthesized IY-80843 is most inhibitory. 5. The present results indicate that mifentidine and its derivatives not only antagonise the H2-receptor but also inhibit P450 enzymes. PMID:7576828

  15. 17 β-estradiol Protects Male Mice from Cuprizone-induced Demyelination and Oligodendrocyte Loss

    PubMed Central

    Taylor, Lorelei C; Puranam, Kasturi; Gilmore, Wendy; Ting, Jenny P-Y.; Matsushima, G.K.

    2010-01-01

    In addition to regulating reproductive functions in the brain and periphery, estrogen has trophic and neuroprotective functions in the central nervous system (CNS). Estrogen administration has been demonstrated to provide protection in several animal models of CNS disorders, including stroke, brain injury, epilepsy, Parkinson’s disease, Alzheimer’s disease, age-related cognitive decline and multiple sclerosis. Here, we use a model of toxin-induced oligodendrocyte death which results in demyelination, reactive gliosis, recruitment of oligodendrocyte precursor cells and subsequent remyelination to study the potential benefit of 17β-estradiol (E2) administration in male mice. The results indicate that E2 partially ameliorates loss of oligodendrocytes and demyelination in the corpus callosum. This protection is accompanied by a delay in microglia accumulation as well as reduced mRNA expression of the pro-inflammatory cytokine, tumor necrosis factor alpha (TNFα), and insulin-like growth factor-1 (IGF-1). E2 did not significantly alter the accumulation of astrocytes or oligodendrocyte precursor cells, or remyelination. These data obtained from a toxin-induced, T cell-independent model using male mice provide an expanded view of the beneficial effects of estrogen on oligodendrocyte and myelin preservation. PMID:20347981

  16. Fecundity of F/sub 1/ male mice exposed to lead acetate in-utero

    SciTech Connect

    Figgs, L.W.

    1983-01-01

    Four studies were performed to examine the reproductive capacity of male mice exposed to lead in-utero. These studies concerned the fecundity/fertility, sperm and semen analysis, scanning electron microscopic (SEM) analysis of the testis, and the analysis of seminiferous tubule cell populations for chromosomal aberrations. The fecundity study revealed that male mice exposed to lead acetate in-utero showed a significant reduction in the following parameters for the F/sub 2/ litters they produced. There was a significant reduction in the number of pups produced per litter, the number of females per litter, the number of pups weaned per litter, and the percent survival of those pups. Sperm and semen analysis revealed a decrease in sperm numbers and motility. It was concluded that lead acertate exposure in-utero resulted in a decrease in reproductive capacity which was evidenced by the reduction in certain fecundity parameters pups weaned per litter, etc. It was concluded that lead acetate causes a mutation or functional change in the stem cell population of the embryonic gonad that resulted in a slowed transition from spermatocyte to spermatid during spermatogenesis in the adult. This slowed transition may have been translated into decreased sperm production, a decrease in x-bearing sperm, and genetic changes that caused decreased numbers of pups and decreased survivorship of the pups in those litters. This was not demonstrated by microscopic analysis of the sperm and testis but was suggested by an analysis of a sample population of cells from the seminiferous tubules.

  17. Increased bile acids in enterohepatic circulation by short-term calorie restriction in male mice.

    PubMed

    Fu, Zidong Donna; Klaassen, Curtis D

    2013-12-15

    Previous studies showed glucose and insulin signaling can regulate bile acid (BA) metabolism during fasting or feeding. However, limited knowledge is available on the effect of calorie restriction (CR), a well-known anti-aging intervention, on BA homeostasis. To address this, the present study utilized a "dose-response" model of CR, where male C57BL/6 mice were fed 0, 15, 30, or 40% CR diets for one month, followed by BA profiling in various compartments of the enterohepatic circulation by UPLC-MS/MS technique. This study showed that 40% CR increased the BA pool size (162%) as well as total BAs in serum, gallbladder, and small intestinal contents. In addition, CR "dose-dependently" increased the concentrations of tauro-cholic acid (TCA) and many secondary BAs (produced by intestinal bacteria) in serum, such as tauro-deoxycholic acid (TDCA), DCA, lithocholic acid, ω-muricholic acid (ωMCA), and hyodeoxycholic acid. Notably, 40% CR increased TDCA by over 1000% (serum, liver, and gallbladder). Interestingly, 40% CR increased the proportion of 12α-hydroxylated BAs (CA and DCA), which correlated with improved glucose tolerance and lipid parameters. The CR-induced increase in BAs correlated with increased expression of BA-synthetic (Cyp7a1) and conjugating enzymes (BAL), and the ileal BA-binding protein (Ibabp). These results suggest that CR increases BAs in male mice possibly through orchestrated increases in BA synthesis and conjugation in liver as well as intracellular transport in ileum. PMID:24183703

  18. Protective Effect of Royal Jelly on In Vitro Fertilization (IVF) in Male Mice Treated with Oxymetholone

    PubMed Central

    Zahmatkesh, Ensieh; Najafi, Gholamreza; Nejati, Vahid

    2015-01-01

    Objective This study aimed to investigate the effects of royal jelly (RJ) on catalase, total antioxidant capacity and embryo development in adult mice treated with oxymetholone (OXM). Materials and Methods In this exprimental study, 32 male and 96 female adult Naval Medical Research Institute (NMRI) mice (7-9 weeks of age) with a ratio of 1:3 for fertili- zation purposes were randomly divided into 4 groups as follows: i. Control group (n=8) receiving 0.1 ml/mice saline daily by gavage for 30 day, ii. RJ group (n=8) treated with RJ at a dose of 100 mg/kg daily by gavage for 30 days, iii. OXM group (n=8) receiving OXM at the dose of 5 mg/kg daily by gavage for 30 days and iv. RJ+OXM group (n=8) receiving RJ at the dose of 100 mg/kg daily by gavage concomitant with 100 mg/kg OXM adminis- tration for 30 days. Results Analysis revealed a significant reduction in catalase, total antioxidant, as well as embryo development in OXM group (P<0.05). However, RJ group showed a salient recovery in the all of the above mentioned parameters and embryo toxicity. Conclusion The results of this study indicated a partially protective effect of RJ against OXM-induced embryo toxicity. PMID:26464831

  19. Nicotine in Combination With a High-Fat Diet Causes Intramyocellular Mitochondrial Abnormalities in Male Mice

    PubMed Central

    Sinha-Hikim, Indrani; Friedman, Theodore C.; Shin, Chang-Sung; Lee, Desean; Ivey, Rasheed

    2014-01-01

    Smoking is a major risk factor for diabetes, cardiovascular disease, and nonalcoholic fatty liver disease. The health risk associated with smoking can be exaggerated by obesity. We hypothesize that nicotine when combined with a high-fat diet (HFD) can also cause ectopic lipid accumulation in skeletal muscle, similar to recently observed hepatic steatosis. Adult C57BL6 male mice were fed a normal chow diet or HFD and received twice-daily ip injections of nicotine (0.75 mg/kg body weight) or saline for 10 weeks. Transmission electron microscopy of the gastrocnemius muscle revealed substantial intramyocellular lipid accumulation in close association with intramyofibrillar mitochondria along with intramyofibrillar mitochondrial swelling and vacuolization in nicotine-treated mice on an HFD compared with mice on an HFD treated with saline. These abnormalities were reversed by acipimox, an inhibitor of lipolysis. Mechanistically, the detrimental effect of nicotine plus HFD on skeletal muscle was associated with significantly increased oxidative stress, plasma free fatty acid, and muscle triglyceride levels coupled with inactivation of AMP-activated protein kinase and activation of its downstream target, acetyl-coenzyme A-carboxylase. We conclude that 1) greater oxidative stress together with inactivation of AMP-activated protein kinase mediates the effect of nicotine on skeletal muscle abnormalities in diet-induced obesity and 2) adipose tissue lipolysis is an important contributor of muscle steatosis and mitochondrial abnormalities. PMID:24424058

  20. Sodium fluoride and sulfur dioxide affected male reproduction by disturbing blood-testis barrier in mice.

    PubMed

    Zhang, Jianhai; Li, Zhihui; Qie, Mingli; Zheng, Ruibo; Shetty, Jagathpala; Wang, Jundong

    2016-08-01

    Fluoride and sulfur dioxide (SO2), two well-known environmental toxicants, have been implicated to have adverse effects on male reproductive health in humans and animals. The objective of this study to investigate if the BTB is one of the pathways that lead to reproductive toxicity of sodium fluoride and sulfur dioxide alone or in combination, in view of the key role of blood testis barrier (BTB) in testis. The results showed that a marked decrease in sperm quality, and altered morphology and ultrastructure of BTB in testis of mice exposure to fluoride (100 mg NaF/L in drinking water) or/and sulfur dioxide (28 mg SO2/m(3), 3 h/day). Meanwhile, the mRNA expression levels of some vital BTB-associated proteins, including occluding, claudin-11, ZO-1, Ncadherin, α-catenin, and connexin-43 were all strikingly reduced after NaF exposure, although only the reduction of DSG-2 was statistically significant in all treatment groups. Moreover, the proteins expressions also decreased significantly in claudin-11, N-cadherin, α-catenin, connexin-43 and desmoglein-2 in mice treated with fluoride and/or SO2. These changes in BTB structure and constitutive proteins may therefore be connected with the low sperm quality in these mice. The role of fluoride should deserves more attention in this process. PMID:27237588

  1. Lycopene protects against acute zearalenone-induced oxidative, endocrine, inflammatory and reproductive damages in male mice.

    PubMed

    Boeira, Silvana Peterini; Funck, Vinícius Rafael; Borges Filho, Carlos; Del'Fabbro, Lucian; de Gomes, Marcelo Gomes; Donato, Franciele; Royes, Luiz Fernando Freire; Oliveira, Mauro Schneider; Jesse, Cristiano Ricardo; Furian, Ana Flávia

    2015-03-25

    Male mice received lycopene for 10 days before a single oral administration of zearalenone (ZEA). After 48 h testes and blood were collected. Mice treated with lycopene/ZEA exhibited amelioration of the hematological changes. Lycopene prevented the reduction in the number and motility of spermatozoa and testosterone levels, indicating a protective effect in the testicular damage induced by ZEA. Lycopene was also effective in protecting against the decrease in glutathione-S-transferase, glutathione peroxidase, glutathione reductase and δ-aminolevulinic acid dehydratase activities caused by ZEA in the testes. Exposure of animals to ZEA induced modification of antioxidant and inflammatory status with increase of reduced glutathione (GSH) levels and increase of the oxidized glutathione, interleukins 1β, 2, 6, 10, tumor necrosis factor-α and bilirubin levels. Lycopene prevented ZEA-induced changes in GSH levels and inhibited the processes of inflammation, reducing the damage induced by ZEA. Altogether, our results indicate that lycopene was able to prevent ZEA-induced damage in the mice. PMID:25682699

  2. Adult male mice conceived by in vitro fertilization exhibit increased glucocorticoid receptor expression in fat tissue.

    PubMed

    Simbulan, R K; Liu, X; Feuer, S K; Maltepe, E; Donjacour, A; Rinaudo, P

    2016-02-01

    Prenatal development is highly plastic and readily influenced by the environment. Adverse conditions have been shown to alter organ development and predispose offspring to chronic diseases, including diabetes and hypertension. Notably, it appears that the changes in glucocorticoid hormones or glucocorticoid receptor (GR) levels in peripheral tissues could play a role in the development of chronic diseases. We have previously demonstrated that in vitro fertilization (IVF) and preimplantation embryo culture is associated with growth alterations and glucose intolerance in mice. However, it is unknown if GR signaling is affected in adult IVF offspring. Here we show that GR expression is increased in inbred (C57Bl6/J) and outbred (CF-1× B6D2F1/J) blastocysts following in vitro culture and elevated levels are also present in the adipose tissue of adult male mice. Importantly, genes involved in lipolysis and triglyceride synthesis and responsive to GR were also increased in adipose tissue, indicating that increased GR activates downstream gene pathways. The promoter region of GR, previously reported to be epigenetically modified by perinatal manipulation, showed no changes in DNA methylation status. Our findings demonstrate that IVF results in a long-term change in GR gene expression in a sex- and tissue-specific manner. These changes in adipose tissues may well contribute to the metabolic phenotype in mice conceived by IVF. PMID:26511158

  3. Central Fibroblast Growth Factor 21 Browns White Fat via Sympathetic Action in Male Mice.

    PubMed

    Douris, Nicholas; Stevanovic, Darko M; Fisher, Ffolliott M; Cisu, Theodore I; Chee, Melissa J; Nguyen, Ngoc L; Zarebidaki, Eleen; Adams, Andrew C; Kharitonenkov, Alexei; Flier, Jeffrey S; Bartness, Timothy J; Maratos-Flier, Eleftheria

    2015-07-01

    Fibroblast growth factor 21 (FGF21) has multiple metabolic actions, including the induction of browning in white adipose tissue. Although FGF21 stimulated browning results from a direct interaction between FGF21 and the adipocyte, browning is typically associated with activation of the sympathetic nervous system through cold exposure. We tested the hypothesis that FGF21 can act via the brain, to increase sympathetic activity and induce browning, independent of cell-autonomous actions. We administered FGF21 into the central nervous system via lateral ventricle infusion into male mice and found that the central treatment increased norepinephrine turnover in target tissues that include the inguinal white adipose tissue and brown adipose tissue. Central FGF21 stimulated browning as assessed by histology, expression of uncoupling protein 1, and the induction of gene expression associated with browning. These effects were markedly attenuated when mice were treated with a β-blocker. Additionally, neither centrally nor peripherally administered FGF21 initiated browning in mice lacking β-adrenoceptors, demonstrating that an intact adrenergic system is necessary for FGF21 action. These data indicate that FGF21 can signal in the brain to activate the sympathetic nervous system and induce adipose tissue thermogenesis. PMID:25924103

  4. Central Fibroblast Growth Factor 21 Browns White Fat via Sympathetic Action in Male Mice

    PubMed Central

    Douris, Nicholas; Stevanovic, Darko M.; Fisher, ffolliott M.; Cisu, Theodore I.; Chee, Melissa J.; Nguyen, Ngoc L.; Zarebidaki, Eleen; Adams, Andrew C.; Kharitonenkov, Alexei; Flier, Jeffrey S.; Bartness, Timothy J.

    2015-01-01

    Fibroblast growth factor 21 (FGF21) has multiple metabolic actions, including the induction of browning in white adipose tissue. Although FGF21 stimulated browning results from a direct interaction between FGF21 and the adipocyte, browning is typically associated with activation of the sympathetic nervous system through cold exposure. We tested the hypothesis that FGF21 can act via the brain, to increase sympathetic activity and induce browning, independent of cell-autonomous actions. We administered FGF21 into the central nervous system via lateral ventricle infusion into male mice and found that the central treatment increased norepinephrine turnover in target tissues that include the inguinal white adipose tissue and brown adipose tissue. Central FGF21 stimulated browning as assessed by histology, expression of uncoupling protein 1, and the induction of gene expression associated with browning. These effects were markedly attenuated when mice were treated with a β-blocker. Additionally, neither centrally nor peripherally administered FGF21 initiated browning in mice lacking β-adrenoceptors, demonstrating that an intact adrenergic system is necessary for FGF21 action. These data indicate that FGF21 can signal in the brain to activate the sympathetic nervous system and induce adipose tissue thermogenesis. PMID:25924103

  5. Protective Effects of Thymoquinone against Methotrexate-Induced Germ Cell Apoptosis in Male Mice

    PubMed Central

    Sheikhbahaei, Fatemeh; Khazaei, Mozafar; Rabzia, Arezou; Mansouri, Kamran; Ghanbari, Ali

    2016-01-01

    Background Toxic effects of anti-cancer and other drugs on the normal tissues could be reduced by the herbal plants and their fractions. This study investigated the protective effect of thymoquinone (TQ) as a fraction of Nigella sativa on methotrexate (MTX)- induced germ cell apoptosis in male mice. Materials and Methods In this experimental study, thirty male Balb/c mice were divided randomly into 5 groups (n=6). A single dose of MTX (20 mg/kg) and different concentrations of TQ were administrated for 4 consecutive days. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed on paraffin embedded tissue sections to analysis the occurrence of apoptosis in the testis. Reverse transcription polymerase chain reaction (RT-PCR) of apoptosis-related genes was performed with RNA extracted from testes of the mice. Statistical analysis was done using one-way ANOVA. Results In the MTX group, there was a significant increase in morphologic sign of germ cell degeneration of tubules (48 ± 0.6%), apoptotic index (AI; 2.3 ± 0.6%), as well as mRNA expression of p53 (P=0.008), caspase 8 (P=0.002), caspase 3 (P=0.005), caspase 9 (P=0.000), bax (P=0.004) and the ratio of bax/bcl-2 (P=0.000), whereas there was an decrease in the expression of bcl-2 (P=0.003), as compared to control group. In MTX+TQ groups, the data showed that different concentrations of TQ could improve the harmful effects caused by the MTX. The best protective effects were achieved in MTX+TQ (10 mg/kg). Conclusion TQ protects testicular germ cell against MTX-induced apoptosis by affecting related genes regulation. PMID:26985343

  6. Androgen Deficiency Exacerbates High-Fat Diet-Induced Metabolic Alterations in Male Mice.

    PubMed

    Dubois, Vanessa; Laurent, Michaël R; Jardi, Ferran; Antonio, Leen; Lemaire, Katleen; Goyvaerts, Lotte; Deldicque, Louise; Carmeliet, Geert; Decallonne, Brigitte; Vanderschueren, Dirk; Claessens, Frank

    2016-02-01

    Androgen deficiency is associated with obesity, metabolic syndrome, and type 2 diabetes mellitus in men, but the mechanisms behind these associations remain unclear. In this study, we investigated the combined effects of androgen deficiency and high-fat diet (HFD) on body composition and glucose homeostasis in C57BL/6J male mice. Two models of androgen deficiency were used: orchidectomy (ORX) and androgen receptor knockout mice. Both models displayed higher adiposity and serum leptin levels upon HFD, whereas no differences were seen on a regular diet. Fat accumulation in HFD ORX animals was accompanied by increased sedentary behavior and occurred in spite of reduced food intake. HFD ORX mice showed white adipocyte hypertrophy, correlated with decreased mitochondrial content but not function as well as increased lipogenesis and decreased lipolysis suggested by the up-regulation of fatty acid synthase and the down-regulation of hormone-sensitive lipase. Both ORX and androgen receptor knockout exacerbated HFD-induced glucose intolerance by impairing insulin action in liver and skeletal muscle, as evidenced by the increased triglyceride and decreased glycogen content in these tissues. In addition, serum IL-1β levels were elevated, and pancreatic insulin secretion was impaired after ORX. Testosterone but not dihydrotestosterone supplementation restored the castration effects on body composition and glucose homeostasis. We conclude that sex steroid deficiency in combination with HFD exacerbates adiposity, insulin resistance, and β-cell failure in 2 preclinical male mouse models. Our findings stress the importance of a healthy diet in a clinical context of androgen deficiency and may have implications for the prevention of metabolic alterations in hypogonadal men. PMID:26562264

  7. Influence of the thymus on the capacity of female mice to reject male skin grafts

    SciTech Connect

    De Pirro, E.S.; Goldberg, E.H.

    1989-05-01

    The ability of female mice to reject H-Y-incompatible, but otherwise histocompatible, male skin grafts differs greatly from strain to strain, as is illustrated particularly by the C57BL strain (B6 and other sublines), termed ''H-Y rejector,'' because females invariably and promptly reject C57BL male skin, in comparison with the C3H strain, termed ''H-Y nonrejector,'' because females characteristically accept male C3H skin. To assess the extent to which the thymus governs this rejector vs. nonrejector status, two studies were made. In the first, lethally irradiated B6 (C57BL) and C3H females were restored with (B6 X C3H)F1 female cells, providing a graft-vs.-host-free milieu for differentiation of the same immunopoietic cell population in B6 vs. C3H hosts. With respect to (B6 X C3H)F1 male skin grafts, B6 hosts responded as rejectors and C3H hosts as nonrejectors, signifying that rejector vs. nonrejector status was determined by the host during immunopoiesis. That the main organ responsible for rejector vs. nonrejector determination is the thymus was shown in a second study. Previously thymectomized (B6 X C3H)F1 females received a histocompatible graft of thymus from either B6 or C3H neonatal females and were restored with donor-marked (B6-Ly-5a X C3H)F1 female cells after lethal irradiation. With respect to (B6 X C3H)F1 male skin grafts, the recipients of B6 thymus grafts responded generally as rejectors and the recipients of C3H thymus grafts responded uniformly as nonrejectors.

  8. Sigma-2 receptor binding is decreased in female, but not male, APP/PS1 mice.

    PubMed

    Sahlholm, Kristoffer; Liao, Fan; Holtzman, David M; Xu, Jinbin; Mach, Robert H

    2015-05-01

    The sigma-2 receptor is a steroid-binding membrane-associated receptor which has been implicated in cell survival. Sigma-2 has recently been shown to bind amyloid-β (Aβ) oligomers in Alzheimer's disease (AD) brain. Furthermore, blocking this interaction was shown to prevent or reverse the effects of Aβ to cause cognitive impairment in mouse models and synaptic loss in neuronal cultures. In the present work, the density of sigma-2 receptors was measured in a double transgenic mouse model of amyloid-β deposition (APP/PS1). Comparisons were made between males and females and between transgenic and wt animals. Sigma-2 receptor density was assessed by quantitative autoradiography performed on coronal brain slices using [(3)H]N-[4-(3,4-dihydro-6,7-dimethoxyisoquinolin-2(1H)-yl)butyl]-2-methoxy-5-methyl-benzamide ([(3)H]RHM-1), which has a 300-fold selectivity for the sigma-2 receptor over the sigma-1 receptor. The translocator protein of 18 kDa (TSPO) is expressed on activated microglia and is a marker for neuroinflammation. TSPO has been found to be upregulated in neurodegenerative disorders, including AD. Therefore, in parallel with the sigma-2 autoradiography experiments, we measured TSPO expression using the selective radioligand, [(3)H]PBR28. We also quantified Aβ plaque burden in the same animals using a monoclonal antibody raised against aggregated Aβ. Sigma-2 receptor density was significantly decreased in piriform and motor cortices as well as striata of 16-month old female, but not male, APP/PS1 mice as compared to their wt counterparts. [(3)H]PBR28 binding and immunostaining for Aβ plaques were significantly increased in piriform and motor cortices of both male and female transgenic mice. In striatum however, significant increases were observed only in females. PMID:25796326

  9. Aqueous Stability and Oral Pharmacokinetics of Meloxicam and Carprofen in Male C57BL/6 Mice

    PubMed Central

    Ingrao, Joelle C; Johnson, Ron; Tor, Elizabeth; Gu, Yu; Litman, Marcus; Turner, Patricia V

    2013-01-01

    We found that carprofen and meloxicam under 3 environmental conditions (ambient dark, ambient light, and 4 °C) remained stable for at least 7 d. We then evaluated the oral pharmacokinetics of meloxicam (20 mg/kg) and carprofen (10 mg/kg) in male C57BL/6 mice after oral gavage or administration in the drinking water. Mice did not drink meloxicam-medicated water but readily consumed carprofen-medicated water, consuming an average of 14.19 mL carprofen-medicated water per 100 g body weight daily; mice drank more during the dark phase than during the light phase. Plasma analyzed by HPLC (meloxicam) and tandem mass spectrometry (carprofen) revealed that the peak meloxicam and carprofen concentrations were 16.7 and 20.3 μg/mL and occurred at 4 and 2 h after oral gavage, respectively. Similar blood levels were achieved after 12 h access to the carprofen-medicated water bottle. At 24 h after oral gavage, the drugs were not detectable in plasma. Meloxicam plasma AUC, elimination half-life, apparent volume of distribution, and apparent oral clearance were 160.4 mg/L × h, 7.4 h, 0.36 L/kg, and 0.125 mL/h × kg, respectively. Carprofen plasma AUC, elimination half-life, apparent volume of distribution, and apparent oral clearance were 160.8 mg/L × h, 7.4 h, 0.42 L/kg, and 0.062 mL/h × kg, respectively. No gross or microscopic evidence of toxicity was seen in any mouse. Our findings indicate that carprofen can be administered in drinking water to mice and that medicated water bottles should be placed 12 to 24 h prior to painful procedures. PMID:24041210

  10. Effects of methylphenidate on the behavior of male 5xFAD mice.

    PubMed

    Schneider, F; Baldauf, K; Wetzel, W; Reymann, K G

    2015-01-01

    Alzheimer's disease is a neurodegenerative disorder characterized by a loss of memory and spatial orientation. It is also reported that the dopamine system is affected. Dopamine plays a prominent role in motor functions, motivation, emotion, arousal and reward, and it is important for learning and memory. One model that represents characteristic hallmarks of Alzheimer's disease is the 5xFAD mouse model, in which parenchymal plaque load starts at 2months of age. Transgenic 5xFAD mice show the first behavioral deficits at 6months, which are evident at 9months of age. In this study, we investigated the pharmacological influence of methylphenidate (MPH) on behavioral deficits of 5xFAD mice. Using a battery of behavioral tests, we observed no influence of MPH on anxiety in the elevated plus maze, whereas the locomotion and explorative activity in the open field was increased in transgenic and non-transgenic 5xFAD mice after the application of MPH. Further MPH inhibits habituation in the open field in healthy 5xFAD littermates after the application of 10mg/kg MPH. On the other hand, 10mg/kg MPH improved spatial memory in 6-month-old transgenic 5xFAD males, i.e., at a time point when deficits start to occur. However, in 9-month-old transgenic mice, MPH did not improve persisting learning and memory deficits. We concluded that MPH might improve the non-cognitive, apathy-like behavior (indicated by a reduced exploration), but it has no influence on sustained Alzheimer typical learning and memory deficits. PMID:25449360

  11. The effects of imperatorin on anxiety and memory-related behavior in male Swiss mice.

    PubMed

    Budzynska, Barbara; Kruk-Slomka, Marta; Skalicka-Wozniak, Krystyna; Biala, Grazyna; Glowniak, Kazimierz

    2012-08-01

    The purpose of the reported experiments was to examine the effects of imperatorin [9-(3-methylbut-2-enyloxy)-7H-furo[3,2-g]chromen-7-one], a bioactive furanocoumarin isolated from the fruits of Angelica archangelica (Angelica officinalis) on anxiety and memory-related behaviors of mice. Male Swiss mice were tested for anxiety and cognition, in the elevated plus maze test (EPM), using two different procedures. In the present experiments, imperatorin was administered acutely (at the doses of 5, 10, 20, 30, and 50 mg/kg); injections were made 15, 30, and 60 min before test (anxiety); 30 min before the first trial (memory acquisition); or immediately after the first trial (memory consolidation), as well as subchronically, twice a day for 6 days. On the seventh day, the mice were injected once with imperatorin (10 and 20 mg/kg, i.p.) 30 min before the test (anxiety) and 30 min before the first trial (memory acquisition), or immediately after the first trial (memory consolidation). We observed that imperatorin when administered acutely and repeatedly, at the doses of 10 and 20 mg/kg, exerted an anxiolytic effect on mice tested 30 min after the injection measured in the EPM test. By contrast, no such effect was observed after the acute administration of imperatorin at the doses of 5, 30 and 50 mg/kg. Moreover, other observations carried out 15 and 60 min after a single injection of the drug did not reveal any effect of imperatorin on anxiety behavior in the EPM test. Furthermore, acute and repeated administration of imperatorin (10 and 20 mg/kg) improved different stages of memory processes (both acquisition and consolidation) in a modified EPM test (mEPM). The results of our research suggest imperatorin to be an interesting therapeutical option in disorders with high anxiety levels and memory impairment. PMID:22686497

  12. Induction of Suppressor Cells and Increased Tumor Growth following Chronic Psychosocial Stress in Male Mice

    PubMed Central

    Schmidt, Dominic; Peterlik, Daniel; Reber, Stefan O.; Lechner, Anja; Männel, Daniela N.

    2016-01-01

    To study the impact of psychosocial stress on the immune system, male mice were subjected to chronic subordinate colony housing (CSC), a preclinically validated mouse model for chronic psychosocial stress. CSC substantially affected the cell composition of the bone marrow, blood, and spleen by inducing myelopoiesis and enhancing the frequency of regulatory T cells in the CD4 population. Expansion of the myeloid cell compartment was due to cells identified as immature inflammatory myeloid cells having the phenotype of myeloid-derived suppressor cells of either the granulocytic or the monocytic type. Catecholaminergic as well as TNF signaling were implicated in these CSC-induced cellular shifts. Although the frequency of regulatory cells was enhanced following CSC, the high capacity for inflammatory cytokine secretion of total splenocytes indicated an inflammatory immune status in CSC mice. Furthermore, CSC enhanced the suppressive activity of bone marrow-derived myeloid-derived suppressor cells towards proliferating T cells. In line with the occurrence of suppressor cell types such as regulatory T cells and myeloid-derived suppressor cells, transplanted syngeneic fibrosarcoma cells grew better in CSC mice than in controls, a process accompanied by pronounced angiogenesis and clustering of immature myeloid cells in the tumor tissue. In addition, tumor implantation after CSC reinforced the CSC-induced increase in myeloid-derived suppressor cells and regulatory T cell frequencies while the CSC-induced cellular changes eased off in mice without tumor. Together, our data suggest a role for suppressor cells such as regulatory T cells and myeloid-derived suppressor cells in the enhanced tumor growth after chronic psychosocial stress. PMID:27391954

  13. NMDA receptor antagonists attenuate the proconvulsant effect of juvenile social isolation in male mice.

    PubMed

    Amiri, Shayan; Haj-Mirzaian, Arya; Amini-Khoei, Hossein; Momeny, Majid; Shirzadian, Armin; Balaei, Maryam Rahimi; Zarrinrad, Ghazaleh; Ghazi-Khansari, Mahmoud; Azizi, Romina; Dehpour, Ahmad Reza; Mehr, Shahram Ejtemaei

    2016-03-01

    Experiencing psychosocial stress in early life, such as social isolation stress (SIS), is known to have negative enduring effects on the development of the brain and behavior. In addition to anxiety and depressive-like behaviors, we previously showed that juvenile SIS increases susceptibility to pentylenetetrazole (PTZ)-induced seizures in mice through enhancing the nitrergic system activity in the hippocampus. In this study, we investigated the possible involvement of N-methyl-d-aspartate (NMDA) receptors in proconvulsant effects of juvenile SIS. Applying 4 weeks of SIS to juvenile male mice at postnatal day 21-23, we observed an increased susceptibility to PTZ as well as anxiety and depressive-like behaviors in adult mice. Intraperitoneal (i.p.) administration of NMDA receptor antagonists, MK-801 (0.05mg/kg) and ketamine (0.5mg/kg), reversed the proconvulsant effects of SIS in Isolated (and not social) housed animals. Co-administration of non-effective doses of nitric oxide synthase (NOS) inhibitors, 7NI (25mg/kg) and L-NAME (10mg/kg), with NMDA receptor antagonists, MK-801 (0.01mg/kg) and ketamine (0.1mg/kg) attenuated the proconvulsant effects of juvenile SIS only in isolated housed mice. Also, using real time RT-PCR, we showed that hippocampal upregulation of NR2B subunit of NMDA receptor may play a critical role in proconvulsant effects of juvenile SIS by dysregulation of NMDA/NO pathway. In conclusion, results of present study revealed that experiencing SIS during adolescence predisposes the co-occurrence of seizure disorders with psychiatric comorbidities and also, alteration of NMDA receptor structure and function in hippocampus plays a role in proconvulsant effects of juvenile SIS through enhancing the NMDA/NO pathway. PMID:26836272

  14. Docosahexaenoic acid supplementation fully restores fertility and spermatogenesis in male delta-6 desaturase-null mice

    PubMed Central

    Roqueta-Rivera, Manuel; Stroud, Chad K.; Haschek, Wanda M.; Akare, Sandeep J.; Segre, Mariangela; Brush, Richard S.; Agbaga, Martin-Paul; Anderson, Robert E.; Hess, Rex A.; Nakamura, Manabu T.

    2010-01-01

    Delta-6 desaturase-null mice (−/−) are unable to synthesize highly unsaturated fatty acids (HUFAs): arachidonic acid (AA), docosahexaenoic acid (DHA), and n6-docosapentaenoic acid (DPAn6). The −/− males exhibit infertility and arrest of spermatogenesis at late spermiogenesis. To determine which HUFA is essential for spermiogenesis, a diet supplemented with either 0.2% (w/w) AA or DHA was fed to wild-type (+/+) and −/− males at weaning until 16 weeks of age (n = 3–5). A breeding success rate of DHA-supplemented −/− was comparable to +/+. DHA-fed −/− showed normal sperm counts and spermiogenesis. Dietary AA was less effective in restoring fertility, sperm count, and spermiogenesis than DHA. Testis fatty acid analysis showed restored DHA in DHA-fed −/−, but DPAn6 remained depleted. In AA-fed −/−, AA was restored at the +/+ level, and 22:4n6, an AA elongated product, accumulated in testis. Cholesta-3,5-diene was present in testis of +/+ and DHA-fed −/−, whereas it diminished in −/− and AA-fed −/−, suggesting impaired sterol metabolism in these groups. Expression of spermiogenesis marker genes was largely normal in all groups. In conclusion, DHA was capable of restoring all observed impairment in male reproduction, whereas 22:4n6 formed from dietary AA may act as an inferior substitute for DHA. PMID:19690334

  15. Reduced melanocortin production causes sexual dysfunction in male mice with POMC neuronal insulin and leptin insensitivity.

    PubMed

    Faulkner, Latrice D; Dowling, Abigail R; Stuart, Ronald C; Nillni, Eduardo A; Hill, Jennifer W

    2015-04-01

    Proopiomelanocortin (POMC)-derived peptides like α-melanocyte-stimulating hormone (MSH) substantially improve hepatic insulin sensitivity and regulate energy expenditure. Melanocortinergic agents are also powerful inducers of sexual arousal that are being investigated for a possible therapeutic role in erectile dysfunction. It is currently unclear whether reduced melanocortin (MC) activity may contribute to the sexual dysfunction accompanying obesity and type 2 diabetes. Male rodents with leptin and insulin resistance targeted to POMC neurons (leptin receptor [LepR]/insulin receptor [IR]POMC mice) exhibit obesity, hyperinsulinemia, hyperglycemia, and systemic insulin resistance. In this study, we demonstrate that LepR/IRPOMC males are also subfertile due to dramatic alterations in sexual behavior. Remarkably, these reproductive changes are accompanied by decreased α-MSH production not present when a single receptor type is deleted. Unexpectedly, behavioral sensitivity to α-MSH and MC receptor expression are also reduced in LepR/IRPOMC males, a potential adaptation of the MC system to altered α-MSH production. Together, these results suggest that concurrent insulin and leptin resistance in POMC neurons in individuals with obesity or type 2 diabetes can reduce endogenous α-MSH levels and impair sexual function. PMID:25590244

  16. Reduced Melanocortin Production Causes Sexual Dysfunction in Male Mice With POMC Neuronal Insulin and Leptin Insensitivity

    PubMed Central

    Faulkner, Latrice D.; Dowling, Abigail R.; Stuart, Ronald C.; Nillni, Eduardo A.

    2015-01-01

    Proopiomelanocortin (POMC)-derived peptides like α-melanocyte-stimulating hormone (MSH) substantially improve hepatic insulin sensitivity and regulate energy expenditure. Melanocortinergic agents are also powerful inducers of sexual arousal that are being investigated for a possible therapeutic role in erectile dysfunction. It is currently unclear whether reduced melanocortin (MC) activity may contribute to the sexual dysfunction accompanying obesity and type 2 diabetes. Male rodents with leptin and insulin resistance targeted to POMC neurons (leptin receptor [LepR]/insulin receptor [IR]POMC mice) exhibit obesity, hyperinsulinemia, hyperglycemia, and systemic insulin resistance. In this study, we demonstrate that LepR/IRPOMC males are also subfertile due to dramatic alterations in sexual behavior. Remarkably, these reproductive changes are accompanied by decreased α-MSH production not present when a single receptor type is deleted. Unexpectedly, behavioral sensitivity to α-MSH and MC receptor expression are also reduced in LepR/IRPOMC males, a potential adaptation of the MC system to altered α-MSH production. Together, these results suggest that concurrent insulin and leptin resistance in POMC neurons in individuals with obesity or type 2 diabetes can reduce endogenous α-MSH levels and impair sexual function. PMID:25590244

  17. Effects of Saikokaryukotsuboreito on Spermatogenesis and Fertility in Aging Male Mice

    PubMed Central

    Zang, Zhi-Jun; Ji, Su-Yun; Zhang, Ya-Nan; Gao, Yong; Zhang, Bin

    2016-01-01

    Background: Aspermia caused by exogenous testosterone limit its usage in late-onset hypogonadism (LOH) patients desiring fertility. Saikokaryukotsuboreito (SKRBT) is reported to improve serum testosterone and relieve LOH-related symptoms. However, it is unclear whether SKRBT affects fertility. We aimed to examine the effects of SKRBT on spermatogenesis and fertility in aging male mice. Methods: Thirty aging male mice were randomly assigned to three groups. Mice were orally administered with phosphate-buffer solution or SKRBT (300 mg/kg, daily) or received testosterone by subcutaneous injections (10 mg/kg, every 3 days). Thirty days later, each male mouse was mated with two female mice. All animals were sacrificed at the end of 90 days. Intratesticular testosterone (ITT) levels, quality of sperm, expression of synaptonemal complex protein 3 (SYCP3), and fertility were assayed. Results: In the SKRBT-treated group, ITT, quality of sperm, and expression of SYCP3 were all improved compared with the control group (ITT: 85.50 ± 12.31 ng/g vs. 74.10 ± 11.45 ng/g, P = 0.027; sperm number: [14.94 ± 4.63] × 106 cells/ml vs. [8.79 ± 4.38] × 106 cells/ml, P = 0.002; sperm motility: 43.16 ± 9.93% vs. 33.51 ± 6.98%, P = 0.015; the number of SYCP3-positive cells/tubule: 77.50 ± 11.01 ng/ml vs. 49.30 ± 8.73 ng/ml, P < 0.001; the expression of SYCP3 protein: 1.23 ± 0.09 vs. 0.84 ± 0.10, P < 0.001), but fertility was not significantly changed (P > 0.05, respectively). In the testosterone-treated group, ITT, quality of sperm, and expression of SYCP3 were markedly lower than the control group (ITT: 59.00 ± 8.67, P = 0.005; sperm number: [4.34 ± 2.45] × 106 cells/ml, P = 0.018; sperm motility: 19.53 ± 7.69%, P = 0.001; the number of SYCP3-positive cells/tubule: 30.00 ± 11.28, P < 0.001; the percentage of SYCP3-positive tubules/section 71.98 ± 8.88%, P = 0.001; the expression of SYCP3 protein: 0.71 ± 0.09, P < 0.001), and fertility was also suppressed (P < 0

  18. Behavioral, cognitive and biochemical responses to different environmental conditions in male Ts65Dn mice, a model of Down syndrome.

    PubMed

    Martínez-Cué, Carmen; Rueda, Noemí; García, Eva; Davisson, Muriel T; Schmidt, Cecilia; Flórez, Jesús

    2005-09-01

    Ts65Dn mouse is the most widely accepted model for Down syndrome. We previously showed that environmental enrichment improved spatial learning in female but deteriorated it in male Ts65Dn mice. This study analyzed the factors contributing to the disturbed cognition of male Ts65Dn mice after enriched housing, by allocating male control and Ts65Dn mice in four conditions after weaning: small (n = 2-3) and large group (n = 8-10) housing, and enriched housing in small (2-3) and large groups (8-10). Learning, aggressive behavior, anxiety-like behavior and biochemical correlates of stress were evaluated when Ts65Dn and control mice were 4-5 months old. Environmental enrichment in large mixed colonies of Ts65Dn and diploid littermates disturbed behavioral and learning skills of Ts65Dn mice in the Morris water maze. ACTH and testosterone levels were not modified in any group of mice. Ts65Dn and control mice subjected to enriched housing in large groups and Ts65Dn mice housed in large groups showed higher corticosterone levels. Aggressive behavior was evaluated by measuring the number of attacks performed in the presence of an intruder. Ts65Dn mice performed less attacks than controls in all conditions, especially after enriched housing, indicating subordination. In the plus maze, cognitive aspects (i.e. risk assessment) and motor components (open arm avoidance) of anxiety behavior were evaluated; no difference in any condition was found. It is suggested that an excess of social and/or physical stimulation in Ts65Dn mice may affect cognition by disturbing the emotional and behavioral components of the learning process. PMID:15941601

  19. Weekly administration of rapamycin improves survival and biomarkers in obese male mice on high-fat diet.

    PubMed

    Leontieva, Olga V; Paszkiewicz, Geraldine M; Blagosklonny, Mikhail V

    2014-08-01

    Recent discoveries have revealed the key role of mTOR (target of rapamycin) in aging. Furthermore, rapamycin extends lifespan in mice, especially in female mice. Here, we treated obese male mice on high-fat diet with rapamycin given intermittently: either weekly (once a week) or alternating bi-weekly (three injections every other week). While only marginally reducing obesity, intermittent administration of rapamycin significantly extended lifespan. Significance was achieved for weekly treated group and for the three rapamycin-received groups combined. In weekly treatment group, 100% mice were alive by the age of 2 years, whereas 60% of mice died in untreated group by this age. The effect of weekly treatment on survival was highly significant and cannot be fully explained by partial reduction in obesity. Alternating bi-weekly treatments seem to be less effective than weekly treatment, although effects of additional factors (see ) may not be excluded. After one year of treatment, all survived mice were sacrificed 8 days after the last administration of rapamycin to avoid its direct interference with parameters examined. Fasting levels of cardiac and hepatic p-S6, a marker of mTORC1 activity, were lower in weekly treatment group compared with control mice. In contrast, levels of p-Akt (S473), glucose, triglycerides and insulin were unchanged, whereas leptin and IGF-1 tended to be lower. Thus, weekly treatment with rapamycin may slow down aging in obese male mice on high-fat diet. PMID:24655348

  20. Lead-induced modifications of immune responses in aging male and female mice

    SciTech Connect

    Genova, T.F.

    1982-01-01

    This study was designed to analyze the effects of lead intoxication on the immunological responses of aging male and female Balb/c mice. Both males and females on the lead diet exhibited a loss of weight after one week of treatment. The animals began to gain weight again after eight or fifteen weeks for males and females respectively. Although both groups continued to gain weight at a rate consistent with control animals, they never reached the same weights as their same-sex control counterparts. Immunofluorescent staining indicated the presence of greater renal pathology in lead-fed animals as compared to controls. Lead-fed males demonstrated the greatest pathology of any group. Both T and B cell mitogenic responses declined during the early phases of the experiment. This was followed, at age 25-27 weeks, by an increase in activity to levels greater than those of control animals. The depression and subsequent increase in mitogenic responses was mirrored in the ability of T cells to regulate B cell plaque formation when stimulated with sheep red blood cells. T cell function returned to control levels in coincidence with the increase in T and B cell mitogenicity. The return of T cell functionality to control levels coincides with the increased mitogenesis noted in T and B cell populations and the onset of weight gains by lead-fed animals. This coincidence suggests the occurrence of a physiological or immunological change which is compensating for the continued lead intoxication. One such change may be a lead induced reduction in the number or function of a T cell subset, eg. T suppressors.

  1. Adult Male Mice Emit Context-Specific Ultrasonic Vocalizations That Are Modulated by Prior Isolation or Group Rearing Environment

    PubMed Central

    Ey, Elodie; Bellier, Ludovic; Aubin, Thierry; Bourgeron, Thomas; Granon, Sylvie

    2012-01-01

    Social interactions in mice are frequently analysed in genetically modified strains in order to get insight of disorders affecting social interactions such as autism spectrum disorders. Different types of social interactions have been described, mostly between females and pups, and between adult males and females. However, we recently showed that social interactions between adult males could also encompass cognitive and motivational features. During social interactions, rodents emit ultrasonic vocalizations (USVs), but it remains unknown if call types are differently used depending of the context and if they are correlated with motivational state. Here, we recorded the calls of adult C57BL/6J male mice in various behavioral conditions, such as social interaction, novelty exploration and restraint stress. We introduced a modulator for the motivational state by comparing males maintained in isolation and males maintained in groups before the experiments. Male mice uttered USVs in all social and non-social situations, and even in a stressful restraint context. They nevertheless emitted the most important number of calls with the largest diversity of call types in social interactions, particularly when showing a high motivation for social contact. For mice maintained in social isolation, the number of calls recorded was positively correlated with the duration of social contacts, and most calls were uttered during contacts between the two mice. This correlation was not observed in mice maintained in groups. These results open the way for a deeper understanding and characterization of acoustic signals associated with social interactions. They can also help evaluating the role of motivational states in the emission of acoustic signals. PMID:22238608

  2. Epidermal growth factor receptor plays a role in the regulation of liver and plasma lipid levels in adult male mice

    PubMed Central

    Zhang, Xiuqi; Garcia, Oscar A.; Wang, Rebecca F.; Stevenson, Mary C.; Threadgill, David W.; Russell, William E.

    2014-01-01

    Dsk5 mice have a gain of function in the epidermal growth factor receptor (EGFR), caused by a point mutation in the kinase domain. We analyzed the effect of this mutation on liver size, histology, and composition. We found that the livers of 12-wk-old male Dsk5 heterozygotes (+/Dsk5) were 62% heavier compared with those of wild-type controls (+/+). The livers of the +/Dsk5 mice compared with +/+ mice had larger hepatocytes with prominent, polyploid nuclei and showed modestly increased cell proliferation indices in both hepatocytes and nonparenchymal cells. An analysis of total protein, DNA, and RNA (expressed relative to liver weight) revealed no differences between the mutant and wild-type mice. However, the livers of the +/Dsk5 mice had more cholesterol but less phospholipid and fatty acid. Circulating cholesterol levels were twice as high in adult male +/Dsk5 mice but not in postweaned young male or female mice. The elevated total plasma cholesterol resulted mainly from an increase in low-density lipoprotein (LDL). The +/Dsk5 adult mouse liver expressed markedly reduced protein levels of LDL receptor, no change in proprotein convertase subtilisin/kexin type 9, and a markedly increased fatty acid synthase and 3-hydroxy-3-methyl-glutaryl-CoA reductase. Increased expression of transcription factors associated with enhanced cholesterol synthesis was also observed. Together, these findings suggest that the EGFR may play a regulatory role in hepatocyte proliferation and lipid metabolism in adult male mice, explaining why elevated levels of EGF or EGF-like peptides have been positively correlated to increased cholesterol levels in human studies. PMID:24407590

  3. [Synaptonemal complexes of chromosomes of male mice after prolonged administration of neoaquasept].

    PubMed

    Kolomiets, O L; Mazurova, T F; Bogdanov, Iu F; Bogush, T A; Mal'tsev, M V

    1993-12-01

    A long-term (during 4 months) daily peroral injections of neoaquasept (NA) (a drinking water disinfections agent) at a dose corresponding to the normal level of consumption increases the number of spermatocytes in which the sexual bivalent associates with normal autosomal bivalents (up to 18.2%). In single cells a premature desynapsis of sex chromosomes at late pachytene was observed. There was the appearance of single cells with the X0 karyotype. A 3-fold excess of the normal consumption of NA causes an increase in the number of cells with the above disturbance in the SC structure and behaviour and causes the appearance of heteromorphic bivalents. On the 7th day after a single MTD injection of NA male mice displayed a sharp (up to 27.9%) increase in the number of cells in which the sexual bivalent associated with autosomal bivalents, formation of univalents of autosomal and sex chromosomes, SC degeneration. PMID:8119577

  4. Progesterone reduces brain mitochondrial dysfunction after transient focal ischemia in male and female mice.

    PubMed

    Gaignard, Pauline; Fréchou, Magalie; Schumacher, Michael; Thérond, Patrice; Mattern, Claudia; Slama, Abdelhamid; Guennoun, Rachida

    2016-03-01

    This study investigated the effect of intranasal administration of progesterone on the early brain mitochondrial respiratory chain dysfunction and oxidative damage after transient middle cerebral occlusion in male and female mice. We showed that progesterone (8 mg/kg at 1 h post-middle cerebral occlusion) restored the mitochondrial reduced glutathione pool and the nicotinamide adenine dinucleotide-linked respiration in both sexes. Progesterone also reversed the decrease of the flavin adenine dinucleotide-linked respiration, which was only observed in females. Our findings point to a sex difference in stroke effects on the brain respiratory chain and suggest that the actions of progesterone on mitochondrial function may participate in its neuroprotective properties. PMID:26661198

  5. Dietary fats influence consumption and metabolic measures in male and female laboratory mice.

    PubMed

    Brain, P F; Maimanee, T A; Andrade, M

    2000-04-01

    Juvenile and adult male and female Swiss mice in metabolism cages were fed one of four specially-formulated, pelleted diets containing respectively 8% saturated vegetable fat, 8% soya oil, 8% olive oil and 2% soya oil. The identities of the diets were hidden from the experimenter. Subjects were individually housed in metabolism cages and their consumption of food, growth and eliminative activities were measured. Clearly, these non-isocaloric diets differed in palatability, producing complex effects on growth as well as metabolic measures. Many indices were influenced by age, sex, and the duration of dietary exposure. Interactions between factors were common. Dietary fats appear to have subtle effects on the physiology and behaviour of rodents and may account for some differences between studies. PMID:10817454

  6. Immunomodulatory effects of maternal atrazine exposure on male Balb/c mice

    SciTech Connect

    Rowe, Alexander M.; Brundage, Kathleen M.; Schafer, Rosana; Barnett, John B. . E-mail: jbarnett@hsc.wvu.edu

    2006-07-01

    Atrazine is a widely used herbicide applied to corn, sugar and other crops as a broad leaf weed inhibitor. Using the Balb/c mouse model, we have determined that prenatal/lactational exposure to atrazine alters adult immune function. Pregnant Balb/c dams were exposed subcutaneously for 21 days via time release pellets to 700 {mu}g per day of atrazine beginning between days 10 and 12 of pregnancy. Prenatal/Lactational exposure caused no overt physical malformations in the offspring and had no effect on the number of litters carried to term or the litter size. Upon reaching early adulthood (approximately 3 months of age), the state of their immune system was evaluated. There were no changes in body weight or in the organ to body weight ratio of the spleen. Additionally, no changes were observed in the number of CD8{sup +} T cell, CD4{sup +} T cell, or B220{sup +} B cell subpopulations in the spleen. T cell function was assessed by measuring proliferation and cytolytic activity after in vitro allogeneic stimulation. Male mice which had been prenatally/lactationally exposed to atrazine had an increase in both T cell proliferation and cytolytic activity. The humoral immune response was assessed after immunization with heat killed Streptococcus pneumoniae (HKSP). There was a significant increase in the number of HKSP-specific IgM secreting B cells in the spleen of prenatal/lactational exposed male mice. Inasmuch as atrazine is a widespread environmental contaminant, this immunopotentiation raises concerns that it may potentiate clinical diseases, such as autoimmune disease and hypersensitivity, and needs to be carefully monitored and studied.

  7. Chronic MPTP treatment produces hyperactivity in male mice which is not alleviated by concurrent trehalose treatment.

    PubMed

    Ferguson, Sherry A; Law, C Delbert; Sarkar, Sumit

    2015-10-01

    The chronic MPTP+probenecid treatment paradigm has been used to successfully model the neurochemical, neuropathological, and behavioral effects associated with Parkinson's disease. Here, adult male C57Bl/6 mice were injected ip with 25 mg/kg MPTP and 250 mg/kg probenecid (MPTPp) or saline twice weekly for a total of 10 injections. Behavioral assessments included motor coordination, grip strength, spatial learning/memory, locomotor activity, and anhedonia. Those assessments were repeated up to 8 weeks post-treatment. In a subsequent experiment, adult male mice were treated with saline or MPTPp as described above. One-half of each group was allowed access to 1% trehalose in the water bottle. Trehalose intake averaged 1.90-2.34 g/kg. Behavioral assessments included locomotor activity, olfaction, motor coordination, grip strength, and exploratory behavior. Those assessments were repeated 4 weeks post-treatment. The strongest MPTPp effect was hyperactivity as exhibited in the open field. This increased activity was apparent in both experiments and occurred at all time points post-treatment. Assessments of grip strength, water maze performance, olfaction, and exploratory behavior did not indicate MPTPp-related alterations. When the specifications for the motor coordination test were made somewhat easier in the second experiment, there were deficits exhibited by the MPTPp group, the MPTPp+trehalose group and the trehalose group. The addition of trehalose did not alleviate any of the MPTPp-induced behavioral alterations; however, trehalose treatment significantly attenuated the striatal decreases in DA, DOPAC, HVA and 5-HIAA. These results provide a more comprehensive description of the behavioral alterations resulting from the chronic MPTPp treatment regimen and suggest that trehalose at this concentration does not act as a complete neuroprotectant. PMID:26111725

  8. A new, albino-beige mouse: giant granules in retinal pigment epithelium.

    PubMed

    Robison, W G; Kuwabara, T

    1978-04-01

    Albino-beige mice were produced in order to combine two experimentally useful characteristics, albinism and lysosomal dysfunction, in the same animal. The retinal pigment epithelium of albino-beige mice formed giant intracellular granules. Exposure of albino-beige mice to white light of 150 foot-candles for 3 to 10 hr induced marked phagocytosis of rod outer segment fragments by the retinal pigment epithelium, resulting in intracellular accumulations of undigested disk membranes within the giant granules. Additional, incompletely processed membranes accumulated as the mice aged or were exposed to 150 foot-candle light for longer periods. Such accumulations of ingested membranes were not observed in the pigment epithelium of exposed or aging albino mice heterozygous for the beige gene. Because of its altered processing of ingested outer segment membranes, this new albino mouse should be useful for studying the possible roles of the retinal pigment epithelium in the maintenance of photoreceptor cells and in their recovery from light damage and other insults. PMID:640784

  9. Toll-like receptor signaling adapter proteins govern spread of neuropathic pain and recovery following nerve injury in male mice

    PubMed Central

    2013-01-01

    Background Spinal Toll-like receptors (TLRs) and signaling intermediaries have been implicated in persistent pain states. We examined the roles of two major TLR signaling pathways and selected TLRs in a mononeuropathic allodynia. Methods L5 spinal nerve ligation (SNL) was performed in wild type (WT, C57BL/6) male and female mice and in male Tlr2 -/- Tlr3 -/- , Tlr4 -/- , Tlr5 -/- , Myd88 -/- , Trif lps2 , Myd88/Trif lps2 , Tnf -/- , and Ifnar1 -/- mice. We also examined L5 ligation in Tlr4 -/- female mice. We examined tactile allodynia using von Frey hairs. Iba-1 (microglia) and GFAP (astrocytes) were assessed in spinal cords by immunostaining. Tactile thresholds were analyzed by 1- and 2-way ANOVA and the Bonferroni post hoc test was used. Results In WT male and female mice, SNL lesions resulted in a persistent and robust ipsilateral, tactile allodynia. In males with TLR2, 3, 4, or 5 deficiencies, tactile allodynia was significantly, but incompletely, reversed (approximately 50%) as compared to WT. This effect was not seen in female Tlr4 -/- mice. Increases in ipsilateral lumbar Iba-1 and GFAP were seen in mutant and WT mice. Mice deficient in MyD88, or MyD88 and TRIF, showed an approximately 50% reduction in withdrawal thresholds and reduced ipsilateral Iba-1. In contrast, TRIF and interferon receptor null mice developed a profound ipsilateral and contralateral tactile allodynia. In lumbar sections of the spinal cords, we observed a greater increase in Iba-1 immunoreactivity in the TRIF-signaling deficient mice as compared to WT, but no significant increase in GFAP. Removing MyD88 abrogated the contralateral allodynia in the TRIF signaling-deficient mice. Conversely, IFNβ, released downstream to TRIF signaling, administered intrathecally, temporarily reversed the tactile allodynia. Conclusions These observations suggest a critical role for the MyD88 pathway in initiating neuropathic pain, but a distinct role for the TRIF pathway and interferon in regulating

  10. Inhalation reproductive toxicology studies: Male dominant lethal study of n-hexane in Swiss (CD-1) mice: Final report

    SciTech Connect

    Mast, T.J.; Rommereim, R.L.; Evanoff, J.J.; Sasser, L.B.; Decker, J.R.; Stoney, K.H.; Weigel, R.J.; Westerberg, R.B.

    1988-08-01

    The straight-chain hydrocarbon, n-hexane, is a volatile, ubiquitous solvent routinely used in industrial environments; consequently, the opportunity for industrial, environmental or accidental exposure to hexane vapors is significant. Although myelinated nerve tissue is the primary target organ of hexane, the testes have also been identified as being sensitive to hexacarbon exposure. The objective of this study was to evaluate male dominant lethal effects in Swiss (CD-1) mice after exposure to 0, 200, 1000, or 5000 ppM n-hexane, 20 h/day for 5 consecutive days. Each exposure concentration consisted of 30 randomly selected, proven male breeders; 4 groups. The mice were weighed just prior to the first day of exposure and at weekly intervals until sacrifice. Ten males in each dose group were sacrificed one day after the cessation of exposure, and their testes and epididymides were removed for evaluation of the germinal epithelium. The remaining male mice, 20 per group, were individually housed in hanging wire-mesh breeding cages where they were mated with unexposed, virgin females for eight weekly intervals; new females were provided each week. The mated females were sacrificed 12 days after the last day of cohabitation and their reproductive status and the number and viability of the implants were recorded. The appearance and behavior of the male mice were unremarkable throughout the study period and no evidence of n-hexane toxicity was observed. 18 refs., 3 figs., 11 tabs.

  11. The testicular form of hormone-sensitive lipase HSLtes confers rescue of male infertility in HSL-deficient mice.

    PubMed

    Vallet-Erdtmann, Virginie; Tavernier, Geneviève; Contreras, Juan Antonio; Mairal, Aline; Rieu, Cécile; Touzalin, Anne-Marie; Holm, Cecilia; Jégou, Bernard; Langin, Dominique

    2004-10-01

    Inactivation of the hormone-sensitive lipase gene (HSL) confers male sterility with a major defect in spermatogenesis. Several forms of HSL are expressed in testis. HSLtes mRNA and protein are found in early and elongated spermatids, respectively. The other forms are expressed in diploid germ cells and interstitial cells of the testis. To determine whether the absence of the testis-specific form of HSL, HSLtes, was responsible for the infertility in HSL-null mice, we generated transgenic mice expressing HSLtes under the control of its own promoter. The transgenic animals were crossed with HSL-null mice to produce mice deficient in HSL in nongonadal tissues but expressing HSLtes in haploid germ cells. Cholesteryl ester hydrolase activity was almost completely blunted in HSL-deficient testis. Mice with one allele of the transgene showed an increase in enzymatic activity and a small elevation in the production of spermatozoa. The few fertile hemizygous male mice produced litters of very small to small size. The presence of the two alleles led to a doubling in cholesteryl ester hydrolase activity, which represented 25% of the wild type values associated with a qualitatively normal spermatogenesis and a partial restoration of sperm reserves. The fertility of these mice was totally restored with normal litter sizes. In line with the importance of the esterase activity, HSLtes transgene expression reversed the cholesteryl ester accumulation observed in HSL-null mice. Therefore, expression of HSLtes and cognate cholesteryl ester hydrolase activity leads to a rescue of the infertility observed in HSL-deficient male mice. PMID:15292223

  12. Immune Alterations in Male and Female Mice after 2-Deoxy-D-Glucose Administration

    NASA Technical Reports Server (NTRS)

    Dreau, Didier; Morton, Darla S.; Foster, Mareva; Swiggett, Jeanene P.; Sonnenfeld, Gerald

    1995-01-01

    Administration of 2-deoxy-D-glucose (2-DG), an analog of glucose which inhibits glycolysis by competitive antagonism for phosphohexose isomerase, results in acute periods of intracellular glucoprivation and hyperglycemia resulting in hyperphagia. In addition to these changes in the carbohydrate metabolism, injection of 2-DG results in alterations of both the endocrine and neurological systems as suggested by modifications in oxytocin and glucocorticoid levels and norepinephrine production. Moreover, alterations of the immune response, such as a decrease in the in vitro proliferation of splenocytes after mitogen-stimulation, were observed in mice injected with 2-DG. Sex, genotype and environment are among the factors that may modulate effects of catecholamines and hypothalamo-pituitary-adrenal axis on these immune changes. Sexual dimorphism in immune function resulting from the effects of sex hormones on immune effector cells has been shown in both animals and humans. These observations have important implications, especially with regard to higher incidence of many autoimmune diseases in females. Evidence exists that reproductive hormones influence the immune system and increase the risk of immunologically related disorders in both animals and humans. Indeed, immunological responses in stressful situations may also be confounded by fluctuations of sex hormones especially in females. Lymphocyte distribution, cytoldne production, and the ability of lymphocyte to proliferate in vitro were analyzed in male and female mice to determine if sex influenced 2-DG immunomodulation. In addition, the influence of hormones, especially sex hormones, on these changes were evaluated.

  13. Pairmate-dependent pup retrieval as parental behavior in male mice.

    PubMed

    Liang, Mingkun; Zhong, Jing; Liu, Hong-Xiang; Lopatina, Olga; Nakada, Ryusuke; Yamauchi, Agnes-Mikiko; Higashida, Haruhiro

    2014-01-01

    Appropriate parental care by fathers can greatly facilitate healthy human family life. However, much less is known about paternal behavior in animals compared to those regarding maternal behavior. Previously, we reported that male ICR strain laboratory mice, although not spontaneously parental, can be induced to display maternal-like parental care (pup retrieval) when separated from their pups by signals from the pairmate dam (Liu et al., 2013). This parental behavior by the ICR sires, which are not genetically biparental, is novel and has been designated as pairmate-dependent paternal behavior. However, the factors critical for this paternal behavior are unclear. Here, we report that the pairmate-dependent paternal retrieval behavior is observed especially in the ICR strain and not in C57BL/6 or BALB/c mice. An ICR sire displays retrieval behavior only toward his biological pups. A sire co-housed with an unrelated non-pairing dam in a new environment, under which 38-kHz ultrasonic vocalizations are not detected, does not show parenting behavior. It is important for sires to establish their own home territory (cage) by continuous housing and testing to display retrieval behavior. These results indicated that the ICR sires display distinct paternity, including father-child social interaction, and shed light on parental behavior, although further analyses of paternal care at the neuroendocrinological and neurocircuitry levels are required. PMID:25071431

  14. Xylitol affects the intestinal microbiota and metabolism of daidzein in adult male mice.

    PubMed

    Tamura, Motoi; Hoshi, Chigusa; Hori, Sachiko

    2013-01-01

    This study examined the effects of xylitol on mouse intestinal microbiota and urinary isoflavonoids. Xylitol is classified as a sugar alcohol and used as a food additive. The intestinal microbiota seems to play an important role in isoflavone metabolism. Xylitol feeding appears to affect the gut microbiota. We hypothesized that dietary xylitol changes intestinal microbiota and, therefore, the metabolism of isoflavonoids in mice. Male mice were randomly divided into two groups: those fed a 0.05% daidzein with 5% xylitol diet (XD group) and those fed a 0.05% daidzein-containing control diet (CD group) for 28 days. Plasma total cholesterol concentrations were significantly lower in the XD group than in the CD group (p < 0.05). Urinary amounts of equol were significantly higher in the XD group than in the CD group (p < 0.05). The fecal lipid contents (% dry weight) were significantly greater in the XD group than in the CD group (p < 0.01). The cecal microbiota differed between the two dietary groups. The occupation ratios of Bacteroides were significantly greater in the CD than in the XD group (p < 0.05). This study suggests that xylitol has the potential to affect the metabolism of daidzein by altering the metabolic activity of the intestinal microbiota and/or gut environment. Given that equol affects bone health, dietary xylitol plus isoflavonoids may exert a favorable effect on bone health. PMID:24336061

  15. Radiolabeling and autoradiographic tracing of Toxocara canis larvae in male mice

    SciTech Connect

    Wade, S.E.; Georgi, J.R.

    1987-02-01

    Artificially hatched infective larvae of Toxocara canis were labeled with /sup 75/Se in Medium 199 (Gibco) containing /sup 75/Se-methionine. Male CD-1 mice were infected with radiolabeled larvae by intragastric intubation or by intraperitoneal injection. At intervals of 3-56 days mice were killed and the organs prepared for compressed organ autoradiography. Radioactivity of parasitic larvae showed an exponential decrease with time, reflecting catabolism of label with a biological half life of 26 days (effective half life of 21 days) making possible experiments lasting several months. Total body larva counts, estimated by total body autoradiography, displayed an overall downward trend, but the rate of reduction was probably not constant because no significant positive or negative trends were noted from day 14 onward in the numbers of larvae. The carcass accumulated the greatest number of larvae followed by the central nervous system, liver, and lung in that order. When the numbers of larvae were considered in relationship to the mass of tissue, there were 4 groupings: central nervous system, liver, lung, carcass, and kidney, and genito-urinary organ, pelt, and intestine. No significant difference between intragastric and intraperitoneal administration was observed in the larval distribution after the larvae had left the initial site of deposition.

  16. Neural and behavioural changes in male periadolescent mice after prolonged nicotine-MDMA treatment.

    PubMed

    Adeniyi, Philip A; Ishola, Azeez O; Laoye, Babafemi J; Olatunji, Babawale P; Bankole, Oluwamolakun O; Shallie, Philemon D; Ogundele, Olalekan M

    2016-02-01

    The interaction between MDMA and Nicotine affects multiple brain centres and neurotransmitter systems (serotonin, dopamine and glutamate) involved in motor coordination and cognition. In this study, we have elucidated the effect of prolonged (10 days) MDMA, Nicotine and a combined Nicotine-MDMA treatment on motor-cognitive neural functions. In addition, we have shown the correlation between the observed behavioural change and neural structural changes induced by these treatments in BALB/c mice. We observed that MDMA (2 mg/Kg body weight; subcutaneous) induced a decline in motor function, while Nicotine (2 mg/Kg body weight; subcutaneous) improved motor function in male periadolescent mice. In combined treatment, Nicotine reduced the motor function decline observed in MDMA treatment, thus no significant change in motor function for the combined treatment versus the control. Nicotine or MDMA treatment reduced memory function and altered hippocampal structure. Similarly, a combined Nicotine-MDMA treatment reduced memory function when compared with the control. Ultimately, the metabolic and structural changes in these neural systems were seen to vary for the various forms of treatment. It is noteworthy to mention that a combined treatment increased the rate of lipid peroxidation in brain tissue. PMID:26088184

  17. [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. PMID:26601507

  18. Protective effect of allicin against glycidamide-induced toxicity in male and female mice.

    PubMed

    Wang, En-Ting; Chen, Dong-Yan; Liu, Huang-You; Yan, Hai-Yang; Yuan, Yuan

    2015-04-01

    Acrylamide is known to be a neurotoxic, genotoxic, and carcinogenic compound. Glycidamide has a close relationship to the toxic mechanism of acrylamide. In order to explore the toxic mechanism of acrylamide, we further discussed the effects of oral administration of allicin on glycidamide-induced toxicity by determining the hematological parameters like AST, ALT, LDH, BUN, creatinine, ROS, and 8-OHdG, and biochemical parameters such as MDA, MPO, SOD, GST and GSH in the kidney, liver, brain and lung of male and female mice for the first time. We found that the same dose of glycidamide had more toxic effects and damage effects to the mice compared to the previous study of acrylamide. It could markedly increase the level of AST, ALT, LDH, BUN, ROS, 8-OHdG, MDA, MPO while decrease the SOD, GST and GSH. However, our data showed the oral administered allicin with a concentration of 5, 10, and 20 mg/kg b.w./day could significantly decrease the damage indexes of AST, ALT, LDH, BUN, ROS, 8-OHdG, MDA, and MPO, while increase the antioxidant indicators of SOD, GST and GSH. Thus allicin could be used as an effective dietary supplement for the chemoprevention of glycidamide genotoxicity internally, and to prevent the tissue damage and toxicity induced by glycidamide. PMID:25730897

  19. Xylitol Affects the Intestinal Microbiota and Metabolism of Daidzein in Adult Male Mice

    PubMed Central

    Tamura, Motoi; Hoshi, Chigusa; Hori, Sachiko

    2013-01-01

    This study examined the effects of xylitol on mouse intestinal microbiota and urinary isoflavonoids. Xylitol is classified as a sugar alcohol and used as a food additive. The intestinal microbiota seems to play an important role in isoflavone metabolism. Xylitol feeding appears to affect the gut microbiota. We hypothesized that dietary xylitol changes intestinal microbiota and, therefore, the metabolism of isoflavonoids in mice. Male mice were randomly divided into two groups: those fed a 0.05% daidzein with 5% xylitol diet (XD group) and those fed a 0.05% daidzein-containing control diet (CD group) for 28 days. Plasma total cholesterol concentrations were significantly lower in the XD group than in the CD group (p < 0.05). Urinary amounts of equol were significantly higher in the XD group than in the CD group (p < 0.05). The fecal lipid contents (% dry weight) were significantly greater in the XD group than in the CD group (p < 0.01). The cecal microbiota differed between the two dietary groups. The occupation ratios of Bacteroides were significantly greater in the CD than in the XD group (p < 0.05). This study suggests that xylitol has the potential to affect the metabolism of daidzein by altering the metabolic activity of the intestinal microbiota and/or gut environment. Given that equol affects bone health, dietary xylitol plus isoflavonoids may exert a favorable effect on bone health. PMID:24336061

  20. Cimetidine and Clobenpropit Attenuate Inflammation-Associated Colorectal Carcinogenesis in Male ICR Mice

    PubMed Central

    Tanaka, Takuji; Kochi, Takahiro; Shirakami, Yohei; Mori, Takayuki; Kurata, Ayumi; Watanabe, Naoki; Moriwaki, Hisataka; Shimizu, Masahito

    2016-01-01

    Histamine and histamine receptors (Hrhs) have been identified as critical molecules during inflammation and carcinogenesis. This study was conducted to determine the effects of Hrh1-Hrh3 antagonists on inflammation-associated colorectal carcinogenesis. Male ICR mice were treated with azoxymethane (AOM, 10 mg/kg bw, i.p.) and 1.5% dextran sodium sulfate (DSS, drinking water for 7 days) to induce colorectal carcinogenesis. The mice were then fed diets containing test chemical (500 ppm terfenadine, 500 ppm cimetidine or 10 ppm clobenpropit) for 15 weeks. At week 18, feeding with the diets containing cimetidine (Hrh2 antagonist) and clobenpropit (Hrh3 antagonist/inverse agonist) significantly lowered the multiplicity of colonic adenocarcinoma. Terfenadine (Hrh1 antagonist) did not affect AOM-DSS-induced colorectal carcinogenesis. Adenocarcinoma cells immunohistochemically expressed Hrh1, Hrh2, Hrh3 and Hrh4 with varied intensities. Because clobenpropit is also known to be a Hrh4 receptor agonist, Hrh2, Hrh3 and Hrh4 may be involved in inflammation-related colorectal carcinogenesis. Additional data, including the mRNA expression of pro-inflammatory cytokines and inducible inflammatory enzymes in the colonic mucosa, are also presented. PMID:26907350

  1. Promotive Effect of Topical Ketoconazole, Minoxidil, and Minoxidil with Tretinoin on Hair Growth in Male Mice

    PubMed Central

    Aldhalimi, Muhsin A.; Hadi, Najah R.; Ghafil, Fadaa A.

    2014-01-01

    Recently topical use of 2% Ketoconazole solution has been reported to have a therapeutic effect on androgenic alopecia. Minoxidil is a vasodilatory medication used primarily as antihypertensive drug. It was discovered to have the side effect of hair growth and reversing baldness. Tretinoin is commonly used topically for acne treatment and in the treatment of photoaging. It is used by some as hair loss treatment. Objective. To compare the stimulatory effect of Ketoconazole, Minoxidil, and Minoxidil with Tretinoin on hair growth in a mouse model. Materials and Methods. Coat hairs on the dorsal skin of seven weeks old male mice were gently clipped and then stained by using commercial dye. These mice were divided into four groups each of five treated with topical application of ethanol 95%, Ketoconazole solution 2%, Minoxidil solution 5%, and Minoxidil with Tretinoin solution 0.1%, respectively. The drugs were applied once daily for three weeks, the clipped area was photographed, and the ratio of regrown coat area was calculated. Results. The results demonstrated that Ketoconazole, Minoxidil, and Minoxidil with Tretinoin had a significant stimulatory effect on hair growth compared with the control group and Minoxidil was the most effective drug among them. PMID:24734193

  2. Promotive effect of topical ketoconazole, minoxidil, and minoxidil with tretinoin on hair growth in male mice.

    PubMed

    Aldhalimi, Muhsin A; Hadi, Najah R; Ghafil, Fadaa A

    2014-01-01

    Recently topical use of 2% Ketoconazole solution has been reported to have a therapeutic effect on androgenic alopecia. Minoxidil is a vasodilatory medication used primarily as antihypertensive drug. It was discovered to have the side effect of hair growth and reversing baldness. Tretinoin is commonly used topically for acne treatment and in the treatment of photoaging. It is used by some as hair loss treatment. Objective. To compare the stimulatory effect of Ketoconazole, Minoxidil, and Minoxidil with Tretinoin on hair growth in a mouse model. Materials and Methods. Coat hairs on the dorsal skin of seven weeks old male mice were gently clipped and then stained by using commercial dye. These mice were divided into four groups each of five treated with topical application of ethanol 95%, Ketoconazole solution 2%, Minoxidil solution 5%, and Minoxidil with Tretinoin solution 0.1%, respectively. The drugs were applied once daily for three weeks, the clipped area was photographed, and the ratio of regrown coat area was calculated. Results. The results demonstrated that Ketoconazole, Minoxidil, and Minoxidil with Tretinoin had a significant stimulatory effect on hair growth compared with the control group and Minoxidil was the most effective drug among them. PMID:24734193

  3. Middle age has a significant impact on gene expression during skin wound healing in male mice.

    PubMed

    Yanai, Hagai; Lumenta, David Benjamin; Vierlinger, Klemens; Hofner, Manuela; Kitzinger, Hugo-Benito; Kamolz, Lars-Peter; Nöhammer, Christa; Chilosi, Marco; Fraifeld, Vadim E

    2016-08-01

    The vast majority of research on the impact of age on skin wound healing (WH) compares old animals to young ones. The middle age is often ignored in biogerontological research despite the fact that many functions that decline in an age-dependent manner have starting points in mid-life. With this in mind, we examined gene expression patterns during skin WH in late middle-aged versus young adult male mice, using the head and back punch models. The rationale behind this study was that the impact of age would first be detectable at the transcriptional level. We pinpointed several pathways which were over-activated in the middle-aged mice, both in the intact skin and during WH. Among them were various metabolic, immune-inflammatory and growth-promoting pathways. These transcriptional changes were much more pronounced in the head than in the back. In summary, the middle age has a significant impact on gene expression in intact and healing skin. It seems that the head punch model is more sensitive to the effect of age than the back model, and we suggest that it should be more widely applied in aging research on wound healing. PMID:27241672

  4. No evidence found for induction of dominant lethal mutations and heritable translocations in male mice by calcium cyclamate

    SciTech Connect

    Cain, K.T.; Cornett, C.V.; Cacheiro, L.A.; Hughes, L.A.; Owens, J.G.; Generoso, W.M.

    1988-01-01

    Calcium cyclamate, an artificial sweetener, was studied for its effectiveness in inducing transmissible chromosomal aberrations in germ cells of male mice. Both the dominant-lethal and the heritable translocation tests were carried out following daily treatment (on weekdays) of males by oral intubation with the maximum tolerated dose for 6 weeks. Calcium cyclamate is negative in both tests; therefore, there is no evidence of induced chromosome breakage and exchange.

  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. Effects of ambient temperature on glucose tolerance and insulin sensitivity test outcomes in normal and obese C57 male mice.

    PubMed

    Dudele, Anete; Rasmussen, Gitte Marie; Mayntz, David; Malte, Hans; Lund, Sten; Wang, Tobias

    2015-05-01

    Mice are commonly used as animal models to study human metabolic diseases, but experiments are typically performed at room temperature, which is far below their thermoneutral zone and is associated with elevated heart rate, food intake, and energy expenditure. We set out to study how ambient temperature affects glucose tolerance and insulin sensitivity in control and obese male mice. Adult male C57BL/6J mice were housed at room temperature (23°C) for 6 weeks and fed either control or high fat diet. They were then fasted for 6 h before glucose or insulin tolerance tests were performed at 15, 20, 25, or 30°C. To ensure that behavioral thermoregulation did not counterbalance the afflicted ambient temperatures, oxygen consumption was determined on mice with the same thermoregulatory opportunities as during the tests. Decreasing ambient temperatures increased oxygen consumption and body mass loss during fasting in both groups. Mice fed high fat diet had improved glucose tolerance at 30°C and increased levels of fasting insulin followed by successive decrease of fasting glucose. However, differences between control and high-fat diet mice were present at all temperatures. Ambient temperature did not affect glucose tolerance in control group and insulin tolerance in either of the groups. Ambient temperature affects glucose metabolism in mice and this effect is phenotype specific. PMID:25991720

  7. Effects of ambient temperature on glucose tolerance and insulin sensitivity test outcomes in normal and obese C57 male mice

    PubMed Central

    Dudele, Anete; Rasmussen, Gitte Marie; Mayntz, David; Malte, Hans; Lund, Sten; Wang, Tobias

    2015-01-01

    Mice are commonly used as animal models to study human metabolic diseases, but experiments are typically performed at room temperature, which is far below their thermoneutral zone and is associated with elevated heart rate, food intake, and energy expenditure. We set out to study how ambient temperature affects glucose tolerance and insulin sensitivity in control and obese male mice. Adult male C57BL/6J mice were housed at room temperature (23°C) for 6 weeks and fed either control or high fat diet. They were then fasted for 6 h before glucose or insulin tolerance tests were performed at 15, 20, 25, or 30°C. To ensure that behavioral thermoregulation did not counterbalance the afflicted ambient temperatures, oxygen consumption was determined on mice with the same thermoregulatory opportunities as during the tests. Decreasing ambient temperatures increased oxygen consumption and body mass loss during fasting in both groups. Mice fed high fat diet had improved glucose tolerance at 30°C and increased levels of fasting insulin followed by successive decrease of fasting glucose. However, differences between control and high-fat diet mice were present at all temperatures. Ambient temperature did not affect glucose tolerance in control group and insulin tolerance in either of the groups. Ambient temperature affects glucose metabolism in mice and this effect is phenotype specific. PMID:25991720

  8. The Magea gene cluster regulates male germ cell apoptosis without affecting the fertility in mice

    PubMed Central

    Hou, Siyuan; Xian, Li; Shi, Peiliang; Li, Chaojun; Lin, Zhaoyu; Gao, Xiang

    2016-01-01

    While apoptosis is essential for male germ cell development, improper activation of apoptosis in the testis can affect spermatogenesis and cause reproduction defects. Members of the MAGE-A (melanoma antigen family A) gene family are frequently clustered in mammalian genomes and are exclusively expressed in the testes of normal animals but abnormally activated in a wide variety of cancers. We investigated the potential roles of these genes in spermatogenesis by generating a mouse model with a 210-kb genomic deletion encompassing six members of the Magea gene cluster (Magea1, Magea2, Magea3, Magea5, Magea6 and Magea8). Male mice carrying the deletion displayed smaller testes from 2 months old with a marked increase in apoptotic germ cells in the first wave of spermatogenesis. Furthermore, we found that Magea genes prevented stress-induced spermatogenic apoptosis after N-ethyl-N-nitrosourea (ENU) treatment during the adult stage. Mechanistically, deletion of the Magea gene cluster resulted in a dramatic increase in apoptotic germ cells, predominantly spermatocytes, with activation of p53 and induction of Bax in the testes. These observations demonstrate that the Magea genes are crucial in maintaining normal testicular size and protecting germ cells from excessive apoptosis under genotoxic stress. PMID:27226137

  9. The Magea gene cluster regulates male germ cell apoptosis without affecting the fertility in mice.

    PubMed

    Hou, Siyuan; Xian, Li; Shi, Peiliang; Li, Chaojun; Lin, Zhaoyu; Gao, Xiang

    2016-01-01

    While apoptosis is essential for male germ cell development, improper activation of apoptosis in the testis can affect spermatogenesis and cause reproduction defects. Members of the MAGE-A (melanoma antigen family A) gene family are frequently clustered in mammalian genomes and are exclusively expressed in the testes of normal animals but abnormally activated in a wide variety of cancers. We investigated the potential roles of these genes in spermatogenesis by generating a mouse model with a 210-kb genomic deletion encompassing six members of the Magea gene cluster (Magea1, Magea2, Magea3, Magea5, Magea6 and Magea8). Male mice carrying the deletion displayed smaller testes from 2 months old with a marked increase in apoptotic germ cells in the first wave of spermatogenesis. Furthermore, we found that Magea genes prevented stress-induced spermatogenic apoptosis after N-ethyl-N-nitrosourea (ENU) treatment during the adult stage. Mechanistically, deletion of the Magea gene cluster resulted in a dramatic increase in apoptotic germ cells, predominantly spermatocytes, with activation of p53 and induction of Bax in the testes. These observations demonstrate that the Magea genes are crucial in maintaining normal testicular size and protecting germ cells from excessive apoptosis under genotoxic stress. PMID:27226137

  10. Maternal immune activation differentially impacts mature and adult-born hippocampal neurons in male mice.

    PubMed

    Zhang, Zhi; van Praag, Henriette

    2015-03-01

    Schizophrenia is associated with deficits in the hippocampus, a brain area important for learning and memory. The dentate gyrus (DG) of the hippocampus develops both before and after birth. To study the relative contribution of mature and adult-born DG granule cells to disease etiology, we compared both cell populations in a mouse model of psychiatric illness resulting from maternal immune activation. Polyriboinosinic-polyribocytidilic acid (PolyIC, 5mg/kg) or saline was given on gestation day 15 to pregnant female C57Bl/6 mice. Male offspring (n=105), was administered systemic bromodeoxyuridine (BrdU, 50mg/kg) (n=52) or intracerebral retroviral injection into the DG (n=53), to label dividing cells at one month of age. Two months later behavioral tests were performed to evaluate disease phenotype. Immunohistochemistry and whole-cell patch clamping were used to assess morphological and physiological characteristics of DG cells. Three-month-old PolyIC exposed male offspring exhibited deficient pre-pulse inhibition, spatial maze performance and motor coordination, as well as increased depression-like behavior. Histological analysis showed reduced DG volume and parvalbumin positive interneuron number. Both mature and new hippocampal neurons showed modifications in intrinsic properties such as increased input resistance and lower current threshold, and decreased action potential number. Reduced GABAergic inhibitory transmission was observed only in mature DG neurons. Differential impairments in mature DG cells and adult-born new neurons may have implications for behavioral deficits associated with maternal immune activation. PMID:25449671

  11. Measures of anxiety, sensorimotor function, and memory in male and female mGluR4-/- mice

    PubMed Central

    Davis, Matthew J.; Haley, Tammie; Duvoisin, Robert M.; Raber, Jacob

    2012-01-01

    Metabotropic glutamate receptors (mGluRs) are coupled to second messenger pathways via G proteins and modulate synaptic transmission. Of the eight different types of mGluRs (mGluR1-mGluR8), mGluR4, mGluR6, mGluR7, and mGluR8 are members of group III. Group III receptors are generally located presynaptically, where they regulate neurotransmitter release. Because of their role in modulating neurotransmission, mGluRs are attractive targets for therapies aimed at treating anxiety disorders. Previously we showed that the mGluR4-selective allosteric agonist VU 0155041 reduces anxiety-like behavior in wild-type male mice. Here, we explore the role of mGluR4 in adult (6-month-old) and middle-aged (12-month-old) male and female mice lacking this receptor. Compared to age- and sex-matched wild-type mice, middle-aged mGluR4-/- male mice showed increased measures of anxiety in the open field and elevated zero maze and impaired sensorimotor function on the rotarod. These changes were not seen in adult 6-month old male mice. In contrast to the male mice, mGluR4-/- female mice showed reduced measures of anxiety in the open field and elevated zero maze and enhanced rotarod performance. During the hidden platform training sessions of the water maze, mGluR4-/-mice swam father away from the platform than wild-type mice at 6, but not at 12, months of age. mGluR4-/- mice also showed enhanced amygdala-dependent cued fear conditioning. No genotype differences were seen in hippocampus-dependent contextual fear conditioning. These data indicate that effects of mGluR4 on sensorimotor function and measures of anxiety, but not cued fear conditioning, are critically modulated by sex and age. PMID:22227508

  12. Adult Behavior in Male Mice Exposed to E-Cigarette Nicotine Vapors during Late Prenatal and Early Postnatal Life

    PubMed Central

    Smith, Dani; Aherrera, Angela; Lopez, Armando; Neptune, Enid; Winickoff, Jonathan P.; Klein, Jonathan D.; Chen, Gang; Lazarus, Philip; Collaco, Joseph M.; McGrath-Morrow, Sharon A.

    2015-01-01

    Nicotine exposure has been associated with an increased likelihood of developing attention deficit hyperactivity disorder (ADHD) in offspring of mothers who smoked during pregnancy. The goal of this study was to determine if exposure to E-cigarette nicotine vapors during late prenatal and early postnatal life altered behavior in adult mice. Methods Timed-pregnant C57BL/6J mice were exposed to 2.4% nicotine in propylene glycol (PG) or 0% nicotine /PG once a day from gestational day 15 until delivery. After delivery, offspring and mothers were exposed to E-cigarette vapors for an additional 14 days from postnatal day 2 through 16. Following their last exposure serum cotinine levels were measured in female juvenile mice. Male mice underwent behavioral testing at 14 weeks of age to assess sensorimotor, affective, and cognitive functional domains. Results Adult male mice exposed to 2.4% nicotine/PG E-cigarette vapors had significantly more head dips in the zero maze test and higher levels of rearing activity in the open field test compared to 0% nicotine/PG exposed mice and untreated controls. In the water maze test after reversal training, the 2.4% nicotine/PG mice spent more than 25% of time in the new location whereas the other groups did not. Conclusion Adult male mice exhibited increased levels of activity in the zero maze and open field tests when exposed to E-cigarette vapor containing nicotine during late prenatal and early postnatal life. These findings indicate that nicotine exposure from E-cigarettes may cause persistent behavioral changes when exposure occurs during a period of rapid brain growth. PMID:26372012

  13. Increased 4E-BP1 Expression Protects against Diet-Induced Obesity and Insulin Resistance in Male Mice.

    PubMed

    Tsai, Shih-Yin; Rodriguez, Ariana A; Dastidar, Somasish G; Del Greco, Elizabeth; Carr, Kaili Lia; Sitzmann, Joanna M; Academia, Emmeline C; Viray, Christian Michael; Martinez, Lizbeth Leon; Kaplowitz, Brian Stephen; Ashe, Travis D; La Spada, Albert R; Kennedy, Brian K

    2016-08-16

    Obesity is a major risk factor driving the global type II diabetes pandemic. However, the molecular factors linking obesity to disease remain to be elucidated. Gender differences are apparent in humans and are also observed in murine models. Here, we link these differences to expression of eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1), which, upon HFD feeding, becomes significantly reduced in the skeletal muscle and adipose tissue of male but not female mice. Strikingly, restoring 4E-BP1 expression in male mice protects them against HFD-induced obesity and insulin resistance. Male 4E-BP1 transgenic mice also exhibit reduced white adipose tissue accumulation accompanied by decreased circulating levels of leptin and triglycerides. Importantly, transgenic 4E-BP1 male mice are also protected from aging-induced obesity and metabolic decline on a normal diet. These results demonstrate that 4E-BP1 is a gender-specific suppressor of obesity that regulates insulin sensitivity and energy metabolism. PMID:27498874

  14. EFFECTS OF HEAT AND BROMOCHLOROACETIC ACID ON MALE REPRODUCTION IN HEAT SHOCK FACTOR-1 GENE KNOCKOUT MICE

    EPA Science Inventory

    Effects of heat and bromochloroacetic acid on male reproduction in heat shock factor-1 gene knockout mice.
    Luft JC1, IJ Benjamin2, JB Garges1 and DJ Dix1. 1Reproductive Toxicology Division, USEPA, RTP, NC, 27711 and 2Dept of Internal Medicine, Univ.of Texas Southwestern Med C...

  15. AGE RELATED CHANGE IN DISPOSITION AND METABOLISM OF BENZENE IN MALE C57B/6N MICE

    EPA Science Inventory

    Benzene disposition and metabolism were examined as a function of age in male C57BL/6N mice aged 3 and 18 months. ice received a single oral dose of either 10 or 200 mg/kg 14-C benzene (approximately 24 uCi/kg). xcretion of 14C derived benzene radioactivity (RA) was monitored in ...

  16. Sexual maturation and fertility of male and female mice exposed prenatally and postnatally to trivalent and hexavalent chromium compounds.

    PubMed

    Al-Hamood, M H; Elbetieha, A; Bataineh, H

    1998-01-01

    The reproductive toxicity of trivalent and hexavalent chromium compounds was investigated in male and female mice exposed to 1000 ppm chromium chloride and potassium dichromate via their mother during gestational and lactational periods. Fertility was reduced in male offspring exposed to either trivalent or hexavalent chromium compounds. Body weights and weights of testes, seminal vesicles and preputial glands were reduced in trivalent-exposed male offspring. The exposure of female mice offspring to trivalent and hexavalent chromium compounds delayed sexual maturation. Fertility was reduced in female offspring exposed to either trivalent or hexavalent chromium compounds. The exposure of female mice to hexavalent chromium compound reduced the number of implantations and viable fetuses respectively. Body weight and weights of ovaries and uteri were reduced in trivalent-exposed female offspring. The results indicate that under our experimental conditions, the exposure of male and female mice offspring to either trivalent or hexavalent chromium compounds during gestational and lactational periods impair reproductive functions and fertility in adulthood. PMID:9801270

  17. GONADAL EFFECTS OF FETAL EXPOSURE TO THE AZO DYE CONGO RED IN MICE: INFERTILITY IN FEMALE BUT NOT MALE OFFSPRING

    EPA Science Inventory

    The present study describes the relationship between gonadal genesis and fertility in male and female mice exposed in utero to the diazo dye Congo red (CR). aternal CR treatment inhibited testicular and ovarian function in the offspring after oral administration of I or 0.5 g/kg/...

  18. GENE ARRAYS FOR ELUCIDATING MECHANISTIC DATA FROM MODELS OF MALE INFERTILITY AND CHEMICAL EXPOSURE IN MICE, RATS AND HUMANS

    EPA Science Inventory

    Gene arrays for elucidating mechanistic data from models of male infertility and chemical exposure in mice, rats and humans
    John C. Rockett and David J. Dix
    Gamete and Early Embryo Biology Branch, Reproductive Toxicology Division, National Health and Environmental Effects ...

  19. Effects of social defeat and of diazepam on behavior in a resident-intruder test in male DBA/2 mice.

    PubMed

    Lumley, L A; Charles, R F; Charles, R C; Hebert, M A; Morton, D M; Meyerhoff, J L

    2000-11-01

    Social stress induces robust behavioral and physiological changes, some of which may alter the responsiveness to pharmacological agents, including diazepam (DZP). We used a resident-intruder paradigm to (1) develop a comprehensive ethogram of behavioral changes following social defeat (SD) in the socially reactive strain, DBA/2 male mice, (2) determine whether acute exposure of DBA/2 mice to low-dose DZP would induce flight or aggressive behavior, both of which have been observed in other rodent models and (3) to test whether prior social stress affects responses to DZP. Behavioral responses to a nonaggressive intruder (NAI) mouse 24 h post-SD were measured in resident subject mice exposed to DZP (0, 0.5, 2.0 mg/kg, ip) either prior to the resident-intruder test (Experiment 1) or immediately post-SD (Experiment 2); control mice were not defeated (NOSD). In general, SD mice displayed increased passive and active avoidance, defense, immobility, and risk assessment relative to NOSD mice. In Experiment 1, mice treated acutely with 0.5 mg/kg DZP had more approach and flight behavior, while those treated with 2.0 mg/kg DZP had more avoidance than vehicle-treated mice, independent of SD. In Experiment 2, acute DZP (2 mg/kg) induced effects 24 h later, possibly secondary to withdrawal. In a nonsocial context (Experiment 3), DZP increased exploratory activity. PMID:11164070

  20. On-ground housing in “Mice Drawer System” (MDS) cage affects locomotor behaviour but not anxiety in male mice

    NASA Astrophysics Data System (ADS)

    Simone, Luciano; Bartolomucci, Alessandro; Palanza, Paola; Parmigiani, Stefano

    2008-03-01

    In the present study adult male mice were housed for 21 days in a housing modules of the Mice Drawer System (MDS). MDS is the facility that will support the research on board the International Space Station (ISS). Our investigation focused on: circadian rhythmicity of wide behavioural categories such as locomotor activity, food intake/drinking and resting; emotionality in the elevated plus maze (EPM); body weight. Housing in the MDS determined a strong up-regulation of activity and feeding behaviour and a concomitant decrease in inactivity. Importantly, housing in the MDS disrupted circadian rhythmicity in mice and also determined a decrease in body weight. Finally, when mice were tested in the EPM a clear hyperactivity (i.e. increased total transitions) was found, while no evidence for altered anxiety was detected. In conclusion, housing adult male mice in the MDS housing modules may affect their behaviour, circadian rhythmicity while having no effect on anxiety. It is suggested that to allow adaptation to the peculiar housing allowed by MDS a longer housing duration is needed.

  1. The male sex pheromone darcin stimulates hippocampal neurogenesis and cell proliferation in the subventricular zone in female mice.

    PubMed

    Hoffman, Emma; Pickavance, Lucy; Thippeswamy, Thimmasettappa; Beynon, Robert J; Hurst, Jane L

    2015-01-01

    The integration of newly generated neurons persists throughout life in the mammalian olfactory bulb and hippocampus, regions involved in olfactory and spatial learning. Social cues can be potent stimuli for increasing adult neurogenesis; for example, odors from dominant but not subordinate male mice increase neurogenesis in both brain regions of adult females. However, little is known about the role of neurogenesis in social recognition or the assessment of potential mates. Dominant male mice scent-mark territories using urine that contains a number of pheromones including darcin (MUP20), a male-specific major urinary protein that stimulates rapid learned attraction to the spatial location and individual odor signature of the scent owner. Here we investigate whether exposure to darcin stimulates neurogenesis in the female brain. Hippocampal neurons and cellular proliferation in the lateral ventricles that supply neurons to the olfactory bulbs increased in females exposed for 7 days to male urine containing at least 0.5 μg/μl darcin. Darcin was effective whether presented alone or in the context of male urine, but other information in male urine appeared to modulate the proliferative response. When exposed to urine from wild male mice, hippocampal proliferation increased only if urine was from the same individual over 7 days, suggesting that consistency of individual scent signatures is important. While 7 days exposure to male scent initiated the first stages of increased neurogenesis, this caused no immediate increase in female attraction to the scent or in the strength or robustness of spatial learning in short-term conditioned place preference tests. The reliable and consistent stimulation of neurogenesis by a pheromone important in rapid social learning suggests that this may provide an excellent model to explore the relationship between the integration of new neurons and plasticity in spatial and olfactory learning in a socially-relevant context. PMID

  2. The male sex pheromone darcin stimulates hippocampal neurogenesis and cell proliferation in the subventricular zone in female mice

    PubMed Central

    Hoffman, Emma; Pickavance, Lucy; Thippeswamy, Thimmasettappa; Beynon, Robert J.; Hurst, Jane L.

    2015-01-01

    The integration of newly generated neurons persists throughout life in the mammalian olfactory bulb and hippocampus, regions involved in olfactory and spatial learning. Social cues can be potent stimuli for increasing adult neurogenesis; for example, odors from dominant but not subordinate male mice increase neurogenesis in both brain regions of adult females. However, little is known about the role of neurogenesis in social recognition or the assessment of potential mates. Dominant male mice scent-mark territories using urine that contains a number of pheromones including darcin (MUP20), a male-specific major urinary protein that stimulates rapid learned attraction to the spatial location and individual odor signature of the scent owner. Here we investigate whether exposure to darcin stimulates neurogenesis in the female brain. Hippocampal neurons and cellular proliferation in the lateral ventricles that supply neurons to the olfactory bulbs increased in females exposed for 7 days to male urine containing at least 0.5 μg/μl darcin. Darcin was effective whether presented alone or in the context of male urine, but other information in male urine appeared to modulate the proliferative response. When exposed to urine from wild male mice, hippocampal proliferation increased only if urine was from the same individual over 7 days, suggesting that consistency of individual scent signatures is important. While 7 days exposure to male scent initiated the first stages of increased neurogenesis, this caused no immediate increase in female attraction to the scent or in the strength or robustness of spatial learning in short-term conditioned place preference tests. The reliable and consistent stimulation of neurogenesis by a pheromone important in rapid social learning suggests that this may provide an excellent model to explore the relationship between the integration of new neurons and plasticity in spatial and olfactory learning in a socially-relevant context. PMID

  3. The aromatase inhibitor letrozole increases epiphyseal growth plate height and tibial length in peripubertal male mice.

    PubMed

    Eshet, R; Maor, G; Ben Ari, T; Ben Eliezer, M; Gat-Yablonski, G; Phillip, M

    2004-07-01

    Sex hormones may influence longitudinal growth, either indirectly, by affecting the growth-hormone-insulin-like growth factor I (IGF-I) axis, or directly, by affecting changes within the epiphyseal growth plate (EGP). The aim of the present study was to investigate the effects of letrozole, an aromatase inhibitor, on longitudinal growth and changes in the EGP in vivo. Eighteen peripubertal male mice were divided into three groups. The first group was killed at baseline, the second was injected with letrozole (Femara) s.c., 2 mg/kg body weight/day, for 10 days, and the third was injected with the vehicle alone. Serum testosterone levels were found to be significantly higher in the treated group than in the controls. Letrozole induced a significant increase in body weight, tail length and serum growth hormone level, but had no significant effect on the level of serum IGF-I. On histomorphometric study, there was a significant increase (12%) in EGP height in the treated animals compared with controls. Immunohistochemistry showed a 3.4-fold letrozole-induced increase in the proliferation of the EGP chondrocytes, as estimated by the number of proliferation cell nuclear antigen-stained cells, and a decrease in the differentiation of the EGP chondrocytes, as estimated by type X collagen staining. Letrozole did not interfere with type II collagen levels. The study group also showed a twofold increase in the number of IGF-I receptor-positive cells compared with controls. In conclusion, the aromatase inhibitor, letrozole, appears to increase the linear growth potential of the EGP in mice. PMID:15225141

  4. FABP-1 gene ablation impacts brain endocannabinoid system in male mice.

    PubMed

    Martin, Gregory G; Chung, Sarah; Landrock, Danilo; Landrock, Kerstin K; Huang, Huan; Dangott, Lawrence J; Peng, Xiaoxue; Kaczocha, Martin; Seeger, Drew R; Murphy, Eric J; Golovko, Mikhail Y; Kier, Ann B; Schroeder, Friedhelm

    2016-08-01

    Liver fatty acid-binding protein (FABP1, L-FABP) has high affinity for and enhances uptake of arachidonic acid (ARA, C20:4, n-6) which, when esterified to phospholipids, is the requisite precursor for synthesis of endocannabinoids (EC) such as arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG). The brain derives most of its ARA from plasma, taking up ARA and transporting it intracellularly via cytosolic fatty acid-binding proteins (FABPs 3,5, and 7) localized within the brain. In contrast, the much more prevalent cytosolic FABP1 is not detectable in the brain but is instead highly expressed in the liver. Therefore, the possibility that FABP1 outside the central nervous system may regulate brain AEA and 2-AG was examined in wild-type (WT) and FABP1 null (LKO) male mice. LKO increased brain levels of AA-containing EC (AEA, 2-AG), correlating with increased free and total ARA in brain and serum. LKO also increased brain levels of non-ARA that contain potentiating endocannabinoids (EC*) such as oleoyl ethanolamide (OEA), PEA, 2-OG, and 2-PG. Concomitantly, LKO decreased serum total ARA-containing EC, but not non-ARA endocannabinoids. LKO did not elicit these changes in the brain EC and EC* as a result of compensatory up-regulation of brain protein levels of enzymes in EC synthesis (NAPEPLD, DAGLα) or cytosolic EC chaperone proteins (FABPs 3, 5, 7, SCP-2, HSP70), or cannabinoid receptors (CB1, TRVP1). These data show for the first time that the non-CNS fatty acid-binding protein FABP1 markedly affected brain levels of both ARA-containing endocannabinoids (AEA, 2-AG) as well as their non-ARA potentiating endocannabinoids. Fatty acid-binding protein-1 (FABP-1) is not detectable in brain but instead is highly expressed in liver. The possibility that FABP1 outside the central nervous system may regulate brain endocannabinoids arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG) was examined in wild-type (WT) and FABP-1 null (LKO) male mice. LKO

  5. Ultrasonic vocalizations of adult male Foxp2-mutant mice: behavioral contexts of arousal and emotion.

    PubMed

    Gaub, S; Fisher, S E; Ehret, G

    2016-02-01

    Adult mouse ultrasonic vocalizations (USVs) occur in multiple behavioral and stimulus contexts associated with various levels of arousal, emotion and social interaction. Here, in three experiments of increasing stimulus intensity (water; female urine; male interacting with adult female), we tested the hypothesis that USVs of adult males express the strength of arousal and emotion via different USV parameters (18 parameters analyzed). Furthermore, we analyzed two mouse lines with heterozygous Foxp2 mutations (R552H missense, S321X nonsense), known to produce severe speech and language disorders in humans. These experiments allowed us to test whether intact Foxp2 function is necessary for developing full adult USV repertoires, and whether mutations of this gene influence instinctive vocal expressions based on arousal and emotion. The results suggest that USV calling rate characterizes the arousal level, while sound pressure and spectrotemporal call complexity (overtones/harmonics, type of frequency jumps) may provide indices of levels of positive emotion. The presence of Foxp2 mutations did not qualitatively affect the USVs; all USV types that were found in wild-type animals also occurred in heterozygous mutants. However, mice with Foxp2 mutations displayed quantitative differences in USVs as compared to wild-types, and these changes were context dependent. Compared to wild-type animals, heterozygous mutants emitted mainly longer and louder USVs at higher minimum frequencies with a higher occurrence rate of overtones/harmonics and complex frequency jump types. We discuss possible hypotheses about Foxp2 influence on emotional vocal expressions, which can be investigated in future experiments using selective knockdown of Foxp2 in specific brain circuits. PMID:26566793

  6. The scent of urine spots of male mice, Mus musculus: Changes in chemical composition over time.

    PubMed

    Cavaggioni, Andrea; Mucignat-Caretta, Carla; Redaelli, Marco; Zagotto, Giuseppe

    2006-01-01

    A dominant male mouse scent-marks his territory very frequently by emitting small urinary spots. The urine spots release in the air a variety of odorants that transmit different information to other mice, especially those concerning the time of deposition. To investigate this effect, small spots of urine of a dominant male mouse were left to freely release the odorants in the air for time intervals ranging from 0 min to 24 h prior to sampling. Thereupon, the odorants remaining in the spot were sampled at diffusion equilibrium (45 degrees C) in a small vial by means of headspace solid-phase microextraction followed by gas chromatography coupled to flame ionisation detection and mass spectrometry. Thirteen odorants were consistently found. Nine odorants were identified and four were matched. The rate of release of each odorant was characteristic and was described using principal component analysis. A first principal component was based on nine early odorants that showed a decreasing release over time. The odorants were 2,4-dehydro-exo-brevicomin, an unknown with 78% matching to 4-acetonilcycloheptanone, linalool, 2,4-dimethyl-phenol, 4-ethylphenol, indole, 2-butyl-1-octanol, an unknown with 83% matching to 2-ethyl-1-decanol, and 2,4-bis-(1,1-dimethylethyl)phenol. A second principal component, based on two unknowns with 73% matching to yohimban-17-one and 71% matching to the 2-methyl-3-hydroxy-2,4,4-trimethyl ester of propanoic acid, had an irregular release after deposition. A third principal component of late odorants, based on 2-sec-butyl-4,5-dihydrothiazole and 6,10-dimethyl-5,9-undecaden-2-one, had a peak of release at about 22 min. In conclusion, the release of the odorants in the headspace of a urine spot may code and transmit information on the deposition time. PMID:17120277

  7. Increased 4-hydroxynonenal protein adducts in male GSTA4–4/PPAR-alpha double knockout mice enhance injury during early stages of alcoholic liver disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To test the significance of lipid peroxidation in the development of alcoholic liver injury, an ethanol (EtOH) liquid diet was fed to male wild type 129/SvJ mice, and glutathione S-transferase A4-4 null (GSTA4-/-) mice for 40 d. GSTA4-/- mice were also crossed with peroxisome proliferator-activated ...

  8. Analysis of motor function in 6-month-old male and female 3xTg-AD mice.

    PubMed

    Stover, Kurt R; Campbell, Mackenzie A; Van Winssen, Christine M; Brown, Richard E

    2015-03-15

    The 3xTg-AD mouse has high validity as a model of Alzheimer's disease (AD) because it develops both amyloid beta plaques and neurofibrillary tangles. Human patients with AD typically develop motor deficits, which worsen as the disease progresses, but 3xTg-AD mice have been reported to show enhanced motor abilities. We investigated the motor behaviour phenotype of male and female 3xTg-AD and B6129SF2 wildtype mice on a battery of motor behaviours at 6 months of age. Compared to wildtype mice, the 3xTg-AD mice had enhanced motor performance on the Rotarod, but worse performance on the grid suspension task. In gait analysis 3xTg-AD mice had a longer stride length and made more foot slips on the balance beam than wildtype mice. There was no overall difference in voluntary wheel-running activity between genotypes, but there was a disruption in circadian activity rhythm in 3xTg-AD mice. In some motor tasks, such as the Rotarod and balance beam, females appeared to perform better than males, but this sex differences was accounted for by differences in body weight. Our results indicate that while the 3xTg-AD mice show enhanced performance on the Rotarod, they have poorer performance on other motor behaviour tasks, indicating that their motor behaviour phenotype is more complex than previously reported. The presence of the P301L transgene may explain the enhancement of Rotarod performance but the poorer performance on other motor behaviour tasks may be due to other transgenes. PMID:25486177

  9. Estrogen receptors modulate striatal metabotropic receptor type 5 in intact and MPTP male mice model of Parkinson's disease.

    PubMed

    Al-Sweidi, S; Morissette, M; Di Paolo, T

    2016-07-01

    Glutamate is the most important brain excitatory neurotransmitter and glutamate overactivity is well documented in Parkinson's disease (PD). Metabotropic glutamate (mGlu) receptors are reported to interact with membrane estrogen receptors (ERs) and more specifically the mGlu5 receptor subtype. 17β-estradiol and mGlu5 antagonists have neuroprotective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. We previously reported that ERα and ERβ are involved in neuroprotection following MPTP toxicity. The present study investigated the implication of ERs on the mGlu5 receptor adaptive response to MPTP toxicity in the brain of wild type (WT), ER knockout (ERKO)α and ERKOβ male mice. Autoradiography of [(3)H]ABP688 specific binding to striatal mGlu5 receptors showed a dorsal/ventral gradient similar for WT, ERKOα and ERKOβ mice with higher values ventrally. The lateral septum had highest [(3)H]ABP688 specific binding that remained unchanged in all experimental groups. ERKOα and ERKOβ mice had similarly lower striatal [(3)H]ABP688 specific binding than WT mice as measured also by Western blots. MPTP dose-dependently decreased striatal [(3)H]ABP688 specific binding in WT but not in ERKOα and ERKOβ mice; this correlated positively with striatal dopamine concentrations. A 17β-estradiol treatment for 10 days left unchanged striatal [(3)H]ABP688 specific binding of unlesioned mice of the three genotypes. 17β-estradiol treatment for 5 days before MPTP and for 5 days after partially prevented the mGlu5 receptor decrease only in WT MPTP mice and this was associated with higher BDNF striatal contents. These results thus show that in male mice ERs affect striatal mGlu5 receptor levels and their response to MPTP. PMID:26873133

  10. Testosterone and 17β-estradiol induce glandular prostatic growth, bladder outlet obstruction, and voiding dysfunction in male mice.

    PubMed

    Nicholson, Tristan M; Ricke, Emily A; Marker, Paul C; Miano, Joseph M; Mayer, Robert D; Timms, Barry G; vom Saal, Frederick S; Wood, Ronald W; Ricke, William A

    2012-11-01

    Benign prostatic hyperplasia (BPH) and bladder outlet obstruction (BOO) are common in older men and can contribute to lower urinary tract symptoms that significantly impact quality of life. Few existing models of BOO and BPH use physiological levels of hormones associated with disease progression in humans in a genetically manipulable organism. We present a model of BPH and BOO induced in mice with testosterone (T) and 17β-estradiol (E(2)). Male mice were surgically implanted with slow-releasing sc pellets containing 25 mg T and 2.5 mg E(2) (T+E(2)). After 2 and 4 months of hormone treatment, we evaluated voiding patterns and examined the gross morphology and histology of the bladder, urethra, and prostate. Mice treated with T+E(2) developed significantly larger bladders than untreated mice, consistent with BOO. Some mice treated with T+E(2) had complications in the form of bladder hypertrophy, diverticula, calculi, and eventual decompensation with hydronephrosis. Hormone treatment caused a significant decrease in the size of the urethral lumen, increased prostate mass, and increased number of prostatic ducts associated with the prostatic urethra, compared with untreated mice. Voiding dysfunction was observed in mice treated with T+E(2), who exhibited droplet voiding pattern with significantly decreased void mass, shorter void duration, and fewer sustained voids. The constellation of lower urinary tract abnormalities, including BOO, enlarged prostates, and voiding dysfunction seen in male mice treated with T+E(2) is consistent with BPH in men. This model is suitable for better understanding molecular mechanisms and for developing novel strategies to address BPH and BOO. PMID:22948219

  11. Suppressive effects of rosa damascena essential oil on naloxone- precipitated morphine withdrawal signs in male mice.

    PubMed

    Abbasi Maleki, Navid; Abbasi Maleki, Saeid; Bekhradi, Reza

    2013-01-01

    This research was done to test the effect of Rosa damascena essential oil on withdrawal signs of naloxone-precipitated morphine in male mice. Morphine dependence was induced by injection (IP) three times daily at doses of 50, 50 and 75 mg/kg, respectively, for 3 days. On day 4, after the last administration of morphine, Rosa damascena essential oil was administered at different concentrations (5, 2 and 40%, IP) 30 min before administration of naloxone (5 mg/kg, IP). The following actions were taken as signs of withdrawal and records taken for jumping as a number and scores of 0 to 3 were given for incidences of grooming, teeth chattering, rearing, writing, diarrhea, wet dog shakes and climbing during a 30 min period. Results showed that different concentrations of Rosa damascena essential oil significantly reduced signs of morphine withdrawal compared to the control group in terms of number of jumps (p < 0.05 and p < 0.01), grooming, teeth chattering, rearing, climbing, wet dog shakes and writhing, but not for diarrhea (p < 0.05). In conclusion it seems that GABAergic activity induced by flavonoids from Rosa damascena essential oil can alleviate signs of morphine withdrawal, but further studies need to be done to better understand this mechanism. PMID:24250642

  12. The small heterodimer partner is a gonadal gatekeeper of sexual maturation in male mice

    PubMed Central

    Volle, David H.; Duggavathi, Rajesha; Magnier, Benjamin C.; Houten, Sander M.; Cummins, Carolyn L.; Lobaccaro, Jean-Marc A.; Verhoeven, Guido; Schoonjans, Kristina; Auwerx, Johan

    2007-01-01

    The small heterodimer partner (SHP) is an atypical nuclear receptor known mainly for its role in bile acid homeostasis in the enterohepatic tract. We explore here the role of SHP in the testis. SHP is expressed in the interstitial compartment of the adult testes, which contain the Leydig cells. SHP there inhibits the expression of steroidogenic genes, on the one hand by inhibiting the expression of the nuclear receptors steroidogenic factor-1 and liver receptor homolog-1 (lrh-1), and on the other hand by directly repressing the transcriptional activity of LRH-1. Consequently, in SHP knockout mice, testicular testosterone synthesis is increased independently of the hypothalamus–pituitary axis. Independent of its action on androgen synthesis, SHP also determines the timing of germ cell differentiation by controlling testicular retinoic acid metabolism. Through the inhibition of the transcriptional activity of retinoic acid receptors, SHP controls the expression of stimulated by retinoic acid gene 8 (stra8)—a gene that is indispensable for germ cell meiosis and differentiation. Together, our data demonstrate new roles for SHP in testicular androgen and retinoic acid metabolism, making SHP a testicular gatekeeper of the timing of male sexual maturation. PMID:17289919

  13. Mechanisms of nanosized titanium dioxide-induced testicular oxidative stress and apoptosis in male mice

    PubMed Central

    2014-01-01

    Background Due to the increased application of titanium dioxide nanoparticles (TiO2 NPs) in the food industry and daily life, their potential toxic effects in humans and animals have been investigated. However, very few studies have focused on testicular oxidative stress and/or apoptosis. Methods In order to understand the possible molecular mechanisms of testicular lesions following exposure to TiO2 NPs, male mice were exposed to 2.5, 5, or 10 mg/kg body weight TiO2 NPs for 90 consecutive days. Testicular oxidative stress and apoptosis were then evaluated, and the testicular mRNA expression of several genes and their proteins involved in oxidative stress and/or apoptosis was investigated. Results TiO2 NPs entered Sertoli cells and caused severe testicular oxidative damage and/or apoptosis, accompanied by excessive production of reactive oxygen species and peroxidation of lipids, proteins and DNA as well as a significant reduction in antioxidant capacity. Furthermore, exposure to TiO2 NPs resulted in the up-regulation of caspase-3, Nrbp2, and cytochrome c expression, and caused down-regulation of SOD, CAT, GPx, GST, GR, Cyp1b1, Car3, Bcl-2, Acaa2, and Axud1 expression in mouse testis. Conclusions TiO2 NPs entered Sertoli cells via the blood-testis barrier and were deposited in mouse seminiferous cord and/or Sertoli cells, causing oxidative damage and apoptosis. PMID:25209749

  14. Antidiabetic potential of Citrus sinensis and Punica granatum peel extracts in alloxan treated male mice.

    PubMed

    Parmar, Hamendra Singh; Kar, Anand

    2007-01-01

    An investigation on the effects of four different concentrations of peel extract from Citrus sinensis (CS) or Punica granatum (PG) in male mice revealed the maximum glucose lowering and antiperoxidative activities at 25 mg/kg of CS and 200 mg/kg of PG. In a separate experiment their potential was evaluated with respect to the regulation of alloxan induced diabetes mellitus. While a single dose of alloxan (120 mg/kg) increased the serum levels of glucose and alpha-amylase activity, rate of water consumption and lipid peroxidation (LPO) in hepatic, cardiac and renal tissues with a parallel decrease in serum insulin level, administration of 25 mg/kg of CS or 200 mg/kg of PG was found to normalize all the adverse changes induced by alloxan, revealing the antidiabetic and anti peroxidative potential of test fruit peel extracts. Subsequent phytochemical analysis indicated that the high content of total polyphenols in the test peels might be related to the antidiabetic and antiperoxidative effects of the test peels. PMID:18806305

  15. Impact of maternal cigarette smoke exposure on brain inflammation and oxidative stress in male mice offspring.

    PubMed

    Chan, Yik Lung; Saad, Sonia; Pollock, Carol; Oliver, Brian; Al-Odat, Ibrahim; Zaky, Amgad A; Jones, Nicole; Chen, Hui

    2016-01-01

    Maternal cigarette smoke exposure (SE) during gestation can cause lifelong adverse effects in the offspring's brain. Several factors may contribute including inflammation, oxidative stress and hypoxia, whose changes in the developing brain are unknown. Female Balb/c mice were exposed to cigarette smoke prior to mating, during gestation and lactation. Male offspring were studied at postnatal day (P) 1, P20 and 13 weeks (W13). SE dams had reduced inflammatory mediators (IL-1β, IL-6 and toll like receptor (TLR)4 mRNA), antioxidant (manganese superoxide dismutase (MnSOD)), and increased mitochondrial activities (OXPHOS-I, III and V) and protein damage marker nitrotyrosine. Brain hypoxia-inducible factor (HIF)1α and its upstream signalling molecule early growth response factor (EGR)1 were not changed in the SE dams. In the SE offspring, brain IL-1R, IL-6 and TLR4 mRNA were increased at W13. The translocase of outer mitochondrial membrane, and MnSOD were reduced at W13 with higher nitrotyrosine staining. HIF-1α was also increased at W13, although EGR1 was only reduced at P1. In conclusion, maternal SE increased markers of hypoxia and oxidative stress with mitochondrial dysfunction and cell damage in both dams and offspring, and upregulated inflammatory markers in offspring, which may render SE dams and their offspring vulnerable to additional brain insults. PMID:27169932

  16. Impact of maternal cigarette smoke exposure on brain inflammation and oxidative stress in male mice offspring

    PubMed Central

    Chan, Yik Lung; Saad, Sonia; Pollock, Carol; Oliver, Brian; Al-Odat, Ibrahim; Zaky, Amgad A.; Jones, Nicole; Chen, Hui

    2016-01-01

    Maternal cigarette smoke exposure (SE) during gestation can cause lifelong adverse effects in the offspring’s brain. Several factors may contribute including inflammation, oxidative stress and hypoxia, whose changes in the developing brain are unknown. Female Balb/c mice were exposed to cigarette smoke prior to mating, during gestation and lactation. Male offspring were studied at postnatal day (P) 1, P20 and 13 weeks (W13). SE dams had reduced inflammatory mediators (IL-1β, IL-6 and toll like receptor (TLR)4 mRNA), antioxidant (manganese superoxide dismutase (MnSOD)), and increased mitochondrial activities (OXPHOS-I, III and V) and protein damage marker nitrotyrosine. Brain hypoxia-inducible factor (HIF)1α and its upstream signalling molecule early growth response factor (EGR)1 were not changed in the SE dams. In the SE offspring, brain IL-1R, IL-6 and TLR4 mRNA were increased at W13. The translocase of outer mitochondrial membrane, and MnSOD were reduced at W13 with higher nitrotyrosine staining. HIF-1α was also increased at W13, although EGR1 was only reduced at P1. In conclusion, maternal SE increased markers of hypoxia and oxidative stress with mitochondrial dysfunction and cell damage in both dams and offspring, and upregulated inflammatory markers in offspring, which may render SE dams and their offspring vulnerable to additional brain insults. PMID:27169932

  17. Integrated action of pheromone signals in promoting courtship behavior in male mice.

    PubMed

    Haga-Yamanaka, Sachiko; Ma, Limei; He, Jie; Qiu, Qiang; Lavis, Luke D; Looger, Loren L; Yu, C Ron

    2014-01-01

    The mammalian vomeronasal organ encodes pheromone information about gender, reproductive status, genetic background and individual differences. It remains unknown how pheromone information interacts to trigger innate behaviors. In this study, we identify vomeronasal receptors responsible for detecting female pheromones. A sub-group of V1re clade members recognizes gender-identifying cues in female urine. Multiple members of the V1rj clade are cognate receptors for urinary estrus signals, as well as for sulfated estrogen (SE) compounds. In both cases, the same cue activates multiple homologous receptors, suggesting redundancy in encoding female pheromone cues. Neither gender-specific cues nor SEs alone are sufficient to promote courtship behavior in male mice, whereas robust courtship behavior can be induced when the two cues are applied together. Thus, integrated action of different female cues is required in pheromone-triggered mating behavior. These results suggest a gating mechanism in the vomeronasal circuit in promoting specific innate behavior.DOI: http://dx.doi.org/10.7554/eLife.03025.001. PMID:25073926

  18. Thermoregulatory and Cardiovascular Consequences of a Transient Thyrotoxicosis and Recovery in Male Mice.

    PubMed

    Hoefig, Carolin S; Harder, Lisbeth; Oelkrug, Rebecca; Meusel, Moritz; Vennström, Björn; Brabant, Georg; Mittag, Jens

    2016-07-01

    Thyroid hormones play a major role in body homeostasis, regulating energy expenditure and cardiovascular function. Given that obese people or athletes might consider rapid weight loss as beneficial, voluntary intoxication with T4 preparations is a growing cause for thyrotoxicosis. However, the long-lasting effects of transient thyrotoxicosis are poorly understood. Here we examined metabolic, thermoregulatory, and cardiovascular function upon induction and recovery from a 2-week thyrotoxicosis in male C57BL/6J mice. Our results showed that T4 treatment caused tachycardia, decreased hepatic glycogen stores, and higher body temperature as expected; however, we did not observe an increase in brown fat thermogenesis or decreased tail heat loss, suggesting that these tissues do not contribute to the hyperthermia induced by thyroid hormone. Most interestingly, when the T4 treatment was ended, a pronounced bradycardia was observed in the animals, which was likely caused by a rapid decline of T3 even below baseline levels. On the molecular level, this was accompanied by an overexpression of cardiac phospholamban and Serca2a mRNA, supporting the hypothesis that the heart depends more on T3 than T4. Our findings therefore demonstrate that a transient thyrotoxicosis can have pathological effects that even persist beyond the recovery of serum T4 levels, and in particular the observed bradycardia could be of clinical relevance when treating hyperthyroid patients. PMID:27145010

  19. Vulnerability to chronic subordination stress-induced depression-like disorders in adult 129SvEv male mice.

    PubMed

    Dadomo, Harold; Sanghez, Valentina; Di Cristo, Luisana; Lori, Andrea; Ceresini, Graziano; Malinge, Isabelle; Parmigiani, Stefano; Palanza, Paola; Sheardown, Malcolm; Bartolomucci, Alessandro

    2011-08-01

    Exposure to stressful life events is intimately linked with vulnerability to neuropsychiatric disorders such as major depression. Pre-clinical animal models offer an effective tool to disentangle the underlying molecular mechanisms. In particular, the 129SvEv strain is often used to develop transgenic mouse models but poorly characterized as far as behavior and neuroendocrine functions are concerned. Here we present a comprehensive characterization of 129SvEv male mice's vulnerability to social stress-induced depression-like disorders and physiological comorbidities. We employed a well characterized mouse model of chronic social stress based on social defeat and subordination. Subordinate 129SvEv mice showed body weight gain, hyperphagia, increased adipose fat pads weight and basal plasma corticosterone. Home cage phenotyping revealed a suppression of spontaneous locomotor activity and transient hyperthermia. Subordinate 129SvEv mice also showed marked fearfulness, anhedonic-like response toward a novel but palatable food, increased anxiety in the elevated plus maze and social avoidance of an unfamiliar male mouse. A direct measured effect of the stressfulness of the living environment, i.e. the amount of daily aggression received, predicted the degree of corticosterone level and locomotor activity but not of the other parameters. This is the first study validating a chronic subordination stress paradigm in 129SvEv male mice. Results demonstrated remarkable stress vulnerability and establish the validity to use this mouse strain as a model for depression-like disorders. PMID:21093519

  20. Deletion of the forebrain mineralocorticoid receptor impairs social discrimination and decision-making in male, but not in female mice

    PubMed Central

    ter Horst, Judith P.; van der Mark, Maaike; Kentrop, Jiska; Arp, Marit; van der Veen, Rixt; de Kloet, E. Ronald; Oitzl, Melly S.

    2014-01-01

    Social interaction with unknown individuals requires fast processing of information to decide whether it is friend or foe. This process of discrimination and decision-making is stressful and triggers secretion of corticosterone activating mineralocorticoid receptor (MR) and glucocorticoid receptor (GR). The MR is involved in appraisal of novel experiences and risk assessment. Recently, we have demonstrated in a dual-solution memory task that MR plays a role in the early stage of information processing and decision-making. Here we examined social approach and social discrimination in male and female mice lacking MR from hippocampal-amygdala-prefrontal circuitry and controls. The social approach task allows the assessment of time spent with an unfamiliar mouse and the ability to discriminate between familiar and unfamiliar conspecifics. The male and female test mice were both more interested in the social than the non-social experience and deletion of their limbic MR increased the time spent with an unfamiliar mouse. Unlike controls, the male MRCaMKCre mice were not able to discriminate between an unfamiliar and the familiar mouse. However, the female MR mutant had retained the discriminative ability between unfamiliar and familiar mice. Administration of the MR antagonist RU28318 to male mice supported the role of the MR in the discrimination between an unfamiliar mouse and a non-social stimulus. No effect was found with a GR antagonist. Our findings suggest that MR is involved in sociability and social discrimination in a sex-specific manner through inhibitory control exerted putatively via limbic-hippocampal efferents. The ability to discriminate between familiar and unfamiliar conspecifics is of uttermost importance for territorial defense and depends on a role of MR in decision-making. PMID:24567706

  1. Male contraception via simultaneous knockout of α1A-adrenoceptors and P2X1-purinoceptors in mice

    PubMed Central

    White, Carl W.; Choong, Yan-Ting; Short, Jennifer L.; Exintaris, Betty; Malone, Daniel T.; Allen, Andrew M.; Evans, Richard J.; Ventura, Sabatino

    2013-01-01

    Therapeutic targets for male contraception are associated with numerous problems due to their focus on disrupting spermatogenesis or hormonal mechanisms to produce dysfunctional sperm. Here we describe the dual genetic deletion of α1A-adrenergic G protein-coupled receptors (adrenoceptors) and P2X1-purinoceptor ligand gated ion channels in male mice, thereby blocking sympathetically mediated sperm transport through the vas deferens during the emission phase of ejaculation. This modification produced 100% infertility without effects on sexual behavior or function. Sperm taken from the cauda epididymides of double knockout mice were microscopically normal and motile. Furthermore, double knockout sperm were capable of producing normal offspring following intracytoplasmic sperm injection into wild-type ova and implantation of the fertilized eggs into foster mothers. Blood pressure and baroreflex function was reduced in double knockout mice, but no more than single knockout of α1A-adrenoceptors alone. These results suggest that this autonomic method of male contraception appears free of major physiological and behavioral side effects. In addition, they provide conclusive proof of concept that pharmacological antagonism of the P2X1-purinoceptor and α1A-adrenoceptor provides a safe and effective therapeutic target for a nonhormonal, readily reversible male contraceptive. PMID:24297884

  2. Male contraception via simultaneous knockout of α1A-adrenoceptors and P2X1-purinoceptors in mice.

    PubMed

    White, Carl W; Choong, Yan-Ting; Short, Jennifer L; Exintaris, Betty; Malone, Daniel T; Allen, Andrew M; Evans, Richard J; Ventura, Sabatino

    2013-12-17

    Therapeutic targets for male contraception are associated with numerous problems due to their focus on disrupting spermatogenesis or hormonal mechanisms to produce dysfunctional sperm. Here we describe the dual genetic deletion of α1A-adrenergic G protein-coupled receptors (adrenoceptors) and P2X1-purinoceptor ligand gated ion channels in male mice, thereby blocking sympathetically mediated sperm transport through the vas deferens during the emission phase of ejaculation. This modification produced 100% infertility without effects on sexual behavior or function. Sperm taken from the cauda epididymides of double knockout mice were microscopically normal and motile. Furthermore, double knockout sperm were capable of producing normal offspring following intracytoplasmic sperm injection into wild-type ova and implantation of the fertilized eggs into foster mothers. Blood pressure and baroreflex function was reduced in double knockout mice, but no more than single knockout of α1A-adrenoceptors alone. These results suggest that this autonomic method of male contraception appears free of major physiological and behavioral side effects. In addition, they provide conclusive proof of concept that pharmacological antagonism of the P2X1-purinoceptor and α1A-adrenoceptor provides a safe and effective therapeutic target for a nonhormonal, readily reversible male contraceptive. PMID:24297884

  3. Early Postnatal Exposure to Ultrafine Particulate Matter Air Pollution: Persistent Ventriculomegaly, Neurochemical Disruption, and Glial Activation Preferentially in Male Mice

    PubMed Central

    Allen, Joshua L.; Liu, Xiufang; Pelkowski, Sean; Palmer, Brian; Conrad, Katherine; Oberdörster, Günter; Weston, Douglas; Mayer-Pröschel, Margot

    2014-01-01

    Background: Air pollution has been associated with adverse neurological and behavioral health effects in children and adults. Recent studies link air pollutant exposure to adverse neurodevelopmental outcomes, including increased risk for autism, cognitive decline, ischemic stroke, schizophrenia, and depression. Objectives: We sought to investigate the mechanism(s) by which exposure to ultrafine concentrated ambient particles (CAPs) adversely influences central nervous system (CNS) development. Methods: We exposed C57BL6/J mice to ultrafine (< 100 nm) CAPs using the Harvard University Concentrated Ambient Particle System or to filtered air on postnatal days (PNDs) 4–7 and 10–13, and the animals were euthanized either 24 hr or 40 days after cessation of exposure. Another group of males was exposed at PND270, and lateral ventricle area, glial activation, CNS cytokines, and monoamine and amino acid neurotransmitters were quantified. Results: We observed ventriculomegaly (i.e., lateral ventricle dilation) preferentially in male mice exposed to CAPs, and it persisted through young adulthood. In addition, CAPs-exposed males generally showed decreases in developmentally important CNS cytokines, whereas in CAPs-exposed females, we observed a neuroinflammatory response as indicated by increases in CNS cytokines. We also saw changes in CNS neurotransmitters and glial activation across multiple brain regions in a sex-dependent manner and increased hippocampal glutamate in CAPs-exposed males. Conclusions: We observed brain region– and sex-dependent alterations in cytokines and neurotransmitters in both male and female CAPs-exposed mice. Lateral ventricle dilation (i.e., ventriculomegaly) was observed only in CAPs-exposed male mice. Ventriculomegaly is a neuropathology that has been associated with poor neurodevelopmental outcome, autism, and schizophrenia. Our findings suggest alteration of developmentally important neurochemicals and lateral ventricle dilation may be

  4. Dynamics of chromosomal aberrations in male mice of various strains during aging.

    PubMed

    Rozenfel'd, S V; Togo, E F; Mikheev, V S; Popovich, I G; Zabezhinskii, M A; Anisimov, V N

    2001-05-01

    We studied the incidence of chromosome aberrations in bone marrow cells and primary spermatocytes in various mouse strains. Experiments were performed on SAMP mice (accelerated aging), control SAMR mice, and long-living CBA and SHR mice. Experiments revealed a positive correlation between the age and the incidence of mutations in their somatic cells and gametes. PMID:11550060

  5. Arsenic antagonism studies with monoisoamyl DMSA and zinc in male mice.

    PubMed

    Modi, Manoj; Pathak, Uma; Kalia, Kiran; Flora, S J S

    2005-01-01

    Administration of zinc either alone or in combination with monoisoamyl dimercaptosuccinic acid (DMSA) during and post-arsenic exposure was investigated in male mice. The animals were administered 2mgkg(-1) arsenic as sodium arsenite, intraperitoneally, once daily for 5 days either alone or in combination with 10mgkg(-1), zinc (as zinc acetate, orally), 50mgkg(-1) monoisoamyl dimercaptosuccinic acid (MiADMSA) given orally (p.o.), 2h after arsenic administration. Another group of arsenic treated animals was given both zinc (10mgkg(-1)) and MiADMSA (50mgkg(-1), p.o.). Animals were sacrificed 24h after the last dose. In another set of experimentation, arsenic pre-exposed mice (2mgkg(-1), i.p. for 5 days) were treated with saline, zinc, MiADMSA or zinc plus MiADMSA for next 3 days and sacrificed thereafter. Exposure to arsenic led to a significant inhibition of blood δ-aminolevulinic acid dehydratase (ALAD), depletion of glutathione (GSH) level and marginal elevations of zinc protoporphyrin (ZPP). Arsenic exposure caused a significant decrease in hepatic and renal GSH level and an increase in liver oxidized glutathione (GSSG) and liver and kidney thiobarbituric acid reactive substance (TBARS) levels. Concomitant administration of zinc with arsenic provided significant protection to blood ALAD activity while, GSH and ZPP levels remained unaltered. Co-administration of MiADMSA with arsenic significantly prevented accumulation of arsenic in blood, liver and kidney while, zinc had no effect on tissue arsenic concentration. Combined administration of zinc and MiADMSA had no major additional beneficial effects over their individual effects. Interestingly, post-arsenic exposure treatment with MiADMSA provided significant recovery in blood ALAD activity while, zinc supplementation alone had no effect. The best results however, were obtained when MiADMSA was administered along-with zinc. Most of the biochemical variables indicative of hepatic oxidative stress responded

  6. Effect of glatiramer acetate on short-term memory impairment induced by lipopolysaccharide in male mice.

    PubMed

    Mohammadi, Fatemeh; Rahimian, Reza; Fakhraei, Nahid; Rezayat, Seyed Mahdi; Javadi-Paydar, Mehrak; Dehpour, Ahmad R; Afshari, Khashayar; Ejtemaei Mehr, Shahram

    2016-08-01

    Glatiramer acetate (GA) demonstrates neuroprotective, neurogenesis, and anti-inflammatory properties. This study examines the probable protective effect of acute GA on lipopolysaccharide (LPS)-induced memory impairment in male mice and further explores which routes of administration [subcutaneous (s.c.) or intracerebroventricular (i.c.v.)] exert optimum effect. Memory performance was evaluated in two-trial recognition Y-maze and passive-avoidance tasks evaluating special recognition memory and fear memory, respectively. Memory impairment was induced by LPS [100 μg/kg, intraperitoneally (i.p.)], 4 h before training. In Y-maze, GA (10, 2.5, 0.625, 0.153, and 0.03 mg/kg, s.c.; 250 μg/mouse; i.c.v.) was administered 10 min following LPS, and special memory was assayed in Y-maze apparatus. In passive avoidance, LPS (100, 250 μg/kg; i.p.) was injected 4 h before receiving foot shock, and GA (10, 2.5; s.c.) or (250 μg/mouse; i.c.v.) was administered 4 h before the shock. Following 24 h, the fear memory was evaluated. Memory impaired significantly following LPS (100, 250 μg/kg; i.p.) in Y-maze and passive-avoidance tasks, P < 0.001 and P < 0.05, respectively. The data revealed that GA (250 μg/mouse, i.c.v.) and GA (10, 2.5 mg/kg; s.c.) in Y-maze reversed memory impairment (LPS 100 μg/kg, i.p.) (P < 0.01). In passive-avoidance task, GA (2.5, 10 mg/kg; s.c.) reversed LPS-induced impairment and the mice showed significantly longer latency times during the retention trial (P < 0.01). GA improved memory impairment both centrally and systemically. It improved spatial recognition memory increasing the average time in the novel arm and improved fear memory increasing latency time. GA administration improved memory impairment profoundly through both systemic and central routs. PMID:27129444

  7. Transgenic mice with inactive alleles for procollagen N-proteinase (ADAMTS-2) develop fragile skin and male sterility.

    PubMed Central

    Li, S W; Arita, M; Fertala, A; Bao, Y; Kopen, G C; Långsjö, T K; Hyttinen, M M; Helminen, H J; Prockop, D J

    2001-01-01

    Transgenic mice were prepared with inactive alleles for procollagen N-proteinase (ADAMTS-2; where ADAMTS stands for a disintegrin and metalloproteinase with thrombospondin repeats). Homozygous mice were grossly normal at birth, but after 1-2 months they developed thin skin that tore after gentle handling. Although the gene was inactivated, a large fraction of the N-propeptides of type I procollagen in skin and the N-propeptides of type II procollagen in cartilage were cleaved. Therefore the results suggested the tissues contained one or more additional enzymes that slowly process the proteins. Electron microscopy did not reveal any defects in the morphology of collagen fibrils in newborn mice. However, in two-month-old mice, the collagen fibrils in skin were seen as bizarre curls in cross-section and the mean diameters of the fibrils were approx. half of the controls. Although a portion of the N-propeptides of type II procollagen in cartilage were not cleaved, no defects in the morphology of the fibrils were seen by electron microscopy or by polarized-light microscopy. Female homozygous mice were fertile, but male mice were sterile with a marked decrease in testicular sperm. Therefore the results indicated that ADAMTS-2 plays an essential role in the maturation of spermatogonia. PMID:11284712

  8. Genetic variation in male sexual behaviour in a population of white-footed mice in relation to photoperiod

    PubMed Central

    Sharp, Kathy; Bucci, Donna; Zelensky, Paul K.; Chesney, Alanna; Tidhar, Wendy; Broussard, David R.; Heideman, Paul D.

    2015-01-01

    In natural populations, genetic variation in seasonal male sexual behaviour could affect behavioural ecology and evolution. In a wild-source population of white-footed mice, Peromyscus leucopus, from Virginia, U.S.A., males experiencing short photoperiod show high levels of genetic variation in reproductive organ mass and neuroendocrine traits related to fertility. We tested whether males from two divergent selection lines, one that strongly suppresses fertility under short photoperiod (responder) and one that weakly suppresses fertility under short photoperiod (nonresponder), also differ in photoperiod-dependent sexual behaviour and responses to female olfactory cues. Under short, but not long, photoperiod, there were significant differences between responder and nonresponder males in sexual behaviour and likelihood of inseminating a female. Males that were severely oligospermic or azoospermic under short photoperiod failed to display sexual behaviour in response to an ovariectomized and hormonally primed receptive female. However, on the day following testing, females were positive for spermatozoa only when paired with a male having a sperm count in the normal range for males under long photoperiod. Males from the nonresponder line showed accelerated reproductive development under short photoperiod in response to urine-soiled bedding from females, but males from the responder line did not. The results indicate genetic variation in sexual behaviour that is expressed under short, but not long, photoperiod, and indicate a potential link between heritable neuroendocrine variation and male sexual behaviour. In winter in a natural population, this heritable behavioural variation could affect fitness, seasonal life history trade-offs and population growth. PMID:25983335

  9. Soy Protein Isolate Protects Against Ethanol-Mediated Tumor Progression in Diethylnitrosamine-Treated Male Mice.

    PubMed

    Mercer, Kelly E; Pulliam, Casey; Hennings, Leah; Lai, Keith; Cleves, Mario; Jones, Ellen; Drake, Richard R; Ronis, Martin

    2016-06-01

    In this study, diethylnitrosamine-treated male mice were assigned to three groups: (i) a 35% high fat ethanol liquid diet (EtOH) with casein as the protein source, (ii) the same EtOH liquid diet with soy protein isolate as the sole protein source (EtOH/SPI), (iii) and a chow group. EtOH feeding continued for 16 weeks. As expected, EtOH increased the incidence and multiplicity of basophilic lesions and adenomas compared with the chow group, P < 0.05. Soy protein replacement of casein in the EtOH diet significantly reduced adenoma progression when compared with the EtOH and EtOH/SPI group (P < 0.05). Tumor reduction in the EtOH/SPI group corresponded to reduced liver injury associated with decreased hepatic Tnfα and Cd14 antigen (Cd14) expression and decreased nuclear accumulation of NF-κB1 protein compared with the EtOH group (P < 0.05). Detection of sphingolipids using high-resolution matrix-assisted laser desorption/ionization-Fourier transform ion cyclotron resonance (MALDI-FTICR) imaging mass spectrometry revealed increased accumulation of long acyl chain ceramide species, and sphingosine-1-phosphate (S1P) in the EtOH group that were significantly reduced in the EtOH/SPI group. Chronic EtOH feeding also increased mRNA expression of β-catenin transcriptional targets, including cyclin D1 (Ccnd1), matrix metallopeptidase 7 (Mmp7), and glutamine synthetase (Glns), which were reduced in the EtOH/SPI group (P < 0.05). We conclude that soy prevents tumorigenesis by reducing proinflammatory and oxidative environment resulting from EtOH-induced hepatic injury, and by reducing hepatocyte proliferation through inhibition of β-catenin signaling. These mechanisms may involve changes in sphingolipid signaling. Cancer Prev Res; 9(6); 466-75. ©2016 AACR. PMID:27006377

  10. Atorvastatin attenuates the antinociceptive tolerance of morphine via nitric oxide dependent pathway in male mice.

    PubMed

    Hassanipour, Mahsa; Amini-Khoei, Hossein; Shafaroodi, Hamed; Shirzadian, Armin; Rahimi, Nastaran; Imran-Khan, Muhammad; Rezayat, Seyed-Mahdi; Dehpour, Ahmadreza

    2016-07-01

    The development of morphine-induced antinociceptive tolerance limits its therapeutic efficacy in pain management. Atorvastatin, or competitive inhibitor of 3-hydroxy-methyl-glutaryl coenzyme A (HMG-CoA) reductase, is mainstay agent in hypercholesterolemia treatment. Beyond the cholesterol-lowering activity, exploration of neuroprotective properties of this statin indicates its potential benefit in central nervous disorders. The aim of the present study was to assess the effects of atorvastatin in development and expression of morphine-induced analgesic tolerance in male mice and probable involvement of nitric oxide. Chronic and acute treatment with atorvastatin 10 and 20mg/kg, respectively, could alleviate morphine tolerance in development and expression phases. Chronic co-administration of nitric oxide synthase (NOS) inhibitors including L-NAME (non selective NOS inhibitor; 2mg/kg), aminoguanidine (selective inducible NOS inhibitor; 50mg/kg) and 7-NI (selective neuronal NOS inhibitor; 15mg/kg) with atorvastatin blocked the protective effect of atorvastatin in tolerance reversal. Moreover, reversing the atorvastatin effect was also observed in acute simultaneous treatment of L-NAME (5mg/kg) and aminoguanidine (100mg/kg) with atorvastatin. Co-treatment of guanylyl cyclase inhibitor, ODQ (chronic dose: 10mg/kg and acute dose: 20mg/kg) was associated with prevention of atorvastatin anti-tolerance properties. Our results revealed that the atorvastatin modulating role in morphine antinociceptive tolerance is mediated at least in part via nitric oxide in animal pain models of hot plate and tail flick. PMID:27381980

  11. A chimera embryo assay reveals a decrease in embryonic cellular proliferation induced by sperm from X-irradiated male mice

    SciTech Connect

    Obasaju, M.F.; Wiley, L.M.; Oudiz, D.J.; Raabe, O.; Overstreet, J.W.

    1989-05-01

    Male mice were divided into three experimental groups and a control group. Mice in the experimental groups received one of three doses of acute X irradiation (1.73, 0.29, and 0.05 Gy) and together with the control unirradiated mice were then mated weekly to unirradiated female mice for a 9-week experimental period. Embryos were recovered from the weekly matings at the four-cell stage and examined by the chimera assay for proliferative disadvantage. Aggregation chimeras were constructed of embryos from female mice mated to irradiated males (experimental embryos) and embryos from females mated to unexposed males (control embryos) and contained either one experimental embryo and one control embryo (heterologous chimera) or two control embryos (control chimera). The control embryo in heterologous chimeras and either embryo in control chimeras were prelabeled with the vital dye fluorescein isothiocyanate (FITC), and the chimeras were cultured for 40 h and viewed under phase-contrast and epifluorescence microscopy to obtain total embryo cell number and the cellular contribution from the FITC-labeled embryo. Experimental and control embryos that were cultured singly were also examined for embryo cell number at the end of the 40-h culture period. In control chimeras, the mean ratio of the unlabeled cells:total chimera cell number (henceforth referred to as ''mean ratio'') was 0.50 with little or no weekly variation over the 9-week experimental period. During Weeks 4-7, the mean ratios of heterologous chimeras differed significantly from the mean ratio of control chimeras with the greatest differences occurring during Week 7 (0.41 for chimeras of 0.05 Gy dose group, 0.40 for chimeras of the 0.29 Gy dose group, and 0.17 for chimeras of the 1.73 Gy dose group).

  12. Evaluation of toxic effects of CdTe quantum dots on the reproductive system in adult male mice.

    PubMed

    Li, Xiaohui; Yang, Xiangrong; Yuwen, Lihui; Yang, Wenjing; Weng, Lixing; Teng, Zhaogang; Wang, Lianhui

    2016-07-01

    Fluorescent quantum dots (QDs) are highly promising nanomaterials for various biological and biomedical applications because of their unique optical properties, such as robust photostability, strong photoluminescence, and size-tunable fluorescence. Several studies have reported the in vivo toxicity of QDs, but their effects on the male reproduction system have not been examined. In this study, we investigated the reproductive toxicity of cadmium telluride (CdTe) QDs at a high dose of 2.0 nmol per mouse and a low dose of 0.2 nmol per mouse. Body weight measurements demonstrated there was no overt toxicity for both dose at day 90 after exposure, but the high dose CdTe affected body weight up to 15 days after exposure. CdTe QDs accumulated in the testes and damaged the tissue structure for both doses on day 90. Meanwhile, either of two CdTe QDs treatments did not significantly affect the quantity of sperm, but the high dose CdTe significantly decreased the quality of sperm on day 60. The serum levels of three major sex hormones were also perturbed by CdTe QDs treatment. However, the pregnancy rate and delivery success of female mice that mated with the treated male mice did not differ from those mated with untreated male mice. These results suggest that CdTe QDs can cause testes toxicity in a dose-dependent manner. The low dose of CdTe QDs is relatively safe for the reproductive system of male mice. Our preliminary result enables better understanding of the reproductive toxicity induced by cadmium-containing QDs and provides insight into the safe use of these nanoparticles in biological and environmental systems. PMID:27135714

  13. Effects of Repeated Anesthesia Containing Urethane on Tumor Formation and Health Scores in Male C57BL/6J Mice.

    PubMed

    Rex, Tonia S; Boyd, Kelli; Apple, Troy; Bricker-Anthony, Courtney; Vail, Krystal; Wallace, Jeanne

    2016-01-01

    Repeated injection of urethane (ethyl carbamate) is carcinogenic in susceptible strains of mice. Most recent cancer studies involving urethane-induced tumor formation use p53(+/-) mice, which lack one copy of the p53 tumor suppressor gene. In contrast, the same protocol elicits at most a single tumor in wildtype C57BL/6 mice. The effect of repeatedly injecting urethane as a component of a ketamine-xylazine anesthetic mixture in the highly prevalent mouse strain C57BL/6 is unknown. Male C57BL/6J mice (n = 30; age, 3 mo) were anesthetized once monthly for 4 mo by using 560 mg/kg urethane, 28 mg/kg ketamine, and 5.6 mg/kg xylazine. The physical health of the mice was evaluated according to 2 published scoring systems. The average body condition score (scale, 1 to 5; normal, 3) was 3.3, 3.3, and 3.4 after the 2nd, 3rd, and 4th injections, respectively. The visual assessment score was 0 (that is, normal) at all time points examined. Within 1 wk after the 4th injection, the mice were euthanized, necropsied, and evaluated histopathologically. No histopathologic findings were noteworthy. We conclude that repeated monthly injection with urethane as a component of an anesthetic cocktail does not cause clinically detectable abnormalities or induce neoplasia in C57BL/6J mice. These findings are important because urethane combined with low-dose ketamine, unlike other anesthetic regimens, allows for accurate recording of neuronal activity in both the brain and retina. Longitudinal neuronal recordings minimize the number of mice needed and improve the analysis of disease progression and potential therapeutic interventions. PMID:27177562

  14. Adenosinergic regulation of binge-like ethanol drinking and associated locomotor effects in male C57BL/6J mice

    PubMed Central

    Fritz, Brandon M; Boehm, Stephen L

    2015-01-01

    We recently observed that the addition of caffeine (a nonselective adenosine receptor antagonist) to a 20% ethanol solution significantly altered the intoxication profile of male C57BL/6J (B6) mice induced by voluntary binge-like consumption in the ‘Drinking-in-the-Dark’ (DID) paradigm. In the current study, the roles of A1 and A2A adenosine receptor subtypes, specifically, in binge-like ethanol consumption and associated locomotor effects were explored. Adult male B6 mice (PND 60-70) were allowed to consume 20% ethanol (v/v) or 2% sucrose (w/v) for 6 days via DID. On day 7, mice received a systemic administration (i.p.) of the A1 antagonist DPCPX (1, 3, 6 mg/kg), the A2A antagonist MSX-3 (1, 2, 4 mg/kg), or vehicle immediately prior to fluid access in DID. Antagonism of the A1 receptor via DPCPX was found to dose-dependently decrease binge-like ethanol intake and associated blood ethanol concentrations (p’s < 0.05), although no effect was observed on sucrose intake. Antagonism of A2A had no effect on ethanol or sucrose consumption, however, MSX-3 elicited robust locomotor stimulation in mice consuming either solution (p’s < 0.05). Together, these findings suggest unique roles for the A1 and A2A adenosine receptor subtypes in binge-like ethanol intake and its associated locomotor effects. PMID:26033424

  15. Photoperiod Mediated Changes in Olfactory Bulb Neurogenesis and Olfactory Behavior in Male White-Footed Mice (Peromyscus leucopus)

    PubMed Central

    Weil, Zachary M.; Nelson, Randy J.

    2012-01-01

    Brain plasticity, in relation to new adult mammalian neurons generated in the subgranular zone of the hippocampus, has been well described. However, the functional outcome of new adult olfactory neurons born in the subventricular zone of the lateral ventricles is not clearly defined, as manipulating neurogenesis through various methods has given inconsistent and conflicting results in lab mice. Several small rodent species, including Peromyscus leucopus, display seasonal (photoperiodic) brain plasticity in brain volume, hippocampal function, and hippocampus-dependent behaviors; plasticity in the olfactory system of photoperiodic rodents remains largely uninvestigated. We exposed adult male P. leucopus to long day lengths (LD) and short day lengths (SD) for 10 to 15 weeks and then examined olfactory bulb cell proliferation and survival using the thymidine analog BrdU, olfactory bulb granule cell morphology using Golgi-Cox staining, and behavioral investigation of same-sex conspecific urine. SD mice did not differ from LD counterparts in granular cell morphology of the dendrites or in dendritic spine density. Although there were no differences due to photoperiod in habituation to water odor, SD mice rapidly habituated to male urine, whereas LD mice did not. In addition, short day induced changes in olfactory behavior were associated with increased neurogenesis in the caudal plexiform and granule cell layers of the olfactory bulb, an area known to preferentially respond to water-soluble odorants. Taken together, these data demonstrate that photoperiod, without altering olfactory bulb neuronal morphology, alters olfactory bulb neurogenesis and olfactory behavior in Peromyscus leucopus. PMID:22912730

  16. Alternate day fasting impacts the brain insulin-signaling pathway of young adult male C57BL/6 mice.

    PubMed

    Lu, Jianghua; E, Lezi; Wang, Wenfang; Frontera, Jennifer; Zhu, Hao; Wang, Wen-Tung; Lee, Phil; Choi, In Young; Brooks, William M; Burns, Jeffrey M; Aires, Daniel; Swerdlow, Russell H

    2011-04-01

    Dietary restriction (DR) has recognized health benefits that may extend to brain. We examined how DR affects bioenergetics-relevant enzymes and signaling pathways in the brains of C57BL/6 mice. Five-month-old male mice were placed in ad libitum or one of two repeated fasting and refeeding (RFR) groups, an alternate day (intermittent fed; IF) or alternate day plus antioxidants (blueberry, pomegranate, and green tea extracts) (IF + AO) fed group. During the 24-h fast blood glucose levels initially fell but stabilized within 6 h of starting the fast, thus avoiding frank hypoglycemia. DR in general appeared to enhance insulin sensitivity. After six weeks brain AKT and glycogen synthase kinase 3 beta phosphorylation were lower in the RFR mice, suggesting RFR reduced brain insulin-signaling pathway activity. Pathways that mediate mitochondrial biogenesis were not activated; AMP kinase phosphorylation, silent information regulator 2 phosphorylation, peroxisomal proliferator-activated receptor-gamma coactivator 1 alpha levels, and cytochrome oxidase subunit 4 levels did not change. ATP levels also did not decline, which suggests the RFR protocols did not directly impact brain bioenergetics. Antioxidant supplementation did not affect the brain parameters we evaluated. Our data indicate in young adult male C57BL/6 mice, RFR primarily affects brain energy metabolism by reducing brain insulin signaling, which potentially results indirectly as a consequence of reduced peripheral insulin production. PMID:21244426

  17. Alternate Day Fasting Impacts the Brain Insulin Signaling Pathway of Young Adult Male C57BL/6 Mice

    PubMed Central

    Lu, Jianghua; Lezi, E; Wang, WenFang; Frontera, Jennifer; Zhu, Hao; Wang, Wen-Tung; Lee, Sang-Pil; Choi, In Young; Brooks, William M.; Burns, Jeffrey M.; Aires, Daniel; Swerdlow, Russell H.

    2011-01-01

    Dietary restriction (DR) has recognized health benefits that may extend to brain. We examined how DR affects bioenergetics-relevant enzymes and signaling pathways in the brains of C57BL/6 mice. Five month-old male mice were placed in ad libitum (AL) or one of two repeated fasting and refeeding (RFR) groups, an alternate day (intermittent fed; IF) or alternate day plus antioxidants (blueberry, pomegranate, and green tea extracts) (IF+AO) fed group. During the 24 hour fast blood glucose levels initially fell but stabilized within 6 hours of starting the fast, thus avoiding frank hypoglycemia. DR in general appeared to enhance insulin sensitivity. After six weeks brain AKT and GSK3β phosphorylation were lower in the RFR mice, suggesting RFR reduced brain insulin signaling pathway activity. Pathways that mediate mitochondrial biogenesis were not activated; AMPK phosphorylation, SIRT1 phosphorylation, PGC1a levels, and COX4 levels did not change. ATP levels also did not decline, which suggests the RFR protocols did not directly impact brain bioenergetics. Antioxidant supplementation did not affect the brain parameters we evaluated. Our data indicate in young adult male C57BL/6 mice, RFR primarily affects brain energy metabolism by reducing brain insulin signaling, which potentially results indirectly as a consequence of reduced peripheral insulin production. PMID:21244426

  18. Long-term wheel running changes on sensorimotor activity and skeletal muscle in male and female mice of accelerated senescence.

    PubMed

    Sanchez-Roige, Sandra; Lalanza, Jaume F; Alvarez-López, María Jesús; Cosín-Tomás, Marta; Griñan-Ferré, Christian; Pallàs, Merce; Kaliman, Perla; Escorihuela, Rosa M

    2014-01-01

    The senescence-accelerated mouse prone 8 (SAMP8) is considered a useful non-transgenic model for studying aspects of aging. Using SAM resistant 1 (SAMR1) as controls, the long-term effects of wheel running on skeletal muscle adaptations and behavioral traits were evaluated in senescent (P8) and resistant (R1) male and female mice. Long-term wheel running (WR) led to increases in locomotor activity, benefits in sensorimotor function, and changes in body weight in a gender-dependent manner. WR increased body weight and baseline levels of locomotor activity in female mice and improved balance and strength in male mice, compared to sedentary-control mice. WR resulted in key metabolic adaptations in skeletal muscle, associated with an increased activity of the sirtuin 1-AMP-activated protein kinase (AMPK)-PGC-1 alpha axis and changes in vascular endothelial growth factor A (Vegfa), glucose transporter type 4 (Glut4), and Cluster of Differentiation 36 (Cd36) gene expression. Overall, our data indicate that activity, balance, and strength decrease with age and that long-term WR may significantly improve the motor function in a mouse model of senescence in a gender-dependent manner. PMID:25129573

  19. Mutations that affect meiosis in male mice influence the dynamics of the mid-preleptotene and bouquet stages

    SciTech Connect

    Liebe, B.; Petukhova, G.; Barchi, M.; Bellani, M.; Braselmann, H.; Nakano, T.; Pandita, T.K.; Jasin, M.; Fornace, A.; Meistrich, M.L.; Baarends, W.M.; Schimenti, J.; Lange, T. de; Keeney, S.; Camerini-Otero, R.D.; Scherthan, H. . E-mail: scherth@web.de

    2006-11-15

    Meiosis pairs and segregates homologous chromosomes and thereby forms haploid germ cells to compensate the genome doubling at fertilization. Homologue pairing in many eukaryotic species depends on formation of DNA double strand breaks (DSBs) during early prophase I when telomeres begin to cluster at the nuclear periphery (bouquet stage). By fluorescence in situ hybridization criteria, we observe that mid-preleptotene and bouquet stage frequencies are altered in male mice deficient for proteins required for recombination, ubiquitin conjugation and telomere length control. The generally low frequencies of mid-preleptotene spermatocytes were significantly increased in male mice lacking recombination proteins SPO11, MEI1, MLH1, KU80, ubiquitin conjugating enzyme HR6B, and in mice with only one copy of the telomere length regulator Terf1. The bouquet stage was significantly enriched in Atm {sup -/-}, Spo11 {sup -/-}, Mei1 {sup m1Jcs/m1Jcs}, Mlh1 {sup -/-}, Terf1 {sup +/-} and Hr6b {sup -/-} spermatogenesis, but not in mice lacking recombination proteins DMC1 and HOP2, the non-homologous end-joining DNA repair factor KU80 and the ATM downstream effector GADD45a. Mice defective in spermiogenesis (Tnp1 {sup -/-}, Gmcl1 {sup -/-}, Asm {sup -/-}) showed wild-type mid-preleptotene and bouquet frequencies. A low frequency of bouquet spermatocytes in Spo11 {sup -/-} Atm {sup -/-} spermatogenesis suggests that DSBs contribute to the Atm {sup -/-}-correlated bouquet stage exit defect. Insignificant changes of bouquet frequencies in mice with defects in early stages of DSB repair (Dmc1 {sup -/-}, Hop2 {sup -/-}) suggest that there is an ATM-specific influence on bouquet stage duration. Altogether, it appears that several pathways influence telomere dynamics in mammalian meiosis.

  20. Gene expression in the liver of female, but not male mice treated with rapamycin resembles changes observed under dietary restriction.

    PubMed

    Yu, Zhen; Sunchu, Bharath; Fok, Wilson C; Alshaikh, Nahla; Pérez, Viviana I

    2015-01-01

    It is well known that in mice the extension in lifespan by rapamycin is sexually dimorphic, in that it has a larger effect in females than males. In a previous study we showed that in male C57BL6 mice, rapamycin had less profound effects in both gene expression and liver metabolites when compared to dietary restriction (DR), but no data was available in females. Because recent studies showed that rapamycin increases longevity in a dose dependent manner and at every dose tested the effect remains larger in females than in males, we hypothesized that rapamycin should have a stronger effect on gene expression in females, and this effect could be dose dependent. To test this hypothesis, we measured the changes in liver gene expression induced by rapamycin (14 ppm) with a focus on several genes involved in pathways known to play a role in aging and that are altered by DR. To investigate whether any effects are dose dependent, we also analyzed females treated with two additional doses of rapamycin (22 and 42 ppm). We observed striking differences between male and female in gene expression at 14 ppm, where females have a larger response to rapamycin than males, and the effects of rapamycin in females resemble what we observed under DR. However, these effects were generally not dose dependent. These data support the notion that female mice respond better to rapamycin, and at least with the set of genes studied here, the effect of rapamycin in females resemble the effect of DR. PMID:26034704

  1. High Fetal Estrogen Concentrations: Correlation with Increased Adult Sexual Activity and Decreased Aggression in Male Mice

    NASA Astrophysics Data System (ADS)

    Vom Saal, Frederick S.; Grant, William M.; McMullen, Carol W.; Laves, Kurt S.

    1983-06-01

    In the house mouse (Mus musculus), fetuses may develop in utero next to siblings of the same or opposite sex. The amniotic fluid of the female fetuses contains higher concentrations of estradiol than that of male fetuses. Male fetuses that developed in utero between female fetuses had higher concentrations of estradiol in their amniotic fluid than males that were located between other male fetusesw during intrauterine development. They were also more sexually active as adults, less aggressive, and had smaller seminal vesicles than males that had developed between other male fetuses in utero. These findings raise the possibility that during fetal life circulating estrogens may interact with circulating androgens both in regulating the development of sex differences between males and females and in producing variation in phenotype among males and among females.

  2. Two of a Kind or a Full House? Reproductive Suppression and Alloparenting in Laboratory Mice.

    PubMed

    Garner, Joseph P; Gaskill, Brianna N; Pritchett-Corning, Kathleen R

    2016-01-01

    Alloparenting, a behavior in which individuals other than the actual parents act in a parental role, is seen in many mammals, including house mice. In wild house mice, alloparental care is only seen when familiar sibling females simultaneously immigrate to a male's territory, so in the laboratory, when a pair of unfamiliar female wild mice are mated with a male, alloparenting does not occur because one female will typically be reproductively suppressed. In contrast, laboratory mice are assumed to alloparent regardless of familiarity or relatedness and are therefore routinely trio bred to increase productivity. Empirical evidence supporting the presence of alloparental care in laboratory mice is lacking. Albino and pigmented inbred mice of the strain C57BL/6NCrl (B6) and outbred mice of the stock Crl:CF1 (CF1) were used to investigate alloparenting in laboratory mice since by mating pigmented and albino females with albino males of the same stock or strain, maternal parentage was easily determined. We housed pairs (M:F) or trios (M:2F) of mice in individually ventilated cages containing nesting material and followed reproductive performance for 16 weeks. Females in trios were tested to determine dominance at the start of the experiment, and again 5 days after the birth of a litter to determine if a female's dominance shifted with the birth of pups. Results showed a significant and expected difference in number of offspring produced by B6 and CF1 (p < 0.0001). Pigmented mice nursed and nested with albino pups and vice-versa, confirming empirical observations from many that group nesting and alloparenting occurs in unrelated laboratory mice. When overall production of both individual mice and cages was examined, reproductive suppression was seen in trio cages. Dominance testing with the tube test did not correlate female reproduction with female dominance in a female-female dyad. Due to the reproductive suppression noted in trios, on a per-mouse basis, pair mating

  3. The PGE2 EP3 Receptor Regulates Diet-Induced Adiposity in Male Mice.

    PubMed

    Ceddia, Ryan P; Lee, DaeKee; Maulis, Matthew F; Carboneau, Bethany A; Threadgill, David W; Poffenberger, Greg; Milne, Ginger; Boyd, Kelli L; Powers, Alvin C; McGuinness, Owen P; Gannon, Maureen; Breyer, Richard M

    2016-01-01

    Mice carrying a targeted disruption of the prostaglandin E2 (PGE2) E-prostanoid receptor 3 (EP3) gene, Ptger3, were fed a high-fat diet (HFD), or a micronutrient matched control diet, to investigate the effects of disrupted PGE2-EP3 signaling on diabetes in a setting of diet-induced obesity. Although no differences in body weight were seen in mice fed the control diet, when fed a HFD, EP3(-/-) mice gained more weight relative to EP3(+/+) mice. Overall, EP3(-/-) mice had increased epididymal fat mass and adipocyte size; paradoxically, a relative decrease in both epididymal fat pad mass and adipocyte size was observed in the heaviest EP3(-/-) mice. The EP3(-/-) mice had increased macrophage infiltration, TNF-α, monocyte chemoattractant protein-1, IL-6 expression, and necrosis in their epididymal fat pads as compared with EP3(+/+) animals. Adipocytes isolated from EP3(+/+) or EP3(-/-) mice were assayed for the effect of PGE2-evoked inhibition of lipolysis. Adipocytes isolated from EP3(-/-) mice lacked PGE2-evoked inhibition of isoproterenol stimulated lipolysis compared with EP3(+/+). EP3(-/-) mice fed HFD had exaggerated ectopic lipid accumulation in skeletal muscle and liver, with evidence of hepatic steatosis. Both blood glucose and plasma insulin levels were similar between genotypes on a control diet, but when fed HFD, EP3(-/-) mice became hyperglycemic and hyperinsulinemic when compared with EP3(+/+) fed HFD, demonstrating a more severe insulin resistance phenotype in EP3(-/-). These results demonstrate that when fed a HFD, EP3(-/-) mice have abnormal lipid distribution, developing excessive ectopic lipid accumulation and associated insulin resistance. PMID:26485614

  4. Female Mice Avoid Male Odor from the Same Strain via the Vomeronasal System in an Estrogen-Dependent Manner.

    PubMed

    Yano, Saori; Sakamoto, Kentaro Q; Habara, Yoshiaki

    2015-11-01

    Inbreeding avoidance is essential to providing offspring with genetic diversity. Females' mate choice is more crucial than males' for successful reproduction because of the high cost of producing gametes and limited chances to mate. However, the mechanism of female inbreeding avoidance is still unclear. To elucidate the mechanism underlying inbreeding avoidance by females, we conducted Y-maze behavioral assays using BALB/c and C57BL/6 female mice. In both strains, the avoidance of male urine from the same strain was lower in the low estrogen phase than in the high estrogen phase. The estrous cycle-dependent avoidance was completely prevented by vomeronasal organ (VNO) removal. To assess the regulation of the vomeronasal system by estrogen, the neural excitability was evaluated by immunohistochemistry of the immediate early gene products. Although estrogen did not affect neural excitability in the VNO, estrogen enhanced the neural excitability of the mitral cell layer in the AOB induced by urine from the cognate males. These results suggest that female mice avoid odor from genetically similar males in an estrogen-dependent manner via the vomeronasal system and the excitability of the mitral cells in the AOB is presumed to be regulated by estrogen. PMID:26377346

  5. The bed nucleus of the stria terminalis has developmental and adult forms in mice, with the male bias in the developmental form being dependent on testicular AMH.

    PubMed

    Wittmann, Walter; McLennan, Ian S

    2013-09-01

    Canonically, the sexual dimorphism in the brain develops perinatally, with adult sexuality emerging due to the activating effects of pubescent sexual hormones. This concept does not readily explain why children have a gender identity and exhibit sex-stereotypic behaviours. These phenomena could be explained if some aspects of the sexual brain networks have childhood forms, which are transformed at puberty to generate adult sexuality. The bed nucleus of stria terminalis (BNST) is a dimorphic nucleus that is sex-reversed in transsexuals but not homosexuals. We report here that the principal nucleus of the BNST (BNSTp) of mice has developmental and adult forms that are differentially regulated. In 20-day-old prepubescent mice, the male bias in the principal nucleus of the BNST (BNSTp) was moderate (360 ± 6 vs 288 ± 12 calbindin(+ve) neurons, p < 0.0001), and absent in mice that lacked a gonadal hormone, AMH. After 20 days, the number of BNSTp neurons increased in the male mice by 25% (p < 0.0001) and decreased in female mice by 15% (p = 0.0012), independent of AMH. Adult male AMH-deficient mice had a normal preference for sniffing female pheromones (soiled bedding), but exhibited a relative disinterest in both male and female pheromones. This suggests that male mice require AMH to undergo normal social development. The reported observations provide a rationale for examining AMH levels in children with gender identity disorders and disorders of socialization that involve a male bias. PMID:24012942

  6. Urethral Obstruction by Seminal Coagulum is Associated with Medetomidine–Ketamine Anesthesia in Male Mice on C57BL/6J and Mixed Genetic Backgrounds

    PubMed Central

    Wells, Sara; Trower, Chris; Hough, Tertius A; Stewart, Michelle; Cheeseman, Michael T

    2009-01-01

    Male and female mice were anesthetized by intraperitoneal injection with a mixture delivering 0.5 mg/kg medetomidine and 50 mg/kg ketamine to achieve immobilization for whole-body radiographs and bone densitometry, as part of a phenotypic screen for bone and mineral disorders in mice carrying genetic modifications induced through mutagenesis with N′-ethyl-N′-nitrosourea. Morbidity and mortality occurred in 19 of 628 (3%) of male mice 24 to 72 h after a seemingly uneventful recovery from anesthesia. No morbidity or mortality occurred in 1564 female mice that were similar in age to the affected male mice and that underwent the same procedure. Of the 7 male mice that underwent postmortem examinations, 5 had urinary bladders grossly distended with urine and 1 had ascites. In addition, the pelvic or penile urethra in 5 of the examined male mice was obstructed with seminal coagulum associated with varying degrees of erosion of the urothelial lining and inflammation of the urethra. In 2 of these animals, from which plasma samples were recovered, azotemia, hyperphosphatemia, and hyperkalemia were present. The predilection for delayed morbidity and mortality in males after anesthesia suggests that anesthesia with 0.5 mg/kg medetomidine and 50 mg/kg ketamine is a potential risk factor for obstructive uropathy due to release of seminal coagulum. This adverse effect did not recur when we altered our anesthesia protocol to 10 mg/kg xylazine and 100 mg/kg ketamine. PMID:19476720

  7. Thrombospondin 1 Mediates High-Fat Diet-Induced Muscle Fibrosis and Insulin Resistance in Male Mice

    PubMed Central

    Jiang, Yibin; Barnes, Richard H.; Tokunaga, Masakuni; Martinez-Santibañez, Gabriel; Geletka, Lynn; Lumeng, Carey N.; Buchner, David A.

    2013-01-01

    Thrombospondin 1 (THBS1 or TSP-1) is a circulating glycoprotein highly expressed in hypertrophic visceral adipose tissues of humans and mice. High-fat diet (HFD) feeding induces the robust increase of circulating THBS1 in the early stages of HFD challenge. The loss of Thbs1 protects male mice from diet-induced weight gain and adipocyte hypertrophy. Hyperinsulinemic euglycemic clamp study has demonstrated that Thbs1-null mice are protected from HFD-induced insulin resistance. Tissue-specific glucose uptake study has revealed that the insulin-sensitive phenotype of Thbs1-null mice is mostly mediated by skeletal muscles. Further assessments of the muscle phenotype using RNA sequencing, quantitative PCR, and histological studies have demonstrated that Thbs1-null skeletal muscles are protected from the HFD-dependent induction of Col3a1 and Col6a1, coupled with a new collagen deposition. At the same time, the Thbs1-null mice display a better circadian rhythm and higher amplitude of energy expenditure with a browning phenotype in sc adipose tissues. These results suggest that THBS1, which circulates in response to a HFD, may induce insulin resistance and fibrotic tissue damage in skeletal muscles as well as the de-browning of sc adipose tissues in the early stages of a HFD challenge. Our study may shed new light on the pathogenic role played by a circulating extracellular matrix protein in the cross talk between adipose tissues and skeletal muscles during obesity progression. PMID:24140711

  8. Thrombospondin 1 mediates high-fat diet-induced muscle fibrosis and insulin resistance in male mice.

    PubMed

    Inoue, Mayumi; Jiang, Yibin; Barnes, Richard H; Tokunaga, Masakuni; Martinez-Santibañez, Gabriel; Geletka, Lynn; Lumeng, Carey N; Buchner, David A; Chun, Tae-Hwa

    2013-12-01

    Thrombospondin 1 (THBS1 or TSP-1) is a circulating glycoprotein highly expressed in hypertrophic visceral adipose tissues of humans and mice. High-fat diet (HFD) feeding induces the robust increase of circulating THBS1 in the early stages of HFD challenge. The loss of Thbs1 protects male mice from diet-induced weight gain and adipocyte hypertrophy. Hyperinsulinemic euglycemic clamp study has demonstrated that Thbs1-null mice are protected from HFD-induced insulin resistance. Tissue-specific glucose uptake study has revealed that the insulin-sensitive phenotype of Thbs1-null mice is mostly mediated by skeletal muscles. Further assessments of the muscle phenotype using RNA sequencing