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Sample records for isolated male mice

  1. Social isolation reduces serotonergic fiber density in the inferior colliculus of female, but not male, mice.

    Science.gov (United States)

    Keesom, Sarah M; Morningstar, Mitchell D; Sandlain, Rebecca; Wise, Bradley M; Hurley, Laura M

    2018-05-12

    Early-life experiences, including maternal deprivation and social isolation during adolescence, have a profound influence on a range of adult social behaviors. Post-weaning social isolation in rodents influences behavior in part through the alteration of neuromodulatory systems, including the serotonergic system. Of significance to social behavior, the serotonergic system richly innervates brain areas involved in vocal communication, including the auditory system. However, the influence of isolation on serotonergic input to the auditory system remains underexplored. Here, we assess whether 4 weeks of post-weaning individual housing alters serotonergic fiber density in the inferior colliculus (IC), an auditory midbrain nucleus in which serotonin alters auditory-evoked activity. Individually housed male and female mice were compared to conspecifics housed socially in groups of three. Serotonergic projections were subsequently visualized with an antibody to the serotonin transporter, which labels serotonergic fibers with relatively high selectivity. Fiber densities were estimated in the three major subregions of the IC using line-scan intensity analysis. Individually housed female mice showed a significantly reduced fiber density relative to socially housed females, which was accompanied by a lower body weight in individually housed females. In contrast, social isolation did not affect serotonergic fiber density in the IC of males. This finding suggests that sensitivity of the serotonergic system to social isolation is sex-dependent, which could be due to a sex difference in the effect of isolation on psychosocial stress. Since serotonin availability depends on social context, this finding further suggests that social isolation can alter the acute social regulation of auditory processing. Copyright © 2018. Published by Elsevier B.V.

  2. Social Isolation Stress Induces Anxious-Depressive-Like Behavior and Alterations of Neuroplasticity-Related Genes in Adult Male Mice

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    Alessandro Ieraci

    2016-01-01

    Full Text Available 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.

  3. Social isolation-induced aggression potentiates anxiety and depressive-like behavior in male mice subjected to unpredictable chronic mild stress.

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    Xian-cang Ma

    Full Text Available Accumulating epidemiological evidence shows that life event stressors are major vulnerability factors for psychiatric diseases such as major depression. It is also well known that social isolation in male mice results in aggressive behavior. However, it is not known how social isolation-induced aggression affects anxiety and depressive-like behavior in isolated male mice subjected to unpredictable chronic mild stress (CMS, an animal model of depression.C57/B6 male mice were divided into 3 groups; non-stressed controls, in Group I; isolated mice subjected to the CMS protocol in Group II and aggression by physical contact in socially isolated mice subjected to the CMS protocol in Group III. In the sucrose intake test, ingestion of a 1% sucrose solution by mice in Groups II and III was significantly lower than in Group I. Furthermore, intake of this solution in Group III mice was significantly lower than in Group II mice. In the open field test, mice in Group III, showed reduced locomotor activity and reduced entry and retention time in the central zone, compared to Groups I and II mice. Moreover, the distances moved in 1 hour by Group III mice did not differ between night and morning. In the light/black box test, Groups II and III animals spent significantly less time in the light box compared to Group I animals. In the tail suspension test (TST and forced swimming test (FST, the immobility times of Group II and Group III mice were significantly longer than in Group I mice. In addition, immobility times in the FST were significantly longer in Group III than in Group II mice.These findings show that social isolation-induced aggression could potentiate anxiety and depressive-like behaviors in isolated male mice subjected to CMS.

  4. Effect Of Aqueous And Hydroalcoholic Extract Of Beberis Vulgaris On Insulin Secretion From Islets Of Langerhans Isolated From Male Mice

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    A Ahangarpour

    2012-10-01

    Full Text Available Background & Aim: considering the use of Beberis vulgaris in traditional medicine as a blood sugar depressant, in this study, the effect of Beberis vulgaris extracts were investigated on the level of insulin secretion from islets isolated of langerhans in male mice. Methods: This experimental study was carried out on 90 adult male mice, NMARI strains weighing 20-25 g. Pancreatic islets from normal mice were isolated by collagenase digestion method. Then the aqueous and hydro-alcoholic extract of Beberis vulgaris at 0.05, 0.1, and 1 mg/ml concentrations and glyburide at 1 and 10 μM concentrations were applied on islets isolated in three different concentration of glucose solution (2.8, 5.6 and 16.7 mM. Insulin secretion from hand-picked islets were evaluated in the static incubation system. The level of Insulin secretion was measured by the ELISA insulin kit. Data were analyzed with variance analysis. Results: Insulin secretion was significantly increased at 16.7 mM glucose concentration in comparison with 2.8 and 5.6 mM glucose concentration (p<0.05. Incubation of pancreatic islets isolated at 2.8 and 5.6 mM glucose concentration and low concentrations of extract (0.05 and 0.1mg/ml significantly increased the insulin secretion (p<0.05. Glyburide at 10 μM concentration was more effective than aqueous and hydro alcoholic extract of Beberis vulgaris at 16.7 mM glucose. Conclusion: The present study supported the anti-diabetic effect of Beberis vulgaris extracts in vitro with low glucose concentration and it suggests that one of the anti diabetic mechanisms of this plant is via pancreatic islets.

  5. KChIP2 genotype dependence of transient outward current (Ito) properties in cardiomyocytes isolated from male and female mice.

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    Waldschmidt, Lara; Junkereit, Vera; Bähring, Robert

    2017-01-01

    The transient outward current (Ito) in cardiomyocytes is largely mediated by Kv4 channels associated with Kv Channel Interacting Protein 2 (KChIP2). A knockout model has documented the critical role of KChIP2 in Ito expression. The present study was conducted to characterize in both sexes the dependence of Ito properties, including current magnitude, inactivation kinetics, recovery from inactivation and voltage dependence of inactivation, on the number of functional KChIP2 alleles. For this purpose we performed whole-cell patch-clamp experiments on isolated left ventricular cardiomyocytes from male and female mice which had different KChIP2 genotypes; i.e., wild-type (KChIP2+/+), heterozygous knockout (KChIP2+/-) or complete knockout of KChIP2 (KChIP2-/-). We found in both sexes a KChIP2 gene dosage effect (i.e., a proportionality between number of alleles and phenotype) on Ito magnitude, however, concerning other Ito properties, KChIP2+/- resembled KChIP2+/+. Only in the total absence of KChIP2 (KChIP2-/-) we observed a slowing of Ito kinetics, a slowing of recovery from inactivation and a negative shift of a portion of the voltage dependence of inactivation. In a minor fraction of KChIP2-/- myocytes Ito was completely lost. The distinct KChIP2 genotype dependences of Ito magnitude and inactivation kinetics, respectively, seen in cardiomyocytes were reproduced with two-electrode voltage-clamp experiments on Xenopus oocytes expressing Kv4.2 and different amounts of KChIP2. Our results corroborate the critical role of KChIP2 in controlling Ito properties. They demonstrate that the Kv4.2/KChIP2 interaction in cardiomyocytes is highly dynamic, with a clear KChIP2 gene dosage effect on Kv4 channel surface expression but not on inactivation gating.

  6. Attenuation of oxidative and nitrosative stress in cortical area associates with antidepressant-like effects of tropisetron in male mice following social isolation stress.

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    Haj-Mirzaian, Arya; Amiri, Shayan; Amini-Khoei, Hossein; Rahimi-Balaei, Maryam; Kordjazy, Nastaran; Olson, Carl O; Rastegar, Mojgan; Naserzadeh, Parvaneh; Marzban, Hassan; Dehpour, Ahmad Reza; Hosseini, Mir-Jamal; Samiei, Elika; Mehr, Shahram Ejtemaei

    2016-06-01

    Tropisetron, a 5-HT3 receptor antagonist widely used as an antiemetic, has been reported to have positive effects on mood disorders. Adolescence is a critical period during the development of brain, where exposure to chronic stress during this time is highly associated with the development of depression. In this study, we showed that 4 weeks of juvenile social isolation stress (SIS) provoked depressive-like behaviors in male mice, which was associated with disruption of mitochondrial function and nitric oxide overproduction in the cortical areas. In this study, tropisetron (5mg/kg) reversed the negative behavioral effects of SIS in male mice. We found that the effects of tropisetron were mediated through mitigating the negative activity of inducible nitric oxide synthase (iNOS) on mitochondrial activity. Administration of aminoguanidine (specific iNOS inhibitor, 20mg/kg) augmented the protective effects of tropisetron (1mg/kg) on SIS. Furthermore, l-arginine (nitric oxide precursor, 100mg/kg) abolished the positive effects of tropisetron. These results have increased our knowledge on the pivotal role of mitochondrial function in the pathophysiology of depression, and highlighted the role of 5-HT3 receptors in psychosocial stress response during adolescence. Finally, we observed that tropisetron alleviated the mitochondrial dysfunction through decreased nitrergic system activity in the cerebral cortex. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Early-Life Social Isolation Influences Mouse Ultrasonic Vocalizations during Male-Male Social Encounters.

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    Keesom, Sarah M; Finton, Caitlyn J; Sell, Gabrielle L; Hurley, Laura M

    2017-01-01

    Early-life social isolation has profound effects on adult social competence. This is often expressed as increased aggression or inappropriate displays of courtship-related behaviors. The social incompetence exhibited by isolated animals could be in part due to an altered ability to participate in communicatory exchanges. House mice (Mus musculus) present an excellent model for exploring this idea, because social isolation has a well-established influence on their social behavior, and mice engage in communication via multiple sensory modalities. Here, we tested the prediction that social isolation during early life would influence ultrasonic vocalizations (USVs) emitted by adult male mice during same-sex social encounters. Starting at three weeks of age, male mice were housed individually or in social groups of four males for five weeks, after which they were placed in one of three types of paired social encounters. Pair types consisted of: two individually housed males, two socially housed males, or an individually housed and a socially housed male ("mixed" pairs). Vocal behavior (USVs) and non-vocal behaviors were recorded from these 15-minute social interactions. Pairs of mice consisting of at least one individually housed male emitted more and longer USVs, with a greater proportional use of USVs containing frequency jumps and 50-kHz components. Individually housed males in the mixed social pairs exhibited increased levels of mounting behavior towards the socially housed males. Mounting in these pairs was positively correlated with increased number and duration of USVs as well as increased proportional use of spectrally more complex USVs. These findings demonstrate that USVs are part of the suite of social behaviors influenced by early-life social isolation, and suggest that altered vocal communication following isolation reflects reduced social competence.

  8. Semiquinone glucoside derivative isolated from Bacillus sp. INM-1 offers protection to male reproductive system of mice against γ-radiation induced toxicity

    International Nuclear Information System (INIS)

    Singh, Praveen K.; Malhotra, Poonam; Gupta, Ashutosh; Chhachhia, Neha; Singh, Shravan K.; Kumar, Raj; Dubey, Kashyap Kumar

    2014-01-01

    Ionizing radiation causes reversible/irreversible damages to the testis by inducing oxidative stress through reactive oxygen species lead to impotency in young cancer patients undergoing lower abdomen radiotherapy. Therefore, protection of testicular cells against gamma radiation is of utmost significance. Present study was focused to evaluate radioprotective efficacy of a semiquinone rich fraction isolated from radioresistant bacterium Bacillus sp. INM-1. In the present study, mice were pre-treated with semiquinone glucoside derivative (SQGD; 50 mg/ kg.b.wt. i.p.) 2h before irradiation (5Gy) and various radioprotective cellular parameters including histology, quantitative analysis of spermatids, spermatocytes, sperm counts, sperm abnormalities, structural and morphological analysis of seminiferous tubules were observed for complete two cycles (70 days) of spermatogenesis and compared with irradiated (5 Gy) control group. Results of the study demonstrated that untreated control and SQGD treated groups showed no significant difference in sperm counts even after 70 days post treatment time. However, whole body irradiation reduced the sperm count significantly (p<0.05%) from the day 1 st to day 70 th . SQGD treatment to irradiated mice significantly increased the sperm count, reduced morphological abnormality in the sperms as compared to irradiated group. Untreated control mice showed a higher seminiferous tubular area compared to irradiation control at 35 th and 70 th day post irradiation time. SQGD pretreatment to irradiated mice led to significant increase in seminiferous tubule area compared to irradiated control. Concomitantly, seminiferous lumen size increases in radiation control mice compared to SQGD pre-treated mice at 35 th and 70 th day due to germ cells depletion. Qualitative histological study of testis at all tested time points suggests that drug treatment protects the spermatogenesis by enhancing the spermatogonial proliferation, enhancing the stem cell

  9. Proteomic Analysis of Pachytene Spermatocytes of Sterile Hybrid Male Mice.

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    Wang, Lu; Guo, Yueshuai; Liu, Wenjing; Zhao, Weidong; Song, Gendi; Zhou, Tao; Huang, Hefeng; Guo, Xuejiang; Sun, Fei

    2016-09-01

    Incompatibilities in interspecific hybrids, such as reduced hybrid fertility and lethality, are common features resulting from reproductive isolation that lead to speciation. Subspecies crosses of house mice produce offspring in which one sex is infertile or absent, yet the molecular mechanisms of hybrid sterility are poorly understood. In this study, we observed extensive asynapsis of chromosomes and disturbance of the sex body in pachytene spermatocytes of sterile F1 males (PWK/Ph female × C57BL/6J male). We report the high-confidence identification of 4005 proteins in the pachytene spermatocytes of fertile F1 males (PWK/Ph male × C57BL/6J female) and sterile F1 males (PWK/Ph female × C57BL/6J male), of which 215 were upregulated and 381 were downregulated. Bioinformatics analysis of the proteome led to the identification of 43 and 59 proteins known to be essential for male meiosis and spermatogenesis in mice, respectively. Characterization of the proteome of pachytene spermatocytes associated with hybrid male sterility provides an inventory of proteins that is useful for understanding meiosis and the mechanisms of hybrid male infertility. © 2016 by the Society for the Study of Reproduction, Inc.

  10. Genetics and evolution of hybrid male sterility in house mice.

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    White, Michael A; Stubbings, Maria; Dumont, Beth L; Payseur, Bret A

    2012-07-01

    Comparative genetic mapping provides insights into the evolution of the reproductive barriers that separate closely related species. This approach has been used to document the accumulation of reproductive incompatibilities over time, but has only been applied to a few taxa. House mice offer a powerful system to reconstruct the evolution of reproductive isolation between multiple subspecies pairs. However, studies of the primary reproductive barrier in house mice-hybrid male sterility-have been restricted to a single subspecies pair: Mus musculus musculus and Mus musculus domesticus. To provide a more complete characterization of reproductive isolation in house mice, we conducted an F(2) intercross between wild-derived inbred strains from Mus musculus castaneus and M. m. domesticus. We identified autosomal and X-linked QTL associated with a range of hybrid male sterility phenotypes, including testis weight, sperm density, and sperm morphology. The pseudoautosomal region (PAR) was strongly associated with hybrid sterility phenotypes when heterozygous. We compared QTL found in this cross with QTL identified in a previous F(2) intercross between M. m. musculus and M. m. domesticus and found three shared autosomal QTL. Most QTL were not shared, demonstrating that the genetic basis of hybrid male sterility largely differs between these closely related subspecies pairs. These results lay the groundwork for identifying genes responsible for the early stages of speciation in house mice.

  11. Effect of Soybean on Male Reproductive Physiology in Male Mice

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    M Modaresi

    2011-01-01

    Full Text Available Introduction & Objective: Soybean (Soja hispida Moench is a member of Fabaceae family. It is a species of legume native to East Asia. Soy contains significant amount of all the essential amino acids for humans therefore, is a good source of protein .Soy has an important role in the improvement and treatment of some cancers such as colon, prostate, and breast. The aim of this study was to investigate the effect of soybeans on reproductive system in male mice. Materials & Methods: This experimental study was conducted at Isfahan Payam e Noor University in 2009. In this research, 32 male mice were randomly grouped into four experimental groups. The control group was fed with soy-free basic diet. The experimental groups 1, 2, and 3 were fed with a diet containing 20%, 30% and 50% soy diet respectively.At the end of 9 weeks of treatment, blood samples were collected and serum levels of testosterone, LH and FSH were measured. The collected data was analyzed with SPSS software using one way ANOVA with Dunnett's post test and Duncan test. Results : In the experimental group which received 20% soy diet, the level of testosterone had a meaningful decrease in comparison with the control group (P<0.05, but in the experimental group which received a 50% soy diet, the level of testosterone had a meaningful increase (P<0.05 .The LH level in 30% and 50% groups had a meaningful increase but no significant differences were observed in FSH level & weight of testicles (P<0.05.The number of sperms in all of the treatment regimes had a meaningful decrease (P0.05 Conclusion: Results of this research indicated that the 20, 30, and 50 percent soy diet had a negative effect on the male reproductive system in mice.

  12. Social isolation during puberty affects female sexual behavior in mice

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    Jasmina eKercmar

    2014-09-01

    Full Text Available Exposure to stress during puberty can lead to long-term behavioral alterations in adult rodents coincident with sex steroid hormone-dependent brain remodeling and reorganization. Social isolation is a stress for social animals like mice, but little is known about the effects of such stress during adolescence on later reproductive behaviors. The present study examined sexual behavior of ovariectomized, estradiol and progesterone primed female mice that were individually housed from 25 days of age until testing at approximately 95 days, or individually housed from day 25 until day 60 (during puberty, followed by housing in social groups. Mice in these isolated groups were compared to females that were group housed throughout the experiment. Receptive sexual behaviors of females and behaviors of stimulus males were recorded. Females housed in social groups displayed greater levels of receptive behaviors in comparison to both socially isolated groups. Namely, social females had higher lordosis quotients and more often displayed stronger lordosis postures in comparison to isolated females. No differences between female groups were observed in stimulus male sexual behavior suggesting that female ’attractiveness’ was not affected by their social isolation. Females housed in social groups had fewer cells containing immunoreactive estrogen receptor (ER α in the anteroventral periventricular nucleus (AVPV and in the ventromedial nucleus of the hypothalamus (VMH than both isolated groups. These results suggest that isolation during adolescence affects female sexual behavior and re-socialization for one month in adulthood is insufficient to rescue lordosis behavior from the effects of social isolation during the pubertal period.

  13. Retardation of muscle growth in castrated male mice: further ...

    African Journals Online (AJOL)

    Retardation of muscle growth in castrated male mice was studied as an evidence for the influence of hormones on the development of muscle mass. Male albino mice were castrated at 28days of age by open castration method. The weights and the muscle mass indices (mg muscle weight per gram body weight) of the ...

  14. Characterization of urinary volatiles in Swiss male mice (Mus ...

    Indian Academy of Sciences (India)

    Unknown

    Information about diet is also available in guinea pigs. (Beauchamp ... change in diet can alter urine odours. Urinary ... adult male mice, which are dependent upon high levels of ... a protein or protein related substance (Marchlewska-Koj. 1977 ...

  15. The role of p38 in mitochondrial respiration in male and female mice.

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    Ju, Xiaohua; Wen, Yi; Metzger, Daniel; Jung, Marianna

    2013-06-07

    p38 is a mitogen-activated protein kinase and mediates cell growth, cell differentiation, and synaptic plasticity. The aim of this study is to determine the extent to which p38 plays a role in maintaining mitochondrial respiration in male and female mice under a normal condition. To achieve this aim, we have generated transgenic mice that lack p38 in cerebellar Purkinje neurons by crossing Pcp2 (Purkinje cell protein 2)-Cre mice with p38(loxP/loxP) mice. Mitochondria from cerebellum were then isolated from the transgenic and wild-type mice to measure mitochondrial respiration using XF24 respirometer. The mRNA and protein expression of cytochrome c oxidase (COX) in cerebellum were also measured using RT-PCR and immunoblot methods. Separately, HT22 cells were used to determine the involvement of 17β-estradiol (E2) and COX in mitochondrial respiration. The genetic knockout of p38 in Purkinje neurons suppressed the mitochondrial respiration only in male mice and increased COX expression only in female mice. The inhibition of COX by sodium azide (SA) sharply suppressed mitochondrial respiration of HT22 cells in a manner that was protected by E2. These data suggest that p38 is required for the mitochondrial respiration of male mice. When p38 is below a normal level, females may maintain mitochondrial respiration through COX up-regulation. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  16. Endothelial arginine resynthesis contributes to the maintenance of vasomotor function in male diabetic mice.

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    Ramesh Chennupati

    Full Text Available Argininosuccinate synthetase (ASS is essential for recycling L-citrulline, the by-product of NO synthase (NOS, to the NOS substrate L-arginine. Here, we assessed whether disturbed arginine resynthesis modulates endothelium-dependent vasodilatation in normal and diabetic male mice.Endothelium-selective Ass-deficient mice (Assfl/fl/Tie2Cretg/- = Ass-KOTie2 were generated by crossing Assfl/fl mice ( = control with Tie2Cre mice. Gene ablation in endothelial cells was confirmed by immunohistochemistry. Blood pressure (MAP was recorded in 34-week-old male mice. Vasomotor responses were studied in isolated saphenous arteries of 12- and 34-week-old Ass-KOTie2 and control animals. At the age of 10 weeks, diabetes was induced in control and Ass-KOTie2 mice by streptozotocin injections. Vasomotor responses of diabetic animals were studied 10 weeks later. MAP was similar in control and Ass-KOTie2 mice. Depletion of circulating L-arginine by arginase 1 infusion or inhibition of NOS activity with L-NAME resulted in an increased MAP (10 and 30 mmHg, respectively in control and Ass-KOTie2 mice. Optimal arterial diameter, contractile responses to phenylephrine, and relaxing responses to acetylcholine and sodium nitroprusside were similar in healthy control and Ass-KOTie2 mice. However, in diabetic Ass-KOTie2 mice, relaxation responses to acetylcholine and endothelium-derived NO (EDNO were significantly reduced when compared to diabetic control mice.Absence of endothelial citrulline recycling to arginine did not affect blood pressure and systemic arterial vasomotor responses in healthy mice. EDNO-mediated vasodilatation was significantly more impaired in diabetic Ass-KOTie2 than in control mice demonstrating that endothelial arginine recycling becomes a limiting endothelial function in diabetes.

  17. [The reproductive correlates of social hierarchy in laboratory male mice].

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    Osadchuk, L B; Salomacheva, I N; Bragin, A V; Osadchuk, A V

    2007-01-01

    In laboratory male mice the effects of social hierarchy on hormonal and spermatogenic testicular function, accessory organs and testicular weights, sexual behaviour have been investigated using an experimental model of social hierarchy, which is characterised by a minimal size (two male mice) and 5 days period of social interactions. The social rank of the partners was detected by asymmetry in aggressive behaviour. Using the experimental condition, when the both partners have no preferences for exclusive use of area we demonstrated that there were no rank differences in the number of mounts and testicular testosterone content. Nevertheless a rank asymmetry in the male sniffing behaviour towards a receptive female, weights of the testes, seminal vesicles, epididymes and the number of epididymal sperm was kept up in a stable social group. Social dominance was found to affect negatively on testicular testosterone increase in response to introduction of a receptive female and sexual attractiveness of male to a receptive female in both dominant and subordinate males. The results obtained demonstrate the impact of social hierarchy on reproduction in laboratory male mice, particular in respect of spermatogenesis and the testicular testosterone in response to a receptive female.

  18. Endothelial arginine resynthesis contributes to the maintenance of vasomotor function in male diabetic mice

    DEFF Research Database (Denmark)

    Chennupati, Ramesh; Meens, Merlijn J P M T; Marion, Vincent

    2014-01-01

    AIM: Argininosuccinate synthetase (ASS) is essential for recycling L-citrulline, the by-product of NO synthase (NOS), to the NOS substrate L-arginine. Here, we assessed whether disturbed arginine resynthesis modulates endothelium-dependent vasodilatation in normal and diabetic male mice. METHODS...... of endothelial citrulline recycling to arginine did not affect blood pressure and systemic arterial vasomotor responses in healthy mice. EDNO-mediated vasodilatation was significantly more impaired in diabetic Ass-KOTie2 than in control mice demonstrating that endothelial arginine recycling becomes a limiting...... responses were studied in isolated saphenous arteries of 12- and 34-week-old Ass-KOTie2 and control animals. At the age of 10 weeks, diabetes was induced in control and Ass-KOTie2 mice by streptozotocin injections. Vasomotor responses of diabetic animals were studied 10 weeks later. MAP was similar...

  19. Metabolic and affective consequences of fatherhood in male California mice.

    Science.gov (United States)

    Zhao, Meng; Garland, Theodore; Chappell, Mark A; Andrew, Jacob R; Saltzman, Wendy

    2017-08-01

    Physiological and affective condition can be modulated by the social environment and parental state in mammals. However, in species in which males assist with rearing offspring, the metabolic and affective effects of pair bonding and fatherhood on males have rarely been explored. In this study we tested the hypothesis that fathers, like mothers, experience energetic costs as well as behavioral and affective changes (e.g., depression, anxiety) associated with parenthood. We tested this hypothesis in the monogamous, biparental California mouse (Peromyscus californicus). Food intake, blood glucose and lipid levels, blood insulin and leptin levels, body composition, pain sensitivity, and depression-like behavior were compared in males from three reproductive groups: virgin males (VM, housed with another male), non-breeding males (NB, housed with a tubally ligated female), and breeding males (BM, housed with a female and their first litter). We found statistically significant (Pfatherhood influences several metabolic, morphological, and affective measures in male California mice. Overall, the changes we observed in breeding males were minor, but stronger effects might occur in long-term breeding males and/or under more challenging environmental conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Histomorphological effects of isoniazid induced hepatotoxicity in male albino mice

    International Nuclear Information System (INIS)

    Humayun, F.; Zareen, N.

    2017-01-01

    To observe the histomorphological changes of isoniazid induced hepatotoxicity in male albino mice. Methodology: This experimental study was carried out at University of Health Sciences, Lahore, Pakistan from January to December 2013. Forty male albino mice selected by simple random technique, were divided into two groups; A-Control, and B-experimental. Group A comprised of 15, while Group B comprised 25 mice. Both the groups were kept under identical conditions and diet. However, experimental group was treated with an additional oral hepatotoxic dose of isoniazid i.e. 100mg/kg bodyweight daily for 30 days. After 30 days, the animals were sacrificed and livers were dissected out. Gross comparison of the organ and stained sections were histologically compared for morphological differences between the groups. Fischer Exact test was used to analyze the qualitative data and a p<0.05 was considered significant. Results: Group A animals showed the normal liver architecture. Whereas, those of Group B showed deranged hepatic histomorphology. Conclusion: Hepatotoxic dose of Isoniazid caused histomorphological alterations in the liver of male albino mice. (author)

  1. Iron overload induces hypogonadism in male mice via extrahypothalamic mechanisms.

    Science.gov (United States)

    Macchi, Chiara; Steffani, Liliana; Oleari, Roberto; Lettieri, Antonella; Valenti, Luca; Dongiovanni, Paola; Romero-Ruiz, Antonio; Tena-Sempere, Manuel; Cariboni, Anna; Magni, Paolo; Ruscica, Massimiliano

    2017-10-15

    Iron overload leads to multiple organ damage including endocrine organ dysfunctions. Hypogonadism is the most common non-diabetic endocrinopathy in primary and secondary iron overload syndromes. To explore the molecular determinants of iron overload-induced hypogonadism with specific focus on hypothalamic derangements. A dysmetabolic male murine model fed iron-enriched diet (IED) and cell-based models of gonadotropin-releasing hormone (GnRH) neurons were used. Mice fed IED showed severe hypogonadism with a significant reduction of serum levels of testosterone (-83%) and of luteinizing hormone (-86%), as well as reduced body weight gain, body fat and plasma leptin. IED mice had a significant increment in iron concentration in testes and in the pituitary. Even if iron challenge of in vitro neuronal models (GN-11 and GT1-7 GnRH cells) resulted in 10- and 5-fold iron content increments, respectively, no iron content changes were found in vivo in hypothalamus of IED mice. Conversely, mice placed on IED showed a significant increment in hypothalamic GnRH gene expression (+34%) and in the intensity of GnRH-neuron innervation of the median eminence (+1.5-fold); similar changes were found in the murine model HFE -/- , resembling human hemochromatosis. IED-fed adult male mice show severe impairment of hypothalamus-pituitary-gonadal axis without a relevant contribution of the hypothalamic compartment, which thus appears sufficiently protected from systemic iron overload. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Asymmetry and polymorphism of hybrid male sterility during the early stages of speciation in house mice.

    Science.gov (United States)

    Good, Jeffrey M; Handel, Mary Ann; Nachman, Michael W

    2008-01-01

    House mice offer a powerful system for dissecting the genetic basis of phenotypes that isolate species in the early stages of speciation. We used a series of reciprocal crosses between wild-derived strains of Mus musculus and M. domesticus to examine F(1) hybrid male sterility, one of the primary phenotypes thought to isolate these species. We report four main results. First, we found significantly smaller testes and fewer sperm in hybrid male progeny of most crosses. Second, in some crosses hybrid male sterility was asymmetric and depended on the species origin of the X chromosome. These observations confirm and extend previous findings, underscoring the central role that the M. musculus X chromosome plays in reproductive isolation. Third, comparisons among reciprocal crosses revealed polymorphism at one or more hybrid incompatibilities within M. musculus. Fourth, the spermatogenic phenotype of this polymorphic interaction appears distinct from previously described hybrid incompatibilities between these species. These data build on previous studies of speciation in house mice and show that the genetic basis of hybrid male sterility is fairly complex, even at this early stage of divergence.

  3. Ameliorative Effects of Operculina turpethum and its Isolated Stigma-5,22dien-3-o-β-D-glucopyranoside on the Hematological Parameters of Male Mice Exposed to N-Nitrosodimethylamine, a Potent Carcinogen

    Science.gov (United States)

    Sharma, Veena; Singh, Manu

    2014-01-01

    Objectives: Enormous propensity of plants to synthesize a variety of structurally diverse bioactive compounds, has made the plant kingdom a potential source of chemical constituents with various therapeutic values, including antitumor and cytotoxic activities. Blood is a good indicator to determine the physiological and pathological status of man and animal. The objective of the present study is to determine the effect of Operculina turpethum root extract and its isolated glycoside treatment on the hematological parameters in the mice with N-Nitrosodimethylamine (NDMA) induced cancer. Materials and Methods: The body weights of the animals were recorded before and after the experiment. Non-coagulated blood was tested for total erythrocyte count, total leukocyte count, hemoglobin, differential leukocyte count (DLC) and for other blood indices. Results: A significant (P < 0.01), (P < 0.001) recovery of the red blood cell and white blood cell counts, packed cell volume and hemoglobin content in the host after 21 day treatment was shown. Conclusion: These results show that the extract of Operculina turpethum is relatively safe following oral administration and have possible stimulatory effect on red blood cell production and there was dose dependent therapeutic effect. PMID:24748732

  4. Hypogonadism alters cecal and fecal microbiota in male mice.

    Science.gov (United States)

    Harada, Naoki; Hanaoka, Ryo; Hanada, Kazuki; Izawa, Takeshi; Inui, Hiroshi; Yamaji, Ryoichi

    2016-11-01

    Low testosterone levels increase the risk for cardiovascular disease in men and lead to shorter life spans. Our recent study showed that androgen deprivation via castration altered fecal microbiota and exacerbated risk factors for cardiovascular disease, including obesity, impaired fasting glucose, excess hepatic triglyceride accumulation, and thigh muscle weight loss only in high-fat diet (HFD)-fed male mice. However, when mice were administered antibiotics that disrupted the gut microbiota, castration did not increase cardiovascular risks or decrease the ratio of dried feces to food intake. Here, we show that changes in cecal microbiota (e.g., an increased Firmicutes/Bacteroidetes ratio and number of Lactobacillus species) were consistent with changes in feces and that there was a decreased cecal content secondary to castration in HFD mice. Castration increased rectal body temperature and plasma adiponectin, irrespective of diet. Changes in the gut microbiome may provide novel insight into hypogonadism-induced cardiovascular diseases.

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

    Science.gov (United States)

    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

  6. Chronic Co-species Housing Mice and Rats Increased the Competitiveness of Male Mice.

    Science.gov (United States)

    Liu, Ying-Juan; Li, Lai-Fu; Zhang, Yao-Hua; Guo, Hui-Fen; Xia, Min; Zhang, Meng-Wei; Jing, Xiao-Yuan; Zhang, Jing-Hua; Zhang, Jian-Xu

    2017-03-01

    Rats are predators of mice in nature. Nevertheless, it is a common practice to house mice and rats in a same room in some laboratories. In this study, we investigated the behavioral and physiological responsively of mice in long-term co-species housing conditions. Twenty-four male mice were randomly assigned to their original raising room (control) or a rat room (co-species-housed) for more than 6 weeks. In the open-field and light-dark box tests, the behaviors of the co-species-housed mice and controls were not different. In a 2-choice test of paired urine odors [rabbit urine (as a novel odor) vs. rat urine, cat urine (as a natural predator-scent) vs. rabbit urine, and cat urine vs. rat urine], the co-species-housed mice were more ready to investigate the rat urine odor compared with the controls and may have adapted to it. In an encounter test, the rat-room-exposed mice exhibited increased aggression levels, and their urines were more attractive to females. Correspondingly, the levels of major urinary proteins were increased in the co-species-housed mouse urine, along with some volatile pheromones. The serum testosterone levels were also enhanced in the co-species-housed mice, whereas the corticosterone levels were not different. The norepinephrine, dopamine, and 5-HT levels in the right hippocampus and striatum were not different between the 2. Our findings indicate that chronic co-species housing results in adaptation in male mice; furthermore, it appears that long-term rat-odor stimuli enhance the competitiveness of mice, which suggests that appropriate predator-odor stimuli may be important to the fitness of prey animals. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. Sphingomyelin Synthase 1 Is Essential for Male Fertility in Mice.

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    Anke Wittmann

    Full Text Available Sphingolipids and the derived gangliosides have critical functions in spermatogenesis, thus mutations in genes involved in sphingolipid biogenesis are often associated with male infertility. We have generated a transgenic mouse line carrying an insertion in the sphingomyelin synthase gene Sms1, the enzyme which generates sphingomyelin species in the Golgi apparatus. We describe the spermatogenesis defect of Sms1-/- mice, which is characterized by sloughing of spermatocytes and spermatids, causing progressive infertility of male homozygotes. Lipid profiling revealed a reduction in several long chain unsaturated phosphatidylcholins, lysophosphatidylcholins and sphingolipids in the testes of mutants. Multi-Spectral Optoacoustic Tomography indicated blood-testis barrier dysfunction. A supplementary diet of the essential omega-3 docosahexaenoic acid and eicosapentaenoic acid diminished germ cell sloughing from the seminiferous epithelium and restored spermatogenesis and fertility in 50% of previously infertile mutants. Our findings indicate that SMS1 has a wider than anticipated role in testis polyunsaturated fatty acid homeostasis and for male fertility.

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

    Science.gov (United States)

    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.

  9. Male sterility in plants. Induction, isolation and utilization

    International Nuclear Information System (INIS)

    Driscoll, C.J.; Barlow, K.K.

    1976-01-01

    Both induced and spontaneously arising male sterility mutants exist in a number of important plant species. These mutants are somewhat unique in that they effect procedures for breeding improved varieties. They allow for the possibility of easily obtaining large numbers of hybrids, population breeding systems and the production of hybrid varieties. These mutants are normally classified as cytoplasmic mutants or chromosomal mutants, the latter also being referred to as nuclear or genic mutants. Specific examples of these types of sterility are examined in relation to the breeding system of the species and their potential use for varietal development. Male sterility in diploid and polyploid species is compared, with reference to gene duplication in polyploids. The mechanism of male sterility is examined in the various species at the anatomical and biochemical levels. Methods of isolating male sterility mutants are compared and a specific example is outlined for hexaploid wheat. Future use of male sterility mutants for improving varieties of various crops is examined. (author)

  10. Regulatory divergence of X-linked genes and hybrid male sterility in mice.

    Science.gov (United States)

    Oka, Ayako; Shiroishi, Toshihiko

    2014-01-01

    Postzygotic reproductive isolation is the reduction of fertility or viability in hybrids between genetically diverged populations. One example of reproductive isolation, hybrid male sterility, may be caused by genetic incompatibility between diverged genetic factors in two distinct populations. Genetic factors involved in hybrid male sterility are disproportionately located on the X chromosome. Recent studies showing the evolutionary divergence in gene regulatory networks or epigenetic effects suggest that the genetic incompatibilities occur at much broader levels than had previously been thought (e.g., incompatibility of protein-protein interactions). The latest studies suggest that evolutionary divergence of transcriptional regulation causes genetic incompatibilities in hybrid animals, and that such incompatibilities preferentially involve X-linked genes. In this review, we focus on recent progress in understanding hybrid sterility in mice, including our studies, and we discuss the evolutionary significance of regulatory divergence for speciation.

  11. Isolation and characterization of string-forming female germline stem cells from ovaries of neonatal mice.

    Science.gov (United States)

    Liu, Jing; Shang, Dantong; Xiao, Yao; Zhong, Pei; Cheng, Hanhua; Zhou, Rongjia

    2017-09-29

    Germline stem cells are essential in the generation of both male and female gametes. In mammals, the male testis produces sperm throughout the entire lifetime, facilitated by testicular germline stem cells. Oocyte renewal ceases in postnatal or adult life in mammalian females, suggesting that germline stem cells are absent from the mammalian ovary. However, studies in mice, rats, and humans have recently provided evidence for ovarian female germline stem cells (FGSCs). A better understanding of the role of FGSCs in ovaries could help improve fertility treatments. Here, we developed a rapid and efficient method for isolating FGSCs from ovaries of neonatal mice. Notably, our FGSC isolation method could efficiently isolate on average 15 cell "strings" per ovary from mice at 1-3 days postpartum. FGSCs isolated from neonatal mice displayed the string-forming cell configuration at mitosis ( i.e. a "stringing" FGSC (sFGSC) phenotype) and a disperse phenotype in postnatal mice. We also found that sFGSCs undergo vigorous mitosis especially at 1-3 days postpartum. After cell division, the sFGSC membranes tended to be connected to form sFGSCs. Moreover, F-actin filaments exhibited a cell-cortex distribution in sFGSCs, and E-cadherin converged in cell-cell connection regions, resulting in the string-forming morphology. Our new method provides a platform for isolating FGSCs from the neonatal ovary, and our findings indicate that FGCSs exhibit string-forming features in neonatal mice. The sFGSCs represent a valuable resource for analysis of ovary function and an in vitro model for future clinical use to address ovarian dysfunction. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. [Study of genome instability using DNA fingerprinting of the offspring of male mice subjected to chronic low dose gamma irradiation].

    Science.gov (United States)

    Bezlepkin, V G; Vasil'eva, G V; Lomaeva, M G; Sirota, N P; Gaziev, A I

    2000-01-01

    By a polymerase chain reaction with an arbitrary primer (AP-PCR), the possibility of transmission of genome instability to somatic cells of the offspring (F1 generation) from male parents of mice exposed to chronic low-level gamma-radiation was studied. Male BALB/c mice 15 days after exposure to 10-50 cGy were mated with unirradiated females. Biopsies were taken from tale tips of two month-old offspring mice and DNA was isolated. The primer in the AP-PCR was a 20-mer oligonucleotide flanking the microsatellite locus Atp1b2 on chromosome 11 of the mouse. A comparative analysis of individual fingerprints of AP-PCR products on DNA-templates from the offspring of irradiated and unirradiated male mice revealed an increased variability of microsatellite-associated sequences in the genome of the offspring of the males exposed to 25 and 50 cGy. The DNA-fingerprints of the offspring of male mice exposed to chronic irradiation with the doses 10 and 25 cGy 15 days before fertilization (at the post-meiotic stage of spermatogenesis) showed an increased frequency of "non-parent bands". The results of the study point to the possibility of transmission to the offspring somatic cells of changes increasing genome instability from male parents exposed to chronic low-level radiation prior to fertilization.

  13. Effect of inulin supplementation in male mice fed with high fat diet on ...

    African Journals Online (AJOL)

    Purpose: To evaluate the preventive and therapeutic effects of inulin supplementation in Naval Medical Research Institute (NMRI) male mice fed with high fat diet. Methods: NMRI male mice (n = 36) were divided into three groups. Control (C1), obese (O1) and experimental mice (E1) were fed during 8 weeks as follows: C1 ...

  14. Male mice ultrasonic vocalizations enhance female sexual approach and hypothalamic kisspeptin neuron activity.

    Science.gov (United States)

    Asaba, Akari; Osakada, Takuya; Touhara, Kazushige; Kato, Masahiro; Mogi, Kazutaka; Kikusui, Takefumi

    2017-08-01

    Vocal communication in animals is important for ensuring reproductive success. Male mice emit song-like "ultrasonic vocalizations (USVs)" when they encounter female mice, and females show approach to the USVs. However, it is unclear whether USVs of male mice trigger female behavioral and endocrine responses in reproduction. In this study, we first investigated the relationship between the number of deliveries in breeding pairs for 4months and USVs syllables emitted from those paired males during 3min of sexual encounter with unfamiliar female mice. There was a positive correlation between these two indices, which suggests that breeding pairs in which males could emit USVs more frequently had more offspring. Further, we examined the effect of USVs of male mice on female sexual behavior. Female mice showed more approach behavior towards vocalizing males than devocalized males. Finally, to determine whether USVs of male mice could activate the neural system governing reproductive function in female mice, the activation of kisspeptin neurons, key neurons to drive gonadotropin-releasing hormone neurons in the hypothalamus, was examined using dual-label immunocytochemistry with cAMP response element-binding protein phosphorylation (pCREB). In the arcuate nucleus (Arc), the number of kisspeptin neurons expressing pCREB significantly increased after exposure to USVs of male as compared with noise exposure group. In conclusion, our results suggest that USVs of male mice promote fertility in female mice by activating both their approaching behavior and central kisspeptin neurons. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Weight cycling enhances adipose tissue inflammatory responses in male mice.

    Directory of Open Access Journals (Sweden)

    Sandra Barbosa-da-Silva

    Full Text Available BACKGROUND: Obesity is associated with low-grade chronic inflammation attributed to dysregulated production, release of cytokines and adipokines and to dysregulated glucose-insulin homeostasis and dyslipidemia. Nutritional interventions such as dieting are often accompanied by repeated bouts of weight loss and regain, a phenomenon known as weight cycling (WC. METHODS: In this work we studied the effects of WC on the feed efficiency, blood lipids, carbohydrate metabolism, adiposity and inflammatory markers in C57BL/6 male mice that WC two or three consecutive times by alternation of a high-fat (HF diet with standard chow (SC. RESULTS: The body mass (BM grew up in each cycle of HF feeding, and decreased after each cycle of SC feeding. The alterations observed in the animals feeding HF diet in the oral glucose tolerance test, in blood lipids, and in serum and adipose tissue expression of adipokines were not recuperated after WC. Moreover, the longer the HF feeding was (two, four and six months, more severe the adiposity was. After three consecutive WC, less marked was the BM reduction during SC feeding, while more severe was the BM increase during HF feeding. CONCLUSION: In conclusion, the results of the present study showed that both the HF diet and WC are relevant to BM evolution and fat pad remodeling in mice, with repercussion in blood lipids, homeostasis of glucose-insulin and adipokine levels. The simple reduction of the BM during a WC is not able to recover the high levels of adipokines in the serum and adipose tissue as well as the pro-inflammatory cytokines enhanced during a cycle of HF diet. These findings are significant because a milieu with altered adipokines in association with WC potentially aggravates the chronic inflammation attributed to dysregulated production and release of adipokines in mice.

  16. Yangjing Capsule Ameliorates Spermatogenesis in Male Mice Exposed to Cyclophosphamide

    Directory of Open Access Journals (Sweden)

    Hongle Zhao

    2015-01-01

    Full Text Available Yangjing capsule (YC, a traditional Chinese compound herbal preparation, has been proven as an effective drug to improve spermatogenesis in clinical practice. However, its pharmacological mechanisms were not fully clarified. This study was designed to investigate the protective effects of YC on spermatogenesis in the mouse model of spermatogenesis dysfunction induced by cyclophosphamide (CP. The administration of YC significantly increased the epididymal index, sperm count, and sperm motility of model mice. Histopathological changes demonstrated that CP caused obvious structural damage to testis, which were reversed by the administration of YC. Results from TUNEL assay showed that treatment with YC dramatically decreased the apoptosis of spermatogenic cell induced by CP. Moreover, YC treatment could inhibit the mRNA and protein expression of Bax to Bcl-2 and also raised expression of AR at both mRNA and protein levels. These data suggest that YC might ameliorate spermatogenesis in male mice exposed to CP through inhibiting the apoptosis of spermatogenic cell and enhancing the actions of testosterone in spermatogenesis.

  17. Early weaning impairs body composition in male mice

    Directory of Open Access Journals (Sweden)

    Maria Carolina Borges

    2009-12-01

    Full Text Available This study aimed to evaluate the effect of early weaning on body composition and on parameters related to nutritional status in mice. The experimental group consisted of male Swiss Webster mice that were weaned early (at postnatal day fourteen and fed an appropriate diet for growing rodents until postnatal day twenty-one (EW group. The control group consisted of male mice breastfed until postnatal day twenty-one (CON group. All animals were sacrificed on the twenty-first day of life. The EW group showed a decrease in liver and muscle protein content and concentration, brain protein concentration, brain DNA content and concentration, as well as liver and muscle protein/RNA ratio (pO presente estudo objetivou avaliar o efeito do desmame precoce sobre a composição corporal e sobre parâmetros indicativos do estado nutricional de camundongos. O grupo experimental consistiu de camundongos Swiss Webster, machos, desmamados precocemente (14º dia de vida e alimentados com ração apropriada para roedores em crescimento até o 21º dia pós-natal (grupo DESM. O grupo controle consistiu de camundongos amamentados até o 21º dia pós-natal (grupo CON. Todos os animais foram sacrificados no 21º dia de vida. O grupo DESM apresentou redução da concentração e conteúdo hepático e muscular de proteínas, da concentração cerebral de proteínas, da concentração e conteúdo cerebral de DNA e da razão proteína/RNA hepática e muscular (p<0,05. Quanto à composição corporal, o grupo DESM apresentou maior conteúdo de umidade, maior percentual de umidade e lipídios e menor conteúdo e percentual de cinzas e proteína na carcaça (p<0,05. Os resultados indicam que o desmame precoce acarreta em prejuízo à composição corporal e a parâmetros indicativos do estado nutricional, o que pode estar relacionado ao retardo do processo de maturação química. Os dados do presente estudo podem contribuir para o entendimento da influência da alimenta

  18. Treatment of Experimental Acute Radiation Disease in Mice with Probiotics, Quinolones, and General Gnotobiological Isolation

    Science.gov (United States)

    1998-09-01

    isolates recovered from the saline- des (5 isolates ), Eubacterium spp . (4), Peptococcus treated mice (14 isolates ) and from the other groups, spp . (2...high bifidobacterial counts were found These Bifidobacterium spp . isolates demonstrated the in the feces of a majority of the mice at day 5 after same...intes- Leuconostoc spp . (26), and Lactobacillus spp . (13). tinal aerobic bacteria in the saline-treated mice were Other frequent isolates (19) were

  19. Strain-specific aggressive behavior of male mice submitted to different husbandry procedures

    NARCIS (Netherlands)

    Loo, P.L.P. van; Meer, E. van der; Kruitwagen, C.L.J.J.; Koolhaas, J.M.; Zutphen, L.F.M. van; Baumans, V.

    Severe aggression within groups of male laboratory mice can cause serious welfare problems. Previous experiments have shown that the transfer of specific olfactory cues during cage cleaning and the provision of nesting material decrease aggression and stress in group-housed male mice. In this study,

  20. Modulation of aggression in male mice : Influence of cage cleaning regime and scent marks

    NARCIS (Netherlands)

    Van Loo, PLP; Kruitwagen, CLJJ; Van Zutphen, LFM; Koolhaas, JM; Baumans, [No Value

    Group housing of male laboratory mice often leads to welfare problems due to aggressive behaviour. From a welfare perspective, individual housing is not a preferred solution to these problems - and so we sought other ways of reducing aggression between male mice. Aggression peaks after disturbances

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

    Science.gov (United States)

    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.

  2. Thyroid states regulate subcellular glucose phosphorylation activity in male mice

    Directory of Open Access Journals (Sweden)

    Flavia Letícia Martins Peçanha

    2017-07-01

    Full Text Available The thyroid hormones (THs, triiodothyronine (T3 and thyroxine (T4, are very important in organism metabolism and regulate glucose utilization. Hexokinase (HK is responsible for the first step of glycolysis, catalyzing the conversion of glucose to glucose 6-phosphate. HK has been found in different cellular compartments, and new functions have been attributed to this enzyme. The effects of hyperthyroidism on subcellular glucose phosphorylation in mouse tissues were examined. Tissues were removed, subcellular fractions were isolated from eu- and hyperthyroid (T3, 0.25 μg/g, i.p. during 21 days mice and HK activity was assayed. Glucose phosphorylation was increased in the particulate fraction in soleus (312.4% ± 67.1, n = 10, gastrocnemius (369.2% ± 112.4, n = 10 and heart (142.2% ± 13.6, n = 10 muscle in the hyperthyroid group compared to the control group. Hexokinase activity was not affected in brain or liver. No relevant changes were observed in HK activity in the soluble fraction for all tissues investigated. Acute T3 administration (single dose of T3, 1.25 μg/g, i.p. did not modulate HK activity. Interestingly, HK mRNA levels remained unchanged and HK bound to mitochondria was increased by T3 treatment, suggesting a posttranscriptional mechanism. Analysis of the AKT pathway showed a 2.5-fold increase in AKT and GSK3B phosphorylation in the gastrocnemius muscle in the hyperthyroid group compared to the euthyroid group. Taken together, we show for the first time that THs modulate HK activity specifically in particulate fractions and that this action seems to be under the control of the AKT and GSK3B pathways.

  3. Isolation of pulmonary artery smooth muscle cells from neonatal mice.

    Science.gov (United States)

    Lee, Keng Jin; Czech, Lyubov; Waypa, Gregory B; Farrow, Kathryn N

    2013-10-19

    Pulmonary hypertension is a significant cause of morbidity and mortality in infants. Historically, there has been significant study of the signaling pathways involved in vascular smooth muscle contraction in PASMC from fetal sheep. While sheep make an excellent model of term pulmonary hypertension, they are very expensive and lack the advantage of genetic manipulation found in mice. Conversely, the inability to isolate PASMC from mice was a significant limitation of that system. Here we described the isolation of primary cultures of mouse PASMC from P7, P14, and P21 mice using a variation of the previously described technique of Marshall et al. that was previously used to isolate rat PASMC. These murine PASMC represent a novel tool for the study of signaling pathways in the neonatal period. Briefly, a slurry of 0.5% (w/v) agarose + 0.5% iron particles in M199 media is infused into the pulmonary vascular bed via the right ventricle (RV). The iron particles are 0.2 μM in diameter and cannot pass through the pulmonary capillary bed. Thus, the iron lodges in the small pulmonary arteries (PA). The lungs are inflated with agarose, removed and dissociated. The iron-containing vessels are pulled down with a magnet. After collagenase (80 U/ml) treatment and further dissociation, the vessels are put into a tissue culture dish in M199 media containing 20% fetal bovine serum (FBS), and antibiotics (M199 complete media) to allow cell migration onto the culture dish. This initial plate of cells is a 50-50 mixture of fibroblasts and PASMC. Thus, the pull down procedure is repeated multiple times to achieve a more pure PASMC population and remove any residual iron. Smooth muscle cell identity is confirmed by immunostaining for smooth muscle myosin and desmin.

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

    Directory of Open Access Journals (Sweden)

    Mariana Angoa-Pérez

    Full Text Available 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.

  5. Individual variation in paternal responses of virgin male California mice (Peromyscus californicus): behavioral and physiological correlates

    NARCIS (Netherlands)

    de Jong, T.R.; Korosi, A.; Harris, B.N.; Perea-Rodriguez, J.P.; Saltzman, W.

    2012-01-01

    California mice Peromyscus californicus are a rodent species in which fathers provide extensive paternal care; however, behavioral responses of virgin males toward conspecific neonates vary from paternal behavior to tolerance to infanticide. Indirect evidence suggests that paternal responses might

  6. Desacyl Ghrelin Decreases Anxiety-like Behavior in Male Mice.

    Science.gov (United States)

    Mahbod, Parinaz; Smith, Eric P; Fitzgerald, Maureen E; Morano, Rachel L; Packard, Benjamin A; Ghosal, Sriparna; Scheimann, Jessie R; Perez-Tilve, Diego; Herman, James P; Tong, Jenny

    2018-01-01

    Ghrelin is a 28-amino acid polypeptide that regulates feeding, glucose metabolism, and emotionality (stress, anxiety, and depression). Plasma ghrelin circulates as desacyl ghrelin (DAG) or, in an acylated form, acyl ghrelin (AG), through the actions of ghrelin O-acyltransferase (GOAT), exhibiting low or high affinity, respectively, for the growth hormone secretagogue receptor (GHSR) 1a. We investigated the role of endogenous AG, DAG, and GHSR1a signaling on anxiety and stress responses using ghrelin knockout (Ghr KO), GOAT KO, and Ghsr stop-floxed (Ghsr null) mice. Behavioral and hormonal responses were tested in the elevated plus maze and light/dark (LD) box. Mice lacking both AG and DAG (Ghr KO) increased anxiety-like behaviors across tests, whereas anxiety reactions were attenuated in DAG-treated Ghr KO mice and in mice lacking AG (GOAT KO). Notably, loss of GHSR1a (Ghsr null) did not affect anxiety-like behavior in any test. Administration of AG and DAG to Ghr KO mice with lifelong ghrelin deficiency reduced anxiety-like behavior and decreased phospho-extracellular signal-regulated kinase phosphorylation in the Edinger-Westphal nucleus in wild-type mice, a site normally expressing GHSR1a and involved in stress- and anxiety-related behavior. Collectively, our data demonstrate distinct roles for endogenous AG and DAG in regulation of anxiety responses and suggest that the behavioral impact of ghrelin may be context dependent. Copyright © 2018 Endocrine Society.

  7. Behavioural strategies of aggressive and non-aggressive male mice in response to inescapable shock

    NARCIS (Netherlands)

    Benus, R.F.; Bohus, B.; Koolhaas, J.M.; Oortmerssen, G.A. van

    1990-01-01

    The effect of exposure to inescapable long-duration shocks of moderate intensity on intershock activity and on subsequent escape or avoidance performance was studied in aggressive and non-aggressive male mice. The activity of the non-aggressive mice was severely suppressed during the inescapable

  8. Therapeutic Effect of Taurine on Gamma Radiation Induced Genetic Injuries in Germ Cells of Male Mice and Their Male Offspring

    International Nuclear Information System (INIS)

    El-Dawy, H.A.; Tawfik, S.S.; El-Khafif, M.A.; Ragab, M.H.

    2005-01-01

    The efficiency of taurine therapy for treatment of male mice exposed to a dose of (3 Gy) whole body gamma irradiation and their male offspring was studied after administration taurine 1% in drinking water post irradiation. Administration of taurine therapy resulted in a significant decrease in the effect of irradiation on chromosomal aberrations in irradiated animals and their male offspring. The efficiency of taurine as radio therapeutic agent is greatly dependent on its chemical properties as strong oxidants scavenger and biological activities as osmoregulator and membrane stabilizer. The probable mechanism of taurine therapy was discussed

  9. Differential influence of social versus isolate housing on vicarious fear learning in adolescent mice.

    Science.gov (United States)

    Panksepp, Jules B; Lahvis, Garet P

    2016-04-01

    Laboratory rodents can adopt the pain or fear of nearby conspecifics. This phenotype conceptually lies within the domain of empathy, a bio-psycho-social process through which individuals come to share each other's emotion. Using a model of cue-conditioned fear, we show here that the expression of vicarious fear varies with respect to whether mice are raised socially or in solitude during adolescence. The impact of the adolescent housing environment was selective: (a) vicarious fear was more influenced than directly acquired fear, (b) "long-term" (24-h postconditioning) vicarious fear memories were stronger than "short-term" (15-min postconditioning) memories in socially reared mice whereas the opposite was true for isolate mice, and (c) females were more fearful than males. Housing differences during adolescence did not alter the general mobility of mice or their vocal response to receiving the unconditioned stimulus. Previous work with this mouse model underscored a genetic influence on vicarious fear learning, and the present study complements these findings by elucidating an interaction between the adolescent social environment and vicarious experience. Collectively, these findings are relevant to developing models of empathy amenable to mechanistic exploitation in the laboratory. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  10. First Chemical Evaluation and Toxicity of Casinga-cheirosa to Balb-c Male Mice

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    Dirce M. Estork

    2014-04-01

    Full Text Available Laetia suaveolens, known as “casinga-cheirosa”, crude extract EB719 has previously shown cytotoxic activity against prostate cancer and squamous cell carcinoma. For the first time, seven molecules were isolated from its apolar—α-tocopherol (1 and sitosterol (2—and polar—3-O-caffeoylquinic acid (3, 4-O-caffeoylquinic acid (4, 5-O-feruloylquinic acid (5, hyperoside (6, and isoquercitrin (7—fractions. Acute toxicity was determined in a two-stage experiment: (1 a reduced number of Balb-c male mice received 5000 mg/kg of EB719 to allow evaluation of general activity and other 27 parameters, plus death, up to the establishment of non-lethal dose (NLD, as well as lethal dose 50% (LD50; (2 NLD was administered and diazepam introduced as reference drug. EB719 showed LD50 = 178.0 mg/kg, and NLD 156.3 mg/kg. In stage one EB719 did not influence general activity, but provoked impairment in grasp reflexes, tail squeeze and breathing; piloerection and cyanosis were increased. In stage two, alterations occurred in auricular reflex, piloerection and breathing after diazepam administration, but not in response to EB719. Intestinal hemorrhage caused by local bleeding was observed after necropsy, and may be the main cause of animals’ death other than a systemic effect of the extract. Although the isolated compounds are biologically and pharmacologically active in both men and animal systems, it is premature to relate their occurrence in EB719 to the observed intestine hemorrhage in mice.

  11. Comparison of the course of infection with Giardia muris in male and female mice.

    Science.gov (United States)

    Daniels, C W; Belosevic, M

    1995-01-01

    The infection with Giardia muris in male and female C57BL/6 mice was characterized by enumerating cyst release in the feces and trophozoite burden in the small intestine. Cyst release differed between males and females during the course of the primary and challenge infections. Males and females released similar numbers of cysts in the feces during the acute phase of the infection. However, the trophozoite burden was significantly higher in males during the same period. Males released cysts in their feces longer than females and trophozoites present in their intestines for a longer period than females. From day 18 of infection the females did not release cysts in their feces, while males continued to do so for at least 60 days. Thus, distinct differences exist between male and female mice in their ability to harbor and eliminate this intestinal parasite.

  12. Androgen receptor disruption increases the osteogenic response to mechanical loading in male mice

    NARCIS (Netherlands)

    Callewaert, F.; Bakker, A.; Schrooten, J.; Van Meerbeek, B.; Verhoeven, G.; Boonen, S.; Vanderschueren, D.

    2010-01-01

    In female mice, estrogen receptor-alpha (ERα) mediates the anabolic response of bone to mechanical loading. Whether ERα plays a similar role in the male skeleton and to what extent androgens and androgen receptor (AR) affect this response in males remain unaddressed. Therefore, we studied the

  13. Effect of Fenbendazole on Three Behavioral Tests in Male C57BL/6N Mice

    OpenAIRE

    Gadad, Bharathi S; Daher, João P L; Hutchinson, Eric K; Brayton, Cory F; Dawson, Ted M; Pletnikov, Mikhail V; Watson, Julie

    2010-01-01

    Pinworms are highly contagious parasites of laboratory rodents that often are treated with fenbendazole. To our knowledge, the effect of fenbendazole at therapeutic dosages on behavioral tests in mice has not been evaluated. Here we studied 6-wk-old male C57BL/6N mice. We compared the behavior of control mice (fed regular diet) with 3 groups of mice treated with dietary fenbendazole. Treatment groups were 4 wk of fenbendazole, 2 wk of fenbendazole followed by 2 wk of regular diet, and 2 wk of...

  14. Dominant lethal mutations in male mice fed γ-irradiated diet

    International Nuclear Information System (INIS)

    Chauhan, P.S.; Aravindakshan, M.; Aiyer, A.S.; Sundaram, K.

    1975-01-01

    Three groups of Swiss male mice were fed a stock ration of an unirradiated or irradiated (2.5 Mrad) test diet for 8 wk. After the feeding period, the males were mated with groups of untreated female mice for 4 consecutive weeks. The females were autopsied at mid-term pregnancy for evaluation of dominant lethal mutations. Numbers of dead implantations, including deciduomas and dead embryos, showed no significant differences among the different groups, thus producing no evidence of any induced post-implantation lethality in mice fed on irradiated diet. Similarly, there was no indication of preimplantation lethality, since implantation rates remained comparable among different groups. Consumption of irradiated diet did not affect the fertility of mice. Total pre- and post-implantation loss, as indicated by the numbers of live implantations remained comparable among all the groups of mice. (author)

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

    Science.gov (United States)

    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.

  16. Effects of leached components from a hybrid resin composite on the reproductive system of male mice

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    Taher Akbari Saeed

    2012-01-01

    Full Text Available Background and Aims: There is concern that leached components from dental composites may cause adverse changes in the reproductive health. This study aimed to assess the effects of leached components from a hybrid resin composite on the reproductive system of male mice.Materials and Methods: In the present animal study, twenty adult Syrian male mice were divided into two groups of 10 mice each. In the test group, components which leached from samples made from Filtek Z250 resin composite into 75% ethanol were daily administered to the mice for 28 days. In the control group, the procedure was repeated in the same way as the test group but without placing composite samples in the solution. Then, the body weight, weights of paired testes, Gonado Somatic Index, sperm viability, sperm motility, epididymal sperm reserve and daily sperm production were recorded. Four male mice in each group were mated with untreated female mice for 10 days. After that, the number of pregnant females and number of infants were recorded. The data were analyzed using repeated measures ANOVA, Chi-square test and t-test.Results: There was a significant reduction in the sperm viability and sperm motility of male mice in the test group compared to the control group (P=0.001. There was no any significant differences in other parameters between two groups (P>0.05.Conclusion: This study showed that the leached components from resin composites cannot cause infertility but they could potentially cause some adverse effects on the reproductive system of male mice.

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

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    Jonathan eChabout

    2015-04-01

    Full Text Available In 2005 Holy & 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.

  18. Chronic nicotine differentially alters spontaneous recovery of contextual fear in male and female mice.

    Science.gov (United States)

    Tumolo, Jessica M; Kutlu, Munir Gunes; Gould, Thomas J

    2018-04-02

    Post-traumatic stress disorder (PTSD) is a devastating disorder with symptoms such as flashbacks, hyperarousal, and avoidance of reminders of the traumatic event. Exposure therapy, which attempts to extinguish fear responses, is a commonly used treatment for PTSD but relapse following successful exposure therapy is a frequent problem. In rodents, spontaneous recovery (SR), where extinguished fear responses resurface following extinction treatment, is used as a model of fear relapse. Previous studies from our lab showed that chronic nicotine impaired fear extinction and acute nicotine enhanced SR of contextual fear in adult male mice. In addition, we showed that acute nicotine's effects were specific to SR as acute nicotine did not affect recall of contextual fear conditioning in the absence of extinction. However, effects of chronic nicotine administration on SR are not known. Therefore, in the present study, we investigated if chronic nicotine administration altered SR or recall of contextual fear in adult male and female C57BL/6J mice. Our results showed that chronic nicotine significantly enhanced SR in female mice and significantly decreased SR in males. Chronic nicotine had no effect on recall of contextual fear in males or females. Female sham mice also had significantly less baseline SR than male sham mice. Overall, these results demonstrate sex differences in SR of fear memories and that chronic nicotine modulates these effects on SR but nicotine does not alter recall of contextual fear. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Male mice with deleted Wolframin (Wfs1 gene have reduced fertility

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    Aunapuu Marina

    2009-08-01

    Full Text Available Abstract Background Wolfram Syndrome (WS is an autosomal recessive disorder characterised by non-autoimmune diabetes mellitus, optic atrophy, cranial diabetes insipidus and sensorineural deafness. Some reports have described hypogonadism in male WS patients. The aim of our study was to find out whether Wfs1 deficient (Wfs1KO male mice have reduced fertility and, if so, to examine possible causes. Methods Wfs1KO mice were generated by homologous recombination. Both Wfs1KO and wild type (wt male mice were mated with wt female mice. The number of litters and the number of pups were counted and pregnancy rates calculated. The motility and morphology of the sperm and the histology of testes were analysed. Serum testosterone and FSH concentrations were also measured. Results The pregnancy rate in wt females mated with Wfs1KO males was significantly lower than in the control group (15% vs. 32%; p Conclusion The impaired fertility of Wfs1KO male mice is most likely due to changes in sperm morphology and reduced number of spermatogenic cells. The exact mechanism through which the Wfs1 gene influences sperm morphology needs to be clarified in further studies.

  20. Dopamine D5 receptor modulates male and female sexual behavior in mice.

    Science.gov (United States)

    Kudwa, A E; Dominguez-Salazar, E; Cabrera, D M; Sibley, D R; Rissman, E F

    2005-07-01

    Dopamine exerts its actions through at least five receptor (DAR) isoforms. In female rats, D5 DAR may be involved in expression of sexual behavior. We used a D5 knockout (D5KO) mouse to assess the role of D5 DAR in mouse sexual behavior. Both sexes of D5KO mice are fertile and exhibit only minor disruptions in exploratory locomotion, startle, and prepulse inhibition responses. This study was conducted to characterize the sexual behavior of male and female D5KO mice relative to their WT littermates. Female WT and D5KO littermates were ovariectomized and given a series of sexual behavior tests after treatment with estradiol benzoate (EB) and progesterone (P). Once sexual performance was optimal the dopamine agonist, apomorphine (APO), was substituted for P. Male mice were observed in pair- and trio- sexual behavior tests. To assess whether the D5 DAR is involved in rewarding aspects of sexual behavior, WT and D5KO male mice were tested for conditioned place preference. Both WT and D5KO females can display receptivity after treatment with EB and P, but APO was only able to facilitate receptivity in EB-primed WT, not in D5KO, mice. Male D5KO mice display normal masculine sexual behavior in mating tests. In conditioned preference tests, WT males formed a conditioned preference for context associated with either intromissions alone or ejaculation as the unconditioned stimulus. In contrast, D5KO males only showed a place preference when ejaculation was paired with the context. In females, the D5 DAR is essential for the actions of dopamine on receptivity. In males, D5 DAR influences rewarding aspects of intromissions. Taken together, the work suggests that the D5 receptor mediates dopamine's action on sexual behavior in both sexes, perhaps via a reward pathway.

  1. Effects of social isolation, re-socialization and age on cognitive and aggressive behaviors of Kunming mice and BALB/c mice.

    Science.gov (United States)

    An, Dong; Chen, Wei; Yu, De-Qin; Wang, Shi-Wei; Yu, Wei-Zhi; Xu, Hong; Wang, Dong-Mei; Zhao, Dan; Sun, Yi-Ping; Wu, Jun-Cheng; Tang, Yi-Yuan; Yin, Sheng-Ming

    2017-05-01

    Both Kunming (KM) mice and BALB/c mice have been widely used as rodent models to investigate stress-associated mental diseases. However, little is known about the different behaviors of KM mice and BALB/c mice after social isolation, particularly cognitive and aggressive behaviors. In this study, the behaviors of KM and BALB/c mice isolated for 2, 4 and 8 weeks and age-matched controls were evaluated using object recognition, object location and resident-intruder tests. The recovery of behavioral deficits by re-socialization was also examined for the isolated mice in adolescence. Our study showed that isolation for 2, 4 and 8 weeks led to cognitive deficits and increased aggressiveness for both KM and BALB/c mice. An important finding is that re-socialization could completely recover spatial/non-spatial cognitive deficits resulted from social isolation for both KM and BALB/c mice. In addition, age only impacted aggressiveness of KM mice. Moreover, isolation duration showed different impacts on cognitive and aggressive behaviors for both KM and BALB/c mice. Furthermore, BALB/c mice showed weak spatial/non-spatial memory and low aggressiveness when they were at the same age and isolation duration, compared to KM mice. In conclusion, KM mice and BALB/c mice behaved characteristically under physiology and isolation conditions. © 2016 Japanese Society of Animal Science.

  2. Reduced bone mass and muscle strength in male 5α-reductase type 1 inactivated mice.

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    Sara H Windahl

    Full Text Available Androgens are important regulators of bone mass but the relative importance of testosterone (T versus dihydrotestosterone (DHT for the activation of the androgen receptor (AR in bone is unknown. 5α-reductase is responsible for the irreversible conversion of T to the more potent AR activator DHT. There are two well established isoenzymes of 5α-reductase (type 1 and type 2, encoded by separate genes (Srd5a1 and Srd5a2. 5α-reductase type 2 is predominantly expressed in male reproductive tissues whereas 5α-reductase type 1 is highly expressed in liver and moderately expressed in several other tissues including bone. The aim of the present study was to investigate the role of 5α-reductase type 1 for bone mass using Srd5a1⁻/⁻ mice. Four-month-old male Srd5a1⁻/⁻ mice had reduced trabecular bone mineral density (-36%, p<0.05 and cortical bone mineral content (-15%, p<0.05 but unchanged serum androgen levels compared with wild type (WT mice. The cortical bone dimensions were reduced in the male Srd5a1⁻/⁻ mice as a result of a reduced cortical periosteal circumference compared with WT mice. T treatment increased the cortical periosteal circumference (p<0.05 in orchidectomized WT mice but not in orchidectomized Srd5a1⁻/⁻ mice. Male Srd5a1⁻/⁻ mice demonstrated a reduced forelimb muscle grip strength compared with WT mice (p<0.05. Female Srd5a1⁻/⁻ mice had slightly increased cortical bone mass associated with elevated circulating levels of androgens. In conclusion, 5α-reductase type 1 inactivated male mice have reduced bone mass and forelimb muscle grip strength and we propose that these effects are due to lack of 5α-reductase type 1 expression in bone and muscle. In contrast, the increased cortical bone mass in female Srd5a1⁻/⁻ mice, is an indirect effect mediated by elevated circulating androgen levels.

  3. Cytokine gene expression and pathology in mice experimentally infected with different isolates of Trypanosoma evansi.

    Science.gov (United States)

    Krishnamoorthy, P; Sengupta, P P; Das, Sangita; Ligi, M; Shome, B R; Rahman, H

    2016-11-01

    Aim of the present study was to assess the cytokine gene expression in liver, kidney and spleen and histopathological changes in mice infected with buffalo and dog isolates of Trypanosoma evansi. Forty-four Swiss albino mice was divided into eleven groups of four mice each and injected subcutaneously with 1 × 10 5 trypanosomes of buffalo and dog isolate to twenty mice each, four mice served as control. Mice were examined for clinical signs, blood smear for trypanosome counts. Blood for PCR, liver, kidney, spleen, heart, lung, testis and abdominal muscle for histopathology and liver, kidney, spleen for cytokine gene expression studies, were collected. Mice showed dullness, lethargy, hunched back, sluggish movements on D4 and D5 in buffalo and dog isolate, respectively. Parasite count in blood varied between the two isolates of T. evansi. By PCR, trypanosome DNA was detected on D1 and D2 for buffalo and dog isolate, respectively. Splenomegaly was observed in mice infected with buffalo isolate but not with dog isolate. Histopathological changes were observed in liver, kidney, spleen and heart of mice but no changes in testis and abdominal muscles. Blood vessels of liver, heart, lung showed presence of trypanosomes in mice infected with buffalo isolate but not for dog isolate. Cytokine gene expression of IL-2, IL-4, IL-6, IL-12, TNF-α and IFN-γ increased in liver, kidney and spleen in both these isolates. However, the buffalo isolate exhibited pronounced increase in cytokine gene expression when compare to dog isolate of T. evansi. Anti-inflammatory cytokine gene IL-10 showed 50-60 and 10-20 folds increment in buffalo and dog isolates, respectively. This is the first report of IL-4, IL-6, IL-10 and IL-12 cytokine changes in mice infected with T. evansi. A variation in pathogenicity between buffalo and dog isolates was recorded indicating buffalo isolate of T. evansi remained more pathogenic in mice. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Effect of Vomeronasal Organ Removal From Male Mice on Their Preference for and Neural Fos Responses to Female Urinary Odors

    OpenAIRE

    Pankevich, Diana E.; Cherry, James A.; Baum, Michael J.

    2006-01-01

    Four experiments were conducted to determine whether vomeronasal organ (VNO) inputs in male mice mediate the rewarding properties of estrous female urinary odors. Sexually naive male mice with either an intact (VNOi) or lesioned (VNOx) VNO preferred to investigate female urine over water in Y-maze tests. Subsequently, VNOi males ran significantly more quickly and remained in nasal contact longer with estrous female urine than with male urine, whereas VNOx males investigated these odors equall...

  5. Quinine controls body weight gain without affecting food intake in male C57BL6 mice

    Directory of Open Access Journals (Sweden)

    Cettour-Rose Philippe

    2013-02-01

    Full Text Available Abstract Background Quinine is a natural molecule commonly used as a flavouring agent in tonic water. Diet supplementation with quinine leads to decreased body weight and food intake in rats. Quinine is an in vitro inhibitor of Trpm5, a cation channel expressed in taste bud cells, the gastrointestinal tract and pancreas. The objective of this work is to determine the effect of diet supplementation with quinine on body weight and body composition in male mice, to investigate its mechanism of action, and whether the effect is mediated through Trpm5. Results Compared with mice consuming AIN, a regular balanced diet, mice consuming AIN diet supplemented with 0.1% quinine gained less weight (2.89 ± 0.30 g vs 5.39 ± 0.50 g and less fat mass (2.22 ± 0.26 g vs 4.33 ± 0.43 g after 13 weeks of diet, and had lower blood glucose and plasma triglycerides. There was no difference in food intake between the mice consuming quinine supplemented diet and those consuming control diet. Trpm5 knockout mice gained less fat mass than wild-type mice. There was a trend for a diet-genotype interaction for body weight and body weight gain, with the effect of quinine less pronounced in the Trpm5 KO than in the WT background. Faecal weight, energy and lipid contents were higher in quinine fed mice compared to regular AIN fed mice and in Trpm5 KO mice compared to wild type mice. Conclusion Quinine contributes to weight control in male C57BL6 mice without affecting food intake. A partial contribution of Trpm5 to quinine dependent body weight control is suggested.

  6. Male aromatase-knockout mice exhibit normal levels of activity, anxiety and "depressive-like" symptomatology.

    Science.gov (United States)

    Dalla, C; Antoniou, K; Papadopoulou-Daifoti, Z; Balthazart, J; Bakker, J

    2005-09-08

    It is well known that estradiol derived from neural aromatization of testosterone plays a crucial role in the development of the male brain and the display of sexual behaviors in adulthood. It was recently found that male aromatase knockout mice (ArKO) deficient in estradiol due to a mutation in the aromatase gene have general deficits in coital behavior and are sexually less motivated. We wondered whether these behavioral deficits of ArKO males could be related to changes in activity, exploration, anxiety and "depressive-like" symptomatology. ArKO and wild type (WT) males were subjected to open field (OF), elevated plus maze (EPM), and forced swim tests (FST), after being exposed or not to chronic mild stress (CMS). CMS was used to evaluate the impact of chronic stressful procedures and to unveil possible differences between genotypes. There was no effect of genotype on OF, EPM and FST behavioral parameters. WT and ArKO mice exposed to CMS or not exhibited the same behavioral profile during these three types of tests. However, all CMS-exposed mice (ArKO and WT) spent less time in the center of the EPM. Additionally, floating duration measured in the FST increased between two tests in both WT and ArKO mice, though that increase was less prominent in mice previously subjected to CMS than in controls. Therefore, both ArKO and WT males displayed the same behavior and had the same response to CMS however CMS exposure slightly modified the behavior displayed by mice of both genotypes in the FST and EPM paradigms. These results show that ArKO males display normal levels of activity, exploration, anxiety and "depressive-like" symptomatology and thus their deficits in sexual behavior are specific in nature and do not result indirectly from other behavioral changes.

  7. Juvenile spermatogonial depletion (jsd): a genetic defect of germ cell proliferation of male mice.

    Science.gov (United States)

    Beamer, W G; Cunliffe-Beamer, T L; Shultz, K L; Langley, S H; Roderick, T H

    1988-05-01

    Adult C57BL/6J male mice homozygous for the mutant gene, juvenile spermatogonial depletion (jsd/jsd), show azoosper4ia and testes reduced to one-third normal size, but are otherwise phenotypically normal. In contrast, adult jsd/jsd females are fully fertile. This feature facilitated mapping the jsd gene to the centromeric end of chromosome 1; the gene order is jsd-Isocitrate dehydrogenase-1 (Idh-1)-Peptidase-3 (Pep-3). Analysis of testicular histology from jsd/jsd mice aged 3-10 wk revealed that these mutant mice experience one wave of spermatogenesis, but fail to continue mitotic proliferation of type A spermatogonial cells at the basement membrane. As a consequence, histological sections of testes from mutant mice aged 8-52 wk showed tubules populated by modest numbers of Sertoli cells, with only an occasional spermatogonial cell. Some sperm with normal morphology and motility were observed in epididymides of 6.5- but not in 8-wk or older mutants. Treatment with retinol failed to alter the loss of spermatogenesis in jsd/jsd mice. Analyses of serum hormones of jsd/jsd males showed that testosterone levels were normal at all ages--a finding corroborated by normal seminal vesicle and vas deferens weights, whereas serum follicle-stimulating hormone levels were significantly elevated in mutant mice from 4 to 20 wk of age. We hypothesize the jsd/jsd male may be deficient in proliferative signals from Sertoli cells that are needed for spermatogenesis.

  8. Sclerostin Blockade and Zoledronic Acid Improve Bone Mass and Strength in Male Mice With Exogenous Hyperthyroidism.

    Science.gov (United States)

    Tsourdi, Elena; Lademann, Franziska; Ominsky, Michael S; Rijntjes, Eddy; Köhrle, Josef; Misof, Barbara M; Roschger, Paul; Klaushofer, Klaus; Hofbauer, Lorenz C; Rauner, Martina

    2017-11-01

    Hyperthyroidism in mice is associated with low bone mass, high bone turnover, and high concentrations of sclerostin, a potent Wnt inhibitor. Here, we explored the effects of either increasing bone formation with sclerostin antibodies (Scl-Ab) or reducing bone turnover with bisphosphonates on bone mass and strength in hyperthyroid mice. Twelve-week-old C57BL/6 male mice were rendered hyperthyroid using l-thyroxine (T4; 1.2 µg/mL added to the drinking water) and treated with 20 mg/kg Scl-Ab twice weekly or 100 µg/kg zoledronic acid (ZOL) once weekly or phosphate-buffered saline for 4 weeks. Hyperthyroid mice displayed a lower trabecular bone volume at the spine (-42%, P hyperthyroid mice increased trabecular bone volume at the spine by threefold and twofold, respectively. Serum bone formation and resorption markers were increased in hyperthyroid mice and suppressed by treatment with ZOL but not Scl-Ab. Trabecular bone stiffness at the lumbar vertebra was 63% lower in hyperthyroid mice (P hyperthyroidism, was increased by Scl-Ab by 71% and ZOL by 22% (both P hyperthyroid mice was restored by treatment with Scl-Ab and ZOL. Thus, bone-forming and antiresorptive drugs prevent bone loss in hyperthyroid mice via different mechanisms. Copyright © 2017 Endocrine Society.

  9. Functions of TAM RTKs in regulating spermatogenesis and male fertility in mice.

    Science.gov (United States)

    Chen, Yongmei; Wang, Huizhen; Qi, Nan; Wu, Hui; Xiong, Weipeng; Ma, Jing; Lu, Qingxian; Han, Daishu

    2009-10-01

    Mice lacking TYRO3, AXL and MER (TAM) receptor tyrosine kinases (RTKs) are male sterile. The mechanism of TAM RTKs in regulating male fertility remains unknown. In this study, we analyzed in more detail the testicular phenotype of TAM triple mutant (TAM(-/-)) mice with an effort to understand the mechanism. We demonstrate that the three TAM RTKs cooperatively regulate male fertility, and MER appears to be more important than AXL and TYRO3. TAM(-/-) testes showed a progressive loss of germ cells from elongated spermatids to spermatogonia. Young adult TAM(-/-) mice exhibited oligo-astheno-teratozoospermia and various morphological malformations of sperm cells. As the mice aged, the germ cells were eventually depleted from the seminiferous tubules. Furthermore, we found that TAM(-/-) Sertoli cells have an impaired phagocytic activity and a large number of differentially expressed genes compared to wild-type controls. By contrast, the function of Leydig cells was not apparently affected by the mutation of TAM RTKs. Therefore, we conclude that the suboptimal function of Sertoli cells leads to the impaired spermatogenesis in TAM(-/-) mice. The results provide novel insight into the mechanism of TAM RTKs in regulating male fertility.

  10. Paternal responsiveness is associated with, but not mediated by reduced neophobia in male California mice (Peromyscus californicus).

    Science.gov (United States)

    Chauke, Miyetani; de Jong, Trynke R; Garland, Theodore; Saltzman, Wendy

    2012-08-20

    Hormones associated with pregnancy and parturition have been implicated in facilitating the onset of maternal behavior via reductions in neophobia, anxiety, and stress responsiveness. To determine whether the onset of paternal behavior has similar associations in biparental male California mice (Peromyscus californicus), we compared paternal responsiveness, neophobia (novel-object test), and anxiety-like behavior (elevated plus maze, EPM) in isolated virgins (housed alone), paired virgins (housed with another male), expectant fathers (housed with pregnant pairmate), and new fathers (housed with pairmate and pups). Corticotropin-releasing hormone (CRH) and Fos immunoreactivity (IR) were quantified in brain tissues following exposure to a predator-odor stressor or under baseline conditions. New fathers showed lower anxiety-like behavior than expectant fathers and isolated virgins in EPM tests. In all housing conditions, stress elevated Fos-IR in the hypothalamic paraventricular nucleus (PVN). Social isolation reduced overall (baseline and stress-induced) Fos- and colocalized Fos/CRH-IR, and increased overall CRH-IR, in the PVN. In the central nucleus of the amygdala, social isolation increased stress-induced CRH-IR and decreased stress-induced activation of CRH neurons. Across all housing conditions, paternally behaving males displayed more anxiety-related behavior than nonpaternal males in the EPM, but showed no differences in CRH- or Fos-IR. Finally, the latency to engage in paternal behavior was positively correlated with the latency to approach a novel object. These results suggest that being a new father does not reduce anxiety, neophobia, or neural stress responsiveness. Low levels of neophobia, however, were associated with, but not necessary for paternal responsiveness. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Potential contribution of progesterone receptors to the development of sexual behavior in male and female mice.

    Science.gov (United States)

    Desroziers, Elodie; Brock, Olivier; Bakker, Julie

    2017-04-01

    We previously showed that estradiol can have both defeminizing and feminizing effects on the developing mouse brain. Pre- and early postnatal estradiol defeminized the ability to show lordosis in adulthood, whereas prepubertal estradiol feminized this ability. Furthermore, we found that estradiol upregulates progesterone receptors (PR) during development, inducing both a male-and female-typical pattern of PR expression in the mouse hypothalamus. In the present study, we took advantage of a newly developed PR antagonist (ZK 137316) to determine whether PR contributes to either male- or female-typical sexual differentiation. Thus groups of male and female C57Bl/6j mice were treated with ZK 137316 or OIL as control: males were treated neonatally (P0-P10), during the critical period for male sexual differentiation, and females were treated prepubertally (P15-P25), during the critical period for female sexual differentiation. In adulthood, mice were tested for sexual behavior. In males, some minor effects of neonatal ZK treatment on sexual behavior were observed: latencies to the first mount, intromission and ejaculation were decreased in neonatally ZK treated males; however, this effect disappeared by the second mating test. By contrast, female mice treated with ZK during the prepubertal period showed significantly less lordosis than OIL-treated females. Mate preferences were not affected in either males or females treated with ZK during development. Taken together, these results suggest a role for PR and thus perhaps progesterone in the development of lordosis behavior in female mice. By contrast, no obvious role for PR can be discerned in the development of male sexual behavior. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Reproductive effects of lipid soluble components of Syzygium aromaticum flower bud in male mice

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    Raghav Kumar Mishra

    2013-01-01

    Full Text Available Background: The flower buds of Syzygium aromaticum (clove have been used in indigenous medicines for the treatment of male sexual disorders in Indian subcontinent. Objective: To evaluate the effect of Syzygium aromaticum flower bud on male reproduction, using Parkes (P strain mice as animal model. Materials and Methods: Mice were orally administered lipid soluble components of Syzygium aromaticum flower bud in doses of 15, 30, and 60 mg/kg body weight for 35 days, and several male reproductive endpoints were evaluated. Results: Treatment with lower dose (15 mg of Syzygium increased the motility of sperm and stimulated the secretory activities of epididymis and seminal vesicle, while higher doses (30 and 60 mg had adverse effects on sperm dynamics of cauda epididymidis and on the secretory activities of epididymis and seminal vesicle. Libido was not affected in treated males; however, a significant decrease in litter in females sired by males treated with higher doses of Syzygium was recorded. Conclusion: Treatment with Syzygium aromaticum flower bud causes dose-dependent biphasic effect on male reproductive indices in P mice; lower dose of Syzygium appears stimulatory, while the higher doses have adverse effect on male reproduction. The results suggest that the lower dose of Syzygium may have androgenic effect, but further studies are needed to support this contention.

  13. Behavioral and endocrine consequences of placentophagia in male California mice (Peromyscus californicus).

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    Perea-Rodriguez, Juan P; Zhao, Meng; Harris, Breanna N; Raqueno, Joel; Saltzman, Wendy

    2018-05-01

    Ingestion of placenta by mammalian mothers can lead to changes in pain sensitivity, hormone levels, and behavioral responses to newborns. In some biparental mammals, males, in addition to females, ingest placenta when their offspring are born. In the monogamous, biparental California mouse (Peromyscus californicus), males first become attracted to placenta when cohabitating with their pregnant mate, and virgin males administered placenta are less neophobic than males given oil vehicle. In this study, we investigated the effects of placentophagia on pain sensitivity, anxiety-like behavior, behavioral responses to pups, and circulating corticosterone levels of both breeding and nonbreeding male California mice. We orally administered either a conspecific placenta or oil vehicle to male mice from three reproductive conditions (first-time fathers, first-time expectant fathers, and virgin males) and tested their pain sensitivity 1 h later, as well as their exploratory behavior and paternal responsiveness in an open field 4 h post-treatment. We measured plasma corticosterone immediately after the open-field test. We found that placenta-treated males, independent of reproductive condition, traveled significantly longer distances in the open field than males treated with oil, indicative of lower anxiety. Additionally, fathers had shorter latencies to approach and to care for pups (i.e., huddling and licking pups), and spent more time engaging in these behaviors, than did age-matched expectant fathers and virgin males, independent of treatment. We found no effect on plasma corticosterone levels or pain sensitivity as a result of either treatment or reproductive condition. These findings indicate that placenta ingestion decreases anxiety-related behaviors in male California mice, but might not influence pain sensitivity, paternal responsiveness, or plasma corticosterone concentrations. Published by Elsevier Inc.

  14. Spatial learning and memory in male mice with altered growth hormone action.

    Science.gov (United States)

    Basu, Amrita; McFarlane, Hewlet G; Kopchick, John J

    2017-07-01

    Growth hormone (GH) has a significant influence on cognitive performance in humans and other mammals. To understand the influence of altered GH action on cognition, we assessed spatial learning and memory using a Barnes maze (BM) comparing twelve-month old, male, bovine GH (bGH) and GH receptor antagonist (GHA) transgenic mice and their corresponding wild type (WT) littermates. During the acquisition training period in the BM, bGH mice showed increased latency, traveled longer path lengths and made more errors to reach the target than WT mice, indicating significantly poorer learning. Short-term memory (STM) and long-term memory (LTM) trials showed significantly suppressed memory retention in bGH mice when compared to the WT group. Conversely, GHA mice showed significantly better learning parameters (latency, path length and errors) and increased use of an efficient search strategy than WT mice. Our study indicates a negative impact of GH excess and a beneficial effect of the inhibition of GH action on spatial learning and memory and, therefore, cognitive performance in male mice. Further research to elucidate GH's role in brain function will facilitate identifying therapeutic applications of GH or GHA for neuropathological and neurodegenerative conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Expression of GAT1 in male reproductive system and its effects on reproduction in mice.

    Science.gov (United States)

    Zhang, JinFu; Gui, YaPing; Yuan, Tao; Bian, CuiDong; Guo, LiHe

    2009-12-01

    The present study was carried out to identify GABA (gamma-aminobutyric acid) transport protein I (GAT1) in male reproductive organs and to study the effect of GAT1 overexpression on the male reproductive system in GAT1 transgenic mice (TG). Expression and location of GAT1 in testes, epididymis, and sperm of wild-type (WT) mice were identified by immunohistochemistry and western-blot. Histological changes of testes, epididymis, and sperm of transgenic mice overexpressing GAT1 were detected by immunofluorenscent staining and haematoxylin and eosin (HE) staining. GAT1 expression was detected in the testes, epididymis, and sperm of non-transgenic mice. Vacuolization and deformity of spermatogenic cells were observed in the transgenic mice, but the epididymis was unremarkable. Immunofluorenscent staining showed that the number of diastrophic and decapitated sperm increased significantly in transgenic mice to 46.9% from 7.3% in nontransgenic mice. These results suggest that abnormal expression of GAT1 could result in spermiogenesis function injury, sperm paramorphia and dysgenesis.

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

    Science.gov (United States)

    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. © 2016 Society for Endocrinology.

  17. Synaptonemal complex analysis of X-7 translocations in male mice

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    Ashley, T. (Univ. of Tennessee, Knoxville); Russell, L.B.; Cacheiro, N.L.A.

    1982-01-01

    The synaptonemal complexes of surface-spread spermatocytes of mice heterozygous for one of two reciprocal translations (R3 and R5) between the X and chromosome 7 have been examined by light and electron microscopy (EM). The break points of R3 were determined to be at 70% of chromosome 7, as measured from the centromere, and at 22% of the X. Translocation quadrivalents were formed almost exclusively. The break points of R5 were at 21% of chromosome 7 as measured from the centromere, and at 83% of the X. There was little indication that the break in the X interfered with sex-chromosome synapis between the 7X and Y. Univalent Y's were not observed in R3, and only seldom observed (8-14%) in R5. However, in contrast to R3, R5 formed quadrivalents relatively rarely (20% in the EM study of 100 nuclei), and hetermorphic bivalents of 7X-Y and X7-7 quite frequently (72%). Possible causes of this high bivalent frequency are discussed. Light-microsope (LM) analysis alone was found to be inadequate for interpreting synaptic configurations (quadrivalents vs. bivalents) in R5. The LM analysis was further complicated by the occurrence of nonhomologous synapsis in the heteromorphic bivalents of R5, a phenomonon easily recognized and interpreted in the EM portion of the study.

  18. Chronic High Fat Diet Consumption Impairs Metabolic Health of Male Mice.

    Science.gov (United States)

    Morselli, Eugenia; Criollo, Alfredo; Rodriguez-Navas, Carlos; Clegg, Deborah J

    We show that chronic high fat diet (HFD) feeding affects the hypothalamus of male but not female mice. In our study we demonstrate that palmitic acid and sphingolipids accumulate in the central nervous system of HFD-fed males. Additionally, we show that HFD-feeding reduces proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) thus reducing estrogen receptor α (ERα) and driving hypothalamic inflammation in male but not female mice. Hypothalamic inflammation correlates with markers of metabolic dysregulation as indicated by dysregulation in glucose intolerance and myocardial function. Lastly, we demonstrate that there are blockages in mitophagy and lipophagy in hypothalamic tissues in males. Our data suggest there is a sexually dimorphic response to chronic HDF exposure, females; despite gaining the same amount of body weight following HFD-feeding, appear to be protected from the adverse metabolic effects of the HFD.

  19. Chromosome aberrations in F1 from irradiated male mice studied by their synaptonemal complexes

    International Nuclear Information System (INIS)

    Kalikinskaya, E.I.; Kolomiets, O.L.; Shevchenko, V.A.; Bogdanov, Yu.F.

    1986-01-01

    Possible implications of surface-spread synaptonemal complex (SC) karyotyping in analysing the causes of sterility of F 1 from irradiated male mice are demonstrated in this work. After irradiation by 137 Cs γ-rays at a dose of 5 Gy the males were mated to unirradiated females and genetic analysis of fertility in the F 1 progeny was carried out. Males with abnormal fertility were examined for the presence of chromosome aberrations in diakinesis-metaphase I and in pachytene by the method of surface-spread SC karyotyping. In most cases, SC karyotyping provides additional information and permits the detection and analysis of aberrations that are not revealed in diakinesis. Two reciprocal translocations, one X autosomal and one nonreciprocal translocation were discovered in five F 1 males studied. It is concluded that the method is efficient in detecting translocations in pachytene in partially fertile F 1 hybrids of irradiated and normal mice. (orig.)

  20. A complex genetic basis to X-linked hybrid male sterility between two species of house mice.

    Science.gov (United States)

    Good, Jeffrey M; Dean, Matthew D; Nachman, Michael W

    2008-08-01

    The X chromosome plays a central role in the evolution of reproductive isolation, but few studies have examined the genetic basis of X-linked incompatibilities during the early stages of speciation. We report the results of a large experiment focused on the reciprocal introgression of the X chromosome between two species of house mice, Mus musculus and M. domesticus. Introgression of the M. musculus X chromosome into a wild-derived M. domesticus genetic background produced male-limited sterility, qualitatively consistent with previous experiments using classic inbred strains to represent M. domesticus. The genetic basis of sterility involved a minimum of four X-linked factors. The phenotypic effects of major sterility QTL were largely additive and resulted in complete sterility when combined. No sterility factors were uncovered on the M. domesticus X chromosome. Overall, these results revealed a complex and asymmetric genetic basis to X-linked hybrid male sterility during the early stages of speciation in mice. Combined with data from previous studies, we identify one relatively narrow interval on the M. musculus X chromosome involved in hybrid male sterility. Only a handful of spermatogenic genes are within this region, including one of the most rapidly evolving genes on the mouse X chromosome.

  1. A vasoactive role for endogenous relaxin in mesenteric arteries of male mice.

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    Chen Huei Leo

    Full Text Available 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.

  2. Serum antibody responses by male and female C57Bl/6 mice infected with Giardia muris.

    Science.gov (United States)

    Daniels, C W; Belosevic, M

    1994-09-01

    We compared the levels of serum antibodies in male and female C57Bl/6 mice during the primary and after challenge infection with Giardia muris. Male mice began passing cysts in their faeces earlier than females, and were shedding cysts for over 60 days, while females stopped shedding cysts by day 20 after infection. In both males and females there were significant increases in parasite-specific IgM 10 and 20 days after infection. No differences in parasite-specific serum IgA were observed until 40 days after infection. Parasite-specific IgG (whole) levels were elevated on days 20 and 40 in females, while males showed no significant increases. In addition, females had a much stronger IgG2b and IgG3 response than males. After challenge with either cysts or soluble parasite protein only the females had significant increases in specific anti-parasite IgG2b. Our data show differential ability of males and females to control the infection with G. muris is paralleled by a difference in the anti-parasite serum IgG response of the mice.

  3. Dietary controlled carcinogenicity study of chloral hydrate in male B6C3F1 mice

    International Nuclear Information System (INIS)

    Leakey, Julian E.A.; Seng, John E.; Latendresse, John R.; Hussain, Nursreen; Allen, Laura J.; Allaben, William T.

    2003-01-01

    Chloral hydrate, which is used as a sedative in pediatric medicine and is a by-product of water chlorination, is hepatocarcinogenic in B6C3F 1 mice, a strain that can exhibit high rates of background liver tumor incidence, which are associated with increased body weight. In this study, dietary control was used to manipulate body growth in male B6C3F 1 mice in a 2-year bioassay of chloral hydrate. Male B6C3F 1 mice were treated with water or 25, 50, or 100 mg/kg chloral hydrate by gavage. The study compared ad libitum-fed mice with dietary controlled mice. The latter received variably restricted feed allocations to maintain their body weights on a predetermined 'idealized' weight curve predictive of a terminal background liver tumor incidence of 15-20%. These mice exhibited less individual body weight variation than did their ad libitum-fed counterparts. This was associated with a decreased variation in liver to body weight ratios, which allowed the demonstration of a statistically significant dose response to chloral hydrate in the dietary controlled, but not the ad libitum-fed, test groups. Chloral hydrate increased terminally adjusted liver tumor incidence in both dietary controlled (23.4, 23.9, 29.7, and 38.6% for the four dose groups, respectively) and ad libitum-fed mice (33.4, 52.6, 50.6, and 46.2%), but a statistically significant dose response was observed only in the dietary controlled mice. This dose response positively correlated with markers of peroxisomal proliferation in the dietary controlled mice only. The study suggests that dietary control not only improves terminal survival and decreases interassay variation, but also can increase assay sensitivity by decreasing intra-assay variation

  4. The SocioBox: A novel paradigm to assess complex social recognition in male mice

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    Dilja Krueger-Burg

    2016-08-01

    Full Text Available 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 memory. 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 memory deficits is provided using male PSD-95 heterozygous knockout mice, a mouse model related to psychiatric pathophysiology.

  5. Reproductive performance of male mice after hypothalamic ghrelin administration.

    Science.gov (United States)

    Poretti, Maria Belen; Frautschi, Camila; Luque, Eugenia Mercedes; Bianconi, Santiago; Martini, Ana Carolina; Stutz, Graciela; Vincenti, Laura Maria; Santillán, María Emilia; Ponzio, Marina Flavia; Schiöth, Helgi; Fiol De Cuneo, Marta Haydee; Carlini, Valeria Paola

    2018-05-23

    It has been demonstrated that food intake and reproductive physiology are both simultaneously modulated to optimize reproductive success under fluctuating metabolic conditions. Ghrelin (Ghr) is an orexigenic peptide identified as the endogenous ligand of the growth hormone secretagogue receptor that is being investigated for its potential role on reproduction. Considering that data available so far are still limited and characterization of Ghr action mechanism on the reproductive system has not been fully elucidated, we studied the hypothalamus participation in Ghr effects on sperm functional activity, plasma levels of gonodotropins and histological morphology in mice testes after hypothalamic infusion of 0.3 or 3.0 nmol/day Ghr or artificial cerebrospinal fluid (ACSF) at different treatment periods. We found that Ghr 3.0 nmol/day administration for 42 days significantly reduced sperm concentration (Ghr 3.0 nmol/day=14.05±2.44 x106/ml vs. ACSF=20.33±1.35 x106/ml, p< 0.05) and motility (Ghr 3.0 nmol/day=59.40±4.20% vs. ACSF=75.80±1.40%, p< 0.05). In addition, histological studies showed a significant decrease percentage of spermatogonia (Ghr 3.0 nmol/day=6,76±0,68% vs. ACSF=9,56±0,41%, p< 0.05) and sperm (Ghr 3.0 nmol/day=24,24±1,92% vs. ACSF=31,20±3,06%, p< 0.05). These results were associated with a significant reduction in luteinizing hormone and testosterone plasma levels (p<0.05). As Ghr is an orexigenic peptide, body weight and food intake were measured. Results showed that Ghr increases both parameters; however, the effect did not last beyond the first week of treatment. Results presented in this work confirm that central Ghr administration impairs spermatogenesis and suggest that this effect is mediated by inhibition of hypothalamic-pituitary-gonadal axis.

  6. Female scent signals enhance the resistance of male mice to influenza.

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    Ekaterina A Litvinova

    Full Text Available BACKGROUND: The scent from receptive female mice functions as a signal, which stimulates male mice to search for potential mating partners. This searching behavior is coupled with infection risk due to sniffing both scent marks as well as nasal and anogenital areas of females, which harbor bacteria and viruses. Consideration of host evolution under unavoidable parasitic pressures, including helminthes, bacteria, viruses, etc., predicts adaptations that help protect hosts against the parasites associated with mating. METHODS AND FINDINGS: We propose that the perception of female signals by BALB/c male mice leads to adaptive redistribution of the immune defense directed to protection against respiratory infection risks. Our results demonstrate migration of macrophages and neutrophils to the upper airways upon exposure to female odor stimuli, which results in an increased resistance of the males to experimental influenza virus infection. This moderate leukocyte intervention had no negative effect on the aerobic performance in male mice. CONCLUSIONS: Our data provide the first demonstration of the adaptive immunological response to female odor stimuli through induction of nonspecific immune responses in the upper respiratory tract.

  7. Histological and Physiological Alterations Induced by Thermal Neutron Fluxes in Male Swiss Albino Mice

    International Nuclear Information System (INIS)

    Alzergy, A.A.; Emara, N.M.; Abd El-Latif, A.A.; El-Saady, S.M.M.; Emara, N.M.; Abd El-Latif, A.A.

    2010-01-01

    This work was performed to investigate the biological effects of different thermal neutron fluxes (0.27x10 8 , 0.52X10 8 , 1.089X10 8 , 2.16X10 8 and 4.32X10 8 ) on liver and kidney of male mice using neutron irradiation cell with Ra-Be(α,n) 3 mCi neutron source Leybold (55930). Exposed to various fluxes of thermal neutron induced a dramatic alterations in hepatic and renal functions as indicated by biochemical estimation of several parameters (bilirubin, SGT, and alkaline phosphate .Urea , total protein, and albumin) and confirmed by histological examinations Thermal neutron exposure induces marked increase in the serum activities of total bilirubin, alanine amino transaminase (ALT or GPT), and alkaline phosphate, whereas, urea, total protein and albumin showed marked decline as compared to control group. The physiological changes induced in thermal neutron fluxes dependent manner. Histopathological results revealed mild to severe type of necrosis, and degenerative changes in liver and kidney of male mice exposed to thermal neutron fluxes. Also it was found that the histopathological alterations induced in thermal neutron fluxes dependent manner. It was found that exposed to thermal neutron fluxes irradiation plays prominent role in the development of the physiological alterations in male Swiss albino mice. The Former up normalities as a result of the sequence events followed interaction of radiation with the former biological mater (liver and kidney) of male Swiss albino mice, which are, physical, physicochemical, chemical, and biological stages.

  8. Behavioral profiles of genetically selected aggressive and nonaggressive male wild house mice in two anxiety tests

    NARCIS (Netherlands)

    Hogg, S; Wurbel, H; Steimer, T; de Ruiter, A; Koolhaas, J; Sluyter, F; Driscoll, Peter

    2000-01-01

    Artificially selected aggressive (SAL) and non-aggressive (LAL) male house mice were tested in a hexagonal tunnel maze and light-dark preference (LD) box to determine if the bidirectional selection for aggressive behavior leads to a coselection for different levels of trait anxiety. The tunnel maze

  9. Social isolation induces behavioral and neuroendocrine disturbances relevant to depression in female and male prairie voles.

    Science.gov (United States)

    Grippo, Angela J; Gerena, Davida; Huang, Jonathan; Kumar, Narmda; Shah, Maulin; Ughreja, Raj; Carter, C Sue

    2007-01-01

    Supportive social interactions may be protective against stressors and certain mental and physical illness, while social isolation may be a powerful stressor. Prairie voles are socially monogamous rodents that model some of the behavioral and physiological traits displayed by humans, including sensitivity to social isolation. Neuroendocrine and behavioral parameters, selected for their relevance to stress and depression, were measured in adult female and male prairie voles following 4 weeks of social isolation versus paired housing. In Experiment 1, oxytocin-immunoreactive cell density was higher in the hypothalamic paraventricular nucleus (PVN) and plasma oxytocin was elevated in isolated females, but not in males. In Experiment 2, sucrose intake, used as an operational definition of hedonia, was reduced in both sexes following 4 weeks of isolation. Animals then received a resident-intruder test, and were sacrificed either 10 min later for the analysis of circulating hormones and peptides, or 2h later to examine neural activation, indexed by c-Fos expression in PVN cells immunoreactive for oxytocin or corticotropin-releasing factor (CRF). Compared to paired animals, plasma oxytocin, ACTH and corticosterone were elevated in isolated females and plasma oxytocin was elevated in isolated males, following the resident-intruder test. The proportion of cells double-labeled for c-Fos and oxytocin or c-Fos and CRF was elevated in isolated females, and the proportion of cells double-labeled for c-Fos and oxytocin was elevated in isolated males following this test. These findings suggest that social isolation induces behavioral and neuroendocrine responses relevant to depression in male and female prairie voles, although neuroendocrine responses in females may be especially sensitive to isolation.

  10. Genotype modulates testosterone-dependent activity and reactivity in male mice.

    Science.gov (United States)

    Broida, J; Svare, B

    1983-03-01

    Adult castration significantly reduced the homecage locomotor activity of both inbred C57BL/6J and DBA/2J and outbred Rockland-Swiss (R-S) male mice. Castrated C57BL animals exhibited greater reductions in this behavior than did the other genotypes. Locomotor activity in a novel environment (reactivity) was also reduced by castration but only for inbred males. In both test situations, postcastration reductions in ambulation were prevented by implants of testosterone (T)-containing Silastic capsules. Thus, testicular hormones promote activity and reactivity in the male mouse in a genotype-dependent fashion.

  11. Chronic social isolation and chronic variable stress during early development induce later elevated ethanol intake in adult C57BL/6J mice.

    Science.gov (United States)

    Lopez, Marcelo F; Doremus-Fitzwater, Tamara L; Becker, Howard C

    2011-06-01

    Experience with stress situations during early development can have long-lasting effects on stress- and anxiety-related behaviors. Importantly, this can also favor drug self-administration. These studies examined the effects of chronic social isolation and/or variable stress experiences during early development on subsequent voluntary ethanol intake in adult male and female C57BL/6J mice. The experiments were conducted to evaluate the effect of chronic isolation between weaning and adulthood (Experiment 1), chronic isolation during adulthood (Experiment 2), and chronic variable stress (CVS) alone or in combination with chronic social isolation between weaning and adulthood (Experiment 3) on subsequent voluntary ethanol intake. Mice were born in our facility and were separated into two housing conditions: isolate housed (one mouse/cage) or group housed (four mice/cage) according to sex. Separate groups were isolated for 40 days starting either at time of weaning postnatal day 21 (PD 21) (early isolation, Experiments 1 and 3) or at adulthood (PD 60: late isolation, Experiment 2). The effects of housing condition on subsequent ethanol intake were assessed starting at around PD 65 in Experiments 1 and 3 or PD 105 days in Experiment 2. In Experiment 3, starting at PD 32, isolate-housed and group-housed mice were either subjected to CVS or left undisturbed. CVS groups experienced random presentations of mild stressors for 14 days, including exposure to an unfamiliar open field, restraint, physical shaking, and forced swim, among others. All mice were tested for ethanol intake for 14 days using a two-bottle choice (ethanol 15% vol/vol vs. water) for a 2-h limited access procedure. Early social isolation resulted in greater ethanol intake compared with the corresponding group-housed mice (Experiment 1). In contrast, social isolation during adulthood (late isolation) did not increase subsequent ethanol intake compared with the corresponding group-housed mice (Experiment 2

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

    Science.gov (United States)

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

    2015-07-01

    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.

  13. Sim1 Neurons Are Sufficient for MC4R-Mediated Sexual Function in Male Mice.

    Science.gov (United States)

    Semple, Erin; Hill, Jennifer W

    2018-01-01

    Sexual dysfunction is a poorly understood condition that affects up to one-third of men around the world. Existing treatments that target the periphery do not work for all men. Previous studies have shown that central melanocortins, which are released by pro-opiomelanocortin neurons in the arcuate nucleus of the hypothalamus, can lead to male erection and increased libido. Several studies specifically implicate the melanocortin 4 receptor (MC4R) in the central control of sexual function, but the specific neural circuitry involved is unknown. We hypothesized that single-minded homolog 1 (Sim1) neurons play an important role in the melanocortin-mediated regulation of male sexual behavior. To test this hypothesis, we examined the sexual behavior of mice expressing MC4R only on Sim1-positive neurons (tbMC4Rsim1 mice) in comparison with tbMC4R null mice and wild-type controls. In tbMC4Rsim1 mice, MC4R reexpression was found in the medial amygdala and paraventricular nucleus of the hypothalamus. These mice were paired with sexually experienced females, and their sexual function and behavior was scored based on mounting, intromission, and ejaculation. tbMC4R null mice showed a longer latency to mount, a reduced intromission efficiency, and an inability to reach ejaculation. Expression of MC4R only on Sim1 neurons reversed the sexual deficits seen in tbMC4R null mice. This study implicates melanocortin signaling via the MC4R on Sim1 neurons in the central control of male sexual behavior. Copyright © 2018 Endocrine Society.

  14. Hydrolyzed Casein Reduces Diet-Induced Obesity in Male C57BL/6J Mice

    DEFF Research Database (Denmark)

    Lillefosse, Haldis H.; Tastesen, Hanne Sørup; Du, Zhen-Yu

    2013-01-01

    used a factorial ANOVA design to investigate the effects of protein form (intact vs. hydrolyzed casein) and protein level (16 vs. 32 energy percent protein) on body mass gain and adiposity in obesity-prone male C57BL/6J mice fed Western diets with 35 energy percent fat. Mice fed the hydrolyzed casein......The digestion rate of dietary protein is a regulating factor for postprandial metabolism both in humans and animal models. However, few data exist about the habitual consumption of proteins with different digestion rates with regard to the development of body mass and diet-induced obesity. Here, we...... diets had higher spontaneous locomotor activity than mice fed intact casein. During the light phase, mice fed hydrolyzed casein tended (P = 0.08) to have a lower respiratory exchange ratio, indicating lower utilization of carbohydrates as energy substrate relative to those fed intact casein. In further...

  15. Male mice emit distinct ultrasonic vocalizations when the female leaves the social interaction arena

    Directory of Open Access Journals (Sweden)

    Mu eYang

    2013-11-01

    Full Text Available Adult male mice emit large number of complex ultrasonic vocalizations (USVs when interacting with adult females. Call numbers and call categories differ greatly among inbred mouse strains. Little is known about USV emissions when the social partner departs. To investigate whether call repertoires and call rates are different when the male is interacting with a female and after the removal of the female, we designed a novel male-female social interaction test in which vocalizations were recorded across three phases. During phase 1, the male subject freely interacts with an unfamiliar estrus female mouse in a clean cage for 5 minutes. During phase 2, the female is removed while the male remains in the cage for 3 minutes. During phase 3, the same female is returned to the cage to rejoin the male subject mouse for 3 minutes. C57BL/6J (B6, FVB.129P2-Pde6b(+ Tyr(c-ch/Ant (FVB, and BTBR T+ tf/J (BTBR male subject mice were tested in this paradigm. All three strains emitted USVs during the absence of the estrous female, although at lower rates. When the female was reintroduced in phase 3, numbers of USVs were similar to the initial introductory phase 1. Strain comparisons indicated fewer calls in pairs of BTBR males and stimulus females than in pairs of B6 males and stimulus females and pairs of FVB males and stimulus females. In the absence of the female, all FVB males vocalized, while only one third of B6 males and one third of BTBR males vocalized. In all three strains, changes in call repertoires were detected after the female was removed. Call categories reverted to the phase 1 pattern when the female was returned in phase 3. Present findings indicate that males of commonly used inbred strains emit USVs when a partner female leaves the testing arena, suggesting that removing a salient social stimulus may be a unique approach to elicit USVs from mice. Our three-phase paradigm may also be useful for studying attention to social cues, and qualitative

  16. Exposure to bifenthrin causes immunotoxicity and oxidative stress in male mice.

    Science.gov (United States)

    Jin, Yuanxiang; Pan, Xiuhong; Fu, Zhengwei

    2014-09-01

    Bifenthrin (BF) is one of the most commonly used pesticides among the synthetic pyrethroids. The effects of BF exposure on the induction of immunotoxicity and oxidative stress were studied both in adolescent and adult male ICR mice. Both the weights of the spleen and thymus decreased significantly in the adolescent mice when they were treated with 20 mg/kg BF for 3 weeks. We found that the 3-week oral administration of BF during puberty increased the transcriptional levels of the genes TNF and IL2 in the spleen and IL2 as well as IL4 in the thymus. The effect of BF exposure on the induction of oxidative stress was also studied in serum and liver samples. The total antioxidant capacity and activity of superoxide dismutase were altered significantly in the serum of the 20 mg/kg BF-treated adolescent mice, and the activity of glutathione peroxidase (GPX) decreased significantly in the serum of adolescent and adult mice after 3 weeks of oral administration of 20 mg/kg BF. Compared to serum, hepatic GSH content increased significantly in both the adolescent and adult mice exposed to 20 mg/kg BF; hepatic CAT and GPX activities were altered significantly, even in adolescent mice, after treatment with 10 mg/kg BF. Taken together, the results of this study suggest that exposure to BF, especially during puberty, has the potential to induce immunotoxicity accompanied by oxidative stress in male mice. These findings will help in elucidating the mechanism of toxicity induced by BF in mice. Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.

  17. Meiotic chromosomal translocations in male mice induced by X-irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Savkovic, N.; Pecevski; Vuksanovic, L.; Radivojevic, D.; Alavantic, D.

    1983-01-01

    The dose-response curve for reciprocal translocations induced by acute exposure of spermatogonial stem cells to X-rays in treated mice and their F-1 sons was examined. Male mice were totally irradiated with doses of 1Gy;5x1Gy and 5Gy. The obtained results show that frequency of the chromosomal translocations in directly treated animals is dose dependent. The percentage of animals irradiated with 1Gy which had the chromosomal translocations was 60, while this percentage in animals irradiated with single and fractionated dose of 5Gy was 100. The frequency of chromosomal translocations varies from 1.5% to 8.0%. Multivalent configurations in F-1 males were observed after exposure to 5Gy only. The incidence of F-1 translocated males was 17.5%.

  18. Induction of dominant lethals in male mice treated as embryos with 35S

    International Nuclear Information System (INIS)

    Reddy, K.S.; Reddy, P.P.; Reddy, O.S.

    1980-01-01

    Pregnant female mice were injected (ip) with 20 μCi of 35 S or 0.5 ml of saline (control) on 3.5 day of gestation. The animals were allowed to litter and the (CBA female x C 3 H/He male) F 1 males treated as embryos were tested at maturity (8-10 weeks) for dominant lethal incidence. Each male was mated to 3 untreated virgin females for a period of 3 weeks. The pregnant animals were killed at mid gestation and the uterine contents and corpora lutea were examined. There was a significant increase in the frequency of dominant lethals both at pre- and post-implantation stages in the treated group when compared to controls. As a result a significant increase in dead implantations/female and reduction in live implantations/female were noticed in the treated group. Thus the results clearly delineate the genetic effects of sulfur-35 in mice. (auth.)

  19. Sex-specific effects of docosahexaenoic acid (DHA) on the microbiome and behavior of socially-isolated mice.

    Science.gov (United States)

    Davis, Daniel J; Hecht, Patrick M; Jasarevic, Eldin; Beversdorf, David Q; Will, Matthew J; Fritsche, Kevin; Gillespie, Catherine H

    2017-01-01

    Dietary supplementation with the long-chain omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) has been shown to have a beneficial effect on reducing the symptoms associated with several neuropsychiatric conditions including anxiety and depression. However, the mechanisms underlying this effect remain largely unknown. Increasing evidence suggests that the vast repertoire of commensal bacteria within the gut plays a critical role in regulating various biological processes in the brain and may contribute to neuropsychiatric disease risk. The present study determined the contribution of DHA on anxiety and depressive-like behaviors through modulation of the gut microbiota in a paradigm of social isolation. Adult male and female mice were subjected to social isolation for 28days and then placed either on a control diet or a diet supplemented with 0.1% or 1.0% DHA. Fecal pellets were collected both 24h and 7days following the introduction of the new diets. Behavioral testing revealed that male mice fed a DHA diet, regardless of dose, exhibited reduced anxiety and depressive-like behaviors compared to control fed mice while no differences were observed in female mice. As the microbiota-brain-axis has been recently implicated in behavior, composition of microbial communities were analyzed to examine if these sex-specific effects of DHA may be associated with changes in the gut microbiota (GM). Clear sex differences were observed with males and females showing distinct microbial compositions prior to DHA supplementation. The introduction of DHA into the diet also induced sex-specific interactions on the GM with the fatty acid producing a significant effect on the microbial profiles in males but not in females. Interestingly, levels of Allobaculum and Ruminococcus were found to significantly correlate with the behavioral changes observed in the male mice. Predictive metagenome analysis using PICRUSt was performed on the fecal samples collected from males and

  20. Modified forelimb grip strength test detects aging-associated physiological decline in skeletal muscle function in male mice.

    Science.gov (United States)

    Takeshita, Hikari; Yamamoto, Koichi; Nozato, Satoko; Inagaki, Tadakatsu; Tsuchimochi, Hirotsugu; Shirai, Mikiyasu; Yamamoto, Ryohei; Imaizumi, Yuki; Hongyo, Kazuhiro; Yokoyama, Serina; Takeda, Masao; Oguro, Ryosuke; Takami, Yoichi; Itoh, Norihisa; Takeya, Yasushi; Sugimoto, Ken; Fukada, So-Ichiro; Rakugi, Hiromi

    2017-02-08

    The conventional forelimb grip strength test is a widely used method to assess skeletal muscle function in rodents; in this study, we modified this method to improve its variability and consistency. The modified test had lower variability among trials and days than the conventional test in young C57BL6 mice, especially by improving the variabilities in male. The modified test was more sensitive than the conventional test to detect a difference in motor function between female and male mice, or between young and old male mice. When the modified test was performed on male mice during the aging process, reduction of grip strength manifested between 18 and 24 months of age at the group level and at the individual level. The modified test was similar to the conventional test in detecting skeletal muscle dysfunction in young male dystrophic mice. Thus, the modified forelimb grip strength test, with its improved validity and reliability may be an ideal substitute for the conventional method.

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

    Science.gov (United States)

    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. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Effect of Variable Doses of Zinc Oxide Nanoparticles on Male Albino Mice Behavior.

    Science.gov (United States)

    Zahra, Javeria; Iqbal, Shahid; Zahra, Kiran; Javed, Zulha; Shad, Muhammad Aslam; Akbar, Atif; Ashiq, Muhammad Naeem; Iqbal, Furhan

    2017-02-01

    Zinc oxide nanoparticles (ZnO NPs) have diverse utility these days ranging from being part of nanosensors to be ingredient of cosmetics. Present study was designed to report the effect of variable doses of ZnO NPs on selected aspects of male albino mice behavior. Nano particles were synthesized by sol-gel auto-combustion method (Data not shown here). 10 week old male albino mice were divided into four experimental groups; group A, B and C were orally supplemented with 50 (low dose), 300 (medium dose) and 600 mg/ml solvent/kg body weight (high dose) of ZnO NPs for 4 days. Group D (control) orally received 0.2 M sodium phosphate buffer (solvent for ZnO NPs) for the same duration. A series of neurological tests (Rota rod, open field, novel object and light-dark box test) were conducted in all groups and performance was compared between ZnO NPs treated and control group. Muscular functioning during rota rod test was significantly improved in all ZnO NPs treated mice as compared to control group. While no significant differences in open field, novel object and light-dark box test performance were observed when data from studied parameters of specific ZnO NPs treatment were compared with the control group indicating that applied doses of ZnO NPs did not affect the exploratory, anxiolytic behavior and object recognition capability of adult male albino mice.

  3. Efficacy of protocols for induction of chronic hyperthyroidism in male and female mice.

    Science.gov (United States)

    Engels, Kathrin; Rakov, Helena; Zwanziger, Denise; Hönes, Georg Sebastian; Rehders, Maren; Brix, Klaudia; Köhrle, Josef; Möller, Lars Christian; Führer, Dagmar

    2016-10-01

    Protocols for induction of hyperthyroidism in mice are highly variable and mostly involve short-term thyroid hormone (TH) treatment. In addition, little is known about a possible influence of sex on experimental TH manipulation. Here we analyzed the efficacy of intraperitoneal vs. oral levothyroxine (T4) administration to induce chronic hyperthyroidism in male and female mice and asked which T4 dosing intervals are required to achieve stable organ thyrotoxicosis. T4 was administered intraperitoneally or orally over a period of 6/7 weeks. Assessment included monitoring of body weight, TH serum concentrations, and serial quantitative TH target gene expression analysis in liver and heart. Our results show that both intraperitoneal and oral T4 treatment are reliable methods for induction of chronic hyperthyroidism in mice. Thereby T4 injection intervals should not exceed 48 h and oral levothyroxine should be administered continuously during experiments and up to sacrifice to ensure a hyperthyroid organ state. Furthermore, we found a sex-dependent variation in levothyroxine-induced TH serum state, with significantly higher T4 concentrations in female mice, while expression of investigated classical TH responsive genes in liver and heart did not vary with animal's sex. In summary, our study shows that common approaches for rendering rodents thyrotoxic can also be used for induction of chronic hyperthyroidism in male and female mice. Thereby T4 dosing intervals are critical as are read-out parameters to verify a chronic thyrotoxic organ state.

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

    Science.gov (United States)

    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. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. An X chromosome effect responsible for asymmetric reproductive isolation between male Drosophila virilis and heterospecific females.

    Science.gov (United States)

    Nickel, Desirée; Civetta, Alberto

    2009-01-01

    Reproductive isolation between closely related species is expressed through uncoordinated courtship, failed fertilization, and (or) postzygotic barriers. Behavioural components of mating often form an initial barrier to hybridization between species. In many animals, females are responsible for mating discrimination in both intra- and interspecific crosses; males of Drosophila virilis group represent an exception to this trend. Using overall productivity tests, we show that a lower proportion of D. virilis males sire progeny when paired with a heterospecific female (Drosophila novamexicana or Drosophila americana texana) for 2 weeks. This suggests male mate discrimination or some other kind of asymmetrical incompatibility in courtship and mating or early zygote mortality. We used males from D. virilis-D. novamexicana and from D. virilis-D. a. texana backcross populations to map chromosome effects responsible for male reproductive isolation. Results from the analysis of both backcross male populations indicate a major X chromosome effect. Further, we conduct a male behavioural analysis to show that D. virilis males significantly fail to continue courtship after the first step of courtship, when they tap heterospecific females. The combined results of a major X chromosome effect and the observation that D. virilis males walk away from females after tapping suggest that future studies should concentrate on the identification of X-linked genes affecting the ability of males to recognize conspecific females.

  6. Nucleus Accumbens Dopamine Signaling Regulates Sexual Preference for Females in Male Mice.

    Science.gov (United States)

    Beny-Shefer, Yamit; Zilkha, Noga; Lavi-Avnon, Yael; Bezalel, Nadav; Rogachev, Ilana; Brandis, Alexander; Dayan, Molly; Kimchi, Tali

    2017-12-12

    Sexual preference for the opposite sex is a fundamental behavior underlying reproductive success, but the neural mechanisms remain unclear. Here, we examined the role of dopamine signaling in the nucleus accumbens core (NAcc) in governing chemosensory-mediated preference for females in TrpC2 -/- and wild-type male mice. TrpC2 -/- males, deficient in VNO-mediated signaling, do not display mating or olfactory preference toward females. We found that, during social interaction with females, TrpC2 -/- males do not show increased NAcc dopamine levels, observed in wild-type males. Optogenetic stimulation of VTA-NAcc dopaminergic neurons in TrpC2 -/- males during exposure to a female promoted preference response to female pheromones and elevated copulatory behavior toward females. Additionally, we found that signaling through the D1 receptor in the NAcc is necessary for the olfactory preference for female-soiled bedding. Our study establishes a critical role for the mesolimbic dopaminergic system in governing pheromone-mediated responses and mate choice in male mice. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Nucleus Accumbens Dopamine Signaling Regulates Sexual Preference for Females in Male Mice

    Directory of Open Access Journals (Sweden)

    Yamit Beny-Shefer

    2017-12-01

    Full Text Available Sexual preference for the opposite sex is a fundamental behavior underlying reproductive success, but the neural mechanisms remain unclear. Here, we examined the role of dopamine signaling in the nucleus accumbens core (NAcc in governing chemosensory-mediated preference for females in TrpC2−/− and wild-type male mice. TrpC2−/− males, deficient in VNO-mediated signaling, do not display mating or olfactory preference toward females. We found that, during social interaction with females, TrpC2−/− males do not show increased NAcc dopamine levels, observed in wild-type males. Optogenetic stimulation of VTA-NAcc dopaminergic neurons in TrpC2−/− males during exposure to a female promoted preference response to female pheromones and elevated copulatory behavior toward females. Additionally, we found that signaling through the D1 receptor in the NAcc is necessary for the olfactory preference for female-soiled bedding. Our study establishes a critical role for the mesolimbic dopaminergic system in governing pheromone-mediated responses and mate choice in male mice.

  8. Effect of fenbendazole on three behavioral tests in male C57BL/6N mice.

    Science.gov (United States)

    Gadad, Bharathi S; Daher, João P L; Hutchinson, Eric K; Brayton, Cory F; Dawson, Ted M; Pletnikov, Mikhail V; Watson, Julie

    2010-11-01

    Pinworms are highly contagious parasites of laboratory rodents that often are treated with fenbendazole. To our knowledge, the effect of fenbendazole at therapeutic dosages on behavioral tests in mice has not been evaluated. Here we studied 6-wk-old male C57BL/6N mice. We compared the behavior of control mice (fed regular diet) with 3 groups of mice treated with dietary fenbendazole. Treatment groups were 4 wk of fenbendazole, 2 wk of fenbendazole followed by 2 wk of regular diet, and 2 wk of regular diet followed by 2 wk of fenbendazole. At the end of dietary treatment all groups were tested by open field for central, peripheral and vertical activity; elevated plus maze for anxiety; and rotarod for motor ability and then evaluated by clinical pathology and selected histopathology. Treated and control groups showed no differences in open field or elevated plus maze testing, histopathology, or clinical pathology. However mice treated for 4 wk with fenbendazole or 2 wk of fenbendazole followed by 2 wk regular diet stayed on the rotarod for shorter periods than did controls, and mice treated with 2 wk of regular diet followed by 2 wk fenbendazole showed a trend toward shorter rotarod times. In light of this study, we suggest that open field and elevated plus maze testing is unlikely to be affected by 4 wk fenbendazole treatment in male C57BL/6 mice; however, behavioral tests of motor ability such as rotarod tests may be affected during and for at least 2 wk after fenbendazole treatment.

  9. Identification of SOX3 as an XX male sex reversal gene in mice and humans.

    Science.gov (United States)

    Sutton, Edwina; Hughes, James; White, Stefan; Sekido, Ryohei; Tan, Jacqueline; Arboleda, Valerie; Rogers, Nicholas; Knower, Kevin; Rowley, Lynn; Eyre, Helen; Rizzoti, Karine; McAninch, Dale; Goncalves, Joao; Slee, Jennie; Turbitt, Erin; Bruno, Damien; Bengtsson, Henrik; Harley, Vincent; Vilain, Eric; Sinclair, Andrew; Lovell-Badge, Robin; Thomas, Paul

    2011-01-01

    Sex in mammals is genetically determined and is defined at the cellular level by sex chromosome complement (XY males and XX females). The Y chromosome-linked gene sex-determining region Y (SRY) is believed to be the master initiator of male sex determination in almost all eutherian and metatherian mammals, functioning to upregulate expression of its direct target gene Sry-related HMG box-containing gene 9 (SOX9). Data suggest that SRY evolved from SOX3, although there is no direct functional evidence to support this hypothesis. Indeed, loss-of-function mutations in SOX3 do not affect sex determination in mice or humans. To further investigate Sox3 function in vivo, we generated transgenic mice overexpressing Sox3. Here, we report that in one of these transgenic lines, Sox3 was ectopically expressed in the bipotential gonad and that this led to frequent complete XX male sex reversal. Further analysis indicated that Sox3 induced testis differentiation in this particular line of mice by upregulating expression of Sox9 via a similar mechanism to Sry. Importantly, we also identified genomic rearrangements within the SOX3 regulatory region in three patients with XX male sex reversal. Together, these data suggest that SOX3 and SRY are functionally interchangeable in sex determination and support the notion that SRY evolved from SOX3 via a regulatory mutation that led to its de novo expression in the early gonad.

  10. Identification of SOX3 as an XX male sex reversal gene in mice and humans

    Science.gov (United States)

    Sutton, Edwina; Hughes, James; White, Stefan; Sekido, Ryohei; Tan, Jacqueline; Arboleda, Valerie; Rogers, Nicholas; Knower, Kevin; Rowley, Lynn; Eyre, Helen; Rizzoti, Karine; McAninch, Dale; Goncalves, Joao; Slee, Jennie; Turbitt, Erin; Bruno, Damien; Bengtsson, Henrik; Harley, Vincent; Vilain, Eric; Sinclair, Andrew; Lovell-Badge, Robin; Thomas, Paul

    2010-01-01

    Sex in mammals is genetically determined and is defined at the cellular level by sex chromosome complement (XY males and XX females). The Y chromosome–linked gene sex-determining region Y (SRY) is believed to be the master initiator of male sex determination in almost all eutherian and metatherian mammals, functioning to upregulate expression of its direct target gene Sry-related HMG box–containing gene 9 (SOX9). Data suggest that SRY evolved from SOX3, although there is no direct functional evidence to support this hypothesis. Indeed, loss-of-function mutations in SOX3 do not affect sex determination in mice or humans. To further investigate Sox3 function in vivo, we generated transgenic mice overexpressing Sox3. Here, we report that in one of these transgenic lines, Sox3 was ectopically expressed in the bipotential gonad and that this led to frequent complete XX male sex reversal. Further analysis indicated that Sox3 induced testis differentiation in this particular line of mice by upregulating expression of Sox9 via a similar mechanism to Sry. Importantly, we also identified genomic rearrangements within the SOX3 regulatory region in three patients with XX male sex reversal. Together, these data suggest that SOX3 and SRY are functionally interchangeable in sex determination and support the notion that SRY evolved from SOX3 via a regulatory mutation that led to its de novo expression in the early gonad. PMID:21183788

  11. Growth and development of male "little" mice assessed with Parks' theory of feeding and growth.

    Science.gov (United States)

    Puche, Rodolfo C; Alloatti, Rosa; Chapo, Gustavo

    2002-01-01

    This work was designed to characterize the appetite kinetics and growth of male C57BL/6J (lit) mice. Those variables were assessed with Parks' function of ad libitum feeding and growth. Heterozygous mice (lit/+) attained their mature weight at 12-15 weeks of age, peak growth rate (3.5 g/week) at 5 weeks and displayed the normal decay of food conversion efficiency as a function of age. The homozygous genotype has a chronic defect in the synthesis and secretion of growth hormone (GH). Homozygous mice could not be assessed with Park's function. From the 4th to the 15th week of age, body weight increased linearly and exhibited constant food conversion efficiency. Food intake of both genotypes was commensurate with their body weights. Lit/lit mice became progressively obese. At 40 weeks of age, body fat of lit/lit mice was fivefold that of lit/+ and their body weight was similar to their heterozygous controls. The chronic deficiency of growth hormone produced a lower bone mass (compared to heterozygous controls). Bone mass of both genotypes attained maturity at 12-15 weeks with a maximum growth rate at 5 weeks. Body weight and bone mass grow harmoniously in lit/+ but not in lit/lit mice.

  12. Male and female contributions to behavioral isolation in darters as a function of genetic distance and color distance

    Science.gov (United States)

    Moran, Rachel L.; Zhou, Muchu; Catchen, Julian M.; Fuller, Rebecca C.

    2017-01-01

    Abstract Determining which reproductive isolating barriers arise first between geographically isolated lineages is critical to understanding allopatric speciation. We examined behavioral isolation among four recently diverged allopatric species in the orangethroat darter clade (Etheostoma: Ceasia). We also examined behavioral isolation between each Ceasia species and the sympatric rainbow darter Etheostoma caeruleum. We asked (1) is behavioral isolation present between allopatric Ceasia species, and how does this compare to behavioral isolation with E. caeruleum, (2) does male color distance and/or genetic distance predict behavioral isolation between species, and (3) what are the relative contributions of female choice, male choice, and male competition to behavioral isolation? We found that behavioral isolation, genetic differentiation, and male color pattern differentiation were present between allopatric Ceasia species. Males, but not females, discerned between conspecific and heterospecific mates. Males also directed more aggression toward conspecific rival males. The high levels of behavioral isolation among Ceasia species showed no obvious pattern with genetic distance or male color distance. However, when the E. caeruleum was included in the analysis, an association between male aggression and male color distance was apparent. We discuss the possibility that reinforcement between Ceasia and E. caeruleum is driving behavioral isolation among allopatric Ceasia species. PMID:28776645

  13. Isolation, Culture, and Motility Measurements of Epidermal Melanocytes from GFP-Expressing Reporter Mice.

    Science.gov (United States)

    Dagnino, Lina; Crawford, Melissa

    2018-03-27

    In this article, we provide a method to isolate primary epidermal melanocytes from reporter mice, which also allow targeted gene inactivation. The mice from which these cells are isolated are bred into a Rosa26 mT/mG reporter background, which results in GFP expression in the targeted melanocytic cell population. These cells are isolated and cultured to >95% purity. The cells can be used for gene expression studies, clonogenic experiments, and biological assays, such as capacity for migration. Melanocytes are slow moving cells, and we also provide a method to measure motility using individual cell tracking and data analysis.

  14. The contribution of the Y chromosome to hybrid male sterility in house mice.

    Science.gov (United States)

    Campbell, Polly; Good, Jeffrey M; Dean, Matthew D; Tucker, Priscilla K; Nachman, Michael W

    2012-08-01

    Hybrid sterility in the heterogametic sex is a common feature of speciation in animals. In house mice, the contribution of the Mus musculus musculus X chromosome to hybrid male sterility is large. It is not known, however, whether F1 male sterility is caused by X-Y or X-autosome incompatibilities or a combination of both. We investigated the contribution of the M. musculus domesticus Y chromosome to hybrid male sterility in a cross between wild-derived strains in which males with a M. m. musculus X chromosome and M. m. domesticus Y chromosome are partially sterile, while males from the reciprocal cross are reproductively normal. We used eight X introgression lines to combine different X chromosome genotypes with different Y chromosomes on an F1 autosomal background, and we measured a suite of male reproductive traits. Reproductive deficits were observed in most F1 males, regardless of Y chromosome genotype. Nonetheless, we found evidence for a negative interaction between the M. m. domesticus Y and an interval on the M. m. musculus X that resulted in abnormal sperm morphology. Therefore, although F1 male sterility appears to be caused mainly by X-autosome incompatibilities, X-Y incompatibilities contribute to some aspects of sterility.

  15. No evidence for female discrimination against male house mice carrying a selfish genetic element.

    Science.gov (United States)

    Sutter, Andreas; Lindholm, Anna K

    2016-12-01

    Meiotic drivers distort transmission to the next generation in their favor, with detrimental effects on the fitness of their homologues and the rest of the genome. Male carriers of meiotic drivers commonly inflict costs on their mates through genetic incompatibility, reduced fecundity, or biased brood sex ratios. Given these costs, evidence for female discrimination against male carriers is surprisingly rare. One of few examples is the t haplotype in house mice, a meiotic driver that shows strong transmission distortion in males and is typically homozygote lethal. As a consequence, mating between 2 t heterozygous (+/ t ) mice leads to high embryo mortality. Previous experiments showing that +/ t females avoid this incompatibility cost by preferring +/+ versus +/ t males have inferred preference based on olfactory cues or brief social interactions. Evidence from mating contexts in laboratory settings and semi-natural populations has been inconclusive. Here, we investigated female choice from a large number of no-choice mating trials. We found no evidence for discrimination against +/ t males based on mating, remating, and copulatory behavior. Further, we found no evidence for avoidance of incompatibility through selective interactions between gametes. The likelihood of mating showed significant effects of female weight and genotype, suggesting that our test paradigm enabled females to exhibit mate choice. We discuss the strengths and limitations of our approach. By explicitly considering selection at both the individual and gene level, we argue why precopulatory female discrimination by +/ t females may be less evolutionarily stable than discrimination by all females based on postcopulatory mechanisms.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  18. Constitutive luteinizing hormone receptor signaling causes sexual dysfunction and Leydig cell adenomas in male mice.

    Science.gov (United States)

    Hai, Lan; Hiremath, Deepak S; Paquet, Marilène; Narayan, Prema

    2017-05-01

    The luteinizing hormone receptor (LHCGR) is necessary for fertility, and genetic mutations cause defects in reproductive development and function. Activating mutations in LHCGR cause familial male-limited precocious puberty (FMPP). We have previously characterized a mouse model (KiLHRD582G) for FMPP that exhibits the same phenotype of precocious puberty, Leydig cell hyperplasia, and elevated testosterone as boys with the disorder. We observed that KiLHRD582G male mice became infertile by 6 months of age, although sperm count and motility were normal. In this study, we sought to determine the reason for the progressive infertility and the long-term consequences of constant LHCGR signaling. Mating with superovulated females showed that infertile KiLHRD582G mice had functional sperm and normal accessory gland function. Sexual behavior studies revealed that KiLHRD582G mice mounted females, but intromission was brief and ejaculation was not achieved. Histological analysis of the reproductive tract showed unique metaplastic changes resulting in pseudostratified columnar epithelial cells with cilia in the ampulla and chondrocytes in the penile body of the KiLHRD582G mice. The infertile KiLHRD582G exhibited enlarged sinusoids and a decrease in smooth muscle content in the corpora cavernosa of the penile body. However, collagen content was unchanged. Leydig cell adenomas and degenerating seminiferous tubules were seen in 1-year-old KiLHRD582G mice. We conclude that progressive infertility in KiLHRD582G mice is due to sexual dysfunction likely due to functional defects in the penis. © The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please journals.permissions@oup.com.

  19. Hepatoprotective Effects of Met-enkephalin on Acetaminophen-Induced Liver Lesions in Male CBA Mice

    OpenAIRE

    Martinić, Roko; Šošić, Hrvoje; Turčić, Petra; Konjevoda, Paško; Fučić, Aleksandra; Stojković, Ranko; Aralica, Gorana; Gabričević, Mario; Weitner, Tin; Štambuk, Nikola

    2014-01-01

    Recent histopathological investigations in patients with hepatitis suggested possible involvement of Met-enkephalin and its receptors in the pathophysiology of hepatitis. Consequently, we evaluated the potential hepatoprotective effects of this endogenous opioid pentapeptide in the experimental model of acetaminophen induced hepatotoxicity in male CBA mice. Met-enkephalin exhibited strong hepatoprotective effects in a dose of 7.5 mg/kg, which corresponds to the protective dose reported for se...

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

    International Nuclear Information System (INIS)

    Minamisawa, Takeru; Hirokaga, Kouichi; Sasaki, Shunsaku; Noda, Yutaka.

    1992-01-01

    Aggressive behavior (AB) in first generation (F 1 ) hybrid male C57BL/6 x C3H 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. (author)

  1. Cis-bifenthrin induces immunotoxicity in adolescent male C57BL/6 mice.

    Science.gov (United States)

    Wang, Xia; Gao, Xingli; He, Bingnan; Zhu, Jiawei; Lou, Huihui; Hu, Qinglian; Jin, Yuanxiang; Fu, Zhengwei

    2017-07-01

    Bifenthrin (BF) is an important synthetic pyrethroid. Previous studies have demonstrated that cis-BF exhibits toxic effects on development, the neurological, reproductive and endocrine system. In this study, we evaluated the immunotoxicity caused by cis-BF in adolescent male C57BL/6 mice. Mice were exposed orally to 0, 5, 10, and 20 mg/kg/d for 3 weeks. The results showed that body weight, spleen weight, and splenic cellularity decreased in mice exposed to 20 mg/kg/d cis-BF. Additionally, we found that the mRNA levels of the pro-inflammatory factors IL-1β, IL-6, CXCL-1, and TNF-α, in peritoneal macrophages, the spleen, and the thymus were inhibited in the cis-BF-treated groups. Moreover, MTT assays demonstrated that cis-BF inhibited splenocyte proliferation stimulated by LPS or Con A, as well as the secretion of IFN-γ on Con A stimulation. Collectively, the results of this study suggest that exposure to cis-BF has the potential to induce immunotoxicity in adolescent male C57BL/6 mice. © 2017 Wiley Periodicals, Inc.

  2. Silk amino acids improve physical stamina and male reproductive function of mice.

    Science.gov (United States)

    Shin, Sunhee; Yeon, Seongho; Park, Dongsun; Oh, Jiyoung; Kang, Hyomin; Kim, Sunghyun; Joo, Seong Soo; Lim, Woo-Taek; Lee, Jeong-Yong; Choi, Kyung-Chul; Kim, Ki Yon; Kim, Seung Up; Kim, Jong-Choon; Kim, Yun-Bae

    2010-01-01

    The effects of a silk amino acid (SAA) preparation on the physical stamina and male reproductive function of mice were investigated. Eight-week-old male ICR mice (29-31 g) were orally administered SAA (50, 160 or 500 mg/kg) for 44 d during 30-min daily swimming exercise. The mice were subjected to a weight-loaded (5% of body weight) forced swimming on the 14th, 28th and 42nd day to determine maximum swimming time, and after a 2-d recovery period (treated with SAA without swimming exercise), parameters related to fatigue and reproductive function were analyzed from blood, muscles and reproductive organs. Repeated swimming exercise increased the maximum swimming time to some extent, in spite of a marked reduction in body weight gain, and SAA further enhanced the stamina in a dose-dependent manner. Forced swimming exercises increased blood parameters of tissue injury, but depleted blood glucose and tissue glycogen, which were substantially prevented by SAA treatment. In addition, SAA significantly reduced the muscular thiobarbituric acid-reactive substances and blood corticosterone content increased by forced swimming. Swimming exercise decreased the blood testosterone level, which was recovered by SAA, leading to enhanced sperm counts. These combined results indicate that SAA not only enhances physical stamina by minimizing damage to tissues, including muscles, as well as preventing energy depletion caused by swimming stress, but also improves male reproductive function by increasing testosterone and sperm counts.

  3. Genetic and hormonal control of hepatic steatosis in female and male mice.

    Science.gov (United States)

    Norheim, Frode; Hui, Simon T; Kulahcioglu, Emre; Mehrabian, Margarete; Cantor, Rita M; Pan, Calvin; Parks, Brian W; Lusis, Aldons J

    2017-01-01

    The etiology of nonalcoholic fatty liver disease is complex and influenced by factors such as obesity, insulin resistance, hyperlipidemia, and sex. We now report a study on sex difference in hepatic steatosis in the context of genetic variation using a population of inbred strains of mice. While male mice generally exhibited higher concentration of hepatic TG levels on a high-fat high-sucrose diet, sex differences showed extensive interaction with genetic variation. Differences in percentage body fat were the best predictor of hepatic steatosis among the strains and explained about 30% of the variation in both sexes. The difference in percent gonadal fat and HDL explained 9.6% and 6.7% of the difference in hepatic TGs between the sexes, respectively. Genome-wide association mapping of hepatic TG revealed some striking differences in genetic control of hepatic steatosis between females and males. Gonadectomy increased the hepatic TG to body fat percentage ratio among male, but not female, mice. Our data suggest that the difference between the sexes in hepatic TG can be partly explained by differences in body fat distribution, plasma HDL, and genetic regulation. Future studies are required to understand the molecular interactions between sex, genetics, and the environment. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  4. Focal lesions within the ventral striato-pallidum abolish attraction for male chemosignals in female mice.

    Science.gov (United States)

    Agustín-Pavón, Carmen; Martínez-García, Fernando; Lanuza, Enrique

    2014-02-01

    In rodents, socio-sexual behaviour is largely mediated by chemosensory cues, some of which are rewarding stimuli. Female mice display an innate attraction towards male chemosignals, dependent on the vomeronasal system. This behaviour likely reflects the hedonic value of sexual chemosignals. The anteromedial aspect of the olfactory tubercle, along with its associated islands of Calleja, receives vomeronasal inputs and sexually-dimorphic vasopressinergic innervation. Thus, we hypothesised that this portion of the ventral striato-pallidum, known to be involved in reward processing, might be important for sexual odorant-guided behaviours. In this study, we demonstrate that lesions of this region, but not of regions in the posterolateral striato-pallidum, abolish the attraction of female mice for male chemosignals, without affecting significantly their preference for a different natural reward (a sucrose solution). These results show that, at least in female mice, the integrity of the anterior aspect of the medioventral striato-pallidum, comprising a portion of the olfactory tubercle and associated islands of Calleja, is necessary for the attraction for male chemosignals. We suggest that this region contributes to the processing of the hedonic properties of biologically significant odorants. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Social isolation induces behavioral and neuroendocrine disturbances relevant to depression in female and male prairie voles

    OpenAIRE

    Grippo, Angela J.; Gerena, Davida; Huang, Jonathan; Kumar, Narmda; Shah, Maulin; Ughreja, Raj; Carter, C. Sue

    2007-01-01

    Supportive social interactions may be protective against stressors and certain mental and physical illness, while social isolation may be a powerful stressor. Prairie voles are socially monogamous rodents that model some of the behavioral and physiological traits displayed by humans, including sensitivity to social isolation. Neuroendocrine and behavioral parameters, selected for their relevance to stress and depression, were measured in adult female and male prairie voles following 4 weeks o...

  6. Study on The Reproductive Organs and Fertility of The Male Mice following Administration of Metronidazole

    Directory of Open Access Journals (Sweden)

    Poonam Singh

    2013-01-01

    Full Text Available Background: Metronidazole (MTZ is commonly used as an antibacterial and antiprotozoaldrug. Various doses of MTZ have been reported to inhibit spermatogenic activityand sperm indices.Materials and Methods: In this experimental study, dose-dependent effects of MTZ onthe structural and functional integrity of the testis and accessory reproductive organshave been investigated. Adult male mice of Swiss strain were administered orally withMTZ at the doses of 250 mg/kgBW/day and 500 mg/kgBW/day for 28 consecutive daysto study the changes in the testis, epididymis, seminal vesicle, sperm indices and fertility.Reversal effects of the drug were also studied on the same mice, 42 days after cessationof the treatment.Results: Therapeutic dose of MTZ (250 mg/kgBW/day neither altered the weights ofthe testis, epididymis and seminal vesicle nor their histoarchitecture and sperm indices.The drug at the high dose (500 mg/kg BW/day caused significant reductions in theweights of the testis and epididymis. Histoarchitecture of the testis and epididymis at thehigh dose revealed marked regressive changes while that of seminal vesicle remainedunaffected. Significant reductions were noticed in the motility, viability and count ofepididymal spermatozoa while the concentrations of epididymal sialic acid and seminalvesicular fructose remained unaltered after the treatment. No significant changes werenoticed in the mating ability as well as in the level of serum testosterone in the treatedmice. Fertility of the male mice treated with high dose of MTZ declined markedly leadingto an increase in pre- and postimplantation loss while a significant decrease wasnoticed in the number of live blastocysts in females impregnated with such males. MTZinducedchanges in the male reproductive organs and fertility were reinstated 42 daysafter cessation of the treatment.Conclusion: High dose of MTZ induced reversible deleterious effects on the male reproductionand fertility.

  7. Effects of Psychosocial Stress on Subsequent Hemorrhagic Shock and Resuscitation in Male Mice.

    Science.gov (United States)

    Langgartner, Dominik; Wachter, Ulrich; Hartmann, Clair; Gröger, Michael; Vogt, Josef; Merz, Tamara; McCook, Oscar; Fink, Marina; Kress, Sandra; Georgieff, Michael; Kunze, Julia F; Radermacher, Peter L; Reber, Stefan O; Wepler, Martin

    2018-06-08

    Hypoxemia and tissue ischemia during hemorrhage as well as formation of oxygen and nitrogen radicals during resuscitation promote hyperinflammation and, consequently, trigger severe multiple-organ-failure (MOF). Individuals diagnosed with stress-related disorders or reporting a life history of psychosocial stress are characterized by chronic low-grade inflammation and a reduced glucocorticoid (GC) signaling. We hypothesized that exposure to chronic psychosocial stress during adulthood prior to hemorrhagic shock increases oxidative/nitrosative stress and therefore the risk of developing MOF in mice. To induce chronic psychosocial stress linked to mild immune activation and reduced GC signaling in male mice, the chronic subordinate colony housing (CSC) paradigm was employed. Single-housed (SHC) mice were used as controls. Subsequently, CSC and SHC mice were exposed to hemorrhagic shock following resuscitation to investigate the effects of prior psychosocial stress load on survival, organ function, metabolism, oxidative/nitrosative stress, and inflammatory readouts. An increased adrenal weight in CSC mice indicates that the stress paradigm reliably worked. However, no effect of prior psychosocial stress on outcome after subsequent hemorrhage and resuscitation could be detected. Chronic psychosocial stress during adulthood is not sufficient to promote hemodynamic complications, organ dysfunction, metabolic disturbances and did not increase the risk of MOF after subsequent hemorrhage and resuscitation. Intravenous norepinephrine to keep target hemodynamics might have led to a certain level of oxidative stress in both groups and, therefore, disguised potential effects of chronic psychosocial stress on organ function after hemorrhagic shock in the present murine trauma model.

  8. An Essential Physiological Role for MCT8 in Bone in Male Mice.

    Science.gov (United States)

    Leitch, Victoria D; Di Cosmo, Caterina; Liao, Xiao-Hui; O'Boy, Sam; Galliford, Thomas M; Evans, Holly; Croucher, Peter I; Boyde, Alan; Dumitrescu, Alexandra; Weiss, Roy E; Refetoff, Samuel; Williams, Graham R; Bassett, J H Duncan

    2017-09-01

    T3 is an important regulator of skeletal development and adult bone maintenance. Thyroid hormone action requires efficient transport of T4 and T3 into target cells. We hypothesized that monocarboxylate transporter (MCT) 8, encoded by Mct8 on the X-chromosome, is an essential thyroid hormone transporter in bone. To test this hypothesis, we determined the juvenile and adult skeletal phenotypes of male Mct8 knockout mice (Mct8KO) and Mct8D1D2KO compound mutants, which additionally lack the ability to convert the prohormone T4 to the active hormone T3. Prenatal skeletal development was normal in both Mct8KO and Mct8D1D2KO mice, whereas postnatal endochondral ossification and linear growth were delayed in both Mct8KO and Mct8D1D2KO mice. Furthermore, bone mass and mineralization were decreased in adult Mct8KO and Mct8D1D2KO mice, and compound mutants also had reduced bone strength. Delayed bone development and maturation in Mct8KO and Mct8D1D2KO mice is consistent with decreased thyroid hormone action in growth plate chondrocytes despite elevated serum T3 concentrations, whereas low bone mass and osteoporosis reflects increased thyroid hormone action in adult bone due to elevated systemic T3 levels. These studies identify an essential physiological requirement for MCT8 in chondrocytes, and demonstrate a role for additional transporters in other skeletal cells during adult bone maintenance.

  9. Neonatal maternal separation increases susceptibility to experimental colitis and acute stress exposure in male mice

    Directory of Open Access Journals (Sweden)

    Isabella M. Fuentes

    2016-12-01

    Full Text Available Experiencing early life stress can result in maladjusted stress response via dysregulation of the hypothalamic-pituitary-adrenal axis and serves as a risk factor for developing chronic pelvic pain disorders. We investigated whether neonatal maternal separation (NMS would increase susceptibility to experimental colitis or exposure to acute or chronic stress. Male mice underwent NMS from postnatal day 1–21 and as adults were assessed for open field behavior, hindpaw sensitivity, and visceromotor response (VMR to colorectal distension (CRD. VMR was also measured before and after treatment with intracolonic trinitrobenzene sulfonic acid (TNBS or exposure to acute or chronic water avoidance stress (WAS. Myeloperoxidase (MPO activity, proinflammatory gene and corticotropin-releasing factor (CRF receptor expression were measured in distal colon. Baseline VMR was not affected by NMS, but undergoing CRD increased anxiety-like behaviors and mechanical hindpaw sensitivity of NMS mice. Treatment with TNBS dose-dependently decreased body weight and survival only in NMS mice. Following TNBS treatment, IL-6 and artemin mRNA levels were decreased in the distal colon of NMS mice, despite increased MPO activity. A single WAS exposure increased VMR during CRD in NMS mice and increased IL-6 mRNA and CRF2 protein levels in the distal colon of naïve mice, whereas CRF2 protein levels were heightened in NMS colon both at baseline and post-WAS exposure. Taken together, these results suggest that NMS in mice disrupts inflammatory- and stress-induced gene expression in the colon, potentially contributing towards an exaggerated response to specific stressors later in life.

  10. Skeletal response of male mice to anabolic hormone therapy in the absence of the Igfals gene.

    Science.gov (United States)

    Kennedy, Oran D; Sun, Hui; Wu, Yingjie; Courtland, Hayden-William; Williams, Garry A; Cardoso, Luis; Basta-Pljakic, Jelena; Schaffler, Mitchell B; Yakar, Shoshana

    2014-03-01

    IGF-I is a critical regulator of skeletal acquisition, which acts in endocrine and autocrine/paracrine modes. In serum, IGF-I is carried by the IGF-binding proteins in binary complexes. Further stabilization of these complexes is achieved by binding to the acid labile subunit (ALS) in a ternary complex (of IGF-I-IGF-binding protein 3/5-ALS). Ablation of the Igfals gene in humans (ALS deficiency) and mice (ALS knockout [ALSKO]) leads to markedly decreased serum IGF-I levels, growth retardation, and impaired skeletal acquisition. To investigate whether hormonal replacement therapy would improve the skeletal phenotype in cases of Igfals gene ablation, we treated male ALSKO mice with GH, IGF-I, or a combination of both. Treatments were administered to animals between 4 and 16 weeks of age or from 8 to 16 weeks of age. Although all treatment groups showed an increase (20%) in serum IGF-I levels, there was no increase in body weight, weight gain, or bone length in either age group. Despite the blunted linear growth in response to hormone therapy, ALSKO mice treated with GH showed radial bone growth, which contributed to bone strength tested by 4-point bending. We found that ALSKO mice treated with GH showed increased total cross-sectional area, cortical bone area, and cortical thickness by microtomography. Dynamic histomorphometry showed that although GH and double treatment groups resulted in trends towards increased bone formation parameters, these did not reach significance. However, bone resorption parameters were significantly increased in all treatment groups. ALSKO mice treated between 4 and 16 weeks of age showed minor differences in bone traits compared with vehicle-treated mice. In conclusion, treatment with GH and IGF-I do not work synergistically to rescue the stunted growth found in mice lacking the Igfals gene. Although GH alone appears to increase bone parameters slightly, it does not affect body weight or linear growth.

  11. Phase-Specific Vocalizations of Male Mice at the Initial Encounter during the Courtship Sequence.

    Directory of Open Access Journals (Sweden)

    Yui K Matsumoto

    Full Text Available 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.

  12. Dietary Mung Bean Protein Reduces Hepatic Steatosis, Fibrosis, and Inflammation in Male Mice with Diet-Induced, Nonalcoholic Fatty Liver Disease.

    Science.gov (United States)

    Watanabe, Hitoshi; Inaba, Yuka; Kimura, Kumi; Asahara, Shun-Ichiro; Kido, Yoshiaki; Matsumoto, Michihiro; Motoyama, Takayasu; Tachibana, Nobuhiko; Kaneko, Shuichi; Kohno, Mitsutaka; Inoue, Hiroshi

    2017-01-01

    As the prevalence of nonalcoholic fatty liver disease (NAFLD), including steatosis and nonalcoholic steatohepatitis, is increasing, novel dietary approaches are required for the prevention and treatment of NAFLD. We evaluated the potential of mung bean protein isolate (MuPI) to prevent NAFLD progression. In Expts. 1 and 2, the hepatic triglyceride (TG) concentration was compared between 8-wk-old male mice fed a high-fat diet (61% of energy from fat) containing casein, MuPI, and soy protein isolate and an MuPI-constituent amino acid mixture as a source of amino acids (18% of energy) for 4 wk. In Expt. 3, hepatic fatty acid synthase (Fasn) expression was evaluated in 8-wk-old male Fasn-promoter-reporter mice fed a casein- or MuPI-containing high-fat diet for 20 wk. In Expt. 4, hepatic fibrosis was examined in 8-wk-old male mice fed an atherogenic diet (61% of energy from fat, containing 1.3 g cholesterol/100 g diet) containing casein or MuPI (18% of energy) as a protein source for 20 wk. In the high fat-diet mice, the hepatic TG concentration in the MuPI group decreased by 66% and 47% in Expt. 1 compared with the casein group (P hepatic TG concentration were lower in the MuPI group than in those fed casein (P hepatic fibrosis was not induced in the MuPI group, whereas it developed overtly in the casein group. MuPI potently reduced hepatic lipid accumulation in mice and may be a potential foodstuff to prevent NAFLD onset and progression. © 2017 American Society for Nutrition.

  13. Comparative study of different methods used to isolate Trypanosoma cruz i for defibrinated blood of irradiated mice

    International Nuclear Information System (INIS)

    Fontes, G.; Romanha, A.J.; Brener, Z.

    1991-01-01

    Different methods are being used for the isolation and purification of Trypanosoma cruzi blood forms from infected vertebrate hosts. In this study, we compare four of these methods (differential centrifugation, Ficoll-Hypaque, Histopaque 1077 and metrizamide) in terms of parasite recovery rates, contamination with cells, duration of the process and role of host irradiation. Male albino Swiss mice irradiated in a Gamma Cell 220(500 rads) were inoculated with C L and V-10 T.cruzi strains and bled at the peak of parasitemia. Infected defibrinated blood was then used for the isolation. Although all methods permitted the recovery of viable trypomastigotes, the best results were obtained with Ficoll-Hypaque and Histopaque 1077. Recovery rates ranged between 71% to 88% and parasite-enriched preparations were obtained in approximately 75 min. Irradiation and blood defibrination drastically reduced platelet and leukocyte contamination of the preparations. (author)

  14. Animal models of physiologic markers of male reproduction: genetically defined infertile mice

    Energy Technology Data Exchange (ETDEWEB)

    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.

  15. Silymarin and Nigella sativa extract ameliorate paracetamol induced oxidative stress and renal dysfunction in male mice

    Directory of Open Access Journals (Sweden)

    Reham Zakaria Hamza

    2015-06-01

    Full Text Available Objective: To evaluate the ameliorative role of silymarin or/and Nigella sativa (N. sativa water extract against N-acetyl-p-aminophenol (APAP-induced renal function deterioration in male mice at the biochemical levels. Methods: The mice were divided into seven groups (10/group. The first group was served as control. The second group was treated with dose of APAP. The third and fourth groups were treated with silymarin alone and N. sativa water extract alone, respectively. The fifth and sixth groups were treated with combination of APAP with silymarin and APAP with N. sativa water extract, respectively. The seventh group was treated with a combination of both ameliorative compounds (silymarin and N. sativa water extract with APAP and all animals were treated for a period of 30 days. Results: Exposure to APAP at the treated dose for mice led to an alteration of kidney function parameters, increase in the level of serum urea and creatinine. Also, paracetamol administration induced oxidative stress in kidney homogenates by increasing malondialdhyde level and decreasing superoxide dismutase and catalase activities and this stress was ameliorated by administration of either silymarin or N. sativa water extract. Conclusions: Administration of silymarin or/and N. sativa water extract to APAP-treated mice alleviate the toxicity of APAP, and this appeared clearly by biochemical improvement of kidney function parameters and antioxidant parameters. But, the alleviation is more pronounced with the both antioxidants. Thus, the pronounce effect of silymarin and N. sativa water extract is most effective in reducing the toxicity induced by APAP and improving the kidney function parameters and antioxidant status of kidney of male mice.

  16. Relationships among estrogen receptor, oxytocin and vasopressin gene expression and social interaction in male mice.

    Science.gov (United States)

    Murakami, G; Hunter, R G; Fontaine, C; Ribeiro, A; Pfaff, D

    2011-08-01

    The incidence of social disorders such as autism and schizophrenia is significantly higher in males, and the presentation more severe, than in females. This suggests the possible contribution of sex hormones to the development of these psychiatric disorders. There is also evidence that these disorders are highly heritable. To contribute toward our understanding of the mechanisms underlying social behaviors, particularly social interaction, we assessed the relationship of social interaction with gene expression for two neuropeptides, oxytocin (OT) and arginine vasopressin (AVP), using adult male mice. Social interaction was positively correlated with: oxytocin receptor (OTR) and vasopressin receptor (V1aR) mRNA expression in the medial amygdala; and OT and AVP mRNA expression in the paraventricular nucleus of the hypothalamus (PVN). When mice representing extremes of social interaction were compared, all of these mRNAs were more highly expressed in high social interaction mice than in low social interaction mice. OTR and V1aR mRNAs were highly correlated with estrogen receptor α (ERα) mRNA in the medial amygdala, and OT and AVP mRNAs with estrogen receptor β (ERβ) mRNA in the PVN, indicating that OT and AVP systems are tightly regulated by estrogen receptors. A significant difference in the level of ERα mRNA in the medial amygdala between high and low social interaction mice was also observed. These results support the hypothesis that variations of estrogen receptor levels are associated with differences in social interaction through the OT and AVP systems, by upregulating gene expression for those peptides and their receptors. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  17. GPR56 is essential for testis development and male fertility in mice.

    Science.gov (United States)

    Chen, Guangchun; Yang, Liquan; Begum, Shahinoor; Xu, Lei

    2010-12-01

    Testis development is critical for male fertility and continuation of the mammalian species. Essential structural components of testes are seminiferous tubules, which are lined by Sertoli cells and provide nutrients and physical protection for the maturation of sperm. Seminiferous tubule formation is initiated in embryos as testis cords and relies on their remodeling for maturation during development. Recently, three-dimensional image analyses showed that testis cords in different parts of embryonic gonads undergo distinct remodeling processes. How this asymmetric remodeling is regulated has not been investigated. We report here that the absence of an adhesion G protein-coupled receptor, GPR56, leads to partial disruption of seminiferous tubules and reduced fertility in male mice. The defects appear to originate asymmetrically in embryonic gonads, but subsequent to the initial establishment of testis cords, suggesting that GPR56 might act to establish a spatial and/or temporal cue for asymmetric cord remodeling during male gonad development. © 2010 Wiley-Liss, Inc.

  18. Differences in peripheral sensory input to the olfactory bulb between male and female mice

    Science.gov (United States)

    Kass, Marley D.; Czarnecki, Lindsey A.; Moberly, Andrew H.; McGann, John P.

    2017-04-01

    Female mammals generally have a superior sense of smell than males, but the biological basis of this difference is unknown. Here, we demonstrate sexually dimorphic neural coding of odorants by olfactory sensory neurons (OSNs), primary sensory neurons that physically contact odor molecules in the nose and provide the initial sensory input to the brain’s olfactory bulb. We performed in vivo optical neurophysiology to visualize odorant-evoked OSN synaptic output into olfactory bub glomeruli in unmanipulated (gonad-intact) adult mice from both sexes, and found that in females odorant presentation evoked more rapid OSN signaling over a broader range of OSNs than in males. These spatiotemporal differences enhanced the contrast between the neural representations of chemically related odorants in females compared to males during stimulus presentation. Removing circulating sex hormones makes these signals slower and less discriminable in females, while in males they become faster and more discriminable, suggesting opposite roles for gonadal hormones in influencing male and female olfactory function. These results demonstrate that the famous sex difference in olfactory abilities likely originates in the primary sensory neurons, and suggest that hormonal modulation of the peripheral olfactory system could underlie differences in how males and females experience the olfactory world.

  19. Male fertility is reduced by chronic intermittent hypoxia mimicking sleep apnea in mice.

    Science.gov (United States)

    Torres, Marta; Laguna-Barraza, Ricardo; Dalmases, Mireia; Calle, Alexandra; Pericuesta, Eva; Montserrat, Josep M; Navajas, Daniel; Gutierrez-Adan, Alfonso; Farré, Ramon

    2014-11-01

    Obstructive sleep apnea (OSA) is characterized by intermittent hypoxia and oxidative stress. However, it is unknown whether intermittent hypoxia mimicking OSA modifies male fertility. We tested the hypothesis that male fertility is reduced by chronic intermittent hypoxia mimicking OSA in a mouse model. Case-control comparison in a murine model. University research laboratory. Eighteen F1 (C57BL/6xCBA) male mice. Mice were subjected to a pattern of periodic hypoxia (20 sec at 5% O2 followed by 40 sec of room air) 6 h/day for 60 days or normoxia. After this period, mice performed a mating trial to determine effective fertility by assessing the number of pregnant females and fetuses. After euthanasia, oxidative stress in testes was assessed by measuring the expression of glutathione peroxidase 1 (Gpx1) and superoxide dismutase-1 (Sod1) by reverse-transcription polymerase chain reaction. Sperm motility was determined by Integrated Semen Analysis System (ISAS). Intermittent hypoxia significantly increased testicular oxidative stress, showing a reduction in the expression of Gpx1 and Sod1 by 38.9% and 34.4%, respectively, as compared with normoxia (P intermittent hypoxia group (P = 0.04). The proportion of pregnant females and number of fetuses per mating was significantly lower in the intermittent hypoxia group (0.33 ± 0.10 and 2.45 ± 0.73, respectively) than in normoxic controls (0.72 ± 0.16 and 5.80 ± 1.24, respectively). These results suggest that the intermittent hypoxia associated with obstructive sleep apnea (OSA) could induce fertility reduction in male patients with this sleep breathing disorder.

  20. Differential effects of social isolation in adolescent and adult mice on behavior and cortical gene expression.

    Science.gov (United States)

    Lander, Sharon S; Linder-Shacham, Donna; Gaisler-Salomon, Inna

    2017-01-01

    Intact function of the medial prefrontal cortex (mPFC) function relies on proper development of excitatory and inhibitory neuronal populations and on integral myelination processes. Social isolation (SI) affects behavior and brain circuitry in adulthood, but previous rodent studies typically induced prolonged (post-weaning) exposure and failed to directly compare between the effects of SI in adolescent and adulthood. Here, we assessed the impact of a 3-week SI period, starting in mid-adolescence (around the onset of puberty) or adulthood, on a wide range of behaviors in adult male mice. Additionally, we asked whether adolescent SI would differentially affect the expression of excitatory and inhibitory neuronal markers and myelin-related genes in mPFC. Our findings indicate that mid-adolescent or adult SI increase anxiogenic behavior and locomotor activity. However, SI in adolescence uniquely affects the response to the psychotomimetic drug amphetamine, social and novelty exploration and performance in reversal and attentional set shifting tasks. Furthermore, adolescent but not adult SI increased the expression of glutamate markers in the adult mPFC. Our results imply that adolescent social deprivation is detrimental for normal development and may be particularly relevant to the investigation of developmental psychopathology. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Recombination rate variation in mice from an isolated island.

    Science.gov (United States)

    Wang, Richard J; Gray, Melissa M; Parmenter, Michelle D; Broman, Karl W; Payseur, Bret A

    2017-01-01

    Recombination rate is a heritable trait that varies among individuals. Despite the major impact of recombination rate on patterns of genetic diversity and the efficacy of selection, natural variation in this phenotype remains poorly characterized. We present a comparison of genetic maps, sampling 1212 meioses, from a unique population of wild house mice (Mus musculus domesticus) that recently colonized remote Gough Island. Crosses to a mainland reference strain (WSB/EiJ) reveal pervasive variation in recombination rate among Gough Island mice, including subchromosomal intervals spanning up to 28% of the genome. In spite of this high level of polymorphism, the genomewide recombination rate does not significantly vary. In general, we find that recombination rate varies more when measured in smaller genomic intervals. Using the current standard genetic map of the laboratory mouse to polarize intervals with divergent recombination rates, we infer that the majority of evolutionary change occurred in one of the two tested lines of Gough Island mice. Our results confirm that natural populations harbour a high level of recombination rate polymorphism and highlight the disparities in recombination rate evolution across genomic scales. © 2016 John Wiley & Sons Ltd.

  2. Excessive growth hormone expression in male GH transgenic mice adversely alters bone architecture and mechanical strength.

    Science.gov (United States)

    Lim, S V; Marenzana, M; Hopkinson, M; List, E O; Kopchick, J J; Pereira, M; Javaheri, B; Roux, J P; Chavassieux, P; Korbonits, M; Chenu, C

    2015-04-01

    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.

  3. Prolyl Endopeptidase (PREP) is Associated With Male Reproductive Functions and Gamete Physiology in Mice.

    Science.gov (United States)

    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. © 2015 Wiley Periodicals, Inc.

  4. Influence of chronic exposure to uranium on male reproduction in mice

    International Nuclear Information System (INIS)

    Llobet, J.M.; Sirvent, J.J.; Ortega, A.; Domingo, J.L.

    1991-01-01

    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

  5. Social experiences during adolescence affect anxiety-like behavior but not aggressiveness in male mice.

    Science.gov (United States)

    Meyer, Neele; Jenikejew, Julia; Richter, S Helene; Kaiser, Sylvia; Sachser, Norbert

    2017-05-30

    Adolescence has lately been recognized as a key developmental phase during which an individual's behavior can be shaped. In a recent study with male mice varying in the expression of the serotonin transporter, escapable adverse social experiences during adolescence led to decreased anxiety-like behavior and increased exploratory and aggressive behavior compared to throughout beneficial experiences. Since in this study some behavioral tests took place with a delay of one week after the last social experiences have been made, it was not clear whether the observed effects really reflected the consequences of the experienced different social environments. To test this, the present study focused on the direct effects of beneficial and adverse social experiences on aggressiveness and anxiety-like behavior in C57BL/6J mice. In contrast to the previous study, behavioral testing took place immediately after the last social experiences had been made. Interestingly, whereas individuals from an escapable adverse environment showed significantly lower levels of anxiety-like and higher levels of exploratory behavior than animals from a beneficial environment, aggressive behavior was not affected. From this, we conclude that different social experiences during adolescence exert immediate effects on anxiety-like but not aggressive behavior in male mice. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Induction of external abnormalities in offspring of male mice irradiated with 252Cf neutron

    International Nuclear Information System (INIS)

    Kurishita, Akihiro; Ono, Tetsuya; Mori, Yuriko; Okada, Shigefumi; Sawada, Syozo

    1992-01-01

    To assess the genetic effects of fission neutron, the induction of external malformations was studied in F 1 fetuses after F 0 male mice were irradiated. Male mice of the ICR:MCH strain were irradiated with 252 Cf neutron at doses of 0.238, 0.475, 0.95 and 1.9 Gy. They were mated with non-irradiated female mice at 71-120 days after irradiation. Pregnant females were autopsied on day 18 of gestation and their fetuses were examined for deaths and external abnormalities. No increases of pre- and post-implantation losses were noted at any dose. External abnormalities were observed at rates of 1.40% in the 0.238 Gy, 2.23% in the 0.475 Gy, 3.36% in the 0.95 and 3.26% in the 1.9 Gy groups; the rate in the control group was 1.65%. The dose-response curve was linear up to 0.95 Gy, and then flattened out; the induction rate of external abnormalities was 2.7x10 -4 /gamete/cGy based on the linear regression. These results indicated that fission neutron effectively induces external abnormalities in F 1 fetuses after spermatogonial irradiation. (author). 29 refs.; 1 fig.; 2 tabs

  7. Social isolation after stroke leads to depressive-like behavior and decreased BDNF levels in mice.

    Science.gov (United States)

    O'Keefe, Lena M; Doran, Sarah J; Mwilambwe-Tshilobo, Laetitia; Conti, Lisa H; Venna, Venugopal R; McCullough, Louise D

    2014-03-01

    Social isolation prior to stroke leads to poorer outcomes after an ischemic injury in both animal and human studies. However, the impact of social isolation following stroke, which may be more clinically relevant as a target for therapeutic intervention, has yet to be examined. In this study, we investigated both the sub-acute (2 weeks) and chronic (7 weeks) effects of social isolation on post-stroke functional and histological outcome. Worsened histological damage from ischemic injury and an increase in depressive-like behavior was observed in isolated mice as compared to pair-housed mice. Mice isolated immediately after stroke showed a decrease in the levels of brain-derived neurotrophic factor (BDNF). These changes, both histological and behavioral, suggest an overall negative effect of social isolation on stroke outcome, potentially contributing to post-stroke depression and anxiety. Therefore, it is important to identify patients who have perceived isolation post-stroke to hopefully prevent this exacerbation of histological damage and subsequent depression. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Comparison of Neurological Function in Males and Females from Two Substrains of C57BL/6 Mice

    Directory of Open Access Journals (Sweden)

    Amy Ashworth

    2014-12-01

    Full Text Available 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.

  9. A role for the endocannabinoid 2-arachidonoyl-sn-glycerol for social and high-fat food reward in male mice.

    Science.gov (United States)

    Wei, Don; Lee, DaYeon; Li, Dandan; Daglian, Jennifer; Jung, Kwang-Mook; Piomelli, Daniele

    2016-05-01

    The endocannabinoid system is an important modulator of brain reward signaling. Investigations have focused on cannabinoid (CB1) receptors, because dissection of specific contributions of individual endocannabinoids has been limited by the available toolset. While we recently described an important role for the endocannabinoid anandamide in the regulation of social reward, it remains to be determined whether the other major endocannabinoid, 2-arachidonoyl-sn-glycerol (2-AG), serves a similar or different function. To study the role of 2-AG in natural reward, we used a transgenic mouse model (MGL-Tg mice) in which forebrain 2-AG levels are selectively reduced. We complemented behavioral analysis with measurements of brain 2-AG levels. We tested male MGL-Tg mice in conditioned place preference (CPP) tasks for high-fat food, social contact, and cocaine. We measured 2-AG content in the brain regions of interest by liquid chromatography/mass spectrometry. Male MGL-Tg mice are impaired in developing CPP for high-fat food and social interaction, but do develop CPP for cocaine. Furthermore, compared to isolated mice, levels of 2-AG in socially stimulated wild-type mice are higher in the nucleus accumbens and ventral hippocampus (183 and 140 % of controls, respectively), but unchanged in the medial prefrontal cortex. The results suggest that reducing 2-AG-mediated endocannabinoid signaling impairs social and high-fat food reward in male mice, and that social stimulation mobilizes 2-AG in key brain regions implicated in the control of motivated behavior. The time course of this response differentiates 2-AG from anandamide, whose role in mediating social reward was previously documented.

  10. Acute endocrine correlates of attack by lactating females in male mice: effects on plasma prolactin, luteinizing hormone and corticosterone levels.

    Science.gov (United States)

    Broida, J; Michael, S D; Svare, B

    1984-05-01

    Immediately following defeat inflicted by lactating Rockland-Swiss (R-S) albino mice, adult R-S male mice exhibited significant reductions in circulating prolactin (PRL) and luteinizing hormone (LH), but not corticosterone (CORT). These results suggest that acute neuroendocrine responses to intersex competition may be as dramatic as those previously reported for intermale encounters.

  11. Estradiol-induced, endothelial progenitor cell-mediated neovascularization in male mice with hind-limb ischemia

    NARCIS (Netherlands)

    Ruifrok, Willem-Peter T.; de Boer, Rudolf A.; Iwakura, Atsushi; Silver, Marcy; Kusano, Kengo; Tio, Rene A.; Losordo, Douglas W.

    We investigated whether administration of estradiol to male mice augments mobilization of bone marrow-derived endothelial progenitor cells (EPC) and incorporation into foci of neovascularization after hind-limb ischemia, thereby contributing to blood flow restoration. Mice were randomized and

  12. Hierarchy in the home cage affects behaviour and gene expression in group-housed C57BL/6 male mice.

    Science.gov (United States)

    Horii, Yasuyuki; Nagasawa, Tatsuhiro; Sakakibara, Hiroyuki; Takahashi, Aki; Tanave, Akira; Matsumoto, Yuki; Nagayama, Hiromichi; Yoshimi, Kazuto; Yasuda, Michiko T; Shimoi, Kayoko; Koide, Tsuyoshi

    2017-08-01

    Group-housed male mice exhibit aggressive behaviour towards their cage mates and form a social hierarchy. Here, we describe how social hierarchy in standard group-housed conditions affects behaviour and gene expression in male mice. Four male C57BL/6 mice were kept in each cage used in the study, and the social hierarchy was determined from observation of video recordings of aggressive behaviour. After formation of a social hierarchy, the behaviour and hippocampal gene expression were analysed in the mice. Higher anxiety- and depression-like behaviours and elevated gene expression of hypothalamic corticotropin-releasing hormone and hippocampal serotonin receptor subtypes were observed in subordinate mice compared with those of dominant mice. These differences were alleviated by orally administering fluoxetine, which is an antidepressant of the selective serotonin reuptake inhibitor class. We concluded that hierarchy in the home cage affects behaviour and gene expression in male mice, resulting in anxiety- and depression-like behaviours being regulated differently in dominant and subordinate mice.

  13. X-y interactions underlie sperm head abnormality in hybrid male house mice.

    Science.gov (United States)

    Campbell, Polly; Nachman, Michael W

    2014-04-01

    The genetic basis of hybrid male sterility in house mice is complex, highly polygenic, and strongly X linked. Previous work suggested that there might be interactions between the Mus musculus musculus X and the M. m. domesticus Y with a large negative effect on sperm head morphology in hybrid males with an F1 autosomal background. To test this, we introgressed the M. m. domesticus Y onto a M. m. musculus background and measured the change in sperm morphology, testis weight, and sperm count across early backcross generations and in 11th generation backcross males in which the opportunity for X-autosome incompatibilities is effectively eliminated. We found that abnormality in sperm morphology persists in M. m. domesticus Y introgression males, and that this phenotype is rescued by M. m. domesticus introgressions on the X chromosome. In contrast, the severe reductions in testis weight and sperm count that characterize F1 males were eliminated after one generation of backcrossing. These results indicate that X-Y incompatibilities contribute specifically to sperm morphology. In contrast, X-autosome incompatibilities contribute to low testis weight, low sperm count, and sperm morphology. Restoration of normal testis weight and sperm count in first generation backcross males suggests that a small number of complex incompatibilities between loci on the M. m. musculus X and the M. m. domesticus autosomes underlie F1 male sterility. Together, these results provide insight into the genetic architecture of F1 male sterility and help to explain genome-wide patterns of introgression across the house mouse hybrid zone.

  14. Oral L-Arginine Stimulates GLP-1 Secretion to Improve Glucose Tolerance in Male Mice

    DEFF Research Database (Denmark)

    Clemmensen, Christoffer; Smajilovic, Sanela; Smith, Eric P

    2013-01-01

    Pharmacological and surgical interventions that increase glucagon-like peptide 1 (GLP-1) action are effective to improve glucose homeostasis in type 2 diabetes mellitus. In light of this, nutritional strategies to enhance postprandial GLP-1 secretion, particularly in the context of diet......-induced obesity, may provide an alternative therapeutic approach. Importantly, recent evidence suggests the amino acid l-arginine, a well-known insulin secretagogue, can also stimulate release of GLP-1 from isolated rat intestine. Here we tested the hypothesis that oral l-arginine acts as a GLP-1 secretagogue...... in vivo, to augment postprandial insulin secretion and improve glucose tolerance. To test this, we administered l-arginine or vehicle by oral gavage, immediately prior to an oral glucose tolerance test in lean and diet-induced obese mice. In both lean and obese mice oral l-arginine increased plasma GLP-1...

  15. Embryonic effects transmitted by male mice irradiated with 512 MeV/u 56Fe nuclei

    International Nuclear Information System (INIS)

    Wiley, L.M.; Van Beek, M.E.A.B.; Raabe, O.G.

    1994-01-01

    High-energy, high-charge nuclei may contribute substantially to the yearly equivalent dose in space flight from galactic cosmic radiation (GCR) at solar minimum. The largest single heavy-ion component is 56 Fe. We used the mouse embryo chimera assay to test 512 MeV/u 56 Fe nuclei for effects on the rate of proliferation of embryonic cells transmitted by sperm from irradiated mice. Male CD1 mice were acutely irradiated with 0.01, 0.05, or 0.1 Gy (LET, 184 keV/μm; fluence, 3.5 x 10 4 -3.3 x 10 5 nuclei/cm 2 ; average dose rate, 0.02 Gy/min) at the Lawrence Berkeley Laboratory BEVATRON/BEVALAC Facility in Berkeley, CA. Irradiated males were bred weekly for 7 weeks to nonirradiated females and their four-cell embryos were paired with control embryos, forming aggregation chimeras. After 30-35 h of culture, chimeras were dissociated to obtain open-quotes proliferation ratiosclose quotes (number of cells contributed by the embryo from the irradiated male/total number of cells in the chimera). Significant dose-dependent decreases in proliferation ratios were obtained across all three dose groups for postirradiation week 2 (P 56 Fe nuclei. However, up to 47% of sperm during postirradiation weeks 1 and 2 transmitted proliferation ratios that were at or below one standard deviation from control mean proliferation ratios. 26 refs., 4 figs., 10 tabs

  16. Age-related and 224Ra-induced abnormalities in the teeth of male mice

    International Nuclear Information System (INIS)

    Humphreys, E.R.; Stones, V.A.

    1985-01-01

    A high incidence of incisor abnormalities was found in aged control and aged 224 Ra-treated male CBA mice. Visual examination of the abnormalities in both controls and treated mice revealed extreme shortening of the upper incisors and hypoplastic, grooved or undulating enamel. The administration of 865 or 1730 nCi of 224 Ra hastened the onset of incisor abnormalities although no specific feature was attributable solely to radium toxicity. Radiography and histology revealed corrugated incisors, obliteration of the pulp cavity, extension and disorganized growth of incisors basally, secondary incisors, open pulp and fractures within the alveoli. There was a statistically-significant reduction in the number of molars present in animals given 432, 865 or 1730 nCi 224 Ra. (author)

  17. Xylitol Affects the Intestinal Microbiota and Metabolism of Daidzein in Adult Male Mice

    Science.gov (United States)

    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 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

  18. Evaluation of caffeine as a radioprotector in gamma-irradiated C57BL/6N male mice

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ji Hyang; Yoon, Yong Dal [Hanyang University, Seoul (Korea, Republic of); Kim, Jin Kyu [KAERI, Taejon (Korea, Republic of)

    2002-10-01

    Caffeine is the main psychoactive ingredient of coffee, tea, even colas with a high frequency of concurrent use in humans. Caffeine has been recently reported as a scavenger of hydroxyl radical in millimolar levels and a potential radioprotector in chronically exposed rodent. This study was performed to investigate the functional radioprotection of caffeine in gamma-irradiated mice. Eight-week-old male C57BL/6N mice were irradiated with 6.5 Gy. A caffeine treated group was administrated 80 mg/ kg body weight by i.p injection, a single exposure, at 1 hour before irradiation. The remaining mice were kept as sham controls. At 6 hours after irradiation, we measured the body and organ weight, collected serum, and testes were removed and processed for paraffin sections and isolation of total RNA. Hormonal analysis was performed by means of radioimmunoassay (RIA) in serum. Semiquantitative reverse transcription-reverse chain reaction (RT-PCR) was used to evaluate the expression kinetics of the apoptotic genes after irradiation. The weight of body and organ and H-E stained slide did not show a difference between groups. The circulating testosterone significantly decreased in irradiated group. RT-PCR data represented that the expression of Fas antigen, p21, p53, bax, and bcl2 related radiation-induced apoptosis showed the specific patterns comparable to that of caffeine-untreated group. Specially, bax mRNA dramatically increased in irradiated group, except caffeine-treated irradiated. Taken together, caffeine can protect an early apoptotic initiation against gamma radiation and may act as a radioprotector.

  19. Evaluation of caffeine as a radioprotector in gamma-irradiated C57BL/6N male mice

    International Nuclear Information System (INIS)

    Kim, Ji Hyang; Yoon, Yong Dal; Kim, Jin Kyu

    2002-01-01

    Caffeine is the main psychoactive ingredient of coffee, tea, even colas with a high frequency of concurrent use in humans. Caffeine has been recently reported as a scavenger of hydroxyl radical in millimolar levels and a potential radioprotector in chronically exposed rodent. This study was performed to investigate the functional radioprotection of caffeine in gamma-irradiated mice. Eight-week-old male C57BL/6N mice were irradiated with 6.5 Gy. A caffeine treated group was administrated 80 mg/ kg body weight by i.p injection, a single exposure, at 1 hour before irradiation. The remaining mice were kept as sham controls. At 6 hours after irradiation, we measured the body and organ weight, collected serum, and testes were removed and processed for paraffin sections and isolation of total RNA. Hormonal analysis was performed by means of radioimmunoassay (RIA) in serum. Semiquantitative reverse transcription-reverse chain reaction (RT-PCR) was used to evaluate the expression kinetics of the apoptotic genes after irradiation. The weight of body and organ and H-E stained slide did not show a difference between groups. The circulating testosterone significantly decreased in irradiated group. RT-PCR data represented that the expression of Fas antigen, p21, p53, bax, and bcl2 related radiation-induced apoptosis showed the specific patterns comparable to that of caffeine-untreated group. Specially, bax mRNA dramatically increased in irradiated group, except caffeine-treated irradiated. Taken together, caffeine can protect an early apoptotic initiation against gamma radiation and may act as a radioprotector

  20. Early impact of social isolation and breast tumor progression in mice.

    Science.gov (United States)

    Madden, Kelley S; Szpunar, Mercedes J; Brown, Edward B

    2013-03-01

    Evidence from cancer patients and animal models of cancer indicates that exposure to psychosocial stress can promote tumor growth and metastasis, but the pathways underlying stress-induced cancer pathogenesis are not fully understood. Social isolation has been shown to promote tumor progression. We examined the impact of social isolation on breast cancer pathogenesis in adult female severe combined immunodeficiency (SCID) mice using the human breast cancer cell line, MDA-MB-231, a high β-adrenergic receptor (AR) expressing line. When group-adapted mice were transferred into single housing (social isolation) one week prior to MB-231 tumor cell injection into a mammary fat pad (orthotopic), no alterations in tumor growth or metastasis were detected compared to group-housed mice. When social isolation was delayed until tumors were palpable, tumor growth was transiently increased in singly-housed mice. To determine if sympathetic nervous system activation was associated with increased tumor growth, spleen and tumor norepinephrine (NE) was measured after social isolation, in conjunction with tumor-promoting macrophage populations. Three days after transfer to single housing, spleen weight was transiently increased in tumor-bearing and non-tumor-bearing mice in conjunction with reduced splenic NE concentration and elevated CD11b+Gr-1+ macrophages. At day 10 after social isolation, no changes in spleen CD11b+ populations or NE were detected in singly-housed mice. In the tumors, social isolation increased CD11b+Gr-1+, CD11b+Gr-1-, and F4/80+ macrophage populations, with no change in tumor NE. The results indicate that a psychological stressor, social isolation, elicits dynamic but transient effects on macrophage populations that may facilitate tumor growth. The transiency of the changes in peripheral NE suggest that homeostatic mechanisms may mitigate the impact of social isolation over time. Studies are underway to define the neuroendocrine mechanisms underlying the

  1. Bisphenol A impairs hepatic glucose sensing in C57BL/6 male mice.

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    Leigh Perreault

    Full Text Available 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.

  2. Metformin Impairs Spatial Memory and Visual Acuity in Old Male Mice.

    Science.gov (United States)

    Thangthaeng, Nopporn; Rutledge, Margaret; Wong, Jessica M; Vann, Philip H; Forster, Michael J; Sumien, Nathalie

    2017-02-01

    Metformin is an oral anti-diabetic used as first-line therapy for type 2 diabetes. Because benefits of metformin extend beyond diabetes to other age-related pathology, and because its effect on gene expression profiles resembles that of caloric restriction, metformin has a potential as an anti-aging intervention and may soon be assessed as an intervention to extend healthspan. However, beneficial actions of metformin in the central nervous system have not been clearly established. The current study examined the effect of chronic oral metformin treatment on motor and cognitive function when initiated in young, middle-aged, or old male mice. C57BL/6 mice aged 4, 11, or 22 months were randomly assigned to either a metformin group (2 mg/ml in drinking water) or a control group. The mice were monitored weekly for body weight, as well as food and water intake and a battery of behavioral tests for motor, cognitive and visual function was initiated after the first month of treatment. Liver, hippocampus and cortex were collected at the end of the study to assess redox homeostasis. Overall, metformin supplementation in male mice failed to affect blood glucose, body weights and redox homeostasis at any age. It also had no beneficial effect on age-related declines in psychomotor, cognitive or sensory functions. However, metformin treatment had a deleterious effect on spatial memory and visual acuity, and reduced SOD activity in brain regions. These data confirm that metformin treatment may be associated with deleterious effect resulting from the action of metformin on the central nervous system.

  3. Immunotoxicity evaluation of novel bioactive composites in male mice as promising orthopaedic implants

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    Gehan T. El-Bassyouni

    2017-05-01

    Full Text Available Objective : In orthopaedics, novel bioactive composites are largely needed to improve the synthetic achievement of the implants. In this work, semiconducting metal oxides such as SiO 2 , TiO 2 , and ZrO 2 particles (Ps were used individually and in different ratios to obtain different biphasic composites. The immunotoxicity of these composites was tested to inspect the potential toxicity prior to their use in further medical applications. Materials and methods : In vitro mineralisation ability was inspected by soaking the composites in simulated body fluid (SBF. Additionally, in vivo experiments were performed consuming male mice using ISSR-PCR, micronucleus (MN test, comet assay, glutathione peroxidase activity, and determination of albumin, globulin, lymphocyte population, ALT, and AST levels. Several groups of adult male albino mice were treated with 100, 200, and 400 mg/kg body weight of SiO 2 , TiO 2 , and ZrO 2 -Ps in pure or mixed forms. Results : Our findings revealed that treatment of mice with low and medium doses of SiO 2 , TiO 2 , and ZrO 2 -Ps in pure or mixed form revealed values relatively similar to the control group. However, using 400 mg/kg especially from TiO 2 -Ps in genuine form or mixed with SiO 2 showed proliferation in the toxicity rates compared with the high dose of SiO 2 and ZrO 2 -Ps. Conclusions : The results suggest that TiO 2 composite induced in vivo toxicity, oxidative DNA damage, bargain of the antioxidant enzymes, and variations in the levels of albumin, globulin, lymphocyte population, ALT, and AST in a dose-dependent manner. However, SiO 2 , and ZrO 2 composites revealed a lower toxicity in mice compared with that of TiO 2 .

  4. Comparison of radioprotective effects of caffeine and ascorbic acid in male mice

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Kyu; Kim, Ji Hyang; Lee, Byoung Hun [KAERI, Taejon (Korea, Republic of); Yoon, Yong Dal [Hanyang Univ., Seoul (Korea, Republic of)

    2003-04-01

    The oxygen effect in radiation biology is well known. Since oxygen enhances radiation-induced biological damage, antioxidants should be radioprotectors. Ascorbic acid (vitamin C) or caffeine is an essential component in the diet of humans and a small range of other mammals. Radioprotective effects of vitamin C have been demonstrated in certain cells and animals, which would result from scavenging free radicals. Caffeine is the main psychoactive ingredient of coffee, tea, even coke with a high frequency of concurrent use in humans. Caffeine has been recently reported as a scavenger of hydroxyl radical in millimolar levels and a potently radioprotector in a chronically exposed rodent. This study investigates functional radioprotection of caffeine and ascorbic acid against gamma irradiation in male mice. Eight-week-old male C57BL/6N mice were irradiated with 6.5 Gy. A caffeine treated group was administered with 80 mg/kg body weight by i.p injection, a single exposure 1 hour before irradiation. Ascorbic acid was administered 330 mg/liter in drinking water through all the experimental period. The remaining mice were kept as sham controls. After collecting a serum from the experimental mice 6 hr after irradiation, qualitative analysis of testosterone was performed by means of radioimmunoassay (RIA). For histological investigation, testes were removed 1 week after irradiation and fixed in NBF. Fixed testes were processed for paraffin sections and stained by H-E. The circulating testosterone significantly decreased in all irradiated groups. The harmful effect of radiation on the body and organ weight and the appearance of semiferous tubules were significantly improved in the caffeine - or ascorbic acid-treated group. In conclusion, caffeine and ascorbic acid protected spermatogenesis from impairment against gamma radiation, acting as a radioprotector.

  5. Radioprotective effects of shark cartilage mucopolysaccharide preparation on immune nad reproductive organs in male mice

    International Nuclear Information System (INIS)

    Luan Jie; Shen Xianrong; Jiang Dingwen; Chen Wei; Lu Min

    2008-01-01

    Objective: To evaluate the protective effects of shark cartilage mucopolysaccharide preparation (SCMP) on immune and reproductive organs in male mice with irradiation damage induced by γ-rays. Methods: 50 mice were randomly divided into normal control group,model control group, the 0.5g/kg. d SCMP group, the 1.0g/kg. d SCMP group, and the 2.0g/kg. d SCMP group. SCMP was administrated by intragastric infusion with the volume of 0.4ml per 20g. Normal control group and model control group were given the same volume of water. 2 weeks later, all of the mice were irradiated by γ-ray of 60 Co(0.83Gy/h) with the dose of 5 Gy. Peripheral blood WBC, the spleen index(SI), thymus index(TI), the gMNC, testicle index, germ cells were detected. Results: Compared with the modal control group, peripheral blood WBC became significantly higher in the treated groups with 1.0g/kg. d and 2.0g/kg. d SCMP after 3 days by irradiation (P<0.05). TI, BMNC and germ cells were significantly higher in the treated groups with 1.0g/kg. d and 2.0g/kg. d SCMP comparing with the control model group (P<0.05) and SI, and Testicle index was significantly compared with the model group (P<0.05) only in 2.0g/ kg. d SCMP treated group. The germ abnormality rate became lower in SCMP treated groups (P<0.01) in 1.0 and 2.0g/kg. d SCMP group. Conclusion: SCMP has radioprotective effects on immune and reproductive organs in male mice. (authors)

  6. Dose-dependent adverse effects of salinomycin on male reproductive organs and fertility in mice.

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    Olajumoke Omolara Ojo

    Full Text Available 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

  7. Comparison of radioprotective effects of caffeine and ascorbic acid in male mice

    International Nuclear Information System (INIS)

    Kim, Jin Kyu; Kim, Ji Hyang; Lee, Byoung Hun; Yoon, Yong Dal

    2003-01-01

    The oxygen effect in radiation biology is well known. Since oxygen enhances radiation-induced biological damage, antioxidants should be radioprotectors. Ascorbic acid (vitamin C) or caffeine is an essential component in the diet of humans and a small range of other mammals. Radioprotective effects of vitamin C have been demonstrated in certain cells and animals, which would result from scavenging free radicals. Caffeine is the main psychoactive ingredient of coffee, tea, even coke with a high frequency of concurrent use in humans. Caffeine has been recently reported as a scavenger of hydroxyl radical in millimolar levels and a potently radioprotector in a chronically exposed rodent. This study investigates functional radioprotection of caffeine and ascorbic acid against gamma irradiation in male mice. Eight-week-old male C57BL/6N mice were irradiated with 6.5 Gy. A caffeine treated group was administered with 80 mg/kg body weight by i.p injection, a single exposure 1 hour before irradiation. Ascorbic acid was administered 330 mg/liter in drinking water through all the experimental period. The remaining mice were kept as sham controls. After collecting a serum from the experimental mice 6 hr after irradiation, qualitative analysis of testosterone was performed by means of radioimmunoassay (RIA). For histological investigation, testes were removed 1 week after irradiation and fixed in NBF. Fixed testes were processed for paraffin sections and stained by H-E. The circulating testosterone significantly decreased in all irradiated groups. The harmful effect of radiation on the body and organ weight and the appearance of semiferous tubules were significantly improved in the caffeine - or ascorbic acid-treated group. In conclusion, caffeine and ascorbic acid protected spermatogenesis from impairment against gamma radiation, acting as a radioprotector

  8. Increased bile acids in enterohepatic circulation by short-term calorie restriction in male mice

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Zidong Donna [Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS, 66160 (United States); Klaassen, Curtis D., E-mail: cklaasse@kumc.edu [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, 66160 (United States)

    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.

  9. Dearth and Delayed Maturation of Testicular Germ Cells in Fanconi Anemia E Mutant Male Mice.

    Directory of Open Access Journals (Sweden)

    Chun Fu

    Full Text Available 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.

  10. Butyl paraben and propyl paraben modulate bisphenol A and estradiol concentrations in female and male mice

    Energy Technology Data Exchange (ETDEWEB)

    Pollock, Tyler; Weaver, Rachel E.; Ghasemi, Ramtin; Catanzaro, Denys de, E-mail: decatanz@mcmaster.ca

    2017-06-15

    People are routinely exposed to the antimicrobial preservatives butyl paraben (BP) and propyl paraben (PP), as well as the monomer of polycarbonate plastics, bisphenol A (BPA). These chemicals are reliably detected in human urine and potentially interact. We investigated whether BP or PP exposure can modulate the concentrations of {sup 14}C-BPA and 17β-estradiol (E{sub 2}). Female and male CF1 mice were each given a subcutaneous injection of oil containing 0 (vehicle), 1, 3, or 9 mg BP or PP, then given a dietary supplement containing 50 μg/kg {sup 14}C-BPA. Radioactivity was measured in tissues through liquid scintillation counting. Significantly elevated {sup 14}C-BPA concentrations were observed following BP treatment in blood serum of both sexes, as well as the lungs, uterus, and ovaries of females and the testes and epididymides of males. Treatment with PP significantly elevated {sup 14}C-BPA concentrations in the uterus only. In another experiment, female and male CF1 mice were each injected with vehicle, 3 mg BP, or 3 mg PP, and E{sub 2} was measured in urine 2–12 h later. Whereas PP did not affect E{sub 2}, BP significantly elevated E{sub 2} 6–10 h after injection in females and 8 h after injection in males. These data indicate that BP and PP can alter the pharmacokinetics of BPA in vivo, and that BP can modulate E{sub 2} concentrations. These results are consistent with evidence that parabens inhibit enzymes that are critical for BPA and E{sub 2} metabolism, and demonstrate the importance of considering concurrent exposure to multiple chemicals when determining regulatory exposure limits. - Highlights: • We studied whether paraben exposure affects the distribution of oral {sup 14}C-BPA. • Elevated {sup 14}C–BPA was observed in mice given butyl or propyl paraben. • We also studied whether paraben exposure affects natural E{sub 2} levels in urine. • Elevated E{sub 2} was observed in mice given butyl, but not propyl, paraben. • Parabens may

  11. Isolated low follicle stimulating hormone (FSH in infertile males – a preliminary report

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    Nader Salama

    2013-09-01

    Full Text Available Objectives: High levels of follicle stimulating hormone (FSH in infertile males received a significant attention and exploration. Studies investigating the isolated deficiency of FSH in males are few, and its real prevalence is still unknown. Therefore, the objectives of the current study was to report the prevalence of isolated low FSH in infertile males and highlight their demographics and standard sperm parameters. Methods: Records of 3335 infertile men were retrospectively checked. Patients with isolated low FSH were retrieved. FSH levels were categorized into 3 groups based on the number of affected sperm parameter (s. Study variables were also arranged into 2 groups in relation to smoking history. A control group was included to document the changes in sperm morphology. Results: Isolated low FSH (1.146 ± 0.219 mIU/mL was found in 29 (0.87% patients. All patients showed at least one abnormal sperm parameter. The abnormal parameters were present in different combinations within the same patient but with no significant correlations with the FSH levels. The FSH levels got lower as the number of the affected sperm parameters increased although the decline was insignificant. The most frequent abnormal parameter presented was sperm morphology (86.2%. Anomalous sperm morphology was highly and significantly demonstrated in the head; specifically in acrosome. Abnormal sperm parameters were present in both smoking and nonsmoking groups but with no significant differences in between. Conclusions: Isolated low FSH among infertile males has a low prevalence. This may be associated with abnormality in semen parameters; particularly sperm morphology. These patients are suggested to be found as a primary entity. However, an additional work-up is highly recommended to validate this hypothesis.

  12. Whole Genome Sequence Analysis of Salmonella Enteritidis Isolated from Wild Mice

    Science.gov (United States)

    Salmonella Enteritidis is a foodborne pathogen of global concern because of the high frequency isolated from foods and patients. Draft genomes of 64 S. Enteritidis strains from intestines and spleens of mice were reported. The availability of these genomes provides useful information on genomic dive...

  13. Caffeine plus nicotine improves motor function, spatial and non-spatial working memory and functional indices in BALB/c male mice.

    Science.gov (United States)

    Adeniyi, P A; Omatsuli, E P; Akinyemi, A J; Ishola, A O

    2016-12-01

    There is a greater prevalence of cigarette smoking among caffeine dependent individuals. This study therefore sought to assess the effect of nicotine and/or caffeine on some key biochemical indices and neurobehavioural parameters associated with brain function in male mice. Forty male BALB/c mice were divided into 4 groups of 10 animals each; Group A serve as the control and received normal saline (s.c), Group B received 2mg/kg body weight of nicotine (s.c), Group C received 2mg/kg body weight of caffeine (s.c) and Group D received 2mg/kg of nicotine and 2mg/kg of caffeine (s.c). The experiment lasted for 21 days, and then the animals were subjected to behavioral test. Thereafter the animals were sacrificed and their brain isolated for the determination of endothelial nitric oxide (NO) level, acetylcholinesterase (AChE), arginase (Arg) and adenosine deaminase (ADA) activities; as well as some antioxidant indices. Administration of nicotine or caffeine caused a significant (Pcaffeine cognitive properties through a significant increase in non-spatial working memory whereas; it was otherwise on the spatial working memory and motor coordination. Therefore, we can suggest from our present study that caffeine enhances the effect of nicotine either synergistically or additively on memory and motor function and some key biochemical indices associated with brain function in male mice. Copyright © 2016. Published by Elsevier B.V.

  14. Isolation of pathogenic Yersinia enterocolitica 1B/O:8 from Apodemus mice in Japan.

    Science.gov (United States)

    Oda, Shinya; Kabeya, Hidenori; Sato, Shingo; Shimonagane, Ai; Inoue, Kai; Hayashidani, Hideki; Takada, Nobuhiro; Fujita, Hiromi; Kawabata, Hiroki; Maruyama, Soichi

    2015-01-01

    Yersinia enterocolitica was isolated from 15.7% (88/560) of wild rodents captured in 15 prefectures in Japan. Prevalences by rodent species were 18.0% (70/388) in Japanese field mice (Apodemus speciosus), 20% (14/71) in small Japanese field mice (Apodemus argenteus), and 11% (4/38) in gray red-backed vole (Myodes rufocanus bedfordiae), suggesting that these rodent species are important reservoirs of Y. enterocolitica. Although most of the isolates were identified as biotype 1A, the pathogenic bioserotype 1B/O:8 was detected in one of the A. speciosus and in three of the A. argenteus captured in Aomori Prefecture. It is suggested that Apodemus mice may be an important reservoir of Y. enterocolitica, and that there are foci of the pathogenic bioserotype 1B/O:8 in Aomori Prefecture, because human sporadic cases by the serotype have been reported in this prefecture.

  15. Isolation of hair follicle bulge stem cells from YFP-expressing reporter mice.

    Science.gov (United States)

    Nakrieko, Kerry-Ann; Irvine, Timothy S; Dagnino, Lina

    2013-01-01

    In this article we provide a method to isolate hair follicle stem cells that have undergone targeted gene inactivation. The mice from which these cells are isolated are bred into a Rosa26-yellow fluorescent protein (YFP) reporter background, which results in YFP expression in the targeted stem cell population. These cells are isolated and purified by fluorescence-activated cell sorting, using epidermal stem cell-specific markers in conjunction with YFP fluorescence. The purified cells can be used for gene expression studies, clonogenic experiments, and biological assays, such as viability and capacity for directional migration.

  16. A disparity between locomotor economy and territory-holding ability in male house mice.

    Science.gov (United States)

    Morris, Jeremy S; Ruff, James S; Potts, Wayne K; Carrier, David R

    2017-07-15

    Both economical locomotion and physical fighting are important performance traits to many species because of their direct influence on components of Darwinian fitness. Locomotion represents a substantial portion of the total daily energy budget of many animals. Fighting performance often determines individual reproductive fitness through the means of resource control, social dominance and access to mates. However, phenotypic traits that improve either locomotor economy or fighting ability may diminish performance in the other. Here, we tested for a predicted disparity between locomotor economy and competitive ability in wild-derived house mice ( Mus musculus ). We used 8 week social competition trials in semi-natural enclosures to directly measure male competitive ability through territorial control and female occupancy within territories. We also measured oxygen consumption during locomotion for each mouse using running trials in an enclosed treadmill and open-flow respirometry. Our results show that territory-holding males have higher absolute and mass-specific oxygen consumption when running (i.e. reduced locomotor economy) compared with males that do not control territories. This relationship was present both before and after 8 week competition trials in semi-natural enclosures. This disparity between physical competitive ability and economical locomotion may impose viability costs on males in species for which competition over mates is common and may constrain the evolution of behavioral and phenotypic diversity, particularly in natural settings with environmental and resource variability. © 2017. Published by The Company of Biologists Ltd.

  17. Promotion of hepatic preneoplastic lesions in male B6C3F1 mice by unleaded gasoline.

    Science.gov (United States)

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

    1995-01-01

    In previous studies, unleaded gasoline (UG) vapor was found to be a liver tumor promoter 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 B6C3F1 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 non-initiated mice. Altered hepatic foci (AHF), which were predominantly basophilic in phenotype, were found almost exclusively in DEN-initiated mice. UG treatment significantly increased both the mean volume (threefold) and the volume fraction (twofold) of the AHF without increasing the number of AHF per unit area. UG also induced hepatic pentoxyresorufin-O-dealkylase (PROD) activity, a marker of CYP2B, by more than 12-fold over control with or without DEN cotreatment. 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 BrdU labeling index (LI) in AHF and nonlesioned liver.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 1. PMID:7588481

  18. Action of the schistosomotic spleen in male mices on the regulation of thyroid hormones

    International Nuclear Information System (INIS)

    Neves, S.R.S.; Silva, I.M.S.; Pereira, S.S.L.; Lima Filho, G.L.; Catanho, M.T.J.A.; Neves, E.S.; Silveira, M.F.G.

    1997-01-01

    For the purpose to study the action of the schistosomotic spleen on the regulation of TSH, T4 and albumin levels in serum, spleens from adults mice infected by Schistosoma mansoni were homogeneized, centrifuged and cromatographed in a column of Sephadex G-100, resulting in two proteans fractions (I and II). The biologic activity was determinated through the administration of the fractions by intraperitoneal way (IP), in male mice aged 27-30 days, in a period of three following days. Five days after the last administration, the animals were sacrified and their blood was collected for obtainment of serum and determination of TSH, T4 and albumin levels. Obtained results showed that the albumin levels no change when compared to control and that fraction I infected change the TSH and T4 levels, but the fraction II infected no change this levels. These results suggest that spleens from mice infected by S. mansoni have a factor that modifies the hormonal regulation in level hypophysial and the synthesis of thyroid hormones (T4), changing the basal metabolism. The seric levels of TSH and T4 were determined by radioimmunoassay using I-125. (author). 12 refs., 1 tab

  19. [Genotype-related changes in the reproductive function under social hierarchy in laboratory male mice].

    Science.gov (United States)

    Osadchuk, L V; Salomacheva, I N; Osadchuk, A V

    2010-01-01

    The study was designed to investigate genetic differences in reproductive consequences of social hierarchy using inbred mice strains BALB/cLac, PT and CBA/Lac. Two adult males of different genotypes were housed together for 5 days. Hierarchical status of both partners was determined by asymmetry in agonistic behavior. The number of epididymal sperm and a proportion of abnormal sperm, weights of reproductive organs, serum concentration and testicular content of testosterone, and the testosterone response to introduction of a receptive female were determined. The testosterone measures were significantly decreased in the PT strain, the epididymal sperm number was significantly decreased in the BALB/cLac strain and a proportion of abnormal sperm heads was significantly increase in the CBA/Lac (in both dominants and subordinates) as compared to control mice. The testicular testosterone response to a receptive female and precopulatory behavior was unchanged in dominants and suppressed in subordinates of the BALB/cLac strain. The results indicate that in laboratory mice the pattern of reproductive response to social hierarchy is determined by genetic background.

  20. Central Fibroblast Growth Factor 21 Browns White Fat via Sympathetic Action in Male Mice.

    Science.gov (United States)

    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.

  1. IGF1 stimulates greater muscle hypertrophy in the absence of myostatin in male mice.

    Science.gov (United States)

    Hennebry, Alexander; Oldham, Jenny; Shavlakadze, Tea; Grounds, Miranda D; Sheard, Philip; Fiorotto, Marta L; Falconer, Shelley; Smith, Heather K; Berry, Carole; Jeanplong, Ferenc; Bracegirdle, Jeremy; Matthews, Kenneth; Nicholas, Gina; Senna-Salerno, Mônica; Watson, Trevor; McMahon, Christopher D

    2017-08-01

    Insulin-like growth factors (IGFs) and myostatin have opposing roles in regulating the growth and size of skeletal muscle, with IGF1 stimulating, and myostatin inhibiting, growth. However, it remains unclear whether these proteins have mutually dependent, or independent, roles. To clarify this issue, we crossed myostatin null ( Mstn -/- ) mice with mice overexpressing Igf1 in skeletal muscle ( Igf1 + ) to generate six genotypes of male mice; wild type ( Mstn +/+ ), Mstn +/- , Mstn -/- , Mstn +/+ :Igf1 + , Mstn +/- :Igf1 + and Mstn -/- :Igf1 + Overexpression of Igf1 increased the mass of mixed fibre type muscles (e.g. Quadriceps femoris ) by 19% over Mstn +/+ , 33% over Mstn +/- and 49% over Mstn -/- ( P  Myostatin regulated the number, while IGF1 regulated the size of myofibres, and the deletion of Mstn and Igf1 + independently increased the proportion of fast type IIB myosin heavy chain isoforms in T. anterior (up to 10% each, P  myostatin is absent and IGF1 is in excess. Finally, we show that myostatin and IGF1 regulate skeletal muscle size, myofibre type and gonadal fat through distinct mechanisms that involve increasing the total abundance and phosphorylation status of AKT and rpS6. © 2017 Society for Endocrinology.

  2. Reproductive, cytological and biochemical toxicity of Yohimbe in male Swiss albino mice.

    Science.gov (United States)

    Al-Majed, Abdulhakeem A; Al-Yahya, Abdulaziz A; Al-Bekairi, A M; Al-Shabanah, Othman A; Qureshi, Shoeb

    2006-07-01

    To study the effect of Corynanthe Yohimbe (Yohimbe) on germ cells in Swiss albino mice. Adult male mice were orally (gavage) treated with different doses (188, 375 and 750 mg/[kg x day]) of aqueous suspension of Yohimbe for 90 days. The following parameters were evaluated: (i) reproductive organ weight, (ii) motility and count of sperm, (iii) study on rate of pregnancy and mean implants, (iv) spermatozoa morphology, (v) cytology of the testes chromosomes, and (vi) biochemical study on estimation of proteins, RNA, DNA, malondialdehyde, nonprotein sulfhydryl (NP-SH) and hormones. The treatment caused significant increase in the weight of seminal vesicles, motility and count of spermatozoa, pre- and post-implants. Male fertility was decreased. These results are confirmed by our data on spermatozoa abnormalities and chromosomal aberrations. The data on biochemical parameters showed increase of malondialdehyde and depletion of NP-SH, proteins, RNA and DNA in the testicular cells. Our results elucidated the role of free radical species in cytological and reproductive changes, possibly, under the influence of yohimbine (principal constituent of Yohimbe) on neurotransmitters, including norephinephrine. These data warrant careful use of Yohimbe.

  3. Cyclophosphamide-induced male subfertility in mice: An assessment of the potential benefits of Maca supplement.

    Science.gov (United States)

    Onaolapo, A Y; Oladipo, B P; Onaolapo, O J

    2018-04-01

    Effects of Lepidium meyenii (Maca) on cyclophosphamide (CYP)-induced gonadal toxicity in male mice were investigated. Mice were assigned to six treatment groups: Vehicle control, CYP control, CYP plus oral Maca (500 or 1,000 mg/kg), and oral Maca (500 or 1,000 mg/kg). CYP was administered via the intraperitoneal route (days 1-2), while vehicle or Maca were administered daily for 28 days. On day 28, half of the animals in each group were either sacrificed or paired with age-matched females for fertility assessment. Plasma testosterone assay, sperm analysis and assessment of tissue antioxidant/morphological status were also carried out. CYP administration was associated with oxidative stress, subfertility and morphometric/morphological indices of gonadal injury, while administration of Maca mitigated CYP-induced gonadal toxicity and subfertility. This study shows that Maca is beneficial in the mitigation of CYP-induced male gonadal insufficiency and/or testicular morphological changes; however, further studies will be needed to ascertain its usability for this purpose in humans. © 2017 Blackwell Verlag GmbH.

  4. Influence of electromagnetic pulse on the offspring sex ratio of male BALB/c mice.

    Science.gov (United States)

    Li, Jin-Hui; Jiang, Da-Peng; Wang, Ya-Feng; Yan, Jia-Jia; Guo, Qi-Yan; Miao, Xia; Lang, Hai-Yang; Xu, Sheng-Long; Liu, Jun-Ye; Guo, Guo-Zhen

    2017-09-01

    Public concern is growing about the exposure to electromagnetic fields (EMF) and its effect on male reproductive health. Detrimental effect of EMF exposure on sex hormones, reproductive performance and sex-ratio was reported. The present study was designed to clarify whether paternal exposure to electromagnetic pulse (EMP) affects offspring sex ratio in mice. 50 male BALB/c mice aged 5-6 weeks were exposed to EMP daily for 2 weeks before mated with non-exposed females at 0d, 7d, 14d, 21d and 28d after exposure. Sex hormones including total testosterone, LH, FSH, and GnRH were detected using radioimmunoassay. The sex ratio was examined by PCR and agarose gel electrophoresis. The results of D0, D21 and D28 showed significant increases compared with sham-exposed groups. The serum testosterone increased significantly in D0, D14, D21, and D28 compared with sham-exposed groups (p<0.05). Overall, this study suggested that EMP exposure may lead to the disturbance of reproductive hormone levels and affect the offspring sex ratio. Copyright © 2017. Published by Elsevier B.V.

  5. Effects of 6-mercaptopurine treatment on sperm production and reproductive performance: a study in male mice.

    Science.gov (United States)

    Ligumsky, Moshe; Badaan, Shadi; Lewis, Hadassa; Meirow, Dror

    2005-04-01

    Azathioprine and 6-mercaptopurine interact in purine metabolism and DNA synthesis, thus their potential mutagenic effects have been of concern in the management of inflammatory bowel disease (IBD), especially in patients of childbearing age. Although several clinical studies have indicated their safety in both reproduction and pregnancy, in a recent large epidemiological study concerns were raised about their adverse effects in pregnant patients with IBD, and experimental or basic data on this subject are limited. The aim of this study was to investigate sperm production, sperm quality, and reproductive outcome following prolonged 6-MP administration to male mice. Highly inbred Balb/c adult male mice were used. 6-MP at doses of 2, 5, and 8 mg/kg (n = 9 for each group) was given daily for 51 days and the treatment group was compared with controls. After 45 days of treatment, the mice were mated with females. Following 13 days of pregnancy, the products of conception were evaluated and live fetuses were examined for gross malformations. Sperm production and morphology were examined after 51 days of 6-MP administration. Treatment with 6-MP at all doses did not affect sperm morphology and sperm production in the testicular tubules, as compared with controls (70% normal sperm). However, pregnancy rates were inversely related to escalating doses of 6-MP: 55%, 41%, 28%, and 16% for control, 2, 5, and 8 mg/kg groups, respectively. Resorption rates (abortions) were 21% in the control group as compared with 45-50% in all the treatment groups, but the incidence of major congenital malformations was not increased. Long-term 6-MP treatment in male mice did not impair sperm production and sperm morphology. However, a significantly high rate of embryonic resorption indicated occult sperm damage. Thus, normal sperm analysis does not necessarily imply that sperm damage at genetic level did not occur. It is difficult to extrapolate from these results to the clinical use of 6-MP

  6. Effects of obesity and exercise on testicular leptin signal transduction and testosterone biosynthesis in male mice.

    Science.gov (United States)

    Yi, Xuejie; Gao, Haining; Chen, Dequan; Tang, Donghui; Huang, Wanting; Li, Tao; Ma, Tie; Chang, Bo

    2017-04-01

    To explore the role of the testicular leptin and JAK-STAT[leptin (LEP)-JAK-STAT] pathway in testosterone biosynthesis during juvenile stages and exercise for weight loss, male C57BL/6J mice were randomly divided into normal-diet and high-fat diet groups. After 10 wk, mice in the high-fat diet-fed group were further divided randomly into obese control, obese moderate-volume exercise, and obese high-volume exercise groups. Mice in the obese moderate-volume exercise group were provided with 2 h/day, 6 days/wk swimming exercise for 8 wk, and mice in the obese high-volume exercise group underwent twice the amount of daily exercise intervention as the obese moderate-volume exercise group. The results showed that a high-fat diet causes obesity, leptin resistance, inhibition of the testicular LEP-JAK-STAT pathway, decreased mRNA and protein expression of steroidogenic factor-1, steroidogenic acute regulatory protein, and the P -450 side-chain cleavage enzyme, a decrease in the serum testosterone-to-estradiol ratio, and declines in sperm quality parameters. Both moderate and high-volume exercise were able to reduce body fat and increase the mRNA and protein expression of LEP-JAK-STAT, but only moderate exercise significantly increased the mRNA and protein expression of steroidogenic factor-1, steroidogenic acute regulatory protein, and P -450 side-chain cleavage enzyme and significantly reversed the serum testosterone-to-estradiol ratio and sperm quality parameters. These findings suggest that by impairing the testicular LEP-JAK-STAT pathway, early-stage obesity inhibits the biosynthesis of testosterone and sexual development and reduces male reproductive potential. Long-term moderate and high-volume exercise can effectively reduce body fat and improve obesity-induced abnormalities in testicular leptin signal transduction, whereas only moderate-volume exercise can reverse the negative impacts of obesity on male reproductive function. Copyright © 2017 the American

  7. Impaired glucocorticoid-mediated HPA axis negative feedback induced by juvenile social isolation in male rats.

    Science.gov (United States)

    Boero, Giorgia; Pisu, Maria Giuseppina; Biggio, Francesca; Muredda, Laura; Carta, Gianfranca; Banni, Sebastiano; Paci, Elena; Follesa, Paolo; Concas, Alessandra; Porcu, Patrizia; Serra, Mariangela

    2018-05-01

    We previously demonstrated that socially isolated rats at weaning showed a significant decrease in corticosterone and adrenocorticotropic hormone (ACTH) levels, associated with an enhanced response to acute stressful stimuli. Here we shown that social isolation decreased levels of total corticosterone and of its carrier corticosteroid-binding globulin, but did not influence the availability of the free active fraction of corticosterone, both under basal conditions and after acute stress exposure. Under basal conditions, social isolation increased the abundance of glucocorticoid receptors, while it decreased that of mineralocorticoid receptors. After acute stress exposure, socially isolated rats showed long-lasting corticosterone, ACTH and corticotrophin releasing hormone responses. Moreover, while in the hippocampus and hypothalamus of group-housed rats glucocorticoid receptors expression increased with time and reached a peak when corticosterone levels returned to basal values, in socially isolated rats expression of glucocorticoid receptors did not change. Finally, social isolation also affected the hypothalamic endocannabinoid system: compared to group-housed rats, basal levels of anandamide and cannabinoid receptor type 1 were increased, while basal levels of 2-arachidonoylglycerol were decreased in socially isolated rats and did not change after acute stress exposure. The present results show that social isolation in male rats alters basal HPA axis activity and impairs glucocorticoid-mediated negative feedback after acute stress. Given that social isolation is considered an animal model of several neuropsychiatric disorders, such as generalized anxiety disorder, depression, post-traumatic stress disorder and schizophrenia, these data could contribute to better understand the alterations in HPA axis activity observed in these disorders. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. Protective Effects of Thymoquinone against Methotrexate-Induced Germ Cell Apoptosis in Male Mice

    Directory of Open Access Journals (Sweden)

    Fatemeh Sheikhbahaei

    2016-12-01

    Full Text Available 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.

  9. Hippocampal gene expression patterns in oxytocin male knockout mice are related to impaired social interaction.

    Science.gov (United States)

    Lazzari, Virginia Meneghini; Zimmermann-Peruzatto, Josi Maria; Agnes, Grasiela; Becker, Roberta Oriques; de Moura, Ana Carolina; Almeida, Silvana; Guedes, Renata Padilha; Giovenardi, Marcia

    2017-11-02

    Social interaction between animals is crucial for the survival and life in groups. It is well demonstrated that oxytocin (OT) and vasopressin (AVP) play critical roles in the regulation of social behaviors in mammals, however, other neurotransmitters and hormones are involved in the brain circuitry related to these behaviors. The present study aimed to investigate the gene expression of neurotransmitter receptors in the brain of OT knockout (OTKO) male mice. In this study, we evaluated the expression levels of the OT receptor (Oxtr), AVP receptors 1a and 1b (Avpr1a; Avpr1b), dopamine receptor 2 (Drd2), and the estrogen receptors alpha and beta (Esr1; Esr2) genes in the hippocampus (HPC), olfactory bulb (OB), hypothalamus (HPT) and prefrontal cortex (PFC). AVP gene (Avp) expression was analyzed in the HPT. Gene expression results were discussed regarding to social interaction and sexual behavior findings. Additionally, we analyzed the influence of OT absence on the Avp mRNA expression levels in the HPT. RNA extraction and cDNAs synthesis followed by quantitative polymerase chain reaction were performed for gene expression determination. Results were calculated with the 2 -ΔΔCt method. Our main finding was that HPC is more susceptible to gene expression changes due to the lack of OT. OTKOs exhibited decreased expression of Drd2 and Avpr1b, but increased expression of Oxtr in the HPC. In the PFC, Esr2 was increased. In the HPT, there was a reduced Avp expression in the OTKO group. No differences were detected in the OB and HPT. Despite these changes in gene expression, sexual behavior was not affected. However, OTKO showed higher social investigation and lower aggressive performance than wild-type mice. Our data highlight the importance of OT for proper gene expression of neurotransmitter receptors related to the regulation of social interaction in male mice. Copyright © 2017. Published by Elsevier B.V.

  10. Early cannabinoid exposure influences neuroendocrine and reproductive functions in male mice: I. Prenatal exposure.

    Science.gov (United States)

    Dalterio, S; Steger, R; Mayfield, D; Bartke, A

    1984-01-01

    Maternal exposure to delta 9-tetrahydrocannabinol (THC), the major psychoactive constituent in marihuana, or to the non-psychoactive cannabinol (CBN) or cannabidiol (CBD) alters endocrine functions and concentrations of brain biogenic amines in their male offspring. Prenatal CBN exposure on day 18 of gestation resulted in decreased plasma FSH levels, testicular testosterone (T) concentrations, and seminal vesicles weights, but increased plasma levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) post-castration in adulthood. Prenatal exposure to THC significantly enhanced the responsiveness of the testes to intratesticular LH injection in vivo and tended to increase human chorionic gonadotropin (hCG)-stimulated T production by decapsulated testes in vitro. In the CBN-exposed mice, hCG-stimulated T production was enhanced, while CBD exposure had no effect. Prenatal THC exposure altered the negative feedback effects of exogenous gonadal steroids in castrated adults, with lower plasma T and FSH levels after 20 micrograms T than in castrated controls. In contrast, CBD-exposed mice had higher levels of LH in plasma post-castration. In CBN-exposed adults, two weeks post-castration the concentration of norepinephrine (NE) and dopamine (DA) in hypothalamus and remaining brain were reduced, while levels of serotonin (5-HT) and its metabolite, 5-HIAA, were elevated compared to that in castrated OIL-controls. Prenatal CBD-exposure also reduced NE and elevated 5-HT and 5-HIAA, but did not affect DA levels post-castration. Concentrations of brain biogenic amines were not influenced by prenatal THC exposure in the present study. A single prenatal exposure to psychoactive or non-psychoactive components of marihuana results in long term alterations in the function of the hypothalamo-pituitary-gonadal axis. Changes in the concentrations of brain biogenic amines may be related to these effects of prenatal cannabinoids on endocrine function in adult male mice.

  11. Genetic architecture of hybrid male sterility in Drosophila: analysis of intraspecies variation for interspecies isolation.

    Directory of Open Access Journals (Sweden)

    Laura K Reed

    Full Text Available BACKGROUND: The genetic basis of postzygotic isolation is a central puzzle in evolutionary biology. Evolutionary forces causing hybrid sterility or inviability act on the responsible genes while they still are polymorphic, thus we have to study these traits as they arise, before isolation is complete. METHODOLOGY/PRINCIPAL FINDINGS: Isofemale strains of D. mojavensis vary significantly in their production of sterile F(1 sons when females are crossed to D. arizonae males. We took advantage of the intraspecific polymorphism, in a novel design, to perform quantitative trait locus (QTL mapping analyses directly on F(1 hybrid male sterility itself. We found that the genetic architecture of the polymorphism for hybrid male sterility (HMS in the F(1 is complex, involving multiple QTL, epistasis, and cytoplasmic effects. CONCLUSIONS/SIGNIFICANCE: The role of extensive intraspecific polymorphism, multiple QTL, and epistatic interactions in HMS in this young species pair shows that HMS is arising as a complex trait in this system. Directional selection alone would be unlikely to maintain polymorphism at multiple loci, thus we hypothesize that directional selection is unlikely to be the only evolutionary force influencing postzygotic isolation.

  12. Genetic architecture of hybrid male sterility in Drosophila: analysis of intraspecies variation for interspecies isolation.

    Science.gov (United States)

    Reed, Laura K; LaFlamme, Brooke A; Markow, Therese A

    2008-08-27

    The genetic basis of postzygotic isolation is a central puzzle in evolutionary biology. Evolutionary forces causing hybrid sterility or inviability act on the responsible genes while they still are polymorphic, thus we have to study these traits as they arise, before isolation is complete. Isofemale strains of D. mojavensis vary significantly in their production of sterile F(1) sons when females are crossed to D. arizonae males. We took advantage of the intraspecific polymorphism, in a novel design, to perform quantitative trait locus (QTL) mapping analyses directly on F(1) hybrid male sterility itself. We found that the genetic architecture of the polymorphism for hybrid male sterility (HMS) in the F(1) is complex, involving multiple QTL, epistasis, and cytoplasmic effects. The role of extensive intraspecific polymorphism, multiple QTL, and epistatic interactions in HMS in this young species pair shows that HMS is arising as a complex trait in this system. Directional selection alone would be unlikely to maintain polymorphism at multiple loci, thus we hypothesize that directional selection is unlikely to be the only evolutionary force influencing postzygotic isolation.

  13. Expanded simple tandem repeat (ESTR) mutation induction in the male germline: Lessons learned from lab mice

    Energy Technology Data Exchange (ETDEWEB)

    Somers, Christopher M. [University of Regina, Department of Biology, 3737 Wascana Parkway, Regina, SK, S4S 0A2 (Canada)]. E-mail: chris.somers@uregina.ca

    2006-06-25

    Expanded simple tandem repeat (ESTR) DNA loci that are unstable in the germline have provided the most sensitive tool ever developed for investigating low-dose heritable mutation induction in laboratory mice. Ionizing radiation exposures have shown that ESTR mutations occur mainly in pre-meiotic spermatogonia and stem cells. The average spermatogonial doubling dose is 0.62-0.69 Gy for low LET, and 0.18-0.34 Gy for high LET radiation. Chemical alkylating agents also cause significant ESTR mutation induction in pre-meiotic spermatogonia and stem cells, but are much less effective per unit dose than radiation. ESTR mutation induction efficiency is maximal at low doses of radiation or chemical mutagens, and may decrease at higher dose ranges. DNA repair deficient mice (SCID and PARP-1) with elevated levels of single and double-strand DNA breaks have spontaneously elevated ESTR mutation frequencies, and surprisingly do not show additional ESTR mutation induction following irradiation. In contrast, ESTR mutation induction in p53 knock-outs is indistinguishable from that of wild-type mice. Studies of sentinel mice exposed in situ to ambient air pollution showed elevated ESTR mutation frequencies in males exposed to high levels of particulate matter. These studies highlight the application of the ESTR assay for assessing environmental hazards under real-world conditions. All ESTR studies to date have shown untargeted mutations that occur at much higher frequencies than predicted. The mechanism of this untargeted mutation induction is unknown, and must be elucidated before we can fully understand the biological significance of ESTR mutations, or use these markers for formal risk assessment. Future studies should focus on the mechanism of ESTR mutation induction, refining dose responses, and developing ESTR markers for other animal species.

  14. Aqueous stability and oral pharmacokinetics of meloxicam and carprofen in male C57BL/6 mice.

    Science.gov (United States)

    Ingrao, Joelle C; Johnson, Ron; Tor, Elizabeth; Gu, Yu; Litman, Marcus; Turner, Patricia V

    2013-09-01

    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.

  15. Expanded simple tandem repeat (ESTR) mutation induction in the male germline: Lessons learned from lab mice

    International Nuclear Information System (INIS)

    Somers, Christopher M.

    2006-01-01

    Expanded simple tandem repeat (ESTR) DNA loci that are unstable in the germline have provided the most sensitive tool ever developed for investigating low-dose heritable mutation induction in laboratory mice. Ionizing radiation exposures have shown that ESTR mutations occur mainly in pre-meiotic spermatogonia and stem cells. The average spermatogonial doubling dose is 0.62-0.69 Gy for low LET, and 0.18-0.34 Gy for high LET radiation. Chemical alkylating agents also cause significant ESTR mutation induction in pre-meiotic spermatogonia and stem cells, but are much less effective per unit dose than radiation. ESTR mutation induction efficiency is maximal at low doses of radiation or chemical mutagens, and may decrease at higher dose ranges. DNA repair deficient mice (SCID and PARP-1) with elevated levels of single and double-strand DNA breaks have spontaneously elevated ESTR mutation frequencies, and surprisingly do not show additional ESTR mutation induction following irradiation. In contrast, ESTR mutation induction in p53 knock-outs is indistinguishable from that of wild-type mice. Studies of sentinel mice exposed in situ to ambient air pollution showed elevated ESTR mutation frequencies in males exposed to high levels of particulate matter. These studies highlight the application of the ESTR assay for assessing environmental hazards under real-world conditions. All ESTR studies to date have shown untargeted mutations that occur at much higher frequencies than predicted. The mechanism of this untargeted mutation induction is unknown, and must be elucidated before we can fully understand the biological significance of ESTR mutations, or use these markers for formal risk assessment. Future studies should focus on the mechanism of ESTR mutation induction, refining dose responses, and developing ESTR markers for other animal species

  16. Streptozotocin induced oxidative stress, innate immune system responses and behavioral abnormalities in male mice.

    Science.gov (United States)

    Amiri, Shayan; Haj-Mirzaian, Arya; Momeny, Majid; Amini-Khoei, Hossein; Rahimi-Balaei, Maryam; Poursaman, Simin; Rastegar, Mojgan; Nikoui, Vahid; Mokhtari, Tahmineh; Ghazi-Khansari, Mahmoud; Hosseini, Mir-Jamal

    2017-01-06

    Recent evidence indicates the involvement of inflammatory factors and mitochondrial dysfunction in the etiology of psychiatric disorders such as anxiety and depression. To investigate the possible role of mitochondrial-induced sterile inflammation in the co-occurrence of anxiety and depression, in this study, we treated adult male mice with the intracerebroventricular (i.c.v.) infusion of a single low dose of streptozotocin (STZ, 0.2mg/mouse). Using valid and qualified behavioral tests for the assessment of depressive and anxiety-like behaviors, we showed that STZ-treated mice exhibited behaviors relevant to anxiety and depression 24h following STZ treatment. We observed that the co-occurrence of anxiety and depressive-like behaviors in animals were associated with abnormal mitochondrial function, nitric oxide overproduction and, the increased activity of cytosolic phospholipase A 2 (cPLA 2 ) in the hippocampus. Further, STZ-treated mice had a significant upregulation of genes associated with the innate immune system such as toll-like receptors 2 and 4. Pathological evaluations showed no sign of neurodegeneration in the hippocampus of STZ-treated mice. Results of this study revealed that behavioral abnormalities provoked by STZ, as a cytotoxic agent that targets mitochondria and energy metabolism, are associated with abnormal mitochondrial activity and, consequently the initiation of innate-inflammatory responses in the hippocampus. Our findings highlight the role of mitochondria and innate immunity in the formation of sterile inflammation and behaviors relevant to anxiety and depression. Also, we have shown that STZ injection (i.c.v.) might be an animal model for depression and anxiety disorders based on sterile inflammation. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. 2-Methoxyestradiol Reduces Angiotensin II-Induced Hypertension and Renal Dysfunction in Ovariectomized Female and Intact Male Mice.

    Science.gov (United States)

    Pingili, Ajeeth K; Davidge, Karen N; Thirunavukkarasu, Shyamala; Khan, Nayaab S; Katsurada, Akemi; Majid, Dewan S A; Gonzalez, Frank J; Navar, L Gabriel; Malik, Kafait U

    2017-06-01

    Cytochrome P450 1B1 protects against angiotensin II (Ang II)-induced hypertension and associated cardiovascular changes in female mice, most likely via production of 2-methoxyestradiol. This study was conducted to determine whether 2-methoxyestradiol ameliorates Ang II-induced hypertension, renal dysfunction, and end-organ damage in intact Cyp1b1 -/- , ovariectomized female, and Cyp1b1 +/+ male mice. Ang II or vehicle was infused for 2 weeks and administered concurrently with 2-methoxyestradiol. Mice were placed in metabolic cages on day 12 of Ang II infusion for urine collection for 24 hours. 2-Methoxyestradiol reduced Ang II-induced increases in systolic blood pressure, water consumption, urine output, and proteinuria in intact female Cyp1b1 -/- and ovariectomized mice. 2-Methoxyestradiol also reduced Ang II-induced increase in blood pressure, water intake, urine output, and proteinuria in Cyp1b1 +/+ male mice. Treatment with 2-methoxyestradiol attenuated Ang II-induced end-organ damage in intact Cyp1b1 -/- and ovariectomized Cyp1b1 +/+ and Cyp1b1 -/- female mice and Cyp1b1 +/+ male mice. 2-Methoxyestradiol mitigated Ang II-induced increase in urinary excretion of angiotensinogen in intact Cyp1b1 -/- and ovariectomized Cyp1b1 +/+ and Cyp1b1 -/- female mice but not in Cyp1b1 +/+ male mice. The G protein-coupled estrogen receptor 1 antagonist G-15 failed to alter Ang II-induced increases in blood pressure and renal function in Cyp1b1 +/+ female mice. These data suggest that 2-methoxyestradiol reduces Ang II-induced hypertension and associated end-organ damage in intact Cyp1b1 -/- , ovariectomized Cyp1b1 +/+ and Cyp1b1 -/- female mice, and Cyp1b1 +/+ male mice independent of G protein-coupled estrogen receptor 1. Therefore, 2-methoxyestradiol could serve as a therapeutic agent for treating hypertension and associated pathogenesis in postmenopausal females, and in males. © 2017 American Heart Association, Inc.

  18. Adult Behavior in Male Mice Exposed to E-Cigarette Nicotine Vapors during Late Prenatal and Early Postnatal Life.

    Directory of Open Access Journals (Sweden)

    Dani Smith

    Full Text Available 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.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.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.

  19. Adult Behavior in Male Mice Exposed to E-Cigarette Nicotine Vapors during Late Prenatal and Early Postnatal Life.

    Science.gov (United States)

    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

    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. 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. 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.

  20. Cognitive performance of male and female C57BL/6J mice after repetitive concussive brain injuries.

    Science.gov (United States)

    Velosky, Alexander G; Tucker, Laura B; Fu, Amanda H; Liu, Jiong; McCabe, Joseph T

    2017-05-01

    In contact sports, repetitive concussive brain injury (rCBI) is the prevalent form of head injury seen in athletes. The need for effective treatment is urgent as rCBI has been associated with a host of cognitive, behavioral and neurological complaints. There has been a growing trend in the use of female animals in pre-clinical research, but few studies have investigated possible sex differences following rCBI. The goal of the current study was to determine any differences between male and female C57BL/6J mice on assessments of learning and memory after repetitive concussive injury. Following rCBI by impact to the scalp, male mice exhibited longer righting reflexes during acute recovery. In both sexes, there were no evident histopathological changes observed in the underlying cerebral cortex or hippocampus. Reactive astrogliosis was elevated in the corpus callosum and optic tract, and astrogliosis was slightly less in the optic tract of female mice. rCBI mice exhibited impairment during the learning phase of the Morris water maze (MWM), but female mice, in comparison to male mice, were observed to have superior spatial memory during standard MWM probe trials. Female mice were overall more active, evidenced by greater distances traveled in the y-maze and greater swim speeds in the MWM. The results of this study demonstrate sex differences in cognitive performance following rCBI and support previous research suggesting the neuroprotective role of sex in brain injury. Published by Elsevier B.V.

  1. Influence of the thymus on the capacity of female mice to reject male skin grafts

    International Nuclear Information System (INIS)

    De Pirro, E.S.; Goldberg, E.H.

    1989-01-01

    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

  2. Late gestational intermittent hypoxia induces metabolic and epigenetic changes in male adult offspring mice.

    Science.gov (United States)

    Khalyfa, Abdelnaby; Cortese, Rene; Qiao, Zhuanhong; Ye, Honggang; Bao, Riyue; Andrade, Jorge; Gozal, David

    2017-04-15

    Late gestation during pregnancy has been associated with a relatively high prevalence of obstructive sleep apnoea (OSA). Intermittent hypoxia, a hallmark of OSA, could impose significant long-term effects on somatic growth, energy homeostasis and metabolic function in offspring. Here we show that late gestation intermittent hypoxia induces metabolic dysfunction as reflected by increased body weight and adiposity index in adult male offspring that is paralleled by epigenomic alterations and inflammation in visceral white adipose tissue. Fetal perturbations by OSA during pregnancy impose long-term detrimental effects manifesting as metabolic dysfunction in adult male offspring. Pregnancy, particularly late gestation (LG), has been associated with a relatively high prevalence of obstructive sleep apnoea (OSA). Intermittent hypoxia (IH), a hallmark of OSA, could impose significant long-term effects on somatic growth, energy homeostasis, and metabolic function in offspring. We hypothesized that IH during late pregnancy (LG-IH) may increase the propensity for metabolic dysregulation and obesity in adult offspring via epigenetic modifications. Time-pregnant female C57BL/6 mice were exposed to LG-IH or room air (LG-RA) during days 13-18 of gestation. At 24 weeks, blood samples were collected from offspring mice for lipid profiles and insulin resistance, indirect calorimetry was performed and visceral white adipose tissues (VWAT) were assessed for inflammatory cells as well as for differentially methylated gene regions (DMRs) using a methylated DNA immunoprecipitation on chip (MeDIP-chip). Body weight, food intake, adiposity index, fasting insulin, triglycerides and cholesterol levels were all significantly higher in LG-IH male but not female offspring. LG-IH also altered metabolic expenditure and locomotor activities in male offspring, and increased number of pro-inflammatory macrophages emerged in VWAT along with 1520 DMRs (P < 0.0001), associated with 693

  3. Meiotic sex chromosome inactivation is disrupted in sterile hybrid male house mice.

    Science.gov (United States)

    Campbell, Polly; Good, Jeffrey M; Nachman, Michael W

    2013-03-01

    In male mammals, the X and Y chromosomes are transcriptionally silenced in primary spermatocytes by meiotic sex chromosome inactivation (MSCI) and remain repressed for the duration of spermatogenesis. Here, we test the longstanding hypothesis that disrupted MSCI might contribute to the preferential sterility of heterogametic hybrid males. We studied a cross between wild-derived inbred strains of Mus musculus musculus and M. m. domesticus in which sterility is asymmetric: F1 males with a M. m. musculus mother are sterile or nearly so while F1 males with a M. m. domesticus mother are normal. In previous work, we discovered widespread overexpression of X-linked genes in the testes of sterile but not fertile F1 males. Here, we ask whether this overexpression is specifically a result of disrupted MSCI. To do this, we isolated cells from different stages of spermatogenesis and measured the expression of several genes using quantitative PCR. We found that X overexpression in sterile F1 primary spermatocytes is coincident with the onset of MSCI and persists in postmeiotic spermatids. Using a series of recombinant X genotypes, we then asked whether X overexpression in hybrids is controlled by cis-acting loci across the X chromosome. We found that it is not. Instead, one large interval in the proximal portion of the M. m. musculus X chromosome is associated with both overexpression and the severity of sterility phenotypes in hybrids. These results demonstrate a strong association between X-linked hybrid male sterility and disruption of MSCI and suggest that trans-acting loci on the X are important for the transcriptional regulation of the X chromosome during spermatogenesis.

  4. Kisspeptin neurones in the posterodorsal medial amygdala modulate sexual partner preference and anxiety in male mice.

    Science.gov (United States)

    Adekunbi, D A; Li, X F; Lass, G; Shetty, K; Adegoke, O A; Yeo, S H; Colledge, W H; Lightman, S L; O'Byrne, K T

    2018-03-01

    The posterodorsal medial amygdala (MePD) is a neural site in the limbic brain involved in regulating emotional and sexual behaviours. There is, however, limited information available on the specific neuronal cell type in the MePD functionally mediating these behaviours in rodents. The recent discovery of a significant kisspeptin neurone population in the MePD has raised interest in the possible role of kisspeptin and its cognate receptor in sexual behaviour. The present study therefore tested the hypothesis that the MePD kisspeptin neurone population is involved in regulating attraction towards opposite sex conspecifics, sexual behaviour, social interaction and the anxiety response by selectively stimulating these neurones using the novel pharmacosynthetic DREADDs (designer receptors exclusively activated by designer drugs) technique. Adult male Kiss-Cre mice received bilateral stereotaxic injections of a stimulatory DREADD viral construct (AAV-hSyn-DIO-hM 3 D(Gq)-mCherry) targeted to the MePD, with subsequent activation by i.p. injection of clozapine-N-oxide (CNO). Socio-sexual behaviours were assessed in a counter-balanced fashion after i.p. injection of either saline or CNO (5 mg kg -1 ). Selective activation of MePD kisspeptin neurones by CNO significantly increased the time spent by male mice in investigating an oestrous female, as well as the duration of social interaction. Additionally, after CNO injection, the mice appeared less anxious, as indicated by a longer exploratory time in the open arms of the elevated plus maze. However, levels of copulatory behaviour were comparable between CNO and saline-treated controls. These data indicate that DREADD-induced activation of MePD kisspeptin neurones enhances both sexual partner preference in males and social interaction and also decreases anxiety, suggesting a key role played by MePD kisspeptin in sexual motivation and social behaviour. © 2018 The Authors. Journal of Neuroendocrinology published by John Wiley

  5. Age-Related Decrease in Stress Responsiveness and Proactive Coping in Male Mice.

    Science.gov (United States)

    Oh, Hee-Jin; Song, Minah; Kim, Young Ki; Bae, Jae Ryong; Cha, Seung-Yun; Bae, Ji Young; Kim, Yeongmin; You, Minsu; Lee, Younpyo; Shim, Jieun; Maeng, Sungho

    2018-01-01

    Coping is a strategic approach to dealing with stressful situations. Those who use proactive coping strategies tend to accept changes and act before changes are expected. In contrast, those who use reactive coping are less flexible and more likely to act in response to changes. However, little research has assessed how coping style changes with age. This study investigated age-related changes in coping strategies and stress responsiveness and the influence of age on the processing of conditioned fear memory in 2-, 12- and 23-month-old male mice. Coping strategy was measured by comparing the escape latency in an active avoidance test and by comparing responses to a shock prod. The results showed that proactivity in coping response gradually decreased with age. Stress responsiveness, measured by stress-induced concentration of corticosterone, was also highest in 2-month-old mice and decreased with age. Consolidation of fear memory was highest in 12-month-old mice and was negatively correlated with the degree of stress responsiveness and proactivity in coping. Fear extinction did not differ among age groups and was not correlated with stress responsiveness or the proactivity of coping. However, the maintenance of extinct fear memory, which was best in 2-month-old mice and worst in 12-month-old mice, was negatively correlated with stress responsiveness but not with coping style. Age-dependent changes in the expression of glucocorticoid receptor (GR) and its regulatory co-chaperones, which are accepted mechanisms for stress hormone stimulation, were measured in the hippocampus. The expression of GR was increased at 12 months compared to other age groups. There were no differences in Hsp70 and BAG1 expression by age. These results can be summarized as follows: (1) stress responsiveness and proactivity in coping decreased with age class; (2) consolidation of fear memory was negatively correlated with both stress responsiveness and proactivity; however, maintenance of

  6. Selection on plant male function genes identifies candidates for reproductive isolation of yellow monkeyflowers.

    Directory of Open Access Journals (Sweden)

    Jan E Aagaard

    Full Text Available Understanding the genetic basis of reproductive isolation promises insight into speciation and the origins of biological diversity. While progress has been made in identifying genes underlying barriers to reproduction that function after fertilization (post-zygotic isolation, we know much less about earlier acting pre-zygotic barriers. Of particular interest are barriers involved in mating and fertilization that can evolve extremely rapidly under sexual selection, suggesting they may play a prominent role in the initial stages of reproductive isolation. A significant challenge to the field of speciation genetics is developing new approaches for identification of candidate genes underlying these barriers, particularly among non-traditional model systems. We employ powerful proteomic and genomic strategies to study the genetic basis of conspecific pollen precedence, an important component of pre-zygotic reproductive isolation among yellow monkeyflowers (Mimulus spp. resulting from male pollen competition. We use isotopic labeling in combination with shotgun proteomics to identify more than 2,000 male function (pollen tube proteins within maternal reproductive structures (styles of M. guttatus flowers where pollen competition occurs. We then sequence array-captured pollen tube exomes from a large outcrossing population of M. guttatus, and identify those genes with evidence of selective sweeps or balancing selection consistent with their role in pollen competition. We also test for evidence of positive selection on these genes more broadly across yellow monkeyflowers, because a signal of adaptive divergence is a common feature of genes causing reproductive isolation. Together the molecular evolution studies identify 159 pollen tube proteins that are candidate genes for conspecific pollen precedence. Our work demonstrates how powerful proteomic and genomic tools can be readily adapted to non-traditional model systems, allowing for genome-wide screens

  7. Interaction between Sex Hormones and Matricaria Chamomilla Hydroalcholic Extract on Motor Activity Behavior in Gonadectomized Male and Female Mice

    Directory of Open Access Journals (Sweden)

    H. Raie

    2006-04-01

    Full Text Available Introduction & Objective: Locomotor activity is an important physiologic phenomenon that is influenced by several factors. In previous study we showed that the matricaria chamomilla (chamomile hydroalcholic extract acts differently in male and female mice. Therefore in this study, the role of sex hormones and chamomile hydroalcholic extract were investigated on motor activity behavior in absence of sex glands in adult male and female NMRI mice. Materials and Methods: Gonadectomized male and female mice were divided into groups (seven mice in each group including: receiving testosterone (2 mg/kg S.C., estradiol benzoate (0.1 mg/kg S.C., and progesterone (0.5 mg/kg S.C. with and without hydroalcholic extract of chamomile (50 mg/kg i.p. Motor activity monitor system was used to evaluate locomotor activity parameters (fast and slow activity, fast and slow stereotype activity, fast and slow rearing in all groups. Results: 1 Testosterone had no any effect on motor activity parameters, but extract of chamomile with and without testosterone decreased motor activity parameters in male mice. 2 Estradiol benzoate and chamomile hydroalcholic extract in presence and absence of each other increased locomotor activity parameters in female mice. 3 Progesterone also did not change motor activity parameters in presence and absence of chamomile hydroalcholic extract in female mice. 4 Administration of Estradiol benzoate with progestrone in presence and absence of chamomile hydroalcholic extract did not alter motor activity parameters in female mice. Conclusion: It seems both of the chamomile hydroalcholic extract and estradiol enhance motor activity and probably act through same system and potentiate the effect of each other. Also it seems there are interaction between estradiol and progesterone and also between chamomile extract and progesterone. Testosterone probably did not have any interaction with chamomile extract in locomotor activity.

  8. Exercise training and antioxidant supplementation independently improve cognitive function in adult male and female GFAP-APOE mice

    OpenAIRE

    Kiran Chaudhari; Jessica M. Wong; Philip H. Vann; Nathalie Sumien

    2014-01-01

    Purpose: The purpose of this study was to determine if antioxidant supplementation, moderate exercise, and the combination of both treatments could ameliorate cognitive performance in adult mice and whether the apolipoprotein E (APOE) genotype as well as sex could influence the functional outcomes of the treatments. Methods: For a period of 16 weeks, separate groups of male and female mice expressing either the human APOE3 or APOE4 isoforms were fed either a control diet (NIH-31) or the co...

  9. Puberty Is Delayed in Male Mice With Dextran Sodium Sulfate Colitis Out of Proportion to Changes in Food Intake, Body Weight, and Serum Levels of Leptin

    OpenAIRE

    DEBOER, MARK D.; LI, YONGLI

    2011-01-01

    In boys, inflammatory bowel disease often results in delayed puberty associated with decreased bone mineral density and decreased linear growth. Our goal was to investigate whether pubertal timing and levels of leptin differed between prepubertal male mice with colitis and food-restricted (FR) mice maintained at a similar weight. We induced colitis in 32-d-old male mice using dextran sodium sulfate (DSS), resulting in 10 d of worsening colitis. We followed up these mice for separation of the ...

  10. Cumulative genetic effects from exposure of male mice to tritium for ten generations

    International Nuclear Information System (INIS)

    Mewissen, D.J.; Ugarte, A.S.

    1979-01-01

    Three sublines of C57 Black/6M mice were propagated from three sibling pairs from the same litter. All breeders were weaned at 28+-2 days of age. At each generation in experimental lines weaned male breeders aged 35 days either received a single injection of tritiated thymidine (1 μCi/g of body weight) or were exposed for 5 weeks to tritiated drinking water (10 μCi/ml). At 10 weeks of age all breeders were sibling-mated. The time of delivery, the litter size and sex ratio was recorded. At each generation the offspring in the three lines were sibling-mated in the same sequence as their parents. At the 6th generation total offspring in the sibling line receiving tritiated thymidine numbered 108 versus 336 in the sibling line exposed to tritiated water, in contrast with 721 in the control sibling line. The 6th generation couples (20 in either subline) generated at the 9th generation 624 animals in the control subline versus 386 and 476 in the subline exposed to tritium. The data suggest a trend toward reduction in the subpopulation of offspring propagated from male parents exposed to tritiated water or tritiated thymidine. At the 9th generation 50 couples were assigned to a special study on reproductive fitness. The litter size was decreased and infant mortality was increased in experimental sublines (chi-square test, P<0.05). In control, as well as in experimental lines, at 70 days of age males were sibling-mated with their sisters. All animals received tap water and were not exposed at any time to tritiated thymidine or tritiated water. Preimplantation loss values were significantly increased in experimental versus control sublines (chi-square test, P<0.01). The dose to male sperm over a 35-day period was estimated at 3.7 rads from tritiated water and at 3.9 rads from tritiated thymidine under our experimental conditions

  11. Hepatoprotective Effects of Met-enkephalin on Acetaminophen-Induced Liver Lesions in Male CBA Mice

    Directory of Open Access Journals (Sweden)

    Roko Martinić

    2014-08-01

    Full Text Available Recent histopathological investigations in patients with hepatitis suggested possible involvement of Met-enkephalin and its receptors in the pathophysiology of hepatitis. Consequently, we evaluated the potential hepatoprotective effects of this endogenous opioid pentapeptide in the experimental model of acetaminophen induced hepatotoxicity in male CBA mice. Met-enkephalin exhibited strong hepatoprotective effects in a dose of 7.5 mg/kg, which corresponds to the protective dose reported for several different animal disease models. In this group plasma alanine aminotransferase and aspartate aminotransferase enzyme activities, as well as liver necrosis score were significantly reduced in comparison to control animals treated with physiological saline (p > 0.01. The specificity of the peptide hepatoprotection was investigated from the standpoint of the receptor and peptide blockade. It was concluded that Met-enkephalin effects on the liver were mediated via δ and ζ opioid receptors. Genotoxic testing of Met-enkephalin confirmed the safety of the peptide.

  12. The Effects of Dietary Macronutrient Balance on Skin Structure in Aging Male and Female Mice

    Science.gov (United States)

    McMahon, Aisling C.; Ruohonen, Kari; Raubenheimer, David; Ballard, J. William O.; Le Couteur, David G.; Nicholls, Caroline; Li, Zhe; Maitz, Peter K. M.; Wang, Yiwei; Simpson, Stephen J.

    2016-01-01

    Nutrition influences skin structure; however, a systematic investigation into how energy and macronutrients (protein, carbohydrate and fat) affects the skin has yet to be conducted. We evaluated the associations between macronutrients, energy intake and skin structure in mice fed 25 experimental diets and a control diet for 15 months using the Geometric Framework, a novel method of nutritional analysis. Skin structure was associated with the ratio of dietary macronutrients eaten, not energy intake, and the nature of the effect differed between the sexes. In males, skin structure was primarily associated with protein intake, whereas in females carbohydrate intake was the primary correlate. In both sexes, the dermis and subcutaneous fat thicknesses were inversely proportional. Subcutaneous fat thickness varied positively with fat intake, due to enlarged adipocytes rather than increased adipocyte number. We therefore demonstrated clear interactions between skin structure and macronutrient intakes, with the associations being sex-specific and dependent on dietary macronutrient balance. PMID:27832138

  13. Male mate recognition via cuticular hydrocarbons facilitates sexual isolation between sympatric leaf beetle sister species.

    Science.gov (United States)

    Zhang, Bin; Xue, Huai-Jun; Song, Ke-Qing; Liu, Jie; Li, Wen-Zhu; Nie, Rui-E; Yang, Xing-Ke

    2014-11-01

    Chemical signals in insects have been documented to play an important role in mate recognition, and divergence in chemical signals can often cause sexual isolation between closely related species or populations within species. We investigated the role of cuticular hydrocarbons (CHCs), short distance chemical signals, in male mate recognition between the two sympatric elm leaf beetles, Pyrrhalta maculicollis and Pyrrhaltaaenescens. Mating experiments demonstrated that strong sexual isolation between the two species was driven by CHCs divergence. Males preferred to mate with conspecific females with intact conspecific CHCs or conspecific CHCs reapplied after removal. Males also preferred heterospecific females that were treated with conspecific CHCs. Chemical analysis showed that the CHC profiles differ significantly between species. In P. maculicollis dimethyl-branched alkanes between C29 and C35 account for the majority of the saturated alkanes while the CHC profile of P. aenescens mostly consisted of monomethyl-branched alkanes between C22 and C29. Additionally, some compounds, such as 12,18-diMeC32, 12,18-diMeC34, are unique to P. maculicollis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Adult Gli2+/-;Gli3Δ699/+ Male and Female Mice Display a Spectrum of Genital Malformation.

    Directory of Open Access Journals (Sweden)

    Fei He

    Full Text Available Disorders of sexual development (DSD encompass a broad spectrum of urogenital malformations and are amongst the most common congenital birth defects. Although key genetic factors such as the hedgehog (Hh family have been identified, a unifying postnatally viable model displaying the spectrum of male and female urogenital malformations has not yet been reported. Since human cases are diagnosed and treated at various stages postnatally, equivalent mouse models enabling analysis at similar stages are of significant interest. Additionally, all non-Hh based genetic models investigating DSD display normal females, leaving female urogenital development largely unknown. Here, we generated compound mutant mice, Gli2+/-;Gli3Δ699/+, which exhibit a spectrum of urogenital malformations in both males and females upon birth, and also carried them well into adulthood. Analysis of embryonic day (E18.5 and adult mice revealed shortened anogenital distance (AGD, open ventral urethral groove, incomplete fusion of scrotal sac, abnormal penile size and structure, and incomplete testicular descent with hypoplasia in male mice, whereas female mutant mice displayed reduced AGD, urinary incontinence, and a number of uterine anomalies such as vaginal duplication. Male and female fertility was also investigated via breeding cages, and it was identified that male mice were infertile while females were unable to deliver despite becoming impregnated. We propose that Gli2+/-;Gli3Δ699/+ mice can serve as a genetic mouse model for common DSD such as cryptorchidism, hypospadias, and incomplete fusion of the scrotal sac in males, and a spectrum of uterine and vaginal abnormalities along with urinary incontinence in females, which could prove essential in revealing new insights into their equivalent diseases in humans.

  15. Enantioselective disruption of the endocrine system by Cis-Bifenthrin in the male mice.

    Science.gov (United States)

    Jin, Yuanxiang; Wang, Jiangcong; Pan, Xiuhong; Miao, Wenyu; Lin, Xiaojian; Wang, Linggang; Fu, Zhengwei

    2015-07-01

    Bifenthrin (BF), as a chiral pyrethroid, is widely used to control field and household pests in China. At present, the commercial BF is a mixed compound containing cis isomers (cis-BF) including two enantiomers of 1R-cis-BF and 1S-cis-BF. In the present study, the two individual cis-BF enantiomers were separated by a preparative supercritical fluid chromatography. Then, four week-old adolescent male ICR mice were orally administered 1R-cis-BF and 1S-cis-BF separately daily for 3 weeks at doses of 0, 7.5 and 15 mg/kg/day, respectively. Results showed that the transcription status of some genes involved in cholesterol synthesis and transport as well as testosterone (T) synthesis in the testes were influenced by cis-BF enantiomers. Especially, we observed that the transcription status of key genes on the pathway of T synthesis including cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc) and cytochrome P450 17α-hydroxysteroid dehydrogenase (P45017α)) were selectively altered in the testis of mice when treated with 1S-cis-BF, suggesting that it is the possible reason to explain why the lower serum T concentration in 1S-cis-BF treated group. Taken together, it concluded that both of the cis-BF enantiomers have the endocrine disruption activities, while 1S-cis-BF was higher than 1R-cis-BF in mice when exposed during the puberty. The data was helpful to understand the toxicity of cis-BF in mammals under enantiomeric level. © 2014 Wiley Periodicals, Inc.

  16. Dietary arginine depletion reduces depressive-like responses in male, but not female, mice.

    Science.gov (United States)

    Workman, Joanna L; Weber, Michael D; Nelson, Randy J

    2011-09-30

    Previous behavioral studies have manipulated nitric oxide (NO) production either by pharmacological inhibition of its synthetic enzyme, nitric oxide synthase (NOS), or by deletion of the genes that code for NOS. However manipulation of dietary intake of the NO precursor, L-arginine, has been understudied in regard to behavioral regulation. L-Arginine is a common amino acid present in many mammalian diets and is essential during development. In the brain L-arginine is converted into NO and citrulline by the enzyme, neuronal NOS (nNOS). In Experiment 1, paired mice were fed a diet comprised either of an L-arginine-depleted, L-arginine-supplemented, or standard level of L-arginine during pregnancy. Offspring were continuously fed the same diets and were tested in adulthood in elevated plus maze, forced swim, and resident-intruder aggression tests. L-Arginine depletion reduced depressive-like responses in male, but not female, mice and failed to significantly alter anxiety-like or aggressive behaviors. Arginine depletion throughout life reduced body mass overall and eliminated the sex difference in body mass. Additionally, arginine depletion significantly increased corticosterone concentrations, which negatively correlated with time spent floating. In Experiment 2, adult mice were fed arginine-defined diets two weeks prior to and during behavioral testing, and again tested in the aforementioned tests. Arginine depletion reduced depressive-like responses in the forced swim test, but did not alter behavior in the elevated plus maze or the resident intruder aggression test. Corticosterone concentrations were not altered by arginine diet manipulation in adulthood. These results indicate that arginine depletion throughout development, as well as during a discrete period during adulthood ameliorates depressive-like responses. These results may yield new insights into the etiology and sex differences of depression. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. Cadmium Exposure Impairs Cognition and Olfactory Memory in Male C57BL/6 Mice.

    Science.gov (United States)

    Wang, Hao; Zhang, Liang; Abel, Glen M; Storm, Daniel R; Xia, Zhengui

    2018-01-01

    Cadmium (Cd) is a heavy metal of high interest to the superfund initiative. Recent epidemiology studies have suggested a possible association between Cd exposure and cognitive as well as olfactory impairments in humans. However, studies in animal models are needed to establish a direct causal relationship between Cd exposure and impairments in cognition and olfaction. This study aims to investigate the toxic effect of Cd on cognition and olfactory function in mice. One group of 8-week-old C57BL/6 male mice was exposed to 3 mg/l Cd (in the form of CdCl2) through drinking water for 20 weeks for behavior tests and final blood Cd concentration analysis. The behavior tests were conducted before, during, and after Cd exposure to analyze the effects of Cd on cognition and olfactory function. Upon completion of behavior tests, blood was collected to measure final blood Cd concentration. Two additional groups of mice were similarly exposed to Cd for 5 or 13 weeks for peak blood Cd concentration measurement. The peak blood Cd concentration was 2.125-2.25 μg/l whereas the final blood Cd concentration was 0.18 μg/l. At this exposure level, Cd impaired hippocampus-dependent learning and memory in novel object location test, T-maze test, and contextual fear memory test. It also caused deficits in short-term olfactory memory and odor-cued olfactory learning and memory. Results in this study demonstrate a direct relationship between Cd exposure and cognitive as well as olfactory impairments in an animal model. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Precopulatory sexual behavior of male mice is changed by the exposure to tannery effluent.

    Science.gov (United States)

    Quintão, Thales Chagas; Rabelo, Letícia Martins; Alvarez, T G S; Guimarães, A T; Rodrigues, A S L; Cardoso, L S; Ferreira, R O; Malafaia, Guilherme

    2018-03-01

    Although the toxic potential of tannery effluents (TE) is acknowledged, the impacts these residues have on mammals who intake water contaminated with this pollutant are not completely known. Thus, in order to broaden the knowledge about how these contaminants affect the biota, the aim of the current study is to assess different behavioral categories (e.g.: sexual odor preference, opposite-sex attraction, and sexual discrimination) related to the sexual motivation and pre-copulation of male Swiss mice subjected to TE intake for 30 days, at concentrations 0.8% and 22%. The animals were subjected to locomotor performance evaluation through the Basso Mouse Scale (BMS), as well as to the open field (OF), odor preference (OPT), sexual orientation (SOT) and to scent marking tests (SMT) one week before the experiment ended. Our results evidenced that the treatments did not affect the animals' locomotor activity (in OF and BMS) or caused changes compatible to anxiogenic or anxiolytic behavior (in OF). However, mice exposed to TE (at both concentrations) presented discriminatory capacity deficit in the OPT test at the time to distinguish conspecific odors from the same sex, and from the opposite sex. They randomly explored (without preference) males and females, did not responded to stimuli in the SOT test, as well as did not appear capable of detecting female odor (in estrus phase) during the SMT. Thus, the current study was pioneer in evidencing that TE can influence the reproduction and the population dynamics of small rodents who intake water contaminated with the pollutant. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Immunomodulatory effects of maternal atrazine exposure on male Balb/c mice

    International Nuclear Information System (INIS)

    Rowe, Alexander M.; Brundage, Kathleen M.; Schafer, Rosana; Barnett, John B.

    2006-01-01

    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 μg 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 + T cell, CD4 + T cell, or B220 + 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

  20. Protective effects of caffeoylxanthiazonoside isolated from fruits of Xanthium strumarium on sepsis mice.

    Science.gov (United States)

    Wang, Yan-Hong; Li, Tie-Hua; Wu, Ben-Quan; Liu, Hui; Shi, Yun-Feng; Feng, Ding-Yun

    2015-01-01

    The fruit of Xanthium strumarium L. (Asteraceae) has been used for the treatment of various inflammatory diseases. This study investigates the protective effect of caffeoylxanthiazonoside (CYXD) isolated from fruits of X. strumarium on sepsis mice in vitro and in vivo. Cecal ligation and puncture (CLP) operation was used to establish the sepsis mice model, and sham mice were also performed. CYXD was administered by intraperitoneal injection (10, 20, and 40 mg/kg/d), then the survival rate was measured in 96 h. Additionally, sepsis mice were induced by injection LPS (2 mg/kg); CYXD was administered by intraperitoneal injection (10, 20, and 40 mg/kg/d), then mice were sacrificed, and serum levels of TNF-α and IL-6 were determined by ELISA assay. Furthermore, the ability of CYXD to neutralize LPS was measured by using the LAL test, and expressions of TNF-α, IL-6 were determined by using real-time fluorogenic PCR. Results indicated that CYXD significantly elevated survival rates of sepsis mice induced by CLP (p < 0.05) with survival rates of 35%, 45%, and 65%. Furthermore, the LPS level was decreased obviously by CYXD (1, 2, and 4 mg/L) (p < 0.05). Additionally, CYXD (10, 20, and 40 mg/kg) can not only significantly decrease TNF-α and IL-6 levels induced by LPS in mice's serum (p < 0.05), but also inhibit mRNA expressions of TNF-α and IL-6 induced by LPS in RAW 264.7 cells at doses of 20, 40, and 80 μg/mL (p < 0.05). Our study demonstrated that CYXD has significant protective effects on sepsis mice.

  1. The Effects of Melatonin with Memantin on MPTP-Induced Parkinson Model in Male Mice

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    Reza Talebi

    2015-09-01

    Full Text Available Abstract Background: Oxidative stress and severe neuro-excitation have significant effects on pathogenesis of Parkinson’s disease and agents with antioxidant property can potentially prevent these effects. Herein we examined potential protective effects of melatonin as an antioxidant agent and memantine as an uncompetitive receptor of NMDA, on a model of Parkinson’s disease induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP. Materials and Methods: Male mice were divided into 8 groups with 7 mice in each group: saline, ethanol, melatonin, memantin, MPTP, melatonin+MPTP, memantin+ MPTP, melatonin+ memantin+ MPTP. All of agents were injected intraperitoneally once a day for 14 days before beam traversal test. Dopaminergic neurons of the Substantia Nigra Pars compacta (SNPC were determined by immunohistochemical and were counted. Results: Melatonin improved notably movement dysfunction resulted of MPTP such as the number of errors, paces and the time of movement during behavioral test and also the counting of neurons of Substantia Nigra Pars Compacta. Memantin had a synergic effect on the most of improvements. However, the level of improvement and retrieval of signs was not as in saline and ethanol groups. Conclusion: Melatonin especially together with memantine is able to prevent some of the MPTP-induced dysfunctions. However, the protective effects were not enogh, probably because of the amount of dose and the time of injection.

  2. Evaluation the protective effect of diphenhydramine against acute toxicity induced by levamisole in male mice

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    M.Y. Matti

    2015-06-01

    Full Text Available The aim of this study was to evaluate the protective effect of different doses of diphenhydramine against acute toxicosis with Levamisole. The Mechanism of levamisole induced acute toxicity and that of protective effect of diphenhydramine against Levamisole toxicosis also examined on the level of cholinesterase (ChE activity. Subcutanous injection of 100mg/kg levamisole in male mice with induced cholinergic over stimulation and death in 100% of animals. The Toxicosis was not related to the significantly decreased in plasma, red blood cells and brain ChE activity. Injection low dose of diphenhydramin 2.5mg/kg S.C. 15 min before levamisole produced protective effect against acute toxicity with levamisole. Significantly decreased the severity of toxicosis and increased survival rates to 100%. Diphenhydramine at low dose alone or with acute dose of levamisole did not Produced Significantly inhibition in ChE activity.The data suggested that the toxic effect of Levamisole was not related to inhibition of ChE. The low dose of diphenhydramine protected mice from Levamisole toxicity. The antidoatal effect of diphenhydramine not at the level of protection from ChE inhibition. There was no adverse interaction between two drugs.

  3. Neural and behavioural changes in male periadolescent mice after prolonged nicotine-MDMA treatment.

    Science.gov (United States)

    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.

  4. Evaluation of low intensity laser effects in the thyroid glands region of male mice

    International Nuclear Information System (INIS)

    Azevedo, Luciane Hiramatsu

    2002-01-01

    Recent studies have demonstrated that the infra-red laser can cause alterations in thyroid glands. Their normal activity must be preserved, as they produce the thyroidal hormones triiodothyronine (T 3 ) and thyroxine (T 4 ), that stimulate the oxidative metabolism, essential to maintain a healthy organism. The increase or diminution of these hormones results in alteration of the mitochondria's activity, that determines the secondary effects in the metabolism. The purpose of this study was to evaluate if there was any alteration of the thyroidal hormones plasma levels under irradiation from infra-red laser, with energy density of 4J/cm 2 , in the region of thyroid glands of male mice. It was concluded that there was an hormonal level alteration statistically significant between the first day of irradiation and seven days after the last application. Histological studies showed that there was no morphological changes in histological sections of thyroid glands. The optical absorption spectroscopy of mice's serum presented a peak at approximately 280 nm, attributed to tyrosine (this is the amino acid compounding these hormones). (author)

  5. Middle age has a significant impact on gene expression during skin wound healing in male mice.

    Science.gov (United States)

    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.

  6. Gonadal cell kinetics in male mice treated with sulphur-35 during prenatal development

    International Nuclear Information System (INIS)

    Satyanarayana Reddy, K.; Reddy, P.P.; Reddi, O.S.

    1980-01-01

    Investigations on the possible hazards of the use of internally administered radioisotopes in human medicine either as therapeutic or diagnostic agents before or during child bearing age are of late gaining importance. The present investigation has been taken up to screen the effects of sulphur-35 on spermatogonia. CBA pregnant mice were injected (ip) with a dose of 20 μ Ci of sulphur-35 on 3.5, 10.5 or 15.5 days of gestation. At the similar intervals pregnant mice injected with physiological saline were kept for control data. All the animals were allowed to litter and F 1 male progeny were killed at maturity at the age of 10 weeks and the testes collected. Sections of both the testes were prepared and stained by PAS-haematoxylin technique and the survival of spermatogonia types A, Int and B and preleptotene spermatocytes was evaluated. There was a significant reduction in all the cell types in the sulphur-35 treated animals. Thus the results indicate the cell-killing effect of radionuclide. (auth.)

  7. Xylitol Affects the Intestinal Microbiota and Metabolism of Daidzein in Adult Male Mice

    Directory of Open Access Journals (Sweden)

    Motoi Tamura

    2013-12-01

    Full Text Available 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.

  8. Immune Alterations in Male and Female Mice after 2-Deoxy-D-Glucose Administration

    Science.gov (United States)

    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.

  9. Xylitol affects the intestinal microbiota and metabolism of daidzein in adult male mice.

    Science.gov (United States)

    Tamura, Motoi; Hoshi, Chigusa; Hori, Sachiko

    2013-12-10

    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 XD group than in the CD group (p XD group than in the CD group (p 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.

  10. Gonadal cell kinetics in male mice treated with sulphur-35 during prenatal development

    Energy Technology Data Exchange (ETDEWEB)

    Satyanarayana Reddy, K; Reddy, P P; Reddi, O S [Osmania Univ., Hyderabad (India). Inst. of Genetics

    1980-11-01

    Investigations on the possible hazards of the use of internally administered radioisotopes in human medicine either as therapeutic or diagnostic agents before or during child bearing age are of late gaining importance. The present investigation has been taken up to screen the effects of sulphur-35 on spermatogonia. CBA pregnant mice were injected (ip) with a dose of 20 ..mu.. Ci of sulphur-35 on 3.5, 10.5 or 15.5 days of gestation. At the similar intervals pregnant mice injected with physiological saline were kept for control data. All the animals were allowed to litter and F/sub 1/ male progeny were killed at maturity at the age of 10 weeks and the testes collected. Sections of both the testes were prepared and stained by PAS-haematoxylin technique and the survival of spermatogonia types A, Int and B and preleptotene spermatocytes was evaluated. There was a significant reduction in all the cell types in the sulphur-35 treated animals. Thus the results indicate the cell-killing effect of radionuclide.

  11. Pairmate-dependent pup retrieval as parental behavior in male mice

    Directory of Open Access Journals (Sweden)

    Mingkun eLiang

    2014-07-01

    Full Text Available 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., Nat. Commun, 4:1346, 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.

  12. Social isolation induces deficit of latent learning performance in mice: a putative animal model of attention deficit/hyperactivity disorder.

    Science.gov (United States)

    Ouchi, Hirofumi; Ono, Kazuya; Murakami, Yukihisa; Matsumoto, Kinzo

    2013-02-01

    Social isolation of rodents (SI) elicits a variety of stress responses such as increased aggressiveness, hyper-locomotion, and reduced susceptibility to pentobarbital. To obtain a better understanding of the relevance of SI-induced behavioral abnormalities to psychiatric disorders, we examined the effect of SI on latent learning as an index of spatial attention, and discussed the availability of SI as an epigenetic model of attention deficit hyperactivity disorder (ADHD). Except in specially stated cases, 4-week-old male mice were housed in a group or socially isolated for 3-70 days before experiments. The animals socially isolated for 1 week or more exhibited spatial attention deficit in the water-finding test. Re-socialized rearing for 5 weeks after 1-week SI failed to attenuate the spatial attention deficit. The effect of SI on spatial attention showed no gender difference or correlation with increased aggressive behavior. Moreover, SI had no effect on cognitive performance elucidated in a modified Y-maze or an object recognition test, but it significantly impaired contextual and conditional fear memory elucidated in the fear-conditioning test. Drugs used for ADHD therapy, methylphenidate (1-10 mg/kg, i.p.) and caffeine (0.5-1 mg/kg, i.p.), improved SI-induced latent learning deficit in a manner reversible with cholinergic but not dopaminergic antagonists. Considering the behavioral features of SI mice together with their susceptibility to ADHD drugs, the present findings suggest that SI provides an epigenetic animal model of ADHD and that central cholinergic systems play a role in the effect of methylphenidate on SI-induced spatial attention deficit. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Effects of buprenorphine and meloxicam analgesia on induced cerebral ischemia in C57BL/6 male mice

    DEFF Research Database (Denmark)

    Jacobsen, Kirsten R; Fauerby, Natasha; Raida, Zindy

    2013-01-01

    Laboratory mice constitute an extensively used model to study the pathologic and functional outcomes of cerebral ischemic stroke. The middle cerebral artery occlusion (MCAO) model requires surgical intervention, which potentially can result in postsurgical pain and stress. In the present study, we...... investigated whether buprenorphine and meloxicam, at clinically relevant doses provided pain relief without altering infarct volume in male C57BL/6 mice. Common known side-effects of buprenorphine, including decreased food consumption, were noted after surgery in buprenorphine-treated mice, but these effects...

  14. The pathogenesis of Pasteurella multocida local isolates in mice and chicken

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    Supar

    2000-03-01

    Full Text Available Avian cholera or fowl cholera is a bacterial disease caused by Pasteurella multocida strain of serogroup A, has been recognized as important disease in domestic poultry such as ducks and chicken. P. multocida strains derived from overseas and local isolates are stored as freeze dried and kept at the Research hlstitute for Veterinary Science (BALITVET culture collection (BCC. Some of those bacteria are still alive and can be used as vaccine candidates. Each strain or isolate was activated in brain heart infusion broth containing foetal calf serum and incubated at 37°C then it was identitied by biochemical reactions. Field surveys Were conducted in Central Java and South Kalimantan to observe fowl cholera problems and sample collections for isolation of pathogens. Of the 14 of Pasteurella multocida strains or isolates from BCC, II strains (9 imported 2 local isolates were still alive. In addition to this 2 isolates trom chicken and duck were viable. Seven out of 9 imported strains killed mice within 3 x 24 hours, similarly for the local isolates (BCC 299, 2331, DYI, DY2, 12TG, 15TG. However, the only BCC 2331 and DY2 isolates were able to kill two week old chicken witIlin 6 x 24 hours post inoculation. From this experiment indicated that the P. multocida local isolates (BCC 2,331 and DY2 are more pathogenic than that of imported strains. Two strains of imported P. multocida BCC 2331, 1362 and 6 local isolates (BCC 299, 2331, DYI, DY2, 12TG and 15TG would be selected for mono- and polyvalent vaccine candidates in the following experiments and the highly patogenic BCC 2331 and DY2 isolates would be used to challenge the vaccinated animals.

  15. Effects of ambient temperature on glucose tolerance and insulin sensitivity test outcomes in normal and obese C57 male mice.

    Science.gov (United States)

    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. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  16. Neonatal androgenization of hypogonadal (hpg male mice does not abolish estradiol-induced FSH production and spermatogenesis

    Directory of Open Access Journals (Sweden)

    Kerr Jeffrey B

    2005-09-01

    Full Text Available Abstract Background Testicular development is arrested in the hypogonadal (hpg mouse due to a congenital deficiency in hypothalamic gonadotropin-releasing hormone (GnRH synthesis. Chronic treatment of male hpg mice with estradiol induces FSH synthesis and secretion, and causes testicular maturation and qualitatively normal spermatogenesis. As estradiol negative feedback normally inhibits FSH production in the male, this study tested whether this paradoxical response to estradiol in the male hpg mouse might be due to inadequate masculinisation or incomplete defeminization in the neonatal period. Previous studies have demonstrated that treatment of hpg mice with testosterone propionate in the immediate neonatal period is necessary to allow full reproductive behaviors to be expressed following suitable endocrine stimulation at adult ages. Methods Hpg mice were treated with 100 μg testosterone propionate or vehicle on postnatal day 2. At 35 days of age, subgroups of these mice were treated with silastic implants containing estradiol or cholesterol. Reproductive behavior was scored in tests with steroid-primed female mice, then testicular development was assessed histologically, and measures of pituitary FSH content made at 85 days of age. Results The neonatal testosterone propionate treatment successfully defeminized female litter mates, as revealed by impaired vaginal opening and deficiencies in lordosis behavior, and it allowed appropriate male reproductive behavior to be expressed in a proportion of the hpg males when tested at an adult age. However, neonatal androgen supplementation did not block or even reduce the subsequent actions of estradiol in increasing pituitary FSH content, nor did it affect the ability of estradiol to induce qualitatively normal spermatogenesis. Conclusion The ability of the hpg male to show a "female" neuroendocrine response to estradiol is not a result of inadequate androgenization during neonatal development, and

  17. Exposure to chronic variable social stress during adolescence alters affect-related behaviors and adrenocortical activity in adult male and female inbred mice.

    Science.gov (United States)

    Caruso, Michael J; Kamens, Helen M; Cavigelli, Sonia A

    2017-09-01

    Rodent models provide valuable insight into mechanisms that underlie vulnerability to adverse effects of early-life challenges. Few studies have evaluated sex differences in anxiogenic or depressogenic effects of adolescent social stress in a rodent model. Furthermore, adolescent stress studies often use genetically heterogeneous outbred rodents which can lead to variable results. The current study evaluated the effects of adolescent social stress in male and female inbred (BALB/cJ) mice. Adolescent mice were exposed to repeat cycles of alternating social isolation and social novelty for 4 weeks. Adolescent social stress increased anxiety-related behaviors in both sexes and depression-related behavior in females. Locomotion/exploratory behavior was also decreased in both sexes by stress. Previously stressed adult mice produced less basal fecal corticosteroids than controls. Overall, the novel protocol induced sex-specific changes in anxiety- and depression-related behaviors and corticoid production in inbred mice. The chronic variable social stress protocol used here may be beneficial to systematically investigate sex-specific neurobiological mechanisms underlying adolescent stress vulnerability where genetic background can be controlled. © 2017 Wiley Periodicals, Inc.

  18. Soy protein isolate inhibits hepatic tumor promotion in mice fed a high-fat liquid diet.

    Science.gov (United States)

    Mercer, Kelly E; Pulliam, Casey F; Pedersen, Kim B; Hennings, Leah; Ronis, Martin Jj

    2017-03-01

    Alcoholic and nonalcoholic fatty liver diseases are risk factors for development of hepatocellular carcinoma, but the underlying mechanisms are poorly understood. On the other hand, ingestion of soy-containing diets may oppose the development of certain cancers. We previously reported that replacing casein with a soy protein isolate reduced tumor promotion in the livers of mice with alcoholic liver disease after feeding a high fat ethanol liquid diet following initiation with diethylnitrosamine. Feeding soy protein isolate inhibited processes that may contribute to tumor promotion including inflammation, sphingolipid signaling, and Wnt/β-catenin signaling. We have extended these studies to characterize liver tumor promotion in a model of nonalcoholic fatty liver disease produced by chronic feeding of high-fat liquid diets in the absence of ethanol. Mice treated with diethylnitrosamine on postnatal day 14 were fed a high-fat liquid diet made with casein or SPI as the sole protein source for 16 weeks in adulthood. Relative to mice fed normal chow, a high fat/casein diet led to increased tumor promotion, hepatocyte proliferation, steatosis, and inflammation. Replacing casein with soy protein isolate counteracted these effects. The high fat diets also resulted in a general increase in transcripts for Wnt/β-catenin pathway components, which may be an important mechanism, whereby hepatic tumorigenesis is promoted. However, soy protein isolate did not block Wnt signaling in this nonalcoholic fatty liver disease model. We conclude that replacing casein with soy protein isolate blocks development of steatosis, inflammation, and tumor promotion in diethylnitrosamine-treated mice fed high fat diets. Impact statement The impact of dietary components on cancer is a topic of great interest for both the general public and the scientific community. Liver cancer is currently the second leading form of cancer deaths worldwide. Our study has addressed the effect of the protein

  19. Inhalation reproductive toxicology studies: Male dominant lethal study of n-hexane in Swiss (CD-1) mice: Final report

    Energy Technology Data Exchange (ETDEWEB)

    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.

  20. Inhalation reproductive toxicology studies: Male dominant lethal study of n-hexane in Swiss (CD-1) mice: Final report

    International Nuclear Information System (INIS)

    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

  1. Diclofenac sex-divergent drug-drug interaction with Sunitinib: pharmacokinetics and tissue distribution in male and female mice.

    Science.gov (United States)

    Chew, Chii Chii; Ng, Salby; Chee, Yun Lee; Koo, Teng Wai; Liew, Ming Hui; Chee, Evelyn Li-Ching; Modamio, Pilar; Fernández, Cecilia; Mariño, Eduardo L; Segarra, Ignacio

    2017-08-01

    Coadministration of diclofenac and sunitinib, tyrosine kinase inhibitor, led to sex-divergent pharmacokinetic drug-drug interaction outcomes. Male and female mice were administered 60 mg/kg PO sunitinib alone (control groups) or with 30 mg/kg PO diclofenac. Sunitinib concentration in plasma, brain, kidney and liver were determined by HPLC and non-compartmental pharmacokinetic parameters calculated. In male mice, diclofenac decreased AUC 0→∞ 38% in plasma (p diclofenac increased the liver uptake efficiency in male (27%, p diclofenac with probable clinical translatability due to potential different effects in male and female patients requiring careful selection of the NSAID and advanced TDM to implement a personalized treatment.

  2. Effects of 2450 MHz microwave radiation on meiosis and reproduction in male mice

    International Nuclear Information System (INIS)

    Manikowska-Czerska, E.; Czerski, P.; Leach, W.M.

    1988-01-01

    A series of studies to examine effects od continuous wave 2450 MHz radiation on meiosis and on chromosomes of germ cells in male CBA/CAY or ICR mice, by means of the spermatocyte (SCT), heritable translocation (HTT) and dominant lethal (DLT) tests is presented. Animals were exposed in an environmentally controlled waveguide system during two consecutive weeks, 30 minutes daily, six days a week. Specific absorption rates (SAR) were used in the range from 0.05 to 20 W/kg. With the SCT, it was demonstrated that chromosomal translocations can be induced by exposure during the first meiotic prophase, particularly during initial and early pachytene stages. The HTT results demonstrated that balanced translocations may be recovered among offspring of exposed males. The DLT provided confirmatory data on effects during prophase and indicated that chromosomal damage may be also induced by exposure of spermatids, during the maturation stage, and of spermatozoa. No changes were observed in spermatogonia. Thus, the effects of exposure were limited to one spermatogenic cycle. Genetically significant effects were induced at an SAR of 2 W/kg in the testes. For comparison, an SAR of 0.4 W/kg is used commonly as a basis for occupational exposure limits

  3. Long-term Effects of Dexamethasone on Reproductive Parameters in Male Mice

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    jalogoden Gouyandeh

    2015-02-01

    Full Text Available Background & aim: The adverse effect of chemical drugs such as dexamethasone as anti-inflammatory -steroidal drugs on different body systems and infertility and reproductive efficiency is of concern. The purpose of this study was to evaluate the long-term effects of dexamethasone on the reproductive system in male rats. Methods: In the present experimental study, fifty matured male mice were divided into five groups including control, placebo and three treatment groups. Control group had no injections, placebo group only received normal saline and treatments groups received dexamethasone (0.1, 0.5 and 1 mg/kg which was injected in peritoneum every other day for a period of twenty days. Their Testosterone was measured by ELISA and testes were dissected for histological examination. The data were analyzed using SPSS 11.5 software. Results: Significant increases were shown in FSH level in all three groups treated with dexamethasone. LH in treatment group of 0.1 mg/kg decreased, but at dose of 1 mg/kg increased significantly.Testosterone levels in a dose of 1 mg/kg significantly increased compared with the control group (p<0.05. However, testis weight, the rate of testicular germ cells, primary spermatocytes, epididymal sperm and fertility significantly increased in all three groups (p<0.05. Conclusion: Dexamethasone had a negative effect on reproduction therefore, the use of this medication at different doses and time periods considers the possible complications beforehand. Keywords: .

  4. Effects of intermediate frequency magnetic fields on male fertility indicators in mice.

    Science.gov (United States)

    Kumari, K; Capstick, M; Cassara, A M; Herrala, M; Koivisto, H; Naarala, J; Tanila, H; Viluksela, M; Juutilainen, J

    2017-08-01

    Human exposure to intermediate frequency (IF) fields is increasing due to new applications such as electronic article surveillance systems, wireless power transfer and induction heating cookers. However, limited data is available on effects of IF magnetic fields (MF) on male fertility function. This study was conducted to assess possible effects on fertility indicators from exposure to IF MF. Male C57BL/6J mice were exposed continuously for 5 weeks to 7.5kHz MF at 12 and 120μT. Sperm cells from cauda epididymis were analysed for motility, total sperm counts, and head abnormalities. Motile sperm cells were classified as progressive or non-progressive. Testicular spermatid heads were counted as well. The body weight development and reproductive tissue weights were not affected. No exposure-related differences were observed in sperm counts or sperm head abnormalities. Proportion of non-motile cells was significantly decreased in the 120µT group, and a corresponding increase was seen in the percentage of motile cells (significant in non-progressive motile cells). In conclusion, no adverse effects on fertility indicators were observed. Increased sperm motility is an interesting finding that needs to be confirmed in further studies. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  5. SOX4 regulates gonad morphogenesis and promotes male germ cell differentiation in mice.

    Science.gov (United States)

    Zhao, Liang; Arsenault, Michel; Ng, Ee Ting; Longmuss, Enya; Chau, Tevin Chui-Ying; Hartwig, Sunny; Koopman, Peter

    2017-03-01

    The group C SOX transcription factors SOX4, -11 and -12 play important and mutually overlapping roles in development of a number of organs. Here, we examined the role of SoxC genes during gonadal development in mice. All three genes were expressed in developing gonads of both sexes, predominantly in somatic cells, with Sox4 being most strongly expressed. Sox4 deficiency resulted in elongation of both ovaries and testes, and an increased number of testis cords. While female germ cells entered meiosis normally, male germ cells showed reduced levels of differentiation markers Nanos2 and Dnmt3l and increased levels of pluripotency genes Cripto and Nanog, suggesting that SOX4 may normally act to restrict the pluripotency period of male germ cells and ensure their proper differentiation. Finally, our data reveal that SOX4 (and, to a lesser extent, SOX11 and -12) repressed transcription of the sex-determining gene Sox9 via an upstream testis-specific enhancer core (TESCO) element in fetal gonads, raising the possibility that SOXC proteins may function as transcriptional repressors in a context-dependent manner. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Adolescent chronic variable social stress influences exploratory behavior and nicotine responses in male, but not female, BALB/cJ mice.

    Science.gov (United States)

    Caruso, M J; Reiss, D E; Caulfield, J I; Thomas, J L; Baker, A N; Cavigelli, S A; Kamens, H M

    2018-04-01

    Anxiety disorders and nicotine use are significant contributors to global morbidity and mortality as independent and comorbid diseases. Early-life stress, potentially via stress-induced hypothalamic-pituitary-adrenal axis (HPA) dysregulation, can exacerbate both. However, little is known about the factors that predispose individuals to the development of both anxiety disorders and nicotine use. Here, we examined the relationship between anxiety-like behaviors and nicotine responses following adolescent stress. Adolescent male and female BALB/cJ mice were exposed to either chronic variable social stress (CVSS) or control conditions. CVSS consisted of repeated cycles of social isolation and social reorganization. In adulthood, anxiety-like behavior and social avoidance were measured using the elevated plus-maze (EPM) and social approach-avoidance test, respectively. Nicotine responses were assessed with acute effects on body temperature, corticosterone production, locomotor activity, and voluntary oral nicotine consumption. Adolescent stress had sex-dependent effects on nicotine responses and exploratory behavior, but did not affect anxiety-like behavior or social avoidance in males or females. Adult CVSS males exhibited less exploratory behavior, as indicated by reduced exploratory locomotion in the EPM and social approach-avoidance test, compared to controls. Adolescent stress did not affect nicotine-induced hypothermia in either sex, but CVSS males exhibited augmented nicotine-induced locomotion during late adolescence and voluntarily consumed less nicotine during adulthood. Stress effects on male nicotine-induced locomotion were associated with individual differences in exploratory locomotion in the EPM and social approach-avoidance test. Relative to controls, adult CVSS males and females also exhibited reduced corticosterone levels at baseline and adult male CVSS mice exhibited increased corticosterone levels following an acute nicotine injection. Results

  7. Neural androgen receptors affect the number of surviving new neurones in the adult dentate gyrus of male mice.

    Science.gov (United States)

    Swift-Gallant, A; Duarte-Guterman, P; Hamson, D K; Ibrahim, M; Monks, D A; Galea, L A M

    2018-04-01

    Adult hippocampal neurogenesis occurs in many mammalian species. In rats, the survival of new neurones within the hippocampus is modulated by the action of androgen via the androgen receptor (AR); however, it is not known whether this holds true in mice. Furthermore, the evidence is mixed regarding whether androgens act in neural tissue or via peripheral non-neural targets to promote new neurone survival in the hippocampus. We evaluated whether the action of androgen via AR underlies the survival of new neurones in mice, and investigated whether increasing AR selectively in neural tissue would increase new neurone survival in the hippocampus. We used the cre-loxP system to overexpress AR only in neural tissues (Nestin-AR). These males were compared with wild-type males, as well as control males with 1 of the 2 mutations required for overexpression. Mice were gonadectomised and injected with the DNA synthesis marker, bromodeoxyuridine (BrdU) and for 37 days (following BrdU injection), mice were treated with oil or dihydrotestosterone (DHT). Using immunohistochemistry, proliferation (Ki67) and survival (BrdU) of new neurones were both evaluated in the dorsal and ventral dentate gyrus. Dihydrotestosterone treatment increased the survival of new neurones in the entire hippocampus in wild-type mice and control mice that only have 1 of 2 necessary mutations for transgenic expression. However, DHT treatment did not increase the survival of new neurones in mice that overexpressed AR in neural tissue. Cell proliferation (Ki67) and cell death (pyknotic cells) were not affected by DHT treatment in wild-type or transgenic males. These results suggest that androgens act via neural AR to affect hippocampal neurogenesis by promoting cell survival; however, the relationship between androgen dose and new neurone survival is nonlinear. © 2018 British Society for Neuroendocrinology.

  8. Defining Subpopulations of Arcuate Nucleus GABA Neurons in Male, Female, and Prenatally Androgenized Female Mice.

    Science.gov (United States)

    Marshall, Christopher J; Desroziers, Elodie; McLennan, Timothy; Campbell, Rebecca E

    2017-01-01

    Arcuate nucleus (ARN) γ-aminobutyric acid (GABA) neurons are implicated in many critical homeostatic mechanisms, from food intake to fertility. To determine the functional relevance of ARN GABA neurons, it is essential to define the neurotransmitters co-expressed with and potentially co-released from ARN GABA neurons. The present study investigated the expression of markers of specific signaling molecules by ARN GABA neurons in brain sections from male, female, and, in some cases, prenatally androgen-treated (PNA) female, vesicular GABA transporter (VGaT)-ires-Cre/tdTomato reporter mice. Immunofluorescence for kisspeptin, β-endorphin, neuropeptide Y (NPY), tyrosine hydroxylase (TH) and neuronal nitric oxide synthase (nNOS) was detected by confocal microscopy, and co-localization with tdTomato VGaT reporter expression throughout the ARN was quantified. GABA neurons rarely co-localized with kisspeptin (95%) co-localized with VGaT across groups. Both TH and nNOS labeling was co-localized with ∼10% of ARN GABA neurons. The proportion of TH neurons co-localized with VGaT was significantly greater in males than either control or PNA females, and the proportion of nNOS neurons co-localizing VGaT was higher in control and PNA females compared with males. These data highlight NPY as a significant subpopulation of ARN GABA neurons, demonstrate no significant impact of PNA on signal co-expression, and, for the first time, show sexually dimorphic co-expression patterns of TH and nNOS with ARN GABA neurons. © 2016 S. Karger AG, Basel.

  9. Isolated cytochrome c oxidase deficiency in G93A SOD1 mice overexpressing CCS protein.

    Science.gov (United States)

    Son, Marjatta; Leary, Scot C; Romain, Nadine; Pierrel, Fabien; Winge, Dennis R; Haller, Ronald G; Elliott, Jeffrey L

    2008-05-02

    G93A SOD1 transgenic mice overexpressing CCS protein develop an accelerated disease course that is associated with enhanced mitochondrial pathology and increased mitochondrial localization of mutant SOD1. Because these results suggest an effect of mutant SOD1 on mitochondrial function, we assessed the enzymatic activities of mitochondrial respiratory chain complexes in the spinal cords of CCS/G93A SOD1 and control mice. CCS/G93A SOD1 mouse spinal cord demonstrates a 55% loss of complex IV (cytochrome c oxidase) activity compared with spinal cord from age-matched non-transgenic or G93A SOD1 mice. In contrast, CCS/G93A SOD1 spinal cord shows no reduction in the activities of complex I, II, or III. Blue native gel analysis further demonstrates a marked reduction in the levels of complex IV but not of complex I, II, III, or V in spinal cords of CCS/G93A SOD1 mice compared with non-transgenic, G93A SOD1, or CCS/WT SOD1 controls. With SDS-PAGE analysis, spinal cords from CCS/G93A SOD1 mice showed significant decreases in the levels of two structural subunits of cytochrome c oxidase, COX1 and COX5b, relative to controls. In contrast, CCS/G93A SOD1 mouse spinal cord showed no reduction in levels of selected subunits from complexes I, II, III, or V. Heme A analyses of spinal cord further support the existence of cytochrome c oxidase deficiency in CCS/G93A SOD1 mice. Collectively, these results establish that CCS/G93A SOD1 mice manifest an isolated complex IV deficiency which may underlie a substantial part of mutant SOD1-induced mitochondrial cytopathy.

  10. Long-chain fatty acid triglyceride (TG) metabolism disorder impairs male fertility: a study using adipose triglyceride lipase deficient mice.

    Science.gov (United States)

    Masaki, Hidetake; Kim, Namhyo; Nakamura, Hitomi; Kumasawa, Keiichi; Kamata, Eriko; Hirano, Ken-Ichi; Kimura, Tadashi

    2017-07-01

    Does the deletion of adipose triglyceride lipase (Atgl) gene impair male fertility? The deletion of Atgl gene impaired male fertility but the effect was partially reversed by a low long-chain triglyceride (TG) diet. ATGL specifically hydrolyses long-chain fatty acid TG to diacylglycerol and a high level of expression of ATGL in testes has been reported. However, the role of ATGL in male fertility is unknown. To investigate the effect of deletion of Atgl gene on male fertility, cauda epididymides and testes were collected from wild-type, heterozygous and homozygous Atgl-deficient mice at 10 weeks of age and epididymal sperm analysis and histological analysis of the testes were performed. To investigate whether a medium-chain triglycerides (MCTs) replacement diet mitigated the impaired male fertility by deletion of Atgl gene, homozygous Atgl-deficient mice were fed a MCT replacement diet, or a standard diet including long-chain triglycerides (LCTs) in a control group, for 6 weeks from 5 weeks of age (n = 22). The systematic and local effects of the MCT replacement diet on spermatogenesis and sperm maturation in the epididymis were analyzed at 10 weeks of age. Hematoxylin and eosin staining in paraffin-embedded sections of testes and Oil Red O staining in frozen sections of testes were performed. The epididymal sperm concentrations were analyzed. Statistical analyses were performed using the Student's t-test or Mann-Whitney U test with Shapiro-Wilk Normality test. Although heterozygous mice were fertile and showed a similar number of epididymal total and motile sperm concentrations to wild-type mice, the deletion of Atgl gene in homozygous mice led to accumulation of TG deposits in testes and impaired spermatogenesis. The deletion of Atgl gene also impaired the sperm maturation process required for sperm to acquire the ability to move forward in the epididymis. The MCT replacement diet for 6 weeks increased the plasma level of non-esterified fatty acid (NEFA) (1

  11. Increased 4E-BP1 Expression Protects against Diet-Induced Obesity and Insulin Resistance in Male Mice

    Directory of Open Access Journals (Sweden)

    Shih-Yin Tsai

    2016-08-01

    Full Text Available 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.

  12. The Accessory Olfactory System Facilitates the Recovery of the Attraction to Familiar Volatile Female Odors in Male Mice.

    Science.gov (United States)

    Muroi, Yoshikage; Nishimura, Masakazu; Ishii, Toshiaki

    2017-10-31

    Odors in female mice induce sexual arousal in male mice. Repeated exposure to female odors attenuates male attraction, which recovers when the odors are removed. The neuronal mechanisms for the recovery of male attraction have not been clarified. In this study, we examined how olfactory systems are involved in the recovery of male attraction to female odors following habituation in mice. Presentation with volatile female odors for 5 min induced habituation in males. To evaluate male attraction to familiar volatile female odors, we measured the duration for investigating volatile female odors from the same female mouse, which was presented twice for 5 min with 1-, 3-, or 5-min interval. Intranasal irrigation with ZnSO4 solution almost completely suppressed investigating behavior, indicating that the main olfactory system is indispensable for inducing the attraction to volatile female odors. In contrast, removal of the vomeronasal organ, bilateral lesions of the accessory olfactory bulb (AOB), or pharmacological blockage of neurotransmission in the AOB did not affect the investigation time at the first odor presentation. However, each one of the treatments decreased the investigation time in the second presentation, compared to that in the first presentation, at longer intervals than control treatment, indicating that the disturbance of neurotransmission in the accessory olfactory system delayed the recovery of the attraction attenuated by the first presentation. These results suggest that the accessory olfactory system facilitates the recovery of the attraction to familiar volatile female odors in male mice. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. Evaluation of the effect of soybean diet on interferon-α-induced depression in male mice

    Directory of Open Access Journals (Sweden)

    Yazdan Azimi Fashi

    2017-08-01

    Full Text Available Objective: Interferon-α (IFN therapy can cause depressive symptom which may lead to drug discontinuation. By interfering with tryptophan pathway, the available level of tryptophan required for serotonin synthesis decreases which could be related to depression. The aim of this study was to evaluate whether soybean diet could improve IFN-induced depression. Materials and Methods: Male mice weighing 28±3 g were used in the forced swimming test (FST as an animal model of depression; also, locomotor activity was recorded. IFN 16×105 IU/kg was injected subcutaneously for 6 days. Animals were fed with regular diet or soybean diet at 3 concentrations throughout the experiment. Fluoxetine was the reference drug. To check whether the tryptophan content in the soy bean diet was effective, a group of animals was injected with a single dose of tryptophan on the test day. Results: IFN-α increased the immobility time in the FST (192 sec ± 5.4, that denotes depression in mice. Soybean diets caused less immobility that was more profound with 50% soybean (26.4 sec ± 6. This diet overcame the depression caused by IFN in the FST (54 sec±18. This result was parallel with that of tryptophan injected to animals (38 sec±17. All the animals showed normal locomotor activity. Conclusion: For the first time, we showed that soybean diet could counteract with depression caused by IFN-α. Since tryptophan therapy had similar effects, possibly the tryptophan content of soybean had induced the serotonin synthesis. Thus, not only less harmful kynurenine was produced but also more serotonin was available in the brain to overcome depression. However, this interpretation needs further evaluations.

  14. Intraflagellar transporter protein (IFT27), an IFT25 binding partner, is essential for male fertility and spermiogenesis in mice.

    Science.gov (United States)

    Zhang, Yong; Liu, Hong; Li, Wei; Zhang, Zhengang; Shang, Xuejun; Zhang, David; Li, Yuhong; Zhang, Shiyang; Liu, Junpin; Hess, Rex A; Pazour, Gregory J; Zhang, Zhibing

    2017-12-01

    Intraflagellar transport (IFT) is an evolutionarily conserved mechanism essential for the assembly and maintenance of most eukaryotic cilia and flagella. In mice, mutations in IFT proteins have been shown to cause several ciliopathies including retinal degeneration, polycystic kidney disease, and hearing loss. However, little is known about its role in the formation of the sperm tail, which has the longest flagella of mammalian cells. IFT27 is a component of IFT-B complex and binds to IFT25 directly. In mice, IFT27 is highly expressed in the testis. To investigate the role of IFT27 in male germ cells, the floxed Ift27 mice were bred with Stra8-iCre mice so that the Ift27 gene was disrupted in spermatocytes/spermatids. The Ift27: Stra8-iCre mutant mice did not show any gross abnormalities, and all of the mutant mice survived to adulthood. There was no difference between testis weight/body weight between controls and mutant mice. All adult homozygous mutant males examined were completely infertile. Histological examination of the testes revealed abnormally developed germ cells during the spermiogenesis phase. The epididymides contained round bodies of cytoplasm. Sperm number was significantly reduced compared to the controls and only about 2% of them remained significantly reduced motility. Examination of epididymal sperm by light microscopy and SEM revealed multiple morphological abnormalities including round heads, short and bent tails, abnormal thickness of sperm tails in some areas, and swollen tail tips in some sperm. TEM examination of epididymal sperm showed that most sperm lost the "9+2″ axoneme structure, and the mitochondria sheath, fibrous sheath, and outer dense fibers were also disorganized. Some sperm flagella also lost cell membrane. Levels of IFT25 and IFT81 were significantly reduced in the testis of the conditional Ift27 knockout mice, and levels of IFT20, IFT74, and IFT140 were not changed. Sperm lipid rafts, which were disrupted in the

  15. Intraflagellar Transporter Protein (IFT27), an IFT25 binding partner, Is Essential For Male Fertility and Spermiogenesis In Mice

    Science.gov (United States)

    Zhang, Yong; Liu, Hong; Li, Wei; Zhang, Zhengang; Shang, Xuejun; Zhang, David; Li, Yuhong; Zhang, Shiyang; Liu, Junpin; Hess, Rex A; Pazour, Gregory J; Zhang, Zhibing

    2017-01-01

    Intraflagellar transport (IFT) is an evolutionarily conserved mechanism essential for the assembly and maintenance of most eukaryotic cilia and flagella. In mice, mutations in IFT proteins have been shown to cause several ciliopathies including retinal degeneration, polycystic kidney disease, and hearing loss. However, little is known about its role in the formation of the sperm tail, which has the longest flagella of mammalian cells. IFT27 is a component of IFT-B complex and binds to IFT25 directly. In mice, IFT27 is highly expressed in the testis. To investigate the role of IFT27 in male germ cells, the floxed Ift27 mice were bred with Stra8-iCre mice so that the Ift27 gene was disrupted in spermatocytes/spermatids. The Ift27:Stra8-iCre mutant mice did not show any gross abnormalities, and all of the mutant mice survive to adulthood. There was no difference between testis weight/body weight between controls and mutant mice. All adult homozygous mutant males examined were completely infertile. Histological examination of the testes revealed abnormally developed germ cells during the spermiogenesis phase. The epididymis contained round bodies of cytoplasm. Sperm number was significantly reduced compared to the controls and only about 2% of them remained significantly reduced motility. Examination of epididymal sperm by light microscopy and SEM revealed multiple morphological abnormalities including round heads, short and bent tails, abnormal thickness of sperm tails in some areas, and swollen tail tips in some sperm. TEM examination of epididymal sperm showed that most sperm lost the “9+2” axoneme structure, and the mitochondria sheath, fibrous sheath, and outer dense fibers were also disorganized. Some sperm flagella also lost cell membrane. Levels of IFT25 and IFT81 were significantly reduced in the testis of the conditional Ift27 knockout mice, and levels of IFT20, IFT74, and IFT140 were not changed. Sperm lipid rafts, which were disrupted in the conditional

  16. Radio -Protective Role of Zinc Administration Pre-Exposure to Gamma-Irradiation in Male Albino Mice

    International Nuclear Information System (INIS)

    El-Dawy, H.A.; Aly El-Sayed, S.M.

    2004-01-01

    This study was performed to evaluate the potency of zinc chloride injected subcutaneously (30 mg/kg b.w.) in male albino mice as a radio-protective agent pre exposure to gamma-irradiation. The investigation of the radio-protective role of zinc chloride was accomplished through measuring the levels of sex hormones, and observation of the chromosomal aberrations and sperm-head abnormalities after exposure to gamma-irradiation. The average of abnormal cells with chromosomal aberration and abnormal sperm % on the 7 th and 21 th days were 32% and 40%, and 14% and 22% respectively in mice exposed to radiation alone compared to 12% and 16%, and 5% and 12% respectively in mice treated with zinc chloride pre-irradiation. Treatment of mice with zinc chloride pre-irradiation induced significant amelioration in FSH and LH hormone levels on the 7 th day only of experimentation period, and showed non-significant amelioration in testosterone level

  17. Distribution of [14C]acrylamide in male and pregnant Swiss-Webster mice studied by whole-body autoradiography

    International Nuclear Information System (INIS)

    Marlowe, C.; Clark, M.J.; Mast, R.W.; Friedman, M.A.; Waddell, W.J.

    1986-01-01

    Male and 13.5- and 17.5-day pregnant Swiss-Webster mice were administered 120 mg/kg [2,3-14C]acrylamide orally. The male mice were frozen 0.33, 1, 3, 9, 24, 72, and 216 hr later, and the pregnant mice at each gestational period were frozen at 3 and 24 hr. Whole-body autoradiographs from the male mice at early time intervals revealed accumulation of radioactivity in the contents of the gastrointestinal tract, liver, pancreas, testis, brain and gallbladder, and epithelia of oral cavity, esophagus, and bronchi. The distribution appears to be similar in the male and pregnant mice. Absorption from the stomach was virtually complete by 3 hr; renal and hepatic elimination was essentially complete at 24 hr. Radioactivity in the male reproductive tract appeared in the parenchyma of the testis at 1 hr, moved to the seminiferous tubules and head of the epididymis at 9 hr, and by 9 days remained only in the tail of the epididymis and the crypts of the epithelium of the glans penis. This movement parallels that of spermatids. The 13.5-day fetuses were uniformly labeled except for a slightly increased uptake in fetal brain. The distribution of radioactivity in the 17.5-day fetal tissues resembled that in maternal tissues; the remarkable exception was an intense accumulation in fetal skin. This study indicates that acrylamide is efficiently absorbed from the stomach and eliminated by the liver, kidney, and possibly the pancreas. A previously unrecognized affinity of acrylamide or a metabolic product was demonstrated for fetal skin in late gestation and for adult epithelia of oral cavity, esophagus, forestomach, and bronchi. Also, acrylamide or a metabolite appears to bind to spermatids at a specific stage near maturation

  18. Biochemical behavior of Trypanosoma cruzi strains isolated from mice submitted to specific chemotherapy

    Directory of Open Access Journals (Sweden)

    Jesila Pinto M. Marretto

    1994-12-01

    Full Text Available To investigate the influence of chemotherapy on the biochemical beha vior of Trypanosoma cruzi strains, three groups of mice were infected with one of three strains of T. cruzi of different biological and isoenzymic patterns (Peruvian, 21 SF and Colombian strains. Each group was subdivided into subgroups: 1 - treated with nifurtimox; 2 - treated with benznidazole and 3 - untreated infected controls. At the end of treatment, that lasted for 90 days, xenodiagnosis, sub inoculation of blood into new born mice and haemoculture were performed as tests of cure. From the positive tests, 22 samples of T. cruzi were isolated from all subgroups. Electrophoretic analysis of the isoenzymes PGM, GP1, ALAT and AS AT failed to show any difference between parasite strains isolated from treated and untreated mice, which indicates that no detectable clonal selection or parasite genetic markers alterations concerning the isoenzymes analysed have been determined by treatment with drugs of recognized antiparasitic effect, suggesting stability of the phenotypic characteristics of the three biological types of T. cruzi strains.

  19. Early social enrichment provided by communal nest increases resilience to depression-like behavior more in female than in male mice.

    Science.gov (United States)

    D'Andrea, Ivana; Gracci, Fiorenza; Alleva, Enrico; Branchi, Igor

    2010-12-20

    Early experiences produce persistent changes in behavior and brain function. Being reared in a communal nest (CN), consisting of a single nest where three mouse mothers keep their pups together and share care-giving behavior from birth to weaning, provides an highly stimulating social environment to the developing pup since both mother-offspring and peer-to-peer interactions are markedly increased. Here we show that being reared in a CN affects adult behavior of CD-1 mice in a gender-dependent fashion, with reduced depression-like responses in females and increased anxiety-like behavior in males. In particular, CN females showed higher sucrose preference at baseline condition, drinking more sweet solution compared to female mice reared in a standard laboratory condition (SN). In the isolation test, both SN and CN females showed a reduction in sucrose preference after exposure to isolation stress. However, after 24h, only CN females significantly recovered. Finally, in the forced swim test, compared to SN, CN females spent longer time floating, a behavioral response that in the CN model has been inversely associated with display of endophenotypes of depression. With regard to the emotional response, CN males displayed an increased anxiety-like behavior in comparison to SN, spending less time in the open arms and displaying reduced head-dippings in the elevated plus-maze test. No difference was found in females. Overall, our findings show that gender and early experiences interact in modulating adult behavior. In particular, we show that early experiences modified developmental trajectories shaping adult endophenotypes of depression more markedly in females than in males. Copyright 2010 Elsevier B.V. All rights reserved.

  20. Beer Is Less Harmful for the Liver than Plain Ethanol: Studies in Male Mice Using a Binge-Drinking Model.

    Science.gov (United States)

    Landmann, Marianne; Wagnerberger, Sabine; Kanuri, Giridhar; Ziegenhardt, Doreen; Bergheim, Ina

    2015-09-01

    Mechanisms involved in the less damaging effects of beer in comparison to hard spirits have not yet been fully understood. The aim of the study was to determine if the effect of beer intake on the liver differs from that of plain ethanol and if so to determine mechanisms involved. Male C57BL/6J mice received either ethanol, beer (ethanol content: 6 g/kg body weight) or iso-caloric maltodextrin solution. Markers of steatosis, lipogenesis, activation of the toll-like receptor-4 signaling cascade and lipid export in liver and tight junction proteins in duodenum were measured 6 and 12 h after acute ethanol or beer intake. Alcohol ingestion resulted in a significant increase of hepatic triglyceride accumulation 6 and 12 h after ingestion, respectively, being markedly lower in mice fed beer. Expression of sterol regulatory element-binding protein-1c mRNA was significantly lower 12 h after alcohol or beer exposure, while fatty acid synthase mRNA expression was induced in livers of ethanol-fed mice and to a lesser extent in mice fed beer 6 h after acute alcohol ingestion. Protein levels of tight junction proteins in the small intestine were similar between groups while expression of myeloid differentiation primary response gene 88 in livers was significantly induced in ethanol- but not in beer-fed mice. Concentrations of 4-hydroxynonenal protein adducts and inducible nitric oxide synthase protein were also only induced in livers of mice fed ethanol. Protein levels of apolipoprotein B were induced in livers of beer-fed mice only. Our data suggest that beer is less harmful on the development of acute alcohol-induced liver damage than plain ethanol in male mice. © The Author 2015. Medical Council on Alcohol and Oxford University Press. All rights reserved.

  1. Social defeat stress induces a depression-like phenotype in adolescent male c57BL/6 mice.

    Science.gov (United States)

    Iñiguez, Sergio D; Riggs, Lace M; Nieto, Steven J; Dayrit, Genesis; Zamora, Norma N; Shawhan, Kristi L; Cruz, Bryan; Warren, Brandon L

    2014-05-01

    Abstract Exposure to stress is highly correlated with the emergence of mood-related illnesses. Because major depressive disorder often emerges in adolescence, we assessed the effects of social defeat stress on responses to depressive-like behaviors in juvenile mice. To do this, postnatal day (PD) 35 male c57BL/6 mice were exposed to 10 days of social defeat stress (PD35-44), while control mice were handled daily. Twenty-four hours after the last episode of defeat (PD45), separate groups of mice were tested in the social interaction, forced swimming, sucrose preference, and elevated plus-maze behavioral assays (n = 7-12 per group). Also, we examined body weight gain across days of social defeat and levels of blood serum corticosterone 40 min after the last episode of defeat stress. Our data indicates that defeated mice exhibited a depressive-like phenotype as inferred from increased social avoidance, increased immobility in the forced swim test, and reduced sucrose preference (a measure of anhedonia), when compared to non-defeated controls. Defeated mice also displayed an anxiogenic-like phenotype when tested on the elevated plus-maze. Lastly, stressed mice displayed lower body weight gain, along with increased blood serum corticosterone levels, when compared to non-stressed controls. Overall, we show that in adolescent male c57BL/6 mice, social defeat stress induces a depression- and anxiety-like phenotype 24 h after the last episode of stress. These data suggest that the social defeat paradigm may be used to examine the etiology of stress-induced mood-related disorders during adolescence.

  2. Differential Gene Expression in Gonadotropin-Releasing Hormone Neurons of Male and Metestrous Female Mice.

    Science.gov (United States)

    Vastagh, Csaba; Rodolosse, Annie; Solymosi, Norbert; Farkas, Imre; Auer, Herbert; Sárvári, Miklós; Liposits, Zsolt

    2015-01-01

    Gonadotropin-releasing hormone (GnRH) neurons play a pivotal role in the regulation of the hypothalamic-pituitary gonadal axis in a sex-specific manner. We hypothesized that the differences seen in reproductive functions of males and females are associated with a sexually dimorphic gene expression profile of GnRH neurons. We compared the transcriptome of GnRH neurons obtained from intact metestrous female and male GnRH-green fluorescent protein transgenic mice. About 1,500 individual GnRH neurons from each sex were sampled with laser capture microdissection followed by whole-transcriptome amplification for gene expression profiling. Under stringent selection criteria (fold change >1.6, adjusted p value 0.01), Affymetrix Mouse Genome 430 PM array analysis identified 543 differentially expressed genes. Sexual dimorphism was most apparent in gene clusters associated with synaptic communication, signal transduction, cell adhesion, vesicular transport and cell metabolism. To validate microarray results, 57 genes were selected, and 91% of their differential expression was confirmed by real-time PCR. Similarly, 88% of microarray results were confirmed with PCR from independent samples obtained by patch pipette harvesting and pooling of 30 GnRH neurons from each sex. We found significant differences in the expression of genes involved in vesicle priming and docking (Syt1, Cplx1), GABAergic (Gabra3, Gabrb3, Gabrg2) and glutamatergic (Gria1, Grin1, Slc17a6) neurotransmission, peptide signaling (Sstr3, Npr2, Cxcr4) and the regulation of intracellular ion homeostasis (Cacna1, Cacnb1, Cacng5, Kcnq2, Kcnc1). The striking sexual dimorphism of the GnRH neuron transcriptome we report here contributes to a better understanding of the differences in cellular mechanisms of GnRH neurons in the two sexes. © 2015 S. Karger AG, Basel.

  3. Ultrasonic vocalizations of adult male Foxp2-mutant mice: behavioral contexts of arousal and emotion.

    Science.gov (United States)

    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. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  4. The male sex pheromone darcin stimulates hippocampal neurogenesis and cell proliferation in the subventricular zone in female mice

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    Emma eHoffman

    2015-04-01

    Full Text Available 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 seven days to male urine containing at least 0.5µg/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 seven days, suggesting that consistency of individual scent signatures is important. While seven 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

  5. Hormonal and molecular effects of restraint stress on formalin-induced pain-like behavior in male and female mice.

    Science.gov (United States)

    Long, Caela C; Sadler, Katelyn E; Kolber, Benedict J

    2016-10-15

    The evolutionary advantages to the suppression of pain during a stressful event (stress-induced analgesia (SIA)) are obvious, yet the reasoning behind sex-differences in the expression of this pain reduction are not. The different ways in which males and females integrate physiological stress responses and descending pain inhibition are unclear. A potential supraspinal modulator of stress-induced analgesia is the central nucleus of the amygdala (CeA). This limbic brain region is involved in both the processing of stress and pain; the CeA is anatomically and molecularly linked to regions of the hypothalamic pituitary adrenal (HPA) axis and descending pain network. The CeA exhibits sex-based differences in response to stress and pain that may differentially induce SIA in males and females. Here, sex-based differences in behavioral and molecular indices of SIA were examined following noxious stimulation. Acute restraint stress in male and female mice was performed prior to intraplantar injections of formalin, a noxious inflammatory agent. Spontaneous pain-like behaviors were measured for 60min following formalin injection and mechanical hypersensitivity was evaluated 120 and 180min post-injection. Restraint stress altered formalin-induced spontaneous behaviors in male and female mice and formalin-induced mechanical hypersensitivity in male mice. To assess molecular indices of SIA, tissue samples from the CeA and blood samples were collected at the 180min time point. Restraint stress prevented formalin-induced increases in extracellular signal regulated kinase 2 (ERK2) phosphorylation in the male CeA, but no changes associated with pERK2 were seen with formalin or restraint in females. Sex differences were also seen in plasma corticosterone concentrations 180min post injection. These results demonstrate sex-based differences in behavioral, molecular, and hormonal indices of acute stress in mice that extend for 180min after stress and noxious stimulation. Copyright

  6. From the Cover: Lifelong Exposure of C57bl/6n Male Mice to Bisphenol A or Bisphenol S Reduces Recovery From a Myocardial Infarction.

    Science.gov (United States)

    Kasneci, Amanda; Lee, Jun Seong; Yun, Tae Jin; Shang, Jijun; Lampen, Shaun; Gomolin, Tamar; Cheong, Cheolho C; Chalifour, Lorraine E

    2017-09-01

    Bisphenol A (BPA) leaches from plastics to contaminate foodstuffs. Analogs, such as bisphenol S (BPS), are now used increasingly in manufacturing. Greater BPA exposure has been correlated with exacerbation of cardiovascular disease, including myocardial infarction (MI). To test the hypothesis that bisphenol exposure impairs cardiac healing, we exposed C57bl/6n mice to water containing 25ng/ml BPA or BPS from conception and surgically induced an MI in adult male progeny. Increased early death and cardiac dilation, and reduced cardiac function were found post-MI in BPA- and BPS-exposed mice. Flow cytometry revealed increased monocyte and macrophage infiltration that correlated with increased chemokine C-C motif ligand-2 expression in the infarct. In vitro BPA and BPS addition increased matrix metalloproteinase-9 (MMP) protein and secreted activity in RAW264.7 macrophage cells suggesting that invivo increases in MMP2 and MMP9 in exposed infarcts were myeloid-derived. Bone marrow-derived monocytes isolated from exposed mice had greater expression of pro-inflammatory polarization markers when chemokine stimulated indicating an enhanced susceptibility to develop a pro-inflammatory monocyte population. Chronic BPA exposure of estrogen receptor beta (ERβ) deficient mice did not worsen early death, cardiac structure/function, or expression of myeloid markers after an MI. In contrast, BPS exposure of ERβ-deficient mice resulted in greater death and expression of myeloid markers. We conclude that lifelong exposure to BPA or BPS augmented the monocyte/macrophage inflammatory response and adverse remodeling from an MI thereby reducing the ability to survive and successfully recover, and that the adverse effect of BPA, but not BPS, is downstream of ERβ signaling. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  7. Effect of Different Thermal Neutron Fluxes on Blood of Male Mice

    International Nuclear Information System (INIS)

    Abd El-Latif, A.A.; Saeid, Kh. S.; Abd El-Latif, A.A.; Emara, N.M.; Emara, N.M.

    2010-01-01

    This work deals with the exposing of male mice to different fluxes of thermal neutron .Investigation has been performed by calculating of thermal neutron fluxes(0.27x10 8 N/cm 2 . 1h , 0.54x10 8 N/cm 2 . 1h, 1.08x10 8 N/cm 2 . 1h, 2.16x10 8 N/cm 2 . 3h and 4.32x10 8 N/cm 2 . 6h) which emitted from neutron irradiation cell with source Ra - Be (α,n) have activity 3 m. Ci made by leybold(55930) . The number and differential leucocytes counts types of white blood cells in million per cubic millimeter (W. B. Cs. mm -3 ) ,the number of platelets mm -3 ,the number of red blood cells in million per cubic millimeter (R. B. Cs. mm -3 ), the hemoglobin in Blood (mg/dl), the lymphocytes ,and the eosiniphil leucocytes in blood decrease with increasing thermal neutron fluxes. But neutrophile and monocytes in blood increase with increasing the thermal neutron fluxes

  8. Inflammatory and mitochondrial gene expression data in GPER-deficient cardiomyocytes from male and female mice

    Directory of Open Access Journals (Sweden)

    Hao Wang

    2017-02-01

    Full Text Available We previously showed that cardiomyocyte-specific G protein-coupled estrogen receptor (GPER gene deletion leads to sex-specific adverse effects on cardiac structure and function; alterations which may be due to distinct differences in mitochondrial and inflammatory processes between sexes. Here, we provide the results of Gene Set Enrichment Analysis (GSEA based on the DNA microarray data from GPER-knockout versus GPER-intact (intact cardiomyocytes. This article contains complete data on the mitochondrial and inflammatory response-related gene expression changes that were significant in GPER knockout versus intact cardiomyocytes from adult male and female mice. The data are supplemental to our original research article “Cardiomyocyte-specific deletion of the G protein-coupled estrogen receptor (GPER leads to left ventricular dysfunction and adverse remodeling: a sex-specific gene profiling” (Wang et al., 2016 [1]. Data have been deposited to the Gene Expression Omnibus (GEO database repository with the dataset identifier GSE86843.

  9. Effects of Bisphenol A on glucose homeostasis and brain insulin signaling pathways in male mice.

    Science.gov (United States)

    Fang, Fangfang; Chen, Donglong; Yu, Pan; Qian, Wenyi; Zhou, Jing; Liu, Jingli; Gao, Rong; Wang, Jun; Xiao, Hang

    2015-02-01

    The potential effects of Bisphenol A (BPA) on peripheral insulin resistance have recently gained more attention, however, its functions on brain insulin resistance are still unknown. The aim of the present study was to investigate the effects of BPA on insulin signaling and glucose transport in mouse brain. The male mice were administrated of 100 μg/kg/day BPA or vehicle for 15 days then challenged with glucose and insulin tolerance tests. The insulin levels were detected with radioimmunoassay (RIA), and the insulin signaling pathways were investigated by Western blot. Our results revealed that BPA significantly increased peripheral plasma insulin levels, and decreased the insulin signals including phosphorylated insulin receptor (p-IR), phosphorylated insulin receptor substrate 1 (p-IRS1), phosphorylated protein kinase B (p-AKT), phosphorylated glycogen synthase kinase 3β (p-GSK3β) and phosphorylated extracellular regulated protein kinases (p-ERK1/2) in the brain, though insulin expression in both hippocampus and profrontal cortex was increased. In parallel, BPA exposure might contribute to glucose transport disturbance in the brain since the expression of glucose transporters were markedly decreased. In conclusion, BPA exposure perturbs the insulin signaling and glucose transport in the brain, therefore, it might be a risk factor for brain insulin resistance. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Radioprotective effect of both vitamins E and / or C on some blood components of male mice

    International Nuclear Information System (INIS)

    Anwar, W.A.; El-Daway, H.A.E.; Tawfik, S.S.M.; Soliman, S.M.

    1999-01-01

    The protective effects of vitamin C and/or vitamin E on some blood components and serum level of thiobarbituric reactive substances (as indicator to level of lipid peroxidation) of irradiated male mice at dose 3 Gy sacrificed after 15,24 and 46 days of irradiation have been assessed in comparison with control and non-irradiated-treated with vitamin C and/or vitamin E groups. Vit. C, vit. E or in combination decreased the effect of irradiation on blood components and the level of thiobarbituric reactive substances, but average haemoglobin level RBC count, total WBC count, neutrophil count and lymphocyte count did not reach to the original average level even after 36 days of irradiation. Vit. E had a more protective effect than vit. C in case of total white blood cells, while vit. C was more protective in case of lymphocyte count. The combination of vitamins C and E had more protective effect than either of both vitamins alone. The decrease in lipid peroxidation products due to administration of vit. E and vit. C as antioxidants supported the theory that lipid peroxidation increased due to free radicals induced by irradiation

  11. Disruption of CHTF18 causes defective meiotic recombination in male mice.

    Directory of Open Access Journals (Sweden)

    Karen M Berkowitz

    Full Text Available CHTF18 (chromosome transmission fidelity factor 18 is an evolutionarily conserved subunit of the Replication Factor C-like complex, CTF18-RLC. CHTF18 is necessary for the faithful passage of chromosomes from one daughter cell to the next during mitosis in yeast, and it is crucial for germline development in the fruitfly. Previously, we showed that mouse Chtf18 is expressed throughout the germline, suggesting a role for CHTF18 in mammalian gametogenesis. To determine the role of CHTF18 in mammalian germ cell development, we derived mice carrying null and conditional mutations in the Chtf18 gene. Chtf18-null males exhibit 5-fold decreased sperm concentrations compared to wild-type controls, resulting in subfertility. Loss of Chtf18 results in impaired spermatogenesis; spermatogenic cells display abnormal morphology, and the stereotypical arrangement of cells within seminiferous tubules is perturbed. Meiotic recombination is defective and homologous chromosomes separate prematurely during prophase I. Repair of DNA double-strand breaks is delayed and incomplete; both RAD51 and γH2AX persist in prophase I. In addition, MLH1 foci are decreased in pachynema. These findings demonstrate essential roles for CHTF18 in mammalian spermatogenesis and meiosis, and suggest that CHTF18 may function during the double-strand break repair pathway to promote the formation of crossovers.

  12. NEUROPHYSIOLOGICAL STUDY ON THE EFFECT OF ARTIFICIAL FOOD COLOUR AND SWEETENER IN ADULT MALE ALBINO MICE

    International Nuclear Information System (INIS)

    ABDEL-RAHMAN, M.; EL-KHADRAGY, M.F.; ABDEL-AZIZ, R.L.

    2008-01-01

    This study aims to investigate the effect of aspartame (artificial sweetener) and sunset yellow (artificial colour) on monoamines content in different brain areas of the adult male albino mice (cerebellum, brain stem, striatum, hypothalamus and cerebral cortex), and also on testosterone level in serum.The present study showed that the daily intraperitoneal injection of aspartame with dose of 200 mg/kg caused significant increase in monoamines content and testosterone level at most experimental periods. The elevation of monoamines content may be due to increase in phenylalanine concentration which leading to increase the synthesis of monoamines. The elevation of testosterone level may be due to the increment of DA content in hypothalamus which led to increase the release of LHRH. On the other hand, the daily intraperitoneal injection of sunset yellow with a dose of 2.5 mg/kg caused significant decrease in monoamines content and non-significant change in serum testosterone level at most experimental periods. The decrement in monoamines content may be due to the decrease in its uptake by the neurotransmitters or decrease in its synthesis

  13. Thermoregulatory and Cardiovascular Consequences of a Transient Thyrotoxicosis and Recovery in Male Mice.

    Science.gov (United States)

    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.

  14. Reciprocal translocations in germ cells of male mice receiving external γ-irradiation

    International Nuclear Information System (INIS)

    Bayrakova, A.; Filev, G.; Baev, I.

    1987-01-01

    Experiments were undertaken in which yields were recorded of reciprocal translocations in germ cells of male mice exposed to 0.9 Gy of γ-radiation at dose rates ranging from 6.14 x 10 -3 to 6.14 x 10 2 mGy/min (6 levels); comparisons were made with data published up to 1985 from similar studies using other fixed doses. To do this, translocation yields were expressed as relative yields (F) and their relationship to the dose rate (P) for the individual fixed doses was represented by an equation of the type: F = α + β log P. For most of the equations, the regression coefficients were in good agreement and a single relationship was obtained to represent them. From the analysis performed it follows that, within the 0.6-6.0 Gy dose range, the pattern of the F vs. P relationship is unaffected by the dose. This supports the initial assumption that for the dose range up to 6.0 Gy the dose response for the reciprocal translocation yield is a non-threshold straight-line relationship. (Auth.)

  15. Hepcidin protects against lethal E. coli sepsis in mice inoculated with isolates from septic patients.

    Science.gov (United States)

    Stefanova, Deborah; Raychev, Antoan; Deville, Jaime; Humphries, Romney; Campeau, Shelley; Ruchala, Piotr; Nemeth, Elizabeta; Ganz, Tomas; Bulut, Yonca

    2018-05-07

    Iron is an essential micronutrient for most microbes and their hosts. Mammalian hosts respond to infection by inducing the iron-regulatory hormone hepcidin, which causes iron sequestration and a rapid decrease in plasma and extracellular iron concentration (hypoferremia). Previous studies showed that hepcidin regulation of iron is essential for protection from infection-associated mortality with the siderophilic pathogens Yersinia enterocolitica and Vibrio vulnificus However, the evolutionary conservation of the hypoferremic response to infection suggests that not only rare siderophilic bacteria but also common pathogens may be targeted by this mechanism. We tested 10 clinical isolates of E. coli from children with sepsis and found that both genetic (hepcidin knockout, HKO) and iatrogenic iron overload (IV iron) potentiated infection with 8 out of 10 studied isolates: after peritoneal injection of E. coli , iron-loaded mice developed sepsis with 60% to 100% mortality within 24h while control wild type mice suffered 0% mortality. Using one strain for more detailed study, we show that iron overload allowed rapid bacterial multiplication and dissemination. We further found that the presence of non-transferrin bound iron (NTBI) in circulation is more important than total plasma or tissue iron in rendering mice susceptible to infection and mortality. Post infection treatment of HKO mice with just two doses of the hepcidin agonist PR73 abolished NTBI and completely prevented sepsis-associated mortality. We demonstrate that siderophilic phenotype extends to clinically common pathogens. The use of hepcidin agonists promises to be an effective early intervention in patients with infections and dysregulated iron metabolism. Copyright © 2018 American Society for Microbiology.

  16. The role of red dragon fruit peel (Hylocereus polyrhizus) to improvement blood lipid levels of hyperlipidaemia male mice

    Science.gov (United States)

    Hernawati; Setiawan, N. A.; Shintawati, R.; Priyandoko, D.

    2018-05-01

    The purpose of this research was to know the role of red dragon fruit peel powder to total cholesterol, triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and weight in the male hyperlipidaemic Balb-C mice (Mus musculus). This study used a completely randomized design (CRD) and four replicates for each dose treatments. Samples were 24 male mice that divided into six groups i.e. positive and negative controls, doses of 50; 100; 150 and 200 mg/kgBW/days red dragon fruit peel powder. Before being given treatment, mice were given feed containing high fat for 20 days until experiencing conditions hyperlipidaemia. The red dragon fruit peel powder was given at oral with used gavage for 30 days. Blood samples were taken from the tail on vena caudalis. Blood lipid samples were analysed at enzymatic with BIOLABO kits. The results of this study indicate that after administration of red dragon fruit peel powder total cholesterol levels, triglycerides and LDL-c decreased, along with increasing doses of red dragon fruit peel powder for 30 days. Furthermore showed that dragon fruit powder can increase HDL-c levels. The conclusion of this research was The red dragon fruit peel powder can improve blood lipid level of male Balb-c mice hyperlipidaemia.

  17. Differential metabolism of acrylonitrile to cyanide is responsible for the greater sensitivity of male vs female mice: role of CYP2E1 and epoxide hydrolases

    International Nuclear Information System (INIS)

    Chanas, Brian; Wang, Hongbing; Ghanayem, Burhan I.

    2003-01-01

    Acrylonitrile (AN) is a potent toxicant and a known rodent carcinogen. AN epoxidation to cyanoethylene oxide (CEO) via CYP2E1 and its subsequent metabolism via epoxide hydrolases (EH) to yield cyanide is thought to be responsible for the acute toxicity and mortality of AN. Recent reports showed that male mice are more sensitive than females to the acute toxicity/mortality of AN. The present work was undertaken to assess the metabolic and enzymatic basis for the greater sensitivity of male vs female mice to AN toxicity. Male and female wild-type and CYP2E1-null mice received AN at 0, 2.5, 10, 20, or 40 mg/kg by gavage. Cyanide concentrations were measured at 1 or 3 h after dosing. Current data demonstrated that cyanide levels in blood and tissues of AN-treated wild-type mice of both sexes were significantly greater than in vehicle-treated controls and increased in a dose-dependent manner. In contrast, cyanide levels in AN-treated CYP2E1-null mice were not statistically different from those measured in vehicle-treated controls. Furthermore, higher levels of cyanide were detected in male wild-type mice vs females in association with greater sensitivity of males to the acute toxicity/mortality of this chemical. Using Western blot analysis, negligible difference in CYP2E1 expression with higher levels of soluble and microsomal EH (sEH and mEH) was detected in the liver of male vs female mice. In kidneys, male mice exhibited higher expression of both renal CYP2E1 and sEH than did female mice. In conclusion, higher blood and tissue cyanide levels are responsible for the greater sensitivity of male vs female mice to AN. Further, higher expression of CYP2E1 and EH in male mice may contribute to greater formation of CEO and its subsequent metabolism to yield cyanide, respectively

  18. Deletion of the forebrain mineralocorticoid receptor impairs social discrimination and decision-making in male, but not in female mice

    Directory of Open Access Journals (Sweden)

    Judith P Ter Horst

    2014-02-01

    Full Text Available 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 receptors (MR and glucocorticoid receptors (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.

  19. Deletion of the forebrain mineralocorticoid receptor impairs social discrimination and decision-making in male, but not in female mice.

    Science.gov (United States)

    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 MR(CaMKCre) 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.

  20. Dysregulated gene expression in the primary osteoblasts and osteocytes isolated from hypophosphatemic Hyp mice.

    Directory of Open Access Journals (Sweden)

    Kazuaki Miyagawa

    Full Text Available Osteocytes express multiple genes involved in mineral metabolism including PHEX, FGF23, DMP1 and FAM20C. In Hyp mice, a murine model for X-linked hypophosphatemia (XLH, Phex deficiency results in the overproduction of FGF23 in osteocytes, which leads to hypophosphatemia and impaired vitamin D metabolism. In this study, to further clarify the abnormality in osteocytes of Hyp mice, we obtained detailed gene expression profiles in osteoblasts and osteocytes isolated from the long bones of 20-week-old Hyp mice and wild-type (WT control mice. The expression of Fgf23, Dmp1, and Fam20c was higher in osteocytic cells than in osteoblastic cells in both genotypes, and was up-regulated in Hyp cells. Interestingly, the up-regulation of these genes in Hyp bones began before birth. On the other hand, the expression of Slc20a1 encoding the sodium/phosphate (Na+/Pi co-transporter Pit1 was increased in osteoblasts and osteocytes from adult Hyp mice, but not in Hyp fetal bones. The direct effects of extracellular Pi and 1,25-dihydroxyvitamin D3 [1,25(OH2D3] on isolated osteoblastic and osteocytic cells were also investigated. Twenty-four-hour treatment with 10-8 M 1,25(OH2D3 increased the expression of Fgf23 in WT osteoblastic cells but not in osteocytic cells. Dmp1 expression in osteocytic cells was increased due to the 24-hour treatment with 10 mM Pi and was suppressed by 10-8 M 1,25(OH2D3 in WT osteocytic cells. We also found the up-regulation of the genes for FGF1, FGF2, their receptors, and Egr-1 which is a target of FGF signaling, in Hyp osteocytic cells, suggesting the activation of FGF/FGFR signaling. These results implicate the complex gene dysregulation in osteoblasts and osteocytes of Hyp mice, which might contribute to the pathogenesis.

  1. Antioxidant effect of vitamin E treatment on some heavy metals-induced renal and testicular injuries in male mice

    OpenAIRE

    Al-Attar, Atef M.

    2010-01-01

    Toxic heavy metals in water, air and soil are global problems that are a growing threat to humanity. Heavy metals are widely distributed in the environment and some of them occur in food, water, air and tissues even in the absence of occupational exposure. The antioxidant and protective influences of vitamin E on a mixture of some heavy metals (Pb, Hg, Cd and Cu)-induced oxidative stress and renal and testicular injuries were evaluated in male mice. Exposure of mice to these heavy metals in d...

  2. Subchronic Oral Bromocriptine Methanesulfonate Enhances Open Field Novelty-Induced Behavior and Spatial Memory in Male Swiss Albino Mice

    OpenAIRE

    Onaolapo, Olakunle James; Onaolapo, Adejoke Yetunde

    2012-01-01

    This study set out to assess the neurobehavioral effects of subchronic, oral bromocriptine methanesulfonate using the open field and the Y-maze in healthy male mice. Sixty adult Swiss albino mice were assigned into three groups. Controls received normal saline, while test groups received bromocriptine methanesulfonate at 2.5 and 5 mg/kg/day, respectively, for a period of 21 days. Neurobehavioral tests were carried out on days 1 and 21 after administration. Open field assessment on day 1 after...

  3. Isolation and analysis of differentially expressed genes between male fertile and male sterile flower buds of marigold (tagetes erecta L. )

    International Nuclear Information System (INIS)

    Hou, Z.; Tang, N.

    2016-01-01

    Male sterility is an important approach in utilization of heterosis in marigold (Tagetes erecta L.). Study on the mechanism of male sterility is very important, especially in mining of fertility-related genes. Three suppression subtractive hybridization (SSH) cDNA libraries were constructed between male fertile and male sterile flower buds of marigold. Out of 1920 clones, five hundred and six positive clones were verified by dot-blot hybridization. Two hundred and eighty-six non-redundant ESTs were obtained of which, one hundred and ninety-two ESTs corresponding to proteins with known functions. Through GO function annotation, fifteen candidate genes that may have a function in male sterility were identified. These genes involved in hormone pathways and cell cycles as well as encoded transcription factors and protein kinases. Further more, five of them were verified by quantitative real-time PCR, they were CDKB2;1 functioned in cell division, AMS involved in anther wall tapetum development, LAP3 played a role in pollen exine formation, ACOS5 and CYP703A2 involved in sporopollenin biosynthetic process. This is the first study that constructing cDNA libraries containing differentially expressed gene pools associate with male fertility using SSH strategy, and provides a first step to understand the mechanism of male reproductive development in marigold. (author)

  4. Skeletal muscles of aged male mice fail to adapt following contractile activity.

    Science.gov (United States)

    Vasilaki, A; Iwanejko, L M; McArdle, F; Broome, C S; Jackson, M J; McArdle, A

    2003-04-01

    Skeletal muscle adapts rapidly following exercise by the increased production of heat-shock proteins (HSPs). The aim of this study was to examine the ability of muscle from adult and aged mice to produce HSPs following non-damaging exercise. Adult and aged B6XSJL mice were anaesthetized and their hind limbs were subjected to isometric contractions. At different time points, muscles were analysed for HSP production by Western and Northern blotting and by electrophoretic mobility-shift assay. HSP protein and mRNA levels in muscles from adult mice increased significantly following exercise. This was not evident in muscles of aged mice. In contrast, binding of the transcription factor heat-shock factor 1 (HSF1) was not grossly altered in muscles of aged mice compared with adult mice. The data suggest that the inability of muscles of aged mice to produce HSPs appears to be due to alterations during gene transcription.

  5. Aspartame administered in feed, beginning prenatally through life span, induces cancers of the liver and lung in male Swiss mice.

    Science.gov (United States)

    Soffritti, Morando; Belpoggi, Fiorella; Manservigi, Marco; Tibaldi, Eva; Lauriola, Michelina; Falcioni, Laura; Bua, Luciano

    2010-12-01

    Aspartame (APM) is a well-known intense artificial sweetener used in more than 6,000 products. Among the major users of aspartame are children and women of childbearing age. In previous lifespan experiments conducted on Sprague-Dawley rats we have shown that APM is a carcinogenic agent in multiple sites and that its effects are increased when exposure starts from prenatal life. The aim of this study is to evaluate the potential of APM to induce carcinogenic effects in mice. Six groups of 62-122 male and female Swiss mice were treated with APM in feed at doses of 32,000, 16,000, 8,000, 2,000, or 0  ppm from prenatal life (12 days of gestation) until death. At death each animal underwent complete necropsy and all tissues and organs of all animals in the experiment were microscopically examined. APM in our experimental conditions induces in males a significant dose-related increased incidence of hepatocellular carcinomas (P < 0.01), and a significant increase at the dose levels of 32,000  ppm (P < 0.01) and 16,000  ppm (P < 0.05). Moreover, the results show a significant dose-related increased incidence of alveolar/bronchiolar carcinomas in males (P < 0.05), and a significant increase at 32,000  ppm (P < 0.05). The results of the present study confirm that APM is a carcinogenic agent in multiple sites in rodents, and that this effect is induced in two species, rats (males and females) and mice (males). No carcinogenic effects were observed in female mice. Am. J. Ind. Med. 53:1197-1206, 2010. © 2010 Wiley-Liss, Inc.

  6. Absence of Wdr13 Gene Predisposes Mice to Mild Social Isolation – Chronic Stress, Leading to Depression-Like Phenotype Associated With Differential Expression of Synaptic Proteins

    Science.gov (United States)

    Mitra, Shiladitya; Sameer Kumar, Ghantasala S.; Jyothi Lakshmi, B.; Thakur, Suman; Kumar, Satish

    2018-01-01

    We earlier reported that the male mice lacking the Wdr13 gene (Wdr13-/0) showed mild anxiety, better memory retention, and up-regulation of synaptic proteins in the hippocampus. With increasing evidences from parallel studies in our laboratory about the possible role of Wdr13 in stress response, we investigated its role in brain. We observed that Wdr13 transcript gets up-regulated in the hippocampus of the wild-type mice exposed to stress. To further dissect its function, we analyzed the behavioral and molecular phenotypes of Wdr13-/0 mice when subjected to mild chronic psychological stress, namely; mild (attenuated) social isolation. We employed iTRAQ based quantitative proteomics, real time PCR and western blotting to investigate molecular changes. Three weeks of social isolation predisposed Wdr13-/0 mice to anhedonia, heightened anxiety-measured by Open field test (OFT), increased behavior despair- measured by Forced swim test (FST) and reduced dendritic branching along with decreased spine density of hippocampal CA1 neurons as compared to wild-type counterparts. This depression-like-phenotype was however ameliorated when treated with anti-depressant imipramine. Molecular analysis revealed that out of 1002 quantified proteins [1% False discovery rate (FDR), at-least two unique peptides], strikingly, a significant proportion of synaptic proteins including, SYN1, CAMK2A, and RAB3A were down-regulated in the socially isolated Wdr13-/0 mice as compared to its wild-type counterparts. This was in contrast to the elevated levels of these proteins in non-stressed mutants as compared to the controls. We hypothesized that a de-regulated transcription factor upstream of the synaptic genes might be responsible for the observed phenotype. Indeed, in the socially isolated Wdr13-/0 mice, there was an up-regulation of GATA1 – a transcription factor that negatively regulates synaptic genes and has been associated with Major Depression (MD) in humans. The present study

  7. ARGINASE ENZYMES IN ISOLATED AIRWAYS FROM NORMAL AND NITRIC OXIDE SYNTHASE 2-KNOCKOUT MICE EXPOSED TO OVALBUMIN

    Science.gov (United States)

    Bratt, Jennifer M.; Franzi, Lisa M.; Linderholm, Angela L.; Last, Michael S.; Kenyon, Nicholas J.; Last, Jerold A.

    2009-01-01

    Arginase has been suggested to compete with nitric oxide synthase (NOS) for their common substrate, L-arginine. To study the mechanisms underlying this interaction, we compared arginase expression in isolated airways and the consequences of inhibiting arginase activity in vivo with NO production, lung inflammation, and lung function in both C57BL/6 and NOS2 knockout mice undergoing ovalbumin-induced airway inflammation, a mouse model of asthma. Arginases I and II were measured by western blot in isolated airways from sensitized C57BL/6 mice exposed to ovalbumin aerosol. Physiological and biochemical responses---inflammation, lung compliance, airway hyperreactivity, exhaled NO concentration, arginine concentration--were compared with the responses of NOS2 knockout mice. NOS2 knockout mice had increased total cells in lung lavage, decreased lung compliance, and increased airway hyperreactivity. Both arginase I and arginase II were constitutively expressed in the airways of normal C57BL/6 mice. Arginase I was up-regulated approximately 8-fold in the airways of C57BL/6 mice exposed to ovalbumin. Expression of both arginase isoforms were significantly upregulated in NOS2 knockout mice exposed to ovalbumin, with about 40- and 4-fold increases in arginases I and II, respectively. Arginine concentration in isolated airways was not significantly different in any of the groups studied. Inhibition of arginase by systemic treatment of C57BL/6 mice with a competitive inhibitor, Nω-hydroxy-nor-L-arginine (nor-NOHA), significantly decreased the lung inflammatory response to ovalbumin in these animals. We conclude that NOS2 knockout mice are more sensitive to ovalbumin-induced airway inflammation and its sequelae than are C57BL/6 mice, as determined by increased total cells in lung lavage, decreased lung compliance, and increased airway hyperreactivity, and that these findings are strongly correlated with increased expression of both arginase isoforms in the airways of the NOS2

  8. Whole-Body Vibration Mimics the Metabolic Effects of Exercise in Male Leptin Receptor-Deficient Mice.

    Science.gov (United States)

    McGee-Lawrence, Meghan E; Wenger, Karl H; Misra, Sudipta; Davis, Catherine L; Pollock, Norman K; Elsalanty, Mohammed; Ding, Kehong; Isales, Carlos M; Hamrick, Mark W; Wosiski-Kuhn, Marlena; Arounleut, Phonepasong; Mattson, Mark P; Cutler, Roy G; Yu, Jack C; Stranahan, Alexis M

    2017-05-01

    Whole-body vibration (WBV) has gained attention as a potential exercise mimetic, but direct comparisons with the metabolic effects of exercise are scarce. To determine whether WBV recapitulates the metabolic and osteogenic effects of physical activity, we exposed male wild-type (WT) and leptin receptor-deficient (db/db) mice to daily treadmill exercise (TE) or WBV for 3 months. Body weights were analyzed and compared with WT and db/db mice that remained sedentary. Glucose and insulin tolerance testing revealed comparable attenuation of hyperglycemia and insulin resistance in db/db mice following TE or WBV. Both interventions reduced body weight in db/db mice and normalized muscle fiber diameter. TE or WBV also attenuated adipocyte hypertrophy in visceral adipose tissue and reduced hepatic lipid content in db/db mice. Although the effects of leptin receptor deficiency on cortical bone structure were not eliminated by either intervention, exercise and WBV increased circulating levels of osteocalcin in db/db mice. In the context of increased serum osteocalcin, the modest effects of TE and WBV on bone geometry, mineralization, and biomechanics may reflect subtle increases in osteoblast activity in multiple areas of the skeleton. Taken together, these observations indicate that WBV recapitulates the effects of exercise on metabolism in type 2 diabetes.

  9. Puberty is delayed in male mice with dextran sodium sulfate colitis out of proportion to changes in food intake, body weight, and serum levels of leptin.

    Science.gov (United States)

    Deboer, Mark D; Li, Yongli

    2011-01-01

    In boys, inflammatory bowel disease often results in delayed puberty associated with decreased bone mineral density and decreased linear growth. Our goal was to investigate whether pubertal timing and levels of leptin differed between prepubertal male mice with colitis and food-restricted (FR) mice maintained at a similar weight. We induced colitis in 32-d-old male mice using dextran sodium sulfate (DSS), resulting in 10 d of worsening colitis. We followed up these mice for separation of the prepuce from the glans penis as a marker of pubertal progression. Compared with free-feeding control mice, DSS and FR mice had significantly lower weight on d 7-10 of treatment. DSS mice had later puberty than control and FR mice. DSS mice also had smaller testes, lower FSH levels, increased systemic cytokines, and increased colonic inflammation by histology. Leptin levels were similar between DSS and FR mice, whereas both had decreases in leptin compared with controls. We conclude that DSS colitis causes delayed puberty in sexually immature male mice beyond what is seen among FR mice of similar weight, food intake, and leptin levels. These experiments provide support for the hypothesis that pubertal delay in colitis is influenced by factors beyond poor weight gain alone.

  10. Isolation in immunodeficient mice of Sarcocystis neurona from opossum (Didelphis virginiana) faeces, and its differentiation from Sarcocystis falcatula.

    Science.gov (United States)

    Dubey, J P; Lindsay, D S

    1998-12-01

    Sarcocystis neurona was isolated in nude mice and gamma-interferon knockout mice fed sporocysts from faeces of naturally infected opossums (Didelphis virginiana). Mice fed sporocysts became lethargic and developed encephalitis. Protozoa were first found in the brain starting 21 days post-inoculation. Sarcocystis neurona was recovered in cell culture from the homogenate of liver, spleen and brain of a nude mouse 11 days after feeding sporocysts. The protozoa in mouse brain and in cell culture multiplied by schizogony and mature schizonts often had a residual body. Sarcocystis falcatula, which has an avian-opossum cycle, was not infective to nude or knockout mice. Protozoa were not found in tissues of nude mice or knockout mice after subcutaneous injection with culture-derived S. falcatula merozoites and sporocysts from the faeces of opossums presumed to contain only S. falcatula. Results demonstrate that S. neurona is distinct from S. falcatula, and that opossums are hosts for both species.

  11. A quantitative study of the second meiotic metaphase in male mice (Mus musculus).

    Science.gov (United States)

    Beatty, R A; Lim, M C; Coulter, V J

    1975-01-01

    Over 11,000 second meiotic metaphase spreads stained for the pericentromeric region have been studied quantitatively in male mice of 14 strains. The sex-chromosome constitution of a cell could be judged objectively if X and Y chromosomes and ploidy were all scored. A bias arose if only Y chromosomes and ploidy were scored but could be corrected statistically. There was no sign of other forms of bias. The original contiguity of X and Y second metaphases in vivo was very occasionally evident in the preparations. Most of the subhaploid aneuploid counts were assumed to be artifactual. The incidence of truly aneuploid second metaphases in 13 strains was estimated as 0.38+/-0.12%. The estimated average rate per chromosome was 0.019+/-0.006%, with a comparable order of magnitude for the sex chromosomes alone. Simultaneous aneuploidy of two or more chromosomes of the haploid set was estimated to be very rare. Of the spreads from 13 strains, 9.6% were polyploid (2N, 3N, 4N) and showed most of the possible combinations of sex chromosomes. Nearly all the polyploid spreads were considered to arise by artifactual cell fusion at the time of second metaphase during the preparative technique, especially of the X and Y daughter-cell products of the first meiotic division. Other modes of origin (true polyploidy, accidental superposition of cells during preparation) were unlikely. The data could be accommodated by a statistical model with only four parameters. It allowed for artifactual fusion mainly between daughter cells but also between non-daughter cells, bias in one scoring method, and bias in the numbers of cells with given ploidy successfully mounted. Current techniques of chromosome preparation were thought to be wholly unsuitable for the recognition of true polyploidy. The artifactual origin of polyploid spreads was borne out by an absence of polyploid spermatozoa in 14 strains. There appeared to be a virtually constant transmission rate of paternal X and Y chromosomes from

  12. Xiaochaihutang attenuates depressive/anxiety-like behaviors of social isolation-reared mice by regulating monoaminergic system, neurogenesis and BDNF expression.

    Science.gov (United States)

    Ma, Jie; Wang, Fang; Yang, Jingyu; Dong, Yingxu; Su, Guangyue; Zhang, Kuo; Pan, Xing; Ma, Ping; Zhou, Tingshuo; Wu, Chunfu

    2017-08-17

    Xiaochaihutang (XCHT), as a classical herbal formula for the treatment of "Shaoyang syndrome" has been demonstrated to exert an antidepressant effect in multiple animal models of depression as shown in our previous studies. However, the effects of XCHT on social isolation (SI)-reared mice have not been investigated. This study aims to explore the effects of XCHT on depressive/anxiety-like behaviors of SI-reared mice, and its implicated mechanisms, including alterations in the monoaminergic system, neurogenesis and neurotrophin expression. Male C57 BL/6J mice (aged 4 weeks after weaning) were reared isolatedly for 8 weeks and XCHT (0.8, 2.3, 7.0g/kg) were given by gavage once a day. Forced swimming test (FST), tail suspension test (TST), open field test (OFT), elevated-plus maze test (EPM) and intruder-induced aggression test were used to explore the effects of XCHT on depressive/anxiety-like behaviors of SI-reared mice after administration of XCHT for 6 weeks. HPLC-MS/MS was performed to quantify the levels of neurotransmitters in the hippocampus by in vivo microdialysis, while western immunoblotting was used to evaluate the action of XCHT on the synthesis, transport and degradation of monoamine neurotransmitters. Immunofluorescence was used to study the effects of XCHT on neurogenesis and neurotrophin expression, including Ki-67, DCX, BrdU and BDNF. Our results showed that administration of XCHT (0.8, 2.3 and 7.0g/kg) for 6 weeks significantly attenuated the increase in immobility time in TST and FST, improved the anxiety-like behaviors in OFT and EPM, and improved the aggressive behaviors of SI-reared mice. XCHT significantly elevated monoamine neurotransmitters levels and inhibited 5-HT turnover (5-HIAA/5-HT) in hippocampal microdialysates of SI-reared mice. In addition, we found XCHT enhanced monoamine neurotransmitter synthesis enzymes (TPH2 and TH) expressions, inhibited serotonin transporter (SERT) expression and decreased monoamine neurotransmitter

  13. Dim light at night increases depressive-like responses in male C3H/HeNHsd mice.

    Science.gov (United States)

    Fonken, Laura K; Nelson, Randy J

    2013-04-15

    Daily patterns of light exposure have become increasingly variable since the widespread adoption of electrical lighting during the 20th century. Seasonal fluctuations in light exposure, shift-work, and transmeridian travel are all associated with alterations in mood. These studies implicate fluctuations in environmental lighting in the development of depressive disorders. Here we argue that exposure to light at night (LAN) may be causally linked to depression. Male C3H/HeNHsd mice, which produce nocturnal melatonin, were housed in either a standard light/dark (LD) cycle or exposed to nightly dim (5 lux) LAN (dLAN). After four weeks in lighting conditions mice underwent behavioral testing and hippocampal tissue was collected at the termination of the study for qPCR. Here were report that mice exposed to dLAN increase depressive-like responses in both a sucrose anhedonia and forced swim test. In contrast to findings in diurnal grass rats, dLAN mice perform comparably to mice housed under dark nights in a hippocampus-dependent learning and memory task. TNFα and IL1β gene expression do not differ between groups, demonstrating that changes in these pro-inflammatory cytokines do not mediate dLAN induced depressive-like responses in mice. BDNF expression is reduced in the hippocampus of mice exposed to dLAN. These results indicate that low levels of LAN can alter mood in mice. This study along with previous work implicates LAN as a potential factor contributing to depression. Further understanding of the mechanisms through which LAN contributes to changes in mood is important for characterizing and treating depressive disorders. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Dexamethasone treatment induces susceptibility of outbred Webster mice to experimental infection with Besnoitia darlingi isolated from opossums (Didelphis virginiana).

    Science.gov (United States)

    Elsheikha, Hany M; Rosenthal, Benjamin M; Mansfield, Linda S

    2005-04-01

    The Sarcocystidae comprise a diverse, monophyletic apicomplexan parasite family, most of whose members form intracellular cysts in their intermediate hosts. The extent of pathology associated with such cyst formation can range widely. We currently lack experimental animal models for many of these infections. Here we explored dexamethasone treatment as a means to render outbred mice susceptible to Besnoitia darlingi infection and demonstrated that this approach allows viable parasites to be subsequently isolated from these mice and maintained in tissue culture. Besnoitia bradyzoites recovered from crushed cysts derived from naturally infected opossums (Didelphis virginiana) replicated and reproduced the development of besnoitiosis in mice treated with dexamethasone (0.5 mg/ml drinking water) daily for 12 days post infection (DPI). Isolates recovered from the peritoneal exudates of these mice were viable and were maintained in long-term tissue cultures. In contrast, control mice given saline without dexamethasone and challenged with similar bradyzoites remained clinically normal for up to 70 DPI. An additional group of mice challenged with the same inoculum of bradyzoites and given dexamethasone at the same concentration and treated with sulfadiazine (1 mg/ml drinking water) daily for 12 DPI also remained normal for up to 70 DPI. Severe disease developed more rapidly in dexamethasone-treated mice inoculated with culture-derived B. darlingi tachyzoites than in those inoculated with cyst-derived bradyzoites. B. darlingi tachyzoite-infected, untreated control mice developed signs of illness at 18 DPI. In contrast, mice treated with sulfadiazine showed no clinical signs up to 50 DPI. Although dexamethasone treatment was required to establish B. darlingi infection in outbred mice inoculated with opossum-derived B. darlingi bradyzoites, no such treatment was required for mice inoculated with culture-derived B. darlingi tachyzoites. Finally, sulfadiazine was highly

  15. Radiation-induced meiotic autosomal non-disjunction in male mice

    International Nuclear Information System (INIS)

    Nijhoff, J.H.; Boer, P. de

    1980-01-01

    Male mice, heterozygous for the Rb(11.13)4Bnr translocation, were irradiated for 14.5 min with either a dose of 15-rad fission neutrons or 60-rad X-rays. Animals of this karyotype are known to show high levels of spontaneous autosomal non- disjunction (20-30%) after anaphase I. The effects of the irradiation on this process were determined after 2 and 3 h in air-dried preparations. The length of the period from the end of meiosis I till the end of meiosis II was assessed autoradiographically, with the aid of cells showing a labelled Y chromosome only and appeared to last less than 3 h. Inter-mouse variation with regard to the duration of the period last premeiotic S-phase till diakinesis/metaphase I prevented a more accurate estimate. On the basis of this 3-h datum, the induced effects were studied at intervals of 2 and 3 h after the start of the irradiation. The influence of irradiation was assessed by scoring: (1) univalents in primary spermatocytes, (2) delections, aneuploid chromosome counts and precocious centromere separation in secondary spermatocytes, and (3) chromatid gaps and breaks in both cell types. Both radiation types induced comparable levels of chromosomal damage. A neutron X-rays RBE value for these parameters was calculated to be 5.4 for the MI stage and 3.3. for the MII stage. The significantly higher incidence of cells showing damage at MII than at diakinesis/MI is not believed to indicate a difference in radiation sensitivity, but is believed to be merely the consequence of the different chromosomal processes taking place during the irradiation taking place during the irradiation-fixation time interval. (orig.)

  16. Genotoxicity evaluation of buprofezin, petroleum oil and profenofos in somatic and germ cells of male mice.

    Science.gov (United States)

    Fahmy, M A; Abdalla, E F

    1998-01-01

    The two pest control agents, buprofezin and petroleum oil (Super Royal), were tested to evaluate their potential mutagenicity, in comparison with the organophosphorus insecticide profenofos. Chromosomal aberration analysis was used in both somatic and germ cells of male mice. Single oral treatment at three different dose levels (1/16, 1/8 and 1/4 LD50) for each insecticide induced an increase in the percentage of chromosomal aberrations in bone-marrow cells 24 h post-treatment, indicating a dose-dependent relationship. The percentage of chromosomal aberrations reached 23 +/- 0.73, 10.5 +/- 0.64 and 15 +/- 1.4 after treatment with the highest tested dose of profenofos, buprofezin and Super Royal, respectively. Such percentages did not exceed the corresponding value of the positive control, mitomycin C (29.2 +/- 0.69). The percentage of chromosomal aberrations induced by the different doses of profenofos was still highly significant even after excluding gaps. The same trend of results was noticed only at the highest tested dose of buprofezin and Super Royal. With respect to germ cells, profenofos is also a potent inducer of chromosomal aberrations in 1ry spermatocytes, giving percentages of 14 +/- 1.3 and 19 +/- 1.6 at the two higher doses of 4.25 and 8.5 mg kg(-1) body wt., respectively. Buprofezin and Super Royal had no significant effect on mouse spermatocytes at the tested concentrations. The various types of induced aberrations were examined and recorded in both somatic and germ cells. In conclusion, the present investigation indicates that the two pest control agents buprofezin and Super Royal are relatively much safer compounds than the conventional organophosphorus insecticides.

  17. Reproductive activities of Heliotropium indicum isolate against Helopeltis theivora and toxicity evaluation in mice.

    Science.gov (United States)

    Dolui, A K; Debnath, Manabendra; De, B; Kumar, Atul

    2012-05-01

    A new compound E was isolated from the methanolic extract of the leaves of Heliotropium indicum by chromatographic fractionation. In the present study, the effect of the compound E on reproduction of Helopeltis theivora has been evaluated. The acute toxicity study (LD50) and sub-acute toxicity studies (haematological, biochemical and histopathological parameters) in albino Swiss mice were carried out to evaluate the safety aspect of the compound E. The compound showed significant inhibitory effect on the reproductive life of H. theivora. The oviposition period, fecundity and hatching percentage of H. theivora were found to be 15.67 days, 39.33 and 28.00% respectively after treatment with 2% compound E, whereas the control value were found to be 20.33 days, 77.67 and 77.33% respectively. The LD50 of the compound was found to be 780 mg kg(-1) in Swiss albino female mice. The compound did not show any toxicity in mice at sub-lethal dose treatment (78 mg kg(-1) b. wt., once daily) for 21 days as evident from different haematological, biochemical and histopathological parameters in compound E treated group when compared with control.

  18. Effects of acute sublethal gamma radiation exposure on aggressive behavior in male mice: A dose-response study

    International Nuclear Information System (INIS)

    Maier, D.M.; Landauer, M.R.

    1989-01-01

    The resident-intruder paradigm was used to assess the effects of gamma radiation (0, 3, 5, 7 Gray [Gy] cobalt-60) on aggressive offensive behavior in resident male mice over a 3-month period. The defensive behavior of nonirradiated intruder mice was also monitored. A dose of 3 Gy had no effect on either the residents' offensive behavior or the defensive behavior of the intruders paired with them. Doses of 5 and 7 Gy produced decreases in offensive behavior of irradiated residents during the second week postirradiation. The nonirradiated intruders paired with these animals displayed decreases in defensive behavior during this time period, indicating a sensitivity to changes in the residents' behavior. After the third week postirradiation, offensive and defensive behavior did not differ significantly between irradiated mice and sham-irradiated controls. This study suggests that sublethal doses of radiation can temporarily suppress aggressive behavior but have no apparent permanent effect on that behavior

  19. Role of taurine as a treatment for oxidative damage and sperm head abnormalities in irradiated mice and their male offspring

    International Nuclear Information System (INIS)

    El-Dawy, H.; Tawfik, S.S.; EI-Khafif, M.; Ragab, M.H.

    2007-01-01

    The efficiency of taurine therapy in treatment of male mice exposed to a dose of (3 Gy) whole body gamma irradiation and their male offspring was studied. Irradiated mice showed significant increase in plasma malonaldehyde (MDA) level and sperm head abnormality counts in all experiment interval times 1, 3 and 5 weeks. Administration of taurine (1% in drinking water) post-irradiation resulted in significant decrease in the effect of irradiation on MDA level and sperm head abnormalities count. The efficiency of taurine as radiotherapeutic agent is greatly dependent on its chemical properties as strong oxidants scavenger and biological activities as osmoregulator and membrane stabilizer. The probable mechanism of taurine was discussed, as it is a sulphydryl, heterocyclic-nitrogenous and pharmacological therapy

  20. A chimera embryo assay reveals a decrease in embryonic cellular proliferation induced by sperm from X-irradiated male mice

    International Nuclear Information System (INIS)

    Obasaju, M.F.; Wiley, L.M.; Oudiz, D.J.; Raabe, O.; Overstreet, J.W.

    1989-01-01

    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)

  1. Male mice that lack the G-protein-coupled receptor GPR41 have low energy expenditure and increased body fat content.

    Science.gov (United States)

    Bellahcene, Mohamed; O'Dowd, Jacqueline F; Wargent, Ed T; Zaibi, Mohamed S; Hislop, David C; Ngala, Robert A; Smith, David M; Cawthorne, Michael A; Stocker, Claire J; Arch, Jonathan R S

    2013-05-28

    SCFA are produced in the gut by bacterial fermentation of undigested carbohydrates. Activation of the Gαi-protein-coupled receptor GPR41 by SCFA in β-cells and sympathetic ganglia inhibits insulin secretion and increases sympathetic outflow, respectively. A possible role in stimulating leptin secretion by adipocytes is disputed. In the present study, we investigated energy balance and glucose homoeostasis in GPR41 knockout mice fed on a standard low-fat or a high-fat diet. When fed on the low-fat diet, body fat mass was raised and glucose tolerance was impaired in male but not female knockout mice compared to wild-type mice. Soleus muscle and heart weights were reduced in the male mice, but total body lean mass was unchanged. When fed on the high-fat diet, body fat mass was raised in male but not female GPR41 knockout mice, but by no more in the males than when they were fed on the low-fat diet. Body lean mass and energy expenditure were reduced in male mice but not in female knockout mice. These results suggest that the absence of GPR41 increases body fat content in male mice. Gut-derived SCFA may raise energy expenditure and help to protect against obesity by activating GPR41.

  2. Potential paths for male-mediated gene flow to and from an isolated grizzly bear population

    Science.gov (United States)

    Peck, Christopher P.; van Manen, Frank T.; Costello, Cecily M.; Haroldson, Mark A.; Landenburger, Lisa; Roberts, Lori L.; Bjornlie, Daniel D.; Mace, Richard D.

    2017-01-01

    For several decades, grizzly bear populations in the Greater Yellowstone Ecosystem (GYE) and the Northern Continental Divide Ecosystem (NCDE) have increased in numbers and range extent. The GYE population remains isolated and although effective population size has increased since the early 1980s, genetic connectivity between these populations remains a long-term management goal. With only ~110 km distance separating current estimates of occupied range for these populations, the potential for gene flow is likely greater now than it has been for many decades. We sought to delineate potential paths that would provide the opportunity for male-mediated gene flow between the two populations. We first developed step-selection functions to generate conductance layers using ecological, physical, and anthropogenic landscape features associated with non-stationary GPS locations of 124 male grizzly bears (199 bear-years). We then used a randomized shortest path (RSP) algorithm to estimate the average number of net passages for all grid cells in the study region, when moving from an origin to a destination node. Given habitat characteristics that were the basis for the conductance layer, movements follow certain grid cell sequences more than others and the resulting RSP values thus provide a measure of movement potential. Repeating this process for 100 pairs of random origin and destination nodes, we identified paths for three levels of random deviation (θ) from the least-cost path. We observed broad-scale concordance between model predictions for paths originating in the NCDE and those originating in the GYE for all three levels of movement exploration. Model predictions indicated that male grizzly bear movement between the ecosystems could involve a variety of routes, and verified observations of grizzly bears outside occupied range supported this finding. Where landscape features concentrated paths into corridors (e.g., because of anthropogenic influence), they typically

  3. Mutations that affect meiosis in male mice influence the dynamics of the mid-preleptotene and bouquet stages

    International Nuclear Information System (INIS)

    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.

    2006-01-01

    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 -/- , Spo11 -/- , Mei1 m1Jcs/m1Jcs , Mlh1 -/- , Terf1 +/- and Hr6b -/- 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 -/- , Gmcl1 -/- , Asm -/- ) showed wild-type mid-preleptotene and bouquet frequencies. A low frequency of bouquet spermatocytes in Spo11 -/- Atm -/- spermatogenesis suggests that DSBs contribute to the Atm -/- -correlated bouquet stage exit defect. Insignificant changes of bouquet frequencies in mice with defects in early stages of DSB repair (Dmc1 -/- , Hop2 -/- ) suggest that there is an ATM-specific influence on bouquet stage duration. Altogether, it appears that several pathways influence telomere dynamics in mammalian meiosis

  4. Study efficacy of new model of derivative clonazepam on hypnotic, sedative, blood hematology and evaluation reproductive function in male mice

    OpenAIRE

    Adnan M. Jassim; Abbas G. Hamad; Mohammed Abed; Raad Saad

    2016-01-01

    Objectives This study includes the investigation of hypnotic and sedative effect of new generation agent synthesis from parent clonazepam and evaluates adverse effect on the reproductive system and an attempt to improve hypnotic effect and lower toxicity. Methods Sixteen male mice were randomly divided into four groups. The first day of treatment with single dose of 50 mg/kg intraperitoneal (IP) hypnotic effect then analgesic state was recorded in the 4th day of first week only after given...

  5. Photoperiod mediated changes in olfactory bulb neurogenesis and olfactory behavior in male white-footed mice (Peromyscus leucopus.

    Directory of Open Access Journals (Sweden)

    James C Walton

    Full Text Available 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.

  6. Adult neurobehavioral alterations in male and female mice following developmental exposure to paracetamol (acetaminophen): characterization of a critical period.

    Science.gov (United States)

    Philippot, Gaëtan; Gordh, Torsten; Fredriksson, Anders; Viberg, Henrik

    2017-10-01

    Paracetamol (acetaminophen) is a widely used non-prescription drug with analgesic and antipyretic properties. Among pregnant women and young children, paracetamol is one of the most frequently used drugs and is considered the first-choice treatment for pain and/or fever. Recent findings in both human and animal studies have shown associations between paracetamol intake during brain development and adverse behavioral outcomes later in life. The present study was undertaken to investigate if the induction of these effects depend on when the exposure occurs during a critical period of brain development and if male and female mice are equally affected. Mice of both sexes were exposed to two doses of paracetamol (30 + 30 mg kg -1 , 4 h apart) on postnatal days (PND) 3, 10 or 19. Spontaneous behavior, when introduced to a new home environment, was observed at the age of 2 months. We show that adverse effects on adult behavior and cognitive function occurred in both male and female mice exposed to paracetamol on PND 3 and 10, but not when exposed on PND 19. These neurodevelopmental time points in mice correspond to the beginning of the third trimester of pregnancy and the time around birth in humans, supporting existing human data. Considering that paracetamol is the first choice treatment for pain and/or fever during pregnancy and early life, these results may be of great importance for future research and, ultimately, for clinical practice. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  7. Alternate day fasting impacts the brain insulin-signaling pathway of young adult male C57BL/6 mice.

    Science.gov (United States)

    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. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

  8. Camellia sinensis Prevents Perinatal Nicotine-Induced Neurobehavioral Alterations, Tissue Injury, and Oxidative Stress in Male and Female Mice Newborns

    Science.gov (United States)

    Ajarem, Jamaan S.; Al-Basher, Gadh; Allam, Ahmed A.

    2017-01-01

    Nicotine exposure during pregnancy induces oxidative stress and leads to behavioral alterations in early childhood and young adulthood. The current study aimed to investigate the possible protective effects of green tea (Camellia sinensis) against perinatal nicotine-induced behavioral alterations and oxidative stress in mice newborns. Pregnant mice received 50 mg/kg C. sinensis on gestational day 1 (PD1) to postnatal day 15 (D15) and were subcutaneously injected with 0.25 mg/kg nicotine from PD12 to D15. Nicotine-exposed newborns showed significant delay in eye opening and hair appearance and declined body weight at birth and at D21. Nicotine induced neuromotor alterations in both male and female newborns evidenced by the suppressed righting, rotating, and cliff avoidance reflexes. Nicotine-exposed newborns exhibited declined memory, learning, and equilibrium capabilities, as well as marked anxiety behavior. C. sinensis significantly improved the physical development, neuromotor maturation, and behavioral performance in nicotine-exposed male and female newborns. In addition, C. sinensis prevented nicotine-induced tissue injury and lipid peroxidation and enhanced antioxidant defenses in the cerebellum and medulla oblongata of male and female newborns. In conclusion, this study shows that C. sinensis confers protective effects against perinatal nicotine-induced neurobehavioral alterations, tissue injury, and oxidative stress in mice newborns. PMID:28588748

  9. TWEAK Receptor Deficiency Has Opposite Effects on Female and Male Mice Subjected to Neonatal Hypoxia–Ischemia

    Directory of Open Access Journals (Sweden)

    Anton Kichev

    2018-04-01

    Full Text Available Tumor necrosis factor (TNF-like weak inducer of apoptosis (TWEAK is a multifunctional cytokine member of the TNF family. TWEAK binds to its only known receptor, Fn14, enabling it to activate downstream signaling processes in response to tissue injury. The aim of this study was to investigate the role of TWEAK signaling in neonatal hypoxia–ischemia (HI. We found that after neonatal HI, both TWEAK and Fn14 expression were increased to a greater extent in male compared with female mice. To assess the role of TWEAK signaling after HI, the size of the injury was measured in neonatal mice genetically deficient in Fn14 and compared with their wild-type and heterozygote littermates. A significant sex difference in the Fn14 knockout (KO animals was observed. Fn14 gene KO was beneficial in females; conversely, reducing Fn14 expression exacerbated the brain injury in male mice. Our findings indicate that the TWEAK/Fn14 pathway is critical for development of hypoxic–ischemic brain injury in immature animals. However, as the responses are different in males and females, clinical implementation depends on development of sex-specific therapies.

  10. Effects of Lactobacillus kefiranofaciens M1 isolated from kefir grains on germ-free mice.

    Science.gov (United States)

    Chen, Yen-Po; Chen, Ming-Ju

    2013-01-01

    Lactobacillus kefiranofaciens M1 is a novel probiotic strain that was isolated from kefir grains. Previously, we have demonstrated the immunoregulatory, anti-allergic, anti-asthmatic and anti-colitis abilities of L. kefiranofaciens M1 in a number of in-vitro and in-vivo experiments. However, whether the effects of L. kefiranofaciens M1 are elicited directly on the host or act by regulating the host's microbiota remains unknown. A number of studies have used germ-free or gnotobiotic animals to investigate the relationship between probiotics and colitis; therefore the aim of this study was to investigate the effects of L. kefiranofaciens M1 on germ-free mice. Such an approach should help in determining the direct effects of L. kefiranofaciens M1 on the host itself. Four-week-old female germ-free mice were inoculated intragastrically with 2×10(8) CFU/mouse L. kefiranofaciens M1 once or at 2-day intervals for 14 days. Bacterial colonization, the Th1/Th2 cytokine profile of the mice's splenocytes and the anti-colitis effect of L. kefiranofaciens M1 were investigated. The strongest response in terms of splenic Th1 cytokine IFN-γ and IL-12 production upon TLR activation was detected in the continuous treatment group when comparing to the single inoculation group and the germ-free control. In addition, continuous inoculation with L. kefiranofaciens M1 was found to ameliorate the symptoms of DSS-induced colitis in germ-free mice. However, L. kefiranofaciens M1 failed to colonize the host. Thus it would seem that L. kefiranofaciens M1 is likely to act directly on the host and not be involved in microbiota regulation.

  11. Effects of Lactobacillus kefiranofaciens M1 isolated from kefir grains on germ-free mice.

    Directory of Open Access Journals (Sweden)

    Yen-Po Chen

    Full Text Available Lactobacillus kefiranofaciens M1 is a novel probiotic strain that was isolated from kefir grains. Previously, we have demonstrated the immunoregulatory, anti-allergic, anti-asthmatic and anti-colitis abilities of L. kefiranofaciens M1 in a number of in-vitro and in-vivo experiments. However, whether the effects of L. kefiranofaciens M1 are elicited directly on the host or act by regulating the host's microbiota remains unknown. A number of studies have used germ-free or gnotobiotic animals to investigate the relationship between probiotics and colitis; therefore the aim of this study was to investigate the effects of L. kefiranofaciens M1 on germ-free mice. Such an approach should help in determining the direct effects of L. kefiranofaciens M1 on the host itself. Four-week-old female germ-free mice were inoculated intragastrically with 2×10(8 CFU/mouse L. kefiranofaciens M1 once or at 2-day intervals for 14 days. Bacterial colonization, the Th1/Th2 cytokine profile of the mice's splenocytes and the anti-colitis effect of L. kefiranofaciens M1 were investigated. The strongest response in terms of splenic Th1 cytokine IFN-γ and IL-12 production upon TLR activation was detected in the continuous treatment group when comparing to the single inoculation group and the germ-free control. In addition, continuous inoculation with L. kefiranofaciens M1 was found to ameliorate the symptoms of DSS-induced colitis in germ-free mice. However, L. kefiranofaciens M1 failed to colonize the host. Thus it would seem that L. kefiranofaciens M1 is likely to act directly on the host and not be involved in microbiota regulation.

  12. Opioid tolerance in periaqueductal gray neurons isolated from mice chronically treated with morphine.

    Science.gov (United States)

    Bagley, Elena E; Chieng, Billy C H; Christie, MacDonald J; Connor, Mark

    2005-09-01

    The midbrain periaqueductal gray (PAG) is a major site of opioid analgesic action, and a significant site of cellular adaptations to chronic morphine treatment (CMT). We examined mu-opioid receptor (MOP) regulation of voltage-gated calcium channel currents (I(Ca)) and G-protein-activated K channel currents (GIRK) in PAG neurons from CMT mice. Mice were injected s.c. with 300 mg kg(-1) of morphine base in a slow release emulsion three times over 5 days, or with emulsion alone (vehicles). This protocol produced significant tolerance to the antinociceptive effects of morphine in a test of thermal nociception. Voltage clamp recordings were made of I(Ca) in acutely isolated PAG neurons and GIRK in PAG slices. The MOP agonist DAMGO (Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol enkephalin) inhibited I(Ca) in neurons from CMT mice (230 nM) with a similar potency to vehicle (150 nM), but with a reduced maximal effectiveness (37% inhibition in vehicle neurons, 27% in CMT neurons). Inhibition of I(Ca) by the GABA(B) agonist baclofen was not altered by CMT. Met-enkephalin-activated GIRK currents recorded in PAG slices were significantly smaller in neurons from CMT mice than vehicles, while GIRK currents activated by baclofen were unaltered. These data demonstrate that CMT-induced antinociceptive tolerance is accompanied by homologous reduction in the effectiveness of MOP agonists to inhibit I(Ca) and activate GIRK. Thus, a reduction in MOP number and/or functional coupling to G proteins accompanies the characteristic cellular adaptations to CMT previously described in PAG neurons.

  13. Effects of social isolation and re-socialization on cognition and ADAR1 (p110) expression in mice.

    Science.gov (United States)

    Chen, Wei; An, Dong; Xu, Hong; Cheng, Xiaoxin; Wang, Shiwei; Yu, Weizhi; Yu, Deqin; Zhao, Dan; Sun, Yiping; Deng, Wuguo; Tang, Yiyuan; Yin, Shengming

    2016-01-01

    It has been reported that social isolation stress could be a key factor that leads to cognitive deficit for both humans and rodent models. However, detailed mechanisms are not yet clear. ADAR1 (Adenosine deaminase acting on RNA) is an enzyme involved in RNA editing that has a close relation to cognitive function. We have hypothesized that social isolation stress may impact the expression of ADAR1 in the brain of mice with cognitive deficit. To test our hypothesis, we evaluated the cognition ability of mice isolated for different durations (2, 4, and 8 weeks) using object recognition and object location tests; we also measured ADAR1 expression in hippocampus and cortex using immunohistochemistry and western blot. Our study showed that social isolation stress induced spatial and non-spatial cognition deficits of the tested mice. In addition, social isolation significantly increased both the immunoreactivity and protein expression of ADAR1 (p110) in the hippocampus and frontal cortex. Furthermore, re-socialization could not only recover the cognition deficits, but also bring ADAR1 (p110) immunoreactivity of hippocampus and frontal cortex, as well as ADAR1 (p110) protein expression of hippocampus back to the normal level for the isolated mice in adolescence. In conclusion, social isolation stress significantly increases ADAR1 (p110) expression in the hippocampus and frontal cortex of the mice with cognitive deficit. This finding may open a window to better understand the reasons (e.g., epigenetic change) that are responsible for social isolation-induced cognitive deficit and help the development of novel therapies for the resulted diseases.

  14. The Ghrelin/GOAT System Regulates Obesity-Induced Inflammation in Male Mice.

    Science.gov (United States)

    Harvey, Rebecca E; Howard, Victor G; Lemus, Moyra B; Jois, Tara; Andrews, Zane B; Sleeman, Mark W

    2017-07-01

    Ghrelin plays a key role in appetite, energy homeostasis, and glucose regulation. Recent evidence suggests ghrelin suppresses inflammation in obesity; however, whether this is modulated by the acylated and/or des-acylated peptide is unclear. We used mice deficient in acylated ghrelin [ghrelin octanoyl-acyltransferase (GOAT) knockout (KO) mice], wild-type (WT) littermates, and C57BL/6 mice to examine the endogenous and exogenous effects of acyl and des-acyl ghrelin on inflammatory profiles under nonobese and obese conditions. We demonstrate that in the spleen, both ghrelin and GOAT are localized primarily in the red pulp. Importantly, in the thymus, ghrelin was predominantly localized to the medulla, whereas GOAT was found in the cortex, implying differing roles in T cell development. Acute exogenous treatment with acyl/des-acyl ghrelin suppressed macrophage numbers in spleen and thymus in obese mice, whereas only acyl ghrelin increased CD3+ T cells in the thymus in mice fed both chow and a high-fat-diet (HFD). Consistent with this result, macrophages were increased in the spleen of KO mice on a HFD. Whereas there was no difference in CD3+ T cells in the plasma, spleen, or thymus of WT vs KO mice, KO chow and HFD-fed mice displayed decreased leukocytes. Our results suggest that the acylation status affects the anti-inflammatory properties of ghrelin under chow and HFD conditions. Copyright © 2017 Endocrine Society.

  15. Altered lipid partitioning and glucocorticoid availability in CBG-deficient male mice with diet-induced obesity.

    Science.gov (United States)

    Gulfo, José; Ledda, Angelo; Serra, Elisabet; Cabot, Cristina; Esteve, Montserrat; Grasa, Mar

    2016-08-01

    To evaluate how deficiency in corticosteroid-binding globulin (CBG), the specific carrier of glucocorticoids, affects glucocorticoid availability and adipose tissue in obesity. C57BL/6 (WT) and CBG-deficient (KO) male mice were fed during 12 weeks with standard or hyperlipidic diet (HL). Glucocorticoid availability and metabolic parameters were assessed. Body weight and food intake were increased in KO compared with WT mice fed a standard diet and were similar when fed a HL diet. Expression of CBG was found in white adipose tissue by immunochemistry, real-time PCR, and Western blot. In obesity, the subcutaneous depot developed less in KO mice compared with WT, which was associated with a minor adipocyte area and peroxisome proliferator-activated receptor-γ expression. Conversely, the epididymal depot displayed higher weight and adipocyte area in KO than in WT mice. CBG deficiency caused a fall of hepatic 11β-hydroxysteroid dehydrogenase type 2 expression and an increase in epidymal adipose tissue, particularly in HL mice. Deficiency in CBG drives lipid partitioning from subcutaneous to visceral adipose depot under a context of lipid excess and differentially modulates 11β-hydroxysteroid dehydrogenase type 2 expression. © 2016 The Obesity Society.

  16. Early-life Social Isolation Impairs the Gonadotropin-Inhibitory Hormone Neuronal Activity and Serotonergic System in Male Rats

    Directory of Open Access Journals (Sweden)

    Tomoko eSoga

    2015-11-01

    Full Text Available Social isolation in early life deregulates the serotonergic system of the brain, compromising reproductive function. Gonadotropin-inhibitory hormone (GnIH neurons in the dorsomedial hypothalamic nucleus are critical to the inhibitory regulation of gonadotropin-releasing hormone neuronal activity in the brain and release of luteinising hormone by the pituitary gland. Although GnIH responds to stress, the role of GnIH in social isolation-induced deregulation of the serotonin system and reproductive function remains unclear. We investigated the effect of social isolation in early life on the serotonergic–GnIH neuronal system using enhanced green fluorescent protein (EGFP-tagged GnIH-transgenic rats. Socially isolated rats were observed for anxious and depressive behaviours. Using immunohistochemistry, we examined c-Fos protein expression in EGFP–GnIH neurons in 9-week-old adult male rats after 6 weeks post-weaning isolation or group -housing. We also inspected serotonergic fibre juxtapositions in EGFP–GnIH neurons in control and socially isolated male rats. Socially isolated rats exhibited anxious and depressive behaviours. The total number of EGFP–GnIH neurons was the same in control and socially isolated rats, but c-Fos expression in GnIH neurons was significantly reduced in socially isolated rats. Serotonin fibre juxtapositions on EGFP–GnIH neurons was also lower in socially isolated rats. In addition, levels of tryptophan hydroxylase mRNA expression in the dorsal raphe nucleus were significantly attenuated in these rats. These results suggest that social isolation in early life results in lower serotonin levels, which reduce GnIH neuronal activity and may lead to reproductive failure.

  17. Early-Life Social Isolation Impairs the Gonadotropin-Inhibitory Hormone Neuronal Activity and Serotonergic System in Male Rats.

    Science.gov (United States)

    Soga, Tomoko; Teo, Chuin Hau; Cham, Kai Lin; Idris, Marshita Mohd; Parhar, Ishwar S

    2015-01-01

    Social isolation in early life deregulates the serotonergic system of the brain, compromising reproductive function. Gonadotropin-inhibitory hormone (GnIH) neurons in the dorsomedial hypothalamic nucleus are critical to the inhibitory regulation of gonadotropin-releasing hormone neuronal activity in the brain and release of luteinizing hormone by the pituitary gland. Although GnIH responds to stress, the role of GnIH in social isolation-induced deregulation of the serotonin system and reproductive function remains unclear. We investigated the effect of social isolation in early life on the serotonergic-GnIH neuronal system using enhanced green fluorescent protein (EGFP)-tagged GnIH transgenic rats. Socially isolated rats were observed for anxious and depressive behaviors. Using immunohistochemistry, we examined c-Fos protein expression in EGFP-GnIH neurons in 9-week-old adult male rats after 6 weeks post-weaning isolation or group housing. We also inspected serotonergic fiber juxtapositions in EGFP-GnIH neurons in control and socially isolated male rats. Socially isolated rats exhibited anxious and depressive behaviors. The total number of EGFP-GnIH neurons was the same in control and socially isolated rats, but c-Fos expression in GnIH neurons was significantly reduced in socially isolated rats. Serotonin fiber juxtapositions on EGFP-GnIH neurons were also lower in socially isolated rats. In addition, levels of tryptophan hydroxylase mRNA expression in the dorsal raphe nucleus were significantly attenuated in these rats. These results suggest that social isolation in early-life results in lower serotonin levels, which reduce GnIH neuronal activity and may lead to reproductive failure.

  18. Learning and memory deficits in male adult mice treated with a benzodiazepine sleep-inducing drug during the juvenile period

    Directory of Open Access Journals (Sweden)

    Yusuke Furukawa

    2016-07-01

    Full Text Available Gamma-aminobutyric acid (GABA, the major inhibitory neurotransmitter in the mammalian central nervous system, is also known to be important for brain development. Therefore, disturbances of GABA receptor (GABA-R mediated signaling (GABA-R signal during brain development may influence normal brain maturation and cause late-onset brain malfunctions. In this study, we examined whether the temporal stimulation of the GABA-R signal during brain development induces late-onset adverse effects on the brain in adult male mice. To stimulate the GABA-R signal, we used either the benzodiazepine sleep-inducing drug triazolam (TZ or the non-benzodiazepine drug zolpidem (ZP. We detected deficits in learning and memory in mice treated with TZ during the juvenile period, as seen in the fear conditioning test. On the other hand, ZP administration during the juvenile period had little effect. In addition, decreased protein expression of GluR1 and GluR4, which are excitatory neurotransmitter receptors, was detected in the hippocampi of mice treated with TZ during the juvenile period. We measured mRNA expression of the immediate early genes (IEGs, which are neuronal activity markers, in the hippocampus shortly after the administration of TZ or ZP to juvenile mice. Decreased IEG expression was detected in mice with juvenile TZ administration, but not in mice with juvenile ZP administration. Our findings demonstrate that TZ administration during the juvenile period can induce irreversible brain dysfunction in adult mice. It may need to take an extra care for the prescription of benzodiazepine sleep-inducing drugs to juveniles because it might cause late onset learning and memory defects.

  19. Histamine-dependent behavioral response to methamphetamine in 12-month-old male mice

    Science.gov (United States)

    Acevedo, Summer F.; Raber, Jacob

    2011-01-01

    Methamphetamine (MA) use is a growing problem across the United States. Effects of MA include hyperactivity and increased anxiety. Using a mouse model system, we examined behavioral performance in the open field and elevated zero maze and shock-startle response of 12-month-old wild-type mice injected with MA once (1mg/kg) 30 min prior to behavioral testing. MA treatment resulted in behavioral sensitization in the open field, consistent with studies in younger mice. There was an increased activity in the elevated zero maze and an increased shock-startle response 30 and 60 min post-injection. Since histamine mediates some effects of MA in the brain, we assessed whether 12-month-old mice lacking histidine decarboxylase (Hdc−/−), the enzyme required to synthesize histamine, respond differently to MA than wild-type (Hdc+/+) mice. Compared to saline treatment, acute and repeated MA administration increased activity in the open field and measures of anxiety, though more so in Hdc−/− than Hdc+/+ mice. In the elevated zero maze, opposite effects of MA on activity and measures of anxiety were seen in Hdc+/+ mice. In contrast, MA similarly increased the shock-startle response in Hdc−/− and Hdc+/+ mice, compared to saline-treated genotype-matched mice. These results are similar to those in younger mice suggesting that the effects are not age-dependent. Overall, single or repeated MA treatment causes histamine-dependent changes in 12-month-old mice in the open field and elevated zero-maze, but not in the shock-startle response. PMID:21466792

  20. Isolation and culture of primary osteocytes from the long bones of skeletally mature and aged mice

    Science.gov (United States)

    Stern, Amber Rath; Stern, Matthew M.; Van Dyke, Mark E.; Jähn, Katharina; Prideaux, Matthew; Bonewald, Lynda F.

    2013-01-01

    The purpose of this work was to establish a methodology to enable the isolation and study of osteocytes from skeletally mature young (4-month-old) and old (22-month-old) mice. The location of osteocytes deep within bone is ideal for their function as mechanosensors. However, this location makes the observation and study of osteocytes in vivo technically difficult. Osteocytes were isolated from murine long bones through a process of extended collagenase digestions combined with EDTA-based decalcification. A tissue homogenizer was used to reduce the remaining bone fragments to a suspension of bone particles, which were placed in culture to yield an outgrowth of osteocyte-like cells. All of the cells obtained from this outgrowth that displayed an osteocyte-like morphology stained positive for the osteocyte marker E11/GP38.[Q1] The osteocyte phenotype was further confirmed by a lack of staining for alkaline phosphatase and the absence of collagen1a1 expression. The outgrowth of osteocytes also expressed additional osteocyte-specific genes such as Sost and Mepe. This technique facilitates the isolation of osteocytes from skeletally mature bone. This novel enabling methodology should prove useful in advancing our understanding of the roles mature osteocytes play in bone health and disease. PMID:22668415

  1. Neuropsychiatric Symptom Modeling in Male and Female C57BL/6J Mice after Experimental Traumatic Brain Injury

    Science.gov (United States)

    Tucker, Laura B.; Burke, John F.; Fu, Amanda H.

    2017-01-01

    Abstract Psychiatric symptoms such as anxiety and depression are frequent and persistent complaints following traumatic brain injury (TBI). Modeling these symptoms in animal models of TBI affords the opportunity to determine mechanisms underlying behavioral pathologies and to test potential therapeutic agents. However, testing these symptoms in animal models of TBI has yielded inconsistent results. The goal of the current study was to employ a battery of tests to measure multiple anxiety- and depressive-like symptoms following TBI in C57BL/6J mice, and to determine if male and female mice are differentially affected by the injury. Following controlled cortical impact (CCI) at a parietal location, neither male nor female mice showed depressive-like symptoms as measured by the Porsolt forced-swim test and sucrose preference test. Conclusions regarding anxiety-like behaviors were dependent upon the assay employed; CCI-induced thigmotaxis in the open field suggested an anxiogenic effect of the injury; however, results from the elevated zero maze, light-dark box, and marble-burying tests indicated that CCI reduced anxiety-like behaviors. Fewer anxiety-like behaviors were also associated with the female sex. Increased levels of activity were also measured in female mice and injured mice in these tests, and conclusions regarding anxiety should be taken with caution when experimental manipulations induce changes in baseline activity. These results underscore the irreconcilability of results from studies attempting to model TBI-induced neuropsychiatric symptoms. Changes in injury models or better attempts to replicate the clinical syndrome may improve the translational applicability of rodent models of TBI-induced anxiety and depression. PMID:27149139

  2. Gugulipid causes hypercholesterolemia leading to endothelial dysfunction, increased atherosclerosis, and premature death by ischemic heart disease in male mice.

    Directory of Open Access Journals (Sweden)

    Andrea Leiva

    Full Text Available For proper cholesterol metabolism, normal expression and function of scavenger receptor class B type I (SR-BI, a high-density lipoprotein (HDL receptor, is required. Among the factors that regulate overall cholesterol homeostasis and HDL metabolism, the nuclear farnesoid X receptor plays an important role. Guggulsterone, a bioactive compound present in the natural product gugulipid, is an antagonist of this receptor. This natural product is widely used globally as a natural lipid-lowering agent, although its anti-atherogenic cardiovascular benefit in animal models or humans is unknown. The aim of this study was to determine the effects of gugulipid on cholesterol homeostasis and development of mild and severe atherosclerosis in male mice. For this purpose, we evaluated the impact of gugulipid treatment on liver histology, plasma lipoprotein cholesterol, endothelial function, and development of atherosclerosis and/or ischemic heart disease in wild-type mice; apolipoprotein E knockout mice, a model of atherosclerosis without ischemic complications; and SR-B1 knockout and atherogenic-diet-fed apolipoprotein E hypomorphic (SR-BI KO/ApoER61h/h mice, a model of lethal ischemic heart disease due to severe atherosclerosis. Gugulipid administration was associated with histological abnormalities in liver, increased alanine aminotransferase levels, lower hepatic SR-BI content, hypercholesterolemia due to increased HDL cholesterol levels, endothelial dysfunction, enhanced atherosclerosis, and accelerated death in animals with severe ischemic heart disease. In conclusion, our data show important adverse effects of gugulipid intake on HDL metabolism and atherosclerosis in male mice, suggesting potential and unknown deleterious effects on cardiovascular health in humans. In addition, these findings reemphasize the need for rigorous preclinical and clinical studies to provide guidance on the consumption of natural products and regulation of their use in the

  3. Genistein modulation of streptozotocin diabetes in male B6C3F1 mice can be induced by diet

    International Nuclear Information System (INIS)

    Guo, Tai L.; Wang, Yunbiao; Xiong, Tao; Ling, Xiao; Zheng, Jianfeng

    2014-01-01

    Diet and phytoestrogens affect the development and progression of diabetes. The objective of the present study was to determine if oral exposure to phytoestrogen genistein (GE) by gavage changed blood glucose levels (BGL) through immunomodulation in streptozotocin (STZ)-induced diabetic male B6C3F1 mice fed with three different diets. These three diets were: NTP-2000 diet (NTP), soy- and alfalfa-free 5K96 diet (SOF) and high fat diet (HFD) with 60% of kcal from fat, primarily rendered fat of swine. The dosing regimen for STZ consisted of three 100 mg/kg doses (i.p.): the first dose was administered at approximately 2 weeks following the initiation of daily GE (20 mg/kg) gavage, and the second dose was on day 19 following the first dose, and the third dose was on day 57 following the first dose. In mice on the NTP diet, GE treatment decreased BGL with statistical significances observed on days 33 and 82 following the first STZ injection. In mice fed the HFD diet, GE treatment produced a significant decrease and a significant increase in BGL on days 15 and 89 following the first STZ injection, respectively. In mice fed the SOF diet, GE treatment had no significant effects on BGL. Although GE treatment affected phenotypic distributions of both splenocytes (T cells, B cells, natural killer cells and neutrophils) and thymocytes (CD4/CD8 and CD44/CD25), and their mitochondrial transmembrane potential and generation of reactive oxygen species, indicators of cell death (possibly apoptosis), GE modulation of neutrophils was more consistent with its diabetogenic or anti-diabetic potentials. The differential effects of GE on BGL in male B6C3F1 mice fed with three different diets with varied phytoestrogen contents suggest that the estrogenic properties of this compound may contribute to its modulation of diabetes. - Highlights: • Diets affected streptozotocin-induced diabetes in male B6C3F1 mice. • Genistein modulation of streptozotocin diabetes can be induced by diet.

  4. Genistein modulation of streptozotocin diabetes in male B6C3F1 mice can be induced by diet

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Tai L., E-mail: tlguo1@uga.edu [Department of Biosciences and Diagnostic Imaging, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7382 (United States); Wang, Yunbiao [Department of Biosciences and Diagnostic Imaging, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7382 (United States); Key Laboratory of Wetland Ecology and Environment, Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Changchun 130102 (China); Xiong, Tao [College of Animal Science, Yangtze University, Jingzhou City, Hubei Province 434025 (China); Ling, Xiao [Institute for Food and Drug Control of Shandong Province, Jinan City, Shandong 250012 (China); Zheng, Jianfeng [Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298-0613 (United States)

    2014-11-01

    Diet and phytoestrogens affect the development and progression of diabetes. The objective of the present study was to determine if oral exposure to phytoestrogen genistein (GE) by gavage changed blood glucose levels (BGL) through immunomodulation in streptozotocin (STZ)-induced diabetic male B6C3F1 mice fed with three different diets. These three diets were: NTP-2000 diet (NTP), soy- and alfalfa-free 5K96 diet (SOF) and high fat diet (HFD) with 60% of kcal from fat, primarily rendered fat of swine. The dosing regimen for STZ consisted of three 100 mg/kg doses (i.p.): the first dose was administered at approximately 2 weeks following the initiation of daily GE (20 mg/kg) gavage, and the second dose was on day 19 following the first dose, and the third dose was on day 57 following the first dose. In mice on the NTP diet, GE treatment decreased BGL with statistical significances observed on days 33 and 82 following the first STZ injection. In mice fed the HFD diet, GE treatment produced a significant decrease and a significant increase in BGL on days 15 and 89 following the first STZ injection, respectively. In mice fed the SOF diet, GE treatment had no significant effects on BGL. Although GE treatment affected phenotypic distributions of both splenocytes (T cells, B cells, natural killer cells and neutrophils) and thymocytes (CD4/CD8 and CD44/CD25), and their mitochondrial transmembrane potential and generation of reactive oxygen species, indicators of cell death (possibly apoptosis), GE modulation of neutrophils was more consistent with its diabetogenic or anti-diabetic potentials. The differential effects of GE on BGL in male B6C3F1 mice fed with three different diets with varied phytoestrogen contents suggest that the estrogenic properties of this compound may contribute to its modulation of diabetes. - Highlights: • Diets affected streptozotocin-induced diabetes in male B6C3F1 mice. • Genistein modulation of streptozotocin diabetes can be induced by diet.

  5. Brown Adipose Tissue Function Is Enhanced in Long-Lived, Male Ames Dwarf Mice

    Science.gov (United States)

    McFadden, Samuel; Fang, Yimin; Huber, Joshua A.; Zhang, Chi; Sun, Liou Y.; Bartke, Andrzej

    2016-01-01

    Ames dwarf mice (Prop1df/df) are long-lived due to a loss of function mutation, resulting in deficiency of GH, TSH, and prolactin. Along with a marked extension of longevity, Ames dwarf mice have improved energy metabolism as measured by an increase in their oxygen consumption and heat production, as well as a decrease in their respiratory quotient. Along with alterations in energy metabolism, Ames dwarf mice have a lower core body temperature. Moreover, Ames dwarf mice have functionally altered epididymal white adipose tissue (WAT) that improves, rather than impairs, their insulin sensitivity due to a shift from pro- to anti-inflammatory cytokine secretion. Given the unique phenotype of Ames dwarf epididymal WAT, their improved energy metabolism, and lower core body temperature, we hypothesized that Ames dwarf brown adipose tissue (BAT) may function differently from that of their normal littermates. Here we use histology and RT-PCR to demonstrate that Ames dwarf mice have enhanced BAT function. We also use interscapular BAT removal to demonstrate that BAT is necessary for Ames dwarf energy metabolism and thermogenesis, whereas it is less important for their normal littermates. Furthermore, we show that Ames dwarf mice are able to compensate for loss of interscapular BAT by using their WAT depots as an energy source. These findings demonstrate enhanced BAT function in animals with GH and thyroid hormone deficiencies, chronic reduction of body temperature, and remarkably extended longevity. PMID:27740871

  6. Sunitinib-ibuprofen drug interaction affects the pharmacokinetics and tissue distribution of sunitinib to brain, liver, and kidney in male and female mice differently.

    Science.gov (United States)

    Lau, Christine Li Ling; Chan, Sook Tyng; Selvaratanam, Manimegahlai; Khoo, Hui Wen; Lim, Adeline Yi Ling; Modamio, Pilar; Mariño, Eduardo L; Segarra, Ignacio

    2015-08-01

    Tyrosine kinase inhibitor sunitinib (used in GIST, advanced RCC, and pancreatic neuroendocrine tumors) undergoes CYP3A4 metabolism and is an ABCB1B and ABCG2 efflux transporters substrate. We assessed the pharmacokinetic interaction with ibuprofen (an NSAID used by patients with cancer) in Balb/c male and female mice. Mice (study group) were coadministered (30 min apart) 30 mg/kg of ibuprofen and 60 mg/kg of sunitinib PO and compared with the control groups, which received sunitinib alone (60 mg/kg, PO). Sunitinib concentration in plasma, brain, kidney, and liver was measured by HPLC as scheduled and noncompartmental pharmacokinetic parameters estimated. In female control mice, sunitinib AUC0→∞ decreased in plasma (P brain (P male control mice. After ibuprofen coadministration, female mice showed lower AUC0→∞ in plasma (P brain, liver, and kidney (all P male mice, AUC0→∞ remained unchanged in plasma, increased in liver and kidney, and decreased in brain (all P male and female control mice, but changed after ibuprofen coadministration: Male mice showed 1.6-fold higher liver-to-plasma ratio (P female mice and in kidney (male and female mice) but decreased 55% in brain (P differences. The results illustrate the relevance of this DDI on sunitinib pharmacokinetics and tissue uptake. These may be due to gender-based P450 and efflux/transporters differences. © 2015 Société Française de Pharmacologie et de Thérapeutique.

  7. Increased oxidative stress and apoptosis in the hypothalamus of diabetic male mice in the insulin receptor substrate-2 knockout model

    Science.gov (United States)

    Canelles, Sandra; Argente, Jesús; Barrios, Vicente

    2016-01-01

    ABSTRACT Insulin receptor substrate-2-deficient (IRS2−/−) mice are considered a good model to study the development of diabetes because IRS proteins mediate the pleiotropic effects of insulin-like growth factor-I (IGF-I) and insulin on metabolism, mitogenesis and cell survival. The hypothalamus might play a key role in the early onset of diabetes, owing to its involvement in the control of glucose homeostasis and energy balance. Because some inflammatory markers are elevated in the hypothalamus of diabetic IRS2−/− mice, our aim was to analyze whether the diabetes associated with the absence of IRS2 results in hypothalamic injury and to analyze the intracellular mechanisms involved. Only diabetic IRS2−/− mice showed increased cell death and activation of caspase-8 and -3 in the hypothalamus. Regulators of apoptosis such as FADD, Bcl-2, Bcl-xL and p53 were also increased, whereas p-IκB and c-FLIPL were decreased. This was accompanied by increased levels of Nox-4 and catalase, enzymes involved in oxidative stress. In summary, the hypothalamus of diabetic IRS2−/− mice showed an increase in oxidative stress and inflammatory markers that finally resulted in cell death via substantial activation of the extrinsic apoptotic pathway. Conversely, non-diabetic IRS2−/− mice did not show cell death in the hypothalamus, possibly owing to an increase in the levels of circulating IGF-I and in the enhanced hypothalamic IGF-IR phosphorylation that would lead to the stimulation of survival pathways. In conclusion, diabetes in IRS2-deficient male mice is associated with increased oxidative stress and apoptosis in the hypothalamus. PMID:27013528

  8. Imidacloprid Promotes High Fat Diet-Induced Adiposity and Insulin Resistance in Male C57BL/6J Mice.

    Science.gov (United States)

    Sun, Quancai; Xiao, Xiao; Kim, Yoo; Kim, Daeyoung; Yoon, Kyoon Sup; Clark, John M; Park, Yeonhwa

    2016-12-14

    Imidacloprid, a neonicotinoid insecticide widely used in agriculture worldwide, has been reported to promote adipogenesis and cause insulin resistance in vitro. The purpose of the current study was to determine the effects of imidacloprid and its interaction with dietary fat in the development of adiposity and insulin resistance using male C57BL/6J mice. Imidacloprid (0.06, 0.6, or 6 mg/kg bw/day) was mixed in a low-fat (4% w/w) or high-fat (20% w/w) diet and given to mice ad libitum for 12 weeks. Imidacloprid significantly promoted high fat diet-induced body weight gain and adiposity. In addition, imidacloprid treatment with the high fat diet resulted in impaired glucose metabolism. Consistently, there were significant effects of imidacloprid on genes regulating lipid and glucose metabolisms, including the AMP-activated protein kinase-α (AMPKα) pathway in white adipose tissue and liver. These results suggest that imidacloprid may potentiate high fat diet-induced adiposity and insulin resistance in male C57BL/6J mice.

  9. Glucose uptake during contraction in isolated skeletal muscles from neuronal nitric oxide synthase μ knockout mice.

    Science.gov (United States)

    Hong, Yet Hoi; Frugier, Tony; Zhang, Xinmei; Murphy, Robyn M; Lynch, Gordon S; Betik, Andrew C; Rattigan, Stephen; McConell, Glenn K

    2015-05-01

    Inhibition of nitric oxide synthase (NOS) significantly attenuates the increase in skeletal muscle glucose uptake during contraction/exercise, and a greater attenuation is observed in individuals with Type 2 diabetes compared with healthy individuals. Therefore, NO appears to play an important role in mediating muscle glucose uptake during contraction. In this study, we investigated the involvement of neuronal NOSμ (nNOSμ), the main NOS isoform activated during contraction, on skeletal muscle glucose uptake during ex vivo contraction. Extensor digitorum longus muscles were isolated from nNOSμ(-/-) and nNOSμ(+/+) mice. Muscles were contracted ex vivo in a temperature-controlled (30°C) organ bath with or without the presence of the NOS inhibitor N(G)-monomethyl-l-arginine (L-NMMA) and the NOS substrate L-arginine. Glucose uptake was determined by radioactive tracers. Skeletal muscle glucose uptake increased approximately fourfold during contraction in muscles from both nNOSμ(-/-) and nNOSμ(+/+) mice. L-NMMA significantly attenuated the increase in muscle glucose uptake during contraction in both genotypes. This attenuation was reversed by L-arginine, suggesting that L-NMMA attenuated the increase in muscle glucose uptake during contraction by inhibiting NOS and not via a nonspecific effect of the inhibitor. Low levels of NOS activity (~4%) were detected in muscles from nNOSμ(-/-) mice, and there was no evidence of compensation from other NOS isoform or AMP-activated protein kinase which is also involved in mediating muscle glucose uptake during contraction. These results indicate that NO regulates skeletal muscle glucose uptake during ex vivo contraction independently of nNOSμ. Copyright © 2015 the American Physiological Society.

  10. In vitro maturation of cumulus-oocyte complexes for efficient isolation of oocytes from outbred deer mice.

    Directory of Open Access Journals (Sweden)

    Jung Kyu Choi

    Full Text Available The outbred (as with humans deer mice have been a useful animal model of research on human behavior and biology including that of the reproductive system. One of the major challenges in using this species is that the yield of oocyte isolation via superovulation is dismal according to the literature to date less than ∼5 oocytes per animal can be obtained so far.The goal of this study is to improve the yield of oocyte isolation from outbred deer mice close to that of most laboratory mice by in vitro maturation (IVM of cumulus-oocyte complexes (COCs.Oocytes were isolated by both superovulation and IVM. For the latter, COCs were obtained by follicular puncture of antral follicles in both the surface and inner cortical layers of ovaries. Immature oocytes in the COCs were then cultured in vitro under optimized conditions to obtain metaphase II (MII oocytes. Quality of the oocytes from IVM and superovulation was tested by in vitro fertilization (IVF and embryo development.Less than ∼5 oocytes per animal could be isolated by superovulation only. However, we successfully obtained 20.3±2.9 oocytes per animal by IVM (16.0±2.5 and superovulation (4.3±1.3 in this study. Moreover, IVF and embryo development studies suggest that IVM oocytes have even better quality than that from superovulation The latter never developed to beyond 2-cell stage as usual while 9% of the former developed to 4-cells.We have successfully established the protocol for isolating oocytes from deer mice with high yield by IVM. Moreover, this is the first ever success to develop in vitro fertilized deer mice oocytes beyond the 2-cell stage in vitro. Therefore, this study is of significance to the use of deer mice for reproductive biology research.

  11. Genetics of Genome-Wide Recombination Rate Evolution in Mice from an Isolated Island.

    Science.gov (United States)

    Wang, Richard J; Payseur, Bret A

    2017-08-01

    Recombination rate is a heritable quantitative trait that evolves despite the fundamentally conserved role that recombination plays in meiosis. Differences in recombination rate can alter the landscape of the genome and the genetic diversity of populations. Yet our understanding of the genetic basis of recombination rate evolution in nature remains limited. We used wild house mice ( Mus musculus domesticus ) from Gough Island (GI), which diverged recently from their mainland counterparts, to characterize the genetics of recombination rate evolution. We quantified genome-wide autosomal recombination rates by immunofluorescence cytology in spermatocytes from 240 F 2 males generated from intercrosses between GI-derived mice and the wild-derived inbred strain WSB/EiJ. We identified four quantitative trait loci (QTL) responsible for inter-F 2 variation in this trait, the strongest of which had effects that opposed the direction of the parental trait differences. Candidate genes and mutations for these QTL were identified by overlapping the detected intervals with whole-genome sequencing data and publicly available transcriptomic profiles from spermatocytes. Combined with existing studies, our findings suggest that genome-wide recombination rate divergence is not directional and its evolution within and between subspecies proceeds from distinct genetic loci. Copyright © 2017 by the Genetics Society of America.

  12. A High Fat Diet During Pregnancy and Lactation Induces Cardiac and Renal Abnormalities in GLUT4 +/- Male Mice

    Directory of Open Access Journals (Sweden)

    Michael Kruse

    2017-07-01

    Full Text Available Background/Aims: Altered nutrients during the in utero (IU and/or lactation (L period predispose offspring to cardio-renal diseases in adulthood. This study investigates the effect of a high fat diet (HFD fed to female mice during IU/L on gene expression patterns associated with heart and kidney failure and hypertension in male offspring. Methods: Female wild type (WT mice were fed either a HFD or control chow (C prior to mating with males with a genetic heterozygous deletion of GLUT4 (G4+/-, a model of peripheral insulin resistance and hypertension and throughout IU/L. After weaning male offspring were placed on a standard rodent chow until 24 weeks of age. Results: All offspring exposed to a maternal HFD showed increased heart and kidney weight and reduced cardiac insulin responsiveness. G4+/- offspring on a HFD displayed early hypertension associated with increased renal gene expression of renin and the AT1- receptors compared to G4+/- on a C diet. This group showed decreased cardiac expression of key genes involved in fatty acid oxidation compared to WT on a C diet. Conclusions: These results indicate an interaction between a HFD diet and genotype during early life development that can enhance susceptibility to cardio-renal diseases later in life.

  13. High dietary fat intake during lactation promotes development of diet-induced obesity in male offspring of mice.

    Science.gov (United States)

    Tsuduki, Tsuyoshi; Kitano, Yasuna; Honma, Taro; Kijima, Ryo; Ikeda, Ikuo

    2013-01-01

    The maternal nutritional status during pregnancy and lactation influences the risk of obesity in offspring, but the details of this phenomenon are unclear. In particular, there is little information on the influence on the offspring of the maternal nutritional status during lactation only. Therefore, in this study, we examined the influence of high dietary fat intake in dams during lactation on the risk of obesity in offspring, using C57BL/6J mice. The mice were fed a control diet (CD) during pregnancy. After birth, dams were fed a CD or a high-fat diet (HD) during lactation (3 wk). Fat and energy were significantly increased in milk from dams fed a HD during lactation. Male offspring were weaned at 3 wk old and fed a CD for 4 wk, which resulted in no significant difference in their physique. Four weeks after weaning, the offspring (7 wk old) were fed a CD or HD for 4 wk to induce obesity. High dietary fat intake in dams and offspring promoted lipid accumulation in white adipose tissue and adipocyte hypertrophy in male offspring. The underlying mechanism may involve an increase in expression of Lpl and a decrease in expression of Hsl in white adipose tissue of offspring. In conclusion, our results show that high dietary fat intake during lactation promotes development of diet-induced obesity in male offspring.

  14. Biochemical behavior of Trypanosoma cruzi strains isolated from mice submitted to specific chemotherapy

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    Jesila Pinto M. Marretto

    1994-12-01

    Full Text Available To investigate the influence of chemotherapy on the biochemical beha vior of Trypanosoma cruzi strains, three groups of mice were infected with one of three strains of T. cruzi of different biological and isoenzymic patterns (Peruvian, 21 SF and Colombian strains. Each group was subdivided into subgroups: 1 - treated with nifurtimox; 2 - treated with benznidazole and 3 - untreated infected controls. At the end of treatment, that lasted for 90 days, xenodiagnosis, sub inoculation of blood into new born mice and haemoculture were performed as tests of cure. From the positive tests, 22 samples of T. cruzi were isolated from all subgroups. Electrophoretic analysis of the isoenzymes PGM, GP1, ALAT and AS AT failed to show any difference between parasite strains isolated from treated and untreated mice, which indicates that no detectable clonal selection or parasite genetic markers alterations concerning the isoenzymes analysed have been determined by treatment with drugs of recognized antiparasitic effect, suggesting stability of the phenotypic characteristics of the three biological types of T. cruzi strains.Com o objetivo de investigar a influência da quimioterapia no padrão bioquímico de diferentes cepas do Trypanosoma cruzi, três grupos de camundongos foram infectados respectivamente com as cepas Peruana, 21 SF e Colombiana, que correspondem a diferentes padrões biológicos e isoenzimáticos. Cada grupo foi subdividido em subgrupos: 1 - tratados com nifurtimox; 2 - tratados com benzonidazol; 3- controles infectados não tratados. Ao final do tratamento que durou 90 dias, os animais foram submetidos a testes parasitológicos de cura: xenodiagnóstico, subinoculação do sangue em camundongos recém-nascidos e hemocultura em meio Warren. A partir da positivação destes testes, foram isoladas 22 amostras do T. cruzi dos três subgrupos. A análise eletroforética dos extratos enzimáticos obtidos após cultura para as enzimas PGM, GPI, ALAT e

  15. RBE of tritium beta rays for causes of death other than myeloid leukemia in male CBA/H mice

    International Nuclear Information System (INIS)

    Myers, D.K.; Jackson, J.S.; Dunford, D.W.

    1991-05-01

    Causes of death were examined for 5,206 male CBA/H mice which had previously been treated with tritiated water or with X rays at comparable doses and comparable dose rates. Data on induced myeloid leukemia had been examined in detail in a previous report. The purpose of the present study was to examine the relative biological effectiveness of tritium beta rays for causes of death other than mye-loid leukemia. However, no consistent values for the tritium relative biological effectiveness were obtained. The values were spread over a wide range for different endpoints and were generally less reliable than those for induction of myeloid leukemia. A surprising decrease in time to death of animals without tumours was observed in the irradiated groups of mice. This observation suggests that a detailed review of recent data on non-specific life shortening in irradiated animals and humans might be useful

  16. Comparative genomics of Streptococcus pyogenes M1 isolates differing in virulence and propensity to cause systemic infection in mice

    NARCIS (Netherlands)

    Fiebig, A.; Loof, T.G.; Babbar, A.; Itzeg, A.; Koehorst, J.J.; Schaap, P.J.; Nitsche-Schmitz, D.P.

    2015-01-01

    Streptococcus pyogenes serotype M1 is a frequent cause of severe infections in humans. Some M1 isolates are pathogenic in mice and used in studies on infection pathogenesis. We observed marked differences in murine infections caused by M1 strain SF370, 5448, 5448AP or AP1 which prompted us to

  17. Effects of conjugated linoleic acid and exercise on bone mass in young male Balb/C mice

    Directory of Open Access Journals (Sweden)

    O'Shea Marianne

    2006-03-01

    Full Text Available Abstract There is an increase in obesity among the population of industrialized countries, and dietary supplementation with Conjugated Linoleic Acid (CLA has been reported to lower body fat mass. However, weight loss is generally associated with negative effects on bone mass, but CLA is reported to have beneficial effects on bone. Furthermore, another factor that is well established to have a beneficial effect on bone is exercise (EX. However, a combination therapy of CLA and EX on bone health has not been studied. In this paper, we report the beneficial effects of CLA and EX on bone, in four different groups of Balb-C young, male mice. There were 4 groups in our study: 1. Safflower oil (SFO sedentary (SED; 2. SFO EX; 3. CLA SED; 4. CLA EX. Two months old mice, under their respective treatment regimens were followed for 14 weeks. Mice were scanned in vivo using a DEXA scanner before and after treatment. At the end of the treatment period, the animals were sacrificed, the left tibia was removed and scanned using peripheral quantitative computerized tomography (pQCT. The results showed that although CLA decreased gain in body weight by 35%, it however increased bone mass by both reducing bone resorption and increasing bone formation. EX also decreased gain in body weight by 21% and increased bone mass; but a combination of CLA and EX, however, did not show any further increase in bone mass. In conclusion, CLA increases bone mass in both cancellous and cortical bones, and the effects of CLA on bone is not further improved by EX in pure cortical bone of young male mice.

  18. Lactobacillus salivarius Isolated from Patients with Rheumatoid Arthritis Suppresses Collagen-Induced Arthritis and Increases Treg Frequency in Mice.

    Science.gov (United States)

    Liu, Xiaofei; Zhang, Juan; Zou, Qinghua; Zhong, Bing; Wang, Heng; Mou, Fangxiang; Wu, Like; Fang, Yongfei

    2016-12-01

    Previously, we demonstrated that Lactobacillus salivarius was more abundant in patients with rheumatoid arthritis (RA), an inflammatory autoimmune disease wherein the gut microbiota is altered, than in healthy individuals. However, the effect of L. salivarius in RA is unclear. Hence, we investigated the effect of L. salivarius isolated from patients with RA on collagen-induced arthritis (CIA) in mice. L. salivarius UCC118 or L. plantarum WCFS1 isolated from patients with RA was administered orally for 5 weeks, starting from 2 weeks before the induction of arthritis in DBA/1 mice. Clinical score progression, histological changes, serum cytokine concentrations, and the proportion of interleukin (IL)-17-producing T cells [T helper 17 (Th17)] and regulatory T cells (Tregs) in the spleen were evaluated. Bone erosion was evaluated by micro-computed tomography. CIA mice treated with either L. salivarius or L. plantarum showed lower arthritis scores, milder synovial infiltration, and less bone erosion when compared with phosphate-buffered, saline-treated CIA mice. Administration of L. salivarius and L. plantarum reduced the Th17 cell fraction and increased the Treg fraction. L. salivarius-treated CIA mice displayed a significant increase in serum anti-inflammatory IL-10 levels. Thus, pretreatment with L. salivarius could significantly improve CIA in mice and may help alleviate RA in a clinical setting.

  19. Hyperthyroidism and Hypothyroidism in Male Mice and Their Effects on Bone Mass, Bone Turnover, and the Wnt Inhibitors Sclerostin and Dickkopf-1.

    Science.gov (United States)

    Tsourdi, Elena; Rijntjes, Eddy; Köhrle, Josef; Hofbauer, Lorenz C; Rauner, Martina

    2015-10-01

    Thyroid hormones are key regulators of bone homeostasis, and Wnt signaling has been implicated in thyroid hormone-associated bone loss. Here we tested whether hyperthyroidism and hypothyroidism interfere with dickkopf-1 (DKK1) and sclerostin, two inhibitors of Wnt signaling. Twelve-week-old male C57BL/6 mice were rendered either hyperthyroid or hypothyroid. Hyperthyroid mice displayed decreased trabecular (-54%, P hyperthyroid mice and low bone turnover in hypothyroid mice. In vivo, serum DKK1 concentrations were decreased in hyperthyroid mice (-24%, P hyperthyroid mice (+50%, P hyperthyroid (P hyperthyroid but not in hypothyroid mice. Our data show that thyroid hormone-induced changes in bone remodeling are associated with a divergent regulation of DKK1 and sclerostin. Thus, the modulation of Wnt signaling by thyroid hormones may contribute to thyroid hormone-associated bone disease and altered expression of Wnt inhibitors may emerge as potential therapeutic targets.

  20. Over-Expression of Porcine Myostatin Missense Mutant Leads to A Gender Difference in Skeletal Muscle Growth between Transgenic Male and Female Mice.

    Science.gov (United States)

    Ma, Dezun; Gao, Pengfei; Qian, Lili; Wang, Qingqing; Cai, Chunbo; Jiang, Shengwang; Xiao, Gaojun; Cui, Wentao

    2015-08-24

    Myostatin, a transforming growth factor-β family member, is a negative regulator of skeletal muscle development and growth. Piedmontese cattle breeds have a missense mutation, which results in a cysteine to tyrosine substitution in the mature myostatin protein (C313Y). This loss-of-function mutation in myostatin results in a double-muscled phenotype in cattle. Myostatin propeptide is an inhibitor of myostatin activity and is considered a potential agent to stimulate muscle growth in livestock. In this study, we generated transgenic mice overexpressing porcine myostatin missense mutant (pmMS), C313Y, and wild-type porcine myostatin propeptide (ppMS), respectively, to examine their effects on muscle growth in mice. Enhanced muscle growth was observed in both pmMS and ppMS transgenic female mice and also in ppMS transgenic male mice. However, there was no enhanced muscle growth observed in pmMS transgenic male mice. To explore why there is such a big difference in muscle growth between pmMS and ppMS transgenic male mice, the expression level of androgen receptor (AR) mutant AR45 was measured by Western blot. Results indicated that AR45 expression significantly increased in pmMS transgenic male mice while it decreased dramatically in ppMS transgenic male mice. Our data demonstrate that both pmMS and ppMS act as myostatin inhibitors in the regulation of muscle growth, but the effect of pmMS in male mice is reversed by an increased AR45 expression. These results provide useful insight and basic theory to future studies on improving pork quality by genetically manipulating myostatin expression or by regulating myostatin activity.

  1. Short-Term Treatment with Bisphenol-A Leads to Metabolic Abnormalities in Adult Male Mice

    Science.gov (United States)

    Batista, Thiago M.; Alonso-Magdalena, Paloma; Vieira, Elaine; Amaral, Maria Esmeria C.; Cederroth, Christopher R.; Nef, Serge; Quesada, Ivan; Carneiro, Everardo M.; Nadal, Angel

    2012-01-01

    Bisphenol-A (BPA) is one of the most widespread endocrine disrupting chemicals (EDC) used as the base compound in the manufacture of polycarbonate plastics. Although evidence points to consider exposure to BPA as a risk factor for insulin resistance, its actions on whole body metabolism and on insulin-sensitive tissues are still unclear. The aim of the present work was to study the effects of low doses of BPA in insulin-sensitive peripheral tissues and whole body metabolism in adult mice. Adult mice were treated with subcutaneous injection of 100 µg/kg BPA or vehicle for 8 days. Whole body energy homeostasis was assessed with in vivo indirect calorimetry. Insulin signaling assays were conducted by western blot analysis. Mice treated with BPA were insulin resistant and had increased glucose-stimulated insulin release. BPA-treated mice had decreased food intake, lower body temperature and locomotor activity compared to control. In skeletal muscle, insulin-stimulated tyrosine phosphorylation of the insulin receptor β subunit was impaired in BPA-treated mice. This impairment was associated with a reduced insulin-stimulated Akt phosphorylation in the Thr308 residue. Both skeletal muscle and liver displayed an upregulation of IRS-1 protein by BPA. The mitogen-activated protein kinase (MAPK) signaling pathway was also impaired in the skeletal muscle from BPA-treated mice. In the liver, BPA effects were of lesser intensity with decreased insulin-stimulated tyrosine phosphorylation of the insulin receptor β subunit. In conclusion, short-term treatment with low doses of BPA slows down whole body energy metabolism and disrupts insulin signaling in peripheral tissues. Thus, our findings support the notion that BPA can be considered a risk factor for the development of type 2 diabetes. PMID:22470480

  2. Streptococcus azizii sp. nov., isolated from naïve weanling mice.

    Science.gov (United States)

    Shewmaker, Patricia Lynn; Whitney, Anne M; Gulvik, Christopher A; Lipman, Neil S

    2017-12-01

    Three isolates of a previously reported novel catalase-negative, Gram-stain-positive, coccoid, alpha-haemolytic, Streptococcus species that were associated with meningoencephalitis in naïve weanling mice were further evaluated to confirm their taxonomic status and to determine additional phenotypic and molecular characteristics. Comparative 16S rRNA gene sequence analysis showed nearly identical intra-species sequence similarity (≥99.9 %), and revealed the closest phylogenetically related species, Streptococcus acidominimus and Streptococcuscuniculi, with 97.0 and 97.5 % sequence similarity, respectively. The rpoB, sodA and recN genes were identical for the three isolates and were 87.6, 85.7 and 82.5 % similar to S. acidominimus and 89.7, 86.2 and 80.7 % similar to S. cuniculi, respectively. In silico DNA-DNA hybridization analyses of mouse isolate 12-5202 T against S. acidominimus CCUG 27296 T and S. cuniculi CCUG 65085 T produced estimated values of 26.4 and 25.7 % relatedness, and the calculated average nucleotide identity values were 81.9 and 81.7, respectively. These data confirm the taxonomic status of 12-5202 T as a distinct Streptococcus species, and we formally propose the type strain, Streptococcusazizii 12-5202 T (=CCUG 69378 T =DSM 103678 T ). The genome of Streptococcus azizii sp. nov. 12-5202 T contains 2062 total genes with a size of 2.34 Mbp, and an average G+C content of 42.76 mol%.

  3. Neurotoxicity of low bisphenol A (BPA) exposure for young male mice: Implications for children exposed to environmental levels of BPA

    International Nuclear Information System (INIS)

    Zhou, Yuanxiu; Wang, Zhouyu; Xia, Minghan; Zhuang, Siyi; Gong, Xiaobing; Pan, Jianwen; Li, Chuhua; Fan, Ruifang; Pang, Qihua; Lu, Shaoyou

    2017-01-01

    To investigate the neuron toxicities of low-dose exposure to bisphenol A (BPA) in children, mice were used as an animal model. We examined brain cell damage and the effects of learning and memory ability after BPA exposure in male mice (4 weeks of age) that were divided into four groups and chronically received different BPA treatments for 8 weeks. The comet assay and hippocampal neuron counting were used to detect the brain cell damage. The Y-maze test was applied to test alterations in learning and memory ability. Long term potentiation induction by BPA exposure was performed to study the potential mechanism of performance. The percentages of tail DNA, tail length and tail moment in brain cells increased with increasing BPA exposure concentrations. Significant differences in DNA damage were observed among the groups, including between the low-dose and control groups. In the Y-maze test, the other three groups qualified for the learned standard one day earlier than the high-exposed group. Furthermore, the ratio of qualified mice in the high-exposed group was always the lowest among the groups, indicating that high BPA treatment significantly altered the spatial memory performance of mice. Different BPA treatments exerted different effects on the neuron numbers of different regions in the hippocampus. In the CA1 region, the high-exposed group had a significant decrease in neuron numbers. A non-monotonic relationship was observed between the exposure concentrations and neuron quantity in the CA3 region. The hippocampal slices in the control and medium-exposed groups generated long-term potentiation after induction by theta burst stimulation, but the low-exposed group did not. A significant difference was observed between the control and low-exposed groups. In conclusion, chronic exposure to a low level of BPA had adverse effects on brain cells and altered the learning and memory ability of adolescent mice. - Highlights: • Low dose BPA exposure could lead to DNA

  4. Comparison of Ehrlichia muris Strains Isolated from Wild Mice and Ticks and Serologic Survey of Humans and Animals with E. muris as Antigen

    OpenAIRE

    Kawahara, Makoto; Ito, Tadahiko; Suto, Chiharu; Shibata, Shinichiro; Rikihisa, Yasuko; Hata, Kazuhisa; Hirai, Katsuya

    1999-01-01

    In metropolitan Tokyo, the Ehrlichia muris seropositivity rate of 24 wild mice was 63% in Hinohara Village, but in the surrounding areas, it was 0 to 5%. This finding suggests that the reservoir of E. muris is focal. Among the 15 seropositive mice, ehrlichiae were isolated from 9 Apodemus speciosus mice and 1 A. argenteus mouse, respectively. Five ehrlichial isolates were obtained from 10 ticks (Haemaphysalis flava) collected in Asuke Town, Aichi Prefecture, where the E. muris type strain had...

  5. Insulin signaling disruption in male mice due to perinatal bisphenol A exposure: Role of insulin signaling in the brain.

    Science.gov (United States)

    Fang, Fangfang; Gao, Yue; Wang, Tingwei; Chen, Donglong; Liu, Jingli; Qian, Wenyi; Cheng, Jie; Gao, Rong; Wang, Jun; Xiao, Hang

    2016-03-14

    Bisphenol A (BPA), an environmental estrogenic endocrine disruptor, is widely used for producing polycarbonate plastics and epoxy resins. Available data have shown that perinatal exposure to BPA contributes to peripheral insulin resistance, while in the present study, we aimed to investigate the effects of perinatal BPA exposure on insulin signaling and glucose transport in the cortex of offspring mice. The pregnant mice were administrated either vehicle or BPA (100 μg/kg/day) at three perinatal stages. Stage I: from day 6 of gestation until parturition (P6-PND0 fetus exposure); Stage II: from lactation until delactation (PND0-PND21 newborn exposure) and Stage III: from day 6 of pregnancy until delactation (P6-PND21 fetus and newborn exposure). At 8 months of age for the offspring mice, the insulin signaling pathways and glucose transporters (GLUTs) were detected. Our data indicated that the insulin signaling including insulin, phosphorylated insulin receptor (IR), phosphorylated protein kinase B (p-AKT), phosphorylated glycogen synthase kinase 3β (p-GSK3β) and phosphorylated extracellular signal regulated protein kinase (p-ERK) were significantly decreased in the brain. In parallel, GLUTs (GLUT1/3/4) were obviously decreased as well in BPA-treated group in mice brain. Noteworthily, the phosphorylated tau (p-tau) and amyloid precursor protein (APP) were markedly up-regulated in all BPA-treated groups. These results, taken together, suggest the adverse effects of BPA on insulin signaling and GLUTs, which might subsequently contribute to the increment of p-tau and APP in the brain of adult offspring. Therefore, perinatal BPA exposure might be a risk factor for the long-term neurodegenerative changes in offspring male mice. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Illumination of murine gammaherpesvirus-68 cycle reveals a sexual transmission route from females to males in laboratory mice.

    Directory of Open Access Journals (Sweden)

    Sylvie François

    Full Text Available Transmission is a matter of life or death for pathogen lineages and can therefore be considered as the main motor of their evolution. Gammaherpesviruses are archetypal pathogenic persistent viruses which have evolved to be transmitted in presence of specific immune response. Identifying their mode of transmission and their mechanisms of immune evasion is therefore essential to develop prophylactic and therapeutic strategies against these infections. As the known human gammaherpesviruses, Epstein-Barr virus and Kaposi's Sarcoma-associated Herpesvirus are host-specific and lack a convenient in vivo infection model; related animal gammaherpesviruses, such as murine gammaherpesvirus-68 (MHV-68, are commonly used as general models of gammaherpesvirus infections in vivo. To date, it has however never been possible to monitor viral excretion or virus transmission of MHV-68 in laboratory mice population. In this study, we have used MHV-68 associated with global luciferase imaging to investigate potential excretion sites of this virus in laboratory mice. This allowed us to identify a genital excretion site of MHV-68 following intranasal infection and latency establishment in female mice. This excretion occurred at the external border of the vagina and was dependent on the presence of estrogens. However, MHV-68 vaginal excretion was not associated with vertical transmission to the litter or with horizontal transmission to female mice. In contrast, we observed efficient virus transmission to naïve males after sexual contact. In vivo imaging allowed us to show that MHV-68 firstly replicated in penis epithelium and corpus cavernosum before spreading to draining lymph nodes and spleen. All together, those results revealed the first experimental transmission model for MHV-68 in laboratory mice. In the future, this model could help us to better understand the biology of gammaherpesviruses and could also allow the development of strategies that could prevent

  7. Involvement of delta opioid receptors in alcohol withdrawal-induced mechanical allodynia in male C57BL/6 mice.

    Science.gov (United States)

    Alongkronrusmee, Doungkamol; Chiang, Terrance; van Rijn, Richard M

    2016-10-01

    As a legal drug, alcohol is commonly abused and it is estimated that 17 million adults in the United States suffer from alcohol use disorder. Heavy alcoholics can experience withdrawal symptoms including anxiety and mechanical allodynia that can facilitate relapse. The molecular mechanisms underlying this phenomenon are not well understood, which stifles development of new therapeutics. Here we investigate whether delta opioid receptors (DORs) play an active role in alcohol withdrawal-induced mechanical allodynia (AWiMA) and if DOR agonists may provide analgesic relief from AWiMA. To study AWiMA, adult male wild-type and DOR knockout C57BL/6 mice were exposed to alcohol by a voluntary drinking model or oral gavage exposure model, which we developed and validated here. We also used the DOR-selective agonist TAN-67 and antagonist naltrindole to examine the involvement of DORs in AWiMA, which was measured using a von Frey model of mechanical allodynia. We created a robust model of alcohol withdrawal-induced anxiety and mechanical allodynia by orally gavaging mice with 3g/kg alcohol for three weeks. AWiMA was exacerbated and prolonged in DOR knockout mice as well as by pharmacological blockade of DORs compared to control mice. However, analgesia induced by TAN-67 was attenuated during withdrawal in alcohol-gavaged mice. DORs appear to play a protective role in the establishment of AWiMA. Our current results indicate that DORs could be targeted to prevent or reduce the development of AWiMA during alcohol use; however, DORs may be a less suitable target to treat AWiMA during active withdrawal. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Reproductive isolation in hybrid mice due to spermatogenesis defects at three meiotic stages.

    Science.gov (United States)

    Oka, Ayako; Mita, Akihiko; Takada, Yuki; Koseki, Haruhiko; Shiroishi, Toshihiko

    2010-09-01

    Early in the process of speciation, reproductive failures occur in hybrid animals between genetically diverged populations. The sterile hybrid animals are often males in mammals and they exhibit spermatogenic disruptions, resulting in decreased number and/or malformation of mature sperms. Despite the generality of this phenomenon, comparative study of phenotypes in hybrid males from various crosses has not been done, and therefore the comprehensive genetic basis of the disruption is still elusive. In this study, we characterized the spermatogenic phenotype especially during meiosis in four different cases of reproductive isolation: B6-ChrX(MSM), PGN-ChrX(MSM), (B6 × Mus musculus musculus-NJL/Ms) F(1), and (B6 × Mus spretus) F(1). The first two are consomic strains, both bearing the X chromosome of M. m. molossinus; in B6-ChrX(MSM), the genetic background is the laboratory strain C57BL/6J (predominantly M. m. domesticus), while in PGN-ChrX(MSM) the background is the PGN2/Ms strain purely derived from wild M. m. domesticus. The last two cases are F(1) hybrids between mouse subspecies or species. Each of the hybrid males exhibited cell-cycle arrest and/or apoptosis at either one or two of three distinct meiotic stages: premeiotic stage, zygotene-to-pachytene stage of prophase I, and metaphase I. This study shows that the sterility in hybrid males is caused by spermatogenic disruptions at multiple stages, suggesting that the responsible genes function in different cellular processes. Furthermore, the stages with disruptions are not correlated with the genetic distance between the respective parental strains.

  9. Ciguatoxins and Maitotoxins in Extracts of Sixteen Gambierdiscus Isolates and One Fukuyoa Isolate from the South Pacific and Their Toxicity to Mice by Intraperitoneal and Oral Administration

    Science.gov (United States)

    Munday, Rex; Murray, Sam; Rhodes, Lesley L.; Larsson, Michaela E.; Harwood, D. Tim

    2017-01-01

    Ciguatoxins (CTXs), and possibly maitotoxins (MTXs), are responsible for Ciguatera Fish Poisoning, an important health problem for consumers of reef fish (such as inhabitants of islands in the South Pacific Ocean). The habitational range of the Gambierdiscus species is expanding, and new species are being discovered. In order to provide information on the potential health risk of the Gambierdiscus species, and one Fukuyoa species (found in the Cook Islands, the Kermadec Islands, mainland New Zealand, and New South Wales, Australia), 17 microalgae isolates were collected from these areas. Unialgal cultures were grown and extracts of the culture isolates were analysed for CTXs and MTXs by liquid chromatography tandem mass spectrometry (LC-MS/MS), and their toxicity to mice was determined by intraperitoneal and oral administration. An isolate of G. carpenteri contained neither CTXs nor MTXs, while 15 other isolates (including G. australes, G. cheloniae, G. pacificus, G. honu, and F. paulensis) contained only MTX-1 and/or MTX-3. An isolate of G. polynesiensis contained both CTXs and MTX-3. All the extracts were toxic to mice by intraperitoneal injection, but those containing only MTX-1 and/or -3 were much less toxic by oral administration. The extract of G. polynesiensis was highly toxic by both routes of administration. PMID:28665362

  10. Ciguatoxins and Maitotoxins in Extracts of Sixteen Gambierdiscus Isolates and One Fukuyoa Isolate from the South Pacific and Their Toxicity to Mice by Intraperitoneal and Oral Administration

    Directory of Open Access Journals (Sweden)

    Rex Munday

    2017-06-01

    Full Text Available Ciguatoxins (CTXs, and possibly maitotoxins (MTXs, are responsible for Ciguatera Fish Poisoning, an important health problem for consumers of reef fish (such as inhabitants of islands in the South Pacific Ocean. The habitational range of the Gambierdiscus species is expanding, and new species are being discovered. In order to provide information on the potential health risk of the Gambierdiscus species, and one Fukuyoa species (found in the Cook Islands, the Kermadec Islands, mainland New Zealand, and New South Wales, Australia, 17 microalgae isolates were collected from these areas. Unialgal cultures were grown and extracts of the culture isolates were analysed for CTXs and MTXs by liquid chromatography tandem mass spectrometry (LC-MS/MS, and their toxicity to mice was determined by intraperitoneal and oral administration. An isolate of G. carpenteri contained neither CTXs nor MTXs, while 15 other isolates (including G. australes, G. cheloniae, G. pacificus, G. honu, and F. paulensis contained only MTX-1 and/or MTX-3. An isolate of G. polynesiensis contained both CTXs and MTX-3. All the extracts were toxic to mice by intraperitoneal injection, but those containing only MTX-1 and/or -3 were much less toxic by oral administration. The extract of G. polynesiensis was highly toxic by both routes of administration.

  11. Ciguatoxins and Maitotoxins in Extracts of Sixteen Gambierdiscus Isolates and One Fukuyoa Isolate from the South Pacific and Their Toxicity to Mice by Intraperitoneal and Oral Administration.

    Science.gov (United States)

    Munday, Rex; Murray, Sam; Rhodes, Lesley L; Larsson, Michaela E; Harwood, D Tim

    2017-06-30

    Ciguatoxins (CTXs), and possibly maitotoxins (MTXs), are responsible for Ciguatera Fish Poisoning, an important health problem for consumers of reef fish (such as inhabitants of islands in the South Pacific Ocean). The habitational range of the Gambierdiscus species is expanding, and new species are being discovered. In order to provide information on the potential health risk of the Gambierdiscus species, and one Fukuyoa species (found in the Cook Islands, the Kermadec Islands, mainland New Zealand, and New South Wales, Australia), 17 microalgae isolates were collected from these areas. Unialgal cultures were grown and extracts of the culture isolates were analysed for CTXs and MTXs by liquid chromatography tandem mass spectrometry (LC-MS/MS), and their toxicity to mice was determined by intraperitoneal and oral administration. An isolate of G. carpenteri contained neither CTXs nor MTXs, while 15 other isolates (including G. australes, G. cheloniae , G. pacificus , G. honu , and F. paulensis ) contained only MTX-1 and/or MTX-3. An isolate of G. polynesiensis contained both CTXs and MTX-3. All the extracts were toxic to mice by intraperitoneal injection, but those containing only MTX-1 and/or -3 were much less toxic by oral administration. The extract of G. polynesiensis was highly toxic by both routes of administration.

  12. Adsorption of Bisphenol A to a Carbon Nanotube Reduced Its Endocrine Disrupting Effect in Mice Male Offspring

    Directory of Open Access Journals (Sweden)

    Wenwei Wang

    2014-09-01

    Full Text Available Soluble carbon nanotubes (CNTs have shown promise as materials for adsorption of environmental contaminants such as Bisphenol A (BPA, due to the high adsorption capacity and strong desorption hysteresis of BPA on CNTs. The adsorption of BPA to CNTs may change the properties of both BPA and CNTs, and induce different toxicity to human and living systems from that of BPA and CNTs alone. Herein, we report that oral exposure of BPA/MWCNT–COOH (carboxylated multi-walled carbon nantubes adduct to mice during gestation and lactation period decreased the male offspring reproductive toxicity compared with those induced by BPA alone. The adduct decreased malondialdehyde (MDA level in testis and follicle-stimulating hormone (FSH in serum, but increased the level of serum testosterone in male offspring in comparison to BPA alone. Our investigations broadened the knowledge of nanotoxicity and provided important information on the safe application of CNTs.

  13. The influence of chronic stress on anxiety-like behavior and cognitive function in different human GFAP-ApoE transgenic adult male mice.

    Science.gov (United States)

    Meng, Fan-Tao; Zhao, Jun; Fang, Hui; Liu, Ya-Jing

    2015-01-01

    The apolipoprotein E (ApoE) ɛ4 allele (ApoE4) is an important genetic risk factor for the pathogenesis of Alzheimer's disease (AD). In addition to genetic factors, environmental factors such as stress may play a critical role in AD pathogenesis. This study was designed to investigate the anxiety-like behavioral and cognitive changes in different human glial fibrillary acidic protein (GFAP)-ApoE transgenic adult male mice under chronic stress conditions. On the open field test, anxiety-like behavior was increased in the non-stressed GFAP-ApoE4 transgenic mice relative to the corresponding GFAP-ApoE3 (ApoE ɛ3 allele) mice. Anxiety-like behavior was increased in the stressed GFAP-ApoE3 mice relative to non-stressed GFAP-ApoE3 mice, but was unexpectedly decreased in the stressed GFAP-ApoE4 mice relative to non-stressed GFAP-ApoE4 mice. On the novel object recognition task, both GFAP-ApoE4 and GFAP-ApoE3 mice exhibited long-term non-spatial memory impairment after chronic stress. Interestingly, short-term non-spatial memory impairment (based on the novel object recognition task) was observed only in the stressed GFAP-ApoE4 male mice relative to non-stressed GFAP-ApoE4 transgenic mice. In addition, short-term spatial memory impairment was observed in the stressed GFAP-ApoE3 transgenic male mice relative to non-stressed GFAP-ApoE3 transgenic male mice; however, short-term spatial memory performance of GFAP-ApoE4 transgenic male mice was not reduced compared to non-stressed control mice based on the Y-maze task. In conclusion, our findings suggested that chronic stress affects anxiety-like behavior and spatial and non-spatial memory in GFAP-ApoE transgenic mice in an ApoE isoform-dependent manner.

  14. HEMOSTATIC EFFECT OF ETHANOL EXTRACT OF Piper betle, Linn LEAVES TO MALE MICE

    Directory of Open Access Journals (Sweden)

    Sadakata Sinulingga

    2017-05-01

    Full Text Available Hemorrhage occurs in most of the dental care. Untreated hemorrhage could cause excessive blood loss, hypotension, and cyanosis. A Natural resource that reported has an hemostatic effect is ethanol extract of betel leaves (Piper betel, Linn.The aim of this study is to find the minimum concentration of ethanol extract of betel leaves which capable of shortening the bleeding time in mice. The experimental study used pretest-posttest with control group design was conducted on 35 mice that divided into 7 group which are negative control, positive control (feracrylum 1%, the ethanol extract of betel leaves 1%, 5%, 10%, 15%, and 20%. All mice were injected heparin intravenously. Mice’s tail was cut at diameter 3 mm and pretest bleeding time was counted. Mice’s tail was recut at diameter 4 mm, given treatment for 5 seconds and posttest bleeding time was counted. Results of paired t-test showed that reduction of bleeding time between pretest and posttest was significant (p<0,050. The enhancement of ethanol extract of betel leaves concentration leads to better hemostatic effect. Results of ANOVA test showed that comparison of posttest bleeding time among groups was significant (p<0,050. The minimum concentration of ethanol extract of betel leaves which capable of shortening the bleeding time in mice is 5%.

  15. Behavioural strategies of aggressive and non-aggressive male mice in active shock avoidance

    NARCIS (Netherlands)

    Benus, R.F.; Bohus, B.; Koolhaas, J.M.; Oortmerssen, G.A. van

    1989-01-01

    The hypothesis, partly based on findings in social interactions, that aggressive mice generally adopt an active behavioural strategy (cf. fight-flight) in threatening situations, while non-aggressive ones generally assume a passive strategy (cf. conservation-withdrawal) was tested using a two-way

  16. Behavioural and physiological responses to increased foraging effort in male mice

    NARCIS (Netherlands)

    Vaanholt, Lobke M.; De Jong, Berber; Garland, Theodore; Daan, Serge; Visser, G. Henk; Garland, Jr.

    2007-01-01

    Free-living animals must forage for food and hence may face energetic constraints imposed by their natural environmental conditions (e. g. ambient temperature, food availability). Simulating the variation in such constraints, we have experimentally manipulated the rate of work (wheel running) mice

  17. Sustained alterations of hypothalamic tanycytes during posttraumatic hypopituitarism in male mice.

    Science.gov (United States)

    Osterstock, Guillaume; El Yandouzi, Taoufik; Romanò, Nicola; Carmignac, Danielle; Langlet, Fanny; Coutry, Nathalie; Guillou, Anne; Schaeffer, Marie; Chauvet, Norbert; Vanacker, Charlotte; Galibert, Evelyne; Dehouck, Bénédicte; Robinson, Iain C A F; Prévot, Vincent; Mollard, Patrice; Plesnila, Nikolaus; Méry, Pierre-François

    2014-05-01

    Traumatic brain injury is a leading cause of hypopituitarism, which compromises patients' recovery, quality of life, and life span. To date, there are no means other than standardized animal studies to provide insights into the mechanisms of posttraumatic hypopituitarism. We have found that GH levels were impaired after inducing a controlled cortical impact (CCI) in mice. Furthermore, GHRH stimulation enhanced GH to lower level in injured than in control or sham mice. Because many characteristics were unchanged in the pituitary glands of CCI mice, we looked for changes at the hypothalamic level. Hypertrophied astrocytes were seen both within the arcuate nucleus and the median eminence, two pivotal structures of the GH axis, spatially remote to the injury site. In the arcuate nucleus, GHRH neurons were unaltered. In the median eminence, injured mice exhibited unexpected alterations. First, the distributions of claudin-1 and zonula occludens-1 between tanycytes were disorganized, suggesting tight junction disruptions. Second, endogenous IgG was increased in the vicinity of the third ventricle, suggesting abnormal barrier properties after CCI. Third, intracerebroventricular injection of a fluorescent-dextran derivative highly stained the hypothalamic parenchyma only after CCI, demonstrating an increased permeability of the third ventricle edges. This alteration of the third ventricle might jeopardize the communication between the hypothalamus and the pituitary gland. In conclusion, the phenotype of CCI mice had similarities to the posttraumatic hypopituitarism seen in humans with intact pituitary gland and pituitary stalk. It is the first report of a pathological status in which tanycyte dysfunctions appear as a major acquired syndrome.

  18. Performance of Male and Female C57BL/6J Mice on Motor and Cognitive Tasks Commonly Used in Pre-Clinical Traumatic Brain Injury Research

    Science.gov (United States)

    Tucker, Laura B.; Fu, Amanda H.

    2016-01-01

    Abstract To date, clinical trials have failed to find an effective therapy for victims of traumatic brain injury (TBI) who live with motor, cognitive, and psychiatric complaints. Pre-clinical investigators are now encouraged to include male and female subjects in all translational research, which is of particular interest in the field of neurotrauma given that circulating female hormones (progesterone and estrogen) have been demonstrated to exert neuroprotective effects. To determine whether behavior of male and female C57BL6/J mice is differentially impaired by TBI, male and cycling female mice were injured by controlled cortical impact and tested for several weeks with functional assessments commonly employed in pre-clinical research. We found that cognitive and motor impairments post-TBI, as measured by the Morris water maze (MWM) and rotarod, respectively, were largely equivalent in male and female animals. However, spatial working memory, assessed by the y-maze, was poorer in female mice. Female mice were generally more active, as evidenced by greater distance traveled in the first exposure to the open field, greater distance in the y-maze, and faster swimming speeds in the MWM. Statistical analysis showed that variability in all behavioral data was no greater in cycling female mice than it was in male mice. These data all suggest that with careful selection of tests, procedures, and measurements, both sexes can be included in translational TBI research without concern for effect of hormones on functional impairments or behavioral variability. PMID:25951234

  19. Effects of the antitumor drug OSI-906, a dual inhibitor of IGF-1 receptor and insulin receptor, on the glycemic control, β-cell functions, and β-cell proliferation in male mice.

    Science.gov (United States)

    Shirakawa, Jun; Okuyama, Tomoko; Yoshida, Eiko; Shimizu, Mari; Horigome, Yuka; Tuno, Takayuki; Hayasaka, Moe; Abe, Shiori; Fuse, Masahiro; Togashi, Yu; Terauchi, Yasuo

    2014-06-01

    The IGF-1 receptor has become a therapeutic target for the treatment of cancer. The efficacy of OSI-906 (linstinib), a dual inhibitor of IGF-1 receptor and insulin receptor, for solid cancers has been examined in clinical trials. The effects of OSI-906, however, on the blood glucose levels and pancreatic β-cell functions have not yet been reported. We investigated the impact of OSI-906 on glycemic control, insulin secretion, β-cell mass, and β-cell proliferation in male mice. Oral administration of OSI-906 worsened glucose tolerance in a dose-dependent manner in the wild-type mice. OSI-906 at a dose equivalent to the clinical daily dose (7.5 mg/kg) transiently evoked glucose intolerance and hyperinsulinemia. Insulin receptor substrate (IRS)-2-deficient mice and mice with diet-induced obesity, both models of peripheral insulin resistance, exhibited more severe glucose intolerance after OSI-906 administration than glucokinase-haploinsufficient mice, a model of impaired insulin secretion. Phloridzin improved the hyperglycemia induced by OSI-906 in mice. In vitro, OSI-906 showed no effect on insulin secretion from isolated islets. After daily administration of OSI-906 for a week to mice, the β-cell mass and β-cell proliferation rate were significantly increased. The insulin signals in the β-cells were apparently unaffected in those mice. Taken together, the results suggest that OSI-906 could exacerbate diabetes, especially in patients with insulin resistance. On the other hand, the results suggest that the β-cell mass may expand in response to chemotherapy with this drug.

  20. Isolating the role of elevated Phlda2 in asymmetric late fetal growth restriction in mice

    Directory of Open Access Journals (Sweden)

    Simon J. Tunster

    2014-10-01

    Full Text Available Pleckstrin homology-like domain family A member 2 (PHLDA2 is a maternally expressed imprinted gene whose elevated expression has been linked to fetal growth restriction in a number of human studies. In mice, Phlda2 negatively regulates placental growth and limits the accumulation of placental glycogen. We previously reported that a three-copy transgene spanning the Phlda2 locus drove a fetal growth restriction phenotype late in gestation, suggesting a causative role for PHLDA2 in human growth restriction. However, in this mouse model, Phlda2 was overexpressed by fourfold, alongside overexpression of a second imprinted gene, Slc22a18. Here, we genetically isolate the role of Phlda2 in driving late fetal growth restriction in mice. We furthermore show that this Phlda2-driven growth restriction is asymmetrical, with a relative sparing of the brain, followed by rapid catch-up growth after birth, classic features of placental insufficiency. Strikingly, fetal growth restriction showed strain-specific differences, being apparent on the 129S2/SvHsd (129 genetic background and absent on the C57BL6 (BL6 background. A key difference between these two strains is the placenta. Specifically, BL6 placentae possess a more extensive endocrine compartment and substantially greater stores of placental glycogen. Taken together, these data support a direct role for elevated Phlda2 in limiting fetal growth but also suggest that growth restriction only manifests when there is limited placental reserve. These findings should be taken into account in interpreting the results from human studies.

  1. Investigation of genomic instability by assay of DNA fingerprint from the offspring of male mice exposed to chronic low-level γ-radiation

    International Nuclear Information System (INIS)

    Bezlepkin, V.G.; Vasil'eva, G.V.; Lomaeva, M.G.; Sirota, N.P.; Gaziev, A.I.

    2000-01-01

    By polymerase chain reaction with arbitrary primer (AP-PCR), the possibility of transmission of genome instability to somatic cells of the offspring (F 1 generation) from male parents of mice exposed to chronic low-dose γ-radiation was studied. Male mice 15 days after exposure to 10-50 cGy were mated with unirradiated females. Biopsies were taken from tale tips of two month-old mice progeny for DNA separation. Primer in the AP-PCR was 20-mer oligonucleotide flanking the micro-satellite locus Atplb2 on chromosome 11 of the mouse. Comparative analysis of individual fingerprints of AP-PCR products on DNA-templates from the offspring of irradiated and unirradiated male mice revealed an increased variability of micro-satellite-associated sequences in the genome of the offspring of males exposed to 25 and 50 cGy. DNA-fingerprints of the offspring of male mice exposed to chronic irradiation doses 10 and 25 cGy. 15 days before fertilization (at the post-meiotic stage of spermatogenesis) showed an increased frequency of non-parent bands. Result of the study point to the possibility of transmission to the offspring somatic cells of changes increasing genome instability from male parents exposed to chronic low-dose radiation prior to fertilization [ru

  2. Social Isolation Modulates CLOCK Protein and Beta-Catenin Expression Pattern in Gonadotropin-Inhibitory Hormone Neurons in Male Rats

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    Chuin Hau Teo

    2017-09-01

    Full Text Available Postweaning social isolation reduces the amplitude of the daily variation of CLOCK protein in the brain and induces lower reproductive activity. Gonadotropin-inhibitory hormone (GnIH acts as an inhibitor in the reproductive system and has been linked to stress. Social isolation has been shown to lower neuronal activity of GnIH-expressing neurons in the dorsomedial hypothalamus (DMH. The exact mechanism by which social isolation may affect GnIH is still unclear. We investigated the impact of social isolation on regulatory cellular mechanisms in GnIH neurons. We examined via immunohistochemistry the expression of CLOCK protein at four different times throughout the day in GnIH cells tagged with enhanced fluorescent green protein (EGFP-GnIH in 9-week-old adult male rats that have been raised for 6 weeks under postweaning social isolation and compared them with group-raised control rats of the same age. We also studied the expression of β-catenin—which has been shown to be affected by circadian proteins such as Bmal1—in EGFP-GnIH neurons to determine whether it could play a role in linking CLOCK in GnIH neurons. We found that social isolation modifies the pattern of CLOCK expression in GnIH neurons in the DMH. Socially isolated rats displayed greater CLOCK expression in the dark phase, while control rats displayed increased CLOCK expression in the light phase. Furthermore, β-catenin expression pattern in GnIH cells was disrupted by social isolation. This suggests that social isolation triggers changes in CLOCK and GnIH expression, which may be associated with an increase in nuclear β-catenin during the dark phase.

  3. Social Isolation Modulates CLOCK Protein and Beta-Catenin Expression Pattern in Gonadotropin-Inhibitory Hormone Neurons in Male Rats.

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    Teo, Chuin Hau; Soga, Tomoko; Parhar, Ishwar S

    2017-01-01

    Postweaning social isolation reduces the amplitude of the daily variation of CLOCK protein in the brain and induces lower reproductive activity. Gonadotropin-inhibitory hormone (GnIH) acts as an inhibitor in the reproductive system and has been linked to stress. Social isolation has been shown to lower neuronal activity of GnIH-expressing neurons in the dorsomedial hypothalamus (DMH). The exact mechanism by which social isolation may affect GnIH is still unclear. We investigated the impact of social isolation on regulatory cellular mechanisms in GnIH neurons. We examined via immunohistochemistry the expression of CLOCK protein at four different times throughout the day in GnIH cells tagged with enhanced fluorescent green protein (EGFP-GnIH) in 9-week-old adult male rats that have been raised for 6 weeks under postweaning social isolation and compared them with group-raised control rats of the same age. We also studied the expression of β-catenin-which has been shown to be affected by circadian proteins such as Bmal1-in EGFP-GnIH neurons to determine whether it could play a role in linking CLOCK in GnIH neurons. We found that social isolation modifies the pattern of CLOCK expression in GnIH neurons in the DMH. Socially isolated rats displayed greater CLOCK expression in the dark phase, while control rats displayed increased CLOCK expression in the light phase. Furthermore, β-catenin expression pattern in GnIH cells was disrupted by social isolation. This suggests that social isolation triggers changes in CLOCK and GnIH expression, which may be associated with an increase in nuclear β-catenin during the dark phase.

  4. Obesity or Overweight, a Chronic Inflammatory Status in Male Reproductive System, Leads to Mice and Human Subfertility

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    Weimin Fan

    2018-01-01

    Full Text Available Obesity is frequently accompanied with chronic inflammation over the whole body and is always associated with symptoms that include those arising from metabolic and vascular alterations. On the other hand, the chronic inflammatory status in the male genital tract may directly impair spermatogenesis and is even associated with male subfertility. However, it is still unclear if the chronic inflammation induced by obesity damages spermatogenesis in the male genital tract. To address this question, we used a high fat diet (HFD induced obese mouse model and recruited obese patients from the clinic. We detected increased levels of tumor necrosis factor (TNF-α, interleukin-6 (IL-6, and NOD-like receptor family pyrin domain containing-3 (NLRP3 in genital tract tissues including testis, epididymis, seminal vesicle, prostate, and serum from obese mice. Meanwhile, the levels of immunoglobulin G (IgG and corticosterone were significantly higher than those in the control group in serum. Moreover, signal factors regulated by TNF-α, i.e., p38, nuclear factor-κB (NF-κB, Jun N-terminal kinase (JNK, extracellular signal-regulated kinase (ERK, and their phosphorylated status, and inflammasome protein NLRP3 were expressed at higher levels in the testis. For overweight and obese male patients, the increased levels of TNF-α and IL-6 were also observed in their seminal plasma. Furthermore, there was a positive correlation between the TNF-α and IL-6 levels and BMI whereas they were inversely correlated with the sperm concentration and motility. In conclusion, impairment of male fertility may stem from a chronic inflammatory status in the male genital tract of obese individuals.

  5. A Foxp2 mutation implicated in human speech deficits alters sequencing of ultrasonic vocalizations in adult male mice

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    Jonathan Chabout

    2016-10-01

    Full Text Available Development of proficient spoken language skills is disrupted by mutations of the FOXP2 transcription factor. A heterozygous missense mutation in the KE family causes speech apraxia, involving difficulty producing words with complex learned sequences of syllables. Manipulations in songbirds have helped to elucidate the role of this gene in vocal learning, but findings in non-human mammals have been limited or inconclusive. Here we performed a systematic study of ultrasonic vocalizations (USVs of adult male mice carrying the KE family mutation. Using novel statistical tools, we found that Foxp2 heterozygous mice did not have detectable changes in USV syllable acoustic structure, but produced shorter sequences and did not shift to more complex syntax in social contexts where wildtype animals did. Heterozygous mice also displayed a shift in the position of their rudimentary laryngeal motor cortex layer-5 neurons. Our findings indicate that although mouse USVs are mostly innate, the underlying contributions of FoxP2 to sequencing of vocalizations are conserved with humans.

  6. Subchronic Oral Bromocriptine Methanesulfonate Enhances Open Field Novelty-Induced Behavior and Spatial Memory in Male Swiss Albino Mice

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    Olakunle James Onaolapo

    2013-01-01

    Full Text Available This study set out to assess the neurobehavioral effects of subchronic, oral bromocriptine methanesulfonate using the open field and the Y-maze in healthy male mice. Sixty adult Swiss albino mice were assigned into three groups. Controls received normal saline, while test groups received bromocriptine methanesulfonate at 2.5 and 5 mg/kg/day, respectively, for a period of 21 days. Neurobehavioral tests were carried out on days 1 and 21 after administration. Open field assessment on day 1 after administration revealed significant increase in grooming at 2.5 and 5 mg/kg, while horizontal and vertical locomotion showed no significant changes. Day 1 also showed no significant changes in Y-maze alternation. On day 21, horizontal locomotion, rearing, and grooming were increased significantly at 2.5 and 5 mg/kg doses after administration; also, spatial memory was significantly enhanced at 2.5 mg/kg. In conclusion, the study demonstrates the ability of oral bromocriptine to affect neurobehavior in normal mice. It also suggests that there is a cumulative effect of oral bromocriptine on the behaviors studied with more changes being seen after subchronic administration rather than after a single oral dose.

  7. Effect of Tea (Camellia sinensis and Olive (Olea europaea L. Leaves Extracts on Male Mice Exposed to Diazinon

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    Atef M. Al-Attar

    2013-01-01

    Full Text Available The present study was aimed to evaluate the effects of tea and olive leaves extracts and their combination in male mice intoxicated with a sublethal concentration of diazinon. Exposure of mice to 6.5 mg/kg body weight of diazinon for seven weeks resulted in statistical increases of serum alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, alkaline phosphatase, creatine kinase, creatinine, glucose, triglycerides, and cholesterol, while the value of serum total protein was declined. Treating diazinon-intoxicated mice with tea and olive leaves extracts or their combination significantly attenuated the severe alterations in these hematobiochemical parameters. Moreover, the results indicated that the supplementation with combination of tea and olive leaves extracts led to more attenuation effect against diazinon toxicity. Additionally, these new findings suggest that the effect of tea and olive leaves extracts and their combination against toxicity of diazinon may be due to antioxidant properties of their chemical constituents. Finally, the present study indicated that the extracts of tea and olive leaves and their combination can be considered as promising therapeutic agents against hepatotoxicity, cardiotoxicity, nephrotoxicity, and metabolic disorders induced by diazinon and maybe by other toxicants and pathogenic factors.

  8. The combined effect of clothianidin and environmental stress on the behavioral and reproductive function in male mice.

    Science.gov (United States)

    Hirano, Tetsushi; Yanai, Shogo; Omotehara, Takuya; Hashimoto, Rie; Umemura, Yuria; Kubota, Naoto; Minami, Kiichi; Nagahara, Daichi; Matsuo, Eiko; Aihara, Yoshiko; Shinohara, Ryota; Furuyashiki, Tomoyuki; Mantani, Youhei; Yokoyama, Toshifumi; Kitagawa, Hiroshi; Hoshi, Nobuhiko

    2015-10-01

    Neonicotinoids, some of the most widely used pesticides in the world, act as agonists to the nicotinic acetylcholine receptors (nAChRs) of insects, resulting in death from abnormal excitability. Neonicotinoids unexpectedly became a major topic as a compelling cause of honeybee colony collapse disorder, which is damaging crop production that requires pollination worldwide. Mammal nAChRs appear to have a certain affinity for neonicotinoids with lower levels than those of insects; there is thus rising concern about unpredictable adverse effects of neonicotinoids on vertebrates. We hypothesized that the effects of neonicotinoids would be enhanced under a chronic stressed condition, which is known to alter the expression of targets of neonicotinoids, i.e., neuronal nAChRs. We performed immunohistochemical and behavioral analyses in male mice actively administered a neonicotinoid, clothianidin (CTD; 0, 10, 50 and 250 mg/kg/day), for 4 weeks under an unpredictable chronic stress procedure. Vacuolated seminiferous epithelia and a decrease in the immunoreactivity of the antioxidant enzyme glutathione peroxidase 4 were observed in the testes of the CTD+stress mice. In an open field test, although the locomotor activities were not affected, the anxiety-like behaviors of the mice were elevated by both CTD and stress. The present study demonstrates that the behavioral and reproductive effects of CTD become more serious in combination with environmental stress, which may reflect our actual situation of multiple exposure.

  9. Subchronic Oral Bromocriptine Methanesulfonate Enhances Open Field Novelty-Induced Behavior and Spatial Memory in Male Swiss Albino Mice.

    Science.gov (United States)

    Onaolapo, Olakunle James; Onaolapo, Adejoke Yetunde

    2013-01-01

    This study set out to assess the neurobehavioral effects of subchronic, oral bromocriptine methanesulfonate using the open field and the Y-maze in healthy male mice. Sixty adult Swiss albino mice were assigned into three groups. Controls received normal saline, while test groups received bromocriptine methanesulfonate at 2.5 and 5 mg/kg/day, respectively, for a period of 21 days. Neurobehavioral tests were carried out on days 1 and 21 after administration. Open field assessment on day 1 after administration revealed significant increase in grooming at 2.5 and 5 mg/kg, while horizontal and vertical locomotion showed no significant changes. Day 1 also showed no significant changes in Y-maze alternation. On day 21, horizontal locomotion, rearing, and grooming were increased significantly at 2.5 and 5 mg/kg doses after administration; also, spatial memory was significantly enhanced at 2.5 mg/kg. In conclusion, the study demonstrates the ability of oral bromocriptine to affect neurobehavior in normal mice. It also suggests that there is a cumulative effect of oral bromocriptine on the behaviors studied with more changes being seen after subchronic administration rather than after a single oral dose.

  10. Protective effect of hydroalcoholic extract of tribulus terrestris on cisplatin induced renal tissue damage in male mice

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    Amir Raoofi

    2015-01-01

    Full Text Available Background: According beneficial effects of Tribulus terrestris (TT extract on tissue damage, the present study investigated the influence of hydroalcoholic extract of TT plant on cisplatin (CIS (EBEWE Pharma, Unterach, Austria induced renal tissue damage in male mice. Methods: Thirty mice were divided into five groups (n = 6. The first group (control was treated with normal saline (0.9% NaCl and experimental groups with CIS (E1, CIS + 100 mg/kg extract of TT (E2, CIS + 300 mg/kg extract of TT (E3, CIS + 500 mg/kg extract of TT (E4 intraperitoneally. The kidneys were removed after 4 days of injections, and histological evaluations were performed. Results: The data were analyzed using one-way analysis of variance followed by Tukey′s post-hoc test, paired-sample t-test, Kruskal-Wallis and Mann-Whitney tests. In the CIS treated group, the whole kidney tissue showed an increased dilatation of Bowman′s capsule, medullar congestion, and dilatation of collecting tubules and a decreased in the body weight and kidney weight. These parameters reached to the normal range after administration of fruit extracts of TT for 4 days. Conclusions: The results suggested that the oral administration of TT fruit extract at dose 100, 300 and 500 mg/kg body weight provided protection against the CIS induced toxicity in the mice.

  11. Protective Effect of Hydroalcoholic Extract of Tribulus Terrestris on Cisplatin Induced Renal Tissue Damage in Male Mice

    Science.gov (United States)

    Raoofi, Amir; Khazaei, Mozafar; Ghanbari, Ali

    2015-01-01

    Background: According beneficial effects of Tribulus terrestris (TT) extract on tissue damage, the present study investigated the influence of hydroalcoholic extract of TT plant on cisplatin (CIS) (EBEWE Pharma, Unterach, Austria) induced renal tissue damage in male mice. Methods: Thirty mice were divided into five groups (n = 6). The first group (control) was treated with normal saline (0.9% NaCl) and experimental groups with CIS (E1), CIS + 100 mg/kg extract of TT (E2), CIS + 300 mg/kg extract of TT (E3), CIS + 500 mg/kg extract of TT (E4) intraperitoneally. The kidneys were removed after 4 days of injections, and histological evaluations were performed. Results: The data were analyzed using one-way analysis of variance followed by Tukey's post-hoc test, paired-sample t-test, Kruskal–Wallis and Mann–Whitney tests. In the CIS treated group, the whole kidney tissue showed an increased dilatation of Bowman's capsule, medullar congestion, and dilatation of collecting tubules and a decreased in the body weight and kidney weight. These parameters reached to the normal range after administration of fruit extracts of TT for 4 days. Conclusions: The results suggested that the oral administration of TT fruit extract at dose 100, 300 and 500 mg/kg body weight provided protection against the CIS induced toxicity in the mice. PMID:25789143

  12. Protective effect of hydroalcoholic extract of tribulus terrestris on Cisplatin induced renal tissue damage in male mice.

    Science.gov (United States)

    Raoofi, Amir; Khazaei, Mozafar; Ghanbari, Ali

    2015-01-01

    According beneficial effects of Tribulus terrestris (TT) extract on tissue damage, the present study investigated the influence of hydroalcoholic extract of TT plant on cisplatin (CIS) (EBEWE Pharma, Unterach, Austria) induced renal tissue damage in male mice. Thirty mice were divided into five groups (n = 6). The first group (control) was treated with normal saline (0.9% NaCl) and experimental groups with CIS (E1), CIS + 100 mg/kg extract of TT (E2), CIS + 300 mg/kg extract of TT (E3), CIS + 500 mg/kg extract of TT (E4) intraperitoneally. The kidneys were removed after 4 days of injections, and histological evaluations were performed. The data were analyzed using one-way analysis of variance followed by Tukey's post-hoc test, paired-sample t-test, Kruskal-Wallis and Mann-Whitney tests. In the CIS treated group, the whole kidney tissue showed an increased dilatation of Bowman's capsule, medullar congestion, and dilatation of collecting tubules and a decreased in the body weight and kidney weight. These parameters reached to the normal range after administration of fruit extracts of TT for 4 days. The results suggested that the oral administration of TT fruit extract at dose 100, 300 and 500 mg/kg body weight provided protection against the CIS induced toxicity in the mice.

  13. Endocrine-disrupting activity of hydraulic fracturing chemicals and adverse health outcomes after prenatal exposure in male mice

    Science.gov (United States)

    Kassotis, Christopher D.; Klemp, Kara C.; Vu, Danh C.; Lin, Chung-Ho; Meng, Chun-Xia; Besch-Williford, Cynthia L.; Pinatti, Lisa; Zoeller, R. Thomas; Drobnis, Erma Z.; Balise, Victoria D.; Isiguzo, Chiamaka J.; Williams, Michelle A.; Tillitt, Donald E.; Nagel, Susan C.

    2015-01-01

    Oil and natural gas operations have been shown to contaminate surface and ground water with endocrine-disrupting chemicals. In the current study, we fill several gaps in our understanding of the potential environmental impacts related to this process. We measured the endocrine-disrupting activities of 24 chemicals used and/or produced by oil and gas operations for five nuclear receptors using a reporter gene assay in human endometrial cancer cells. We also quantified the concentration of 16 of these chemicals in oil and gas wastewater samples. Finally, we assessed reproductive and developmental outcomes in male C57BL/6J mice after the prenatal exposure to a mixture of these chemicals. We found that 23 commonly used oil and natural gas operation chemicals can activate or inhibit the estrogen, androgen, glucocorticoid, progesterone, and/or thyroid receptors, and mixtures of these chemicals can behave synergistically, additively, or antagonistically in vitro. Prenatal exposure to a mixture of 23 oil and gas operation chemicals at 3, 30, and 300 μg/kg · d caused decreased sperm counts and increased testes, body, heart, and thymus weights and increased serum testosterone in male mice, suggesting multiple organ system impacts. Our results suggest possible adverse developmental and reproductive health outcomes in humans and animals exposed to potential environmentally relevant levels of oil and gas operation chemicals.

  14. The antidepressant-like effect of Mentha spicata essential oil in animal models of depression in male mice

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    Behnam Jedi-Behnia

    2017-06-01

    Full Text Available Background & Objective: Previous researches have revealed analgesic and sedative properties of Mentha spicata (MS. The aim of present study was to evaluate the antidepressant effects of MS essential oil in forced swim test (FST and tail suspension test (TST in male mice. Materials & Methods: In this experimental study, 84 male mice were randomly divided into 14 groups of 6: Negative control groups received normal saline (10 ml/kg,i.p., positive control groups received fluoxetine (20mg/kg, i.p. and imipramine (30mg/kg and treatment groups received MS essential oil (30, 60,120 and 240 mg/kg i.p.. In FST, immobility time, swimming time and climbing time and immobility time in TST were recorded in six minutes. Results: Findings indicated that essential oil at doses of 120 and 240 mg/kg, fluoxetine and imipramine reduced immobility time compared to control group in FST and TST (p0.05. In contrast, imipramine increased climbing time without any significant change in swimming time (p>0.05. Conclusion: Based on the findings of the present study, MS essential oil has antidepressant-like activity similar to fluoxetine and probably their compounds (especially carvone with serotonergic mechanism induced their effect. However, further studies are needed to determine the precise mechanism of its action.

  15. Short-term dermal exposure to tannery effluent does not cause behavioral changes in male Swiss mice

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    Bruna de Oliveira Mendes

    2018-02-01

    Full Text Available Tannery is a highly polluting activity due to the waste generated by bovine skin processing. Although there are several studies highlighting the health issues faced by workers exposed to tannery effluent, there are no records of experiments testing the neurobehavioral effects resulting from direct contact with this pollutant. Thus, the aim of the current study is to assess the possible neurobehavioral effects of dermal exposure to tannery effluent on male Swiss mice. Animals were divided in three groups, which were subjected to the same experimental time period and conditions: effluent group - animals in direct contact with tannery effluent (for 20 days; control group - animals in contact with pure water; and dry-control group - animals not exposed to water or to tannery effluent. Neurobehavioral tests started on the 17th experimental day. Results of the elevated plus-maze test (anxiety prediction showed no anxiogenic or anxiolytic effects, memory deficit or depressive symptoms on animals exposed to tannery effluent. Thus, the current results do not support the hypothesis that male Swiss mice dermal exposure to tannery effluents for the same time period and experimental conditions leads to neurobehavioral changes. Therefore, the herein adopted exposure protocol was not good to study the effects of dermal exposure to tannery effluent on the chosen experimental model.

  16. Evaluation of antidepressant-like effect of hydroalcoholic extract of Passiflora incarnata in animal models of depression in male mice

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    Jafarpoor Nima

    2014-01-01

    Full Text Available Introduction: Passiflora incarnata (PI is one of the commonest herbal anti-anxiety and sedative agents. The aim of the present study was to investigate the antidepressant effect of hydroalcoholic extract of PI in forced swim test (FST and tail suspension test (TST in male mice. Methods: In this experimental study, 48 male mice were randomly divided into 6 groups of 8: Negative and positive control groups received normal saline (10 ml/kg, fluoxetine (20 mg/kg and imipramine (30 mg/kg, respectively and treatment groups received extracts of PI (200, 400 and 800 mg/kg. Immobility, swimming and climbing behaviors were recorded during 6-min. Results: All doses of PI extract compared to control group significantly reduced the duration of immobility time in both of two tests (p<0.001. Also, these extracts increased swimming time (p<0.001 without significant change of climbing time. Conclusion: PI has considerable antidepressant-like effect in animal models of depression. However, further studies are needed to determine its exact mechanism of action.

  17. Studies on chromosomal aberrations and dominant lethal mutations induced by x irradiation in germ cells of male mice

    International Nuclear Information System (INIS)

    Wang Xianli; Wang Mingdong; Wang Bin; Sun Shuqing

    1992-01-01

    After male mice irradiated by 2 Gy X rays mated to normal virginal females superovulated with PMSG and HCG, pronuclei chromosome spreading of first-cleavage embryos were prepared and chromosomal aberrations of paternal pronuclei were observed. The results showed that the frequency of chromosomal aberrations was highest irradiated at spermatic stage among different stages of spermatogenesis. The sequence of radiosensitivity in spermatogenesis was as follows: spermatids > mature sperm > spermatocyte > spermatogonia and stem spermatogonia. The frequencies of paternal chromosomal aberrations resulted from irradiation at spermatids and mature sperms were significantly higher than that in control. The reciprocal translocations of stem spermatogonia induced by 2 Gy X rays in those male mice were also examined in the preparations of diakinesis-metaphase I. The frequency of reciprocal translocations were 0.0429 per cell and significantly higher than that in control. The proportion of unbalanced gametes, resulting in lethal embryos after fertilization, was 0.02145 to be predicted. At the same time, the dominant lethality induced by X rays in stem spermatogonia was measured, being 0.0371. The frequency of dead fetuses in irradiation group was about twice as in control. The regression analysis was found that the reciprocal translocations was markedly related to the dominant lethality

  18. Carbon black nanoparticle exposure during middle and late fetal development induces immune activation in male offspring mice

    International Nuclear Information System (INIS)

    El-Sayed, Yasser S.; Shimizu, Ryuhei; Onoda, Atsuto; Takeda, Ken; Umezawa, Masakazu

    2015-01-01

    Increasing exposure to nanoparticles (NPs) has raised concerns regarding their health and safety profiles in humans and animals, especially in developing organisms, which may display increased sensitivity to NP toxicity. The present study examined the effects of gestational exposure to carbon black NP (CB-NP) on the development of the offspring immune system. Pregnant mice were exposed to CB-NP (95 μg/kg body weight) by intranasal instillation on gestational days 9 and 15. The thymus and spleen were collected from their offspring mice on postnatal day (PND) 1, 3 and 5. Thymocyte and splenocyte phenotypes were examined by determining the expression of cell-surface molecules using flow cytometry. Gene expression in the thymus and spleen was examined using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Prenatal exposure to CB-NP increased total thymocytes and their immunophenotypes (CD4 − CD8 − and CD4 + CD8 + cells). It also induced an increase in total lymphocytes, and CD4 − CD8 − , particularly CD3 − B220 − cells, at PND 5 in the spleen of newborn male offspring, reflecting the stimulation of immature splenocytes. Furthermore, mRNA expression of genes related to the induction of peripheral tolerance (i.e. thymic Traf6) was upregulated. These data suggest that respiratory exposure to CB-NP during middle and late gestation may have allergic or inflammatory effects in male offspring, and may provide initial information on the potential developmental immunotoxicity of nanoparticles

  19. Dominant lethal tests of male mice given 239Pu salt injections

    International Nuclear Information System (INIS)

    Luening, K.G.; Froelen, H.; Nilsson, A.

    1976-01-01

    To study the possible genetic effects of 239 Pu manifesting in dominant lethals, five test series (E1-E5) were performed. Males from an inbred CBA strain were given 239 Pu salt injections intravenously and mated weekly to 3 CBA females each for 12 to 24 weeks. Some interruptions in the mating scheme were made. For the first two test series (E1, E2) 239 Pu nitrate solution and 239 Pu citrate, used in E3-E5, were prepared. The solution was millipore filtered just prior to injection. Among a total of 10255 implants sired by males given Pu-nitrate in E1 and E2 no significant excess of intra-uterine death relative to 7216 control implants occurred. Test series E3-E5 with 60 males each, used three groups of 20, with one control group. In E3, 0.5 μCi and 0.1 μCi were given per male/group, respectively; in E4 and E5, 0.25 μCi and 0.05 μCi, respectively. The males given 0.5 μCi in E3 became successively sterile from the 7th week. The results in E3-E5 point in the same direction with significant excess of intra-uterine death in E3 and E5. In E4 the females from matings from the 9th, 14th and 16th week, and in E5 females from the 9th week, were allowed to litter to give F 1 offspring. Dominant lethal tests of F 1 males gave concordant results in all four samples, showing significantly excessive death in offspring to F 1 males whose fathers had received Pu. The excessive death was evenly distributed and did not indicate the presence of semisterile F 1 males. In tests of Pu-injected males and of F 1 males a remarkable excess of death in late stages of foetal development was observed. Such effects had never before been observed in this CBA strain in tests of extrinsic and intrinsic exposure to ionizing irradiation

  20. Municipal wastewater affects adipose deposition in male mice and increases 3T3-L1 cell differentiation

    International Nuclear Information System (INIS)

    Biasiotto, Giorgio; Zanella, Isabella; Masserdotti, Alice; Pedrazzani, Roberta; Papa, Matteo; Caimi, Luigi; Di Lorenzo, Diego

    2016-01-01

    Trace concentration of EDs (endocrine disrupting compounds) in water bodies caused by wastewater treatment plant effluents is a recognized problem for the health of aquatic organisms and their potential to affect human health. In this paper we show that continuous exposure of male mice from early development to the adult life (140 days) to unrestricted drinking of wastewater collected from a municipal sewage treatment plant, is associated with an increased adipose deposition and weight gain during adulthood because of altered body homeostasis. In parallel, bisphenol A (BPA) at the administration dose of 5 μg/kg/body weight, shows an increasing effect on total body weight and fat mass. In vitro, a solid phase extract (SPE) of the wastewater (eTW), caused stimulation of 3T3-L1 adipocyte differentiation at dilutions of 0.4 and 1 % in the final culture medium which contained a concentration of BPA of 40 nM and 90 nM respectively. Pure BPA also promoted adipocytes differentiation at the concentration of 50 and 80 μM. BPA effect in 3T3-L1 cells was associated to the specific activation of the estrogen receptor alpha (ERα) in undifferentiated cells and the estrogen receptor beta (ERβ) in differentiated cells. BPA also activated the Peroxisome Proliferator Activated Receptor gamma (PPARγ) upregulating a minimal 3XPPARE luciferase reporter and the PPARγ-target promoter of the aP2 gene in adipose cells, while it was not effective in preadipocytes. The pure estrogen receptor agonist diethylstilbestrol (DES) played an opposite action to that of BPA inhibiting PPARγ activity in adipocytes, preventing cell differentiation, activating ERα in preadipocytes and inhibiting ERα and ERβ regulation in adipocytes. The results of this work show that the drinking of chemically-contaminated wastewater promotes fat deposition in male mice and that EDs present in sewage are likely responsible for this effect through a nuclear receptor-mediated mechanism. - Highlights: • Sewage

  1. SPILANTHES ACMELLA AND PHYSICAL EXERCISE INCREASED TESTOSTERONE LEVELS AND OSTEOBLAST CELLS IN GLUCOCORTICOID-INDUCED OSTEOPOROSIS MALE MICE

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    Hening Laswati

    2015-08-01

    Full Text Available Background: Glucocorticoid-induced osteoporosis is leading cause of secondary osteoporosis by decreasing formation activity and increasing resorption activity. Spilanthes acmella, is one of Indonesia medicinal plants that contain of polyphenol and flavonoids. Previously in vitro study showed that buthanol and water fraction from this plant have increased alkaline phosphatase that known as marker of bone formation. The objective of this study to analyze the effect of Spilanthes acmella  and physical exercise in increasing testosterone and  osteoblast cells of femoral’s trabecular glucocorticoid-induced osteoporosis male mice. Method: This study using a posttest control group design, 36 male healthy mice (5 months old  were randomizely devided into 6 groups, there are : 1.Healthy control group (without induction dexamethaxone, 2.Osteoporosis groups (induction with dexamethaxone without treatment, 3.Positive control receive suspension alendronat, 4.70% Ethanol extract of Spilanthes acmella group, 5.Combination group of 70% extract ethanol of Spilanthes acmella and exercise, and 6.Exercise group  (walking using mice treadmill 10m/minute, 5-12 minutes 3 times a week. All of the intervention were given for 4 weeks. The serum levels of testosterone were determined using  immunoserology (ELISA and osteoblast cells were determined histomorphometry by light microscopy.  All statistical test were carried out using SPSS 23 and statistical significance was  set at p<0.05 for all analysis. The testosterone levels  between group were compared using Mann-Whitney test and osteoblast cells between group were compared with multiple comparison. Results: It showed that the alendronate group, combination group and the exercise group increasing testosterone level (p<0.05 from that osteoporotic group. There were also increasing osteoblast cells (p<0.05 in the alendronate group and combination group. There was no correlation between testosterone level and

  2. Municipal wastewater affects adipose deposition in male mice and increases 3T3-L1 cell differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Biasiotto, Giorgio; Zanella, Isabella [Laboratory of Biotechnology, Civic Hospital of Brescia, Brescia (Italy); Department of Molecular and Translational Medicine, University of Brescia, Brescia (Italy); Masserdotti, Alice [Laboratory of Biotechnology, Civic Hospital of Brescia, Brescia (Italy); Pedrazzani, Roberta [DIMI Department of Mechanical and Industrial Engineering, University of Brescia, via Branze 38, I-25123 Brescia (Italy); Papa, Matteo [DICATAM Department of Civil, Environmental, Architectural Engineering and Mathematics, University of Brescia, via Branze 43, I-25123 Brescia (Italy); Caimi, Luigi [Laboratory of Biotechnology, Civic Hospital of Brescia, Brescia (Italy); Department of Molecular and Translational Medicine, University of Brescia, Brescia (Italy); Di Lorenzo, Diego, E-mail: diego.dilorenzo@yahoo.it [Laboratory of Biotechnology, Civic Hospital of Brescia, Brescia (Italy)

    2016-04-15

    Trace concentration of EDs (endocrine disrupting compounds) in water bodies caused by wastewater treatment plant effluents is a recognized problem for the health of aquatic organisms and their potential to affect human health. In this paper we show that continuous exposure of male mice from early development to the adult life (140 days) to unrestricted drinking of wastewater collected from a municipal sewage treatment plant, is associated with an increased adipose deposition and weight gain during adulthood because of altered body homeostasis. In parallel, bisphenol A (BPA) at the administration dose of 5 μg/kg/body weight, shows an increasing effect on total body weight and fat mass. In vitro, a solid phase extract (SPE) of the wastewater (eTW), caused stimulation of 3T3-L1 adipocyte differentiation at dilutions of 0.4 and 1 % in the final culture medium which contained a concentration of BPA of 40 nM and 90 nM respectively. Pure BPA also promoted adipocytes differentiation at the concentration of 50 and 80 μM. BPA effect in 3T3-L1 cells was associated to the specific activation of the estrogen receptor alpha (ERα) in undifferentiated cells and the estrogen receptor beta (ERβ) in differentiated cells. BPA also activated the Peroxisome Proliferator Activated Receptor gamma (PPARγ) upregulating a minimal 3XPPARE luciferase reporter and the PPARγ-target promoter of the aP2 gene in adipose cells, while it was not effective in preadipocytes. The pure estrogen receptor agonist diethylstilbestrol (DES) played an opposite action to that of BPA inhibiting PPARγ activity in adipocytes, preventing cell differentiation, activating ERα in preadipocytes and inhibiting ERα and ERβ regulation in adipocytes. The results of this work show that the drinking of chemically-contaminated wastewater promotes fat deposition in male mice and that EDs present in sewage are likely responsible for this effect through a nuclear receptor-mediated mechanism. - Highlights: • Sewage

  3. Iron oxide nanoparticles modulate heat shock proteins and organ specific markers expression in mice male accessory organs

    Energy Technology Data Exchange (ETDEWEB)

    Sundarraj, Kiruthika; Raghunath, Azhwar; Panneerselvam, Lakshmikanthan; Perumal, Ekambaram, E-mail: ekas2009@buc.edu.in

    2017-02-15

    With increased industrial utilization of iron oxide nanoparticles (Fe{sub 2}O{sub 3}-NPs), concerns on adverse reproductive health effects following exposure have been immensely raised. In the present study, the effects of Fe{sub 2}O{sub 3}-NPs exposure in the seminal vesicle and prostate gland were studied in mice. Mice were exposed to two different doses (25 and 50 mg/kg) of Fe{sub 2}O{sub 3}-NPs along with the control and analyzed the expressions of heat shock proteins (HSP60, HSP70 and HSP90) and organ specific markers (Caltrin, PSP94, and SSLP1). Fe{sub 2}O{sub 3}-NPs decreased food consumption, water intake, and organo-somatic index in mice with elevated iron levels in serum, urine, fecal matter, seminal vesicle and prostate gland. FTIR spectra revealed alterations in the functional groups of biomolecules on Fe{sub 2}O{sub 3}-NPs treatment. These changes are accompanied by increased lactate dehydrogenase levels with decreased total protein and fructose levels. The investigation of oxidative stress biomarkers demonstrated a significant increase in reactive oxygen species, nitric oxide, lipid peroxidation, protein carbonyl content and glutathione peroxidase with a concomitant decrement in the glutathione and ascorbic acid in the male accessory organs which confirmed the induction of oxidative stress. An increase in NADPH-oxidase-4 with a decrease in glutathione-S-transferase was observed in the seminal vesicle and prostate gland of the treated groups. An alteration in HSP60, HSP70, HSP90, Caltrin, PSP94, and SSLP1 expression was also observed. Moreover, accumulation of Fe{sub 2}O{sub 3}-NPs brought pathological changes in the seminal vesicle and prostate gland of treated mice. These findings provide evidence that Fe{sub 2}O{sub 3}-NPs could be an environmental risk factor for reproductive disease. - Highlights: • Fe{sub 2}O{sub 3}-NPs caused adverse effects on the seminal vesicle and prostate gland of mice • Heat shock proteins (Hsp60, 70 and 90) were

  4. Estradiol enhances retention but not organization of hippocampus-dependent memory in intact male mice.

    Science.gov (United States)

    Al Abed, Alice Shaam; Sellami, Azza; Brayda-Bruno, Laurent; Lamothe, Valérie; Noguès, Xavier; Potier, Mylène; Bennetau-Pelissero, Catherine; Marighetto, Aline

    2016-07-01

    Because estrogens have mostly been studied in gonadectomized females, effects of chronic exposure to environmental estrogens in the general population are underestimated. Estrogens can enhance hippocampus-dependent memory through the modulation of information storage. However, declarative memory, the hippocampus-dependent memory of facts and events, demands more than abilities to retain information. Specifically, memory of repetitive events of everyday life such as "where I parked" requires abilities to organize/update memories to prevent proactive interference from similar memories of previous "parking events". Whether such organizational processes are estrogen-sensitive is unknown. We here studied, in intact young and aged adult mice, drinking-water (1μM) estradiol effects on both retention and organizational components of hippocampus-dependent memory, using a radial-maze task of everyday-like memory. Demand on retention vs organization was manipulated by varying the time-interval separating repetitions of similar events. Estradiol increased performance in young and aged mice under minimized organizational demand, but failed to improve the age-associated memory impairment and diminished performance in young mice under high organizational demand. In fact, estradiol prolonged mnemonic retention of successive events without improving organization abilities, hence resulted in more proactive interference from irrelevant memories. c-Fos imaging of testing-induced brain activations showed that the deterioration of young memory was associated with dentate gyrus dysconnectivity, reminiscent of that seen in aged mice. Our findings support the view that estradiol is promnesic but also reveal that such property can paradoxically impair memory. These findings have important outcomes regarding health issues relative to the impact of environmental estrogens in the general population. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Intragastric preloads of l-tryptophan reduce ingestive behavior via oxytocinergic neural mechanisms in male mice.

    Science.gov (United States)

    Gartner, Sarah N; Aidney, Fraser; Klockars, Anica; Prosser, Colin; Carpenter, Elizabeth A; Isgrove, Kiriana; Levine, Allen S; Olszewski, Pawel K

    2018-06-01

    Human and laboratory animal studies suggest that dietary supplementation of a free essential amino acid, l-tryptophan (TRP), reduces food intake. It is unclear whether an acute gastric preload of TRP decreases consumption and whether central mechanisms underlie TRP-driven hypophagia. We examined the effect of TRP administered via intragastric gavage on energy- and palatability-induced feeding in mice. We sought to identify central mechanisms through which TRP suppresses appetite. Effects of TRP on consumption of energy-dense and energy-dilute tastants were established in mice stimulated to eat by energy deprivation or palatability. A conditioned taste aversion (CTA) paradigm was used to assess whether hypophagia is unrelated to sickness. c-Fos immunohistochemistry was employed to detect TRP-induced activation of feeding-related brain sites and of oxytocin (OT) neurons, a crucial component of satiety circuits. Also, expression of OT mRNA was assessed with real-time PCR. The functional importance of OT in mediating TRP-driven hypophagia was substantiated by showing the ability of OT receptor blockade to abolish TRP-induced decrease in feeding. TRP reduced intake of energy-dense standard chow in deprived animals and energy-dense palatable chow in sated mice. Anorexigenic doses of TRP did not cause a CTA. TRP failed to affect intake of palatable yet calorie-dilute or noncaloric solutions (10% sucrose, 4.1% Intralipid or 0.1% saccharin) even for TRP doses that decreased water intake in thirsty mice. Fos analysis revealed that TRP increases activation of several key feeding-related brain areas, especially in the brain stem and hypothalamus. TRP activated hypothalamic OT neurons and increased OT mRNA levels, whereas pretreatment with an OT antagonist abolished TRP-driven hypophagia. We conclude that intragastric TRP decreases food and water intake, and TRP-induced hypophagia is partially mediated via central circuits that encompass OT. Copyright © 2018 Elsevier Ltd. All

  6. Raphanus sativus extract protects against Zearalenone induced reproductive toxicity, oxidative stress and mutagenic alterations in male Balb/c mice.

    Science.gov (United States)

    Ben Salah-Abbès, Jalila; Abbès, Samir; Abdel-Wahhab, Mosaad A; Oueslati, Ridha

    2009-04-01

    Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin produced by several species of Fusarium in cereals and agricultural products. It has been implicated in several mycotoxicosis in farm animals and in humans. There is unequivocal evidence of reproductive toxicity of ZEN in male mice although the mechanism of action is unknown. Several reports suggest that exposure to ZEN resulted in oxidative stress, genotoxicity and perturbation of reproductive parameters. Therefore, the aim of the current study was to evaluate the protective effects of aqueous extract of Raphanus sativus growing in Tunisia against ZEN-induced reproductive toxicity and oxidative stress. Fifty male Balb/c mice were divided into five groups and treated for 28 days as follows: the control group, olive oil-treated groups, another treated with ZEN (40 mg/kg b.w), the last one treated with R. sativus extract alone (15 mg/kg b.w) and the other with ZEN + R. sativus extract. Testis samples were collected for the epididymal sperm count, testosterone concentration, and MDA level, GPx, CAT and SOD activities. Blood samples were collected for different biochemical analyses. Also, RAPD-PCR method was performed to assess the antigenotoxic effect of the extract in germ cells. The results indicated that ZEN-induced toxicological effects in accordance to those reported in the literature: decreasing in the sperm number, testosterone level and antioxidant enzyme status. The RAPD-PCR analysis revealed an alteration in the DNA bands patterns between control and ZEN-treated mice. The extract alone, rich in many antioxidant compounds, was safe and succeeded in counteracting the oxidative stress and protect against the toxicity resulting from ZEN.

  7. Prenatal and early postnatal NOAEL-dose clothianidin exposure leads to a reduction of germ cells in juvenile male mice.

    Science.gov (United States)

    Yanai, Shogo; Hirano, Tetsushi; Omotehara, Takuya; Takada, Tadashi; Yoneda, Naoki; Kubota, Naoto; Yamamoto, Anzu; Mantani, Youhei; Yokoyama, Toshifumi; Kitagawa, Hiroshi; Hoshi, Nobuhiko

    2017-07-07

    Neonicotinoids are pesticides used worldwide. They bind to insect nicotinic acetylcholine receptors (nAChRs) with high affinity. We previously reported that clothianidin (CTD), one of the latest neonicotinoids, reduced antioxidant expression and induced germ cell death in the adult testis of vertebrates. Here, we investigated the male reproductive toxicity of prenatal and early postnatal exposure to CTD, because it is likely that developmental exposure more severely affects the testis compared to adults due to the absence of the blood-testis barrier. Pregnant C57BL/6 mice were given water gel blended with CTD (0, 10 or 50 mg/kg/day; no-observed-adverse-effect-level [NOAEL for mice]: 47.2 mg/kg/day) between gestational day 1 and 14 days post-partum. We then examined the testes of male offspring at postnatal day 14. The testis weights and the numbers of germ cells per seminiferous tubule were decreased in the CTD-50 group, and abnormal tubules containing no germ cells appeared. Nevertheless, the apoptotic cell number and proliferative activity were not significantly different between the control and CTD-exposed groups. There were no significant differences in the androgen-related parameters, such as the Leydig cell volume per testis, the Sertoli cell number and the tubule diameter. The present study is the first demonstration that in utero and lactational exposures to CTD at around the NOAEL for mice reduce the germ cell number, but our findings suggest that these exposures do not affect steroidogenesis in Leydig cells during prenatal or early postnatal life.

  8. Dietary exposure to the endocrine disruptor tolylfluanid promotes global metabolic dysfunction in male mice.

    Science.gov (United States)

    Regnier, Shane M; Kirkley, Andrew G; Ye, Honggang; El-Hashani, Essam; Zhang, Xiaojie; Neel, Brian A; Kamau, Wakanene; Thomas, Celeste C; Williams, Ayanna K; Hayes, Emily T; Massad, Nicole L; Johnson, Daniel N; Huang, Lei; Zhang, Chunling; Sargis, Robert M

    2015-03-01

    Environmental endocrine disruptors are implicated as putative contributors to the burgeoning metabolic disease epidemic. Tolylfluanid (TF) is a commonly detected fungicide in Europe, and previous in vitro and ex vivo work has identified it as a potent endocrine disruptor with the capacity to promote adipocyte differentiation and induce adipocytic insulin resistance, effects likely resulting from activation of glucocorticoid receptor signaling. The present study extends these findings to an in vivo mouse model of dietary TF exposure. After 12 weeks of consumption of a normal chow diet supplemented with 100 parts per million TF, mice exhibited increased body weight gain and an increase in total fat mass, with a specific augmentation in visceral adipose depots. This increased adipose accumulation is proposed to occur through a reduction in lipolytic and fatty acid oxidation gene expression. Dietary TF exposure induced glucose intolerance, insulin resistance, and metabolic inflexibility, while also disrupting diurnal rhythms of energy expenditure and food consumption. Adipose tissue endocrine function was also impaired with a reduction in serum adiponectin levels. Moreover, adipocytes from TF-exposed mice exhibited reduced insulin sensitivity, an effect likely mediated through a specific down-regulation of insulin receptor substrate-1 expression, mirroring effects of ex vivo TF exposure. Finally, gene set enrichment analysis revealed an increase in adipose glucocorticoid receptor signaling with TF treatment. Taken together, these findings identify TF as a novel in vivo endocrine disruptor and obesogen in mice, with dietary exposure leading to alterations in energy homeostasis that recapitulate many features of the metabolic syndrome.

  9. The effects of anticancer drugs TSA and GSK on spermatogenesis in male mice.

    Science.gov (United States)

    Song, Wen-Yan; Yang, Qing-Ling; Zhao, Wan-Li; Jin, Hai-Xia; Yao, Gui-Dong; Peng, Zhao-Feng; Shi, Sen-Lin; Yang, Hong-Yi; Zhang, Xiang-Yang; Sun, Ying-Pu

    2016-01-01

    The effect of anticancer drugs Trichostation A (TSA) and GSK2126458 (GSK) on genetic recombination of sperm meiosis in mice was investigated, and their clinical feasibility of fertility preservation in cancer patients was also assessed. Eighteen Kunming mice were randomly given TSA or GSK at the concentrations of 0, 0.1 and 0.2 umol/L for three months. Immunofluorescence was used to evaluate the genetic recombination of homologous chromosomes and fidelity of chromosome synapsis. Sperm density, motility and viability were also examined to investigate the spermatogenic function. The average number of MLH1 foci in each spermatocyte was greatly higher in TSA (0.1) group than that in control (PTSA (0.2) group (P>0.05). The frequency of SC with no MLH1 foci was lower while the frequency of SC with one MLH1 foci was higher in spermatocyte of mice with different doses of TSA compared with controls (PTSA (0.1) group was significant decreased compared with that in control (PTSA increased genetic recombination frequency of spermatocyte meiosis. GSK had no significant effect on genetic recombination frequency of spermatocyte meiosis and spermatogenic function.

  10. Corticosterone levels and behavioral changes induced by simultaneous exposure to chronic social stress and enriched environments in NMRI male mice.

    Science.gov (United States)

    Mesa-Gresa, Patricia; Ramos-Campos, Marta; Redolat, Rosa

    2016-05-01

    Environmental enrichment (EE) is an experimental model which is believed to counteract some of the effects induced by stressors, although few studies have exposed rodents simultaneously to EE and stress. Our aim was to compare the short- and long-term effects of different housing conditions in mice submitted to chronic stress. 128 NMRI male mice arrived at our laboratory on postnatal day (PND) 21. During Phase I (PND 28), animals were randomly assigned to four experimental conditions: 1) EE+STRESS: mice housed in EE and submitted to social stress (n=32); 2) EE+NO STRESS: mice housed in EE without stress (n=32); 3) SE+STRESS: mice maintained in standard conditions (SE) and submitted to social stress (n=32); and 4) SE+NO STRESS (n=32). At the end of Phase I (PND 77), one cohort of 32 animals was used for behavioral assessment whereas another cohort of 32 was sacrificed for corticosterone analysis. Results indicated that EE animals showed less body weight, higher water and food intake, diminished anxiety response and decreased motor and exploratory behavior than SE mice. Mice exposed to stress gained less body weight, showed higher food and fluid intake and displayed decreased exploratory behavior than non-stressed mice. Furthermore, EE+STRESS group displayed significantly higher corticosterone levels than EE+NO STRESS group whereas EE+NO STRESS group showed lower levels than SE+NO STRESS. On PND 83, Phase II of the study began. Animals (n=96) were assigned to two different housing conditions: EE (n=48) and SE (n=48). On PND 112, corticosterone analysis (n=32) and behavioral study (n=64) were done. The factor "Housing Phase II" reached statistical significance. Results indicated that EE animals showed lower body weight and higher fluid intake than SE group, as well as decreased anxiety. No clear effects on motor and exploratory behavior or learning were observed. When long-term effects were analyzed, results indicated that "Initial Housing" condition was significant

  11. Comparison of the effects of bisphenol A alone and in a combination with X-irradiation on sperm count and quality in male adult and pubescent mice.

    Science.gov (United States)

    Dobrzyńska, Małgorzata M; Jankowska-Steifer, Ewa A; Tyrkiel, Ewa J; Gajowik, Aneta; Radzikowska, Joanna; Pachocki, Krzysztof A

    2014-11-01

    Bisphenol A (BPA) is employed in the manufacturing of epoxy, polyester-styrene, and polycarbonate resins, which are used for the production of baby and water bottles and reusable containers, food and beverage packing, dental fillings and sealants. The study was designed to examine the effects of 8-week exposure (a full cycle of spermatogenesis) to BPA alone and in a combination with X-irradiation on the reproductive organs and germ cells of adult and pubescent male mice. Pzh:Sfis male mice were exposed to BPA (5, 10, and 20 mg/kg) or X-rays (0.05 Gy) or to a combination of both (0.05 Gy + 5 mg/kg bw BPA). The following parameters were examined: sperm count, sperm motility, sperm morphology, and DNA damage in male gametes. Both BPA and X-rays alone diminished sperm quality. BPA exposure significantly reduced sperm count in pubescent males compared to adult mice, with degenerative changes detected in seminiferous epithelium. This may suggest a higher susceptibility of germ cells of younger males to BPA action. Combined BPA with X-ray treatment enhanced the harmful effect induced by BPA alone in male germ cells of adult males, whereas low-dose irradiation showed sometimes protective or additive effects in pubescent mice. Copyright © 2013 Wiley Periodicals, Inc., a Wiley company.

  12. [Testicular testosterone production in male mice of inbred strains PT and CBA/Lac after a long-term period of stable social hierarchy].

    Science.gov (United States)

    Osadchuk, L V; Gutorova, N V; Kleshchev, M A

    2014-04-01

    Social dominance can alter testicular testosterone production, although there is pronounced variability in the relationship between social status and pattern of the testosterone response. The study designed to investigate how a long-term period of stable social hierarchy effects on testicular testosterone production in male mice of inbred strains PT and CBA/Lac. Paired males of different genotypes were housed together for 32 days beginning 38 day of age. Dyadic interactions of males generated dominance-subordination relationships during the first day after a social group has been produced and the social rank of each opponent was assessed by asymmetry in agonistic behaviour. Serum level of testosterone and its testicular content were evaluated in male mice of both inbred strains at 70 day of age after pair housing. Control animals were age- and genotype-matched single males that were housed in conventional cages. After a long-term period of pair housing, the serum testosterone level and its testicular content in males of both PT and CBA/Lac strains were not significantly different from the control. There were no significant differences in androgenic parameters between social ranks in male mice of both strains. The results indicate that in laboratory mice the pattern of testicular testosterone response to social hierarchy determined by a social situation, for example, a stability of social interactions, when the importance of aggressive competition for rank is minimal.

  13. Iron oxide nanoparticles modulate heat shock proteins and organ specific markers expression in mice male accessory organs.

    Science.gov (United States)

    Sundarraj, Kiruthika; Raghunath, Azhwar; Panneerselvam, Lakshmikanthan; Perumal, Ekambaram

    2017-02-15

    With increased industrial utilization of iron oxide nanoparticles (Fe 2 O 3 -NPs), concerns on adverse reproductive health effects following exposure have been immensely raised. In the present study, the effects of Fe 2 O 3 -NPs exposure in the seminal vesicle and prostate gland were studied in mice. Mice were exposed to two different doses (25 and 50 mg/kg) of Fe 2 O 3 -NPs along with the control and analyzed the expressions of heat shock proteins (HSP60, HSP70 and HSP90) and organ specific markers (Caltrin, PSP94, and SSLP1). Fe 2 O 3 -NPs decreased food consumption, water intake, and organo-somatic index in mice with elevated iron levels in serum, urine, fecal matter, seminal vesicle and prostate gland. FTIR spectra revealed alterations in the functional groups of biomolecules on Fe 2 O 3 -NPs treatment. These changes are accompanied by increased lactate dehydrogenase levels with decreased total protein and fructose levels. The investigation of oxidative stress biomarkers demonstrated a significant increase in reactive oxygen species, nitric oxide, lipid peroxidation, protein carbonyl content and glutathione peroxidase with a concomitant decrement in the glutathione and ascorbic acid in the male accessory organs which confirmed the induction of oxidative stress. An increase in NADPH-oxidase-4 with a decrease in glutathione-S-transferase was observed in the seminal vesicle and prostate gland of the treated groups. An alteration in HSP60, HSP70, HSP90, Caltrin, PSP94, and SSLP1 expression was also observed. Moreover, accumulation of Fe 2 O 3 -NPs brought pathological changes in the seminal vesicle and prostate gland of treated mice. These findings provide evidence that Fe 2 O 3 -NPs could be an environmental risk factor for reproductive disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Carcinogenesis in C57BL mice after multigeneration exposure of the male germinal line to tritium

    International Nuclear Information System (INIS)

    Mewissen, D.J.; Ugarte, A.S.; Rust, J.J.

    1986-01-01

    The occurrence of a heritable, multiple intestinal adenocarcinoma (HMIA) was observed in the offspring of an outcross between a male (or female) parent originating from our C57 Black/6M strain and his female (or male) mating counterpart originating from an experimental subline of the same strain, propagated with multigeneration exposure of the male parent to low-level tritium. Multiple intestinal malignancy was observed with a high-expression frequency in all animals examined in five subsequent generations, irrespective of the sex of the initial ascendant originating from the experimental subline, exposed to tritiated water. A digenic inheritance with partial penetrance is postulated, involving at least a two-stage process of tumorigenesis, namely, a dominant mutation at one locus and a second mutation to a recessive which, as long as it remained homozygous, prevented expression of the tumorigenic dominant gene. 10 refs., 2 tabs

  15. Increasing brain angiotensin converting enzyme 2 activity decreases anxiety-like behavior in male mice by activating central Mas receptors.

    Science.gov (United States)

    Wang, Lei; de Kloet, Annette D; Pati, Dipanwita; Hiller, Helmut; Smith, Justin A; Pioquinto, David J; Ludin, Jacob A; Oh, S Paul; Katovich, Michael J; Frazier, Charles J; Raizada, Mohan K; Krause, Eric G

    2016-06-01

    Over-activation of the brain renin-angiotensin system (RAS) has been implicated in the etiology of anxiety disorders. Angiotensin converting enzyme 2 (ACE2) inhibits RAS activity by converting angiotensin-II, the effector peptide of RAS, to angiotensin-(1-7), which activates the Mas receptor (MasR). Whether increasing brain ACE2 activity reduces anxiety by stimulating central MasR is unknown. To test the hypothesis that increasing brain ACE2 activity reduces anxiety-like behavior via central MasR stimulation, we generated male mice overexpressing ACE2 (ACE2 KI mice) and wild type littermate controls (WT). ACE2 KI mice explored the open arms of the elevated plus maze (EPM) significantly more than WT, suggesting increasing ACE2 activity is anxiolytic. Central delivery of diminazene aceturate, an ACE2 activator, to C57BL/6 mice also reduced anxiety-like behavior in the EPM, but centrally administering ACE2 KI mice A-779, a MasR antagonist, abolished their anxiolytic phenotype, suggesting that ACE2 reduces anxiety-like behavior by activating central MasR. To identify the brain circuits mediating these effects, we measured Fos, a marker of neuronal activation, subsequent to EPM exposure and found that ACE2 KI mice had decreased Fos in the bed nucleus of stria terminalis but had increased Fos in the basolateral amygdala (BLA). Within the BLA, we determined that ∼62% of GABAergic neurons contained MasR mRNA and expression of MasR mRNA was upregulated by ACE2 overexpression, suggesting that ACE2 may influence GABA neurotransmission within the BLA via MasR activation. Indeed, ACE2 overexpression was associated with increased frequency of spontaneous inhibitory postsynaptic currents (indicative of presynaptic release of GABA) onto BLA pyramidal neurons and central infusion of A-779 eliminated this effect. Collectively, these results suggest that ACE2 may reduce anxiety-like behavior by activating central MasR that facilitate GABA release onto pyramidal neurons within the

  16. Prenatal exposure to diesel exhaust particles and effect on the male reproductive system in mice

    DEFF Research Database (Denmark)

    Hemmingsen, Jette Gjerke; Hougaard, Karin Sørig; Talsness, Chris

    2009-01-01

    In utero exposure to diesel exhaust particles may reduce sperm production in adulthood. We investigated the effect of prenatal exposure to diesel exhaust particles on the male reproductive system and assessed endocrine disruption and regulation of aquaporin expression as possible mechanisms...... of action. Dams inhaled 20 mg/m(3) of diesel exhaust particle standard reference material 2975 (SRM2975) or clean air for 1h/day on day 7-19 during pregnancy. Male offspring were killed on day 170 after birth. The dams that had inhaled SRM2975 delivered offspring, which in adulthood had reduced daily sperm...

  17. Female-to-male sex reversal in mice caused by transgenic overexpression of Dmrt1

    DEFF Research Database (Denmark)

    Zhao, Liang; Svingen, Terje; Ting Ng, Ee

    2015-01-01

    for primary sex determination and instead maintains Sertoli cell phenotype in postnatal testes. Here, we report that enforced expression of Dmrt1 in XX mouse fetal gonads using a Wt1-BAC transgene system is sufficient to drive testicular differentiation and male secondary sex development. XX transgenic fetal...... into testicular cell types, including steroidogenic fetal Leydig cells and non-meiotic germ cells. As a consequence, male internal and external reproductive organs developed postnatally, with an absence of female reproductive tissues. These results reveal that Dmrt1 has retained its ability to act as the primary...

  18. Splenectomy reduces infarct volume and neuroinflammation in male but not female mice in experimental stroke

    Science.gov (United States)

    Dotson, Abby L.; Wang, Jianming; Saugstad, Julie; Murphy, Stephanie J.; Offner, Halina

    2014-01-01

    The peripheral immune response contributes to neurodegeneration after stroke yet little is known about how this process differs between males and females. The current study demonstrates that splenectomy prior to experimental stroke eliminates sex differences in infarct volume and activated brain monocytes/microglia. In the periphery of both sexes, activated T cells correlate directly with stroke outcome while monocytes are reduced by splenectomy only in males. This study provides new information about the sex specific mechanisms of the peripheral immune response in neurodegeneration after stroke and demonstrates the need for representation of both sexes in basic and clinical stroke research. PMID:25434281

  19. Raphe serotonin neuron-specific oxytocin receptor knockout reduces aggression without affecting anxiety-like behavior in male mice only.

    Science.gov (United States)

    Pagani, J H; Williams Avram, S K; Cui, Z; Song, J; Mezey, É; Senerth, J M; Baumann, M H; Young, W S

    2015-02-01

    Serotonin and oxytocin influence aggressive and anxiety-like behaviors, though it is unclear how the two may interact. That the oxytocin receptor is expressed in the serotonergic raphe nuclei suggests a mechanism by which the two neurotransmitters may cooperatively influence behavior. We hypothesized that oxytocin acts on raphe neurons to influence serotonergically mediated anxiety-like, aggressive and parental care behaviors. We eliminated expression of the oxytocin receptor in raphe neurons by crossing mice expressing Cre recombinase under control of the serotonin transporter promoter (Slc6a4) with our conditional oxytocin receptor knockout line. The knockout mice generated by this cross are normal across a range of behavioral measures: there are no effects for either sex on locomotion in an open-field, olfactory habituation/dishabituation or, surprisingly, anxiety-like behaviors in the elevated O and plus mazes. There was a profound deficit in male aggression: only one of 11 raphe oxytocin receptor knockouts showed any aggressive behavior, compared to 8 of 11 wildtypes. In contrast, female knockouts displayed no deficits in maternal behavior or aggression. Our results show that oxytocin, via its effects on raphe neurons, is a key regulator of resident-intruder aggression in males but not maternal aggression. Furthermore, this reduction in male aggression is quite different from the effects reported previously after forebrain or total elimination of oxytocin receptors. Finally, we conclude that when constitutively eliminated, oxytocin receptors expressed by serotonin cells do not contribute to baseline anxiety-like behaviors or maternal care. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  20. Comparative experimental studies on Trypanosoma isolates in mice and response to diminazene aceturate and isometamidium chloride treatment

    Directory of Open Access Journals (Sweden)

    Muluken Yayeh

    2018-02-01

    Full Text Available The current study was undertaken from December 2015 to May 2016 with the aim of determining and comparing the pathogenicity and response to diminazene aceturate (DA and isometamidium chloride (ISM treatment in experimentally infected mice with trypanosome isolates from Jawi and Birsheleko areas of northwest Ethiopia. A total of 42 mice were used for the experiment. These mice were randomly assigned in to 7 groups of 6 mice per group. Three of the groups (Group 1, 4 and 5 were inoculated with trypanosome isolated from Jawi and three other groups (Group-2, 6 and 7 were inoculated with trypanosome isolated from Birsheleko and the remaining one group (Group 3 was negative control. Each experimental mice were received 0.3 ml of positive blood at the 105 parasites/ml from donor animals intraperitoneally while negative control group were received 0.3 ml sterile water. The mice were clinically observed daily during the study period. Parameters including level of parasitaemia, body weight, PCV and hemoglobin value were recorded once per week for ten consecutive weeks post infection. Trypanocidal treatment was given on day 21 post infection when peak parasitaemia was detected in groups (Group 4-DA-Jawi, 5-ISM-Jawi, 6-DA-BRSH and 7-ISM-BRSH. The treatment doses for DA was at 28 mg/kg and for ISM at 4 mg/kg. In all experimental groups during study period when the mice showed severe clinical signs and at the end of the experiment they were euthanized with 70% ethanol for gross and histopathological examinations. The parameters measured during the study period revealed markers leading to pathological changes in all infected groups. Parasitaemia were detected early in the Jawi isolate infected groups compared to the Birsheleko groups. All infected mice showed clear clinical manifestation of depression, weight loss, reduction in feed intake and huddled together in the corner of the cage. Significant (P < 0.05 reduction was observed in the mean PCV and

  1. Cytosolic malic enzyme 1 (ME1 mediates high fat diet-induced adiposity, endocrine profile, and gastrointestinal tract proliferation-associated biomarkers in male mice.

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    Ahmed Al-Dwairi

    Full Text Available Obesity and associated hormonal disturbances are risk factors for colon cancer. Cytosolic Malic Enzyme (ME1 generates NADPH used for lipogenesis in gastrointestinal (GI, liver and adipose tissues. We have reported that inclusion of soy protein isolate (SPI in the diet lowered body fat content and colon tumor incidence of rats fed AIN-93G diet, while others have demonstrated SPI inhibition of rat hepatic ME1 expression. The present study examined the individual and combined effects of dietary SPI and absence of ME1 on: 1 serum concentrations of hormones implicated in colon cancer development, 2 expression of lipogenic and proliferation-associated genes in the mouse colon and small intestine, and 3 liver and adipose expression of lipogenic and adipocytokine genes that may contribute to colon cancer predisposition.Weanling wild type (WT and ME1 null (MOD-1 male mice were fed high-fat (HF, iso-caloric diets containing either casein (CAS or SPI as sole protein source for 5 wks. Somatic growth, serum hormone and glucose levels, liver and adipose tissue weights, GI tissue parameters, and gene expression were evaluated.The MOD-1 genotype and SPI-HF diet resulted in decreases in: body and retroperitoneal fat weights, serum insulin, serum leptin, leptin/adiponectin ratio, adipocyte size, colon mTOR and cyclin D1 mRNA abundance, and jejunum FASN mRNA abundance, when compared to WT mice fed CAS-HF. Regardless of diet, MOD-1 mice had reductions in liver weight, liver steatosis, and colon crypt depth, and increases in adipose tissue expression of IRS1 and IRS2, compared to WT mice. SPI-HF diet reduced ME1 gene expression only in retroperitoneal fat.Data suggest that the pharmacological targeting of ME1 or the inclusion of soy protein in the diet may provide avenues to reduce obesity and its associated pro-tumorigenic endocrine environment and improve insulin sensitivity, potentially disrupting the obesity-colon cancer connection.

  2. Neural stem cell isolation and culture from C57BL/6 mice

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    S Koirala

    2015-07-01

    Full Text Available INTRODUCTION A widely used in vitro culture, the neurosphere assay (NSA has provided a means to retrospectively identify neural progenitor cells as well as to determine both their selfrenewal capacity. Objective of study was to isolate and compare growth of the embryonic neuronal stem cell and adult neuronal stem cells in presence of Epidermal Growth Factor (EGF and Fibroblastic Growth Factor (FGF2. MATERIALS AND METHODS Embryonic neuronal stem cell were collected from cortical plate of dorsal telencephalon of fifteen C57BL/6 transgenic mice using stereoscopic microscope on 11th gestational day (GD. Adult mammalian neuronal stem cells taken from subventricular zone (SVZ of the lateral ventricles and subgranular layer of the dentate gyrus of the hippocampus were cultured. The growth for the neurosphere was then observed in interval of 24 and 72 hours. RESULT The adult stem cell culture showed few intact cells with high amount of debris and 9% heterogeneous sphere after 24 hours while only 20 % was observed at the end of 72 hours. Higher proliferation rate was observed in embryonic neurospheres than the adult stem cell culture. CONCLUSION Presence of EGF and basic FGF2 is essential for culture of neurospheres.DOI: http://dx.doi.org/10.3126/jcmsn.v10i2.12946 Journal of College of Medical Sciences-Nepal, 2014, Vol.10(2; 1-3

  3. Treatment of Experimental Acute Radiation Disease in Mice with Probiotics, Quinolones, and General Gnotobiological Isolation

    National Research Council Canada - National Science Library

    Korschunov, Valerji

    1998-01-01

    ...) on intestinal microflora, translocation, and mortality was studied in mice treated with 7.0 Gy radiation. Lactobacilli and bifidobacteria, selected by in vitro and in vivo methods, increased survival parameters of the mice...

  4. γ-Oryzanol protects pancreatic β-cells against endoplasmic reticulum stress in male mice.

    Science.gov (United States)

    Kozuka, Chisayo; Sunagawa, Sumito; Ueda, Rei; Higa, Moritake; Tanaka, Hideaki; Shimizu-Okabe, Chigusa; Ishiuchi, Shogo; Takayama, Chitoshi; Matsushita, Masayuki; Tsutsui, Masato; Miyazaki, Jun-ichi; Oyadomari, Seiichi; Shimabukuro, Michio; Masuzaki, Hiroaki

    2015-04-01

    Endoplasmic reticulum (ER) stress is profoundly involved in dysfunction of β-cells under high-fat diet and hyperglycemia. Our recent study in mice showed that γ-oryzanol, a unique component of brown rice, acts as a chemical chaperone in the hypothalamus and improves feeding behavior and diet-induced dysmetabolism. However, the entire mechanism whereby γ-oryzanol improves glucose metabolism throughout the body still remains unclear. In this context, we tested whether γ-oryzanol reduces ER stress and improves function and survival of pancreatic β-cells using murine β-cell line MIN6. In MIN6 cells with augmented ER stress by tunicamycin, γ-oryzanol decreased exaggerated expression of ER stress-related genes and phosphorylation of eukaryotic initiation factor-2α, resulting in restoration of glucose-stimulated insulin secretion and prevention of apoptosis. In islets from high-fat diet-fed diabetic mice, oral administration of γ-oryzanol improved glucose-stimulated insulin secretion on following reduction of exaggerated ER stress and apoptosis. Furthermore, we examined the impact of γ-oryzanol on low-dose streptozotocin-induced diabetic mice, where exaggerated ER stress and resultant apoptosis in β-cells were observed. Also in this model, γ-oryzanol attenuated mRNA level of genes involved in ER stress and apoptotic signaling in islets, leading to amelioration of glucose dysmetabolism. Taken together, our findings demonstrate that γ-oryzanol directly ameliorates ER stress-induced β-cell dysfunction and subsequent apoptosis, highlighting usefulness of γ-oryzanol for the treatment of diabetes mellitus.

  5. Gestational exposure to diethylstilbestrol alters cardiac structure/function, protein expression and DNA methylation in adult male mice progeny

    Energy Technology Data Exchange (ETDEWEB)

    Haddad, Rami, E-mail: rami.haddad@mail.mcgill.ca [Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 chemin Cote Ste Catherine, Montréal, Québec, Canada H3T 1E2 (Canada); Division of Experimental Medicine, Department of Medicine, McGill University, 850 Sherbrooke Street, Montréal, Québec, Canada H3A 1A2 (Canada); Kasneci, Amanda, E-mail: amanda.kasneci@mail.mcgill.ca [Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 chemin Cote Ste Catherine, Montréal, Québec, Canada H3T 1E2 (Canada); Mepham, Kathryn, E-mail: katherine.mepham@mail.mcgill.ca [Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 chemin Cote Ste Catherine, Montréal, Québec, Canada H3T 1E2 (Canada); Division of Experimental Medicine, Department of Medicine, McGill University, 850 Sherbrooke Street, Montréal, Québec, Canada H3A 1A2 (Canada); Sebag, Igal A., E-mail: igal.sebag@mcgill.ca [Division of Cardiology, Jewish General Hospital, 3755 chemin Cote Ste Catherine, Montréal, Québec, Canada H3T 1E2 (Canada); and others

    2013-01-01

    Pregnant women, and thus their fetuses, are exposed to many endocrine disruptor compounds (EDCs). Fetal cardiomyocytes express sex hormone receptors making them potentially susceptible to re-programming by estrogenizing EDCs. Diethylstilbestrol (DES) is a proto-typical, non-steroidal estrogen. We hypothesized that changes in adult cardiac structure/function after gestational exposure to the test compound DES would be a proof in principle for the possibility of estrogenizing environmental EDCs to also alter the fetal heart. Vehicle (peanut oil) or DES (0.1, 1.0 and 10.0 μg/kg/da.) was orally delivered to pregnant C57bl/6n dams on gestation days 11.5–14.5. At 3 months, male progeny were left sedentary or were swim trained for 4 weeks. Echocardiography of isoflurane anesthetized mice revealed similar cardiac structure/function in all sedentary mice, but evidence of systolic dysfunction and increased diastolic relaxation after swim training at higher DES doses. The calcium homeostasis proteins, SERCA2a, phospholamban, phospho-serine 16 phospholamban and calsequestrin 2, are important for cardiac contraction and relaxation. Immunoblot analyses of ventricle homogenates showed increased expression of SERCA2a and calsequestrin 2 in DES mice and greater molecular remodeling of these proteins and phospho-serine 16 phospholamban in swim trained DES mice. DES increased cardiac DNA methyltransferase 3a expression and DNA methylation in the CpG island within the calsequestrin 2 promoter in heart. Thus, gestational DES epigenetically altered ventricular DNA, altered cardiac function and expression, and reduced the ability of adult progeny to cardiac remodel when physically challenged. We conclude that gestational exposure to estrogenizing EDCs may impact cardiac structure/function in adult males. -- Highlights: ► Gestational DES changes cardiac SERCA2a and CASQ2 expression. ► Echocardiography identified systolic dysfunction and increased diastolic relaxation. ► DES

  6. Isolation of Trypanosoma brucei gambiense from cured and relapsed sleeping sickness patients and adaptation to laboratory mice.

    Directory of Open Access Journals (Sweden)

    Patient Pati Pyana

    Full Text Available BACKGROUND: Sleeping sickness due to Trypanosoma brucei (T.b. gambiense is still a major public health problem in some central African countries. Historically, relapse rates around 5% have been observed for treatment with melarsoprol, widely used to treat second stage patients. Later, relapse rates of up to 50% have been recorded in some isolated foci in Angola, Sudan, Uganda and Democratic Republic of the Congo (DRC. Previous investigations are not conclusive on whether decreased sensitivity to melarsoprol is responsible for these high relapse rates. Therefore we aimed to establish a parasite collection isolated from cured as well as from relapsed patients for downstream comparative drug sensitivity profiling. A major constraint for this type of investigation is that T.b. gambiense is particularly difficult to isolate and adapt to classical laboratory rodents. METHODOLOGY/PRINCIPAL FINDINGS: From 360 patients treated in Dipumba hospital, Mbuji-Mayi, D.R. Congo, blood and cerebrospinal fluid (CSF was collected before treatment. From patients relapsing during the 24 months follow-up, the same specimens were collected. Specimens with confirmed parasite presence were frozen in liquid nitrogen in a mixture of Triladyl, egg yolk and phosphate buffered glucose solution. Isolation was achieved by inoculation of the cryopreserved specimens in Grammomys surdaster, Mastomys natalensis and SCID mice. Thus, 85 strains were isolated from blood and CSF of 55 patients. Isolation success was highest in Grammomys surdaster. Forty strains were adapted to mice. From 12 patients, matched strains were isolated before treatment and after relapse. All strains belong to T.b. gambiense type I. CONCLUSIONS AND SIGNIFICANCE: We established a unique collection of T.b. gambiense from cured and relapsed patients, isolated in the same disease focus and within a limited period. This collection is available for genotypic and phenotypic characterisation to investigate the

  7. Chronic minocycline treatment improves social recognition memory in adult male Fmr1 knockout mice.

    Science.gov (United States)

    Yau, Suk Yu; Chiu, Christine; Vetrici, Mariana; Christie, Brian R

    2016-10-01

    Fragile X syndrome (FXS) is caused by a mutation in the Fmr1 gene that leads to silencing of the gene and a loss of its gene product, Fragile X mental retardation protein (FMRP). Some of the key behavioral phenotypes for FXS include abnormal social anxiety and sociability. Here we show that Fmr1 knock-out (KO) mice exhibit impaired social recognition when presented with a novel mouse, and they display normal social interactions in other sociability tests. Administering minocycline to Fmr1 KO mice throughout critical stages of neural development improved social recognition memory in the novel mouse recognition task. To determine if synaptic changes in the prefrontal cortex (PFC) could have played a role in this improvement, we examined PSD-95, a member of the membrane-associated guanylate kinase family, and signaling molecules (ERK1/2, and Akt) linked to synaptic plasticity in the PFC. Our analyses indicated that while minocycline treatment can enhance behavioral performance, it does not enhance expression of PSD-95, ERK1/2 or Akt in the PFC. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. A herbal medicine, saikokaryukotsuboreito, improves serum testosterone levels and affects sexual behavior in old male mice.

    Science.gov (United States)

    Zang, Zhi Jun; Ji, Su Yun; Dong, Wang; Zhang, Ya Nan; Zhang, Er Hong; Bin, Zhang

    2015-06-01

    Late-onset hypogonadism (LOH) is a clinical syndrome characterized with aging and declined serum testosterone levels. Sexual symptoms are also essential for the diagnosis of LOH. Testosterone replacement therapy is used widely to treat LOH. However, the side effects of it should not be ignored, such as fluid retention, hypertension and spermatogenic suppression. Therefore, alternate treatment modalities have been pursued. Herbal medicines used widely in China have achieved satisfying results with little side effects. Nonetheless, there are few pharmacological researches on them. In this study, 24-month-old mice were used as LOH animal models to explore the pharmacological effects of a herbal medicine, saikokaryukotsuboreito (SKRBT), on serum testosterone levels and sexual functions. Furthermore, the expression of steroidogenic acute regulatory (StAR) protein, a kind of rate-limiting enzyme of testosterone synthesis, was also examined. As a result, SKRBT improved the serum testosterone levels of these mice at a dose of 300 and 450 mg/kg. Multiple measures of sexual behavior were enhanced. The expression of StAR was also increased. Therefore, this study suggested that SKRBT can improve the serum testosterone levels by activating the expression of StAR and might be a viable option to treat sexual symptoms caused by LOH.

  9. γ-Aminobutyric acid ameliorates fluoride-induced hypothyroidism in male Kunming mice.

    Science.gov (United States)

    Yang, Haoyue; Xing, Ronge; Liu, Song; Yu, Huahua; Li, Pengcheng

    2016-02-01

    This study evaluated the protective effects of γ-aminobutyric acid (GABA), a non-protein amino acid and anti-oxidant, against fluoride-induced hypothyroidism in mice. Light microscope sample preparation technique and TEM sample preparation technique were used to assay thyroid microstructure and ultrastructure; enzyme immunoassay method was used to assay hormone and protein levels; immunohistochemical staining method was used to assay apoptosis of thyroid follicular epithelium cells. Subacute injection of sodium fluoride (NaF) decreased blood T4, T3 and thyroid hormone-binding globulin (TBG) levels to 33.98 μg/l, 3 2.8 ng/ml and 11.67 ng/ml, respectively. In addition, fluoride intoxication induced structural abnormalities in thyroid follicles. Our results showed that treatment of fluoride-exposed mice with GABA appreciably decreased metabolic toxicity induced by fluoride and restored the microstructural and ultrastructural organisation of the thyroid gland towards normalcy. Compared with the negative control group, GABA treatment groups showed significantly upregulated T4, T3 and TBG levels (42.34 μg/l, 6.54 ng/ml and 18.78 ng/ml, respectively; Plevel and apoptosis inhibition in thyroid follicular epithelial cells. To the best of our knowledge, this is the first study to establish the therapeutic efficacy of GABA as a natural antioxidant in inducing thyroprotection against fluoride-induced toxicity. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Nature of fatty acids in high fat diets differentially delineates obesity-linked metabolic syndrome components in male and female C57BL/6J mice

    Directory of Open Access Journals (Sweden)

    El Akoum Souhad

    2011-12-01

    Full Text Available Abstract Background Adverse effects of high-fat diets (HFD on metabolic homeostasis are linked to adipose tissue dysfunction. The goal of this study was to examine the effect of the HFD nature on adipose tissue activity, metabolic disturbances and glucose homeostasis alterations in male mice compared with female mice. Methods C57BL/6J mice were fed either a chow diet or HFD including vegetal (VD or animal (AD fat. Body weight, plasmatic parameters and adipose tissue mRNA expression levels of key genes were evaluated after 20 weeks of HFD feeding. Results HFD-fed mice were significantly heavier than control at the end of the protocol. Greater abdominal visceral fat accumulation was observed in mice fed with AD compared to those fed a chow diet or VD. Correlated with weight gain, leptin levels in systemic circulation were increased in HFD-fed mice in both sexes with a significant higher level in AD group compared to VD group. Circulating adiponectin levels as well as adipose tissue mRNA expression levels were significantly decreased in HFD-fed male mice. Although its plasma levels remained unchanged in females, adiponectin mRNA levels were significantly reduced in adipose tissue of both HFD-fed groups with a more marked decrease in AD group compared to VD group. Only HFD-fed male mice were diabetic with increased fasting glycaemia. On the other hand, insulin levels were only increased in AD-fed group in both sexes associated with increased resistin levels. VD did not induce any apparent metabolic alteration in females despite the increased weight gain. Peroxisome Proliferator-Activated Receptors gamma-2 (PPARγ2 and estrogen receptor alpha (ERα mRNA expression levels in adipose tissue were decreased up to 70% in HFD-fed mice but were more markedly reduced in male mice as compared with female mice. Conclusions The nature of dietary fat determines the extent of metabolic alterations reflected in adipocytes through modifications in the pattern of

  11. Fatigue and perceptual responses of heavier- and lighter-load isolated lumbar extension resistance exercise in males and females

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    Charlotte Stuart

    2018-03-01

    Full Text Available Background There is a lack of research considering acute fatigue responses to high- and low-load resistance training as well as the comparison between male and female responses. Furthermore, limited studies have considered fatigue response testing with the inclusion of perceptions of discomfort and exertion. Methods The present study included males (n = 9; 23.8 ± 6.4 years; 176.7 ± 6.2 cm; 73.9 ± 9.3 kg and females (n = 8; 21.3 ± 0.9 years; 170.5 ± 6.1 cm; 65.5 ± 10.8 kg who were assessed for differences in fatigue (i.e., loss of torque at maximal voluntary contraction (MVC immediately following isolated lumbar extension (ILEX exercise at heavy- (HL and light-(LL loads (80% and 50% MVC, respectively. Participants also reported perceptual measures of effort (RPE-E and discomfort (RPE-D between different resistance training protocols. Results Analysis of variance revealed significantly greater absolute and relative fatigue following LL compared to HL conditions (p < 0.001. Absolute fatigue significantly differed between males and females (p = 0.012, though relative fatigue was not significantly different (p = 0.160. However, effect sizes for absolute fatigue (HL; Males = −1.84, Females = −0.83; LL; Males = −3.11, Females = −2.39 and relative fatigue (HL; Males = −2.17, Females = −0.76; LL; Males = −3.36, Females = −3.08 were larger for males in both HL and LL conditions. RPE-E was maximal for all participants in both conditions, but RPE-D was significantly higher in LL compared to HL (p < 0.001 with no difference between males and females. Discussion Our data suggests that females do not incur the same degree of fatigue as males following similar exercise protocols, and indeed that females might be able to sustain longer exercise duration at the same relative loads. As such females should manipulate training variables accordingly, perhaps performing greater repetitions at a relative load, or using heavier relative

  12. Viral replication and lung lesions in BALB/c mice experimentally inoculated with avian metapneumovirus subgroup C isolated from chickens.

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    Li Wei

    Full Text Available Avian metapneumovirus (aMPV emerged as an important respiratory pathogen causing acute respiratory tract infection in avian species. Here we used a chicken aMPV subgroup C (aMPV/C isolate to inoculate experimentally BALB/c mice and found that the aMPV/C can efficiently replicate and persist in the lungs of mice for at least 21 days with a peak viral load at day 6 postinoculation. Lung pathological changes were characterized by increased inflammatory cells. Immunochemical assay showed the presence of viral antigens in the lungs and significant upregulation of pulmonary inflammatory cytokines and chemokines including MCP-1, MIP-1α, RANTES, IL-1β, IFN-γ, and TNF-α were detected following inoculation. These results indicate for the first time that chicken aMPV/C may replicate in the lung of mice. Whether aMPV/C has potential as zoonotic pathogen, further investigation will be required.

  13. Viral replication and lung lesions in BALB/c mice experimentally inoculated with avian metapneumovirus subgroup C isolated from chickens.

    Science.gov (United States)

    Wei, Li; Zhu, Shanshan; She, Ruiping; Hu, Fengjiao; Wang, Jing; Yan, Xu; Zhang, Chunyan; Liu, Shuhang; Quan, Rong; Li, Zixuan; Du, Fang; Wei, Ting; Liu, Jue

    2014-01-01

    Avian metapneumovirus (aMPV) emerged as an important respiratory pathogen causing acute respiratory tract infection in avian species. Here we used a chicken aMPV subgroup C (aMPV/C) isolate to inoculate experimentally BALB/c mice and found that the aMPV/C can efficiently replicate and persist in the lungs of mice for at least 21 days with a peak viral load at day 6 postinoculation. Lung pathological changes were characterized by increased inflammatory cells. Immunochemical assay showed the presence of viral antigens in the lungs and significant upregulation of pulmonary inflammatory cytokines and chemokines including MCP-1, MIP-1α, RANTES, IL-1β, IFN-γ, and TNF-α were detected following inoculation. These results indicate for the first time that chicken aMPV/C may replicate in the lung of mice. Whether aMPV/C has potential as zoonotic pathogen, further investigation will be required.

  14. Na+,K+-pump stimulation improves contractility in isolated muscles of mice with hyperkalemic periodic paralysis.

    Science.gov (United States)

    Clausen, Torben; Nielsen, Ole Bækgaard; Clausen, Johannes D; Pedersen, Thomas Holm; Hayward, Lawrence J

    2011-07-01

    In patients with hyperkalemic periodic paralysis (HyperKPP), attacks of muscle weakness or paralysis are triggered by K(+) ingestion or rest after exercise. Force can be restored by muscle work or treatment with β(2)-adrenoceptor agonists. A missense substitution corresponding to a mutation in the skeletal muscle voltage-gated Na(+) channel (Na(v)1.4, Met1592Val) causing human HyperKPP was targeted into the mouse SCN4A gene (mutants). In soleus muscles prepared from these mutant mice, twitch, tetanic force, and endurance were markedly reduced compared with soleus from wild type (WT), reflecting impaired excitability. In mutant soleus, contractility was considerably more sensitive than WT soleus to inhibition by elevated [K(+)](o). In resting mutant soleus, tetrodotoxin (TTX)-suppressible (22)Na uptake and [Na(+)](i) were increased by 470 and 58%, respectively, and membrane potential was depolarized (by 16 mV, P Na(+),K(+) pump-mediated (86)Rb uptake was 83% larger than in WT. Salbutamol stimulated (86)Rb uptake and reduced [Na(+)](i) both in mutant and WT soleus. Stimulating Na(+),K(+) pumps with salbutamol restored force in mutant soleus and extensor digitorum longus (EDL). Increasing [Na(+)](i) with monensin also restored force in soleus. In soleus, EDL, and tibialis anterior muscles of mutant mice, the content of Na(+),K(+) pumps was 28, 62, and 33% higher than in WT, respectively, possibly reflecting the stimulating effect of elevated [Na(+)](i) on the synthesis of Na(+),K(+) pumps. The results confirm that the functional disorders of skeletal muscles in HyperKPP are secondary to increased Na(+) influx and show that contractility can be restored by acute stimulation of the Na(+),K(+) pumps. Calcitonin gene-related peptide (CGRP) restored force in mutant soleus but caused no detectable increase in (86)Rb uptake. Repeated excitation and capsaicin also restored contractility, possibly because of the release of endogenous CGRP from nerve endings in the isolated

  15. Meiotic behaviour and spermatogenesis in male mice heterozygous for translocation types also occurring in man

    International Nuclear Information System (INIS)

    Nijhoff, J.H.

    1981-01-01

    In this thesis a start was made with meiotic observations of mouse translocation types - a Robertsonian translocation and a translocation between a metacentric and an acrocentric chromosome - which also occur in man. As an exogeneous factor of possible influence, the meiotic effects of two types of radiation (fission neutrons and X-rays) administered at relatively low doses 2 and 3 hours before prometaphase-metaphase II (probably during metaphase-anaphase I), were determined in Rb4Bnr/+-males. (Auth.)

  16. Long term rebaudioside A treatment does not alter circadian activity rhythms, adiposity, or insulin action in male mice.

    Directory of Open Access Journals (Sweden)

    Thomas H Reynolds

    Full Text Available Obesity is a major public health problem that is highly associated with insulin resistance and type 2 diabetes, two conditions associated with circadian disruption. To date, dieting is one of the only interventions that result in substantial weight loss, but restricting caloric intake is difficult to maintain long-term. The use of artificial sweeteners, particularly in individuals that consume sugar sweetened beverages (energy drinks, soda, can reduce caloric intake and possibly facilitate weight loss. The purpose of the present study was to examine the effects of the artificial sweetener, rebaudioside A (Reb-A, on circadian rhythms, in vivo insulin action, and the susceptibility to diet-induced obesity. Six month old male C57BL/6 mice were assigned to a control or Reb-A (0.1% Reb-A supplemented drinking water group for six months. Circadian wheel running rhythms, body weight, caloric intake, insulin action, and susceptibility to diet-induced obesity were assessed. Time of peak physical activity under a 12:12 light-dark (LD cycle, mean activity levels, and circadian period in constant dark were not significantly different in mice that consumed Reb-A supplemented water compared to normal drinking water, indicating that circadian rhythms and biological clock function were unaltered. Although wheel running significantly reduced body weight in both Reb-A and control mice (P = 0.0001, consuming Reb-A supplemented water did not alter the changes in body weight following wheel running (P = 0.916. In vivo insulin action, as assessed by glucose, insulin, and pyruvate tolerance tests, was not different between mice that consumed Reb-A treated water compared to normal drinking water. Finally, Reb-A does not appear to change the susceptibility to diet-induced obesity as both groups of mice gained similar amounts of body weight when placed on a high fat diet. Our results indicate that consuming Reb-A supplemented water does not promote circadian disruption

  17. Neuroendocrine stress reactivity of male C57BL/6N mice following chronic oral corticosterone exposure during adulthood or adolescence.

    Science.gov (United States)

    Shahanoor, Ziasmin; Sultana, Razia; Baker, Madelyn R; Romeo, Russell D

    2017-12-01

    Adolescence is associated with the maturation of the hypothalamic-pituitary-adrenal (HPA) axis, the major neuroendocrine axis mediating the hormonal stress response. Adolescence is also a period in development marked by a variety of stress-related vulnerabilities, including psychological and physiological dysfunctions. Many of these vulnerabilities are accompanied by a disrupted HPA axis. In adult mice, a model of disrupted HPA function has been developed using oral chronic corticosterone administration via the drinking water, which results in various physiological and neurobehavioral abnormalities, including changes in stress reactivity and anxiety-like behaviors. In an effort to further complement and extend this model, we tested the impact of HPA disruption in adolescent mice. We also examined whether this disruption led to different outcomes depending on whether the treatment happened during adolescence or adulthood. In the current set of experiments, we exposed adult (70days of age) or adolescent (30days of age) male C57BL/6N mice to 4 weeks of either 0 or 25μg/ml oral corticosterone via their drinking water. We measured body weight during treatment and plasma corticosterone levels and activation of the paraventricular nucleus (PVN), as indexed by FOS immunohistochemistry, before and after a 30min session of restraint stress. Our data indicate that adolescent animals exposed to chronic corticosterone showed weight loss during treatment, an effect not observed in adults. Further, we found stress failed to elevate plasma corticosterone levels in treated mice, regardless of whether exposure occurred in adulthood or adolescence. Despite this reduced hormonal responsiveness, we found significant neural activation in the PVN of both adult- and adolescent-treated mice, indicating a dissociation between stress-induced peripheral and central stress responses following chronic corticosterone exposure. Moreover, stress-induced neural activation in the PVN was unaffected

  18. Isolated oestrogen deficiency in male 30-year-old: persistent growth plates with severe osteopenia

    International Nuclear Information System (INIS)

    Smith, T.; Roberts, J.; Howman-Giles, R.; Cowell, C.; Jeremy, R.

    2000-01-01

    Full text: A 31-year-old male presented with right rib pain and generalised skeletal symptoms. He has a past history of multiple fractures following trauma. No history of childhood fractures. Asthma (No steroids). A product of a consanguineous marriage, he has one child aged 7. Examination showed 178.6cm male with normal sexual characteristics. No abnormality detected apart from tenderness over right ribs. Bone scan showed active growth plates and right and left rib fractures. X-rays demonstrated a bone age of 15 1/2 - 16 yrs and a compression fracture of L2. His bone mineral density is severely reduced. Metabolic investigations revealed Testosterone 27.4 nmol (N 11-35), oestradiol < 70 pmol/L, ultrasensitive assay 14 and 17 pmol/L (consistent with 8-year-old male), LH N, FSH N, 46 XY Karyotype. Alkaline phosphatase. 148 (N<120), Normal glucose tolerance test. This patient illustrates a very rare condition of oestrogen deficiency in a male, probably due to aromatase deficiency. This enzyme converts testosterone to oestradiol. It illustrates the role of oestrogen in fusing growth plates and maintaining bone mass in males with otherwise normal androgen levels. A similar clinical picture can result from an oestrogen receptor abnormality. Copyright (2000) The Australian and New Zealand Society of Nuclear Medicine Inc

  19. Clonality and distribution of clinical Ureaplasma isolates recovered from male patients and infertile couples in China.

    Science.gov (United States)

    Ruan, Zhi; Yang, Ting; Shi, Xinyan; Kong, Yingying; Xie, Xinyou; Zhang, Jun

    2017-01-01

    Ureaplasma spp. have gained increasing recognition as pathogens in both adult and neonatal patients with multiple clinical presentations. However, the clonality of this organism in the male population and infertile couples in China is largely unknown. In this study, 96 (53 U. parvum and 43 U. urealyticum) of 103 Ureaplasma spp. strains recovered from genital specimens from male patients and 15 pairs of infertile couples were analyzed using multilocus sequence typing (MLST)/expanded multilocus sequence typing (eMLST) schemes. A total of 39 sequence types (STs) and 53 expanded sequence types (eSTs) were identified, with three predominant STs (ST1, ST9 and ST22) and eSTs (eST16, eST41 and eST82). Moreover, phylogenetic analysis revealed two distinct clusters that were highly congruent with the taxonomic differences between the two Ureaplasma species. We found significant differences in the distributions of both clusters and sub-groups between the male and female patients (P Ureaplasma spp. The present study also attained excellent agreement of the identification of both Ureaplasma species between paired urine and semen specimens from the male partners (k > 0.80). However, this concordance was observed only for the detection of U. urealyticum within the infertile couples. In conclusion, the distributions of the clusters and sub-groups significantly differed between the male and female patients. U. urealyticum is more likely to transmit between infertile couples and be associated with clinical manifestations by the specific epidemic clonal lineages.

  20. Serum concentrations of buprenorphine after oral and parenteral administration in male mice

    DEFF Research Database (Denmark)

    Kalliokoski, Otto; Jacobsen, Kirsten R; Hau, Jann

    2011-01-01

    Buprenorphine is the most commonly used drug for peri-operative pain relief in laboratory rodents. The systemic concentrations of buprenorphine were measured in mice following administration intravenously (IV), subcutaneously (SC), orally by gavage and by voluntary ingestion, to determine the post-administration...... serum concentration of buprenorphine. Voluntarily ingested buprenorphine resulted in long-lasting high serum concentrations, as did oral gavage administration (24h serum concentration: 110ngh/mL for both routes of administration). In contrast, buprenorphine administered parenterally remained...... in the circulation for a substantially shorter time (24h serum concentration for IV and SC were 40ngh/mL and 30ngh/mL, respectively). This marked difference was probably due to the higher dose used for oral administration, which is regarded necessary for sufficient analgesic effect, and to the slower absorption...

  1. Anticonvulsant properties of the total alkaloid fraction of Rauvolfia ligustrina Roem. et Schult. in male mice

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    Lucindo J. Quintans-Júnior

    Full Text Available Rauvolfia ligustrina Roem et. Schult (Apocynaceae, commonly known as "paratudo" and "arrebenta-boi" is a small tree found in Brazilian Northeastern. Previous studies have demonstrated depressant and anticonvulsant properties of the ethanol extract of Rauvolfia ligustrina. The aim of the present study was the determination of the lethal dose 50% (LD50 and the effects of total alkaloid fraction (TAF of the aerial parts of R. ligustrina in animal models of convulsion. It was found that the acute toxicity of TAF was 127.8 (112.5-145.2 mg/kg (i.p. in mice. TAF (20 mg/kg, ip significantly increased (p < 0.05 the latencies of clonic seizures induced by pentylenetetrazol (PTZ and picrotoxin (PIC. However, TAF did not protect the animals in maximal electroshock (MES induced seizures. These results suggest that TAF of R. ligustrina possesses anticonvulsant properties.

  2. Elevated Hypothalamic Glucocorticoid Levels Are Associated With Obesity and Hyperphagia in Male Mice.

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    Sefton, Charlotte; Harno, Erika; Davies, Alison; Small, Helen; Allen, Tiffany-Jayne; Wray, Jonathan R; Lawrence, Catherine B; Coll, Anthony P; White, Anne

    2016-11-01

    Glucocorticoid (Gc) excess, from endogenous overproduction in disorders of the hypothalamic-pituitary-adrenal axis or exogenous medical therapy, is recognized to cause adverse metabolic side effects. The Gc receptor (GR) is widely expressed throughout the body, including brain regions such as the hypothalamus. However, the extent to which chronic Gcs affect Gc concentrations in the hypothalamus and impact on GR and target genes is unknown. To investigate this, we used a murine model of corticosterone (Cort)-induced obesity and analyzed Cort levels in the hypothalamus and expression of genes relevant to Gc action. Mice were administered Cort (75 μg/mL) or ethanol (1%, vehicle) in drinking water for 4 weeks. Cort-treated mice had increased body weight, food intake, and adiposity. As expected, Cort increased plasma Cort levels at both zeitgeber time 1 and zeitgeber time 13, ablating the diurnal rhythm. Liquid chromatography dual tandem mass spectrometry revealed a 4-fold increase in hypothalamic Cort, which correlated with circulating levels and concentrations of Cort in other brain regions. This occurred despite decreased 11β-hydroxysteroid dehydrogenase (Hsd11b1) expression, the gene encoding the enzyme that regenerates active Gcs, whereas efflux transporter Abcb1 mRNA was unaltered. In addition, although Cort decreased hypothalamic GR (Nr3c1) expression 2-fold, the Gc-induced leucine zipper (Tsc22d3) mRNA increased, which indicated elevated GR activation. In keeping with the development of hyperphagia and obesity, Cort increased Agrp, but there were no changes in Pomc, Npy, or Cart mRNA in the hypothalamus. In summary, chronic Cort treatment causes chronic increases in hypothalamic Cort levels and a persistent elevation in Agrp, a mediator in the development of metabolic disturbances.

  3. Dose-response for X-ray induction of myeloid leukaemia in male CBA/H mice

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    Mole, R H; Papworth, D G; Corp, M J [Medical Research Council, Harwell (UK). Radiobiological Research Unit

    1983-02-01

    The form of the dose-response for induction of malignant diseases in vivo by ionizing radiation is not yet established in spite of its scientific interest and its practical importance. Considerably extended observations have confirmed that the dose-response for acute myeloid leukaemia induced in male CBA/H mice by X-ray exposure is highly curvilinear. The dose-response was well fitted by the expression aD/sup 2/esup(-..gamma..D) (D = dose) in agreement with induction at the cellular level in proportion to D/sup 2/ over the whole dose range 0.25-6.0 Gy. The factor esup(-..gamma..D) accounts for the inescapable concomitant inactivating action of the inducing irradiation. The quantitative aspects of induction of myeloid leukaemia by ionizing radiation are unlike the induction of genetic mutation or cell inactivation and suggest that interaction of two adjoining cells is an essential element in radiation leukaemogenesis.

  4. Protective effect of vitamins C and E on Gamma radiation induced Genetic injuries in male mice germ cells

    International Nuclear Information System (INIS)

    Anwar, W.A.; El-Daway, H.A.E.; Tawfik, S.S.M.

    1999-01-01

    The effects of vitamins C and E on meiotic chromosomal metaphase-8 at diakinesis of the mouse to 3 Gy of whole body gamma- irradiation were studied. These vitamins were injected intraperitoneally as acute doses 2 hr before irradiation. Both vitamins significantly reduced the frequencies of chromosomal aberration in spermatic germ cells. The protective effect of vitamin E was greater than that afforded by vitamin C. A combined treatment of both vitamins resulted in additional protection over that offered by each vitamine alone. In all animal groups the most frequent aberration found was translocation in the from of either ring four (R IV) or chain four (C IV). The percentage of each or them was significantly increased in male mice sacrificed after 15 days post-irradiation. Other types of aberrations as autosomal univalent, X-Gamma univalent and polyploidy were rarely present

  5. Cross-generational impact of a male murine pheromone 2-sec-butyl-4,5-dihydrothiazole in female mice

    Science.gov (United States)

    Koyama, Sachiko; Soini, Helena A.; Wager-Miller, James; Alley, William R.; Pizzo, Matthew J.; Rodda, Cathleen; Alberts, Jeffrey; Crystal, Jonathon D.; Lai, Cary; Foley, John; Novotny, Milos V.

    2015-01-01

    The current understanding of the activity of mammalian pheromones is that endocrine and behavioural effects are limited to the exposed individuals. Here, we demonstrate that the nasal exposure of female mice to a male murine pheromone stimulates expansion of mammary glands, leading to prolonged nursing of pups. Subsequent behavioural testing of the pups from pheromone-exposed dams exhibited enhanced learning. Sialic acid components in the milk are known to be involved in brain development. We hypothesized that the offspring might have received more of this key nutrient that promotes brain development. The mRNA for polysialyltransferase, which produces polysialylated neural cell adhesion molecules related to brain development, was increased in the brain of offspring of pheromone-exposed dams at post-natal day 10, while it was not different at embryonic stages, indicating possible differential brain development during early post-natal life. PMID:26136453

  6. Excessive Vitamin E Intake Does Not Cause Bone Loss in Male or Ovariectomized Female Mice Fed Normal or High-Fat Diets.

    Science.gov (United States)

    Ikegami, Hiroko; Kawawa, Rie; Ichi, Ikuyo; Ishikawa, Tomoko; Koike, Taisuke; Aoki, Yoshinori; Fujiwara, Yoko

    2017-10-01

    Background: Animal studies on the effects of vitamin E on bone health have yielded conflicting and inconclusive results, and to our knowledge, no studies have addressed the effect of vitamin E on bone in animals consuming a high-fat diet (HFD). Objective: This study aimed to evaluate the effect of excessive vitamin E on bone metabolism in normal male mice and ovariectomized female mice fed a normal diet (ND) or HFD. Methods: In the first 2 experiments, 7-wk-old male mice were fed an ND (16% energy from fat) containing 75 (control), 0 (vitamin E-free), or 1000 (high vitamin E) mg vitamin E/kg (experiment 1) or an HFD (46% energy from fat) containing 0, 200, 500, or 1000 mg vitamin E/kg (experiment 2) for 18 wk. In the third experiment, 7-wk-old sham-operated or ovariectomized female mice were fed the ND (75 mg vitamin E/kg) or HFD containing 0 or 1000 mg vitamin E/kg for 8 wk. At the end of the feeding period, blood and femurs were collected to measure bone turnover markers and analyze histology and microcomputed tomography. Results: In experiments 1 and 2, vitamin E intake had no effect on plasma alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) activity, or bone formation, resorption, or volume in femurs in mice fed the ND or HFDs. In experiment 3, bone volume was significantly reduced (85%) in ovariectomized mice compared with that in sham-operated mice ( P vitamin E/kg. Conclusions: The results suggest that excess vitamin E intake does not cause bone loss in normal male mice or in ovariectomized or sham-operated female mice, regardless of dietary fat content. © 2017 American Society for Nutrition.

  7. In vivo toxicity of the culturable marine cyanobacterium Geitlerinema pseudacutissimum CNP 1019 extract on male Swiss albino mice (Mus musculus).

    Science.gov (United States)

    Maruthanayagam, Veerabadhran; Nagarajan, Manivel; Sundararaman, Muthuraman

    2014-01-01

    In this study, we investigated the in vivo toxicity of Geitlerinema pseudacutissimum CNP 1019 organic extract in a murine host. A single intraperitoneal injection of 1 g extract kg⁻¹ body weight (BW) did not exhibit mortality, whereas 3 g extract kg⁻¹ BW (approximate lethal dose) resulted in mortality within 5 days. To perform subchronic exposure toxicity analyses (i.e., daily exposure for a total of 14 days), a maximum concentration of ≤1 g extract kg⁻¹ BW was used. Subchronic toxicity studies in the treated mice, showed fluctuations of feed intake, loss of body weight, increase in specific activity of serum lactate dehydrogenase, alanine aminotransferase and decrease in whole serum protein concentration. LDH isoenzyme expression was found, and levels of the various isoforms were decreased as a result of the treatment. Histopathology studies in liver, kidney, and spleen isolated from the treated mice showed the presence of necrotic debris, hemorrhage, and micronuclei revealing the toxicity of the extract. The dose-dependent alterations in biochemical parameters in conjunction with the histological lesions noted in the animals treated with the prepared extract illustrate the likely potential toxicity to mammals from any encounters with the studied cyanobacterium.

  8. Detailed immunohistochemical characterization of temporal and spatial progression of Alzheimer's disease-related pathologies in male triple-transgenic mice

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    Bowers William J

    2008-08-01

    Full Text Available Abstract Background Several transgenic animal models genetically predisposed to develop Alzheimer's disease (AD-like pathology have been engineered to facilitate the study of disease pathophysiology and the vetting of potential disease-modi