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Sample records for resident male mice

  1. Corticosterone response in a resident-intruder-paradigm depends on social state and coping style in adolescent male Balb-C mice.

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    Pletzer, Belinda; Klimesch, Wolfgang; Oberascher-Holzinger, Karin; Kerschbaum, Hubert H

    2007-10-01

    Social stressors modulate the hypothalamic-pituitary-adrenal axis in rodents. However, reports on the association between corticosterone level and behavioural responses to the stressor are ambivalent. This may depend on the experimental paradigm, species- and strain-differences, duration of exposure to the stressor, but also on using either the social state (dominant or subordinate) or the coping style (proactive or passive) of an animal to correlate the corticosterone level with. We used male Balb-C mice in a resident-intruder paradigm. Adolescent intruders (aged five to eight weeks) were transferred into the cage of an adult resident (aged about four month) for five minutes. The interactions were video-taped for behavioural analysis. Ten minutes after the encounters, intruders were sacrificed and blood samples were collected. Dominant intruders showed offensive behaviours (attack, chase, tail tracking) and won most of the fights, whereas subordinate intrudes showed mainly submissive behaviours (flight, freezing) and were further classified into active and passive subordinates. Active subordinates displayed significantly more flight-behaviour than passive subordinates. Dominant intruders showed significantly higher post-stress levels of corticosterone than subordinates, which did not differ from control mice, which experienced five minutes of novel-cage exposure. Comparing all three behavioural phenotypes we found the lowest corticosterone levels in active subordinates. Social state significantly affects the HPA-axis response to acute social stressors.

  2. 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.

  3. Investigating Black Gay Male Undergraduates' Experiences in Campus Residence Halls

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    Strayhorn, Terrell L.; Mullins, Taris G.

    2012-01-01

    This qualitative study sought to understand the challenges that Black gay male undergraduates confront in campus residence halls and the supports that enabled their success in facing them. Drawing on in-depth interviews with 29 participants, we found that Black gay men report varied encounters with subtle and overt forms of racism among White…

  4. RETARDATION OF MUSCLE GROWTH IN CASTRATED MALE MICE:

    African Journals Online (AJOL)

    the absolute weights and the muscle mass indices of the muscles of castrated males were ... Muscles, Mice. INTRODUCTION rat levator ani muscles. It was noted that the hypertrophy of the muscle was a result. Muscles of adult male mice are invariably of increase in myofibrilar material .... (1976): Skeletal muscle cellularity.

  5. 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 ...

  6. 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

  7. Aiming low: A resident male's rank predicts takeover success by challenging males in Yunnan snub-nosed monkeys.

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    Zhu, Pingfen; Ren, Baoping; Garber, Paul A; Xia, Fan; Grueter, Cyril C; Li, Ming

    2016-09-01

    In many primate species that form one-male breeding units (OMUs), the threat of a takeover by a bachelor male represents a major challenge to group stability and individual reproductive success. In the case of snub-nosed monkeys, which live in large multilevel or modular societies (MLS) comprising several OMUs that travel, feed and rest together and as well as one or more all male units (AMUs), the process by which rival males challenge resident OMU males for access to females is poorly understood. From September 2012 to October 2013, we recorded 48 cases in which rival males visited an OMU in a MLS of Yunnan snub-nosed monkeys (Rhinopithecus bieti) inhabiting the Baimaxueshan National Nature Reserve, Yunnan Province, China. In 40 cases, rival males engaged in mild agonistic interactions (approaching, staring, teeth-baring and chasing) but failed to take over the group; we counted these visits as failed takeovers, recognizing that they may nevertheless allow rival males to assess the competitive ability of residents. During eight successful takeovers, however, there was severe physical aggression between challenging and resident males, with serious injuries to participants. We found that neither the number of adult and subadult females in an OMU, the number of non-pregnant, non-lactating adult females in an OMU, nor the rank of a resident male relative to other resident males in the MLS predicted which OMU a challenging male targeted for takeover. However, a resident male's rank significantly predicted whether takeover attempts were successful. Specifically, challenging males were more successful in displacing a lower-ranking resident male than a higher-ranking male. Given that a Yunnan snub-nosed monkey MLS may contain as many as 40 resident and 36 bachelor males, continued research is required to determine the set of factors that enable resident males to maintain high social rank and successfully defend their harems. Am. J. Primatol. 78:974-982, 2016. © 2016

  8. Male-male combats in a polymorphic lizard: residency and size, but not color, affect fighting rules and contest outcome.

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    Sacchi, Roberto; Pupin, Fabio; Gentilli, Augusto; Rubolini, Diego; Scali, Stefano; Fasola, Mauro; Galeotti, Paolo

    2009-01-01

    Theoretical models predict that the outcome of dyadic agonistic encounters between males is influenced by resource-holding potential, resource value, and intrinsic aggressiveness of contestants. Moreover, in territorial disputes residents enjoy a further obvious competitive advantage from the residency itself, owing to the intimate familiarity with their territory. Costs of physical combats are, however, dramatically high in many instances. Thus, signals reliably reflecting fighting ability of the opponents could easily evolve in order to reduce these costs. For example, variation in color morph in polymorphic species has been associated with dominance in several case studies. In this study, we staged asymmetric resident-intruder encounters in males of the common wall lizard Podarcis muralis, a species showing three discrete morphs (white, yellow, and red) to investigate the effects of asymmetries in color morph, residency, and size between contestants on the outcome of territorial contests. We collected aggression data by presenting each resident male with three intruders of different color morph, in three consecutive tests conducted in different days, and videotaping their interactions. The results showed that simple rules such as residency and body size differences could determine the outcome of agonistic interactions: residents were more aggressive than intruders, and larger males were competitively superior to smaller males. However, we did not find any effect of color on male aggression or fighting success, suggesting that color polymorphism in this species is not a signal of status or fighting ability in intermale conflicts. Copyright 2009 Wiley-Liss, Inc.

  9. Pain reduces sexual motivation in female but not male mice.

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

    2014-04-23

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

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

    OpenAIRE

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

    2014-01-01

    Chronic pain is often associated with sexual dysfunction, suggesting that pain can reduce libido. We find that inflammatory pain reduces sexual motivation, measured via mounting behavior and/or proximity in a paced mating paradigm, in female but not male laboratory mice. Pain was produced by injection of inflammogens zymosan A (0.5 mg/ml) or λ-carrageenan (2%) into genital or nongenital (hind paw, tail, cheek) regions. Sexual behavior was significantly reduced in female mice experiencing pain...

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

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    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.

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

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

    2012-06-01

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

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

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    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

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

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    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.

  15. SOX30 is required for male fertility in mice.

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    Feng, Chun-Wei Allen; Spiller, Cassy; Merriner, Donna J; O'Bryan, Moira K; Bowles, Josephine; Koopman, Peter

    2017-12-15

    Male infertility is a major and growing problem and, in most cases, the specific root cause is unknown. Here we show that the transcription factor SOX30 plays a critical role in mouse spermatogenesis. Sox30-null mice are healthy and females are fertile, but males are sterile. In the absence of Sox30 meiosis initiates normally in both sexes but, in males, germ cell development arrests during the post-meiotic round spermatid period. In the mutant testis, acrosome and axoneme development are aberrant, multinucleated germ cells (symplasts) form and round spermatids unable to process beyond step 3 of spermiogenesis. No elongated spermatids nor spermatozoa are produced. Thus, Sox30 represents a rare example of a gene for which loss of function results in a complete arrest of spermatogenesis at the onset of spermiogenesis. Our results suggest that SOX30 mutations may underlie some instances of unexplained non-obstructive azoospermia in humans.

  16. Effects of high natural radioactivity on reproductivity of male mice

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    Leonard, A.; Meyer, R. (Centre d' Etude de l' Energie Nucleaire, Mol (Belgique)); Delpoux, M.; Leonard, E.D.; Decat, G. (Universite Paul Sabatier, Toulouse (France))

    1983-01-01

    Male mice of the BALB/c strain were placed on the floor of a hut built at a site of Southwest France where the dose rate of ..gamma.. radiation amounts to about 10 mrad/h. Controls were kept near the radioactive site under comparable conditions. The doses of ..gamma.. rays received during a seven month period ranged from 0.1275 rad for the controls to 45 rad and 63 rad for the exposed animals. Due, possibly, to an effect on the libido exposure to 45 rad increased the fertility whereas the animals given 63 rad produced less offspring than the controls.

  17. Castration promotes welfare in group-housed male Swiss outbred mice maintained in educational institutions.

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    Vaughan, Lewis M; Dawson, Jane S; Porter, Paula R; Whittaker, Alexandra L

    2014-01-01

    Educational institutions maintain group-housed mice of both sexes for training veterinarians and technicians in husbandry, medication, and sampling procedures. Mice kept in all-male groups may experience poor welfare due to fighting. Castrated mice may be used to replace gonadally intact males for such training programs. In this prospective cohort study, 80 castrated and 80 control (intact) male mice were studied over 3 mo to monitor aggression frequency and injury levels. Behavioral observations were performed twice weekly by using an all-occurrences sampling method to quantify behavioral events and the number and severity of bite wounds. Under these housing conditions, group-housed male mice castrated postpubertally exhibited significantly less aggression than did intact male mice. Castration therefore improves welfare in group-housed male mice and thus provides a husbandry alternative to individually housing animals in nonstudy situations.

  18. Peripubertal exposure to male chemosignals accelerates vaginal opening and induces male-directed odor preference in female mice

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    Mélanie eJouhanneau

    2015-03-01

    Full Text Available Reproductive physiology in female mouse is profoundly affected by male odor. A well-known effect of male odor is the acceleration of puberty onset in prepubertal female mice exposed to male urine. Whether peripubertal exposure to male odor also influences female sexual behavior in adulthood is poorly known. Recently, we reported that female mice exposed to male-soiled bedding showed advanced vaginal opening associated with early expression of male-directed odor preference in adulthood. The aim of the present study is to determine whether peripubertal exposure to male urinary chemosignals affects both occurrence of vaginal opening and attraction to male odor at older age in female mice. Therefore, we exposed female mice to (1R, 5S, 7R-3,4-dehydro-exo-brevicomin (DHB, 6-hydroxy-6-methyl-3-heptanone (HMH and (S-2-sec-butyl-4,5-dihydrothiazole (SBT, individually or in mixture, from postnatal day (PD 21 to PD38 and monitored the occurrence of vaginal opening. We measured then the time that the female mice spent sniffing male and female mouse urinary volatiles at PD45. As expected, peripubertal exposure to DHB, HMH or SBT accelerated vaginal opening in female mice. In addition, we showed that exposure to a mixture of these three compounds induced expression of male-directed odor preference at PD45, contrary to the single exposure to each of these molecules. In conclusion, the volatile compounds DHB, HMH and SBT in urine of male mice influence both occurrence of vaginal opening and adult expression of male-directed odor preference in female mice.

  19. 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 ...

  20. Effects of exposure to glyphosate in male and female mice behavior in pubertal period

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    Andréia de Oliveira Joaquim

    2014-12-01

    Full Text Available The present study aims to investigate the effects of pre-pubertal exposure of male and female mice to a commercial formulation of glyphosate on sexual dimorphism observed in animal models of emotionality, anxiety and depression. For this, mice were exposed from 23 days of age (PND until PND 45 to glyphosate (50 mg/kg, per os or saline solution, and, ten days after the end of treatments, male and female mice were observed in the open field (OF, elevated plus maze (EPM or forced swimming test (FWT. Results showed that exposure to glyphosate: 1 reduced the locomotion frequency of male mice similarly to female mice in the OF and female mice had an increase in rearing behavior and in the immobility time; 2 reduced in male mice the motor activity both in the OF and EPM, while no effects were observed in female mice; 3 in the SWT male mice had a decreased time of float similarly female mice. We concluded that pre-pubertal exposure to glyphosate reduced in male mice the capacity of exploration in the OF and EPM tests suggesting that the herbicide interfered with the central mechanism related to brain masculinization of exploratory and anxiety behavioral models. In the FWT it was observed a decreased depressive response in male mice while in female an increased response was detected.

  1. Expression of Attractin in male reproductive tract of human and mice and its correlation with male reproduction.

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    Cheng, Dan; Ming, Yu; Li, Jie; Chi, Yan; Li, Hong-Gang; Zou, Yu-Jie; Xiong, Cheng-Liang

    2014-10-01

    The expression of Attractin mRNA and protein in testis and semen of human and male mice was investigated. Human testis and semen samples were all collected from Reproductive Center of Renmin Hospital, Wuhan University in December, 2012. Testis samples were collected from 7 cases of obstructive azoospermias when they were subjected to diagnosed testis biopsy, and 30 normal human semen samples were obtained from those cases of semen analysis. Adult mice testis tissues were obtained from 10 2-month-old male BALB/c mice, and 60 male mice at different ages were classified into 10 groups (day 1, 5, 10, 15, 21, 28, 35, 42, 56, and 120 respectively, n=6 each). The expression of Attractin mRNA and protein in testis was detected by RT-PCR and Western blotting respectively. Human semen samples were centrifuged into sperm plasma (SP) and sperm extract (SE), and mice sperm samples were collected from the epididymis of 10 adult male BALB/c mice. Western blotting was used to determine the Attractin protein expression level. Attractin mRNA and protein were expressed in the testis of both patients with obstructive azoospermias and adult Bcl/B mice. Quantitative RT-PCR revealed that no Attractin mRNA was detectable in day 1 male BALB/c mice group. The Attractin mRNA and protein levels were low on the day 10, and increased with age until day 56. On the day 120, the expression levels of Attractin were decreased. As for human semen samples, Attractin protein was expressed in both SP and SE, but didn't exist in samples from the epididymis of male BALB/c mice. It was suggested that Attractin acted as a novel active substance and was involved in male reproduction in both human and BALB/c mice, but it exerted a different expression profile in different mammal species.

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

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    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.

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

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    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.

  4. Strain-dependent susceptibility for hypertension in mice resides in the natural killer gene complex

    NARCIS (Netherlands)

    Taherzadeh, Zhila; VanBavel, Ed; de Vos, Judith; Matlung, Hanke L.; van Montfrans, Gert; Brewster, Lizzy M.; Seghers, Leonard; Quax, Paul H. A.; Bakker, Erik N. T. P.

    2010-01-01

    Taherzadeh Z, VanBavel E, de Vos J, Matlung HL, van Montfrans G, Brewster LM, Seghers L, Quax PH, Bakker EN. Strain-dependent susceptibility for hypertension in mice resides in the natural killer gene complex. Am J Physiol Heart Circ Physiol 298: H1273-H1282, 2010. First published February 12, 2010;

  5. 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,

  6. 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

  7. A QTL on chromosome 1 modulates inter-male aggression in mice.

    Science.gov (United States)

    Delprato, Anna; Bonheur, Brice; Algéo, Marie-Paule; Murillo, Alba; Dhawan, Esha; Lu, Lu; Williams, Robert W; Crusio, Wim E

    2018-02-19

    Aggression between male conspecifics is a complex social behavior that is likely modulated by multiple gene variants. In this study the BXD recombinant inbred mouse strains (RIS) were used to map quantitative trait loci (QTLs) underlying behaviors associated with intermale aggression. Four hundred and fifty-seven males from 55 strains (including the parentals) were observed at an age of 13 +/- 1 week in a resident-intruder test following 10 days of isolation. Attack latency was measured directly within a 10 minute time period and the test was repeated 24 hours later. The variables we analyzed were the proportion of attacking males in a given strain as well as the attack latency (on days 1 and 2, and both days combined). On day 1, 29% of males attacked, and this increased to 37% on day 2. Large strain differences were obtained for all measures of aggression, indicating substantial heritability (intraclass correlations 0.10-0.18). We identified a significant QTL on chromosome (Chr) 1 and suggestive QTLs on mouse Chrs 1 and 12 for both attack and latency variables. The significant Chr 1 locus maps to a gene-sparse region between 82 and 88.5 Mb with the C57BL/6J allele increasing aggression and explaining about 18% of the variance. The most likely candidate gene modulating this trait is Htr2b which encodes the serotonin 2B receptor and has been implicated in aggressive and impulsive behavior in mice, humans, and other species. This article is protected by copyright. All rights reserved.

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

    Science.gov (United States)

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

    2015-01-01

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

  9. 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.

  10. 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.

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

    Science.gov (United States)

    Noormets, Klari; Kõks, Sulev; Kavak, Ants; Arend, Andres; Aunapuu, Marina; Keldrimaa, Aivi; Vasar, Eero; Tillmann, Vallo

    2009-08-10

    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. 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. The pregnancy rate in wt females mated with Wfs1KO males was significantly lower than in the control group (15% vs. 32%; p Wfs1 gene influences sperm morphology needs to be clarified in further studies.

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

    OpenAIRE

    Noormets, Klari; K?ks, Sulev; Kavak, Ants; Arend, Andres; Aunapuu, Marina; Keldrimaa, Aivi; Vasar, Eero; Tillmann, Vallo

    2009-01-01

    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) ...

  13. Male Hypogonadism Causes Obesity Associated with Impairment of Hepatic Gluconeogenesis in Mice.

    Science.gov (United States)

    Aoki, Akira; Fujitani, Kohei; Takagi, Kohei; Kimura, Tomoki; Nagase, Hisamitsu; Nakanishi, Tsuyoshi

    2016-01-01

    The steroid hormones synthesized by the male gonads play diverse roles in biological processes. Androgens, the primary hormones produced by the male gonads, are key regulators of fat homeostasis, hence androgen-deprivation therapies often induce obesity. However, the molecular mechanism by which male gonadal dysfunction leads to obesity remains unclear, because results from animal studies regarding fat accumulation in the context of gonadal defects do not reflect clinical findings. Here, we investigated the mechanism underlying the development of obesity in animals with male gonadal dysfunction by analyzing the long-term physiological changes in adult male mice with surgical castration. Nine weeks after surgery, white adipose tissue (WAT) mass was higher in the castrated (Cas) mice than in sham-operated (Sham) mice. In addition, castration induced hyperlipidemia and hyperglycemia. However, genes involved in lipid metabolism, including hormone-sensitive lipase, were unchanged in the adipose tissue of the Cas mice, despite the increase in WAT. In contrast, a hepatic gluconeogenesis gene, glucose-6-phosphatase, was significantly upregulated in the Cas mice than in Sham mice. Our findings suggest that long-term hypogonadism in mice mimics the effects in humans, and a potential molecular basis for the induction of obesity in this model is impairment of hepatic gluconeogenesis.

  14. 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

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

    Directory of Open Access Journals (Sweden)

    Gabriel Alejandro Bonaterra

    Full Text Available Fibromyalgia (FM is a chronic musculoskeletal pain disorder, characterized by chronic widespread pain and bodily tenderness and is often accompanied by affective disturbances, however often with unknown etiology. According to recent reports, physical and psychological stress trigger FM. To develop new treatments for FM, experimental animal models for FM are needed to be development and characterized. Using a mouse model for FM including intermittent cold stress (ICS, we hypothesized that ICS leads to morphological alterations in skeletal muscles in mice.Male and female ICS mice were kept under alternating temperature (4 °C/room temperature [22 °C]; mice constantly kept at room temperature served as control. After scarification, gastrocnemius and soleus muscles were removed and snap-frozen in liquid nitrogen-cooled isopentane or fixed for electron microscopy.In gastrocnemius/soleus muscles of male ICS mice, we found a 21.6% and 33.2% decrease of fiber cross sectional area (FCSA, which in soleus muscle concerns the loss of type IIa and IIx FCSA. This phenomenon was not seen in muscles of female ICS mice. However, this loss in male ICS mice was associated with an increase in gastrocnemius of the density of MIF+ (8.6%-, MuRF+ (14.7%-, Fbxo32+ (17.8%-cells, a 12.1% loss of capillary contacts/muscle fiber as well as a 30.7% increase of damaged mitochondria in comparison with male control mice. Moreover, significant positive correlations exist among densities (n/mm(2 of MIF+, MuRF+, Fbxo32+-cells in gastrocnemius/ soleus muscles of male ICS mice; these cell densities inversely correlate with FCSA especially in gastrocnemius muscle of male ICS mice.The ICS-induced decrease of FCSA mainly concerns gastrocnemius muscle of male mice due to an increase of inflammatory and atrogenic cells. In soleus muscle of male ICS and soleus/gastrocnemius muscles of female ICS mice morphological alterations seem to occur not at all or delayed. The sex-specificity of

  16. Distinct Myocardial Mechanisms Underlie Cardiac Dysfunction in Endotoxemic Male and Female Mice.

    Science.gov (United States)

    Hobai, Ion A; Aziz, Kanwal; Buys, Emmanuel S; Brouckaert, Peter; Siwik, Deborah A; Colucci, Wilson S

    2016-12-01

    In male mice, sepsis-induced cardiomyopathy develops as a result of dysregulation of myocardial calcium (Ca) handling, leading to depressed cellular Ca transients (ΔCai). ΔCai depression is partially due to inhibition of sarcoplasmic reticulum Ca ATP-ase (SERCA) via oxidative modifications, which are partially opposed by cGMP generated by the enzyme soluble guanylyl cyclase (sGC). Whether similar mechanisms underlie sepsis-induced cardiomyopathy in female mice is unknown.Male and female C57Bl/6J mice (WT), and mice deficient in the sGC α1 subunit activity (sGCα1), were challenged with lipopolysaccharide (LPS, ip). LPS induced mouse death and cardiomyopathy (manifested as the depression of left ventricular ejection fraction by echocardiography) to a similar degree in WT male, WT female, and sGCα1 male mice, but significantly less in sGCα1 female mice. We measured sarcomere shortening and ΔCai in isolated, externally paced cardiomyocytes, at 37°C. LPS depressed sarcomere shortening in both WT male and female mice. Consistent with previous findings, in male mice, LPS induced a decrease in ΔCai (to 30 ± 2% of baseline) and SERCA inhibition (manifested as the prolongation of the time constant of Ca decay, τCa, to 150 ± 5% of baseline). In contrast, in female mice, the depression of sarcomere shortening induced by LPS occurred in the absence of any change in ΔCai, or SERCA activity. This suggested that, in female mice, the causative mechanism lies downstream of the Ca transients, such as a decrease in myofilament sensitivity for Ca. The depression of sarcomere shortening shortening after LPS was less severe in female sGCα1 mice than in WT female mice, indicating that cGMP partially mediates cardiomyocyte dysfunction.These results suggest, therefore, that LPS-induced cardiomyopathy develops through distinct sex-specific myocardial mechanisms. While in males LPS induces sGC-independent decrease in ΔCai, in female mice LPS acts downstream of

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

    Indian Academy of Sciences (India)

    Unknown

    27 | No. 7 | December 2002. S Achiraman and G Archunan. 680 change in diet can alter urine odours. Urinary steroid metabolites have been quantitatively altered during the starvation and re-feeding experiments for mice with dif- ferent environmental ... pounds were then compared with the standard run under the same ...

  18. Toxicokinetics of phenolphthalein in male and female rats and mice.

    Science.gov (United States)

    Collins, B J; Grizzle, T B; Dunnick, J K

    2000-08-01

    Phenolphthalein (PTH), which has been used as the active ingredient in a number of prescription and over-the-counter laxative products, is a rodent chemical carcinogen in multiple organs in the NTP 2-year bioassay at doses of 291-2927 mg/kg. This paper describes the toxicokinetics and estimates the internal dose of PTH administered as a single iv or gavage dose, or ad libitum for 14 days in feed to F344 rats, B6C3F1 mice, p53 (+/-) mice, and C57BL mice at doses that bracketed those used in the bioassay. Plasma concentrations for free phenolphthalein (PTH-F) and phenolphthalein glucuronide (PTH-G) were obtained for each dose regimen. Total phenolphthalein (PTH-T) was calculated as the sum of the molar concentrations of PTH-F and PTH-G. Noncompartmental pharmacokinetic models were used to calculate the area under the curve (AUC) from 0 h to infinity (AUC(infinity)), clearance (Cl), and oral bioavailability (F) for PTH-F; and were used to calculate AUC(infinity), t((1/2)), and relative absorption (Q) for PTH-T. After iv administration, PTH-F rapidly declined in rats and mice; PTH-T rose rapidly to Cmax and slowly declined 6-8 h after dosing, with no sex-related differences for rats or mice. For feed studies, mean plasma concentration (f1.gif" BORDER="0">(infinity)) and 24-h area under the curve (AUC(24h)) values were calculated. Results from feed studies showed no dose response in rat plasma PTH-F above approximately 50 mg/kg. Rat PTH-T AUC(24h) and f1.gif" BORDER="0">(infinity) were linear with doses up to approximately 650 mg/kg. In B6C3F1 mice, PTH-F and PTH-T AUC(24h) increased nonlinearly with doses above approximately 165 mg/kg. PTH is well absorbed and readily converted to PTH-G when administered in feed to rats and mice, except at the highest bioassay doses, where PTH absorption may be saturated.

  19. 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)

  20. Toxic effects of zearalenone and its derivatives alpha-zearalenol on male reproductive system in mice.

    Science.gov (United States)

    Yang, Jian Ying; Wang, Guo Xin; Liu, Jia Li; Fan, Jing Jing; Cui, Sheng

    2007-01-01

    The current study evaluated effects of zearalenone (ZEA) and its derivative alpha-zearalenol (alpha-ZOL) on male mouse semen quality, fertility and serum testosterone concentrations. Adult male mice were exposed to intraperitoneal (i.p.) injection of ZEA or alpha-ZOL at 0, 25, 50, and 75 mg/kg body weight (b.w.) daily for 7 days, and then mated with sexually mature untreated female mice. Semen quality, serum testosterone concentrations and fertility of treated mice were assessed. The results showed that the number of abnormal spermatozoa increased and the amount of live spermatozoa decreased significantly in males treated with ZEA at all doses. As well, a significant decrease in spermatozoa with integrated acrosome was observed in mice treated with 50 and 75 mg/kg b.w. alpha-ZOL. Significantly low pregnancy rate was observed when females were mated with ZEA or alpha-ZOL exposed males. Male mice exposed to ZEA had significant reductions in b.w. and relative epididymis weights. However, relative seminal vesicle weights were higher than those of controls. Conversely, significant increases in b.w. and relative preputial gland weight were observed in mice exposed to alpha-ZOL. Testicular and cauda epididymal sperm counts, efficiency of sperm production and serum testosterone concentrations were significantly reduced in mice treated with ZEA or alpha-ZOL at all doses in a dose-dependent manner. In conclusion, we demonstrate that ZEA or alpha-ZOL have adverse effects on reproductive system of adult male mice.

  1. Raphe serotonin neuron-specific oxytocin receptor knockout reduces aggression without affecting anxiety-like behavior in male mice only

    Science.gov (United States)

    Pagani, Jerome H.; Williams Avram, Sarah K.; Cui, Zhenzhong; Song, June; Mezey, Éva; Senerth, Julia M.; Baumann, Michael H.; Young, W. Scott

    2015-01-01

    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 eight 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. PMID:25677455

  2. Gonad-related factors promote muscle performance gain during postnatal development in male and female mice.

    Science.gov (United States)

    Ueberschlag-Pitiot, Vanessa; Stantzou, Amalia; Messéant, Julien; Lemaitre, Megane; Owens, Daniel J; Noirez, Philippe; Roy, Pauline; Agbulut, Onnik; Metzger, Daniel; Ferry, Arnaud

    2017-07-01

    To better define the role of male and female gonad-related factors (MGRF, presumably testosterone, and FGRF, presumably estradiol, respectively) on mouse hindlimb skeletal muscle contractile performance/function gain during postnatal development, we analyzed the effect of castration initiated before puberty in male and female mice. We found that muscle absolute and specific (normalized to muscle weight) maximal forces were decreased in 6-mo-old male and female castrated mice compared with age- and sex-matched intact mice, without alteration in neuromuscular transmission. Moreover, castration decreased absolute and specific maximal powers, another important aspect of muscle performance, in 6-mo-old males, but not in females. Absolute maximal force was similarly reduced by castration in 3-mo-old muscle fiber androgen receptor (AR)-deficient and wild-type male mice, indicating that the effect of MGRF was muscle fiber AR independent. Castration reduced the muscle weight gain in 3-mo mice of both sexes and in 6-mo females but not in males. We also found that bone morphogenetic protein signaling through Smad1/5/9 was not altered by castration in atrophic muscle of 3-mo-old mice of both sexes. Moreover, castration decreased the sexual dimorphism regarding muscle performance. Together, these results demonstrated that in the long term, MGRF and FGRF promote muscle performance gain in mice during postnatal development, independently of muscle growth in males, largely via improving muscle contractile quality (force and power normalized), and that MGFR and FGRF also contribute to sexual dimorphism. However, the mechanisms underlying MGFR and FGRF actions remain to be determined. Copyright © 2017 the American Physiological Society.

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

    Science.gov (United States)

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

    2016-06-01

    Phenotypic variation and its epigenetic regulations within the inbred isogenic mice have long intrigued biologists. Here, we used inbred C57BL/6 mice to examine the individual differences and the inheritance of social dominance and male pheromones, expecting to create a model for studying the underlying epigenetic mechanisms for the evolution of these traits. We used a repeated male-male contest paradigm to form stable dominance-submission relationships between paired males and make superior or inferior quality manifest. Females showed olfactory preferences for the urine of dominant males to that of subordinate opponents. Gas chromatography-mass spectrometer analysis revealed that dominance-related or superior quality related pheromones were actually exaggerated male pheromone components (e.g., E-β-farnesene, hexadecanol, and 1-hexadecanol acetate) of preputial gland origin. Although the socially naïve sons of both dominant and subordinate males elicited the same female attraction when reaching adulthood, the former could dominated over the latter during undergoing the male-male competition and then gained more attraction of females. Our results demonstrated that social dominance or superior quality and the related pheromones were heritable and could be expressed through the interaction between aggression-related epigenotypes and male-male contests. It suggested that the evolution of sexually selected traits could be epigenetically determined and promoted through female mate choice. The epigenetic mechanisms driving the individual differences in behavior and male pheromones deserve further studies. © 2016 Wiley Periodicals, Inc.

  4. Abnormal lipid/lipoprotein metabolism and high plasma testosterone levels in male but not female aromatase-knockout mice.

    Science.gov (United States)

    Amano, Akiko; Kondo, Yoshitaka; Noda, Yoshihiro; Ohta, Mitsuhiro; Kawanishi, Noriaki; Machida, Shuichi; Mitsuhashi, Kazuteru; Senmaru, Takafumi; Fukui, Michiaki; Takaoka, Osamu; Mori, Taisuke; Kitawaki, Jo; Ono, Masafumi; Saibara, Toshiji; Obayashi, Hiroshi; Ishigami, Akihito

    2017-05-15

    Sex steroid hormones, such as estrogen and testosterone, are believed to play important roles in lipid metabolism. To elucidate the effects of estrogen depletion on lipid metabolism in male and female mice, we used aromatase-knockout (ArKO) mice, in which Cyp19 gene disruption prevented estrogen synthesis in vivo. These mice were divided into the following 4 groups: male and female ArKO mice and male and female wild-type (WT) mice. These mice were fed a normal-fat diet (13.6% fat) ad libitum. At 159 days after birth, the mice were tested for liver and plasma lipid content and hepatic hormone receptor- and lipid/lipoprotein metabolism-related gene expression. Interestingly, we found that hepatic steatosis was accompanied by markedly elevated plasma testosterone levels in male ArKO mice but not in female ArKO mice. Plasma lipoprotein profiles exhibited concurrent decreases in LDL- and small dense LDL-triglyceride (TG) levels in male ArKO mice. Moreover, male mice, but not female mice, exhibited marked elevations in androgen receptor (AR), sterol regulatory element-binding protein 1 (SREBP1), and CD36 expression. These results strongly suggest that Cyp19 gene disruption, which induces a sexually dimorphic response and high plasma testosterone levels in male mice, also induces hepatic steatosis. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Social instigation and repeated aggressive confrontations in male Swiss mice: analysis of plasma corticosterone, CRF and BDNF levels in limbic brain areas

    Directory of Open Access Journals (Sweden)

    Paula Madeira Fortes

    2017-06-01

    Full Text Available Abstract Introduction: Agonistic behaviors help to ensure survival, provide advantage in competition, and communicate social status. The resident-intruder paradigm, an animal model based on male intraspecific confrontations, can be an ethologically relevant tool to investigate the neurobiology of aggressive behavior. Objectives: To examine behavioral and neurobiological mechanisms of aggressive behavior in male Swiss mice exposed to repeated confrontations in the resident intruder paradigm. Methods: Behavioral analysis was performed in association with measurements of plasma corticosterone of mice repeatedly exposed to a potential rival nearby, but inaccessible (social instigation, or to 10 sessions of social instigation followed by direct aggressive encounters. Moreover, corticotropin-releasing factor (CRF and brain-derived neurotrophic factor (BNDF were measured in the brain of these animals. Control mice were exposed to neither social instigation nor aggressive confrontations. Results: Mice exposed to aggressive confrontations exhibited a similar pattern of species-typical aggressive and non-aggressive behaviors on the first and the last session. Moreover, in contrast to social instigation only, repeated aggressive confrontations promoted an increase in plasma corticosterone. After 10 aggressive confrontation sessions, mice presented a non-significant trend toward reducing hippocampal levels of CRF, which inversely correlated with plasma corticosterone levels. Conversely, repeated sessions of social instigation or aggressive confrontation did not alter BDNF concentrations at the prefrontal cortex and hippocampus. Conclusion: Exposure to repeated episodes of aggressive encounters did not promote habituation over time. Additionally, CRF seems to be involved in physiological responses to social stressors.

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

    Science.gov (United States)

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

    2013-03-20

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

  7. An Exploration of Dietary Acculturation in Hispanic Males Residing in Mississippi

    Directory of Open Access Journals (Sweden)

    Diana Cuy Castellanos

    2016-06-01

    Full Text Available The purpose of this research was to explore dietary acculturation in Hispanic males in the context of the Operant Theory of Acculturation. This was a qualitative study using grounded theory to guide methodological procedures. Semi-structured interviews, a focus group, the Acculturation-Rating Scale for Mexican-Americans-II and the Marginality Scale, and photovoice with follow-up interviews were used to explore dietary acculturation in the participant sample. Thirty-five first- and second-generation Hispanic males residing in Mississippi were recruited and categorized into one of three different bidimensional acculturation groups as determined by the Acculturation-Rating Scale for Mexican-Americans-II and the Marginality Scale. Main dietary influencing themes identified were intrapersonal and environmental dietary factors. The subthemes included values, attitudes, beliefs, knowledge, and preference for the intrapersonal factors and availability; living structure; accessibility; food preparation skill; and time for the environmental factors. The factors are not mutually exclusive and show the complexity of the dietary acculturation process. This research can be used to guide future research and inform nutrition intervention development for this population.

  8. Diet‐induced obesity alters skeletal muscle fiber types of male but not female mice

    Science.gov (United States)

    DeNies, Maxwell S.; Johnson, Jordan; Maliphol, Amanda B.; Bruno, Michael; Kim, Annabelle; Rizvi, Abbas; Rustici, Kevyn; Medler, Scott

    2014-01-01

    Abstract Skeletal muscles are highly plastic tissues capable dramatic remodeling in response to use, disuse, disease, and other factors. Growing evidence suggests that adipose tissues exert significant effects on the basic fiber‐type composition of skeletal muscles. In the current study, we investigated the long‐term effects of a high‐fat diet and subsequent obesity on the muscle fiber types in C57 BLK/6J mice. Litters of mice were randomly assigned to either a high‐fat diet or a control group at the time of weaning, and were maintained on this diet for approximately 1 year. Single fibers were harvested from the soleus and plantaris muscles, and fiber types were determined using SDS‐PAGE. The high‐fat diet mice were significantly heavier than the control mice (39.17 ± 2.7 g vs. 56.87 ± 3.4 g; P muscle masses were not different. In male mice, the high‐fat diet was associated with a significantly lower proportion of slow, type I fibers in the soleus muscle (40.4 ± 3.5% vs. 29.33 ± 2.6%; P < 0.0165). Moreover, the proportion of type I fibers in the soleus of male mice was inversely proportional to the relative fatness of the male mice (P < 0.003; r2 = 0.65), but no association was observed in female mice. In male mice, the decline in type I fibers was correlated with an increase in type I/IIA hybrid fibers, suggesting that the type I fibers were transformed primarily into these hybrids. The reported trends indicate that type I fibers are most susceptible to the effects of obesity, and that these fiber‐type changes can be sex specific. PMID:24744883

  9. Developmental lead effects on behavior and brain gene expression in male and female BALB/cAnNTac mice.

    Science.gov (United States)

    Kasten-Jolly, Jane; Pabello, Nina; Bolivar, Valerie J; Lawrence, David A

    2012-10-01

    Lead (Pb) was one of the first poisons identified, and the developing nervous system is particularly vulnerable to its toxic effects. Relatively low, subclinical doses, of Pb that produce no overt signs of encephalopathy can affect cognitive, emotional, and motor functions. In the present study, the effects of developmental Pb-exposure on behavioral performance and gene expression in BALB/cAnNTac mice were evaluated. Pups were exposed to Pb from gestational-day (gd) 8 to postnatal-day (pnd) 21 and later evaluated in exploratory behavior, rotarod, Morris water maze, and resident-intruder assays as adults. Pb-exposure caused significant alterations in exploratory behavior and water maze performance during the probe trial, but rotarod performance was not affected. Pb-exposed males displayed violent behavior towards their cage mates, but not to a stranger in the resident-intruder assay. Gene expression analysis at pnd21 by microarray and qRT-PCR was performed to provide a molecular link to the behavior changes that were observed. Pb strongly up-regulated gene expression within the signaling pathways of mitogen activated protein kinases (MAPKs), extra-cellular matrix (ECM) receptor, focal adhesion, and vascular endothelial growth-factor (VEGF), but Pb down-regulated gene expression within the pathways for glycan structures-biosynthesis 1, purine metabolism, and N-glycan biosynthesis. Pb increased transcription of genes for major histocompatibility (MHC) proteins, the chemokine Ccl28, chemokine receptors, IL-7, IL7R, and proteases. The qRT-PCR analysis indicated an increase of gene expression in the whole brain for caspase 1 and NOS2. Analysis of IL-1β, caspase 1, NOS2, Trail, IL-18 and IL-33 gene expression of brain regions indicated that Pb perturbed the inter-regional expression pattern of pro-inflammatory genes. Brain region protein concentrations for IL-10, an anti-inflammatory cytokine, showed a significant decrease only within the cortex region. Results indicate

  10. 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.

  11. 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.

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

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    Annette Ehrhardt

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

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

    Science.gov (United States)

    Cettour-Rose, Philippe; Bezençon, Carole; Darimont, Christian; le Coutre, Johannes; Damak, Sami

    2013-02-08

    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. 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. 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.

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

    Science.gov (United States)

    2013-01-01

    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. PMID:23394313

  15. 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.

  16. Distinct myocardial mechanisms underlie cardiac dysfunction in endotoxemic male and female mice

    OpenAIRE

    Hobai, Ion A.; Aziz, Kanwal; Buys, Emmanuel S.; Brouckaert, Peter; Siwik, Deborah A.; Colucci., Wilson S.

    2016-01-01

    In male mice, Sepsis-Induced Cardiomyopathy develops as a result of dysregulation of myocardial calcium (Ca2+) handling, leading to depressed cellular Ca2+ transients (ΔCai). ΔCai depression is partially due to inhibition of sarcoplasmic reticulum Ca2+ ATP-ase (SERCA) via oxidative modifications, which are partially opposed by cGMP generated by the enzyme soluble guanylyl cyclase (sGC). Whether similar mechanisms underlie Sepsis-Induced Cardiomyopathy in female mice is unknown.

  17. Effects of Selective Deletion of Tyrosine Hydroxylase from Kisspeptin Cells on Puberty and Reproduction in Male and Female Mice.

    Science.gov (United States)

    Stephens, Shannon B Z; Rouse, Melvin L; Tolson, Kristen P; Liaw, Reanna B; Parra, Ruby A; Chahal, Navi; Kauffman, Alexander S

    2017-01-01

    The neuropeptide kisspeptin, encoded by Kiss1 , regulates reproduction by stimulating GnRH secretion. Kiss1- syntheizing neurons reside primarily in the hypothalamic anteroventral periventricular (AVPV/PeN) and arcuate (ARC) nuclei. AVPV/PeN Kiss1 neurons are sexually dimorphic, with females expressing more Kiss1 than males, and participate in estradiol (E 2 )-induced positive feedback control of GnRH secretion. In mice, most AVPV/PeN Kiss1 cells coexpress tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis (in this case, dopamine). Dopamine treatment can inhibit GnRH neurons, but the function of dopamine signaling arising specifically from AVPV/PeN Kiss1 cells is unknown. We generated a novel TH flox mouse and used Cre-Lox technology to selectively ablate TH specifically from Kiss1 cells. We then examined the effects of selective TH knock-out on puberty and reproduction in both sexes. In control mice, 90% of AVPV/PeN Kiss1 neurons coexpressed TH , whereas in mice lacking TH exclusively in Kiss1 cells (termed Kiss THKOs), TH was successfully absent from virtually all Kiss1 cells. Despite this absence of TH , both female and male Kiss THKOs displayed normal body weights, puberty onset, and basal gonadotropin levels in adulthood, although testosterone (T) was significantly elevated in adult male Kiss THKOs. The E 2 -induced LH surge was unaffected in Kiss THKO females, and neuronal activation status of kisspeptin and GnRH cells was also normal. Supporting this, fertility and fecundity were normal in Kiss THKOs of both sexes. Thus, despite high colocalization of TH and Kiss1 in the AVPV/PeN, dopamine produced in these cells is not required for puberty or reproduction, and its function remains unknown.

  18. Attenuation of cocaine-induced locomotor activity in male and female mice by active immunization.

    Science.gov (United States)

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

    2014-01-01

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

  19. 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.

  20. 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...... 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...

  1. 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.

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

    Science.gov (United States)

    Mishra, Raghav Kumar; Singh, Shio Kumar

    2013-01-01

    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. PMID:23930041

  3. 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.

  4. DISTINCT BEHAVIORAL PHENOTYPES IN MALE MICE LACKING THE THYROID HORMONE RECEPTOR α1 OR β ISOFORMS

    Science.gov (United States)

    Vasudevan, Nandini; Morgan, Maria; Pfaff, Donald; Ogawa, Sonoko

    2013-01-01

    Thyroid hormones influence both neuronal development and anxiety via the thyroid hormone receptors (TRs). The TRs are encoded by two different genes, TRα and TRβ. The loss of TRα1 is implicated in increased anxiety in males, possibly via a hippocampal increase in GABAergic activity. We compared both social behaviors and two underlying and related non-social behaviors, state anxiety and responses to acoustic and tactile startle in the gonadally intact TRα1 knockout (α1KO) and TRβ (βKO) male mice to their wild-type counterparts. For the first time, we show an opposing effect of the two TR isoforms, TRα1 and TRβ, in the regulation of state anxiety, with α1 knockout animals (α1KO) showing higher levels of anxiety and βKO males showing less anxiety compared to respective wild-type mice. At odds with the increased anxiety in non-social environments, α1KO males also show lower levels of responsiveness to acoustic and tactile startle stimuli. Consistent with the data that T4 is inhibitory to lordosis in female mice, we show subtly increased sex behavior in α1KO male mice. These behaviors support the idea that TRα1 could be inhibitory to ERα driven transcription that ultimately impacts ERα driven behaviors such as lordosis. The behavioral phenotypes point to novel roles for the TRs, particularly in non-social behaviors such as state anxiety and startle. PMID:23567476

  5. Synaptonemal Complex Length Variation in Wild-Type Male Mice

    Directory of Open Access Journals (Sweden)

    Neil M. Vranis

    2010-12-01

    Full Text Available Meiosis yields haploid gametes following two successive divisions of a germ cell in the absence of intervening DNA replication. Balanced segregation of homologous chromosomes in Meiosis I is aided by a proteinaceous structure, the synaptonemal complex (SC. The objective of this study was to determine total average autosomal SC lengths in spermatocytes in three commonly used mouse strains (129S4/SvJae, C57BL/6J, and BALB/c. Our experiments revealed that the total autosomal SC length in BALB/c spermatocytes is 9% shorter than in the two other strains. Shorter SCs are also observed in spermatocytes of (BALB/c × 129S4/SvJae and (C57BL/6J × BALB/c F1 hybrids suggesting a genetic basis of SC length regulation. Along these lines, we studied expression of a selected group of genes implicated in meiotic chromosome architecture. We found that BALB/c testes express up to 6-fold less of Rec8 mRNA and 4-fold less of REC8 protein. These results suggest that the mechanism that defines the SC length operates via a REC8‑dependent process. Finally, our results demonstrate that genetic background can have an effect on meiotic studies in mice.

  6. 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.

  7. Adipocyte Deficiency of Angiotensinogen Prevents Obesity-Induced Hypertension in Male Mice

    Science.gov (United States)

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

    2012-01-01

    Previous studies demonstrated that diet-induced obesity increased plasma angiotensin II concentrations and elevated systolic blood pressures in male mice. Adipocytes express angiotensinogen and secrete angiotensin peptides. We hypothesize that adipocyte-derived angiotensin II mediates obesity-induced increases in systolic blood pressure in male high fat-fed C57BL/6 mice. Systolic blood pressure was measured by radiotelemetry during week 16 of low fat or high fat feeding in Agtfl/fl and adipocyte-angiotensinogen deficient mice (AgtaP2). Adipocyte angiotensinogen deficiency had no effect on diet-induced obesity. Basal 24 hour systolic blood pressure was not different in low fat-fed Agtfl/fl compared to AgtaP2 mice (124 ± 3 vs. 128 ± 3 mmHg, respectively). In Agtfl/fl mice, high fat feeding significantly increased systolic blood pressure (24 hr; 134 ± 2 mmHg; P<0.05). In contrast, high fat-fed AgtaP2 mice did not exhibit an increase in systolic blood pressure (126 ± 2 mmHg). Plasma angiotensin II concentrations were increased by high fat-feeding in Agtfl/fl mice (low fat, 32 ± 14; high fat, 219 ± 58 pg/ml, P<0.05). In contrast, high fat-fed AgtaP2 mice did not exhibit elevated plasma angiotensin II concentrations (high fat, 18 ± 7 pg/ml). Similarly, adipose tissue concentrations of angiotensin II were significantly decreased in low fat and high fat-fed AgtaP2 mice compared to controls. In conclusion, adipocyte angiotensinogen deficiency prevented high fat-induced elevations in plasma angiotensin II concentrations and systolic blood pressure. These results suggest that adipose tissue serves as a major source of angiotensin II in the development of obesity-hypertension. PMID:23108647

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

    Directory of Open Access Journals (Sweden)

    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.

  9. The endocytic recycling regulator EHD1 is essential for spermatogenesis and male fertility in mice

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    Hess Rex A

    2010-04-01

    Full Text Available Abstract Background The C-terminal Eps15 homology domain-containing protein 1 (EHD1 is ubiquitously expressed and regulates the endocytic trafficking and recycling of membrane components and several transmembrane receptors. To elucidate the function of EHD1 in mammalian development, we generated Ehd1-/- mice using a Cre/loxP system. Results Both male and female Ehd1-/- mice survived at sub-Mendelian ratios. A proportion of Ehd1-/- mice were viable and showed smaller size at birth, which continued into adulthood. Ehd1-/- adult males were infertile and displayed decreased testis size, whereas Ehd1-/- females were fertile. In situ hybridization and immunohistochemistry of developing wildtype mouse testes revealed EHD1 expression in most cells of the seminiferous epithelia. Histopathology revealed abnormal spermatogenesis in the seminiferous tubules and the absence of mature spermatozoa in the epididymides of Ehd1-/- males. Seminiferous tubules showed disruption of the normal spermatogenic cycle with abnormal acrosomal development on round spermatids, clumping of acrosomes, misaligned spermatids and the absence of normal elongated spermatids in Ehd1-/- males. Light and electron microscopy analyses indicated that elongated spermatids were abnormally phagocytosed by Sertoli cells in Ehd1-/- mice. Conclusions Contrary to a previous report, these results demonstrate an important role for EHD1 in pre- and post-natal development with a specific role in spermatogenesis.

  10. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. 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

  13. [Effect of Toxoplasma gondii Infection in Female Mice on Dopamine Level in the Brain of the Male Offspring].

    Science.gov (United States)

    Zhou, Yong-hua; Zhu, Hu-ping; Xu, Jin-jun; Zhang, Ying; Mao, Ai-min; Yang, Jing; Fan, Feng; Xu, Yong-liang; Zhao, Zhong-xing; Tao, Jian-ping

    2015-02-01

    To investigate the effect of Toxoplasma gondii infection in female mice on dopamine level in the brain of male offspring. Thirty-six ICR female mice were randomly divided into control group and infection group, 18 mice in each group. Each mouse in infection group was orally infected with 10 cysts of T. gondii Prugniaud strain. On the 90th day after infection, the infected female mice were mated with normal male ICR mice at 1:1 ratio. On the 20th day of pregnancy, 2 mice in each group were delivered for fetal mice by cesarean section, and the brain of male fetal mice (n = 6) in each group were collected. On the 14th and 63rd day after birth, 6 male offspring mice in each group were sacrificed, and the brain were collected. Dopamine levels in the cortex, cerebellum, hippocampus, and striatum were analyzed by high-performance liquid chromatography-electrochemical detection (HPLC-ECD). Three mice in infection group died during the experiment, and 6 out of 15 female mice mated successfully. The number of fetal mice and F1 generation mice in infection group was 12 (male: 7) and 21 (male: 15), respectively. All the mice in control group mated successfully. The number of fetal mice and F1 generation mice was 23 (male: 12) and 179 (male: 92), respectively. The dopamine level in the cerebellum of fetal mice of infection group and control group was (413.25 ± 21.78) ng/g and (346.30 ± 51.83) ng/g, respectively (P 0.05). Compared with the control group, on the 14th day and 63rd day after birth, the dopamine content in cortical areas [(462.50 ± 24.80) ng/g and (1215.77 ± 113.64) ng/g], cerebellum area [(271.55 ± 26.19) ng/g and (1328.82 ± 39.62) ng/g], hippocampus area [(225.78 ± 24.17) ng/g and (1322.70 ± 58.34) ng/g], and striatum area [(455.23 ± 61.53) ng/g and (991.32 ± 54.31) ng/g] of the male offspring in infection group were significantly higher than that of the control (P female mice causes an increase of dopamine level in the brain of F1 generation male mice.

  14. 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.

  15. Perinatal exposure to genistein alters reproductive development and aggressive behavior in male mice.

    Science.gov (United States)

    Wisniewski, Amy B; Cernetich, Amy; Gearhart, John P; Klein, Sabra L

    2005-02-15

    Exposure to endocrine disrupting chemicals adversely affects reproductive development and behavior in males. The goal of this study was to determine if exposure to genistein, an isoflavone found in soy, during early periods of sex differentiation alters reproductive development and behavior in male mice. Female C57BL/6 mice were fed a phytoestrogen-free diet supplemented with 0, 5 or 300 mg/kg of genistein throughout gestation and lactation. Anogenital distance (AGD) and body mass of male offspring was measured weekly from postnatal days 2-21, timing of preputial separation was assessed at puberty, and in adulthood, reproductive organ masses, sperm and testosterone production, and reproductive and aggressive behaviors were assessed. Exposure to genistein resulted in smaller AGD are reduced body mass, with the low-dose diet exerting a greater effect. Timing of preputial separation, adult reproductive behavior, sperm concentrations and testosterone production were not influenced by genistein treatment at either dose. Aggressive behaviors were decreased, whereas defensive behaviors were increased, in males that received the low-dose genistein diet. Exposure to genistein during critical periods of sex differentiation results in concurrent and persistent demasculinization in male mice. Phenotypic and behavioral abnormalities induced by genistein showed a non-monotonic response, where treatment with a low dose exerted a greater effect than treatment with a high dose of genistein. Given the popularity of soy infant formulas, the influence isoflavone exposure on reproductive and behavioral health in boys and men should be considered.

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

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    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

  17. 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.

  18. 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.

  19. 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.

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

    Science.gov (United States)

    Singh, Nidhi; Singh, Shio Kumar

    2016-01-01

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

  1. 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.

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    Sara Caceres

    2016-01-01

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

  4. Adrenocorticosterone alterations in male, albino mice treated with Trichopus zeylanicus, Withania somnifera and Panax ginseng preparations.

    Science.gov (United States)

    Singh, A; Saxena, E; Bhutani, K K

    2000-03-01

    The levels of corticosterone were estimated by the HPLC method in the adrenal glands of stressed (5 h constant swimming) male albino mice treated with Trichopus zeylanicus, Withania somnifera and Panax ginseng preparations and compared with non-treated stressed and normal controls. The treatments increased the corticosterone levels in all the groups. The physical endurance (increased survival time) of swimming mice also increased in all the treated groups, except in the group treated with Withania somnifera powder (500 mg/kg, p.o.). Copyright 2000 John Wiley & Sons, Ltd.

  5. 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.

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

    OpenAIRE

    H. Raie; M. Kesmati; M. Zadkarami

    2006-01-01

    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 ...

  7. NGF induces appearance of adult-like response to spatial novelty in 18-day male mice.

    Science.gov (United States)

    Calamandrei, Gemma; Valanzano, Angela; Ricceri, Laura

    2002-10-17

    We investigated the effects of Nerve Growth Factor (NGF) administration on the maturation of reactivity to spatial and non-spatial novelty in developing mice. CD-1 mice of both sexes received intracerebral administration of NGF on postnatal day (pnd) 15, and their response to object displacement (spatial novelty) and object substitution (object novelty) were assessed in a spatial open-field with four objects on pnd 18 or 28. On pnd 18, NGF induced only in males precocious appearance of spatial novelty discrimination, while increasing choline acetyltransferase activity in neocortex and hippocampus of both sexes. The behavioral and neurochemical effects disappeared by pnd 28. NGF triggers adult-like responding to spatial novelty in developing mice and such effect is gender-specific.

  8. Metabolic consequences and vulnerability to diet-induced obesity in male mice under chronic social stress.

    Directory of Open Access Journals (Sweden)

    Alessandro Bartolomucci

    Full Text Available Social and psychological factors interact with genetic predisposition and dietary habit in determining obesity. However, relatively few pre-clinical studies address the role of psychosocial factors in metabolic disorders. Previous studies from our laboratory demonstrated in male mice: 1 opposite status-dependent effect on body weight gain under chronic psychosocial stress; 2 a reduction in body weight in individually housed (Ind male mice. In the present study these observations were extended to provide a comprehensive characterization of the metabolic consequences of chronic psychosocial stress and individual housing in adult CD-1 male mice. Results confirmed that in mice fed standard diet, dominant (Dom and Ind had a negative energy balance while subordinate (Sub had a positive energy balance. Locomotor activity was depressed in Sub and enhanced in Dom. Hyperphagia emerged for Dom and Sub and hypophagia for Ind. Dom also showed a consistent decrease of visceral fat pads weight as well as increased norepinephrine concentration and smaller adipocytes diameter in the perigonadal fat pad. On the contrary, under high fat diet Sub and, surprisingly, Ind showed higher while Dom showed lower vulnerability to obesity associated with hyperphagia. In conclusion, we demonstrated that social status under chronic stress and individual housing deeply affect mice metabolic functions in different, sometime opposite, directions. Food intake, the hedonic response to palatable food as well as the locomotor activity and the sympathetic activation within the adipose fat pads all represent causal factors explaining the different metabolic alterations observed. Overall this study demonstrates that pre-clinical animal models offer a suitable tool for the investigation of the metabolic consequences of chronic stress exposure and associated psychopathologies.

  9. Metabolic Consequences and Vulnerability to Diet-Induced Obesity in Male Mice under Chronic Social Stress

    Science.gov (United States)

    Bartolomucci, Alessandro; Cabassi, Aderville; Govoni, Paolo; Ceresini, Graziano; Cero, Cheryl; Berra, Daniela; Dadomo, Harold; Franceschini, Paolo; Dell'Omo, Giacomo

    2009-01-01

    Social and psychological factors interact with genetic predisposition and dietary habit in determining obesity. However, relatively few pre-clinical studies address the role of psychosocial factors in metabolic disorders. Previous studies from our laboratory demonstrated in male mice: 1) opposite status-dependent effect on body weight gain under chronic psychosocial stress; 2) a reduction in body weight in individually housed (Ind) male mice. In the present study these observations were extended to provide a comprehensive characterization of the metabolic consequences of chronic psychosocial stress and individual housing in adult CD-1 male mice. Results confirmed that in mice fed standard diet, dominant (Dom) and Ind had a negative energy balance while subordinate (Sub) had a positive energy balance. Locomotor activity was depressed in Sub and enhanced in Dom. Hyperphagia emerged for Dom and Sub and hypophagia for Ind. Dom also showed a consistent decrease of visceral fat pads weight as well as increased norepinephrine concentration and smaller adipocytes diameter in the perigonadal fat pad. On the contrary, under high fat diet Sub and, surprisingly, Ind showed higher while Dom showed lower vulnerability to obesity associated with hyperphagia. In conclusion, we demonstrated that social status under chronic stress and individual housing deeply affect mice metabolic functions in different, sometime opposite, directions. Food intake, the hedonic response to palatable food as well as the locomotor activity and the sympathetic activation within the adipose fat pads all represent causal factors explaining the different metabolic alterations observed. Overall this study demonstrates that pre-clinical animal models offer a suitable tool for the investigation of the metabolic consequences of chronic stress exposure and associated psychopathologies. PMID:19180229

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

    Science.gov (United States)

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

    2014-04-01

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

  11. Effect of Intermittent Feeding on Gonadal Function in Male And Female NMRI Mice During Chronic Stress

    Directory of Open Access Journals (Sweden)

    Badri Zarrin Ehteram

    2017-10-01

    Full Text Available ABSTRACT Stress can inhibit gonadal activity via Hypothalamus-Pituitary-Gonad (HPG axis activity suppression. In the present study, effects of intermittent feeding (IF on gonadal function under stress in male and female mice were evaluated. Twenty eight male and twenty eight female mice's were divided into four groups. The control group received adequate food and water without stress. The second group received four days of electric shock without food deprivation. The third group was deprived of food two hours/day for a week, and the fourth group was deprived of food (2 hours/day for seven consecutive days and then electric foot shock stress was applied to them for four days. Blood samples were collected from all animals for plasma testosterone, estrogen and/or Interlukin-6 (IL-6 evaluation. The animals’ gonads were also removed and fixed for the measure of their weight. Results showed that stress reduces both testosterone and estrogen levels, whereas IF did not change the hormone levels. In addition, stress increases blood IL-6 concentration. The combination of IF and stress, increased the hormone levels in animals. Stress and IF alone had no significant effect on gonadal weight in the male mice, whereas stress decreased gonadal weight in the females. Combination of stress with IF increased gonadal weight in both male and female mice. In conclusion stress showed a negative effect on gonadal function in both animals with more effect on females. Intermittent feeding inhibits the stress effect and even promotes the gonadal function in both sexes. The effect may be due to IL-6 reduction.

  12. 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)

  13. 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.

  14. Staying put or leaving home: endocrine, neuroendocrine and behavioral consequences in male African striped mice.

    Science.gov (United States)

    Schradin, Carsten; Kenkel, Wiliam; Krackow, Sven; Carter, C Sue

    2013-01-01

    Social flexibility occurs when individuals of both sexes can change their social and reproductive tactics, which in turn can influence the social system of an entire population. However, little is known regarding the extent to which individuals of socially flexible species vary in their social behavior and in the underlying physiological mechanisms that support different social tactics. The present study in African striped mice modeled in captivity three male tactics described from the field: (a) philopatric males remaining in the family; (b) solitary roamers; or (c) group-living breeding males. Sixteen pairs and their offspring were kept in captivity, while one male offspring from the family remained as singly housed after he reached 21 days of age. Differences in behavior, morphology, hormone and neuropeptide levels were tested, and physiological measurements were correlated with behavioral measurements. In standardized arena experiments group-living males (philopatrics and breeders) were significantly more aggressive than singly housed males, in agreement with previous data suggesting that group-living, but not roaming males, are territorial. Philopatric males showed signs of reproductive suppression, small testes, lower testosterone and higher corticosterone levels than their singly housed brothers. Higher levels of arginine vasopressin (AVP) were measured in the PVN and BNST of singly housed males compared to group-living males. Based on these findings we hypothesize that roamers are physiologically primed, and capable, if the opportunity to mate arises, to release AVP, form social bonds and become territorial, thus quickly adopting the tactic as breeding male which would yield a higher reproductive success. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Sucralose administered in feed, beginning prenatally through lifespan, induces hematopoietic neoplasias in male swiss mice.

    Science.gov (United States)

    M, Soffritti; M, Padovani; E, Tibaldi; L, Falcioni; F, Manservisi; M, Lauriola; L, Bua; M, Manservigi; F, Belpoggi

    2016-01-01

    Sucralose is an organochlorine artificial sweetener approximately 600 times sweeter than sucrose and used in over 4,500 products. Long-term carcinogenicity bioassays on rats and mice conducted on behalf of the manufacturer have failed to show the evidence of carcinogenic effects. The aim of this study was to evaluate the carcinogenic effect of sucralose in mice, using a sensitive experimental design. Five groups of male (total n = 457) and five groups female (total n = 396) Swiss mice were treated from 12 days of gestation through the lifespan with sucralose in their feed at concentrations of 0, 500, 2,000, 8,000, and 16,000 ppm. We found a significant dose-related increased incidence of males bearing malignant tumors (p neoplasias in males, in particular at the dose levels of 2,000 ppm (p < 0.01) and 16,000 ppm (p < 0.01). These findings do not support previous data that sucralose is biologically inert. More studies are necessary to show the safety of sucralose, including new and more adequate carcinogenic bioassay on rats. Considering that millions of people are likely exposed, follow-up studies are urgent.

  16. 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.

  17. 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.

  18. 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.

  19. Hematopoietic androgen receptor deficiency promotes visceral fat deposition in male mice without impairing glucose homeostasis.

    Science.gov (United States)

    Rubinow, K B; Wang, S; den Hartigh, L J; Subramanian, S; Morton, G J; Buaas, F W; Lamont, D; Gray, N; Braun, R E; Page, S T

    2015-07-01

    Androgen deficiency in men increases body fat, but the mechanisms by which testosterone suppresses fat deposition have not been elucidated fully. Adipose tissue macrophages express the androgen receptor (AR) and regulate adipose tissue remodeling. Thus, testosterone signaling in macrophages could alter the paracrine function of these cells and thereby contribute to the metabolic effects of androgens in men. A metabolic phenotyping study was performed to determine whether the loss of AR signaling in hematopoietic cells results in greater fat accumulation in male mice. C57BL/6J male mice (ages 12-14 weeks) underwent bone marrow transplant from either wild-type (WT) or AR knockout (ARKO) donors (n = 11-13 per group). Mice were fed a high-fat diet (60% fat) for 16 weeks. At baseline, 8 and 16 weeks, glucose and insulin tolerance tests were performed, and body composition was analyzed with fat-water imaging by MRI. No differences in body weight were observed between mice transplanted with WT bone marrow [WT(WTbm)] or ARKO bone marrow [WT(ARKObm)] prior to initiation of the high-fat diet. After 8 weeks of high-fat feeding, WT(ARKObm) mice exhibited significantly more visceral and total fat mass than WT(WTbm) animals. Despite this, no differences between groups were observed in glucose tolerance, insulin sensitivity, or plasma concentrations of insulin, glucose, leptin, or cholesterol, although WT(ARKObm) mice had higher plasma levels of adiponectin. Resultant data indicate that AR signaling in hematopoietic cells influences body fat distribution in male mice, and the absence of hematopoietic AR plays a permissive role in visceral fat accumulation. These findings demonstrate a metabolic role for AR signaling in marrow-derived cells and suggest a novel mechanism by which androgen deficiency in men might promote increased adiposity. The relative contributions of AR signaling in macrophages and other marrow-derived cells require further investigation. © 2015 American

  20. Smoking patterns and sociodemographic factors associated with tobacco use among Chinese rural male residents: a descriptive analysis

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    Feng Xiangxian

    2008-07-01

    Full Text Available Abstract Background Although evidence has shown high prevalence rates of tobacco use in the general urban populations in China, relatively little is known in its rural population. The purposes of this study were to examine smoking patterns and sociodemographic correlates of smoking in a sample of rural Chinese male residents. Methods The study employed a cross-sectional, multi-stage sampling design. Residents (N = 4,414; aged 15 years and older were recruited from four geographic regions in China. Information on participants' tobacco use (of all forms, including their daily use, and sociodemographic characteristics were collected via survey questionnaires and the resultant data were analyzed using chi-square tests and logistic regression procedures. Results The overall smoking prevalence in the study sample was 66.8% (n = 2,950. Of these, the average use of tobacco products per day was 12.70 (SD = 7.99 and over 60% reported daily smoking of more than 10 cigarettes. Geographic regions of the study areas, age of the participants, marital status, ethnicity, education, occupation, and average personal annual income were found to be significantly associated with an increased likelihood of smoking among rural Chinese male residents. Conclusion There is a high smoking prevalence in the Chinese rural population and smoking behaviors are associated with important sociodemographic factors. Findings suggest the need for tobacco control and intervention policies aimed at reducing tobacco use in Chinese rural smoking populations.

  1. 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.

  2. Chronic Water-Pipe Smoke Exposure Induces Injurious Effects to Reproductive System in Male Mice

    Science.gov (United States)

    Ali, Badreldin H.; Al Balushi, Khalid A.; Ashique, Mohammed; Shalaby, Asem; Al Kindi, Mohammed A.; Adham, Sirin A.; Karaca, Turan; Beegam, Sumaya; Yuvaraju, Priya; Nemmar, Abderrahim

    2017-01-01

    There is a global increase in the popularity of water-pipe tobacco smoking including in Europe and North America. Nevertheless, little is known about the male reproductive effects of water-pipe smoke (WPS), especially after long-term exposure. Here, we assessed effects of WPS exposure (30 min/day) in male mice for 6 months. Control mice were exposed to air-only for the same period of time. Twenty-four hours after the last exposure, testicular histopathology, and markers of inflammation and oxidative stress, and the tyrosine–protein kinase vascular endothelial growth factor receptor 1 (VEGFR1) were assessed in testicular homogenates. Moreover, plasma testosterone, estradiol, and luteinizing hormone (LH) concentrations were also measured. Chronic WPS exposure induced a significant decrease of testosterone and estradiol, and a slight but significant increase of LH. Glutathione reductase, catalase, and ascorbic acid were significantly decreased following WPS exposure. Plasma concentration of leptin was significantly decreased by WPS exposure, whereas that of tumor necrosis factor α and interleukin 6 was significantly increased. Histopathological analysis of the testes revealed the presence of a marked reduction in the diameter of the seminiferous tubules with reduced spermatogenesis. Transmission electron microscopy examination showed irregular thickening and wrinkling of the basement membranes with abnormal shapes and structures of the spermatozoa. VEGFR1 was overexpressed in the testis of the mice exposed to WPS and was not detected in the control. The urine concentration of cotinine, the predominant metabolite of nicotine, was significantly increased in the WPS-exposed group compared with the control group. We conclude that chronic exposure to WPS induces damaging effects to the reproductive system in male mice. If this can be confirmed in humans, it would be an additional concern to an already serious public health problem, especially with the increased use of

  3. Administration of melatonin protects against acetylsalicylic acid-induced impairment of male reproductive function in mice.

    Science.gov (United States)

    Emami, Niloufar Hedayati; Lafout, Farzaneh Mahmoudi; Mohammadghasemi, Fahimeh

    2018-02-01

    Melatonin, an important hormone secreted by the epiphysis, is a powerful anti-oxidant with a high potential to neutralize medical toxins. The goal of this study was to demonstrate the beneficial effect of melatonin on epididymal sperm and reproductive parameters in mice treated with acetylsalicylic acid (ASA). Male adult mice were divided into four treatment groups: control, ASA, melatonin, and ASA+melatonin. Mice were administered ASA (50 mg/kg, orally) and/or melatonin (10 mg/kg, intraperitoneally), or vehicle control, for 14 days. Sperm count, sperm motility, and sperm morphology were evaluated to assess fertility. A colorimetric assay was used to measure serum total antioxidant capacity (TAC). A sperm chromatin dispersion (SCD) test was used to assess sperm chromatin integrity. Sex hormone levels were measured by ELISA. Compared to the control group, ASA treatment resulted in a significant decrease in sperm parameters ( P <0.05), as well as a decrease in the integrity of sperm chromatin ( P <0.01). ASA treatment also reduced serum testosterone and TAC levels ( P <0.05). Co-administration of melatonin with ASA significantly improved epididymal sperm parameters and increased serum testosterone and TAC levels compared to the ASA-treated group. LH level was not different in the combined treatment group compared to control or ASA treatment. Short-term administration of ASA (50 mg/kg) has adverse effects on male reproductive function in mice. Co-administration of melatonin protects against ASA-induced impairment of male reproductive function by preventing the reduction in serum TAC and testosterone levels seen with ASA treatment alone.

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

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    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.

  5. Female puberty acceleration by male odour in mice: neural pathway and behavioural consequences.

    Science.gov (United States)

    Jouhanneau, Mélanie; Szymanski, Laura A; Keller, Matthieu

    2014-08-01

    In female mice, exposure to male chemosignals results in early puberty onset characterized by advanced vaginal opening and higher uterine weight. Evidence suggests that the male chemosignals responsible for acceleration of female puberty are androgen-dependent, but not all of the compounds that contribute to puberty acceleration have been identified. The male chemosignals are primarily detected and processed by the vomeronasal system including the vomeronasal organ, the accessory olfactory bulb and the medial amygdala. By contrast, the mechanism by which this olfactory information is integrated in the hypothalamus is poorly understood. In this context, the recent identification of the neuropeptide kisspeptin as a gatekeeper of puberty onset may provide a good candidate neuropeptide system for the transmission of chemosensory information to the gonadotrope axis.

  6. 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.

  7. 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 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.

  8. 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.

  9. Photoperiodic regulation of hippocampal neurogenesis in adult male white-footed mice (Peromyscus leucopus).

    Science.gov (United States)

    Walton, James C; Aubrecht, Taryn G; Weil, Zachary M; Leuner, Benedetta; Nelson, Randy J

    2014-08-01

    Photoperiodic organisms monitor environmental day length to engage in seasonally appropriate adaptions in physiology and behavior. Among these adaptations are changes in brain volume and neurogenesis, which have been well described in multiple species of birds, yet few studies have described such changes in the brains of adult mammals. White-footed mice (Peromyscus leucopus) are an excellent species in which to investigate the effects of day length on adult hippocampal neurogenesis, as males, in addition to having reduced hippocampal volume in short days (SD) with concomitant impairments in hippocampus-mediated behaviors, have photoperiod-dependent changes in olfactory bulb neurogenesis. We performed the current experiment to assess the effects of photoperiod on hippocampal neurogenesis longitudinally, using the thymidine analog bromodeoxyuridine at multiple time points across 10 weeks of SD exposure. Compared with counterparts held in long day (LD) lengths, across the first 8 weeks of SD exposure hippocampal neurogenesis was reduced. However, at 10 weeks in SD lengths neurogenic levels in the hippocampus were elevated above those levels in mice held in LD lengths. The current findings are consistent with the natural photoperiodic cycle of hippocampal function in male white-footed mice, and may help to inform research on photoperiodic plasticity in neurogenesis and provide insight into how the complex interplay among the environment, genes and adaptive responses to changing day lengths affects brain structure, function and behavior at multiple levels. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  10. Reduced Fertility in Male Mice Deficient in the Zinc Metallopeptidase NL1

    Science.gov (United States)

    Carpentier, Mélanie; Guillemette, Christine; Bailey, Janice L.; Boileau, Guy; Jeannotte, Lucie; DesGroseillers, Luc; Charron, Jean

    2004-01-01

    Members of the M13 family of zinc metalloendopeptidases have been shown to play critical roles in the metabolism of various neuropeptides and peptide hormones, and they have been identified as important therapeutic targets. Recently, a mouse NL1 protein, a novel member of the family, was identified and shown to be expressed mainly in the testis as a secreted protein. To define its physiological role(s), we used a gene targeting strategy to disrupt the endogenous murine Nl1 gene by homologous recombination and generate Nl1 mutant mice. The Nl1−/− mice were viable and developed normally, suggesting that zygotic expression of Nl1 is not required for development. However, Nl1−/− males produced smaller litters than their wild-type siblings, indicating specific male fertility problems. Reduced fertility may be explained by two impaired processes, decreased egg fertilization and perturbed early development of fertilized eggs. These two phenotypes did not result from gross anatomical modifications of the testis or from impaired spermatogenesis. Basic sperm parameters were also normal. Thus, our findings suggest that one of the roles of NL1 in mice is related to sperm function and that NL1 modulates the processes of fertilization and early embryonic development in vivo. PMID:15121861

  11. 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.

  12. 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

  13. 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.

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

    Science.gov (United States)

    Walvekar, Madhuri; Shaikh, Nilofar; Sarvalkar, Priti

    2013-09-01

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

  15. 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.

  16. 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

  17. [Chronotoxicity of 1800 MHz microwave radiation on sex hormones and spermatogenesis in male mice].

    Science.gov (United States)

    Chen, Lili; Qin, Fenju; Chen, Yuzhi; Sun, Jinpeng; Tong, Jian

    2014-01-01

    To study the chronotoxicity of 1800 MHz micrwave radiation on the male reproductive system. Sixty healthy male C57 mice with circadian rhythm in a 12:12 h light-dark photoperiod were divided into false radiation group (Sham) and microwave radiation (MR) group exposed to 1800 MHz RF at 208 microW/cm2 power (SAR: 0 .2221 W/kg) density at different zeitgeber times of a day (ZT01:00, ZT05:00, ZT09 : 00, ZT13: 00, ZT17 : 00, ZT21 : 00) for continuous 32 days with 2 h/d. The testicular sperm head was counted with a microscope, and serum testosterone (T) and estradiol (E2) levels were measured by ELISA method. Compared with the sham group,microwave radiation induced reduced level in testicular sperm head count and serum testosterone, while the level of serum estradiol increased. Also, the circadian rhythms of testicular sperm head count and estradiol disappeared after the microwave radiation. 1800 MH2 microwave radiation may disturb the level as well as circadian rhythmicity of the reproductive functions in male mice.

  18. 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

  19. Cohabitation with an Ehrlich tumor-bearing cagemate induces immune but not behavioral changes in male mice.

    Science.gov (United States)

    Machado, Thalita R M; Alves, Glaucie J; Quinteiro-Filho, Wanderley M; Palermo-Neto, João

    2017-02-01

    Cohabitation with Ehrlich ascitic tumor-injected conspecifics induces behavioral, neurochemical, endocrine and immune changes indicative of stress and immune impairment in female mice. The present work analyzed the effects of similar cohabitation in Swiss and Balb/C male mice. At least 12 pairs of male mice were divided into a control group and an experimental group. On experimental day 1 (ED1), one animal within each experimental pair was inoculated with 5×10 6 Ehrlich tumor cells intraperitoneally (i.p.); the other animal was kept undisturbed and was referred to as the CSP (companion of a sick partner). One male mouse of each control pair was treated i.p. with 0.9% NaCl (1mL/kg); the other animal (the CHP, companion of a healthy partner) was kept undisturbed. Cohabitation with a sick partner for 11days did not induce any behavioral, hypothalamic noradrenergic, corticosterone or adrenal weight changes in the Swiss CSP male mice compared to those of the Swiss CHP group. However, impairments in neutrophil phagocytosis and oxidative burst as well as increased levels of catecholamines were observed in Swiss and Balb/C CSP mice relative to CHP male animals of the same strains on ED11 and ED14, respectively. Moreover, after a challenge with 5×10 6 Ehrlich tumor cells on ED11 of cohabitation, the number and concentration of tumor cells found in the ascitic fluid were higher in the Swiss CSP male mice than in the CHP mice. These data suggest that the immune changes observed in Swiss and Balb/C male CSP mice after cohabitation with a sick cagemate might, ultimately, depend on the changes induced by catecholamines, as previously reported for CSP female mice. However, contrary to that reported in Swiss CSP female mice, changes in behavioral and hypothalamic noradrenaline activity were not found in the Swiss CSP male mice analyzed in this work. This fact suggests that male and female CSP mice might use similar immune but different CNS strategies against the threats posed by

  20. 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)

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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 .

  6. 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.

  7. 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.

  8. Stroke increases g protein-coupled estrogen receptor expression in the brain of male but not female mice.

    Science.gov (United States)

    Broughton, Brad R S; Brait, Vanessa H; Guida, Elizabeth; Lee, Seyoung; Arumugam, Thiruma V; Gardiner-Mann, Chantelle V; Miller, Alyson A; Tang, Sung-Chun; Drummond, Grant R; Sobey, Christopher G

    2013-01-01

    The novel estrogen receptor, G protein-coupled estrogen receptor (GPER, previously named GPR30), is widely distributed throughout the male and female brain and, thus, could potentially play a role in estrogen-mediated neuroprotective effects in diseases such as stroke. We hypothesized that GPER distribution and expression in the brain of male, intact female, and ovariectomized (OVX) mice is increased after 0.5 h middle cerebral artery occlusion. Using immunohistochemistry, we found that ischemia reperfusion increased GPER distribution in the peri-infarct brain regions of male mice, but surprisingly not in intact females or OVX mice. Similar differences were observed in the male and female human brain after stroke. In contrast, GPER distribution was decreased in the infarct core of all mice examined. Furthermore, GPER immunofluorescence was co-localized with the endothelial cell marker, von Willebrand factor, and the neuronal marker, NeuN. Consistent with the immunohistochemical findings, Western blot analysis showed GPER expression is only elevated in the ischemic hemisphere of male mice. Moreover, GPER mRNA expression in males was elevated at 4 h but had returned to baseline by 24 h. In conclusion, these findings indicate that GPER may be a potential therapeutic target after stroke, especially in males, in whom estrogen therapy is not feasible. Copyright © 2012 S. Karger AG, Basel.

  9. Differential Influence of Early Life and Adult Stress on Urogenital Sensitivity and Function in Male Mice

    Science.gov (United States)

    Fuentes, Isabella M.; Pierce, Angela N.; Di Silvestro, Elizabeth R.; Maloney, Molly O.; Christianson, Julie A.

    2018-01-01

    Experiences of adverse childhood events have been associated with improper output of the hypothalamic-pituitary-adrenal (HPA) axis in adulthood, as well as development of comorbid functional pain disorders. Symptoms of chronic prostatitis/chronic pelvic pain syndrome frequently overlap with those of interstitial cystitis/painful bladder syndrome and symptom severity is often triggered by stress. The objective of this study was to investigate the influence early life stress and acute adult stress on (1) perigenital sensitivity, (2) micturition, (3) anhedonia, and (4) HPA axis regulation and output in male C56Bl/6 mice. Neonatal maternal separation (NMS) was performed for 3 h a day from postnatal day 1 to 21 and naïve pups remained unhandled during this time. As adults, male mice were tested for referred prostate sensitivity and micturition patterning prior to and 1 and 8 days after exposure to 1 h of water avoidance stress (WAS). Following testing, prostate and bladder tissues were used for mast cell and Western blot analysis and RT-PCR was performed on mRNA from hypothalamus, amygdala, and hippocampus. Serum corticosterone (CORT) was also measured by enzyme-linked immunosorbent assay (ELISA). A significant increase in perigenital sensitivity and micturition frequency was observed in NMS mice and these measures were exacerbated by WAS exposure. Exposure to NMS significantly increased mast cell degranulation in both the bladder and prostate. Mast cell degranulation was also increased in naïve prostate tissue following WAS exposure. Cytokine mRNA levels were influenced by both NMS and WAS exposure, though WAS had a larger impact on central gene expression. Protein levels of CRF1 were differentially regulated by NMS and WAS in the bladder and prostate and serum CORT levels were significantly diminished following stress exposure. Taken together, these data suggest that NMS results in neurogenic inflammation and hypersensitivity within the urogenital organs, coupled

  10. Survey of some heavy metals in sediments from vehicular service stations in Jordan and their effects on social aggression in prepubertal male mice.

    Science.gov (United States)

    Homady, Merza; Hussein, Helmi; Jiries, Anwar; Mahasneh, Ali; Al-Nasir, Farah; Khleifat, Khaled

    2002-05-01

    Vehicle services create the potential for heavy metal accumulation in the working environment. This study assessed five vehicle services, namely body repair, oil exchange, mechanical repair, tire repair, electrical repair, and washing services for three types of vehicles: airplanes, buses, and cars. The results show that there are significant increases in the total contents of Fe, Cu, Pb, Zn, Ni, Mn, and Cr in ambient dust, with Fe being the highest and Cr the lowest. The main cause of the presence of these elements is due to the metals' corrosion from vehicle sources and petroleum residue. Variations in the concentrations with the type of service and within the same service at different locations were observed. In this study, the exposure of prepubertal male mice to industrial metal salts in drinking water at a concentration of 1000 ppm for 90 days was investigated. Exposure of male mice to lead acetate significantly reduced the social aggression of the resident untreated subjects. Additionally, this treatment resulted in decreasing weights of body, testes, preputial glands, and seminal vesicles. In comparison, no such effects were seen in mice given copper chloride or manganese chloride. The results show that only lead acetate produced a pattern of responses clearly indicative of altered gonadal function. 2002 Elsevier Science (USA)

  11. Central oxytocin regulates social familiarity and scent marking behavior that involves amicable odor signals between male mice.

    Science.gov (United States)

    Arakawa, Hiroyuki; Blanchard, D Caroline; Blanchard, Robert J

    2015-07-01

    The effect of oxytocin on social behavior and odor communication was investigated in male C57BL/6J mice. In three-male colonies, in visible burrow systems, icv oxytocin (OT) infusion before colony formation substantially increased huddling together over the initial 8 h of grouping, accompanied by decreased expression of a number of social approaches associated with conspecific aggression and defense. OT antagonist infusion had little impact on expression of social approaches but decreased time engaging in social components including huddle over the initial 8 h. These results demonstrate a linkage of social familiarity to OT availability in the brain. In a scent marking paradigm central infusion of OT reduced territorial marking towards male conspecifics, and this in turn reduced the scent marking of untreated stimulus males to OT-infused subjects. Infusion of an OT antagonist into stimulus mice who were confronted with OT-infused subjects prevented the reduction/suppression of scent marking that was normally seen following exposure of social odors released from OT-injected mice. Odor of pair-housed mice also induced a suppression of territorial scent marking in odor recipients, but OT antagonist administration into pair-housed mice blocked this suppressive effect of odor cue. These results indicate that central OT modulates release as well as detection of amicable signals facilitating/maintaining familiar relationships and suppressing territorial behavior between male mice. Overall, these findings suggest that OT plays a significant role in regulating social familiarity via changing qualities of conspecific odor cues.

  12. 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.

  13. Investigation of the Regulatory Effects of Saccharin on Cytochrome P450s in Male ICR Mice.

    Science.gov (United States)

    Jo, Jun Hyeon; Kim, Sunjoo; Jeon, Tae Won; Jeong, Tae Cheon; Lee, Sangkyu

    2017-01-01

    Saccharin, the first artificial sweetener, was discovered in 1879 that do not have any calories and is approximately 200~700 times sweeter than sugar. Saccharin was the most common domestically produced sweetener in Korea in 2010, and it has been used as an alternative to sugar in many products. The interaction between artificial sweeteners and drugs may affect the drug metabolism in patients with diabetes, cancer, and liver damage, this interaction has not been clarified thus far. Here, we examined the effects of the potential saccharin-drug interaction on the activities of 5 cytochrome P450 (CYPs) in male ICR mice; further, we examined the effects of saccharin (4,000 mg/kg) on the pharmacokinetics of bupropion after pretreatment of mice with saccharin for 7 days and after concomitant administration of bupropion and saccharin. Our results showed saccharin did not have a significant effect on the 5 CYPs in the S9 fractions obtained from the liver of mice. In addition, we observed no differences in the pharmacokinetic parameters of bupropion between the control group and the groups pretreated with saccharin and that receiving concomitant administration of saccharin. Thus, our results showed that saccharin is safe and the risk of saccharin-drug interaction is very low.

  14. Diet-induced obesity in male mice is associated with reduced fertility and potentiation of acrylamide-induced reproductive toxicity.

    Science.gov (United States)

    Ghanayem, Burhan I; Bai, Re; Kissling, Grace E; Travlos, Greg; Hoffler, Undi

    2010-01-01

    The prevalence of human obesity and related chronic disorders such as diabetes, cardiovascular diseases, and cancer is rapidly increasing. Human studies have shown a direct relationship between obesity and infertility. The objective of the current work was to examine the effect of diet-induced obesity on male fertility and the effect of obesity on susceptibility to chemical-induced reproductive toxicity. From 5 to 30 wk of age, genetically intact male C57Bl/6J mice were fed a normal diet or one in which 60% of the kilocalories were from lard. Obese mice exhibited significant differences in the mRNA of several genes within the testes in comparison to lean males. Pparg was increased 2.2-fold, whereas Crem, Sh2b1, Dhh, Igf1, and Lepr were decreased 6.7, 1.4, 3.2, 1.6, and 7.2-fold, respectively. The fertility of male mice was compared through mating with control females. Acrylamide (AA)-induced reproductive toxicity was assessed in obese or lean males treated with water or 25 mg AA kg(-1) day(-1) via gavage for 5 days and then mated to control females. Percent body fat and weight were significantly increased in mice fed a high-fat vs. a normal diet. Obesity resulted in significant reduction in plugs and pregnancies of control females partnered with obese vs. lean males. Serum leptin and insulin levels were each approximately 5-fold higher in obese vs. age-matched lean mice. Sperm from obese males exhibited decreased motility and reduced hyperactivated progression vs. lean mice. Treatment with AA exacerbated male infertility of obese and lean mice; however, this effect was more pronounced in obese mice. Further, females partnered with AA-treated obese mice exhibited a further decrease in the percentage of live fetuses, whereas the percentage of resorptions increased. This work demonstrated that diet-induced obesity in mice caused a significant reduction in male fertility and exacerbated AA-induced reproductive toxicity and germ cell mutagenicity.

  15. 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.

  16. 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.

  17. 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

  18. The effects of imperatorin on anxiety and memory-related behavior in male Swiss mice.

    Science.gov (United States)

    Budzynska, Barbara; Kruk-Slomka, Marta; Skalicka-Wozniak, Krystyna; Biala, Grazyna; Glowniak, Kazimierz

    2012-08-01

    The purpose of the reported experiments was to examine the effects of imperatorin [9-(3-methylbut-2-enyloxy)-7H-furo[3,2-g]chromen-7-one], a bioactive furanocoumarin isolated from the fruits of Angelica archangelica (Angelica officinalis) on anxiety and memory-related behaviors of mice. Male Swiss mice were tested for anxiety and cognition, in the elevated plus maze test (EPM), using two different procedures. In the present experiments, imperatorin was administered acutely (at the doses of 5, 10, 20, 30, and 50 mg/kg); injections were made 15, 30, and 60 min before test (anxiety); 30 min before the first trial (memory acquisition); or immediately after the first trial (memory consolidation), as well as subchronically, twice a day for 6 days. On the seventh day, the mice were injected once with imperatorin (10 and 20 mg/kg, i.p.) 30 min before the test (anxiety) and 30 min before the first trial (memory acquisition), or immediately after the first trial (memory consolidation). We observed that imperatorin when administered acutely and repeatedly, at the doses of 10 and 20 mg/kg, exerted an anxiolytic effect on mice tested 30 min after the injection measured in the EPM test. By contrast, no such effect was observed after the acute administration of imperatorin at the doses of 5, 30 and 50 mg/kg. Moreover, other observations carried out 15 and 60 min after a single injection of the drug did not reveal any effect of imperatorin on anxiety behavior in the EPM test. Furthermore, acute and repeated administration of imperatorin (10 and 20 mg/kg) improved different stages of memory processes (both acquisition and consolidation) in a modified EPM test (mEPM). The results of our research suggest imperatorin to be an interesting therapeutical option in disorders with high anxiety levels and memory impairment.

  19. 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.

  20. 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

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    Surekha Devadasa Shetty

    2015-01-01

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

  3. 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.

  4. 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.

  5. Lack of annexin 1 results in an increase in corticotroph number in male but not female mice.

    Science.gov (United States)

    Morris, J F; Omer, S; Davies, E; Wang, E; John, C; Afzal, T; Wain, S; Buckingham, J C; Flower, R J; Christian, H C

    2006-11-01

    Annexin 1 (ANXA1) is a member of the annexin family of phospholipid- and calcium-binding proteins with a well demonstrated role in early delayed (30 min to 3 h) inhibitory feedback of glucocorticoids in the pituitary. We have examined corticotrophs in wild-type and ANXA1 knockout mice to determine the effects of lack of ANXA1 in male and female animals. Anterior pituitary tissue from ANXA1 wild-type, heterozygote and null mice was fixed and examined (i) by confocal immunocytochemistry to determine the number of corticotrophs and (ii) by electron microscopy to examine the size, secretory granule population and secretory machinery of corticotrophs. No differences in these parameters were detected in female mice. In male ANXA1 null mice, there were approximately four-fold more corticotrophs than in wild-type animals. However, the corticotrophs in ANXA1 null mice were smaller and had reduced numbers of secretory granules (the reduction in granules paralleled the reduction in cell size). No differences in the numerical density of folliculo-stellate, gonadotroph, lactotroph or somatotroph cells were detected in male ANXA1 null mice. Plasma corticosterone, adrenocorticotrophic hormone (ACTH) and pituitary pro-opiomelanocortin mRNA were unchanged but pituitary ACTH content was increased in male ANXA1 null mice. Interleukin (IL)-6 pituitary content was significantly elevated in male and reduced in female ANXA1 null mice compared to wild-type. In conclusion, these data indicate that ANXA1 deficiency is associated with gender-specific changes in corticotroph number and structure, via direct actions of ANXA1 and/or indirect changes in factors such as IL-6.

  6. 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

  7. Psychological characteristics of the male beater of their female partner, residing in city of Bucaramanga, Colombia.

    Directory of Open Access Journals (Sweden)

    Armando Aguilera Torrado

    2004-08-01

    Full Text Available Objective: To evaluate the personalities of the male beater of their female partner. Method: We evaluate, by means of BFQ / IMAFE tests, 50 convicted aggressors, registered by the Attorney General Office. We also interviewedthem. Results: Aggressors had very low marks in general culture, information, cooperativism, cordiality, altruism, friendship, generosity and empathy. They showed a low marks in reflexion, order, and in being meticulous, diligent, perseverant, as wells as, in being energetic and dynamic. High marks in submission, and in being anxious, vulnerable, emotive, impulsive, impatient and irritable. The vast majority identifies the above symptoms as culturally associate with feminism. It is clear through the interview that the economical stability, alcohol abuse or their female partner plays an important role to explain their behavior. They do not consider themselves as being violent with their female partner, rather they blame upon their cultural, social and economical status, as being the direct responsible for beating women. Conclusions: The female aggressor, usually, is a man with traditional ideas, paternal values and resistant to changes. This will be reflected upon his personality characteristics and the meaning he has for his violent behavior. Probably this may, also, reflects a homophobic and misogynist feelings, which, usually, is a product of gender identity and in the process of building his masculinity, no responding, also, to the request from the “macho” pattern asked by his paternal culture.

  8. 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.

  9. 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

  10. Progesterone reduces brain mitochondrial dysfunction after transient focal ischemia in male and female mice.

    Science.gov (United States)

    Gaignard, Pauline; Fréchou, Magalie; Schumacher, Michael; Thérond, Patrice; Mattern, Claudia; Slama, Abdelhamid; Guennoun, Rachida

    2016-03-01

    This study investigated the effect of intranasal administration of progesterone on the early brain mitochondrial respiratory chain dysfunction and oxidative damage after transient middle cerebral occlusion in male and female mice. We showed that progesterone (8 mg/kg at 1 h post-middle cerebral occlusion) restored the mitochondrial reduced glutathione pool and the nicotinamide adenine dinucleotide-linked respiration in both sexes. Progesterone also reversed the decrease of the flavin adenine dinucleotide-linked respiration, which was only observed in females. Our findings point to a sex difference in stroke effects on the brain respiratory chain and suggest that the actions of progesterone on mitochondrial function may participate in its neuroprotective properties. © The Author(s) 2015.

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

    Science.gov (United States)

    Hew, Jonathan; Solon-Biet, Samantha M; 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.

  12. Prenatal exposure to modafinil alters behavioural response to methamphetamine in adult male mice.

    Science.gov (United States)

    Ruda-Kucerova, Jana; Pistovcakova, Jana; Amchova, Petra; Sulcova, Alexandra; Machalova, Alena

    2018-03-20

    Modafinil is a psychostimulant drug prescribed for treatment of narcolepsy. However, it is used as a "smart drug" especially by young adults to increase wakefulness, concentration and mental performance. Therefore, it can also be used by women with childbearing potential and its developmental effects can become a concern. The aim of this study was to assess behavioural and immune effects of prenatal modafinil exposure in mice and to evaluate the reaction to methamphetamine exposure on these animals in adult age. Pregnant female mice were given either saline or modafinil (50 mg/kg orally) from gestation day (GD) 3 to GD 10 and then a challenge dose on GD 17. The male offspring were treated analogously at the age of 10 weeks with methamphetamine (2.5 mg/kg orally). Changes in the spontaneous locomotor/exploratory behaviour and anxiogenic profile in the open field test were assessed in naïve animals, after an acute and 8th modafinil dose and the challenge dose following a 7-day wash-out period. One month after completion of the behavioural study, the leukocyte phagocytosis was examined by zymosan induced and luminol-aided chemiluminiscence assay in vitro. The modafinil prenatally exposed mice showed basal hypolocomotion, increased anxiety, lower locomotor effect of acute methamphetamine and increased vulnerability to behavioural sensitization. The leukocyte activity did not show significant differences. Prenatal modafinil exposure alters basal behavioural profile, decreases acute effect of methamphetamine and enhances vulnerability to development of behavioural sensitization at adulthood. This may lead to higher vulnerability to development of addiction. Copyright © 2018 ISDN. Published by Elsevier Ltd. All rights reserved.

  13. 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.

  14. Peripheral inflammatory pain sensitisation is independent of mast cell activation in male mice.

    Science.gov (United States)

    Lopes, Douglas M; Denk, Franziska; Chisholm, Kim I; Suddason, Tesha; Durrieux, Camille; Thakur, Matthew; Gentry, Clive; McMahon, Stephen B

    2017-07-01

    The immune and sensory systems are known for their close proximity and interaction. Indeed, in a variety of pain states, a myriad of different immune cells are activated and recruited, playing a key role in neuronal sensitisation. During inflammatory pain it is thought that mast cells (MC) are one of the immune cell types involved in this process, but so far the evidence outlining their direct effect on neuronal cells remains unclear. To clarify whether MC are involved in inflammatory pain states, we used a transgenic mouse line (Mctp5Cre-iDTR) in which MC could be depleted in an inducible manner by administration of diphtheria toxin. Our results show that ablation of MC in male mice did not result in any change in mechanical and thermal hypersensitivity in the CFA model of inflammatory pain. Similarly, edema and temperature triggered by CFA inflammation at the injection site remained identical in MC depleted mice compared with their littermate controls. In addition, we show that Mctp5Cre-iDTR mice display normal levels of mechanical hypersensitivity after local injection of nerve growth factor (NGF), a factor well characterised to produce peripheral sensitisation and for being upregulated upon injury and inflammation. We also demonstrate that NGF treatment in vitro does not lead to an increased level of tumor necrosis factor-α in bone marrow-derived MC. Furthermore, our qRT-PCR data reveal that MC express negligible levels of NGF receptors, thereby explaining the lack of response to NGF. Together, our data suggest that MC do not play a direct role in peripheral sensitisation during inflammatory conditions.

  15. Neurochemical and behavioural impact of C18 fatty acids in male mice postweaning.

    Science.gov (United States)

    Yamamuro, Yutaka; Yamaguchi, Yuki; Abe, Shin; Takenaga, Fumio

    2013-06-01

    Dietary components, particularly essential fatty acids, affect the expression and maintenance of normal physiological phenotypes. However, the influence of C18 fatty acids that are abundantly present in the normal diet is unclear. We focused on the behavioural and neurochemical effects of C18 fatty acids during postweaning development in male mice. An AIN-93G diet supplemented with 8% stearic acid (C18:0), 3% oleic acid (C18:1), 3% linoleic acid (C18:2) or 3% α-linolenic acid (C18:3) was provided from four weeks of age for eight weeks. At 12 weeks of age, novel exploratory behaviour and social interaction tests were carried out. One week after the last behavioural test, the brain of each mouse was removed. The frequency of social interactive behaviour was decreased by approximately 70% in the C18:0 group compared to the basal diet group, but there was no difference in cumulative time. The frequency of social interaction showed a positive correlation to cumulative time in mice fed with the experimental diets except for C18:0. Dietary C18 fatty acids following weaning had no impact on brain fatty acid composition except for the C18:3 diet. Furthermore, the neurochemical properties to be especially noted were that choline acetyltransferase activity was absolutely higher in C18:0 diet-fed mice than in the other groups, especially in the frontal cortex where it was 1.7-fold higher than in the basal diet-fed group. The present results reveal a significant possibility of neurochemical and behavioural effects of dietary fatty acids, and saturated fatty acids are of special importance during the postweaning period.

  16. Adult Male Mice Emit Context-Specific Ultrasonic Vocalizations That Are Modulated by Prior Isolation or Group Rearing Environment

    Science.gov (United States)

    Ey, Elodie; Bellier, Ludovic; Aubin, Thierry; Bourgeron, Thomas; Granon, Sylvie

    2012-01-01

    Social interactions in mice are frequently analysed in genetically modified strains in order to get insight of disorders affecting social interactions such as autism spectrum disorders. Different types of social interactions have been described, mostly between females and pups, and between adult males and females. However, we recently showed that social interactions between adult males could also encompass cognitive and motivational features. During social interactions, rodents emit ultrasonic vocalizations (USVs), but it remains unknown if call types are differently used depending of the context and if they are correlated with motivational state. Here, we recorded the calls of adult C57BL/6J male mice in various behavioral conditions, such as social interaction, novelty exploration and restraint stress. We introduced a modulator for the motivational state by comparing males maintained in isolation and males maintained in groups before the experiments. Male mice uttered USVs in all social and non-social situations, and even in a stressful restraint context. They nevertheless emitted the most important number of calls with the largest diversity of call types in social interactions, particularly when showing a high motivation for social contact. For mice maintained in social isolation, the number of calls recorded was positively correlated with the duration of social contacts, and most calls were uttered during contacts between the two mice. This correlation was not observed in mice maintained in groups. These results open the way for a deeper understanding and characterization of acoustic signals associated with social interactions. They can also help evaluating the role of motivational states in the emission of acoustic signals. PMID:22238608

  17. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. 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.

  1. Radiolabeling and autoradiographic tracing of Toxocara canis larvae in male mice

    International Nuclear Information System (INIS)

    Wade, S.E.; Georgi, J.R.

    1987-01-01

    Artificially hatched infective larvae of Toxocara canis were labeled with 75 Se in Medium 199 (Gibco) containing 75 Se-methionine. Male CD-1 mice were infected with radiolabeled larvae by intragastric intubation or by intraperitoneal injection. At intervals of 3-56 days mice were killed and the organs prepared for compressed organ autoradiography. Radioactivity of parasitic larvae showed an exponential decrease with time, reflecting catabolism of label with a biological half life of 26 days (effective half life of 21 days) making possible experiments lasting several months. Total body larva counts, estimated by total body autoradiography, displayed an overall downward trend, but the rate of reduction was probably not constant because no significant positive or negative trends were noted from day 14 onward in the numbers of larvae. The carcass accumulated the greatest number of larvae followed by the central nervous system, liver, and lung in that order. When the numbers of larvae were considered in relationship to the mass of tissue, there were 4 groupings: central nervous system, liver, lung, carcass, and kidney, and genito-urinary organ, pelt, and intestine. No significant difference between intragastric and intraperitoneal administration was observed in the larval distribution after the larvae had left the initial site of deposition

  2. Radiolabeling and autoradiographic tracing of Toxocara canis larvae in male mice

    Energy Technology Data Exchange (ETDEWEB)

    Wade, S.E.; Georgi, J.R.

    1987-02-01

    Artificially hatched infective larvae of Toxocara canis were labeled with /sup 75/Se in Medium 199 (Gibco) containing /sup 75/Se-methionine. Male CD-1 mice were infected with radiolabeled larvae by intragastric intubation or by intraperitoneal injection. At intervals of 3-56 days mice were killed and the organs prepared for compressed organ autoradiography. Radioactivity of parasitic larvae showed an exponential decrease with time, reflecting catabolism of label with a biological half life of 26 days (effective half life of 21 days) making possible experiments lasting several months. Total body larva counts, estimated by total body autoradiography, displayed an overall downward trend, but the rate of reduction was probably not constant because no significant positive or negative trends were noted from day 14 onward in the numbers of larvae. The carcass accumulated the greatest number of larvae followed by the central nervous system, liver, and lung in that order. When the numbers of larvae were considered in relationship to the mass of tissue, there were 4 groupings: central nervous system, liver, lung, carcass, and kidney, and genito-urinary organ, pelt, and intestine. No significant difference between intragastric and intraperitoneal administration was observed in the larval distribution after the larvae had left the initial site of deposition.

  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. 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.

  6. 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.

  7. The tendency for social submission predicts superior cognitive performance in previously isolated male mice.

    Science.gov (United States)

    Matzel, Louis D; Kolata, Stefan; Light, Kenneth; Sauce, Bruno

    2017-01-01

    The imposition of subordination may negatively impact cognitive performance in common social settings (e.g., the classroom), and likewise, laboratory studies of animals indicate that the stress associated with social defeat can impair cognitive performance. It is less clear whether an animal's predisposition for social subordination (i.e., a tendency that is expressed prior to experience with social defeat) is related to its cognitive abilities (e.g., "general" intelligence). Using genetically diverse CD-1 male mice, here we determined that in the absence of adult experience with social hierarchies or social defeat, the predisposition for social subordination was associated with superior general cognitive ability (aggregate performance across a battery of five learning tasks). The tendency for social subordination was not dependent on the mice' body weight, but both general cognitive ability and the tendency for social subordination were directly related to high stress reactivity (i.e., free corticosterone elevations induced by mild stress). This pattern of results suggests that submissive behavior and sensitivity to stress may be associated with superior cognitive potential, and this can reflect a native predisposition that precedes exposure to social pressures. More broadly, these results raise the possibility that socially subordinate animals evolved compensatory strategies to facilitate their survival, and that absent the imposition of subordination, normally submissive individuals may be better prepared for cognitive/academic achievement. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. 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

    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......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...

  9. Similar response in male and female B10.RIII mice in a murine model of allergic airway inflammation

    DEFF Research Database (Denmark)

    Matheu, Victor; Barrios, Ysamar; Arnau, Maria-Rosa

    2009-01-01

    BACKGROUND: Several reports have been published on the gender differences associated with allergies in mice. GOAL: In the present study we investigate the influence of gender on allergy response using a strain of mice, B10.RIII, which is commonly used in the collagen-induced arthritis murine model....... METHODS: Both male and female B10.RIII young mice were immunized with OVA and challenged four times with OVA intranasally. Samples were taken 24 h after the last challenge, and eosinophils in bronchoalveolar lavage (BAL) and parenchyma, Th-2 cytokines in BAL, total and antigen-specific IgE in sera...

  10. Effect of Ovarian Hormones and Mating Experience on the Preference of Female Mice to Investigate Male Urinary Pheromones.

    Science.gov (United States)

    McCarthy, Elizabeth A; Naik, Ajay S; Coyne, Allison F; Cherry, James A; Baum, Michael J

    2018-02-02

    In female mice, the expression of receptive lordosis behavior requires estradiol and progesterone actions in the nervous system; however, the contribution of these hormones to females' motivation to seek out male pheromones is less clear. In an initial experiment, sexually naïve ovary-intact female mice preferred to investigate (make nasal contact with) testes-intact male as opposed to estrous female urine, provided they were in vaginal estrus. In a second experiment, groups of sexually naïve and mating-experienced, ovariectomized females were tested for urinary pheromone preference first without and then with ovarian hormone replacement. Without hormone replacement, sexually naïve ovariectomized females showed no preference for male over female urinary pheromones whereas mating-experienced females preferred to investigate male pheromones. Ovariectomized females in both groups preferred male over female urine after sequential s.c. injections with estradiol benzoate followed 2 days later with progesterone and after prolonged (7 days) exposure to estradiol alone. Our results indicate that in sexually naïve female mice estradiol, perhaps aided by progesterone, is required to motivate a preference to seek out male pheromones whereas after mating experience females' preference to investigate male pheromones persists even in the absence of ovarian hormone action. © The Author(s) 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. 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

  13. 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

  14. 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.

  15. Morphological Characterization of the Action Potential Initiation Segment in GnRH Neuron Dendrites and Axons of Male Mice.

    Science.gov (United States)

    Herde, Michel K; Herbison, Allan E

    2015-11-01

    GnRH neurons are the final output neurons of the hypothalamic network controlling fertility in mammals. In the present study, we used ankyrin G immunohistochemistry and neurobiotin filling of live GnRH neurons in brain slices from GnRH-green fluorescent protein transgenic male mice to examine in detail the location of action potential initiation in GnRH neurons with somata residing at different locations in the basal forebrain. We found that the vast majority of GnRH neurons are bipolar in morphology, elaborating a thick (primary) and thinner (secondary) dendrite from opposite poles of the soma. In addition, an axon-like process arising predominantly from a proximal dendrite was observed in a subpopulation of GnRH neurons. Ankyrin G immunohistochemistry revealed the presence of a single action potential initiation zone ∼27 μm in length primarily in the secondary dendrite of GnRH neurons and located 30 to 140 μm distant from the cell soma, depending on the type of process and location of the cell body. In addition to dendrites, the GnRH neurons with cell bodies located close to hypothalamic circumventricular organs often elaborated ankyrin G-positive axon-like structures. Almost all GnRH neurons (>90%) had their action potential initiation site in a process that initially, or ultimately after a hairpin loop, was coursing in the direction of the median eminence. These studies indicate that action potentials are initiated in different dendritic and axonal compartments of the GnRH neuron in a manner that is dependent partly on the neuroanatomical location of the cell body.

  16. 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.

  17. 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.

  18. Measures of anxiety, sensorimotor function, and memory in male and female mGluR4-/- mice

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    Davis, Matthew J.; Haley, Tammie; Duvoisin, Robert M.; Raber, Jacob

    2012-01-01

    Metabotropic glutamate receptors (mGluRs) are coupled to second messenger pathways via G proteins and modulate synaptic transmission. Of the eight different types of mGluRs (mGluR1-mGluR8), mGluR4, mGluR6, mGluR7, and mGluR8 are members of group III. Group III receptors are generally located presynaptically, where they regulate neurotransmitter release. Because of their role in modulating neurotransmission, mGluRs are attractive targets for therapies aimed at treating anxiety disorders. Previously we showed that the mGluR4-selective allosteric agonist VU 0155041 reduces anxiety-like behavior in wild-type male mice. Here, we explore the role of mGluR4 in adult (6-month-old) and middle-aged (12-month-old) male and female mice lacking this receptor. Compared to age- and sex-matched wild-type mice, middle-aged mGluR4-/- male mice showed increased measures of anxiety in the open field and elevated zero maze and impaired sensorimotor function on the rotarod. These changes were not seen in adult 6-month old male mice. In contrast to the male mice, mGluR4-/- female mice showed reduced measures of anxiety in the open field and elevated zero maze and enhanced rotarod performance. During the hidden platform training sessions of the water maze, mGluR4-/-mice swam father away from the platform than wild-type mice at 6, but not at 12, months of age. mGluR4-/- mice also showed enhanced amygdala-dependent cued fear conditioning. No genotype differences were seen in hippocampus-dependent contextual fear conditioning. These data indicate that effects of mGluR4 on sensorimotor function and measures of anxiety, but not cued fear conditioning, are critically modulated by sex and age. PMID:22227508

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

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    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.

  20. Comparison of Anxiolytic Effect of Matricaria Recutita in Male and Female Mice in the Presence and Absence of Gonads

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    Pourmehdi Rad Goli

    2009-06-01

    Full Text Available Background: Some studies indicated that the chamomile induces sedative and anxiolytic effects. It has been shown that this herbal drug contains some phytoestrogenic components. Concerning the different effects of sexual hormones on various physiological phenomena such as anxiety, it seems this herb has different effects on anxiety in males and females. So in this study we examined anxiolytic property of Iranian spicious of chamomile, Matricaria recutita (MR hydroalcholic extract in presence and absence of sexual glands in male and female animal models. Materials and Methods: This animal study was done in Shahid Chamran University in 2006. NMRI male and female mice were divided in 16 groups of seven mices including: intact, sham, gonadectomized, receiving hydroalcholic extract of MR (10, 30, 50 mg/kg, ip. Elevated plus maze was used to evaluate anxiety and locomotive activity in all groups. Statistical evaluation of data was performed using Student's t-test and analysis of variance (ANOVA with one factor followed by Tukey test. P<0.05 was considered significant. Results: MR induced anxiolytic effect (10, 30 mg/kg in intact (P<0.05 and gonadectomized male mice (P<0.05 while did not significant any effect on intact and gonadectomized females. Testectomized mice were more anxious than sham group (P<0.05. Ovariectomized mice had no difference in level of anxiety with sham group. MR had no effect on locomotive activity in male mice but decreased it in females only in dose of 50 mg/kg (P<0.05. Conclusion: It seems that the anxiolytic effect of MR is sex dependent and probably this different effect in two sexes is related to its phytoestrogenic components

  1. Central ghrelin signaling mediates the metabolic response of C57BL/6 male mice to chronic social defeat stress.

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    Patterson, Z R; Khazall, R; Mackay, H; Anisman, H; Abizaid, A

    2013-03-01

    Chronic stressors promote metabolic disturbances, including obesity and metabolic syndrome. Ghrelin, a peptide that promotes appetite and the accumulation of adipose tissue, is also secreted in response to stressors to protect the brain and peripheral tissues from the effects of these stressors. Here we demonstrate that elevated ghrelin levels produced by chronic exposure to social stress are associated with increased caloric intake and body weight gain in male C57BL mice. In contrast, stressed mice lacking ghrelin receptors (GHSR KO mice) or C57BL mice receiving chronic intracerebroventricular delivery of the ghrelin receptor antagonist [d-Lys(3)]-GHRP-6 show attenuated weight gain and feeding responses under the same social stress paradigm. Interestingly, stressed GHSR KO mice showed depleted sc and intrascapular brown fat depots, whereas stressed young wild-type mice did not. In old wild-type mice, chronic social defeat increased visceral and intrascapular brown fat depots in association with increases in obesity markers like hyperleptinemia and hyperinsulinemia along with increased hypothalamic expression of neuropeptide Y and Agouti related peptide. Importantly, the elevated expression of these peptides persisted least for 2 weeks after cessation of the stressor regimen. In contrast, old GHSR KO mice did not show these alterations after chronic social defeat. These results suggest that ghrelin plays an important role in the metabolic adaptations necessary to meet the energetic demands posed by stressors, but chronic exposure to stress-induced ghrelin elevations ultimately could lead to long lasting metabolic dysfunctions.

  2. Chronic depletion of gonadal testosterone leads to blood-brain barrier dysfunction and inflammation in male mice.

    Science.gov (United States)

    Atallah, Afnan; Mhaouty-Kodja, Sakina; Grange-Messent, Valérie

    2017-09-01

    A dysfunction in the blood-brain barrier (BBB) is associated with many neurological and metabolic disorders. Although sex steroid hormones have been shown to impact vascular tone, endothelial function, oxidative stress, and inflammatory responses, there are still no data on the role of testosterone in the regulation of BBB structure and function. In this context, we investigated the effects of gonadal testosterone depletion on the integrity of capillary BBB and the surrounding parenchyma in male mice. Our results show increased BBB permeability for different tracers and endogenous immunoglobulins in chronically testosterone-depleted male mice. These results were associated with disorganization of tight junction structures shown by electron tomography and a lower amount of tight junction proteins such as claudin-5 and ZO-1. BBB leakage was also accompanied by activation of astrocytes and microglia, and up-regulation of inflammatory molecules such as inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), interleukin 1 beta (IL-1β), and tumor necrosis factor (TNF). Supplementation of castrated male mice with testosterone restored BBB selective permeability, tight junction integrity, and almost completely abrogated the inflammatory features. The present demonstration that testosterone transiently impacts cerebrovascular physiology in adult male mice should help gain new insights into neurological and metabolic diseases linked to hypogonadism in men of all ages.

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

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    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.

  4. The innate immune response to coxsackievirus B3 predicts progression to cardiovascular disease and heart failure in male mice

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    Onyimba Jennifer A

    2011-02-01

    Full Text Available Abstract Background Men are at an increased risk of dying from heart failure caused by inflammatory heart diseases such as atherosclerosis, myocarditis and dilated cardiomyopathy (DCM. We previously showed that macrophages in the spleen are phenotypically distinct in male compared to female mice at 12 h after infection. This innate immune profile mirrors and predicts the cardiac immune response during acute myocarditis. Methods In order to study sex differences in the innate immune response, five male and female BALB/c mice were infected intraperitoneally with coxsackievirus B3 (CVB3 or phosphate buffered saline and their spleens were harvested 12 h later for microarray analysis. Gene expression was determined using an Affymetrix Mouse Gene 1.0 ST Array. Significant gene changes were verified by quantitative real-time polymerase chain reaction or ELISA. Results During the innate immune response to CVB3 infection, infected males had higher splenic expression of genes which are important in regulating the influx of cholesterol into macrophages, such as phospholipase A2 (PLA2 and the macrophage scavenger receptor compared to the infected females. We also observed a higher expression in infected males compared to infected females of squalene synthase, an enzyme used to generate cholesterol within cells, and Cyp2e1, an enzyme important in metabolizing cholesterol and steroids. Infected males also had decreased levels of the translocator protein 18 kDa (TSPO, which binds PLA2 and is the rate-limiting step for steroidogenesis, as well as decreased expression of the androgen receptor (AR, which indicates receptor activation. Gene differences were not due to increased viral replication, which was unaltered between sexes. Conclusions We found that, compared to females, male mice had a greater splenic expression of genes which are important for cholesterol metabolism and activation of the AR at 12 h after infection. Activation of the AR has been linked to

  5. Conditioned odor aversion induces social anxiety towards females in wild-type and TrpC2 knockout male mice.

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    Beny, Y; Kimchi, T

    2016-11-01

    Female-emitted pheromonal inputs possess an intrinsic rewarding value for conspecific males, promoting approach and investigation of the potential mating partner. In mice these inputs are detected mainly by the vomeronasal organ (VNO) and the main olfactory epithelium (MOE). We investigated the role of VNO-mediated inputs in experience-dependent plasticity of reproductive responses. We applied a sex-specific conditioned odor aversion (COA) paradigm on adult, wild-type (WT) male mice and on male mice impaired in VNO-mediated signal transduction (TrpC2 -/- ). We found that WT males, which underwent COA to female-soiled bedding, lost their innate preference to female odors and presented lower motivation to approach a sexually receptive female. COA also abolished the testosterone surge normally seen following exposure to female odors. Moreover, the conditioned males displayed impairments in copulatory behaviors, which lasted for several weeks. Surprisingly, these males also exhibited phobic behaviors towards receptive females, including freezing and fleeing responses. In contrast, WT males which underwent COA specifically to male pheromones showed no change in olfactory preference and only a marginally significant elevation in intermale aggression. Finally, we show that TrpC2 -/- males were able to acquire aversion to female-soiled bedding and presented similar behavioral alterations following COA in their responses to female cues. Our results demonstrate that the intrinsic rewarding value of female pheromones can be overridden through associative olfactory learning, which occurs independently of VNO inputs, probably through MOE signaling. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  6. 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.

  7. Role of gonadal hormones in anxiety and fear memory formation and inhibition in male mice.

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    McDermott, Carmel M; Liu, Dana; Schrader, Laura A

    2012-03-20

    Recent research investigating Pavlovian fear conditioning and fear extinction has elucidated the neurocircuitry involved in acquisition and inhibition of fear responses. Modulatory factors that may underlie individual differences in fear acquisition and inhibition, however, are not well understood. Testosterone is known to affect anxiety-like behavior and cognitive processing. In this study, we hypothesized that castration would increase anxiety and reduce memory for contextual fear conditioning in an age-dependent manner. In addition, castration would reduce the rate of extinction to context, as high levels of testosterone correlate with reduced PTSD-like symptoms. We compared behaviors in male mice that were castrated at one of two different time points, either before puberty (at 4 weeks) or after puberty (at 10 weeks) to sham-operated control mice. The behaviors investigated included: anxiety, cued and contextual fear conditioning, and extinction of the fear memory. An interaction of hormone status and age and a significant effect of age were measured in the elevated plus maze, a measure of anxiety. Castration caused a significant reduction of contextual fear memory, but no effect on cued fear memory. There was no significant effect of castration on extinction. Interestingly, a significant effect of age of the mouse at the time of testing was observed on extinction. These results suggest that endogenous androgens during puberty are important for anxiety and fear memory formation. In addition, these results define a late post-adolescent developmental time point for changes in anxiety and fear extinction. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Hypothalamic-specific proopiomelanocortin deficiency reduces alcohol drinking in male and female mice.

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    Zhou, Y; Rubinstein, M; Low, M J; Kreek, M J

    2017-04-01

    Opioid receptor antagonist naltrexone reduces alcohol consumption and relapse in both humans and rodents. This study investigated whether hypothalamic proopiomelanocortin (POMC) neurons (producing beta-endorphin and melanocortins) play a role in alcohol drinking behaviors. Both male and female mice with targeted deletion of two neuronal Pomc enhancers nPE1 and nPE2 (nPE-/-), resulting in hypothalamic-specific POMC deficiency, were studied in short-access (4-h/day) drinking-in-the-dark (DID, alcohol in one bottle, intermittent access (IA, 24-h cycles of alcohol access every other day, alcohol vs. water in a two-bottle choice) and alcohol deprivation effect (ADE) models. Wild-type nPE+/+ exposed to 1-week DID rapidly established stable alcohol drinking behavior with more intake in females, whereas nPE-/- mice of both sexes had less intake and less preference. Although nPE-/- showed less saccharin intake and preference than nPE+/+, there was no genotype difference in sucrose intake or preference in the DID paradigm. After 3-week IA, nPE+/+ gradually escalated to high alcohol intake and preference, with more intake in females, whereas nPE-/- showed less escalation. Pharmacological blockade of mu-opioid receptors with naltrexone reduced intake in nPE+/+ in a dose-dependent manner, but had blunted effects in nPE-/- of both sexes. When alcohol was presented again after 1-week abstinence from IA, nPE+/+ of both sexes displayed significant increases in alcohol intake (ADE or relapse-like drinking), with more pronounced ADE in females, whereas nPE-/- did not show ADE in either sex. Our results suggest that neuronal POMC is involved in modulation of alcohol 'binge' drinking, escalation and 'relapse', probably via hypothalamic-mediated mechanisms, with sex differences. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

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

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    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.

  10. FABP-1 gene ablation impacts brain endocannabinoid system in male mice.

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    Martin, Gregory G; Chung, Sarah; Landrock, Danilo; Landrock, Kerstin K; Huang, Huan; Dangott, Lawrence J; Peng, Xiaoxue; Kaczocha, Martin; Seeger, Drew R; Murphy, Eric J; Golovko, Mikhail Y; Kier, Ann B; Schroeder, Friedhelm

    2016-08-01

    Liver fatty acid-binding protein (FABP1, L-FABP) has high affinity for and enhances uptake of arachidonic acid (ARA, C20:4, n-6) which, when esterified to phospholipids, is the requisite precursor for synthesis of endocannabinoids (EC) such as arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG). The brain derives most of its ARA from plasma, taking up ARA and transporting it intracellularly via cytosolic fatty acid-binding proteins (FABPs 3,5, and 7) localized within the brain. In contrast, the much more prevalent cytosolic FABP1 is not detectable in the brain but is instead highly expressed in the liver. Therefore, the possibility that FABP1 outside the central nervous system may regulate brain AEA and 2-AG was examined in wild-type (WT) and FABP1 null (LKO) male mice. LKO increased brain levels of AA-containing EC (AEA, 2-AG), correlating with increased free and total ARA in brain and serum. LKO also increased brain levels of non-ARA that contain potentiating endocannabinoids (EC*) such as oleoyl ethanolamide (OEA), PEA, 2-OG, and 2-PG. Concomitantly, LKO decreased serum total ARA-containing EC, but not non-ARA endocannabinoids. LKO did not elicit these changes in the brain EC and EC* as a result of compensatory up-regulation of brain protein levels of enzymes in EC synthesis (NAPEPLD, DAGLα) or cytosolic EC chaperone proteins (FABPs 3, 5, 7, SCP-2, HSP70), or cannabinoid receptors (CB1, TRVP1). These data show for the first time that the non-CNS fatty acid-binding protein FABP1 markedly affected brain levels of both ARA-containing endocannabinoids (AEA, 2-AG) as well as their non-ARA potentiating endocannabinoids. Fatty acid-binding protein-1 (FABP-1) is not detectable in brain but instead is highly expressed in liver. The possibility that FABP1 outside the central nervous system may regulate brain endocannabinoids arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG) was examined in wild-type (WT) and FABP-1 null (LKO) male mice. LKO

  11. Cholesterol-induced hepatic inflammation does not contribute to the development of insulin resistance in male LDL receptor knockout mice.

    Science.gov (United States)

    Funke, Anouk; Schreurs, Marijke; Aparicio-Vergara, Marcela; Sheedfar, Fareeba; Gruben, Nanda; Kloosterhuis, Niels J; Shiri-Sverdlov, Ronit; Groen, Albert K; van de Sluis, Bart; Hofker, Marten H; Koonen, Debby P Y

    2014-02-01

    It is generally assumed that hepatic inflammation in obesity is linked to the pathogenesis of insulin resistance. Several recent studies have shed doubt on this view, which questions the causality of this association. This study focuses on Kupffer cell-mediated hepatic inflammation as a possible driver of insulin resistance in the absence and presence of obesity. We used male mice deficient for the low-density lipoprotein receptor (Ldlr(-/-)) and susceptible to cholesterol-induced hepatic inflammation. Whole body and hepatic insulin resistance was measured in mice fed 4 diets for 2 and 15 weeks, i.e., chow, high-fat (HF), HF-cholesterol (HFC; 0.2% cholesterol) and HF without cholesterol (HFnC). Biochemical parameters in plasma and liver were measured and inflammation was determined using immunohistochemistry and RT-PCR. At 2 weeks, we did not find significant metabolic effects in either diet group, except for the mice fed a HFC diet which showed pronounced hepatic inflammation (p insulin sensitivity. At 15 weeks, a significant increase in insulin levels, HOMA-IR, and hepatic insulin resistance was observed in mice fed a HFC, HFnC, and HF diet compared to chow-fed mice (p HF, HFnC; p insulin resistance in mice fed HFC was no worse compared to mice on a HFnC and HF diet. These data show that cholesterol-induced hepatic inflammation does not contribute to the development of insulin resistance in male Ldlr(-/-) mice. This study suggests that Kupffer cell-driven hepatic inflammation is a consequence, not a cause, of metabolic dysfunction in obesity. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

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

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    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.

  13. 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.

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

    Science.gov (United States)

    Hoffman, Emma; Pickavance, Lucy; Thippeswamy, Thimmasettappa; Beynon, Robert J.; Hurst, Jane L.

    2015-01-01

    The integration of newly generated neurons persists throughout life in the mammalian olfactory bulb and hippocampus, regions involved in olfactory and spatial learning. Social cues can be potent stimuli for increasing adult neurogenesis; for example, odors from dominant but not subordinate male mice increase neurogenesis in both brain regions of adult females. However, little is known about the role of neurogenesis in social recognition or the assessment of potential mates. Dominant male mice scent-mark territories using urine that contains a number of pheromones including darcin (MUP20), a male-specific major urinary protein that stimulates rapid learned attraction to the spatial location and individual odor signature of the scent owner. Here we investigate whether exposure to darcin stimulates neurogenesis in the female brain. Hippocampal neurons and cellular proliferation in the lateral ventricles that supply neurons to the olfactory bulbs increased in females exposed for 7 days to male urine containing at least 0.5 μg/μl darcin. Darcin was effective whether presented alone or in the context of male urine, but other information in male urine appeared to modulate the proliferative response. When exposed to urine from wild male mice, hippocampal proliferation increased only if urine was from the same individual over 7 days, suggesting that consistency of individual scent signatures is important. While 7 days exposure to male scent initiated the first stages of increased neurogenesis, this caused no immediate increase in female attraction to the scent or in the strength or robustness of spatial learning in short-term conditioned place preference tests. The reliable and consistent stimulation of neurogenesis by a pheromone important in rapid social learning suggests that this may provide an excellent model to explore the relationship between the integration of new neurons and plasticity in spatial and olfactory learning in a socially-relevant context. PMID

  15. Effects of High-Fat Diet on Stress Response in Male and Female Wildtype and Prolactin Knockout Mice.

    Science.gov (United States)

    Kalyani, Manu; Hasselfeld, Kathryn; Janik, James M; Callahan, Phyllis; Shi, Haifei

    2016-01-01

    Prolactin (PRL) is well characterized for its roles in initiation and maintenance of lactation, and it also suppresses stress-induced responses. Feeding a high-fat diet (HFD) disrupts activity of the hypothalamic-pituitary-adrenal (HPA) axis. Whether PRL regulates HPA axis activation under HFD feeding is not clear. Male and female wildtype (WT) and PRL knockout (KO) mice were fed either a standard low-fat diet (LFD) or HFD for 12 weeks. Circulating corticosterone (CORT) levels were measured before, during, and after mice were subjected to an acute restraint stress or remained in their home cages as no stress controls. HFD feeding increased leptin levels, but the increase was lower in KO than in WT mice. All stressed female groups and only LFD-fed stressed males had elevated CORT levels compared to their no stress same-sex counterparts regardless of genotype. These results indicated that HFD consumption blunted the HPA axis response to acute stress in males but not females. Additionally, basal hypothalamic CRH content was lower in HFD than LFD males, but was similar among female groups. Furthermore, although basal CORT levels were similar among KO and WT groups, CORT levels were higher in KO mice than their WT counterparts during stress, suggesting that loss of PRL led to greater HPA axis activation. Basal PRL receptor mRNA levels in the choroid plexus were higher in HFD than LFD same-sex counterparts, suggesting activation of central PRL's action by HFD feeding in both males and females. Current results confirmed PRL's roles in suppression of the stress-induced HPA axis activation. Although HFD feeding activated central PRL's action in both sexes, only the male HPA axis was dampened by HFD feeding.

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. 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...

  3. 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.

  4. Dynamic changes in social dominance and mPOA GnRH expression in male mice following social opportunity.

    Science.gov (United States)

    Williamson, Cait M; Romeo, Russell D; Curley, James P

    2017-01-01

    Social competence - the ability of animals to dynamically adjust their social behavior dependent on the current social context - is fundamental to the successful establishment and maintenance of social relationships in group-living species. The social opportunity paradigm, where animals rapidly ascend a social hierarchy following the removal of more dominant individuals, is a well-established approach for studying the neural and neuroendocrine mechanisms underlying socially competent behavior. In the current study, we demonstrate that this paradigm can be successfully adapted for studying socially competent behavior in laboratory mice. Replicating our previous reports, we show that male laboratory mice housed in a semi-natural environment form stable linear social hierarchies. Novel to the current study, we find that subdominant male mice immediately respond to the removal of the alpha male from a hierarchy by initiating a dramatic increase in aggressive behavior towards more subordinate individuals. Consequently, subdominants assume the role of the alpha male. Analysis of brain gene expression in individuals 1h following social ascent indicates elevated gonadotropin-releasing hormone (GnRH) mRNA levels in the medial preoptic area (mPOA) of the hypothalamus compared to individuals that do not experience a social opportunity. Moreover, hormonal analyses indicate that subdominant individuals have increased circulating plasma testosterone levels compared to subordinate individuals. Our findings demonstrate that male mice are able to dynamically and rapidly adjust both behavior and neuroendocrine function in response to changes in social context. Further, we establish the social opportunity paradigm as an ethologically relevant approach for studying social competence and behavioral plasticity in mammals. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Augmented Osteolysis in SPARC-Deficient Mice with Bone-Residing Prostate Cancer

    Directory of Open Access Journals (Sweden)

    N. Patrick McCabe

    2011-01-01

    Full Text Available Prostate cancer preferentially metastasizes to bone, which is rich in structural and matricellular proteins capable of altering prostate cancer progression. This study explores the role of the bone stromal matricellular protein SPARC (osteonectin/BM-40 in the progression of bone metastatic prostate cancer. Quantification of bone destruction analyzed by micro–computed tomography showed augmented osteoclastic resorption, characterized by decreases in several morphometric bone parameters in SPARC knock out (KO tibiae harboring RM1 murine prostate cancer cells compared with wild type (WT animals. Tumor progression stimulated osteoclast formation, which was augmented in SPARC KO mice. In vitro differentiation of SPARC KO osteoclasts indicated accelerated progenitor expansion and formation of tartrate-resistant acid phosphatase–positive osteoclast-like cells with increased resorptive capacity, a mechanism resulting in enhanced tumor-induced bone loss in vivo. Whereas altered bone structure due to SPARC KO played a role in increased osteolysis, the enhanced osteolysis was primarily the result of increased resorption by SPARC KO osteoclasts. Our findings indicate that bone stromal SPARC suppresses tumor-induced bone lesion expansion by limiting osteoclast maturation and function.

  6. 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.

  7. Bone Marrow Chimeras and c-fms Conditional Ablation (Mafia) Mice Reveal an Essential Role for Resident Myeloid Cells in Lipopolysaccharide/TLR4-Induced Corneal Inflammation1

    Science.gov (United States)

    Chinnery, Holly R.; Carlson, Eric C.; Sun, Yan; Lin, Michelle; Burnett, Sandra H.; Perez, Victor L.; McMenamin, Paul G.; Pearlman, Eric

    2012-01-01

    The mammalian cornea contains an extensive network of resident macrophages and dendritic cells. To determine the role of these cells in LPS-induced corneal inflammation, TLR4−/− mice were sublethally irradiated and reconstituted with bone marrow cells from either enhanced GFP (eGFP)+/C57BL/6 or eGFP+/TLR4−/− mice. The corneal epithelium was abraded, LPS was added topically, and cellular infiltration to the corneal stroma and development of corneal haze were examined after 24 h. TLR4−/− mice reconstituted with C57BL/6, but not TLR4−/− bone marrow cells donor cells were found to cause infiltration of eGFP+ cells to the cornea, including neutrophils, and also increased corneal haze compared with saline-treated corneas. In a second experimental approach, corneas of transgenic macrophage Fas induced apoptosis (Mafia) mice were stimulated with LPS. These mice express eGFP and a suicide gene under control of the c-fms promoter, and systemic treatment with the FK506 dimerizer (AP20187) causes Fas-mediated apoptosis of monocytic cells. AP20187-treated mice had significantly fewer eGFP+ cells in the cornea than untreated mice. After stimulation with LPS neutrophil recruitment and development of corneal haze were impaired in AP20187-treated mice compared with untreated controls. Furthermore, LPS induced CXCL1/KC and IL-1α production within 4 h in corneas of untreated Mafia mice, which is before cellular infiltration; however, cytokine production was impaired after AP20187 treatment. Together, results from both experimental approaches demonstrate an essential role for resident corneal monocytic lineage cells (macrophages and dendritic cells) in development of corneal inflammation. PMID:19234168

  8. Bone marrow chimeras and c-fms conditional ablation (Mafia) mice reveal an essential role for resident myeloid cells in lipopolysaccharide/TLR4-induced corneal inflammation.

    Science.gov (United States)

    Chinnery, Holly R; Carlson, Eric C; Sun, Yan; Lin, Michelle; Burnett, Sandra H; Perez, Victor L; McMenamin, Paul G; Pearlman, Eric

    2009-03-01

    The mammalian cornea contains an extensive network of resident macrophages and dendritic cells. To determine the role of these cells in LPS-induced corneal inflammation, TLR4(-/-) mice were sublethally irradiated and reconstituted with bone marrow cells from either enhanced GFP (eGFP)(+)/C57BL/6 or eGFP(+)/TLR4(-/-) mice. The corneal epithelium was abraded, LPS was added topically, and cellular infiltration to the corneal stroma and development of corneal haze were examined after 24 h. TLR4(-/-) mice reconstituted with C57BL/6, but not TLR4(-/-) bone marrow cells donor cells were found to cause infiltration of eGFP(+) cells to the cornea, including neutrophils, and also increased corneal haze compared with saline-treated corneas. In a second experimental approach, corneas of transgenic macrophage Fas induced apoptosis (Mafia) mice were stimulated with LPS. These mice express eGFP and a suicide gene under control of the c-fms promoter, and systemic treatment with the FK506 dimerizer (AP20187) causes Fas-mediated apoptosis of monocytic cells. AP20187-treated mice had significantly fewer eGFP(+) cells in the cornea than untreated mice. After stimulation with LPS neutrophil recruitment and development of corneal haze were impaired in AP20187-treated mice compared with untreated controls. Furthermore, LPS induced CXCL1/KC and IL-1alpha production within 4 h in corneas of untreated Mafia mice, which is before cellular infiltration; however, cytokine production was impaired after AP20187 treatment. Together, results from both experimental approaches demonstrate an essential role for resident corneal monocytic lineage cells (macrophages and dendritic cells) in development of corneal inflammation.

  9. Altered Polarization, Morphology, and Impaired Innate Immunity Germane to Resident Peritoneal Macrophages in Mice with Long-Term Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Hui-Fang Liu

    2012-01-01

    Full Text Available Type 2 diabetes (T2D is associated with perturbed innate immunity. Macrophages, bridging innate immunity and metabolic disturbances, play important roles in controlling immune homeostasis. However, the effect of long-term diabetic milieu (DM on the functions and phenotypes of macrophages is still not clear. In this study, we used resident peritoneal macrophages (RPMs from 5-month-old db/db mice to investigate the changes of macrophages. It was found that RPMs in db/db mice significantly reduced phagocytosis and adhesion capacity. After standardization with body weight, the number of F4/80+ RPMs markedly reduced in db/db mice, and, furthermore, the macrophages skewed to M2-polarizated macrophages. The results of morphology found that the RPMs shape of db/db mice was nearly round, but the RPMs shape of control mice was spindle-shaped and irregular. In this study, we found the cell numbers, morphology, and innate immunity functions of RPMs in 5-month-old type 2 diabetic mice (db/db mice obtained by abdominal cavity lavage were significantly altered. Importantly, we also found the remarkably increased M2-RPMs in diabetic mice for the first time.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. The Effect of Intermittent Feeding on Metabolic Signs of Chronic Stress in Male NMRI Mice

    Directory of Open Access Journals (Sweden)

    Fatemeh Sadat Hoseini Namvar

    2016-03-01

    Full Text Available Background and Objectives: Reduction of calorie (energy intake can lead to stress management and improvement of nervous system function. In this research, the effect of intermittent feeding on metabolic signs of stress was investigated. Methods: Male laboratory mice with mean weight of 27±3g were divided into 4 groups of 7 each. The control group received ad-lib food and water and did not have stress. The second group (experimental was deprived from food 2 hours per day for one week, and then went under stress for 4 days. The third group was only deprived from food 2 hours per day for a week, and the fourth group received electric shock for 4 days without food deprivation. In this investigation, plasma corticosterone level, the amount of food consumption, delay in eating, weight gain, and the amount of feces, were measured. Data were analyzed using one-way ANOVA and Tukey test. The significance level was considered p<0.5. Results: In this study, stress increased the plasma level of corticosterone and fecal materials, and reduced food intake and weight of the animals and increased delay in eating. In the stress with intermittent feeding group, plasma level of corticosterone and delay in eating increased, and food intake and feces decreased. In this group, weight change was not observed, but in animals that only had intermittent feeding, increase in weight and food intake was observed. Also, delay in eating was decreased. Conclusion: The results of this study indicated that intermittent feeding can influence the effect of stress on nutrition and metabolism.

  12. Antidepressant-like effect of Kyllinga brevifolia rhizomes in male mice and chemical characterization of the components of the active ethyl acetate fraction.

    Science.gov (United States)

    Hellión-Ibarrola, M C; Montalbetti, Y; Heinichen, O Y; Kennedy, M L; Campuzano, M A; Alvarenga, N; Ibarrola, D A

    2016-12-24

    Kyllinga brevifolia rhizomes (Cyperaceae) are used in Paraguayan traditional medicine as a refreshing beverage, and is claimed to own digestive, diuretic, sedative, tonic, antispasmodic and sudorific properties. We have previously reported that its hydro- ethanolic rhizome extract possess sedative, anxiolytic and anti-aggressive-like effects in mice. However, information on its potential for treatment of syndromes associated with mood disorders is scarce. The purpose of this study is to characterize the putative antidepressant-like effects of the hydro-ethanolic extract (CEKb) and the ethyl acetate fraction (KbF-ethyl-ac) obtained from the rhizome of K. brevifolia (Rottb) on male mice exposed to forced swimming test. Also, chemical characterization of the components of the active ethyl acetate fraction was described. The antidepressant-like effects of CEKb and KbF-ethyl-ac were measured using the forced swimming test (FST) performance of male mice in single (acute), short-term and chronic modalities. Treatments in all modalities were made 1h before swimming test. The KbF-ethyl-ac was analyzed by LC-DAD-ESI-MS and LC-ESI-MS/MS in order to identify the active components. A single doses (1.0, 10.0 and 100.0mg/kg, p.o; pethyl-ac in male mice, a significant reduction of the immobility time were provoked. Likewise, short-term treatment (7 days) with 1.0, and 10.0mg/kg (pethyl-ac in male mice, a statistically significant reduction of the immobility time, were observed. Imipramine 32mg/kg/days, i.p, induced a statistically significant reduction of immobility time and was used as positive control to validate the method employed. Moreover, it was noted important differences in the onset of the antidepressant-like effect in the FST, depending on the modality of treatment with CEKb or KbF-ethyl-ac (acute, short-term or chronic). Both, efficacy and potency were higher when repeated administration of CEKb was used, and surprisingly the efficacy of 1.0mg/kg of KbF-ethyl-ac (14

  13. 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

  14. 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.

  15. Alteration in some antioxidant enzymes in cardiac tissue upon monosodium glutamate [MSG] administration to adult male mice

    OpenAIRE

    Singh, Kuldip; Pushpa, Ahluwalia

    2005-01-01

    4mg and 8mg monosodium glutamate per gram body weight was administered subcutaneously for 6 consecutive days to normal adult male mice and its effect was seen on 31st day after the last injection on some antioxidant enzymes in heart. A significant dose dependent increase in lipid peroxidation and xanthine oxidase level was observed, whereas the activity of free radical scavenging enzymes such as superoxide dismutase and catalase was decreased in both monosodium glutamate treated groups (Group...

  16. 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.

  17. 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.

  18. Transforming growth factor-beta1 null mutation causes infertility in male mice associated with testosterone deficiency and sexual dysfunction.

    Science.gov (United States)

    Ingman, Wendy V; Robertson, Sarah A

    2007-08-01

    TGFbeta1 is a multifunctional cytokine implicated in gonad and secondary sex organ development, steroidogenesis, and spermatogenesis. To determine the physiological requirement for TGFbeta1 in male reproduction, Tgfb1 null mutant mice on a Prkdc(scid) immunodeficient background were studied. TGFbeta1-deficient males did not deposit sperm or induce pseudopregnancy in females, despite an intact reproductive tract with morphologically normal penis, seminal vesicles, and testes. Serum and intratesticular testosterone and serum androstenedione were severely diminished in TGFbeta1-deficient males. Testosterone deficiency was secondary to disrupted pituitary gonadotropin secretion because serum LH and to a lesser extent serum FSH were reduced, and exogenous LH replacement with human chorionic gonadotropin (hCG) induced serum testosterone to control levels. In the majority of TGFbeta1-deficient males, spermatogenesis was normal and sperm were developmentally competent as assessed by in vitro fertilization. Analysis of sexual behavior revealed that although TGFbeta1 null males showed avid interest in females and engaged in mounting activity, intromission was infrequent and brief, and ejaculation was not attained. Administration of testosterone to adult males, even after neonatal androgenization, was ineffective in restoring sexual function; however, erectile reflexes and ejaculation could be induced by electrical stimulation. These studies demonstrate the profound effect of genetic deficiency in TGFbeta1 on male fertility, implicating this cytokine in essential roles in the hypothalamic-pituitary-gonadal axis and in testosterone-independent regulation of mating competence.

  19. 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.

  20. 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.

  1. Polychlorinated biphenyl 77 augments angiotensin II-induced atherosclerosis and abdominal aortic aneurysms in male apolipoprotein E deficient mice

    Energy Technology Data Exchange (ETDEWEB)

    Arsenescu, Violeta [Graduate Center for Nutritional Sciences, University of Kentucky, 800 Rose Street, Lexington, KY 40536-0200 (United States); Arsenescu, Razvan [Digestive Diseases and Nutrition, University of Kentucky, 800 Rose Street, Lexington, KY 40536-0200 (United States); Parulkar, Madhura; Karounos, Michael [Graduate Center for Nutritional Sciences, University of Kentucky, 800 Rose Street, Lexington, KY 40536-0200 (United States); Zhang, Xuan [Graduate Center for Toxicology, University of Kentucky, 800 Rose Street, Lexington, KY 40536-0200 (United States); Baker, Nicki [Graduate Center for Nutritional Sciences, University of Kentucky, 800 Rose Street, Lexington, KY 40536-0200 (United States); Cassis, Lisa A., E-mail: lcassis@uky.edu [Graduate Center for Nutritional Sciences, University of Kentucky, 800 Rose Street, Lexington, KY 40536-0200 (United States)

    2011-11-15

    Infusion of angiotensin II (AngII) to hyperlipidemic mice augments atherosclerosis and causes formation of abdominal aortic aneurysms (AAAs). Each of these AngII-induced vascular pathologies exhibit pronounced inflammation. Previous studies demonstrated that coplanar polychlorinated biphenyls (PCBs) promote inflammation in endothelial cells and adipocytes, two cell types implicated in AngII-induced vascular pathologies. The purpose of this study was to test the hypothesis that administration of PCB77 to male apolipoprotein E (ApoE) -/- mice promotes AngII-induced atherosclerosis and AAA formation. Male ApoE-/- mice were administered vehicle or PCB77 (49 mg/kg, i.p.) during week 1 and 4 (2 divided doses/week) of AngII infusion. Body weights and total serum cholesterol concentrations were not influenced by administration of PCB77. Systolic blood pressure was increased in AngII-infused mice administered PCB77 compared to vehicle (156 {+-} 6 vs 137 {+-} 5 mmHg, respectively). The percentage of aortic arch covered by atherosclerotic lesions was increased in AngII-infused mice administered PCB77 compared to vehicle (2.0 {+-} 0.4 vs 0.9 {+-} 0.1%, respectively). Lumen diameters of abdominal aortas determined by in vivo ultrasound and external diameters of excised suprarenal aortas were increased in AngII-infused mice administered PCB77 compared to vehicle. In addition, AAA incidence increased from 47 to 85% in AngII-infused mice administered PCB77. Adipose tissue in close proximity to AAAs from mice administered PCB77 exhibited increased mRNA abundance of proinflammatory cytokines and elevated expression of components of the renin-angiotensin system (angiotensinogen, angiotensin type 1a receptor (AT1aR)). These results demonstrate that PCB77 augments AngII-induced atherosclerosis and AAA formation. -- Highlights: Black-Right-Pointing-Pointer Polychlorinated biphenyl 77 (PCB77) promotes AngII-induced hypertension. Black-Right-Pointing-Pointer PCB77 augments Ang

  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. 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

  4. Basigin null mutant male mice are sterile and exhibit impaired interactions between germ cells and Sertoli cells.

    Science.gov (United States)

    Bi, Jiajia; Li, Yanfen; Sun, Fengyun; Saalbach, Anja; Klein, Claudia; Miller, David J; Hess, Rex; Nowak, Romana A

    2013-08-15

    Basigin (BSG) is a multifunctional glycoprotein that plays an important role in male reproduction since male knockout (KO) mice are sterile. The Bsg KO testis lacks elongated spermatids and mature spermatozoa, a phenotype similar to that of alpha-mannosidase IIx (MX) KO mice. MX regulates formation of N-acetylglucosamine (GlcNAc) terminated N-glycans that participate in germ cell-Sertoli cell adhesion. Results showed that Bsg KO spermatocytes displayed normal homologous chromosome synapsis and progression through meiosis. However, only punctate expression of the round spermatid marker SP-10 in the acrosomal granule of germ cells of Bsg KO mice was detected indicating that spermatogenesis in Bsg KO mice was arrested at the early round spermatid stages. We observed a large increase in the number of germ cells undergoing apoptosis in Bsg KO testes. Using lectin blotting, we determined that GlcNAc terminated N-glycans are linked to BSG. GlcNAc terminated N-glycans were significantly reduced in Bsg KO testes. These observations indicate that BSG may act as a germ cell-Sertoli cell attachment molecule. Loss of BSG significantly reduced adhesion between GC-2 and SF7 cells. Moreover, wild type testes showed strong expression of N-cadherin (CDH2) while expression was greatly reduced in the testes of Bsg KO mice. In addition, the integrity of the blood-testis barrier (BTB) was compromised in Bsg KO testes. In conclusion, although some Bsg KO spermatogonia can undergo normal progression to the spermatocyte stage, BSG-mediated germ cell-Sertoli cell interactions appear to be necessary for integrity of the BTB and spermatocyte progression to mature spermatozoa. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. 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.

  6. 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.

  7. A novel adolescent chronic social defeat model: reverse-Resident-Intruder Paradigm (rRIP) in male rats.

    Science.gov (United States)

    Manz, Kevin M; Levine, Wendy A; Seckler, Joshua C; Iskander, Anthony N; Reich, Christian G

    2018-03-01

    Psychosocial stress is linked to the etiology of several neuropsychiatric disorders, including Major Depressive Disorder and Post-Traumatic-Stress-Disorder. Adolescence is a critical neurobehavioral developmental period wherein the maturing nervous system is sensitive to stress-related psychosocial events. The effects of social defeat stress, an animal model of psychosocial stress, on adolescent neurobehavioral phenomena are not well explored. Using the standard Resident-Intruder-Paradigm (RIP), adolescent Long-Evans (LE, residents, n = 100) and Sprague-Dawley (SD, intruders, n = 100) rats interacted for five days to invoke chronic social stress. Tests of depressive behavior (forced-swim-test (FST)), fear conditioning, and long-term synaptic plasticity are affected in various adult rodent chronic stress models, thus we hypothesized that these phenomena would be similarly affected in adolescent rats. Serendipitously, we observed the Intruders became the dominant rats and the Residents were the defeated/submissive rats. This robust and reliable role-reversal resulted in defeated LE-Residents showing a depressive-like state (increased time spent immobile in the FST), enhanced fear conditioning in both hippocampal-dependent and hippocampal-independent fear paradigms and altered hippocampal long-term synaptic plasticity, measured electrophysiologically in vitro in hippocampal slices. Importantly, SD-Intruders, SD and LE controls did not significantly differ from each other in any of these assessments. This reverse-Resident-Intruder-Paradigm (rRIP) represents a novel animal model to study the effects of stress on adolescent neurobehavioral phenomenon.

  8. 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

  9. Increased oxidative stress and apoptosis in the hypothalamus of diabetic male mice in the insulin receptor substrate-2 knockout model.

    Science.gov (United States)

    Baquedano, Eva; Burgos-Ramos, Emma; Canelles, Sandra; González-Rodríguez, Agueda; Chowen, Julie A; Argente, Jesús; Barrios, Vicente; Valverde, Angela M; Frago, Laura M

    2016-05-01

    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. © 2016. Published by The Company of Biologists Ltd.

  10. Biochemical Alterations during the Obese-Aging Process in Female and Male Monosodium Glutamate (MSG-Treated Mice

    Directory of Open Access Journals (Sweden)

    René J. Hernández-Bautista

    2014-06-01

    Full Text Available Obesity, from children to the elderly, has increased in the world at an alarming rate over the past three decades, implying long-term detrimental consequences for individual’s health. Obesity and aging are known to be risk factors for metabolic disorder development, insulin resistance and inflammation, but their relationship is not fully understood. Prevention and appropriate therapies for metabolic disorders and physical disabilities in older adults have become a major public health challenge. Hence, the aim of this study was to evaluate inflammation markers, biochemical parameters and glucose homeostasis during the obese-aging process, to understand the relationship between obesity and health span during the lifetime. In order to do this, the monosodium glutamate (MSG obesity mice model was used, and data were evaluated at 4, 8, 12, 16 and 20 months in both female and male mice. Our results showed that obesity was a major factor contributing to premature alterations in MSG-treated mice metabolism; however, at older ages, obesity effects were attenuated and MSG-mice became more similar to normal mice. At a younger age (four months old, the Lee index, triglycerides, total cholesterol, TNF-α and transaminases levels increased; while adiponectin decreased and glucose tolerance and insulin sensitivity levels were remarkably altered. However, from 16 months old-on, the Lee index and TNF-α levels diminished significantly, while adiponectin increased, and glucose and insulin homeostasis was recovered. In summary, MSG-treated obese mice showed metabolic changes and differential susceptibility by gender throughout life and during the aging process. Understanding metabolic differences between genders during the lifespan will allow the discovery of specific preventive treatment strategies for chronic diseases and functional decline.

  11. Antiepileptic and Antioxidant Effect of Hydroalcoholic Extract of Ferula Assa Foetida Gum on Pentylentetrazole induced Kindling in Male Mice

    Directory of Open Access Journals (Sweden)

    Zahra Kiasalari

    2013-11-01

    Full Text Available Introduction: Considering the prevalence of epilepsy and the failure of available treatments for many epileptic patients, finding more effective drugs in the treatment of epilepsy seems necessary. Oxidative stress has a special role in the pathogenesis of epileptic syndrome. Therefore, in the present study, we have examined the anti-epileptic and anti-oxidant properties of the Ferula Assa Foetida gum extract, using the pentylentetrazole (PTZ kindling method. group which received valproate (100 mg/kg as anti-convulsant drug, 4-5 & 6- the groups of kindled mice that pretreated with 25, 50 and 100 mg/kg doses of Ferula Assa Foetida gum extract. Methods: Kindling has been induced in all groups, except for the control group via 11 PTZ injections (35 mg /kg ip every other day for 22 days. In the 24th day, the PTZ challenge dose was injected (75 mg / kg to all groups except the control group. The intensity of seizures were observed and noted until 30 minutes after PTZ injection. At list, the mice were decapitated and the brains of all the mice were removed.. and their biochemical factors levels including malondialdehyde (MDA, superoxide dismutase (SOD and nitric oxide (NO were determined. Results: Results of this study show that Ferula Assa Foetida gum extract is able to reduce seizure duration and its intensity. In addition, this extract has reduced MDA and NO levels and increased the level of SOD in the brain tissue compared to the PTZ- kindled mice. Discussion: It can be concluded that Ferula Assa Foetida gum extract, in specific doses, is able to show an anti-epileptic effect because of its antioxidant properties, probably acting through an enzyme activity mechanism. In this experimental study, sixty male Albino mice weighing 25-30 g were selected and were randomly divided into 6 groups. 1- the control group, 2- PTZ-kindled mice, 3- positive control

  12. Osteocytic connexin 43 is not required for the increase in bone mass induced by intermittent PTH administration in male mice.

    Science.gov (United States)

    Pacheco-Costa, R; Davis, H M; Atkinson, E G; Katchburian, E; Plotkin, L I; Reginato, R D

    2016-03-01

    To investigate whether osteocytic connexin 43 (Cx43) is required for the bone response to intermittent PTH administration, and whether the connexin is involved in maintaining the bone matrix. Human PTH(1-34) was injected to adult male mice expressing (Cx43(fl/fl)) or not osteocytic Cx43 (Cx43(fl/fl);DMP1-8kb-Cre) daily (100 µg/kg/d) for 14 days. Cx43(fl/fl);DMP1-8kb-Cre mice have no difference in body weight and BMD from 1 to 4 months of age. Intermittent PTH administration increased BMD and BV/TV and induced a similar increase in type I collagen, alkaline phosphatase, runx2, osteocalcin, and bone sialoprotein expression in mice from both genotypes. On the other hand, osteocytic deletion of Cx43 did not alter mRNA levels of glycosaminoglycans, proteoglycans, collagens and osteoblast-related genes. In addition, expression of collagens assessed by immunohistochemistry was not affected by deleting osteocytic Cx43. However, PTH administration increased type II collagen only in Cx43(fl/fl) control mice, whereas hormone increased type I collagen expression only in Cx43(fl/fl);DMP1-8kb-Cre mice. Furthermore, PTH increased maturity of collagen fibers in control, but not in Cx43-deficient mice. Expression of Cx43 in osteocytes is dispensable for bone anabolism induced by intermittent PTH administration; but it can modulate, at least in part, the effect of PTH on the bone matrix environment.

  13. Aphrodisiac activity of 50% ethanolic extracts of Myristica fragrans Houtt. (nutmeg and Syzygium aromaticum (L Merr. & Perry. (clove in male mice: a comparative study

    Directory of Open Access Journals (Sweden)

    Latif Abdul

    2003-10-01

    Full Text Available Abstract Background Spices are considered as sexual invigorators in the Unani System of Medicine. In order to explore the sexual function improving effect of Myristica fragrans Houtt. (nutmeg and Syzygium aromaticum (L Merr. & Perry. (clove an experimental study was conducted in normal male mice. Methods The extracts (50% ethanolic of nutmeg and clove were administered (500 mg/kg; p.o. to different groups of male Swiss mice. Mounting behaviour, mating performance, and general short term toxicity of the test drugs were determined and compared with the standard drug Penegra (Sildenafil citrate. Results The extracts of the nutmeg and clove were found to stimulate the mounting behaviour of male mice, and also to significantly increase their mating performance. The drugs were devoid of any conspicuous general short term toxicity. Conclusion The extracts (50% ethanolic of nutmeg and clove enhanced the sexual behaviour of male mice.

  14. Aphrodisiac activity of 50% ethanolic extracts of Myristica fragrans Houtt. (nutmeg) and Syzygium aromaticum (L) Merr. & Perry. (clove) in male mice: a comparative study.

    Science.gov (United States)

    Tajuddin; Ahmad, Shamshad; Latif, Abdul; Qasmi, Iqbal Ahmad

    2003-10-20

    Spices are considered as sexual invigorators in the Unani System of Medicine. In order to explore the sexual function improving effect of Myristica fragrans Houtt. (nutmeg) and Syzygium aromaticum (L) Merr. & Perry. (clove) an experimental study was conducted in normal male mice. The extracts (50% ethanolic) of nutmeg and clove were administered (500 mg/kg; p.o.) to different groups of male Swiss mice. Mounting behaviour, mating performance, and general short term toxicity of the test drugs were determined and compared with the standard drug Penegra (Sildenafil citrate). The extracts of the nutmeg and clove were found to stimulate the mounting behaviour of male mice, and also to significantly increase their mating performance. The drugs were devoid of any conspicuous general short term toxicity. The extracts (50% ethanolic) of nutmeg and clove enhanced the sexual behaviour of male mice.

  15. Inactivation of ether lipid biosynthesis causes male infertility, defects in eye development and optic nerve hypoplasia in mice.

    Science.gov (United States)

    Rodemer, Claus; Thai, Thanh-Phuong; Brugger, Britta; Kaercher, Thomas; Werner, Hauke; Nave, Klaus-Armin; Wieland, Felix; Gorgas, Karin; Just, Wilhelm W

    2003-08-01

    Although known for almost 80 years, the physiological role of plasmalogens (PLs), the major mammalian ether lipids (ELs), is still enigmatic. Humans that lack ELs suffer from rhizomelic chondrodysplasia punctata (RCDP), a peroxisomal disorder usually resulting in death in early childhood. In order to learn more about the functions of ELs, we generated a mouse model for RCDP by a targeted disruption of the dihydroxyacetonephosphate acyltransferase gene. The mutant mice revealed multiple abnormalities, such as male infertility, defects in eye development, cataract and optic nerve hypoplasia, some of which were also observed in RCDP. Mass spectroscopic analysis demonstrated the presence of highly unsaturated fatty acids including docosahexaenoic acid (DHA) in brain PLs and the occurrence of PLs in lipid raft microdomains (LRMs) isolated from brain myelin. In mutants, PLs were completely absent and the concentration of brain DHA was reduced. The marker proteins flotillin-1 and F3/contactin were found in brain LRMs in reduced concentrations. In addition, the gap junctional protein connexin 43, known to be recruited to LRMs and essential for lens development and spermatogenesis, was down-regulated in embryonic fibroblasts of the EL-deficient mice. Free cholesterol, an important constituent of LRMs, was found in these fibroblasts to be accumulated in a perinuclear compartment. These data suggest that the EL-deficient mice allow the identification of new phenotypes not related so far to EL-deficiency (male sterility, defects in myelination and optic nerve hypoplasia) and indicate that PLs are required for the correct assembly and function of LRMs.

  16. Motor deficits on a ladder rung task in male and female adolescent and adult CGG knock-in mice.

    Science.gov (United States)

    Hunsaker, Michael R; von Leden, Ramona E; Ta, Binh T; Goodrich-Hunsaker, Naomi J; Arque, Gloria; Kim, Kyoungmi; Willemsen, Rob; Berman, Robert F

    2011-09-12

    The fragile X premutation is a tandem CGG trinucleotide repeat expansion on the FMR1 gene between 55 and 200 repeats in length. A CGG knock-in (CGG KI) mouse with CGG trinucleotide repeat lengths between 70 and 350 has been developed and used to model the histopathology and cognitive deficits reported in carriers of the fragile X premutation. Previous studies have shown that CGG KI mice show progressive deficits in processing spatial and temporal information. To characterize the motor deficits associated with the fragile X premutation, male and female CGG KI mice ranging from 2 to 16 months of age with trinucleotide repeats ranging from 72 to 240 CGG in length were tested for their ability to perform a skilled ladder rung walking test. The results demonstrate that both male and female CGG KI mice showed a greater number of foot slips as a function of increased CGG repeat length, independent of the age of the animal or general activity level. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. An improved procedure for integrated behavioral z-scoring illustrated with modified Hole Board behavior of male inbred laboratory mice.

    Science.gov (United States)

    Labots, M Maaike; Laarakker, M C Marijke; Schetters, D Dustin; Arndt, S S Saskia; van Lith, H A Hein

    2018-01-01

    Guilloux et al. introduced: integrated behavioral z-scoring, a method for behavioral phenotyping of mice. Using this method multiple ethological variables can be combined to show an overall description of a certain behavioral dimension or motivational system. However, a problem may occur when the control group used for the calculation has a standard deviation of zero or when no control group is present to act as a reference group. In order to solve these problems, an improved procedure is suggested: taking the pooled data as reference. For this purpose a behavioral study with male mice from three inbred strains was carried out. The integrated behavioral z-scoring methodology was applied, thereby taking five different reference group options. The outcome regarding statistical significance and practical importance was compared. Significant effects and effect sizes were influenced by the choice of the reference group. In some cases it was impossible to use a certain population and condition, because one or more behavioral variables in question had a standard deviation of zero. Based on the improved method, male mice from the three inbred strains differed regarding activity and anxiety. Taking the method described by Guilloux et al. as basis, the present procedure improved the generalizability to all types of experimental designs in animal behavioral research. To solve the aforementioned problems and to avoid getting the diagnosis of data manipulation, the pooled data (combining the data from all experimental groups in a study) as reference option is recommended. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. 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 < 0.05). The tissue-to-plasma partial AUC ratio, the drug tissue targeting index, and the tissue-plasma hysteresis-like plots also showed sex-based ibuprofen-sunitinib drug interaction 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.

  19. Effects of the Female Estrous Cycle on the Sexual Behaviors and Ultrasonic Vocalizations of Male C57BL/6 and Autistic BTBR T+ tf/J Mice.

    Science.gov (United States)

    Kim, Hyopil; Son, Junehee; Yoo, Hyoungseob; Kim, Hakyoo; Oh, Jihae; Han, DaeHee; Hwang, Yoon; Kaang, Bong-Kiun

    2016-08-01

    A primary characteristic of autism, which is a neurodevelopmental disorder, is impaired social interaction and communication. Furthermore, patients with autism frequently show abnormal social recognition. In mouse models of autism, social recognition is usually assessed by examining same-sex social behavior using various tests, such as the three-chamber test. However, no studies have examined the ability of male mice with autism to recognize the estrous cycle of female partners. In this study, we investigated the sexual behaviors, especially mounting and ultrasonic vocal communication (USV), of BTBR T+ tf/J (BTBR) mice, which are used as a well-known mouse model of autism, when they encountered estrus or diestrus female mice. As expected, C57BL/6 mice mounted more female mice in the estrus stage compared with the diestrus stage. We found that BTBR mice also mounted more female mice in the estrus stage than female mice in the diestrus stage. Although the USV emission of male mice was not different between estrus and diestrus female mice in both strains, the mounting result implies that BTBR mice distinguish sexual receptivity of females.

  20. Oral administration of visceral adipose tissue antigens ameliorates metabolic disorders in mice and elevates visceral adipose tissue-resident CD4+CD25+Foxp3+regulatory T cells.

    Science.gov (United States)

    Chen, Xiangyu; Zhang, Dali; Chen, Xiaoling; Meng, Gang; Zheng, Qian; Mai, Wenli; Wu, Yuzhang; Ye, Lilin; Wang, Li

    2017-08-16

    Obesity and type 2 diabetes are linked with chronic, low-grade inflammation in visceral adipose tissue (VAT). A unique population of VAT-resident CD4 + Foxp3 + Tregs plays a crucial role in regulating VAT inflammation and metabolic homeostasis. VAT-resident Tregs display a highly restricted TCR repertoire, suggesting they recognize certain autoantigen(s) in VAT. A dramatic reduction of VAT-resident Tregs has been shown to closely correlate with obesity-related VAT chronic inflammation and metabolic disorders. Oral tolerance strategy may modulate inflammatory response to autoantigens by several mechanisms including induction of autoantigen-specific Tregs. Here, we explored the effects and cellular mechanism of oral administration of VAT pooled antigens on high-fat diet (HFD)-induced metabolic disorders in mice. Indeed, we found that oral treatment of VAT mixture antigens effectively inhibited gain in body weight and fat mass, ameliorated serum lipid parameters, and improved insulin sensitivity in HFD mice. This strategy was shown to significantly restore HFD-induced decrease of VAT-resident Tregs, accompanied by a hampered M2-type to M1-type macrophages phenotypic switch as well as decreased CD8 + T cells infiltration in VAT. Thus, oral administration of VAT antigens may be a novel and safe strategy against obesity and its related metabolic disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Properties of extensor digitorum longus muscle and skinned fibers from adult and aged male and female Actn3 knockout mice.

    Science.gov (United States)

    Chan, Stephen; Seto, Jane T; Houweling, Peter J; Yang, Nan; North, Kathryn N; Head, Stewart I

    2011-01-01

    Absence of α-actinin-3, encoded by the ACTN3 "speed gene," is associated with poorer sprinting performance in athletes and a slowing of relaxation in fast-twitch muscles of Actn3 knockout (KO) mice. Our first aim was to investigate, at the individual-fiber level, possible mechanisms for this slowed relaxation. Our second aim was to characterize the contractile properties of whole extensor digitorum longus (EDL) muscles from KO mice by age and gender. We examined caffeine-induced Ca(2+) release in mechanically skinned EDL fibers from KO mice, and measured isolated whole EDL contractile properties. The sarcoplasmic reticulum of KO muscle fibers loaded Ca(2+) more slowly than that of wild-types (WTs). Whole KO EDL muscles had longer twitch and tetanus relaxation times than WTs, and reduced mass and cross-sectional area. These effects occurred in both male and female mice, but they diminished with age. These changes in KO muscles and fibers help to explain the effects of α-actinin-3 deficiency observed in athletes. Copyright © 2010 Wiley Periodicals, Inc.

  2. Metabolism and disposition of phenolphthalein in male and female F344 rats and B6C3F1 mice.

    Science.gov (United States)

    Griffin, R J; Godfrey, V B; Burka, L T

    1998-04-01

    A recent 2-year carcinogenicity/toxicology study determined that phenolphthalein (PHTH) is a multisite carcinogen in both mice and rats at all doses evaluated. In response to this finding the metabolism and disposition of PHTH has been evaluated in both F344 rats and B6C3F1 mice at a single oral dose of 800 mg/kg. This dose fell within the range previously found to be carcinogenic in rats and mice. Studies were also performed using 1 and 50 mg/kg doses. At 800 mg/kg recovery of [14C]PHTH after 72 h was near 100% in females but closer to 75% in males. Radioactivity was primarily recovered in the feces in rats (> 90%), while mice excreted 30-40% of administered activity in the urine. There was no significant retention of radioactivity in tissues by 72 h and no significant accumulation of radioactivity in any tissue at any time point. Covalent binding to protein in target tissues, bone marrow and ovary, was at or less than the pmol/mg protein range. The major metabolite was PHTH glucuronide. Three minor metabolites were detected. A sulfate conjugate and and a hydroxylated metabolite were identified by comparison of retention times and 1H NMR and/or mass spectra with synthetic standards. A diglucuronide conjugate was tentatively identified. Biliary elimination was extensive in rats (35% of dose within 6 h); the only product detected in bile was phenolphthalein glucuronide.

  3. Relevance of pituitary aromatase and estradiol on the maintenance of the population of prolactin-positive cells in male mice.

    Science.gov (United States)

    García-Barrado, María José; Blanco, Enrique J; Catalano-Iniesta, Leonardo; Sanchez-Robledo, Virginia; Iglesias-Osma, María Carmen; Carretero-Hernández, Marta; Rodríguez-Cobos, Javier; Burks, Deborah Jane; Carretero, José

    2016-07-01

    In previous studies we demonstrated the expression of aromatase in pituitary cells. This expression is gender related, and is also associated with the presence of prolactinomas. To ascertain the relevance of aromatase in modulating the populations of prolactin-positive pituitary cells an immunocytochemical and morphometric study of prolactin-positive pituitary cells was carried out using the pituitary glands of adult male and female aromatase-knockout (ArKO) mice. Additionally has been determined if pituitary aromatase is involved in a gender-linked differentiated regulation of the prolactin-producing pituitary cells. Compared to wild-type mice, the knockout animals of both genders showed a significant decrease (pprolactin cells, as well as in the percentages of the prolactin-positive cells and the proliferating prolactin cells. Our results suggest that estradiol is responsible for the maintenance of the population of prolactin cell in males and, so as not to disturb the endocrine reproductive environment, estradiol is synthesized inside the pituitary by circulating testosterone via means of aromatase P450, which acts in paracrine way. This new role for pituitary aromatase may well explain the previous findings establishing that the pituitary expression of aromatase is higher in males than in females, and the association between the development of prolactinomas and the increased expression of aromatase in tumours. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. 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.

  5. Maternal obese-type gut microbiota differentially impact cognition, anxiety and compulsive behavior in male and female offspring in mice.

    Science.gov (United States)

    Bruce-Keller, Annadora J; Fernandez-Kim, Sun-Ok; Townsend, R Leigh; Kruger, Claudia; Carmouche, Richard; Newman, Susan; Salbaum, J Michael; Berthoud, Hans-Rudolf

    2017-01-01

    Maternal obesity is known to predispose offspring to metabolic and neurodevelopmental abnormalities. While the mechanisms underlying these phenomena are unclear, high fat diets dramatically alter intestinal microbiota, and gut microbiota can impact physiological function. To determine if maternal diet-induced gut dysbiosis can disrupt offspring neurobehavioral function, we transplanted high fat diet- (HFD) or control low fat diet-associated (CD) gut microbiota to conventionally-housed female mice. Recipient mice were then bred and the behavioral phenotype of male and female offspring was tracked. While maternal behavior was unaffected, neonatal offspring from HFD dams vocalized less upon maternal separation than pups from CD dams. Furthermore, weaned male offspring from HFD dams had significant and selective disruptions in exploratory, cognitive, and stereotypical/compulsive behavior compared to male offspring from CD dams; while female offspring from HFD dams had increases in body weight and adiposity. 16S metagenomic analyses confirmed establishment of divergent microbiota in CD and HFD dams, with alterations in diversity and taxonomic distribution throughout pregnancy and lactation. Likewise, significant alterations in gut microbial diversity and distribution were noted in offspring from HFD dams compared to CD dams, and in males compared to females. Regression analyses of behavioral performance against differentially represented taxa suggest that decreased representation of specific members of the Firmicutes phylum predict behavioral decline in male offspring. Collectively, these data establish that high fat diet-induced maternal dysbiosis is sufficient to disrupt behavioral function in murine offspring in a sex-specific manner. Thus these data reinforce the essential link between maternal diet and neurologic programming in offspring and suggest that intestinal dysbiosis could link unhealthy modern diets to the increased prevalence of neurodevelopmental and

  6. Maternal obese-type gut microbiota differentially impact cognition, anxiety and compulsive behavior in male and female offspring in mice.

    Directory of Open Access Journals (Sweden)

    Annadora J Bruce-Keller

    Full Text Available Maternal obesity is known to predispose offspring to metabolic and neurodevelopmental abnormalities. While the mechanisms underlying these phenomena are unclear, high fat diets dramatically alter intestinal microbiota, and gut microbiota can impact physiological function. To determine if maternal diet-induced gut dysbiosis can disrupt offspring neurobehavioral function, we transplanted high fat diet- (HFD or control low fat diet-associated (CD gut microbiota to conventionally-housed female mice. Recipient mice were then bred and the behavioral phenotype of male and female offspring was tracked. While maternal behavior was unaffected, neonatal offspring from HFD dams vocalized less upon maternal separation than pups from CD dams. Furthermore, weaned male offspring from HFD dams had significant and selective disruptions in exploratory, cognitive, and stereotypical/compulsive behavior compared to male offspring from CD dams; while female offspring from HFD dams had increases in body weight and adiposity. 16S metagenomic analyses confirmed establishment of divergent microbiota in CD and HFD dams, with alterations in diversity and taxonomic distribution throughout pregnancy and lactation. Likewise, significant alterations in gut microbial diversity and distribution were noted in offspring from HFD dams compared to CD dams, and in males compared to females. Regression analyses of behavioral performance against differentially represented taxa suggest that decreased representation of specific members of the Firmicutes phylum predict behavioral decline in male offspring. Collectively, these data establish that high fat diet-induced maternal dysbiosis is sufficient to disrupt behavioral function in murine offspring in a sex-specific manner. Thus these data reinforce the essential link between maternal diet and neurologic programming in offspring and suggest that intestinal dysbiosis could link unhealthy modern diets to the increased prevalence of

  7. 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

  8. Effects of BCG, levamisole and PS-K on the rejection of male skin grafts by female mice.

    Science.gov (United States)

    Seo, S; Yasuhara, J; Saeki, K

    1979-10-01

    Rejection of male skin grafts by BALB/c female mice was accelerated by one s.c. injection of BCG (5 X 10(5) microorganisms/mouse) into recipients on the day of transplantation. Levamisole 20 mg/kg injected similarly was without any effect. Protein-bound polysaccharide Kureha (PS-K) injected 250 mg/kg s.c. or i.p. once every other day from the day of transplantation stimulated graft rejection. The s.c. route was more effective than the i.p. route. These results show that, in sex-linked graft rejection in mice, PS-K has an immunostimulant action similar to that of BCG. This property may be important to the antineoplastic activity of PS-K.

  9. Thyroid Dysfunction Associated With Follicular Cell Steatosis in Obese Male Mice and Humans

    Science.gov (United States)

    Lee, Min Hee; Lee, Jung Uee; Joung, Kyong Hye; Kim, Yong Kyung; Ryu, Min Jeong; Lee, Seong Eun; Kim, Soung Jung; Chung, Hyo Kyun; Choi, Min Jeong; Chang, Joon Young; Lee, Sang-Hee; Kweon, Gi Ryang; Kim, Hyun Jin; Kim, Koon Soon; Kim, Seong-Min; Jo, Young Suk; Park, Jeongwon; Cheng, Sheue-Yann

    2015-01-01

    Adult thyroid dysfunction is a common endocrine disorder associated with an increased risk of cardiovascular disease and mortality. A recent epidemiologic study revealed a link between obesity and increased prevalence of hypothyroidism. It is conceivable that excessive adiposity in obesity might lead to expansion of the interfollicular adipose (IFA) depot or steatosis in thyroid follicular cells (thyroid steatosis, TS). In this study, we investigated the morphological and functional changes in thyroid glands of obese humans and animal models, diet-induced obese (DIO), ob/ob, and db/db mice. Expanded IFA depot and TS were observed in obese patients. Furthermore, DIO mice showed increased expression of lipogenesis-regulation genes, such as sterol regulatory element binding protein 1 (SREBP-1), peroxisome proliferator-activated receptor γ (PPARγ), acetyl coenzyme A carboxylase (ACC), and fatty acid synthetase (FASN) in the thyroid gland. Steatosis and ultrastructural changes, including distension of the endoplasmic reticulum (ER) and mitochondrial distortion in thyroid follicular cells, were uniformly observed in DIO mice and genetically obese mouse models, ob/ob and db/db mice. Obese mice displayed a variable degree of primary thyroid hypofunction, which was not corrected by PPARγ agonist administration. We propose that systemically increased adiposity is associated with characteristic IFA depots and TS and may cause or influence the development of primary thyroid failure. PMID:25555091

  10. 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.

  11. 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

    -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...... and insulin and substantially improved glucose clearance. To directly assess the contribution of GLP-1 receptor (GLP-1R)-signaling to these improvements, l-arginine was given to Glp1r knockout mice and their wild-type littermates. In this experiment oral l-arginine significantly augmented insulin secretion...

  12. 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

  13. Short-term treatment with bisphenol-A leads to metabolic abnormalities in adult male mice.

    Directory of Open Access Journals (Sweden)

    Thiago M Batista

    Full Text Available 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 Thr(308 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.

  14. 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.

  15. High fat diet attenuates hyperglycemia, body composition changes, and bone loss in male streptozotocin-induced type 1 diabetic mice.

    Science.gov (United States)

    Carvalho, Adriana Lelis; DeMambro, Victoria E; Guntur, Anyonya R; Le, Phuong; Nagano, Kenichi; Baron, Roland; de Paula, Francisco José Albuquerque; Motyl, Katherine J

    2018-02-01

    There is a growing and alarming prevalence of obesity and the metabolic syndrome in type I diabetic patients (T1DM), particularly in adolescence. In general, low bone mass, higher fracture risk, and increased marrow adipose tissue (MAT) are features of diabetic osteopathy in insulin-deficient subjects. On the other hand, type 2 diabetes (T2DM) is associated with normal or high bone mass, a greater risk of peripheral fractures, and no change in MAT. Therefore, we sought to determine the effect of weight gain on bone turnover in insulin-deficient mice. We evaluated the impact of a 6-week high-fat (HFD) rich in medium chain fatty acids or low-fat diet (LFD) on bone mass and MAT in a streptozotocin (STZ)-induced model using male C57BL/6J mice at 8 weeks of age. Dietary intervention was initiated after diabetes confirmation. At the endpoint, lower non-fasting glucose levels were observed in diabetic mice fed with high fat diet compared to diabetic mice fed the low fat diet (STZ-LFD). Compared to euglycemic controls, the STZ-LFD had marked polydipsia and polyphagia, as well as reduced lean mass, fat mass, and bone parameters. Interestingly, STZ-HFD mice had higher bone mass, namely less cortical bone loss and more trabecular bone than STZ-LFD. Thus, we found that a HFD, rich in medium chain fatty acids, protects against bone loss in a T1DM mouse model. Whether this may also translate to T1DM patients who are overweight or obese in respect to maintenance of bone mass remains to be determined through longitudinal studies. © 2017 Wiley Periodicals, Inc.

  16. 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.

  17. 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

  18. Illumination of murine gammaherpesvirus-68 cycle reveals a sexual transmission route from females to males in laboratory mice.

    Science.gov (United States)

    François, Sylvie; Vidick, Sarah; Sarlet, Mickaël; Desmecht, Daniel; Drion, Pierre; Stevenson, Philip G; Vanderplasschen, Alain; Gillet, Laurent

    2013-01-01

    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 the spread of these

  19. 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.

  20. Neurotoxicity of low bisphenol A (BPA) exposure for young male mice: Implications for children exposed to environmental levels of BPA.

    Science.gov (United States)

    Zhou, Yuanxiu; Wang, Zhouyu; Xia, Minghan; Zhuang, Siyi; Gong, Xiaobing; Pan, Jianwen; Li, Chuhua; Fan, Ruifang; Pang, Qihua; Lu, Shaoyou

    2017-10-01

    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. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Illumination of Murine Gammaherpesvirus-68 Cycle Reveals a Sexual Transmission Route from Females to Males in Laboratory Mice

    Science.gov (United States)

    François, Sylvie; Vidick, Sarah; Sarlet, Mickaël; Desmecht, Daniel; Drion, Pierre; Stevenson, Philip G.; Vanderplasschen, Alain; Gillet, Laurent

    2013-01-01

    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 the spread of these

  2. 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.

  3. 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.

  4. Studies on mutations in male germ cells of transgenic mice following exposure to isopropyl methanesulfonate, ethylnitrosourea or X-ray.

    Science.gov (United States)

    Katoh, M; Inomata, T; Horiya, N; Suzuki, F; Shida, T; Ishioka, K; Shibuya, T

    1994-11-01

    Transgenic mice have recently been used for mutagenesis assays in vivo. The present study was undertaken to clarify whether such assays can detect mutations induced after treatment of male germ cells in mouse with isopropyl methanesulfonate (iPMS), ethylnitrosourea (ENU) or X-ray irradiation. The transgenic mice used for assay are Muta Mouse (MM) strain, which carries 80 copies of the bacterial lacZ gene per cell as targets for mutagenesis. Male MM animals were given a single intraperitoneal injection of 200 mg/kg iPMS, 150 mg/kg ENU or were irradiated with 500 rads of X-rays. Vasa deferential sperm, caudal epididymal sperm and/or whole testes were extracted at various times after treatment with each agent. After the genomic DNA was extracted from each tissue, mutation analysis at the lacZ locus was carried out by the method of Myhr et al. The spontaneous lacZ- mutant frequencies were on the order of 10(-5)-10(-6). The lacZ- mutant frequencies in all treatment groups were increased over the control animals. The iPMS-induced mutant frequency in postmeiotic stages was low. However, ENU induced relatively high mutant frequencies in the spermatogonia. X-rays induced mutant frequencies in the late spermatid and early spermatid stages that were higher than the mutant frequencies in spermatogonia. Mutant frequencies in MM detected after treatment of male germ cells with ENU or X-rays were lower than mutant frequencies detected by the mouse specific-locus test in previous reports. Hence, considering the lower resolution power of the transgenic animal mutagenesis assays using the target lacZ gene compared with the specific locus test, to detect mutations induced in male germ cells, it is not clear whether this assay is a practical alternative to the specific locus test.

  5. 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; McCabe, Joseph T

    2016-05-01

    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.

  6. Male Differentiation of Germ Cells Induced by Embryonic Age-Specific Sertoli Cells in Mice1

    Science.gov (United States)

    Ohta, Kohei; Yamamoto, Miyuki; Lin, Yanling; Hogg, Nathanael; Akiyama, Haruhiko; Behringer, Richard R.; Yamazaki, Yukiko

    2012-01-01

    ABSTRACT Retinoic acid (RA) is a meiosis-inducing factor. Primordial germ cells (PGCs) in the developing ovary are exposed to RA, resulting in entry into meiosis. In contrast, PGCs in the developing testis enter mitotic arrest to differentiate into prospermatogonia. Sertoli cells express CYP26B1, an RA-metabolizing enzyme, providing a simple explanation for why XY PGCs do not initiate meios/is. However, regulation of entry into mitotic arrest is likely more complex. To investigate the mechanisms that regulate male germ cell differentiation, we cultured XX and XY germ cells at 11.5 and 12.5 days postcoitus (dpc) with an RA receptor inhibitor. Expression of Stra8, a meiosis initiation gene, was suppressed in all groups. However, expression of Dnmt3l, a male-specific gene, during embryogenesis was elevated but only in 12.5-dpc XY germ cells. This suggests that inhibiting RA signaling is not sufficient for male germ cell differentiation but that the male gonadal environment also contributes to this pathway. To define the influence of Sertoli cells on male germ cell differentiation, Sertoli cells at 12.5, 15.5, and 18.5 dpc were aggregated with 11.5 dpc PGCs, respectively. After culture, PGCs aggregated with 12.5 dpc Sertoli cells increased Nanos2 and Dnmt3l expression. Furthermore, these PGCs established male-specific methylation imprints of the H19 differentially methylated domains. In contrast, PGCs aggregated with Sertoli cells at late embryonic ages did not commit to the male pathway. These findings suggest that male germ cell differentiation is induced both by inhibition of RA signaling and by molecule(s) production by embryonic age-specific Sertoli cells. PMID:22262692

  7. 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

  8. A Predominant Oxidative Renal Metabolite of Empagliflozin in Male Mice Is Cytotoxic in Mouse Renal Tubular Cells but not Genotoxic.

    Science.gov (United States)

    Smith, James D; Huang, Zimei; Escobar, Patricia A; Foppiano, Pamela; Maw, Hlaing; Loging, William; Yu, Hongbin; Phillips, Jonathan A; Taub, Mitchell; Ku, Warren W

    In a previously reported CD-1 mouse 2-year carcinogenicity study with the sodium glucose cotransporter-2 inhibitor empagliflozin, an increased incidence of renal tubular adenomas and carcinomas was identified only in the male high-dose group. Follow-up investigative studies have shown that the renal tumors in male high-dose mice were preceded by a number of renal degenerative/regenerative findings. Prior cross-species in vitro metabolism studies using microsomes identified an oxidative metabolite (M466/2) predominantly formed in the male mouse kidney and which spontaneously degrades to a metabolite (M380/1) and reactive 4-OH crotonaldehyde (CTA). In order to further evaluate potential modes of action for empagliflozin-associated male mouse renal tumors, we report here a series of in vitro investigative toxicology studies conducted to evaluate the cytotoxic and genotoxic potential of empagliflozin and M466/2. To assess the cytotoxic potential of empagliflozin and M466/2, a primary mouse renal tubular epithelial (mRTE) cell model was used. In mRTE cells, M466/2-derived in vitro 4-OH CTA exposure was cytotoxic, while empagliflozin was not cytotoxic or mitogenic. Empagliflozin and M466/2 were not genotoxic, supporting an indirect mode of action for empagliflozin-associated male mouse renal tumorigenesis. In conclusion, these in vitro data show that M466/2-derived 4-OH CTA exposure is associated with cytotoxicity in renal tubule cells and may be involved in promoting compound-related in vivo renal metabolic stress and chronic low-level renal injury, in turn supporting a nongenotoxic mode of tumor pathogenesis specific to the male mouse.

  9. Obesity or Overweight, a Chronic Inflammatory Status in Male Reproductive System, Leads to Mice and Human Subfertility

    Directory of Open Access Journals (Sweden)

    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.

  10. 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

  11. 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.

  12. A Foxp2 mutation implicated in human speech deficits alters sequencing of ultrasonic vocalizations in adult male mice

    Directory of Open Access Journals (Sweden)

    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.

  13. Effect of Tea (Camellia sinensis and Olive (Olea europaea L. Leaves Extracts on Male Mice Exposed to Diazinon

    Directory of Open Access Journals (Sweden)

    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.

  14. 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.

  15. 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.

  16. 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.

  17. Endocrine-disrupting activity of hydraulic fracturing chemicals and adverse health outcomes after prenatal exposure in male mice

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    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.

  18. 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.

  19. 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

  20. Effects of Noise Exposure on Systemic and Tissue-Level Markers of Glucose Homeostasis and Insulin Resistance in Male Mice.

    Science.gov (United States)

    Liu, Lijie; Wang, Fanfan; Lu, Haiying; Cao, Shuangfeng; Du, Ziwei; Wang, Yongfang; Feng, Xian; Gao, Ye; Zha, Mingming; Guo, Min; Sun, Zilin; Wang, Jian

    2016-09-01

    Epidemiological studies have indicated that noise exposure is associated with an increased risk of type 2 diabetes mellitus (T2DM). However, the nature of the connection between noise exposure and T2DM remains to be explored. We explored whether and how noise exposure affects glucose homeostasis in mice as the initial step toward T2DM development. Male ICR mice were randomly assigned to one of four groups: the control group and three noise groups (N20D, N10D, and N1D), in which the animals were exposed to white noise at 95 decibel sound pressure level (dB SPL) for 4 hr per day for 20 successive days, 10 successive days, or 1 day, respectively. Glucose tolerance and insulin sensitivity were evaluated 1 day, 1 week, and 1 month after the final noise exposure (1DPN, 1WPN, and 1MPN). Standard immunoblots, immunohistochemical methods, and enzyme-linked immunosorbent assays (ELISA) were performed to assess insulin signaling in skeletal muscle, the morphology of β cells, and plasma corticosterone levels. Noise exposure for 1 day caused transient glucose intolerance and insulin resistance, whereas noise exposure for 10 and 20 days had no effect on glucose tolerance but did cause prolonged insulin resistance and an increased insulin response to glucose challenge. Akt phosphorylation and GLUT4 translocation in response to exogenous insulin were decreased in the skeletal muscle of noise-exposed animals. Noise exposure at 95 dB SPL caused insulin resistance in male ICR mice, which was prolonged with longer noise exposure and was likely related to the observed blunted insulin signaling in skeletal muscle. Liu L, Wang F, Lu H, Cao S, Du Z, Wang Y, Feng X, Gao Y, Zha M, Guo M, Sun Z, Wang J. 2016. Effects of noise exposure on systemic and tissue-level markers of glucose homeostasis and insulin resistance in male mice. Environ Health Perspect 124:1390-1398; http://dx.doi.org/10.1289/EHP162.

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

    Science.gov (United States)

    Clemmensen, Christoffer; Smajilovic, Sanela; Smith, Eric P.; Woods, Stephen C.; Bräuner-Osborne, Hans; Seeley, Randy J.; D'Alessio, David A.

    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 and insulin and substantially improved glucose clearance. To directly assess the contribution of GLP-1 receptor (GLP-1R)-signaling to these improvements, l-arginine was given to Glp1r knockout mice and their wild-type littermates. In this experiment oral l-arginine significantly augmented insulin secretion and improved glucose clearance in WT mice, but not in Glp1r knockout littermates. Taken together these findings identify l-arginine as a GLP-1 secretagogue in vivo and demonstrate that improvement of glucose tolerance by oral l-arginine depends on GLP-1R-signaling. These findings raise the intriguing possibility that l-arginine-based nutritional and/or pharmaceutical therapies may benefit glucose tolerance by improving the postprandial GLP-1 response in obese individuals. PMID:23959939

  3. 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

  4. Evaluation of response to restraint stress by salivary corticosterone levels in adult male mice

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    NOHARA, Masakatsu; TOHEI, Atsushi; SATO, Takumi; AMAO, Hiromi

    2016-01-01

    Saliva as a sampling method is a low invasive technique for the detection of physiologically active substances, as opposed to sampling the plasma or serum. In this study, we obtained glucocorticoids transferred from the blood to the saliva from mice treated with 2.0 mg/kg via an intraperitoneal injection of cortisol. Next, to evaluate the effect of restraint stress using mouse saliva—collected under anesthesia by mixed anesthetic agents—we measured plasma and salivary corticosterone levels at 60 min after restraint stress. Moreover, to evaluate salivary corticosterone response to stress in the same individual mouse, an adequate recovery period (1, 3 and 7 days) after anesthesia was examined. The results demonstrate that exogenous cortisol was detected in the saliva and the plasma, in mice treated with cortisol. Restraint stress significantly increased corticosterone levels in both the plasma and saliva (Pmice showed that restraint stress significantly increased salivary corticosterone levels in all three groups (1-, 3- and 7-day recovery). However, the statistical evidence of corticosterone increase is stronger in the 7-day recovery group (Psaliva reflect its levels in the plasma, and salivary corticosterone is a useful, less-invasive biomarker of physical stress in mice. The present study may contribute to concepts of Reduction and Refinement of the three Rs in small animal experiments. PMID:26852731

  5. The Pathophysiological Sequence of Glucocorticoid-Induced Osteonecrosis of the Femoral Head in Male Mice.

    Science.gov (United States)

    Weinstein, Robert S; Hogan, Erin A; Borrelli, Michael J; Liachenko, Serguei; O'Brien, Charles A; Manolagas, Stavros C

    2017-11-01

    In search of the sequence of pathogenic events leading to glucocorticoid-induced osteonecrosis, we determined the molecular, biomechanical, cellular, and vascular changes in the femur of C57BL/6 mice receiving prednisolone for 14, 28, or 42 days. The femoral head, but not the distal femur, of mice treated for 14 days showed a decrease in the expression of the hypoxia-inducible factor (Hif)-1α and vascular endothelial growth factor (VEGF), the number of osteoblasts, and bone formation rate and strength and showed an increase in osteoclasts. These changes were accompanied by conversion of the normal dendritic vasculature to pools of edema as detected by magnetic resonance imaging, providing robust diagnostic evidence of early osteonecrosis. At that time point, there were no detectable changes in bone density, cortical or cancellous bone architecture, midshaft or distal cancellous bone, or osteocyte apoptosis. In mice treated for 28 days, femoral head cancellous density, cortical width, and trabecular thickness decreased, and by 42 days the femoral heads had full-depth cortical penetrations and cancellous tissue osteonecrosis. These results indicate that the femoral head is a particularly sensitive anatomical site to the adverse effects of glucocorticoid excess on bone and that decreases of Hif-1α and VEGF expression, bone vascularity, and strength precede the loss of bone mass and microarchitectural deterioration, thus rendering the femoral head vulnerable to collapse.

  6. 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.

  7. α-Cell Dysfunctions and Molecular Alterations in Male Insulinopenic Diabetic Mice Are Not Completely Corrected by Insulin.

    Science.gov (United States)

    Dusaulcy, Rodolphe; Handgraaf, Sandra; Heddad-Masson, Mounia; Visentin, Florian; Vesin, Christian; Reimann, Franck; Gribble, Fiona; Philippe, Jacques; Gosmain, Yvan

    2016-02-01

    Glucagon and α-cell dysfunction are critical in the development of hyperglycemia during diabetes both in humans and rodents. We hypothesized that α-cell dysfunction leading to dysregulated glucagon secretion in diabetes is due to both a lack of insulin and intrinsic defects. To characterize α-cell dysfunction in diabetes, we used glucagon-Venus transgenic male mice and induced insulinopenic hyperglycemia by streptozotocin administration leading to alterations of glucagon secretion. We investigated the in vivo impact of insulinopenic hyperglycemia on glucagon-producing cells using FACS-sorted α-cells from control and diabetic mice. We demonstrate that increased glucagonemia in diabetic mice is mainly due to increases of glucagon release and biosynthesis per cell compared with controls without changes in α-cell mass. We identified genes coding for proteins involved in glucagon biosynthesis and secretion, α-cell differentiation, and potential stress markers such as the glucagon, Arx, MafB, cMaf, Brain4, Foxa1, Foxa3, HNF4α, TCF7L2, Glut1, Sglt2, Cav2.1, Cav2.2, Nav1.7, Kir6.2/Sur1, Pten, IR, NeuroD1, GPR40, and Sumo1 genes, which were abnormally regulated in diabetic mice. Importantly, insulin treatment partially corrected α-cell function and expression of genes coding for proglucagon, or involved in glucagon secretion, glucose transport and insulin signaling but not those coding for cMAF, FOXA1, and α-cell differentiation markers as well as GPR40, NEUROD1, CAV2.1, and SUMO1. Our results indicate that insulinopenic diabetes induce marked α-cell dysfunction and molecular alteration, which are only partially corrected by in vivo insulin treatment.

  8. 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.

  9. 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

  10. 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

  11. 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

  12. Vitamin D limits chemokine expression in adipocytes and macrophage migration in vitro and in male mice.

    Science.gov (United States)

    Karkeni, Esma; Marcotorchino, Julie; Tourniaire, Franck; Astier, Julien; Peiretti, Franck; Darmon, Patrice; Landrier, Jean-François

    2015-05-01

    Vitamin D (VD) displays immunoregulatory effects and reduces adipocyte inflammation, which may participate to a reduction of adipose tissue macrophage infiltration in the context of obesity-associated low-grade inflammation. These observations have been described mainly in vitro, through the evaluation of a limited number of inflammatory markers. Here, we studied the effects of 1,25 dihydroxy-VD on chemokine network expression in adipocytes (by transcriptomic approach), and we confirm the physiological relevance of these data in vivo, by demonstrating the effect of VD on cytokine and chemokine gene expression as well as on macrophage infiltration in adipose tissue. 1,25 dihydroxy-VD down-regulated (-1.3- to -10.8-fold) the mRNA expression of 29 chemokines and limited macrophage migration in TNFα-conditioned adipocyte medium (1.5-fold; P < .05). This effect was associated with a reduction in p65 and IκB (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha) phosphorylation (2-fold compared with TNFα; P < .05). The effects of VD were confirmed in mice injected ip with lipopolysaccharide (acute inflammation) and diet-induced obese mice (metabolic inflammation), where the levels of mRNA encoding proinflammatory cytokines and chemokines (∼2-fold) were reduced in adipocytes (acute and metabolic inflammation) and adipose tissue and that macrophage infiltration was also inhibited in the adipose tissue of obese mice (metabolic inflammation). Altogether, these results showed that VD displayed a global immunoregulatory impact on adipocytes, notably via the inhibition of chemokine expression and macrophage infiltration in inflamed adipose tissue.

  13. Oxytocin-Oxytocin Receptor Systems Facilitate Social Defeat Posture in Male Mice.

    Science.gov (United States)

    Nasanbuyan, Naranbat; Yoshida, Masahide; Takayanagi, Yuki; Inutsuka, Ayumu; Nishimori, Katsuhiko; Yamanaka, Akihiro; Onaka, Tatsushi

    2018-02-01

    Social stress has deteriorating effects on various psychiatric diseases. In animal models, exposure to socially dominant conspecifics (i.e., social defeat stress) evokes a species-specific defeat posture via unknown mechanisms. Oxytocin neurons have been shown to be activated by stressful stimuli and to have prosocial and anxiolytic actions. The roles of oxytocin during social defeat stress remain unclear. Expression of c-Fos, a marker of neuronal activation, in oxytocin neurons and in oxytocin receptor‒expressing neurons was investigated in mice. The projection of oxytocin neurons was examined with an anterograde viral tracer, which induces selective expression of membrane-targeted palmitoylated green fluorescent protein in oxytocin neurons. Defensive behaviors during double exposure to social defeat stress in oxytocin receptor‒deficient mice were analyzed. After social defeat stress, expression of c-Fos protein was increased in oxytocin neurons of the bed nucleus of the stria terminalis, supraoptic nucleus, and paraventricular hypothalamic nucleus. Expression of c-Fos protein was also increased in oxytocin receptor‒expressing neurons of brain regions, including the ventrolateral part of the ventromedial hypothalamus and ventrolateral periaqueductal gray. Projecting fibers from paraventricular hypothalamic oxytocin neurons were found in the ventrolateral part of the ventromedial hypothalamus and in the ventrolateral periaqueductal gray. Oxytocin receptor‒deficient mice showed reduced defeat posture during the second social defeat stress. These findings suggest that social defeat stress activates oxytocin-oxytocin receptor systems, and the findings are consistent with the view that activation of the oxytocin receptor in brain regions, including the ventrolateral part of the ventromedial hypothalamus and the ventrolateral periaqueductal gray, facilitates social defeat posture.

  14. Gestational exposure to diethylstilbestrol alters cardiac structure/function, protein expression and DNA methylation in adult male mice progeny

    International Nuclear Information System (INIS)

    Haddad, Rami; Kasneci, Amanda; Mepham, Kathryn; Sebag, Igal A.

    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

  15. Food-associated estrogenic compounds induce estrogen receptor-mediated luciferase gene expression in transgenic male mice.

    Science.gov (United States)

    Ter Veld, Marcel G R; Zawadzka, E; van den Berg, J H J; van der Saag, Paul T; Rietjens, Ivonne M C M; Murk, Albertinka J

    2008-07-30

    The present paper aims at clarifying to what extent seven food-associated compounds, shown before to be estrogenic in vitro, can induce estrogenic effects in male mice with an estrogen receptor (ER)-mediated luciferase (luc) reporter gene system. The luc induction was determined in different tissues 8h after dosing the ER-luc male mice intraperitoneally (IP) or 14h after oral dosing. Estradiol-propionate (EP) was used as a positive control at 0.3 and 1mg/kg bodyweight (bw), DMSO as solvent control. The food-associated estrogenic compounds tested at non-toxic doses were bisphenol A (BPA) and nonylphenol (NP) (both at 10 and 50mg/kgbw), dichlorodiphenyldichloroethylene (p,p'-DDE; at 5 and 25mg/kgbw), quercetin (at 1.66 and 16.6mg/kgbw), di-isoheptyl phthalate (DIHP), di-(2-ethylhexyl) phthalate (DEHP) and di-(2-ethylhexyl) adipate (DEHA) all at 30 and 100mg/kgbw. In general IP dosing resulted in higher luc inductions than oral dosing. EP induced luc activity in the liver in a statistically significant dose-related way with the highest induction of all compounds tested which was 20,000 times higher than the induction by the DMSO-control. NP, DDE, DEHA and DIHP did not induce luc activity in any of the tissues tested. BPA induced luc in the liver up to 420 times via both exposure routes. BPA, DEHP and quercetin induced luc activity in the liver after oral exposure. BPA (50mg/kgbw IP) also induced luc activity in the testis, kidneys and tibia. The current study reveals that biomarker-responses in ER-luc male mice occur after a single oral exposure to food-associated estrogenic model compounds at exposure levels 10 to 10(4) times higher than the established TDI's for some of these compounds. Given the facts that (i) the present study did not include chronic exposure and that (ii) simultaneous exposure to multiple estrogenic compounds may be a realistic exposure scenario, it remains to be seen whether this margin is sufficiently high.

  16. Effects of aging on mRNA profiles for drug-metabolizing enzymes and transporters in livers of male and female mice.

    Science.gov (United States)

    Fu, Zidong Donna; Csanaky, Iván L; Klaassen, Curtis D

    2012-06-01

    Aging is a physiological process characterized by progressive functional decline in various organs over time. To reveal possible molecular mechanisms of altered xenobiotic disposition and toxicity in elderly individuals, age-dependent mRNA profiles for 101 xenobiotic-processing genes (XPGs), including seven uptake transporters, 41 phase I enzymes, 36 phase II enzymes, 10 efflux transporters, and seven transcription factors, were characterized in livers of male and female mice from 3 to 27 months of age. Gender differences across the lifespan (significant at five ages or more) were observed for 52 XPGs, including 15 male-predominant genes (e.g., Oatp1a1, Cyp3a11, Ugt1a6a, Comt, and Bcrp) and 37 female-predominant genes (e.g., Oatp1a4, Cyp2b10, Sult1a1, Ugt1a1, and Mrp3). During aging, the mRNA levels for 44% of the 101 XPGs changed in male mice and 63% changed in female mice. In male mice, mRNA levels for 40 XPGs (e.g., Oatp1a1, Ces2c, Gstm4, Gstp1, and Ces1e) were lower in aged mice (more than 21 months of age), whereas mRNA levels for four XPGs (e.g., Oat2 and Gstm2) were higher in aged mice. In female mice, mRNA levels for 43 XPGs (e.g., Oatp1a1, Cyp1a2, Ces1f, Sult3a1, Gstt2, Comt, Ent1, Fmo3, and Mrp6) were lower in aged mice, whereas mRNA levels for 21 XPGs (e.g., Oatp1a4, Nqo1, Adh7, Sult2a1/2, Gsta1, and Mrp4) were higher in aged mice. In conclusion, 51% of the 101 XPGs exhibited gender differences in liver mRNA levels across the lifespan of mice; the mRNA levels for 40% of the XPGs were lower in aged male mice and 43% were lower in aged female mice.

  17. 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

  18. Dissimilar genome response to acute and chronic low-dose radiation in male and female mice

    International Nuclear Information System (INIS)

    Kovalchuk, Olga; Ponton, Andre; Filkowski, Jody; Kovalchuk, Igor

    2004-01-01

    The long-term genetic consequences of chronic exposure to low-dose irradiation constitutes a major concern to the general public and research community, especially as chronic radiation has recently been proven to be much more mutagenic and carcinogenic than previously thought. Here we report the results of the first ever comparison of the effects of acute and chronic whole body low-dose radiation exposure on global gene expression. We found a substantial difference between males and females in the expression of genes involved in signaling, growth control, transcription and other pathways upon acute and chronic radiation exposure. Specifically, we found sex differences in the expression of genes coding for G protein-coupled receptors and nuclear receptors. We also found different induction of PKCδ, PKCβ and PKCμ, members of PKC signaling pathway as well as in TGF and WNT signaling in males and females. Very pronounced difference, that was confirmed on the level of protein, was observed in the expression of WNT5A that plays an important role in carcinogenesis and muscle regeneration. WNT5A expression was significantly elevated only in chronically exposed females. We also provide the first evidence of the effect of ionizing radiation on the estrogen receptor in females. Repetitive irradiation of muscle tissue has been linked to development of rhabdomyosarcoma (RMS), which, enigmatically, occurs more frequently in males. Our data may be used to study possible mechanisms of RMS development upon chronic radiation exposure. They may provide some clues about the molecular background of the sex differences of RMS occurrence and may in the future lead to the discovery of new biomarkers for RMS predisposition in the irradiated tissue. Overall, differences in male and female responses to acute and chronic low-dose radiation obtained by this study were more drastic than we could have predicted. If confirmed in other experimental systems, these findings could potentially lead

  19. 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.)

  20. Long term rebaudioside A treatment does not alter circadian activity rhythms, adiposity, or insulin action in male mice.

    Science.gov (United States)

    Reynolds, Thomas H; Soriano, Rachelle A; Obadi, Obadi A; Murkland, Stanley; Possidente, Bernard

    2017-01-01

    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, insulin

  1. Canonical TSH Regulation of Cathepsin-Mediated Thyroglobulin Processing in the Thyroid Gland of Male Mice Requires Taar1 Expression

    Science.gov (United States)

    Qatato, Maria; Szumska, Joanna; Skripnik, Vladislav; Rijntjes, Eddy; Köhrle, Josef; Brix, Klaudia

    2018-01-01

    Trace amine-associated receptor 1 (Taar1) has been suggested as putative receptor of thyronamines. These are aminergic messengers with potential metabolic and neurological effects countering their contingent precursors, the thyroid hormones (THs). Recently, we found Taar1 to be localized at the primary cilia of rodent thyroid epithelial cells in vitro and in situ. Thus, Taar1 is present in a location of thyroid follicles where it might be involved in regulation of cathepsin-mediated proteolytic processing of thyroglobulin, and consequently TH synthesis. In this study, taar1 knock-out male mice (taar1-/-) were used to determine whether Taar1 function would entail differential alterations in thyroid states of young and adult animals. Analyses of blood serum revealed unaltered T4 and T3 concentrations and unaltered T3-over-T4 ratios upon Taar1 deficiency accompanied, however, by elevated TSH concentrations. Interestingly, TSH receptors, typically localized at the basolateral plasma membrane domain of wild type controls, were located at vesicular membranes in thyrocytes of taar1-/- mice. In addition, determination of epithelial extensions in taar1-/- thyroids showed prismatic cells, which might indicate activation states higher than in the wild type. While gross degradation of thyroglobulin was comparable to controls, deregulated thyroglobulin turnover in taar1-/- mice was indicated by luminal accumulation of covalently cross-linked thyroglobulin storage forms. These findings were in line with decreased proteolytic activities of thyroglobulin-solubilizing and -processing proteases, due to upregulated cystatins acting as their endogenous inhibitors in situ. In conclusion, Taar1-deficient mice are hyperthyrotropinemic in the absence of respective signs of primary hypothyroidism such as changes in body weight or TH concentrations in blood serum. Thyrocytes of taar1-/- mice are characterized by non-canonical TSH receptor localization in intracellular compartments, which is

  2. 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

  3. 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

  4. 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...

  5. Passive Response to Stress in Adolescent Female and Adult Male Mice after Intermittent Nicotine Exposure in Adolescence

    Science.gov (United States)

    Thanos, Panayotis; Delis, Foteini; Rosko, Lauren; Volkow, Nora D

    2013-01-01

    Smoking is frequently co-morbid with depression. Although it is recognized that depression increases the risk for smoking, it is unclear if early smoking exposure may increase the risk for depression. To test this possibility we assessed the effects of adolescent nicotine exposure on the Forced Swim Test (FST), which is used as a measure of passive coping, and depressive-like behavior in rodents, and on the open field test (OFT), which is used as a measure of locomotion and exploratory behavior. Male and female mice received daily saline or nicotine (0.3 or 0.6 mg/kg) injections from postnatal day (PD) 30 to PD 44. FST and OFT were performed either 1 or 30 days after the last injection (PD 45 and PD 74, respectively). In females, treatment with 0.3 mg/kg nicotine lead to increased FST immobility (64%) and decreased OFT locomotor activity (12%) one day following the last nicotine injection (PD 45); while no effects were observed in adulthood (PD 74). In contrast, on PD45, nicotine treatment did not change the male FST immobility but lead to lower OFT locomotor activity (0.6 mg/kg, 10%). In adulthood (PD 74), both nicotine doses lead to higher FST immobility (87%) in males while 0.6 mg/kg nicotine to lower OFT locomotor activity (13%). The results (i) identify females as more vulnerable to the immediate withdrawal that follows nicotine discontinuation in adolescence and (ii) suggest that adolescent nicotine exposure may enhance the risk for passive response towards unavoidable stress in adult males. PMID:24619539

  6. 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

  7. 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.

  8. Resveratrol attenuates intermittent hypoxia-induced macrophage migration to visceral white adipose tissue and insulin resistance in male mice.

    Science.gov (United States)

    Carreras, Alba; Zhang, Shelley X L; Almendros, Isaac; Wang, Yang; Peris, Eduard; Qiao, Zhuanhong; Gozal, David

    2015-02-01

    Chronic intermittent hypoxia during sleep (IH), as occurs in sleep apnea, promotes systemic insulin resistance. Resveratrol (Resv) has been reported to ameliorate high-fat diet-induced obesity, inflammation, and insulin resistance. To examine the effect of Resv on IH-induced metabolic dysfunction, male mice were subjected to IH or room air conditions for 8 weeks and treated with either Resv or vehicle (Veh). Fasting plasma levels of glucose, insulin, and leptin were obtained, homeostatic model assessment of insulin resistance index levels were calculated, and insulin sensitivity tests (phosphorylated AKT [also known as protein kinase B]/total AKT) were performed in 2 visceral white adipose tissue (VWAT) depots (epididymal [Epi] and mesenteric [Mes]) along with flow cytometry assessments for VWAT macrophages and phenotypes (M1 and M2). IH-Veh and IH-Resv mice showed initial reductions in food intake with later recovery, with resultant lower body weights after 8 weeks but with IH-Resv showing better increases in body weight vs IH-Veh. IH-Veh and IH-Resv mice exhibited lower fasting glucose levels, but only IH-Veh had increased homeostatic model assessment of insulin resistance index vs all 3 other groups. Leptin levels were preserved in IH-Veh but were significantly lower in IH-Resv. Reduced VWAT phosphorylated-AKT/AKT responses to insulin emerged in both Mes and Epi in IH-Veh but normalized in IH-Resv. Increases total macrophage counts and in M1 to M2 ratios occurred in IH-Veh Mes and Epi compared all other 3 groups. Thus, Resv ameliorates food intake and weight gain during IH exposures and markedly attenuates VWAT inflammation and insulin resistance, thereby providing a potentially useful adjunctive therapy for metabolic morbidity in the context of sleep apnea.

  9. A study of histological changes in the Diaphragm of male albino mice administered with aqueous extract of chamomileflowers Chamomillarecutita

    Directory of Open Access Journals (Sweden)

    SuraFouad A.Alsaffar

    2017-09-01

    Full Text Available The chamomile is one of the most important medicinal plants recommended for treatment of asthma and some respiratory system diseases. This research was designed to research the effects of aqueous extract of chamomillarecutita on histological structure of Diaphragm of albino mice. The study included 40 male albino mice Musmusculus, their age ranged from (5-7 weeks.The mices were divided randomly to 5 groups and oral administered with 1 ml every day for 10 days:- First Group G1: consider as control group and treated with normal saline,Second Group G2: was treated with aqueous extract of chamomile with concentration of 3 gm /100 ml D.W, Third Group G3: was treated with aqueous extract of chamomile with concentration of 5 gm /100 ml D.W.Fourth Group G4: was treated with aqueous extract of chamomile with concentration of 7 gm /100 ml D.W and the Fifth Group G5: was treated with aqueous extract of chamomile with concentration of 10 gm /100 ml D.W. Theresults of microscopic examination of diaphragm sections of groups G3,G4 and G5 showed degenerative effects on muscular tissue in way of breaking of myofibrils differences in their sizes and degeneration of most of nuclei of muscle fiber and their migration to inside the muscle fiber , it has been found that these treatments cause an alteration in myofibril in fibrotic myofibril. From this study we conclude that low concentration of aqueous extract of chamomile have low side effect on major respiratory muscles and could be used in beneficial treatment to contact diseases of respiratory system but without longer duration

  10. Detailed immunohistochemical characterization of temporal and spatial progression of Alzheimer's disease-related pathologies in male triple-transgenic mice

    Directory of Open Access Journals (Sweden)

    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-modifying therapeutics. The triple transgenic mouse model of AD (3xTg-AD harbors three AD-related genetic loci: human PS1M146V, human APPswe, and human tauP301L. These mice develop both amyloid plaques and neurofibrillary tangle-like pathology in a progressive and age-dependent manner, while these pathological hallmarks are predominantly restricted to the hippocampus, amygdala, and the cerebral cortex the main foci of AD neuropathology in humans. This model represents, at present, one of the most advanced preclinical tools available and is being employed ever increasingly in the study of mechanisms underlying AD, yet a detailed regional and temporal assessment of the subtleties of disease-related pathologies has not been reported. Methods and results In this study, we immunohistochemically documented the evolution of AD-related transgene expression, amyloid deposition, tau phosphorylation, astrogliosis, and microglial activation throughout the hippocampus, entorhinal cortex, primary motor cortex, and amygdala over a 26-month period in male 3xTg-AD mice. Intracellular amyloid-beta accumulation is detectable the earliest of AD-related pathologies, followed temporally by phospho-tau, extracellular amyloid-beta, and finally paired helical filament pathology. Pathology appears to be most severe in medial and caudal hippocampus. While astrocytic staining remains relatively constant at all ages and regions assessed, microglial activation appears to progressively increase temporally, especially within the hippocampal formation. Conclusion These data fulfill an unmet need in the ever-widening community of investigators studying 3xTg-AD mice and provide a foundation upon which to design future experiments that seek to

  11. Repeated brief isoflurane anesthesia during early postnatal development produces negligible changes on adult behavior in male mice.

    Science.gov (United States)

    Rosenholm, Marko; Paro, Emmi; Antila, Hanna; Võikar, Vootele; Rantamäki, Tomi

    2017-01-01

    Brain development is a complex process regulated by genetic programs and activity-dependent neuronal connectivity. Anesthetics profoundly alter neuronal excitability, and anesthesia during early brain development has been consistently associated with neuroapoptosis, altered synaptogenesis, and persistent behavioral abnormalities in experimental animals. However, the depth, and even more the duration and developmental time point(s) of exposure to anesthesia determine the neuropathological and long-term behavioral consequences of anesthetics. Here, we have investigated adulthood phenotypic changes induced by repeated but brief (30 min) isoflurane anesthesia delivered during two distinct developmental periods in male mice. A set of animals were subjected to anesthesia treatments at postnatal days 7, 8 and 9 (P7-9) when the animals are susceptible to anesthesia-induced neuroapoptosis and reduced synaptogenesis. To control the potential influence of (handling) stress, a separate group of animals underwent repeated maternal separations of similar durations. Another set of animals were exposed to the same treatments at postnatal days 15, 16 and 17 (P15-17), a developmental time period when anesthetics have been shown to increase synaptogenesis. Starting from postnatal week 9 the mouse phenotype was evaluated using a battery of behavioral tests that assess general locomotor activity (home cage activity, open field), learning and memory (water maze) and depression- (saccharin preference, forced swim test), anxiety- (light-dark box, stress-induced hyperthermia) and schizophrenia- (nesting, prepulse inhibition) related endophenotypes. Apart from mild impairment in spatial navigation memory, exposure to anesthesia treatments during P7-9 did not bring obvious behavioral alterations in adult animals. Importantly, maternal separation during the same developmental period produced a very similar phenotype during the water maze. Mice exposed to anesthesia during P15-17 showed mild

  12. Evaluation of pomegranate rind (Punica granatum hydroethanolic extract on blood parameters in male mice treated by Irinotecan Hcl

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    N Mirazi

    2015-05-01

    Full Text Available Background & aim: Irinotecan Hcl is the first order drug for some neoplasm treatment in patients. Irinotecan Hcl has side effects on blood such as anemia and leukopeny. The aim of this study was to evaluate erythropoetic effects of the pomegranate hydroethanolic extract were examined on mice which treated by irinotecan Hcl. Methods: In this experimental study, 49 male mice (25-30 g were divided in 7 groups (control, sham, treated by irinotecan Hcl (100 mg/kg, treated by pomegranate extract (100 and 400 mg/kg, i.p, daily for one week and treated by irinotecan Hcl plus pomegranate extract (100 and 400 mg/kg, i.p, daily for one week randomly. Anemia induced by administration of irinotecan in the experimental animal. At the end of experiment the blood samples were collected by cardiac puncture method and analized for RBC, WBC, Hb, Hct parameters. Data were analyzed using one-way ANOVA and Tukey’s test. Results: The results of this study showed that irinotecan has affected on blood factors and cause to significance decrese compared with control group (p<0.001. Also groups which treated with pomegranate extract (100 and 400 mg/kg significantly reduce the side effects of irinotecan and cause to increasing in blood factors (p<0.001. The number of WBC counts in the group which received Irinotecan (100 kg significantly decreased as compared with the control group (p<0.001. Irinotecan affected on blood Hb level and cause to significant decrease compared with control group. Groups which received pomegranate extract (100 and 400 kg had positive effect and significantly increased the blood Hb levels as compared to controls (p<0.001. Conclusion: These results showed that consumption of pomegranate rind extract in a dose-dependent manner has protective effect on blood parameters in mice which treated with Irinotecan Hcl.

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

    Science.gov (United States)

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

    2014-01-01

    The present study was designed to investigate the in vivo effects of monosodium glutamate (MSG) and aspartame (ASM) individually and in combination on the cognitive behavior and biochemical parameters like neurotransmitters and oxidative stress indices in the brain tissue of mice. Forty male Swiss albino mice were randomly divided into four groups of ten each and were exposed to MSG and ASM through drinking water for one month. Group I was the control and was given normal tap water. Groups II and III received MSG (8 mg/kg) and ASM (32 mg/kg) respectively dissolved in tap water. Group IV received MSG and ASM together in the same doses. After the exposure period, the animals were subjected to cognitive behavioral tests in a shuttle box and a water maze. Thereafter, the animals were sacrificed and the neurotransmitters and oxidative stress indices were estimated in their forebrain tissue. Both MSG and ASM individually as well as in combination had significant disruptive effects on the cognitive responses, memory retention and learning capabilities of the mice in the order (MSG+ASM)>ASM>MSG. Furthermore, while MSG and ASM individually were unable to alter the brain neurotransmitters and the oxidative stress indices, their combination dose (MSG+ASM) decreased significantly the levels of neurotransmitters (dopamine and serotonin) and it also caused oxidative stress by increasing the lipid peroxides measured in the form of thiobarbituric acid-reactive substances (TBARS) and decreasing the level of total glutathione (GSH). Further studies are required to evaluate the synergistic effects of MSG and ASM on the neurotransmitters and oxidative stress indices and their involvement in cognitive dysfunctions. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Exposure of neonatal mice to Sevoflurane may induce male germ cell apoptosis in testicular tissue after puberty

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    Maryam Nezhad Sistani

    2017-09-01

    Full Text Available Background: common use of sevoflurane in congenital defects during repeated surgeries may have detrimental effects on spermatogenesis after puberty. Objective: This study investigated sevoflurane effects on spermatogenesis process in male mature mice after exposure in prepubertal time. Materials and Methods: 24 neonatal NMRI male mice were randomly classified in three groups. Experimental 1 and 2 groups (exposure to 1 minimum alveolar concentration (MAC and 2 MAC sevoflurane, respectively in 2 lit/min oxygen (O2 for 7 days (30 min, daily and control. All groups were sacrificed after 2 months. Histological assessment, immunohistochemistry and apoptosis process was done. Bax and Bcl2 expression was evaluated in the testicular tissue by real time Poly Chain Reaction. Results: Our results showed that the integrity of testicular tissue was preserved in both experimental groups. Count of spermatogonial cells had significant decrease in group 2 compared to others. The rate of apoptosis in spermatogonial cells was 15±3% and 9±2% in the group 2 and 1, respectively. Also, Bax/Bcl2 ratio was 0.2615, 1.0070 and 9.3657 in control, experimental group 1 and 2, respectively. This result was significant (p≤0.002 between groups 2 with other groups. Conclusion: Continuous exposure of 2 MAC sevoflurane in 2 lit/min O2 simultaneous during prepubertal may create more testicular tissue damage in terms of cellular and molecular function compared to continuous exposure to lower level of sevoflurane by increase in ratio of Bax/Bcl2 and apoptosis in germ cells after puberty.

  15. Assessing Anticonvulsant Effect of Aqueous Extract of Datura Stramonium Seed on PTZ-Induced Seizures in the Male Mice

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    S Namvar Aghdash

    2015-11-01

    Full Text Available Background: Epilepsy is one of the most common neurological disorders that affect social, economic and biological aspects of the human life. Many epileptic patients have uncontrolled seizures and medication-related side effects despite adequate pharmacological treatment. The use of plant extracts is proposed as a therapeutic modality in order to treat different diseases. Datura plant has long been used in the traditional medicine in regard with some nervous disorders like epilepsy. Thus, this study aimed to provide a scientific basis investigating the effect of Datura aqueous extract on PTZ-induced seizures in the male mice. Methods: In this experimental study, 40 male mice were randomly allocated into 5 equal groups including: one control group, one sham group and three experimental groups. The experimental groups received 50, 100 and 150 mg/kg of aqueous extract of Datura Stramonium seed via gavage for 30 days, and the sham group received stilled water via gavage. Pentylenetetrazol (PTZ 35 mg/kg, i.p were injected into control, sham and experimental groups 30 minutes after gavage in order to induce the seizure. Then latency time of seizure onset, seizure duration and seizure phases were measured and recorded in the experimental, sham and control groups. The data analysis was carried out via one way ANOVA and Tukey post-hoc tests.  Moreover, difference less than 0.05 (P<0.05 was considered significant. Results: The study findings revealed that the aqueous extract of Datura Stramonium seed produced a significant effect on PTZ-induced seizure. In addition, Datura increases latency time of seizure onset (P˂0.01, inhibits progress of seizure stages (P˂0.05 and decreases seizure duration (P˂0.001. Conclusion: The results obtained from the present study indicated that extract of this plant has anticonvulsant effects on PTZ-induced seizure. As a result, it seems to be beneficial to the epilepsy treatment.

  16. Deletion of the Androgen Receptor in Adipose Tissue in Male Mice Elevates Retinol Binding Protein 4 and Reveals Independent Effects on Visceral Fat Mass and on Glucose Homeostasis

    Science.gov (United States)

    McInnes, Kerry J.; Smith, Lee B.; Hunger, Nicole I.; Saunders, Philippa T.K.; Andrew, Ruth; Walker, Brian R.

    2012-01-01

    Testosterone deficiency is epidemic in obese ageing males with type 2 diabetes, but the direction of causality remains unclear. Testosterone-deficient males and global androgen receptor (AR) knockout mice are insulin resistant with increased fat, but it is unclear whether AR signaling in adipose tissue mediates body fat redistribution and alters glucose homoeostasis. To investigate this, mice with selective knockdown of AR in adipocytes (fARKO) were generated. Male fARKO mice on normal diet had reduced perigonadal fat but were hyperinsulinemic and by age 12 months, were insulin deficient in the absence of obesity. On high-fat diet, fARKO mice had impaired compensatory insulin secretion and hyperglycemia, with increased susceptibility to visceral obesity. Adipokine screening in fARKO mice revealed a selective increase in plasma and intra-adipose retinol binding protein 4 (RBP4) that preceded obesity. AR activation in murine 3T3 adipocytes downregulated RBP4 mRNA. We conclude that AR signaling in adipocytes not only protects against high-fat diet–induced visceral obesity but also regulates insulin action and glucose homeostasis, independently of adiposity. Androgen deficiency in adipocytes in mice resembles human type 2 diabetes, with early insulin resistance and evolving insulin deficiency. PMID:22415878

  17. Pitavastatin suppresses diethylnitrosamine-induced liver preneoplasms in male C57BL/KsJ-db/db obese mice

    International Nuclear Information System (INIS)

    Shimizu, Masahito; Tanaka, Takuji; Moriwaki, Hisataka; Yasuda, Yoichi; Sakai, Hiroyasu; Kubota, Masaya; Terakura, Daishi; Baba, Atsushi; Ohno, Tomohiko; Kochi, Takahiro; Tsurumi, Hisashi

    2011-01-01

    Obesity and related metabolic abnormalities, including inflammation and lipid accumulation in the liver, play a role in liver carcinogenesis. Adipocytokine imbalances, such as decreased serum adiponectin levels, are also involved in obesity-related liver tumorigenesis. In the present study, we examined the effects of pitavastatin - a drug used for the treatment of hyperlipidemia - on the development of diethylnitrosamine (DEN)-induced liver preneoplastic lesions in C57BL/KsJ-db/db (db/db) obese mice. Male db/db mice were administered tap water containing 40 ppm DEN for 2 weeks and were subsequently fed a diet containing 1 ppm or 10 ppm pitavastatin for 14 weeks. At sacrifice, feeding with 10 ppm pitavastatin significantly inhibited the development of hepatic premalignant lesions, foci of cellular alteration, as compared to that in the untreated group by inducing apoptosis, but inhibiting cell proliferation. Pitavastatin improved liver steatosis and activated the AMPK-α protein in the liver. It also decreased free fatty acid and aminotransferases levels, while increasing adiponectin levels in the serum. The serum levels of tumor necrosis factor (TNF)-α and the expression of TNF-α and interleukin-6 mRNAs in the liver were decreased by pitavastatin treatment, suggesting attenuation of the chronic inflammation induced by excess fat deposition. Pitavastatin is effective in inhibiting the early phase of obesity-related liver tumorigenesis and, therefore, may be useful in the chemoprevention of liver cancer in obese individuals

  18. Dicer is required for haploid male germ cell differentiation in mice.

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    Hanna M Korhonen

    Full Text Available BACKGROUND: The RNase III endonuclease Dicer is an important regulator of gene expression that processes microRNAs (miRNAs and small interfering RNAs (siRNAs. The best-characterized function of miRNAs is gene repression at the post-transcriptional level through the pairing with mRNAs of protein-encoding genes. Small RNAs can also act at the transcriptional level by controlling the epigenetic status of chromatin. Dicer and other mediators of small RNA pathways are present in mouse male germ cells, and several miRNAs and endogenous siRNAs are expressed in the testis, suggesting that Dicer-dependent small RNAs are involved in the control of the precisely timed and highly organised process of spermatogenesis. PRINCIPAL FINDINGS: Being interested in the Dicer-mediated functions during spermatogenesis, we have analysed here a male germ cell-specific Dicer1 knockout mouse model, in which the deletion of Dicer1 takes place during early postnatal development in spermatogonia. We found that Dicer1 knockout testes were reduced in size and spermatogenesis within the seminiferous tubules was disrupted. Dicer1 knockout epididymides contained very low number of mature sperm with pronounced morphological abnormalities. Spermatogonial differentiation appeared unaffected. However, the number of haploid cells was decreased in knockout testes, and an increased number of apoptotic spermatocytes was observed. The most prominent defects were found during late haploid differentiation, and Dicer was demonstrated to be critical for the normal organization of chromatin and nuclear shaping of elongating spermatids. CONCLUSIONS/SIGNIFICANCE: We demonstrate that Dicer and Dicer-dependent small RNAs are imperative regulators of haploid spermatid differentiation and essential for male fertility.

  19. GABA type B receptor signaling in proopiomelanocortin neurons protects against obesity, insulin resistance, and hypothalamic inflammation in male mice on a high-fat diet.

    OpenAIRE

    Ito Yoshihiro; Banno Ryoichi; Shibata Miyuki; Adachi Koichi; Hagimoto Shigeru; Hagiwara Daisuke; Ozawa Yoshiharu; Goto Motomitsu; Suga Hidetaka; Sugimura Yoshihisa; Bettler Bernhard; Oiso Yutaka; Arima Hiroshi

    2013-01-01

    There is evidence suggesting that the GABA system in the arcuate nucleus, where orexigenic neuropeptide Y and agouti-related peptide as well as anorexigenic proopiomelanocortin (POMC) are expressed, plays an important role in energy balance. In this study, we generated POMC-specific GABAB receptor-deficient [knock-out (KO)] mice. Male KO mice on a high-fat diet (HFD) showed mild increases in body weight (BW) at the age of 9 weeks compared to wild-type (WT) mice, and the differences remained s...

  20. Dominant Lethal Pathologies in Male Mice Engineered to Contain an X-Linked DUX4 Transgene

    Directory of Open Access Journals (Sweden)

    Abhijit Dandapat

    2014-09-01

    Full Text Available Facioscapulohumeral muscular dystrophy (FSHD is an enigmatic disease associated with epigenetic alterations in the subtelomeric heterochromatin of the D4Z4 macrosatellite repeat. Each repeat unit encodes DUX4, a gene that is normally silent in most tissues. Besides muscular loss, most patients suffer retinal vascular telangiectasias. To generate an animal model, we introduced a doxycycline-inducible transgene encoding DUX4 and 3′ genomic DNA into a euchromatic region of the mouse X chromosome. Without induction, DUX4 RNA was expressed at low levels in many tissues and animals displayed a variety of unexpected dominant leaky phenotypes, including male-specific lethality. Remarkably, rare live-born males expressed DUX4 RNA in the retina and presented a retinal vascular telangiectasia. By using doxycycline to induce DUX4 expression in satellite cells, we observed impaired myogenesis in vitro and in vivo. This mouse model, which shows pathologies due to FSHD-related D4Z4 sequences, is likely to be useful for testing anti-DUX4 therapies in FSHD.

  1. Female-to-male sex reversal in mice caused by transgenic overexpression of Dmrt1.

    Science.gov (United States)

    Zhao, Liang; Svingen, Terje; Ng, Ee Ting; Koopman, Peter

    2015-03-15

    Genes related to Dmrt1, which encodes a DNA-binding DM domain transcription factor, act as triggers for primary sex determination in a broad range of metazoan species. However, this role is fulfilled in mammals by Sry, a newly evolved gene on the Y chromosome, such that Dmrt1 has become dispensable 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 gonads showed typical testicular size and vasculature. Key ovarian markers, including Wnt4 and Foxl2, were repressed. Sertoli cells expressing the hallmark testis-determining gene Sox9 were formed, although they did not assemble into normal testis cords. Other bipotential lineages differentiated 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 testis-determining trigger in mammals, even though this function is no longer normally required. Thus, Dmrt1 provides a common thread in the evolution of sex determination mechanisms in metazoans. © 2015. Published by The Company of Biologists Ltd.

  2. BA321, a novel carborane analog that binds to androgen and estrogen receptors, acts as a new selective androgen receptor modulator of bone in male mice

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Kenta [Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588 (Japan); Cooperative Major in Advanced Health Science, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588 (Japan); Hirata, Michiko [Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588 (Japan); Tominari, Tsukasa [Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588 (Japan); Institute of Global Innovation Research, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588 (Japan); Matsumoto, Chiho [Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588 (Japan); Endo, Yasuyuki [Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1, Komatsushima, Aoba-ku, Sendai, 981-8558 (Japan); Murphy, Gillian [Department of Oncology, University of Cambridge, Cancer Research UK, Cambridge Institute, Li Ka Shing Centre, Cambridge, CB2 0RE (United Kingdom); Nagase, Hideaki [Institute of Global Innovation Research, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588 (Japan); Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, OX3 7FY (United Kingdom); and others

    2016-09-09

    Carboranes are a class of carbon-containing polyhedral boron cluster compounds with globular geometry and hydrophobic surface that interact with hormone receptors such as estrogen receptor (ER) and androgen receptor (AR). We have synthesized BA321, a novel carborane compound, which binds to AR. We found here that it also binds to ERs, ERα and ERβ. In orchidectomized (ORX) mice, femoral bone mass was markedly reduced due to androgen deficiency and BA321 restored bone loss in the male, whilst the decreased weight of seminal vesicle in ORX mice was not recovered by administration of BA321. In female mice, BA321 acts as a pure estrogen agonist, and restored both the loss of bone mass and uterine atrophy due to estrogen deficiency in ovariectomized (OVX) mice. In bone tissues, the trabecular bone loss occurred in both ORX and OVX mice, and BA321 completely restored the trabecular bone loss in both sexes. Cortical bone loss occurred in ORX mice but not in OVX mice, and BA321 clearly restored cortical bone loss due to androgen deficiency in ORX mice. Therefore, BA321 is a novel selective androgen receptor modulator (SARM) that may offer a new therapy option for osteoporosis in the male. - Highlights: • A novel carborane compound BA321 binds to both AR and ERs, ERα and ERβ. • BA321 restores bone loss in orchidectomized mice without effects on sex organ. • BA321 acts as an estrogen agonist in bone and uterus in ovariectomized mice. • BA321 may be a new SARM to prevent the loss of musculoskeletal mass in elder men.

  3. Induction of specific-locus and dominant lethal mutations in male mice by n-propyl and isopropyl methanesulfonate.

    Science.gov (United States)

    Ehling, U H; Neuhäuser-Klaus, A

    1995-04-01

    n-Propyl methanesulfonate (nPMS) and isopropyl methanesulfonate (iPMS) induce dominant lethal and specific-locus mutations in male mice. The response of the various spermatogenic stages to the induction of mutations differ markedly for nPMS and iPMS. Independent of the effective dose range the induction of dominant lethal mutations by nPMS is limited to spermatozoa and spermatids. In contrast, the induction of dominant lethal mutations by nPMS is limited to spermatozoa and spermatids. In contrast, the induction of dominant lethal mutations by iPMS is dose dependent: a dose of 20 mg iPMS/kg body weight (bw) is active only in spermatocytes, while a dose of 100 mg/kg bw induces dominant lethal mutations in all postspermatogonial germ cell stages. One other striking difference in the biological effectiveness of both compounds is that iPMS induces a sterile phase in stem-cell spermatogonia, whereas nPMS treated males even at the highest dose are fully fertile.

  4. Melatonin and sesamol protects spleenocytes against 60Co γ-irradiation induced damages in male C57BL/6 mice

    International Nuclear Information System (INIS)

    Khan, Shahanshah; Rizvi, Moshahid; Kumar, Arun; Kalra, Nmita; Adhikari, Jawahar; Chaudhury, Nabo; Khan, Shahanshah

    2013-01-01

    Natural antioxidants have strong potential for development of radioprotectors. In earlier studies we have shown radioprotective efficacy of melatonin/sesamol (100 mg/kg body weight) in recovery of whole-body γ-irradiated (7.5 Gy) induced damages in gastrointestinal tract and germ cells. In the present study, we report detailed studies on spleenocytes. Therefore, the first objectives of these studies, to determine the antioxidant capacity of spleen induced by melatonin/sesamol. Second, to investigate the radioprotective effect of melatonin/sesamol in spleenocytes of whole-body γ-irradiated male C57BL/6 mice. Animals (8-9 week-old) were divided into six groups e.g., control, melatonin/sesamol (100 mg/kg body weight through intra-peritoneal), radiation (7.5 Gy, 1 Gy/minute, whole-body using 60 Co Tele-therapy unit), melatonin/sesamol+radiation (100 mg/kg body weight 30 minute prior to 7.5 Gy). Mice were sacrificed at 30 minutes and their spleen homogenates (10% w/v in PBS) were used for ABTS and DPPH assays.Those mice sacrificed on 4th, 7th, 15th, 21st and 30th day post-irradiation were used for immunological investigations (Annexin-V, CD4/CD8, Cell Cycle) by flow cytometry. Relative spleen mass was determined by dividing spleen mass(mg) with body mass(gm). ABTS and DPPH assays in spleen showed higher level of antioxidant capacity in melatonin/sesamol treated groups (p<0.009) from control group at 30 minute. Melatonin/sesamol+radiation treated groups significantly reduce apoptosis (p<0.026) and recover CD4+ and CD8+ T cells populations (p<0.022) as well as their ratio onwards 4th day post-irradiation in spleen as compared to radiation group. Melatonin/sesamol+radiation treated groups also showed recovery in radiation induced cell cycle perturbation and relative spleen mass from 7th day post-irradiation as compared to radiation group. Therefore, it is concluded that a single dose of 100 mg/kg body weight of melatonin/sesamol prior to 30 minute increase the capacity

  5. 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

    compared to controls. These data indicate that prenatal exposure to SRM2975 was not associated with endocrine disruptor activity in adulthood. There was no significant change in expression levels of aquaporins 7, 8 and 9 in testes tissue, measured as mRNA expression and protein levels......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...... by immunohistochemistry. In conclusion, prenatal exposure to SRM2975 was associated with reduced daily sperm production in adulthood, which was not possible to clearly associate with altered endocrine function or expression of aquaporins in the testes....

  6. Triclosan exacerbates the presence of 14C-bisphenol A in tissues of female and male mice

    International Nuclear Information System (INIS)

    Pollock, Tyler; Tang, Brandon; Catanzaro, Denys de

    2014-01-01

    Current human generations are commonly exposed to both triclosan (TCS), an antimicrobial agent, and bisphenol A (BPA), the monomer of polycarbonate plastics and epoxies. Both are readily absorbed into circulation and found distributed among diverse tissues. Potential interactions between TCS and BPA are largely unstudied. We investigated whether TCS exposure affects the distribution of ingested 14 C-BPA in select tissues. CF-1 mice were each subcutaneously injected with TCS then orally administered 50 μg/kg 14 C-BPA. Females received 0, 0.2, 0.6, 1, 2, or 18 mg TCS (equivalent respectively to 0, 6.3, 16.9, 30.1, 60.5, and 558.9 mg/kg). Males received 0, 0.2, 2, or 18 mg TCS (equivalent respectively to 0, 5.3, 53.4, and 415.0 mg/kg). Levels of radioactivity were measured through liquid scintillation counting in blood serum and brain, reproductive, and other tissues. Significantly elevated levels of radioactivity were observed following combined TCS and 14 C-BPA administration, with minimally effective TCS doses being tissue-dependent (Females: lungs, 0.6 mg; uterus, 1 mg; heart, muscle, ovaries, and serum, 18 mg. Males: serum, 0.2 mg; epididymides, 2 mg). Subsequently, we found that 2 or 6 mg TCS increased radioactivity in the ovaries and serum of females orally given only 5 μg/kg 14 C-BPA. These data indicate that TCS can interact with BPA in vivo, magnifying its presence in certain tissues and serum. The data are consistent with evidence that TCS utilizes enzymes that are critical for metabolism and excretion of BPA. Further research should investigate the mechanisms through which these two chemicals interact at environmentally-relevant doses. - Highlights: • We examined whether triclosan exposure affects the distribution of oral 14 C-BPA. • Radioactivity was elevated in select tissues of mice injected sc with triclosan. • In females, this effect was most pronounced in the uterus, ovaries, and lungs. • In males, this effect was most prominent in the

  7. Triclosan exacerbates the presence of {sup 14}C-bisphenol A in tissues of female and male mice

    Energy Technology Data Exchange (ETDEWEB)

    Pollock, Tyler; Tang, Brandon; Catanzaro, Denys de, E-mail: decatanz@mcmaster.ca

    2014-07-15

    Current human generations are commonly exposed to both triclosan (TCS), an antimicrobial agent, and bisphenol A (BPA), the monomer of polycarbonate plastics and epoxies. Both are readily absorbed into circulation and found distributed among diverse tissues. Potential interactions between TCS and BPA are largely unstudied. We investigated whether TCS exposure affects the distribution of ingested {sup 14}C-BPA in select tissues. CF-1 mice were each subcutaneously injected with TCS then orally administered 50 μg/kg {sup 14}C-BPA. Females received 0, 0.2, 0.6, 1, 2, or 18 mg TCS (equivalent respectively to 0, 6.3, 16.9, 30.1, 60.5, and 558.9 mg/kg). Males received 0, 0.2, 2, or 18 mg TCS (equivalent respectively to 0, 5.3, 53.4, and 415.0 mg/kg). Levels of radioactivity were measured through liquid scintillation counting in blood serum and brain, reproductive, and other tissues. Significantly elevated levels of radioactivity were observed following combined TCS and {sup 14}C-BPA administration, with minimally effective TCS doses being tissue-dependent (Females: lungs, 0.6 mg; uterus, 1 mg; heart, muscle, ovaries, and serum, 18 mg. Males: serum, 0.2 mg; epididymides, 2 mg). Subsequently, we found that 2 or 6 mg TCS increased radioactivity in the ovaries and serum of females orally given only 5 μg/kg {sup 14}C-BPA. These data indicate that TCS can interact with BPA in vivo, magnifying its presence in certain tissues and serum. The data are consistent with evidence that TCS utilizes enzymes that are critical for metabolism and excretion of BPA. Further research should investigate the mechanisms through which these two chemicals interact at environmentally-relevant doses. - Highlights: • We examined whether triclosan exposure affects the distribution of oral {sup 14}C-BPA. • Radioactivity was elevated in select tissues of mice injected sc with triclosan. • In females, this effect was most pronounced in the uterus, ovaries, and lungs. • In males, this effect was

  8. Embryonic effects transmitted by male mice irradiated with 512 MeV/u {sup 56}Fe nuclei

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-06-01

    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 {sup 56}Fe. We used the mouse embryo chimera assay to test 512 MeV/u {sup 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/{mu}m; fluence, 3.5 x 10{sup 4}-3.3 x 10{sup 5} nuclei/cm{sup 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 ratios{close_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 < 0.05 to P < 0.003). The 0.01- and 0.05-Gy dose groups also produced significant decreases in proliferation ratios for postirradiation week 1 (P < 0.05 to P < 0.01) and the 0.05-Gy dose group produced significant decreases in proliferation ratios for postirradiation week 6 (P < 0.05). Postirradiation weeks 1, 2 and 6 correspond to irradiation of epididymal sperm, testicular spermatids and spermatogonia, respectively. We calculate that only about 5% of sperm in the 0.1-Gy, 2.5% in the 0.05-Gy and 0.5% in the 0.01-Gy dose groups sustained direct hits from {sup 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.

  9. Below background levels of blood lead impact cytokine levels in male and female mice

    International Nuclear Information System (INIS)

    Iavicoli, I.; Carelli, G.; Stanek, E.J.; Castellino, N.; Calabrese, E.J.

    2006-01-01

    A number of studies have documented that Pb exerts immunotoxic effects on T lymphocytes. In studies designed to explore this general response over a broad dose range, female Swiss mice were administered six different diets containing Pb acetate 1 day after mating. During lactation, the mothers received the same feed given during pregnancy, and the same diets were administered to the offspring for 9 months after weaning. At the end of exposure, blood Pb level in the offspring was determined, and possible changes in two type 1 cytokines (IL-2, INF-γ) and one type 2 cytokine (IL-4) in the serum were measured. At higher dietary Pb levels (40 and 400 ppm), a significant increase in IL-4 production was associated with a profound decrease in INF-γ and IL-2 production. At the lowest Pb diet level (0.02 ppm), which resulted in a blood lead level of (0.8 μg/dL), which is below background (2-3 μg/dL) values in humans, increases in INF-γ and IL-2 production along with a significant decrease in IL-4 production were observed. The findings provide evidence of a reversal of lead-induced cytokine skewing depending on the blood lead concentration. As blood lead concentration increases, there is a notable skewing toward Th2, while the pattern is reversed favoring Th1 development at lower blood lead values. The present findings are also notable since they indicate the potential for dietary Pb to have significant biological effects below normal background concentrations

  10. Polyporus and Bupleuri radix effectively alter peripheral circadian clock phase acutely in male mice.

    Science.gov (United States)

    Motohashi, Hiroaki; Sukigara, Haruna; Tahara, Yu; Saito, Keisuke; Yamazaki, Mayu; Shiraishi, Takuya; Kikuchi, Yosuke; Haraguchi, Atsushi; Shibata, Shigenobu

    2017-07-01

    In mammals, daily physiological events are precisely regulated by an internal circadian clock system. An important function of this system is to readjust the phase of the clock daily. In Japan, traditional herb medicines, so-called crude drugs (Shoyaku), are widely used for many diseases, and some are reported to affect circadian clock impairment, suggesting that some of them might have an ability to modify clock gene expression rhythms. Therefore, from selected 40 crude drugs, finding candidates that control the circadian clock phases was the first purpose of this study. As there are several crude drugs used for liver- and/or kidney-related diseases, the second aim of the present study was to find some crude drugs affecting liver/kidney circadian clock in vivo. To assess phase changes in the daily circadian rhythm, bioluminescence from the core clock gene product Period 2 was continuously monitored in mouse embryonic fibroblasts in vitro and in some peripheral tissues (kidney, liver, and submandibular gland) of PERIOD2::LUCIFERASE knock-in mice in vivo. In our screening, Polyporus and Bupleuri radix were found to be good candidates to effectively manipulate the peripheral circadian clock phase acutely, with stimulation time-of-day dependency in vitro as well as in vivo. Interestingly, Polyporus and Bupleuri radix are traditional herb medicines use for treating edema and promoting diuresis, and for chronic hepatitis, respectively. These crude drugs may be therefore good modulators of the circadian peripheral clocks including liver and kidney, and circadian clock genes become new molecular targets for these crude drugs. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Circulating Insulin-Like Growth Factor I Regulates Its Receptor in the Brain of Male Mice.

    Science.gov (United States)

    Trueba-Saiz, A; Fernandez, A M; Nishijima, T; Mecha, M; Santi, A; Munive, V; Aleman, I Torres

    2017-02-01

    The role of IGF-1 and its receptor (IGF-1R) in brain pathology is still unclear. Thus, either reduction of IGF-IR or treatment with IGF-1, two apparently opposite actions, has proven beneficial in brain diseases such as Alzheimer's dementia. A possible explanation of this discrepancy is that IGF-1 down-regulates brain IGF-1R levels, as previously seen in a mouse Alzheimer's dementia model. We now explored whether under normal conditions IGF-1 modulates its receptor. We first observed that in vitro, IGF-1 reduced IGF-1R mRNA levels in all types of brain cells including neurons, astrocytes, microglia, endothelial cells, and oligodendrocytes. IGF-1 also inhibited its own expression in neurons and brain endothelium. Next, we analyzed the in vivo actions of IGF-1. Because serum IGF-1 can enter the brain, we injected mice with IGF-1 ip. As soon as 1 hour after the injection, decreased hippocampal IGF-1 levels were observed, followed by increased IGF-1 and IGF-1R mRNAs 6 hours later. Because environmental enrichment (EE) stimulates the entrance of serum IGF-1 into the brain, we analyzed whether a physiological entrance of IGF-1 also produced changes in brain IGF-1R. Stimulation of IGF-1R by EE triggered a gradual decrease in hippocampal IGF-1 levels. After 6 hours of EE exposure, IGF-1 levels reached a significant decrease in parallel with increased IGF-1R expression. After longer times, IGF-1R mRNA levels returned to baseline. Thus, under nonpathological conditions, IGF-1 regulates brain IGF-1R. Because baseline IGF-1R levels are rapidly restored, a tight control of brain IGF-1R expression seems to operate under physiological conditions. Copyright © 2017 by the Endocrine Society.

  12. HLDF-6 peptide affects behavioral reactions and organism functions dependent on androgen hormones in normal and castrated male mice.

    Science.gov (United States)

    Rzhevsky, D I; Zhokhov, S S; Babichenko, I I; Goleva, A V; Goncharenko, E N; Baizhumanov, A A; Murashev, A N; Lipkin, V M; Kostanyan, I A

    2005-04-15

    The hexapeptide Thr-Gly-Glu-Asn-His-Arg (HLDF-6), which was first identified as an active fragment of the human leukemia differentiation factor (HLDF) molecule, displays differentiation-inducing, neuroprotective and anti-drug abuse activities. Most of its in vivo effects were revealed only on male animals. We have studied HLDF-6 effects on a variety of organism functions and behavioral reactions, which are known to be dependent on androgen steroid hormones, both on castrated and normal (sham-operated) animals. Male NMRI mice were castrated or sham-operated at the age of 55 days (after puberty). After that, HLDF-6 peptide was injected daily during 3 weeks, followed by behavioral, morphological and biochemical testing. HLDF-6 increased testosterone level (1.5- to 2-fold) both in sham-operated and castrated animals. Sexual activity and pain sensitivity, which are strongly reduced in castrates, were completely or partially recovered by HLDF-6. At the same time, the peptide caused some effects similar to castration in sham-operated animals: aggression and locomotor activity were decreased; oral grooming was prolonged. Morphological studies of accessory sex glands showed that HLDF-6 partially normalizes the morphology and functional activity of seminal vesicles in castrates, but it does not prevent castration-induced apoptosis of prostate epithelial cells. Based on these observations, we can assume that HLDF-6 peptide displays at least two effects on androgen hormones metabolism in males: it stimulates testosterone biosynthesis by both testes and adrenals and simultaneously inhibits its conversion to dihydrotestosterone (DHT), most probably by diminution of 5alpha-reductase isoform 1 mRNA expression.

  13. Condom-Associated Erection Problems: A Study of High-Risk Young Black Males Residing in the Southern United States.

    Science.gov (United States)

    Graham, Cynthia A; Crosby, Richard; Sanders, Stephanie; Milhausen, Robin; Yarber, William L

    2016-03-01

    Previous research indicates that young men may experience condom-associated erection loss and that these problems may lead to inconsistent or incomplete condom use. The primary aim of this study was to assess, using a retrospective recall period of 2 months, correlates of condom-associated erection problems among young Black men attending sexually transmitted infection (STI) clinics. Data were collected in clinics treating patients with STIs in three southern U.S. cities. Males 15 to 23 years of age who identified as Black/African American and reported recent (past 2 months) condom use were eligible. A total of 494 men participated. Nineteen percent reported that condom-associated erection problems during condom application occurred at least once, and 17.8% indicated erection difficulties occurred during sexual intercourse at least once in the past 2 months. Multivariate analyses identified that condom-associated erection problems were associated with reports of sex with more than one partner during the recall period, reported problems with condom fit and feel, lower motivation to use condoms, and attempts at condom application before having a full erection. Findings suggest that clinic interventions should address possible condom-associated erection problems among young Black men who are at risk of STIs. Encouraging men who may be vulnerable to erection loss when condoms are used to allow sufficient time for sexual arousal to build may be an effective strategy. © The Author(s) 2014.

  14. Bone structure and function in male C57BL/6 mice: Effects of a high-fat Western-style diet with or without trace minerals.

    Science.gov (United States)

    Aslam, Muhammad Nadeem; Jepsen, Karl J; Khoury, Basma; Graf, Kristin H; Varani, James

    2016-12-01

    Osteoporosis occurs in both women and men, but most of what we know about the condition comes from studies in females. The present study examined bone structure and function over an 18-month period in male C57BL/6 mice maintained on either a rodent chow diet (AIN76A) or a high-fat, Western-style diet (HFWD). Effects of mineral supplementation were assessed in both diets. Trabecular and cortical bone structure in femora and vertebrae were assessed by micro-CT analysis. Following this, bone stiffness and strength measurements were made. Finally, bone levels of several cationic trace elements were quantified, and serum biomarkers of bone metabolism evaluated. Bone loss occurred over time in both diets but was more rapid and extensive in mice on the HFWD. Dietary mineral supplementation reduced bone loss in both diets and increased bone stiffness in the femora and bone stiffness and strength in the vertebrae. Bone content of strontium was increased in response to mineral supplementation in both diets. Bone loss was more severe in mice on the HFWD and mineral supplementation mitigated the effects of the HFWD. In comparison to previous findings with female C57BL/6 mice, the present studies indicate that males are more sensitive to diet and benefited from a healthy diet (AIN76A), while females lost as much bone on the healthy diet as on the HFWD. Male mice benefited from mineral supplementation, just as females did in the previous study.

  15. Lung CD4 Tissue-Resident Memory T Cells Mediate Adaptive Immunity Induced by Previous Infection of Mice withBordetella pertussis.

    Science.gov (United States)

    Wilk, Mieszko M; Misiak, Alicja; McManus, Róisín M; Allen, Aideen C; Lynch, Marina A; Mills, Kingston H G

    2017-07-01

    Th1 and Th17 cells have an established role in protective immunity to Bordetella pertussis , but this evidence is based largely on peripheral T cells. There is emerging evidence that local tissue-resident memory T (T RM ) cells that accumulate in tissue following mucosal infection may be crucial for long-term immunity. In this study, we examined the role of respiratory CD4 T RM cells in immunity to B. pertussis Natural immunity to B. pertussis induced by infection is considered long lasting and effective at preventing reinfection. Consistent with this, we found that convalescent mice rapidly cleared the bacteria after reinfection. Furthermore, CD4 T cells with a T RM cell phenotype (CD44 + CD62L - CD69 + or CD44 + CD62L - CD69 + CD103 + ) accumulated in the lungs of mice during infection with B. pertussis and significantly expanded through local proliferation following reinfection. These CD4 T RM cells were B. pertussis specific and secreted IL-17 or IL-17 and IFN-γ. Treatment of mice with FTY720, which prevented migration of T and B cells from lymph nodes to the circulation, significantly exacerbated B. pertussis infection. This was associated with significantly reduced infiltration of central memory T cells and B cells into the lungs. However, the local expansion of T RM cells and the associated rapid clearance of the secondary infection were not affected by treatment with FTY720 before rechallenge. Moreover, adoptive transfer of lung CD4 T RM cells conferred protection in naive mice. Our findings reveal that Ag-specific CD4 T RM cells play a critical role in adaptive immunity against reinfection and memory induced by natural infection with B. pertussis . Copyright © 2017 by The American Association of Immunologists, Inc.

  16. Ghrelin agonists impact on Fos protein expression in brain areas related to food intake regulation in male C57BL/6 mice

    Czech Academy of Sciences Publication Activity Database

    Pirnik, Z.; Bundziková, J.; Holubová, Martina; Pýchová, Miroslava; Fehrentz, J. A.; Martinez, J.; Železná, Blanka; Maletínská, Lenka; Kiss, A.

    2011-01-01

    Roč. 59, č. 6 (2011), s. 889-895 ISSN 0197-0186 R&D Projects: GA ČR GA303/09/0744 Institutional research plan: CEZ:AV0Z40550506 Keywords : ghrelin agonists * Fos immunohistochemistry * male C57BL/6 mice Subject RIV: CC - Organic Chemistry Impact factor: 2.857, year: 2011

  17. Helicobacter pylori Infection Induces Anemia, Depletes Serum Iron Storage, and Alters Local Iron-Related and Adult Brain Gene Expression in Male INS-GAS Mice.

    Directory of Open Access Journals (Sweden)

    Monika Burns

    Full Text Available Iron deficiency anemia (IDA affects > 500 million people worldwide, and is linked to impaired cognitive development and function in children. Helicobacter pylori, a class 1 carcinogen, infects about half of the world's population, thus creating a high likelihood of overlapping risk. This study determined the effect of H. pylori infection on iron homeostasis in INS-GAS mice. Two replicates of INS-GAS/FVB male mice (n = 9-12/group were dosed with H. pylori (Hp strain SS1 or sham dosed at 6-9 weeks of age, and were necropsied at 27-29 weeks of age. Hematologic and serum iron parameters were evaluated, as was gene expression in gastric and brain tissues. Serum ferritin was lower in Hp SS1-infected mice than uninfected mice (p < 0.0001. Infected mice had a lower red blood cell count (p<0.0001, hematocrit (p < 0.001, and hemoglobin concentration (p <0.0001 than uninfected mice. Relative expression of gastric hepcidin antimicrobial peptide (Hamp was downregulated in mice infected with Hp SS1 compared to sham-dosed controls (p<0.001. Expression of bone morphogenic protein 4 (Bmp4, a growth factor upstream of hepcidin, was downregulated in gastric tissue of Hp SS1-infected mice (p<0.001. Hp SS1-infected mice had downregulated brain expression of tyrosine hydroxylase (Th (p = 0.02. Expression of iron-responsive genes involved in myelination (myelin basic protein (Mbp and proteolipid protein 2 (Plp2 was downregulated in infected mice (p = 0.001 and p = 0.02. Expression of synaptic plasticity markers (brain derived neurotrophic factor 3 (Bdnf3, Psd95 (a membrane associated guanylate kinase, and insulin-like growth factor 1 (Igf1 was also downregulated in Hp SS1-infected mice (p = 0.09, p = 0.04, p = 0.02 respectively. Infection of male INS-GAS mice with Hp SS1, without concurrent dietary iron deficiency, depleted serum ferritin, deregulated gastric and hepatic expression of iron regulatory genes, and altered iron-dependent neural processes. The use of Hp SS

  18. Weight Loss After RYGB Is Independent of and Complementary to Serotonin 2C Receptor Signaling in Male Mice.

    Science.gov (United States)

    Carmody, Jill S; Ahmad, Nadia N; Machineni, Sriram; Lajoie, Scott; Kaplan, Lee M

    2015-09-01

    Roux-en-Y gastric bypass (RYGB) typically leads to substantial, long-term weight loss (WL) and diabetes remission, although there is a wide variation in response to RYGB among individual patients. Defining the pathways through which RYGB works should aid in the development of less invasive anti-obesity treatments, whereas identifying weight-regulatory pathways unengaged by RYGB could facilitate the development of therapies that complement the beneficial effects of surgery. Activation of serotonin 2C receptors (5-HT2CR) by serotonergic drugs causes WL in humans and animal models. 5-HT2CR are located on neurons that activate the melanocortin-4 receptors, which are essential for WL after RYGB. We therefore sought to determine whether 5-HT2CR signaling is also essential for metabolic effects of RYGB or whether it is a potentially complementary pathway, the activation of which could extend the benefits of RYGB. Diet-induced obese male mice deficient for the 5-HT2CR and their wild-type littermates underwent RYGB or sham operation. Both groups lost similar amounts of weight after RYGB, demonstrating that the improved metabolic phenotype after RYGB is 5-HT2CR independent. Consistent with this hypothesis, wild-type RYGB-treated mice lost additional weight after the administration of the serotonergic drugs fenfluramine and meta-chlorophenylpiperazine but not the nonserotonergic agent topiramate. The fact that RYGB does not depend on 5-HT2CR signaling suggests that there are important WL mechanisms not fully engaged by surgery that could potentially be harnessed for medical treatment. These results suggest a rational basis for designing medical-surgical combination therapies to optimize clinical outcomes by exploiting complementary physiological mechanisms of action.

  19. Effects of bingeing on fat during adolescence on the reinforcing effects of cocaine in adult male mice.

    Science.gov (United States)

    Blanco-Gandía, M Carmen; Cantacorps, Lídia; Aracil-Fernández, Auxiliadora; Montagud-Romero, Sandra; Aguilar, María A; Manzanares, Jorge; Valverde, Olga; Miñarro, José; Rodríguez-Arias, Marta

    2017-02-01

    Binge eating is a specific form of overeating characterized by intermittent excessive eating. In addition to altering the neurobiological reward system, several studies have highlighted that consumption of palatable food increases vulnerability to drug use. The aim of the present study was to evaluate the effects of a high-fat diet consumed in a binge pattern during adolescence on the reinforcing effects of cocaine. After 40 days of binge-eating for 2 h, three days a week (PND 29-69), the reinforcing effects of cocaine on conditioning place preference and intravenous self-administration paradigm were evaluated in adolescent male mice. Circulating leptin and ghrelin levels and the effects of bingeing on fat on CB1 mu opioid receptor (MOr) and ghrelin receptor (GHSR) gene expression in the Nucleus Accumbens (NAcc) and Ventral Tegmental Area (VTA) were also assessed. Our results showed a significant escalation in the consumption of a high-fat diet between the first and last week. High-fat binge (HFB) animals were more sensitive to the reinforcing effects of a subthreshold dose of cocaine in the paradigms assayed, and animals under fat withdrawal were more vulnerable to the reinstatement of conditioned place preference. HFB mice also showed enhanced cocaine self-administration. After fat withdrawal, exposure to a new fat binge reinstated cocaine seeking. Although HFB did not modify leptin levels, a decrease in plasmatic ghrelin was observed. Moreover, this pattern of fatty diet resulted in a reduction of MOr and CB1 gene expression in the NAcc and an increase in GHSR expression in the VTA. We propose that bingeing on fat during adolescence induces long-lasting changes in the brain through the sensitization of brain reward circuits, which predisposes individuals to seek cocaine during adulthood. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Switching of dominant retrotransposon silencing strategies from posttranscriptional to transcriptional mechanisms during male germ-cell development in mice.

    Directory of Open Access Journals (Sweden)

    Kota Inoue

    2017-07-01

    Full Text Available Mammalian genomes harbor millions of retrotransposon copies, some of which are transpositionally active. In mouse prospermatogonia, PIWI-interacting small RNAs (piRNAs combat retrotransposon activity to maintain the genomic integrity. The piRNA system destroys retrotransposon-derived RNAs and guides de novo DNA methylation at some retrotransposon promoters. However, it remains unclear whether DNA methylation contributes to retrotransposon silencing in prospermatogonia. We have performed comprehensive studies of DNA methylation and polyA(+ RNAs (transcriptome in developing male germ cells from Pld6/Mitopld and Dnmt3l knockout mice, which are defective in piRNA biogenesis and de novo DNA methylation, respectively. The Dnmt3l mutation greatly reduced DNA methylation levels at most retrotransposons, but its impact on their RNA abundance was limited in prospermatogonia. In Pld6 mutant germ cells, although only a few retrotransposons exhibited reduced DNA methylation, many showed increased expression at the RNA level. More detailed analysis of RNA sequencing, nascent RNA quantification, profiling of cleaved RNA ends, and the results obtained from double knockout mice suggest that PLD6 works mainly at the posttranscriptional level. The increase in retrotransposon expression was larger in Pld6 mutants than it was in Dnmt3l mutants, suggesting that RNA degradation by the piRNA system plays a more important role than does DNA methylation in prospermatogonia. However, DNA methylation had a long-term effect: hypomethylation caused by the Pld6 or Dnmt3l mutation resulted in increased retrotransposon expression in meiotic spermatocytes. Thus, posttranscriptional silencing plays an important role in the early stage of germ cell development, then transcriptional silencing becomes important in later stages. In addition, intergenic and intronic retrotransposon sequences, in particular those containing the antisense L1 promoters, drove ectopic expression of nearby

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

    Science.gov (United States)

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

    2015-01-01

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

  2. A comparison of the effects of male pheromone priming and optogenetic inhibition of accessory olfactory bulb forebrain inputs on the sexual behavior of estrous female mice

    Science.gov (United States)

    McCarthy, E.A.; Kunkhyen, T.; Korzan, W.J.; Naik, A.; Maqsudlu, A.; Cherry, J.A.

    2017-01-01

    Previous research has shown that repeated testing with a stimulus male is required for ovariectomized, hormone-primed female mice to become sexually receptive (show maximal lordosis quotients; LQs) and that drug-induced, epigenetic enhancement of estradiol receptor function accelerated the improvement in LQs otherwise shown by estrous females with repeated testing. We asked whether pre-exposure to male pheromones (‘pheromone priming’) would also accelerate the improvement in LQs with repeated tests and whether optogenetic inhibition of accessory olfactory bulb (AOB) projection neurons could inhibit lordosis in sexually experienced estrous female mice. In Experiment 1, repeated priming with soiled male bedding failed to accelerate the progressive improvement in LQs shown by estrous female mice across 5 tests, although the duration of each lordosis response and females’ investigation of male body parts during the first test was augmented by such priming. In Experiment 2, acute optogenetic inhibition of AOB inputs to the forebrain during freely moving behavioral tests significantly reduced LQs, suggesting that continued AOB signaling to the forebrain during mating is required for maximal lordotic responsiveness even in sexually experienced females. Our results also suggest that pheromonal stimulation, by itself, cannot substitute for the full complement of sensory stimulation received by estrous females from mounting males that normally leads to the progressive improvement in their LQs with repeated testing. PMID:28065711

  3. Effects of loaded voluntary wheel exercise on performance and muscle hypertrophy in young and old male C57Bl/6J mice.

    Science.gov (United States)

    Soffe, Z; Radley-Crabb, H G; McMahon, C; Grounds, M D; Shavlakadze, T

    2016-02-01

    This study compared the capacity of young and old male C57Bl/6J mice to exercise with increasing resistance over 10 weeks, and its impact on muscle mass. Young mice (aged 15-25 weeks) were subjected to low (LR) and high (HR) resistance exercise, whereas only LR was used for old mice (107-117 weeks). Weekly patterns of voluntary wheel activity, food consumption and body weights were measured. Running patterns changed over time and with age, with two peaks of activity detected for young, but only one for old mice: speed and distance run was also less for old mice. The mass for six limb muscles was measured at the end of the experiment. The most pronounced increase in mass in response to exercise was for the soleus in young and old mice, and also quadriceps and gastrocnemius in young mice. Soleus and quadriceps muscles were analyzed histologically for myofiber number and size. A striking feature was the many small myofibers in response to exercise in young (but not old) soleus, whereas these were not present after exercise in young or old quadriceps. Overall, there was a striking difference in response to exercise between muscles and this was influenced by age. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Radiation-induced tumours in C57BLf/6JNrs[SPF] and C3Hf/HeMsNrs[SPF] strain male mice

    International Nuclear Information System (INIS)

    Kasuga, T.; Sado, T.; Noda, Y.; Terasima, T.; Kitagawa, T.

    1978-01-01

    Mice at the age of 12 weeks were irradiated with single graded doses of gamma rays delivered from caesium-137. The mice were kept in specific pathogen-free (SPF) conditions until death. In this communication, autopsy data from 385 males of C57BLf/6JNrs[SPF] and 278 males of C3Hf/HeMsNrs[SPF] mice are summarized. The median survival time of unirradiated control mice was 29 months for the C57BL and 25 months for the C3H mice respectively. The incidence of tumour-bearing mice in the control groups was 71.3% for the C57BL and 90.9% for the C3H mice. Major, spontaneous tumour types were reticular cell sarcoma (51.3%), liver tumour (8.8%), lung tumour (11.3%) for the C57BL, and liver tumour (84.6%), lung tumour (8.2%) and non-thymic lymphoma (3.6%) for the C3H mice. Miscellaneous tumours with a low incidence were vascular, bone, muscle, adrenal tumours and others. In the C57BL mice the incidence of reticular cell sarcoma declined gradually with increasing doses of radiation exposure from 0 to 800 R. Histological examination revealed that reticular cell sarcomas normally found in unirradiated C57BL mice originated from abdominal lymphatic tissues whereas lymphoblastic lymphoma in irradiated mice arose from thymus and/or submandibular lymph nodes. It is noteworthy that the peak incidence of thymoma (33.3%) was found after whole-body exposure up to 700 R. Myeloid leukaemia was also included although to a slight extent. The age at death with lymphoreticular tumours and myeloid leukaemias was shortened in a dose-dependent manner. In the C3H mice tumour induction by radiation was generally not remarkable. The incidence of myeloid leukaemia attained a peak (15%) at 200 R. A lowering of the age at death was found to be proportional to the dose delivered

  5. The effects of Vitex agnus castus extract and its interaction with dopaminergic system on LH and testosterone in male mice.

    Science.gov (United States)

    Nasri, Sima; Oryan, Shahrbano; Rohani, Ali Haeri; Amin, Gholam Reza

    2007-07-15

    The purpose of this study was to evaluate the probable effects of Vitex agnus castus (Vac.) on the male reproductive physiology. It is a well known fact that LH secretion from the anterior pituitary of mammals is controlled by many neurotransmiters such as dopamine. In this experiment, we have studied the effect of Vac. extract on the LH and testosterone hormones and its interaction with the dopaminergic system on male mice. In order to evaluate these effects, we used the hydroalcoholic Vac. extract (for extraction we used percolation technique) injection with the following doses: 65, 165, 265, 365 and 465 mg kg-', bromocriptine as a dopamine receptor agonist (5, 10, 20 mg kg(-1)) and haloperidol as a dopamine receptor antagonist (1, 1.5, 2, 2.5, 3 mg kg(-1)). To study the interaction between Vac. extract and dopaminergic system, we injected the optimum doses of Vac. with bromocriptine or haloperidol at the same time. Intraperitoneal injections were applied in all experiments, once a day for 30 days. The control group remained intact and the sham group received vehicle. After the last injection, we collected the animal blood serums for hormonal assays. LH and testosterone were measured by Radio Immuno Assay (RIA). LH and testosterone, showed significant decrease in bromocriptine group and haloperidol increased these hormones. Vac. extract decreased significantly the LH and testosterone levels. The coadministration of Vac. extract and bromocriptine decreased LH and testosterone. Coadministration of Vac. extract and haloperidol decreased LH and testosterone levels. These results suggest: dopamine regulates the gonadotroph-leydig cells axis. It appears that Vac. exertes effects through dopaminergic system and other pathways. The findings of this study show we can use Vac. extract for pathological cases of increasing LH and testosterone.

  6. Effects of duration of stay in temperate area on thermoregulatory responses to passive heat exposure in tropical south-east Asian males residing in Japan

    Directory of Open Access Journals (Sweden)

    Wijayanto Titis

    2012-09-01

    Full Text Available Abstract Background In this study, we investigated the effects of duration of stay in a temperate area on the thermoregulatory responses to passive heat exposure of residents from tropical areas, particularly to clarify whether they would lose their heat tolerance during passive heat exposure through residence in a temperate country, Japan. Methods We enrolled 12 males (mean ± SE age 25.7 ± 1.3 years from south-east Asian countries who had resided in Japan for a mean of 24.5 ± 5.04 months, and 12 Japanese males (age 24.1 ± 0.9 years. Passive heat exposure was induced through leg immersion in hot water (42°C for 60 minutes under conditions of 28°C air temperature and 50% relative humidity. Results Compared with the Japanese group, the tropical group displayed a higher pre-exposure rectal temperature (P P = 0.03. Additionally, the tropical group showed a tendency towards a lower total sweat rate (P = 0.06 and lower local sweat rate on the forehead (P = 0.07. The tropical group also had a significantly longer sweating onset time on the upper back (P = 0.04 compared with the Japanese groups. The tropical group who stayed in Japan for > 23 months sweated earlier on the forehead and upper back than those who stayed in Japan P P = 0.03 for the forehead and upper back, respectively. There was a positive correlation between duration of stay in Japan and total sweat rate (r = 0.58, P r = −0.73, P = 0.01 and on the upper back (r = −0.66, P = 0.02. Other physiological indices measured in this study did not show any difference between the subjects in the tropical group who had lived in Japan for a shorter time and those who had lived there for a longer time. Conclusions We conclude that the nature of heat acclimatization of the sweating responses to passive heat exposure that are acquired from long-term heat acclimatization is decayed by a stay in a temperate area, as shown

  7. Comparison between C-FOS Expression in Male and Female Mice During Morphine Withdrawal in the Presence and Absence of Acute Administration of Matricaria Recutita

    Directory of Open Access Journals (Sweden)

    Kesmati Mahnaz

    2009-06-01

    Full Text Available Background: There are some evidences that indicate there are sexual differences in drug abuse and response to synthetic and herbal drugs. It has been shown that the expression of C-FOS increases in many areas of brain during morphine withdrawal. Concerning the sedative effect of Matricaria recutita extract, the aim of this study was to compare expression of C-FOS transcription factor during morphine withdrawal with and without acute administration of Matricaria recutita on male and female adult mice.Materials and Methods: This study was done at Shahid Chamran University of Ahvaz in 2007 on NMRI mice. Male and female mice were assigned into 8 groups (morphine + saline; morphine + naloxone; morphine + Matricaria recutita + naloxone; and morphine + saline + naloxone. To develop morphine dependency, increasing doses of morphine (20, 40, 80 mg/kg injected subcutaneously for 4 days. Mice received a final morphine injection (40 mg/kg 3hours prior to naloxone (5 mg/kg on the day of testing (day 4. Matricaria recutita extract whit a dose of 30 mg/kg was administered intraperitoneally 5 minutes before naloxone injection. In cellular study, 90minute after naloxone injection, mice were decapitated and their brains were separated, then mRNA was extracted from brain tissue. Using DIG-labeled DNA probe of C-FOS, beta-actin and dot blot technique, expression of C-FOS was analyzed by Zero Dscan software. Statistical evaluation of data was performed using student t-test and ANOVA with one factor followed by Duncan test in SPSS software. P values less than 0.05 were considered significant. Results: The rate of expression of C-FOS increased in male mice but decreased significantly in female mice after naloxone-precipitated abstinence P<0.01(. Matricaria recutita attenuated the rate of expression of C-FOS in male mice but it showed synergistic effect on it in female mice P<0.05(.Conclusion: It seems that the cellular processes involving morphine dependency and

  8. Chickpea supplementation prior to colitis onset reduces inflammation in dextran sodium sulfate-treated C57Bl/6 male mice.

    Science.gov (United States)

    Monk, Jennifer M; Wu, Wenqing; McGillis, Laurel H; Wellings, Hannah R; Hutchinson, Amber L; Liddle, Danyelle M; Graf, Daniela; Robinson, Lindsay E; Power, Krista A

    2018-03-09

    The potential for a chickpea supplemented diet (rich in fermentable non-digestible carbohydrates and phenolic compounds) to modify the colonic microenvironment and attenuate the severity of acute colonic inflammation was investigated. C57Bl/6 male mice were fed a control basal diet (BD) or BD supplemented with 20% cooked chickpea flour for 3 weeks prior to acute colitis onset induced by 7-day exposure to dextran sodium sulfate (DSS, 2% w/v in drinking water) and colon and serum levels of inflammatory mediators were assessed. Despite an equal degree of DSS-induced epithelial barrier histological damage and clinical symptoms between dietary groups, biomarkers of the ensuing inflammatory response were attenuated by CK pre-feeding including reduced colon tissue activation of NFκB and inflammatory cytokine production (TNFα and IL-18). Additionally, colon protein expression of anti-inflammatory (IL-10) and epithelial repair (IL-22 and IL-27) cytokines were increased by CK pre-feeding. Furthermore, during acute colitis CK pre-feeding increased markers of enhanced colonic function including mRNA expression of Relmβ and IgA. Collectively, CK pre-feeding modulated the baseline function of the colonic microenvironment, whereby upon induction of acute colitis, the severity of the inflammatory response was attenuated.

  9. Preventing Electromagnetic Pulse Irradiation Damage on Testis Using Selenium-rich Cordyceps Fungi. A Preclinical Study in Young Male Mice.

    Science.gov (United States)

    Miao, Xia; Wang, Yafeng; Lang, Haiyang; Lin, Yanyun; Guo, Qiyan; Yang, Mingjuan; Guo, Juan; Zhang, Yanjun; Zhang, Jie; Liu, Junye; Liu, Yaning; Zeng, Lihua; Guo, Guozhen

    2017-02-01

    Networked 21st century society, globalization, and communications technologies are paralleled by the rise of electromagnetic energy intensity in our environments and the growing pressure of the environtome on human biology and health. The latter is the entire complement of environmental factors, including the electromagnetic energy and the technologies that generate them, enacting on the digital citizen in the new century. Electromagnetic pulse (EMP) irradiation might have serious damaging effects not only on electronic equipment but also in the whole organism and reproductive health, through nonthermal effects and oxidative stress. We sought to determine whether EMP exposure (1) induces biological damage on reproductive health and (2) the extent to which selenium-rich Cordyceps fungi (daily coadministration) offer protection on the testicles and spermatozoa. In a preclinical randomized study, 3-week-old male BALB/c mice were repeatedly exposed to EMP (peak intensity 200 kV/m, pulse edge 3.5 ns, pulse width 15 ns, 0.1 Hz, and 400 pulses/day) 5 days per week for four consecutive weeks, with or without coadministration of daily selenium-rich Cordyceps fungi (100 mg/kg). Testicular index and spermatozoa formation were measured at baseline and 1, 7, 14, 28, and 60 day time points after EMP exposure. The group without Cordyceps cotreatment displayed decreased spermatozoa formation, shrunk seminiferous tubule diameters, and diminished antioxidative capacity at 28 and 60 days after exposure (p digital citizenship.

  10. Alterations in core body temperature, locomotor activity, and corticosterone following acute and repeated social defeat of male NMRI mice.

    Science.gov (United States)

    Keeney, A J; Hogg, S; Marsden, C A

    Repeated social defeat of male NMRI mice, coupled with the stress of continuously living opposite a dominant animal, induces a citalopram-reversible increase in anxiety. The experiments reported in the present paper were performed in an attempt to further validate this paradigm by studying the effects of acute and repeated social defeat on corticosterone and the circadian rhythms of core body temperature and locomotor activity, measured by telemetry. Acute social defeat induced a large (controls: 37.14+/-0.29 degrees C; subordinates: 39.79+/-0.33 degrees C) increase in core body temperature and corticosterone (controls: 30.14+/-2.70 ng/ml; subordinates: 89.62+/-9.25 ng/ml). Repeated social defeat (24 defeats) induced a chronic elevation in core body temperature across 24-h (controls: 36.62+/-0.04 degrees C; subordinates: 37.11+/-0.16 degrees C) in subordinate animals and a very large increase in corticosterone (controls: 28.60+/-1.27 ng/ml; subordinates: 441.52+/-8.86 ng/ml). These results illustrate that the chronic social defeat procedure described in this paper induces a state of chronic stress in the subordinate animals. Further studies are warranted to ascertain if the chronic hyperthermia and increases in corticosterone observed in the subordinate animals could be attenuated by chronic antidepressant treatment, thus further extending the predictive validity of this model.

  11. The absence of GH signaling affects the susceptibility to high-fat diet-induced hypothalamic inflammation in male mice

    DEFF Research Database (Denmark)

    Baquedano, Eva; Ruiz-Lopez, Ana M; Sustarsic, Elahu G

    2014-01-01

    -JNK levels. After 7 weeks on a HFD, both WT and GHR-/- mice had increased weight gain, with GHR-/- mice having a greater rise in their percentage of body fat. In WT mice, HFD-induced weight gain was associated with increased hypothalamic levels of phospho-JNK and the microglial marker Iba-1 (ionized calcium...

  12. Increased Detection of Sin Nombre Hantavirus RNA in Antibody-Positive Deer Mice from Montana, USA: Evidence of Male Bias in RNA Viremia

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    James N. Mills

    2013-09-01

    Full Text Available Hantaviruses are widespread emergent zoonotic agents that cause unapparent or limited disease in their rodent hosts, yet cause acute, often fatal pulmonary or renal infections in humans. Previous laboratory experiments with rodent reservoir hosts indicate that hantaviruses can be cleared from host blood early in the infection cycle, while sequestered long term in various host organs. Field studies of North American deer mice (Peromyscus maniculatus, the natural reservoir of Sin Nombre hantavirus, have shown that viral RNA can be transiently detected well past the early acute infection stage, but only in the minority of infected mice. Here, using a non-degenerate RT-PCR assay optimized for SNV strains known to circulate in Montana, USA, we show that viral RNA can be repeatedly detected on a monthly basis in up to 75% of antibody positive deer mice for periods up to 3–6 months. More importantly, our data show that antibody positive male deer mice are more than twice as likely to have detectable SNV RNA in their blood as antibody positive females, suggesting that SNV-infected male deer mice are more likely to shed virus and for longer periods of time.

  13. Assessment of the reproductive toxicity of inhalation exposure to ethyl tertiary butyl ether in male mice with normal, low active and inactive ALDH2.

    Science.gov (United States)

    Weng, Zuquan; Ohtani, Katsumi; Suda, Megumi; Yanagiba, Yukie; Kawamoto, Toshihiro; Nakajima, Tamie; Wang, Rui-Sheng

    2014-04-01

    No data are available regarding aldehyde dehydrogenase 2 (ALDH2) polymorphisms related to the reproductive toxicity possibly caused by ethyl tertiary butyl ether (ETBE). In this study, two inhalation experiments were performed in Aldh2 knockout (KO), heterogeneous (HT) and wild type (WT) C57BL/6 male mice exposed to ETBE, and the data about general toxicity, testicular histopathology, sperm head numbers, sperm motility and sperm DNA damage were collected. The results showed that the 13-week exposure to 0, 500, 1,750 and 5,000 ppm ETBE significantly decreased sperm motility and increased levels of sperm DNA strand breaks and 8-hydroxy-deoxyguanosine in both WT and KO mice, the effects were found in 1,750 and 5,000 ppm groups of WT mice, and all of the three exposed groups of KO mice compared to the corresponding control; furthermore, ETBE also caused decrease in the relative weights of testes and epididymides, the slight atrophy of seminiferous tubules of testis and reduction in sperm numbers of KO mice exposed to ≥500 ppm. In the experiment of exposure to lower concentrations of ETBE (0, 50, 200 and 500 ppm) for 9 weeks, the remarkable effects of ETBE on sperm head numbers, sperm motility and sperm DNA damage were further observed in KO and HT mice exposed to 200 ppm ETBE, but not in WT mice. Our findings suggested that only exposure to high concentrations of ETBE might result in reproductive toxicity in mice with normal active ALDH2, while low active and inactive ALDH2 enzyme significantly enhanced the ETBE-induced reproductive toxicity in mice, even exposed to low concentrations of ETBE, mainly due to the accumulation of acetaldehyde as a primary metabolite of ETBE.

  14. Tissue distribution of basigin and monocarboxylate transporter 1 in the adult male mouse: a study using the wild type and basigin gene knockout mice

    Science.gov (United States)

    Nakai, Masaaki; Chen, Li; Nowak, Romana A.

    2013-01-01

    Basigin (Bsg) is a transmembrane protein that is responsible for targeting of monocarboxylate transporters (MCTs) to the cell membrane. The present study was conducted to determine whether or not Bsg was required for the proper localization of MCT isoform 1 (MCT1) in a wide rage of tissues in adult male mice. The tissue distributions of Bsg and MCT1 in wild type (WT) mice, the tissue distribution of MCT1 in Bsg gene knockout (Bsg-KO) mice, and the protein and mRNA levels of MCT1 in both genotypes were studied. Immunohistochemistry demonstrated that Bsg colocalized with MCT1 in the cerebrum, retina, skeletal and cardiac muscle, duodenal epithelium, hepatic sinusoid, proximal uriniferous tubules, Leydig cells and efferent ductule epithelium in WT mice. Bsg was absent but MCT1 was present in Sertoli cells, cauda epididymis, myoepithelial cells and duct of the mandibular gland, surface epithelium of the stomach and bronchioles. In Bsg-KO mice, with the exception of Leydig cells, MCT1 immunostaining was greatly reduced in intensity and its distribution was altered in tissues that expressed both Bsg and MCT1 in WT mice. Levels of the protein and mRNA for MCT1 in these tissues did not change significantly in Bsg-KO mice. On the other hand, immunostaining patterns in cells in which Bsg was absent but MCT1 was present in WT mice remained unchanged in Bsg-KO mice. These observations suggest that Bsg is required for the proper localization of MCT1 in a wide range of cells but not in every cell type. PMID:16612830

  15. Similar reliability and equivalent performance of female and male mice in the open field and water-maze place navigation task.

    Science.gov (United States)

    Fritz, Ann-Kristina; Amrein, Irmgard; Wolfer, David P

    2017-09-01

    Although most nervous system diseases affect women and men differentially, most behavioral studies using mouse models do not include subjects of both sexes. Many researchers worry that data of female mice may be unreliable due to the estrous cycle. Here, we retrospectively evaluated sex effects on coefficient of variation (CV) in 5,311 mice which had performed the same place navigation protocol in the water-maze and in 4,554 mice tested in the same open field arena. Confidence intervals for Cohen's d as measure of effect size were computed and tested for equivalence with 0.2 as equivalence margin. Despite the large sample size, only few behavioral parameters showed a significant sex effect on CV. Confidence intervals of effect size indicated that CV was either equivalent or showed a small sex difference at most, accounting for less than 2% of total group to group variation of CV. While female mice were potentially slightly more variable in water-maze acquisition and in the open field, males tended to perform less reliably in the water-maze probe trial. In addition to evaluating variability, we also directly compared mean performance of female and male mice and found them to be equivalent in both water-maze place navigation and open field exploration. Our data confirm and extend other large scale studies in demonstrating that including female mice in experiments does not cause a relevant increase of data variability. Our results make a strong case for including mice of both sexes whenever open field or water-maze are used in preclinical research. © 2017 The Authors. American Journal of Medical Genetics Part C Published by Wiley Periodicals, Inc.

  16. Maternal Diet-Induced Obesity Programmes Cardiac Dysfunction in Male Mice Independently of Post-Weaning Diet.

    Science.gov (United States)

    Loche, Elena; Blackmore, Heather L; Carpenter, Asha A M; Beeson, Jessica H; Pinnock, Adele; Ashmore, Thomas J; Aiken, Catherine E; de Almeida-Faria, Juliana; Schoonejans, Josca; Giussani, Dino A; Fernandez-Twinn, Denise S; Ozanne, Susan E

    2018-04-04

    Obesity during pregnancy increases risk of cardiovascular disease (CVD) in the offspring and individuals exposed to over-nutrition during fetal life are likely to be exposed to a calorie-rich environment postnatally. Here, we established the consequences of combined exposure to a maternal and post-weaning obesogenic diet on offspring cardiac structure and function using an established mouse model of maternal diet-induced obesity. The impact of the maternal and postnatal environment on the offspring metabolic profile, arterial blood pressure, cardiac structure and function was assessed in 8-week old C57BL/6 male mice. Measurement of cardiomyocyte cell area, the transcriptional re-activation of cardiac fetal genes as well as genes involved in the regulation of contractile function and matrix remodelling in the adult heart were determined as potential mediators of effects on cardiac function. In the adult offspring: a post-weaning obesogenic diet coupled with exposure to maternal obesity increased serum insulin (P<0.0001) and leptin levels (P<0.0001); maternal obesity (P=0.001) and a post-weaning obesogenic diet (P=0.002) increased absolute heart weight; maternal obesity (P=0.01) and offspring obesity (P=0.01) caused cardiac dysfunction but effects were not additive; cardiac dysfunction resulting from maternal obesity was associated with re-expression of cardiac fetal genes (Myh7:Myh6 ratio; P=0.0004), however these genes were not affected by offspring diet; maternal obesity (P=0.02) and offspring obesity (P=0.05) caused hypertension and effects were additive. Maternal diet-induced obesity and offspring obesity independently promote cardiac dysfunction and hypertension in adult male progeny. Exposure to maternal obesity alone programmed cardiac dysfunction, associated with hallmarks of pathological left ventricular hypertrophy, including increased cardiomyocyte area, upregulation of fetal genes and remodelling of cardiac structure. These data highlight that the

  17. Liver-specific rescuing of CEACAM1 reverses endothelial and cardiovascular abnormalities in male mice with null deletion of Ceacam1 gene

    Directory of Open Access Journals (Sweden)

    Lucia Russo

    2018-03-01

    Full Text Available Objective: Mice with global null mutation of Ceacam1 (Cc1−/−, display impairment of insulin clearance that causes hyperinsulinemia followed by insulin resistance, elevated hepatic de novo lipogenesis, and visceral obesity. In addition, they manifest abnormal vascular permeability and elevated blood pressure. Liver-specific rescuing of Ceacam1 reversed all of the metabolic abnormalities in Cc1−/−liver+ mice. The current study examined whether Cc1−/− male mice develop endothelial and cardiac dysfunction and whether this relates to the metabolic abnormalities caused by defective insulin extraction. Methods and results: Myography studies showed reduction of agonist-stimulated nitric oxide production in resistance arterioles in Cc1−/−, but not Cc1−/−liver+ mice. Liver-based rescuing of CEACAM1 also attenuated the abnormal endothelial adhesiveness to circulating leukocytes in parallel to reducing plasma endothelin-1 and recovering plasma nitric oxide levels. Echocardiography studies revealed increased septal wall thickness, cardiac hypertrophy and reduced cardiac performance in Cc1−/−, but not Cc1−/−xliver+ mice. Insulin signaling experiments indicated compromised IRS1/Akt/eNOS pathway leading to lower nitric oxide level, and activated Shc/MAPK pathway leading to more endothelin-1 production in the aortae and hearts of Cc1−/−, but not Cc1−/−xliver+ mice. The increase in the ratio of endothelin-1 receptor A/B indicated an imbalance in the vasomotor activity of Cc1−/− mice, which was normalized in Cc1−/−xliver+ mice. Conclusions: The data underscore a critical role for impaired CEACAM1-dependent hepatic insulin clearance pathways and resulting hyperinsulinemia and lipid accumulation in aortae and heart in regulating the cardiovascular function. Keywords: Insulin clearance, Hyperinsulinemia, Insulin resistance, Endothelial function, Cardiomyopathy

  18. Social defeat stress induces depression-like behavior and alters spine morphology in the hippocampus of adolescent male C57BL/6 mice

    OpenAIRE

    I?iguez, Sergio D.; Aubry, Antonio; Riggs, Lace M.; Alipio, Jason B.; Zanca, Roseanna M.; Flores-Ramirez, Francisco J.; Hernandez, Mirella A.; Nieto, Steven J.; Musheyev, David; Serrano, Peter A.

    2016-01-01

    Social stress, including bullying during adolescence, is a risk factor for common psychopathologies such as depression. To investigate the neural mechanisms associated with juvenile social stress-induced mood-related endophenotypes, we examined the behavioral, morphological, and biochemical effects of the social defeat stress model of depression on hippocampal dendritic spines within the CA1 stratum radiatum. Adolescent (postnatal day 35) male C57BL/6 mice were subjected to defeat episodes fo...

  19. Diet-induced obesity in male C57BL/6 mice decreases fertility as a consequence of disrupted blood-testis barrier.

    Science.gov (United States)

    Fan, Yong; Liu, Yue; Xue, Ke; Gu, Guobao; Fan, Weimin; Xu, Yali; Ding, Zhide

    2015-01-01

    Obesity is a complex metabolic disease that is a serious detriment to both children and adult health, which induces a variety of diseases, such as cardiovascular disease, type II diabetes, hypertension and cancer. Although adverse effects of obesity on female reproduction or oocyte development have been well recognized, its harmfulness to male fertility is still unclear because of reported conflicting results. The aim of this study was to determine whether diet-induced obesity impairs male fertility and furthermore to uncover its underlying mechanisms. Thus, male C57BL/6 mice fed a high-fat diet (HFD) for 10 weeks served as a model of diet-induced obesity. The results clearly show that the percentage of sperm motility and progressive motility significantly decreased, whereas the proportion of teratozoospermia dramatically increased in HFD mice compared to those in normal diet fed controls. Besides, the sperm acrosome reaction fell accompanied by a decline in testosterone level and an increase in estradiol level in the HFD group. This alteration of sperm function parameters strongly indicated that the fertility of HFD mice was indeed impaired, which was also validated by a low pregnancy rate in their mated normal female. Moreover, testicular morphological analyses revealed that seminiferous epithelia were severely atrophic, and cell adhesions between spermatogenic cells and Sertoli cells were loosely arranged in HFD mice. Meanwhile, the integrity of the blood-testis barrier was severely interrupted consistent with declines in the tight junction related proteins, occludin, ZO-1 and androgen receptor, but instead endocytic vesicle-associated protein, clathrin rose. Taken together, obesity can impair male fertility through declines in the sperm function parameters, sex hormone level, whereas during spermatogenesis damage to the blood-testis barrier (BTB) integrity may be one of the crucial underlying factors accounting for this change.

  20. Diet-induced obesity in male C57BL/6 mice decreases fertility as a consequence of disrupted blood-testis barrier.

    Directory of Open Access Journals (Sweden)

    Yong Fan

    Full Text Available Obesity is a complex metabolic disease that is a serious detriment to both children and adult health, which induces a variety of diseases, such as cardiovascular disease, type II diabetes, hypertension and cancer. Although adverse effects of obesity on female reproduction or oocyte development have been well recognized, its harmfulness to male fertility is still unclear because of reported conflicting results. The aim of this study was to determine whether diet-induced obesity impairs male fertility and furthermore to uncover its underlying mechanisms. Thus, male C57BL/6 mice fed a high-fat diet (HFD for 10 weeks served as a model of diet-induced obesity. The results clearly show that the percentage of sperm motility and progressive motility significantly decreased, whereas the proportion of teratozoospermia dramatically increased in HFD mice compared to those in normal diet fed controls. Besides, the sperm acrosome reaction fell accompanied by a decline in testosterone level and an increase in estradiol level in the HFD group. This alteration of sperm function parameters strongly indicated that the fertility of HFD mice was indeed impaired, which was also validated by a low pregnancy rate in their mated normal female. Moreover, testicular morphological analyses revealed that seminiferous epithelia were severely atrophic, and cell adhesions between spermatogenic cells and Sertoli cells were loosely arranged in HFD mice. Meanwhile, the integrity of the blood-testis barrier was severely interrupted consistent with declines in the tight junction related proteins, occludin, ZO-1 and androgen receptor, but instead endocytic vesicle-associated protein, clathrin rose. Taken together, obesity can impair male fertility through declines in the sperm function parameters, sex hormone level, whereas during spermatogenesis damage to the blood-testis barrier (BTB integrity may be one of the crucial underlying factors accounting for this change.

  1. Testosterone plus low-intensity physical training in late life improves functional performance, skeletal muscle mitochondrial biogenesis, and mitochondrial quality control in male mice.

    Directory of Open Access Journals (Sweden)

    Wen Guo

    Full Text Available Testosterone supplementation increases muscle mass in older men but has not been shown to consistently improve physical function and activity. It has been hypothesized that physical exercise is required to induce the adaptations necessary for translation of testosterone-induced muscle mass gain into functional improvements. However, the effects of testosterone plus low intensity physical exercise training (T/PT on functional performance and bioenergetics are unknown. In this pilot study, we tested the hypothesis that combined administration of T/PT would improve functional performance and bioenergetics in male mice late in life more than low-intensity physical training alone. 28-month old male mice were randomized to receive T/PT or vehicle plus physical training (V/PT for 2 months. Compare to V/PT control, administration of T/PT was associated with improvements in muscle mass, grip strength, spontaneous physical movements, and respiratory activity. These changes were correlated with increased mitochondrial DNA copy number and expression of markers for mitochondrial biogenesis. Mice receiving T/PT also displayed increased expression of key elements for mitochondrial quality control, including markers for mitochondrial fission-and-fusion and mitophagy. Concurrently, mice receiving T/PT also displayed increased expression of markers for reduced tissue oxidative damage and improved muscle quality.Testosterone administered with low-intensity physical training improves grip strength, spontaneous movements, and respiratory activity. These functional improvements were associated with increased muscle mitochondrial biogenesis and improved mitochondrial quality control.

  2. Infection with Toxoplasma gondii does not elicit predator aversion in male mice nor increase their attractiveness in terms of mate choice.

    Science.gov (United States)

    Soh, Linda Jing Ting; Vasudevan, Anand; Vyas, Ajai

    2013-09-01

    Behavioral manipulation hypothesis posits that some parasites induce behavioral changes in the host to increase transmission efficiency of the parasite. Protozoan parasite Toxoplasma gondii infecting rats has been widely studied in this context. T. gondii increases attractiveness of infected male rats and reduces innate aversion of rats to cat odor, likely increasing transmission of the parasite by sexual and trophic routes respectively. It is currently unexplored if T. gondii induces gain of male attractiveness in experimental models other than rats. Here we show that laboratory infection of two strains of mice does not induce behavioral manipulation. Moreover, T. gondii infection results in reduction of male attractiveness in one of the strains. In agreement with this observation, T. gondii infection also fails to induce reduction in innate aversion to cat odors in mice. Effects of the parasite on mice mate choice are similar to effects of several other parasites in this animal model. Thus, behavioral change induced by the parasite may be specific to the rodent species.

  3. Bupropion induced changes in exploratory and anxiety-like behaviour in NMRI male mice depends on the age

    NARCIS (Netherlands)

    Carmen Carrasco, M.; Vidal Mollon, Jose; Redolat, Rosa

    The aim of this study was to assess the effects of the antidepressant bupropion on anxiety and novelty-seeking in adolescent mice of different ages and adults. Behavioural differences between early adolescent, late adolescent and adult NMRI mice were measured both in the elevated plus-maze and the

  4. Evaluation of Anticonvulsive ٍEffect of Magnesium Oxide Nanoparticles in Comparison with Conventional MgO in Diabetic and Non-diabetic Male Mice

    Directory of Open Access Journals (Sweden)

    Leila Jahangiri

    2014-05-01

    Full Text Available Introduction: Some studies show magnesium has anticonvulsive effect in some animal models. Despite of the availability of well-studied anticonvulsant drugs, this evaluation was not carried on new kind of magnesium supplement, magnesium oxide nanoparticles (nMgO. According to the interaction between magnesium and convulsion, this study was designed to evaluate the effect of nMgO on strychnine-induced convulsive model in compared to its conventional in diabetic and normal mice. Methods: Healthy male albino mice were divided to 10 groups. Diabete mellitus was induced by streptozocin in 5 groups. Conventional and nanoparticle MgO (5&10mg/kg in presence and absence diabetes injected to mice, then strychnine injected and onset of convulsions and time of death were measured after strychnine administration. Results: Convulsive parameters did not change in normal and diabetic mice. cMgO pretreatment did not have anticonvulsant effect in strychnine-induced convulsion in normal and diabetic mice. But nMgO significantly changed convulsion onset and death time after strychnine administration in normal and diabetic status. Discussion: According to our results It seems that nMgO may be important in prevention or treatment of epilepsy and has more efficacy than its conventional form to showing anticonvulsive effect that probably is related to the physicochemical properties of nMgO, specially in diabetic subjects, a point that need to further investigation.

  5. Removal of a high-fat diet, but not voluntary exercise, reverses obesity and diabetic-like symptoms in male C57BL/6J mice.

    Science.gov (United States)

    Hatzidis, Aikaterini; Hicks, Jasmin A; Gelineau, Rachel R; Arruda, Nicole L; Monteiro De Pina, Isabella; O'Connell, Karyn E; Seggio, Joseph A

    2017-01-01

    Both the consumption of high-fat diets and exercise are known to produce alterations in metabolism and behavior. This study focuses on the effects of a change to a low-fat diet from a high-fat diet and voluntary exercise on obesity, type-2 diabetic-like symptoms, and locomotor behavior in male C57BL/6J mice. Mice were initially given either a high-fat diet or regular chow, along with a cage with a running-wheel to mimic exercise, or one without, to determine to what extend exercise affects these symptoms. Then half of the mice given a high-fat diet were switched to regular chow to ascertain if the switch in diet would improve type-2 diabetic-like and obesity symptoms. Wheel-running alone produced an improvement in insulin in mice continuously fed a high-fat diet (p=0.006), but running-wheels did not produce any further improvements in mice with regular chow replacement (p=0.999) or in controls (p=0.996). Replacement of a high-fat diet with regular chow led to physiological improvements in insulin (p=0.012) and leptin (p obesity (p symptoms and related conditions more so than exercise alone.

  6. Improved survival and reduced phenotypic severity following AAV9/MECP2 gene transfer to neonatal and juvenile male Mecp2 knockout mice.

    Science.gov (United States)

    Gadalla, Kamal K E; Bailey, Mark E S; Spike, Rosemary C; Ross, Paul D; Woodard, Kenton T; Kalburgi, Sahana Nagabhushan; Bachaboina, Lavanya; Deng, Jie V; West, Anne E; Samulski, R Jude; Gray, Steven J; Cobb, Stuart R

    2013-01-01

    Typical Rett syndrome (RTT) is a pediatric disorder caused by loss-of-function mutations in the methyl-CpG binding protein 2 (MECP2) gene. The demonstrated reversibility of RTT-like phenotypes in mice suggests that MECP2 gene replacement is a potential therapeutic option in patients. We report improvements in survival and phenotypic severity in Mecp2-null male mice after neonatal intracranial delivery of a single-stranded (ss) AAV9/chicken β-actin (CBA)-MECP2 vector. Median survival was 16.6 weeks for MECP2-treated versus 9.3 weeks for green fluorescent protein (GFP)-treated mice. ssAAV9/CBA-MECP2-treated mice also showed significant improvement in the phenotype severity score, in locomotor function, and in exploratory activity, as well as a normalization of neuronal nuclear volume in transduced cells. Wild-type (WT) mice receiving neonatal injections of the same ssAAV9/CBA-MECP2 vector did not show any significant deficits, suggesting a tolerance for modest MeCP2 overexpression. To test a MECP2 gene replacement approach in a manner more relevant for human translation, a self-complementary (sc) adeno-associated virus (AAV) vector designed to drive MeCP2 expression from a fragment of the Mecp2 promoter was injected intravenously (IV) into juvenile (4-5 weeks old) Mecp2-null mice. While the brain transduction efficiency in juvenile mice was low (~2-4% of neurons), modest improvements in survival were still observed. These results support the concept of MECP2 gene therapy for RTT.

  7. Running exercise mitigates the negative consequences of chronic stress on dorsal hippocampal long-term potentiation in male mice.

    Science.gov (United States)

    Miller, Roxanne M; Marriott, David; Trotter, Jacob; Hammond, Tyler; Lyman, Dane; Call, Timothy; Walker, Bethany; Christensen, Nathanael; Haynie, Deson; Badura, Zoie; Homan, Morgan; Edwards, Jeffrey G

    2018-03-01

    In the hippocampus, learning and memory are likely mediated by synaptic plasticity, known as long-term potentiation (LTP). While chronic intermittent stress is negatively correlated, and exercise positively correlated to LTP induction, we examined whether exercise could mitigate the negative consequences of stress on LTP when co-occurring with stress. Mice were divided into four groups: sedentary no stress, exercise no stress, exercise with stress, and sedentary with stress. Field electrophysiology performed on brain slices confirmed that stress alone significantly reduced dorsal CA1 hippocampal LTP and exercise alone increased LTP compared to controls. Exercise with stress mice exhibited LTP that was significantly greater than mice undergoing stress alone but were not different from sedentary no stress mice. An ELISA illustrated increased corticosterone in stressed mice compared to no stress mice. In addition, a radial arm maze was used to examine behavioral changes in memory during 6 weeks of stress and/or exercise. Exercised mice groups made fewer errors in week 2. RT-qPCR was used to examine the mRNA expression of components in the stress and exercise pathways in the four groups. Significant changes in the expression of the following targets were detected: BDNF, TrkB, glucocorticoid, mineralocorticoid, and dopamine 5 receptors. Collectively, exercise can mitigate some of the negative impact stress has on hippocampal function when both occur concurrently. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. In utero and lactational exposure to acetamiprid induces abnormalities in socio-sexual and anxiety-related behaviors of male mice

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    Kazuhiro eSano

    2016-06-01

    Full Text Available Neonicotinoid, a widely-used pesticide group designed to selectively bind to insect nicotinic acetylcholine receptors, were considered to be relatively safe for mammalian species. However, it has been found to activate vertebrate nicotinic acetylcholine receptors than ever anticipated, and could be toxic to the mammalian brain. In the present study, we evaluated the developmental neurotoxicity of acetamiprid (ACE, one of the most-widely used neonicotinoid, in C57BL/6J mice whose mothers were administered ACE via gavage at doses of either 0 mg/kg (control, 1.0 mg/kg (low-dose or 10.0 mg/kg (high-dose from gestational day 6 to lactation day 21. As possible endpoints, a battery of behavior tests, socio-sexual and anxiety-related behaviors, as well as testosterone level and the number of vasopressin-immunoreactive cells in the paraventricular nucleus of the hypothalamus were examined. In addition, behavioral flexibility was assessed for mice in a group-housed environment using an IntelliCage, a fully automated mouse behavioral analysis system. In adult male mice exposed to ACE at both low and high doses, significant reduction of anxiety level was found in the light-dark transition test. Males in the low-dose group also showed a significant increase in sexual and aggressive behaviors. In contrast, neither the anxiety nor the sexual behavior of females was altered. No impairments in testosterone level, the number of vasopressin-immunoreactive cells, and behavioral flexibility were detected in either sex. These results suggest the possibility that in utero and lactational ACE exposure interferes with the development of the neural circuits required for executing socio-sexual and anxiety-related behaviors in male mice specifically.

  9. Tumor necrosis factor-alpha during neonatal brain development affects anxiety- and depression-related behaviors in adult male and female mice.

    Science.gov (United States)

    Babri, Shirin; Doosti, Mohammad-Hossein; Salari, Ali-Akbar

    2014-03-15

    A nascent literature suggests that neonatal infection is a risk factor for the development of brain, behavior and hypothalamic-pituitary-adrenal axis which can affect anxiety- and depression-related behaviors in later life. It has been documented that neonatal infection raises the concentrations of tumor necrosis factor-alpha (TNF-α) in neonate rodents and such infections may result in neonatal brain injury, at least in part, through pro-inflammatory cytokines. In addition, previous studies have shown that TNF-α is involved in cellular differentiation, neurogenesis and programmed cell death during the development of the central nervous system. We investigated for the first time whether neonatal exposure to TNF-α can affect body weight, stress-induced corticosterone (COR), anxiety- and depression-related behaviors in adult mice. In the present study, neonatal mice were treated to recombinant mouse TNF-α (0.2, 0.4, 0.7 and 1 μg/kg) or saline on postnatal days 3 and 5, then adult male and female mice were exposed to different behavioral tests. The results indicated that neonatal TNF-α treatment reduced body weight in neonatal period in both sexes. In addition, this study presents findings indicating that high doses of TNF- increase stress-induced COR levels, anxiety- and depression-related behaviors in adult males, but increase levels of anxiety without significantly influencing depression in adult female mice [corrected]. Our findings suggest that TNF-α exposure during neonatal period can alter brain and behavior development in a dose and sex-dependent manner in mice. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Unripe Papaya (Carica papaya L. Seed Hexane Fraction Extract Inhibits Male Mice (Mus musculus Spermatogenesis Stronger Than Unripe Papaya Seed Methanolic Extract

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    Bagus Komang Satriyasa

    2016-06-01

    Full Text Available Background: Men and women have the same rights and obligations in family planning program. Practically, participation in family planning program is still predominated by women while participation of men is still low. Low participation of men in family planning program is due to very limited choices in male contraceptive method. In recent years, studies have been refocused on investigating traditional plants as antifertility herbal medicine for men. Studies on antifertility effects of unripe papaya seeds have been done. However, similar studies on hexane fraction extract have not yet been done. In this study, unripe seeds were collected from local Balinese papaya (Carica papaya fruits. Objective: This study was aimed to assess the effect of unripe papaya seeds hexane fraction extract on spermatogenesis and the testosterone level of male mice. Hexane fraction extract of unripe papaya seeds contains glycosides and triterpenoids, which is assumed to have an antifertility property, so it can be used as a male contraceptive, although the mechanism of action remains to be elucidated. Method: This study used pre-test and post-test control group design, using 30 male mice of balb C strain, 12 weeks of age, weighing 20-22 gram, which were randomly grouped into 3 groups, each consisting of 10 male mice. One control group (P0 = control group was given double-distilled water, and two treatment groups were given hexane fraction extract of unripe Carica papaya seeds 20 mg/20gram/day, and methanolic extract of unripe Carica papaya seeds 20 mg/20 gram/day (P1 and P2, respectively. After 36 days of treatment, evaluation of the testes and blood of the male mice was conducted. Results: Data were analysed by normality test of Kolmogorov-Smirnov Goodness of Fit, homogeneity test, and Anova test. This study showed that spermatogonia A, primary pachytene spermatocytes, spermatid and Sertoli cells were decreased significantly (p < 0,05 but Leydig cells and testosterone

  11. DREADD-induced silencing of the medial amygdala reduces the preference for male pheromones and the expression of lordosis in estrous female mice.

    Science.gov (United States)

    McCarthy, Elizabeth A; Maqsudlu, Arman; Bass, Matthew; Georghiou, Sofia; Cherry, James A; Baum, Michael J

    2017-08-01

    Sexually naïve estrous female mice seek out male urinary pheromones; however, they initially display little receptive (lordosis) behavior in response to male mounts. Vomeronasal-accessory olfactory bulb inputs to the medial amygdala (Me) regulate courtship in female rodents. We used a reversible inhibitory chemogenetic technique (Designer Receptors Exclusively Activated by Designer Drugs; DREADDs) to assess the contribution of Me signaling to females' preference for male pheromones and improvement in receptivity normally seen with repeated testing. Sexually naïve females received bilateral Me injections of an adeno-associated virus carrying an inhibitory DREADD. Females were later ovariectomized, treated with ovarian hormones, and given behavioral tests following intraperitoneal injections of saline or clozapine-N-oxide (CNO; which hyperpolarizes infected Me neurons). CNO attenuated females' preference to investigate male vs. female urinary odors. Repeated CNO treatment also slowed the increase in lordosis otherwise seen in females given saline. However, when saline was given to females previously treated with CNO, their lordosis quotients were as high as other females repeatedly given saline. No disruptive behavioral effects of CNO were seen in estrous females lacking DREADD infections of the Me. Finally, CNO attenuated the ability of male pheromones to stimulate Fos expression in the Me of DREADD-infected mice but not in non-infected females. Our results affirm the importance of Me signaling in females' chemosensory preferences and in the acute expression of lordosis. However, they provide no indication that Me signaling is required for the increase in receptivity normally seen after repeated hormone priming and testing with a male. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  12. Stress resilience: a low-anxiety genotype protects male mice from the consequences of chronic psychosocial stress.

    Science.gov (United States)

    Füchsl, Andrea M; Neumann, Inga D; Reber, Stefan O

    2014-01-01

    Chronic psychosocial stress is a risk factor for the development of affective as well as somatic disorders. However, vulnerability to adverse stress effects varies between individuals, with previous negative life events along with genetic predisposition playing a major role. In support, we previously showed that the consequences of chronic psychosocial stress induced by chronic subordinate colony housing (CSC, 19 days) can be amplified by pre-exposing mice to repeated maternal separation during early life. To test the significance of the genetic predisposition on the effects of CSC, mice selectively bred for high (mHAB) and low (mLAB) anxiety-related behavior and nonselected CD1 mice (mNAB) were exposed to CSC in the present study. In confirmation of our previous results, CSC mice of both mHAB and mNAB lines displayed chronic stress-related symptoms including increased adrenal weight, decreased adrenal in vitro ACTH sensitivity, lower plasma corticosterone to ACTH ratio, and increased interferon-γ secretion from isolated mesenteric lymph node cells compared with single-housed controls of the respective line. However, the CSC-induced anxiogenic effect found in mNAB was not confirmed in mHAB mice, possibly due to a ceiling effect in these highly anxious mice. Interestingly, mHAB were not more vulnerable to CSC than mNAB mice, whereas mLAB mice were resilient to CSC as indicated by all of the above mentioned parameters assessed. Taken together, our findings indicate that the genetic predisposition, in this case the innate anxiety of an individual, affects vulnerability to chronic psychosocial stress, with a low-anxiety phenotype mediating resilience to both affective and somatic consequences of CSC.

  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....... This suggests that studies of exploratory behavior may aid in developing new markers of short-term stroke-related behavioral deficiencies in laboratory mice....

  14. Evidence Supporting a Role for Constitutive Ghrelin Receptor Signaling in Fasting-Induced Hyperphagia in Male Mice.

    Science.gov (United States)

    Fernandez, Gimena; Cabral, Agustina; Andreoli, María F; Labarthe, Alexandra; M'Kadmi, Céline; Ramos, Jorge G; Marie, Jacky; Fehrentz, Jean-Alain; Epelbaum, Jacques; Tolle, Virginie; Perello, Mario

    2018-02-01

    Ghrelin is a potent orexigenic peptide hormone that acts through the growth hormone secretagogue receptor (GHSR), a G protein-coupled receptor highly expressed in the hypothalamus. In vitro studies have shown that GHSR displays a high constitutive activity, whose physiological relevance is uncertain. As GHSR gene expression in the hypothalamus is known to increase in fasting conditions, we tested the hypothesis that constitutive GHSR activity at the hypothalamic level drives the fasting-induced hyperphagia. We found that refed wild-type (WT) mice displayed a robust hyperphagia that continued for 5 days after refeeding and changed their food intake daily pattern. Fasted WT mice showed an increase in plasma ghrelin levels, as well as in GHSR expression levels and ghrelin binding sites in the hypothalamic arcuate nucleus. When fasting-refeeding responses were evaluated in ghrelin- or GHSR-deficient mice, only the latter displayed an ∼15% smaller hyperphagia, compared with WT mice. Finally, fasting-induced hyperphagia of WT mice was significantly smaller in mice centrally treated with the GHSR inverse agonist K-(D-1-Nal)-FwLL-NH2, compared with mice treated with vehicle, whereas it was unaffected in mice centrally treated with the GHSR antagonists D-Lys3-growth hormone-releasing peptide 6 or JMV2959. Taken together, genetic models and pharmacological results support the notion that constitutive GHSR activity modulates the magnitude of the compensatory hyperphagia triggered by fasting. Thus, the hypothalamic GHSR signaling system could affect the set point of daily food intake, independently of plasma ghrelin levels, in situations of negative energy balance. Copyright © 2018 Endocrine Society.

  15. Novel Sperm and Gonadotropin-releasing Hormone-based Recombinant Fusion Protein: Achievement of 100% Contraceptive Efficacy by Co-immunization of Male and Female Mice.

    Science.gov (United States)

    Minhas, Vidisha; Shrestha, Abhinav; Wadhwa, Neerja; Singh, Rita; Gupta, Satish Kumar

    2016-12-01

    Improvements in long-term female contraception can be achieved by vaccinating with sperm-derived proteins. Here, recombinant proteins comprising either (i) N- (amino acid residues 1-80) or C- (amino acid residues 76-126) terminal fragments of mouse sperm protein 17 (Sp17) fused to the promiscuous T non-B cell epitope of tetanus toxoid (TT), amino acid residues 830-844 followed by di-lysine linker (KK) (TT-KK-Sp17 N or TT-KK-Sp17 C , respectively) or (ii) mouse equatorin (amino acid residues 21-185) fused to the T non-B cell epitope of bovine RNase (amino acid residues 94-104) were expressed in Escherichia coli. Immunization of female FVB/J mice, using alum as an adjuvant, led to the generation of high antibody titers against the above proteins. Antibodies against both N- and C-terminal fragments of Sp17 reacted with the entire capacitated mouse spermatozoa, whereas those against equatorin reacted exclusively with the equatorial region. Despite the reactivity of all immune sera, only sera from mice immunized with TT-KK-Sp17 N and TT-KK-Sp17 C significantly reduced mouse in vitro fertilization. Mating studies of the immunized females with un-immunized male mice revealed the highest infertility in the TT-KK-Sp17 C -immunized group. In an attempt to further boost the immune response, the C-terminal fragment of Sp17 was expressed as fusion protein with a tandem repeat of gonadotropin-releasing hormone (GnRH) (Sp17 C -GnRH 2 ). Immunization of both male and female mice with Sp17 C -GnRH 2 led to higher contraceptive efficacy compared to mice immunized with TT-KK-Sp17 C . Interestingly, mating studies wherein partners were both immunized with Sp17 C -GnRH 2 showed a complete failure of female mice to conceive. Thus, immunization of both males and females with Sp17 C -GnRH 2 has the potential to increase contraceptive efficacy. Mol. Reprod. Dev. 83: 1048-1059, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  16. Nutrients differentially regulate nucleobindin-2/nesfatin-1 in vitro in cultured stomach ghrelinoma (MGN3-1 cells and in vivo in male mice.

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    Haneesha Mohan

    Full Text Available Nesfatin-1 is secreted, meal-responsive anorexigenic peptide encoded in the precursor nucleobindin-2 [NUCB2]. Circulating nesfatin-1 increases post-prandially, but the dietary components that modulate NUCB2/nesfatin-1 remain unknown. We hypothesized that carbohydrate, fat and protein differentially regulate tissue specific expression of nesfatin-1. NUCB2, prohormone convertases and nesfatin-1 were detected in mouse stomach ghrelinoma [MGN3-1] cells. NUCB2 mRNA and protein were also detected in mouse liver, and small and large intestines. MGN3-1 cells were treated with glucose, fatty acids or amino acids. Male C57BL/6 mice were chronically fed high fat, high carbohydrate and high protein diets for 17 weeks. Quantitative PCR and nesfatin-1 assays were used to determine nesfatin-1 at mRNA and protein levels. Glucose stimulated NUCB2 mRNA expression in MGN3-1 cells. L-Tryptophan also increased NUCB2 mRNA expression and ghrelin mRNA expression, and nesfatin-1 secretion. Oleic acid inhibited NUCB2 mRNA expression, while ghrelin mRNA expression and secretion was enhanced. NUCB2 mRNA expression was significantly lower in the liver of mice fed a high protein diet compared to mice fed other diets. Chronic intake of high fat diet caused a significant reduction in NUCB2 mRNA in the stomach, while high protein and high fat diet caused similar suppression of NUCB2 mRNA in the large intestine. No differences in serum nesfatin-1 levels were found in mice at 7 a.m, at the commencement of the light phase. High carbohydrate diet fed mice showed significantly elevated nesfatin-1 levels at 1 p.m. Serum nesfatin-1 was significantly lower in mice fed high fat, protein or carbohydrate compared to the controls at 7 p.m, just prior to the dark phase. Mice that received a bolus of high fat had significantly elevated nesfatin-1/NUCB2 at all time points tested post-gavage, compared to control mice and mice fed other diets. Our results for the first time indicate that

  17. Epigenetic events determine tissue-specific toxicity of inhalational exposure to the genotoxic chemical 1,3-butadiene in male C57BL/6J mice.

    Science.gov (United States)

    Chappell, Grace; Kobets, Tetyana; O'Brien, Bridget; Tretyakova, Natalia; Sangaraju, Dewakar; Kosyk, Oksana; Sexton, Kenneth G; Bodnar, Wanda; Pogribny, Igor P; Rusyn, Ivan

    2014-12-01

    1,3-Butadiene (BD), a widely used industrial chemical and a ubiquitous environmental pollutant, is a known human carcinogen. Although genotoxicity is an established mechanism of the tumorigenicity of BD, epigenetic effects have also been observed in livers of mice exposed to the chemical. To better characterize the diverse molecular mechanisms of BD tumorigenicity, we evaluated genotoxic and epigenotoxic effects of BD exposure in mouse tissues that are target (lung and liver) and non-target (kidney) for BD-induced tumors. We hypothesized that epigenetic alterations may explain, at least in part, the tissue-specific differences in BD tumorigenicity in mice. We evaluated the level of N-7-(2,3,4-trihydroxybut-1-yl)guanine adducts and 1,4-bis-(guan-7-yl)-2,3-butanediol crosslinks, DNA methylation, and histone modifications in male C57BL/6 mice exposed to filtered air or 425 ppm of BD by inhalation (6 h/day, 5 days/week) for 2 weeks. Although DNA damage was observed in all three tissues of BD-exposed mice, variation in epigenetic effects clearly existed between the kidneys, liver, and lungs. Epigenetic alterations indicative of genomic instability, including demethylation of repetitive DNA sequences and alterations in histone-lysine acetylation, were evident in the liver and lung tissues of BD-exposed mice. Changes in DNA methylation were insignificant in the kidneys of treated mice, whereas marks of condensed heterochromatin and transcriptional silencing (histone-lysine trimethylation) were increased. These modifications may represent a potential mechanistic explanation for the lack of tumorigenesis in the kidney. Our results indicate that differential tissue susceptibility to chemical-induced tumorigenesis may be attributed to tissue-specific epigenetic alterations. Published by Oxford University Press on behalf of the Society of Toxicology 2014. This work is written by US Government employees and is in the public domain in the US.

  18. Antidiabetic, hypolipidemic and hepatoprotective effects of Arctium lappa root’s hydro-alcoholic extract on nicotinamide-streptozotocin induced type 2 model of diabetes in male mice

    Directory of Open Access Journals (Sweden)

    Akram Ahangarpour

    2017-02-01

    Full Text Available Objective: Arctium lappa (burdock, (A. lappa root has hypoglycemic and antioxidative effects, and has been used for treatment of diabetes in tradition medicine. This study was conducted to evaluate the antidiabetic and hypolipidemic properties of A. lappa root extract on nicotinamide-streptozotocin (NA-STZ-induced type2 diabetes in mice.Materials and Methods: In this investigation, 70 adult male NMRI mice (30-35g randomly divided into 7 groups (n=10 as follow: 1-control, 2-type 2 diabetic mice, 3-diabetic mice that received glibenclamide (0.25 mg/kg as an anti-diabetic drug, 4, 5, 6 and 7- diabetic and normal animals that were pre-treated with 200 and 300 mg/kg A. lappa root extract, respectively, for 28 days. Diabetes has been induced by intraperitoneal injection of NA and STZ. Finally, the blood sample was taken and insulin, glucose, SGOT, SGPT, alkaline phosphatase, leptin and lipid levels was evaluated.Results: Induction of diabetes decreased the level of insulin, leptin and high density lipoprotein (HDL and increased the level of other lipids, glucose, and hepatic enzymes significantly (p

  19. Antidiabetic, hypolipidemic and hepatoprotective effects of Arctium lappa root’s hydro-alcoholic extract on nicotinamide-streptozotocin induced type 2 model of diabetes in male mice

    Science.gov (United States)

    Ahangarpour, Akram; Heidari, Hamid; Oroojan, Ali Akbar; Mirzavandi, Farhang; Nasr Esfehani, Khalil; Dehghan Mohammadi, Zeinab

    2017-01-01

    Objective: Arctium lappa (burdock), (A. lappa) root has hypoglycemic and antioxidative effects, and has been used for treatment of diabetes in tradition medicine. This study was conducted to evaluate the antidiabetic and hypolipidemic properties of A. lappa root extract on nicotinamide-streptozotocin (NA-STZ)-induced type2 diabetes in mice. Materials and Methods: In this investigation, 70 adult male NMRI mice (30-35g) randomly divided into 7 groups (n=10) as follow: 1-control, 2-type 2 diabetic mice, 3-diabetic mice that received glibenclamide (0.25 mg/kg) as an anti-diabetic drug, 4, 5, 6 and 7- diabetic and normal animals that were pre-treated with 200 and 300 mg/kg A. lappa root extract, respectively, for 28 days. Diabetes has been induced by intraperitoneal injection of NA and STZ. Finally, the blood sample was taken and insulin, glucose, SGOT, SGPT, alkaline phosphatase, leptin and lipid levels was evaluated. Results: Induction of diabetes decreased the level of insulin, leptin and high density lipoprotein (HDL) and increased the level of other lipids, glucose, and hepatic enzymes significantly (plappa root extract, at specific doses, has an anti-diabetic effect through its hypolipidemic and insulinotropic properties. Hence, this plant extract may be beneficial in the treatment of diabetes. PMID:28348972

  20. Antidiabetic, hypolipidemic and hepatoprotective effects ofArctium lapparoot's hydro-alcoholic extract on nicotinamide-streptozotocin induced type 2 model of diabetes in male mice.

    Science.gov (United States)

    Ahangarpour, Akram; Heidari, Hamid; Oroojan, Ali Akbar; Mirzavandi, Farhang; Nasr Esfehani, Khalil; Dehghan Mohammadi, Zeinab

    2017-01-01

    Arctium lappa (burdock), (A. lappa) root has hypoglycemic and antioxidative effects, and has been used for treatment of diabetes in tradition medicine. This study was conducted to evaluate the antidiabetic and hypolipidemic properties of A. lappa root extract on nicotinamide-streptozotocin (NA-STZ)-induced type2 diabetes in mice. In this investigation, 70 adult male NMRI mice (30-35g) randomly divided into 7 groups (n=10) as follow: 1-control, 2-type 2 diabetic mice, 3-diabetic mice that received glibenclamide (0.25 mg/kg) as an anti-diabetic drug, 4, 5, 6 and 7- diabetic and normal animals that were pre-treated with 200 and 300 mg/kg A. lappa root extract, respectively, for 28 days. Diabetes has been induced by intraperitoneal injection of NA and STZ. Finally, the blood sample was taken and insulin, glucose, SGOT, SGPT, alkaline phosphatase, leptin and lipid levels was evaluated. Induction of diabetes decreased the level of insulin, leptin and high density lipoprotein (HDL) and increased the level of other lipids, glucose, and hepatic enzymes significantly (plappa root extract, at specific doses, has an anti-diabetic effect through its hypolipidemic and insulinotropic properties. Hence, this plant extract may be beneficial in the treatment of diabetes.

  1. Protective effect of date palm pollen (Phoenix dactylifera on sperm parameters and sexual hormones in male NMRI mice exposed to low frequency electromagnetic field (50 Hz

    Directory of Open Access Journals (Sweden)

    Baharara Javad

    2015-07-01

    Full Text Available Introduction: Exposure to electromagnetic fields (EMFs induces harmful effects on testis and reproductive activities. In traditional medicine, date palm pollen (DPP which has remarkable nutritional values is used for curing male infertility and impotency. The aim of this study was to investigate the protective effect of DPP in preventing the detrimental effects of low frequency electromagnetic field (50 Hz on sperm parameters and sexual hormones. Methods: Adult male mice were randomly divided into 7 groups of 8 and exposed to EMF 4 h/day for 10 days. In this study experimental groups received DPP with doses of 25, 50, 100 and 200 mg/kg, respectively before exposure. At the end of the experiment each group were tested for sperm parameters including: motility, count, morphology, viability and the level of luteinizing hormone (LH and testosterone. Results: Our results revealed that exposure to EMF induced significant reduction (P < .001 in sperm count, viability and progressive motility in comparison with control group. EMF caused abnormalities in sperm and significant decrease in testosterone level while there was no significant difference in level. Administration of DPP before exposure improved the sperm count, viability, motility and testosterone level in experimental groups. In addition, pretreatment with DPP prevented the sperm abnormality induced by EMF. Conclusion: The results indicate the protective effect of DPP against EMF adverse effects on sperm parameters and sexual hormones in male mice.

  2. Biological study on the effect of an anabolic steroidal agent administration pre-exposure to whole body gamma irradiated male mice

    International Nuclear Information System (INIS)

    Aly, S.M.; Eldawy, H.A.E.; Ragab, E.A.

    2002-01-01

    The present study was prepared to evaluate the potency of methoxy dimethylamino phenyl epiandrosterone (an anabolic agent animal in origin with an additive side chain) in a dose of 35 μ/g/kg b.wt in male albino mice as a radio-protective agent pre-exposure to gamma irradiation. This was accomplished through measuring follicular stimulating hormone (FSH), luteinizing hormone (LH) and prostaglandin-E 2 (PGE 2 ) and endothelin in plasma of mice. Meanwhile, observations of the chromosomal aberrations and sperm head abnormalities were recorded. The administration of the anabolic agent pre-irradiation resulted in slightly non-significant amelioration in the pituitary hormone levels and in levels of PGE 2 and endothelin

  3. Toxicology studies of a chemical mixture of 25 groundwater contaminants. III. Male reproduction study in B6C3F1 mice

    Energy Technology Data Exchange (ETDEWEB)

    Chapin, R.E.; Phelps, J.L.; Schwetz, B.A.; Yang, R.S. (National Institute of Environmental Health Sciences, Research Triangle Park, NC (USA))

    1989-10-01

    A mixture of chemicals has been developed that models contaminated groundwater around hazardous waste sites. We investigated the effects of this mixture on spermatogenesis in B6C3F1 mice. The animals consumed three different concentrations of this mixture for 90 days, after which time they were euthanatized. Although there was a concentration-related decrease in the amount of fluid consumed at the higher two concentrations, there were no differences in body weight among the groups. Similarly, there was no effect of mixture consumption upon the histology of liver, kidney, testis, epididymis, or seminal vesicles or upon the absolute organ weights of these organs. Kidney weight relative to body weight was increased in the high dose group. Epididymal sperm number and testicular spermatid count were not affected by treatment. These studies show that, at exposure levels that decrease fluid intake and increase adjusted kidney weight, there were no effects of this mixture on gametogenesis in male mice.

  4. A Difference in Fatty Acid Composition of Isocaloric High-Fat Diets Alters Metabolic Flexibility in Male C57BL/6JOlaHsd Mice.

    Directory of Open Access Journals (Sweden)

    Loes P M Duivenvoorde

    Full Text Available Poly-unsaturated fatty acids (PUFAs are considered to be healthier than saturated fatty acids (SFAs, but others postulate that especially the ratio of omega-6 to omega-3 PUFAs (n6/n3 ratio determines health. Health can be determined with biomarkers, but functional health status is likely better reflected by challenge tests that assess metabolic flexibility. The aim of this study was to determine the effect of high-fat diets with different fatty acid compositions, but similar n6/n3 ratio, on metabolic flexibility. Therefore, adult male mice received isocaloric high-fat diets with either predominantly PUFAs (HFpu diet or predominantly SFAs (HFs diet but similar n6/n3 ratio for six months, during and after which several biomarkers for health were measured. Metabolic flexibility was assessed by the response to an oral glucose tolerance test, a fasting and re-feeding test and an oxygen restriction test (OxR; normobaric hypoxia. The latter two are non-invasive, indirect calorimetry-based tests that measure the adaptive capacity of the body as a whole. We found that the HFs diet, compared to the HFpu diet, increased mean adipocyte size, liver damage, and ectopic lipid storage in liver and muscle; although, we did not find differences in body weight, total adiposity, adipose tissue health, serum adipokines, whole body energy balance, or circadian rhythm between HFs and HFpu mice. HFs mice were, furthermore, less flexible in their response to both fasting- re-feeding and OxR, while glucose tolerance was indistinguishable. To conclude, the HFs versus the HFpu diet increased ectopic fat storage, liver damage, and mean adipocyte size and reduced metabolic flexibility in male mice. This study underscores the physiological relevance of indirect calorimetry-based challenge tests.

  5. Anabolic-androgenic steroid treatment induces behavioral disinhibition and downregulation of serotonin receptor messenger RNA in the prefrontal cortex and amygdala of male mice.

    Science.gov (United States)

    Ambar, G; Chiavegatto, S

    2009-03-01

    Nandrolone is an anabolic-androgenic steroid (AAS) that is highly abused by individuals seeking enhanced physical strength or body appearance. Supraphysiological doses of this synthetic testosterone derivative have been associated with many physical and psychiatric adverse effects, particularly episodes of impulsiveness and overt aggressive behavior. As the neural mechanisms underlying AAS-induced behavioral disinhibition are unknown, we investigated the status of serotonergic system-related transcripts in several brain areas of mice receiving prolonged nandrolone administration. Male C57BL/6J mice received 15 mg/kg of nandrolone decanoate subcutaneously once daily for 28 days, and different sets of animals were used to investigate motor-related and emotion-related behaviors or 5-HT-related messenger RNA (mRNA) levels by real-time quantitative polymerase chain reaction. AAS-injected mice had increased body weight, were more active and displayed anxious-like behaviors in novel environments. They exhibited reduced immobility in the forced swim test, a higher probability of being aggressive and more readily attacked opponents. AAS treatment substantially reduced mRNA levels of most investigated postsynaptic 5-HT receptors in the amygdala and prefrontal cortex. Interestingly,the 5-HT(1B) mRNA level was further reduced in the hippocampus and hypothalamus. There was no alteration of 5-HT system transcript levels in the midbrain. In conclusion,high doses of AAS nandrolone in male mice recapitulate the behavioral disinhibition observed in abusers. Furthermore, these high doses downregulate 5-HT receptor mRNA levels in the amygdala and prefrontal cortex. Our combined findings suggest these areas as critical sites for AAS-induced effects and a possible role for the 5-HT(1B) receptor in the observed behavioral disinhibition.

  6. Whole-body aerosol exposure of cadmium chloride (CdCl{sub 2}) and tetrabromobisphenol A (TBBPA) induced hepatic changes in CD-1 male mice

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yuanhong; Hu, Yabing; Liu, Shuyun; Zheng, Huiying; Wu, Xiaojuan; Huang, Zhengyu; Li, Hao; Peng, Baoqi; Long, Jinlie [Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou 325035 (China); Pan, Bishu [Taizhou Center for Disease Control and Prevention, Taizhou 318000 (China); Huang, Changjiang, E-mail: cjhuang5711@163.com [Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou 325035 (China); Dong, Qiaoxiang, E-mail: dqxdong@163.com [Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou 325035 (China)

    2016-11-15

    Highlights: • Hepatotoxicity of TBBPA and Cd aerosol co-exposure was evaluated in CD-1 male mice. • Hepatic changes include focal necrosis, increased organ weight, and elevated enzymes. • TBBPA group exhibited highest hepatic toxicity followed by co-exposure and Cd groups. • We did not observe any synergistic effect of hepatic toxicity between TBBPA and Cd. • TBBPA/Cd suppressed antioxidant defensive mechanisms and increased oxidative stress. - Abstract: Cadmium (Cd) and tetrabromobisphenol A (TBBPA) are two prevalent contaminants in e-waste recycling facilities. However, the potential adversely health effect of co-exposure to these two types of pollutants in an occupational setting is unknown. In this study, we investigated co-exposure of these two pollutants on hepatic toxicity in CD-1 male mice through a whole-body aerosol inhalation route. Specifically, mice were exposed to solvent control (5% DMSO), Cd (8 μg/m{sup 3}), TBBPA (16 μg/m{sup 3}) and Cd/TBBPA mixture for 8 h/day and 6 days a week for 60 days. Hepatic changes include increased organ weight, focal necrosis, and elevated levels of liver enzymes in serum. These changes were most severe in mice exposed to TBBPA, followed by Cd/TBBPA mixture and Cd. These chemicals also led to suppressed antioxidant defensive mechanisms and increased oxidative stress. Further, these chemicals induced gene expression of apoptosis-related genes, activated genes encoding for phase I detoxification enzymes and inhibited genes encoding for phase II detoxification enzymes. These findings indicate that the hepatic damages induced by subchronic aerosol exposure of Cd and TBBPA may result from the oxidative damages caused by excessive ROS production when these chemicals were metabolized in the liver.

  7. Preventative topical diclofenac treatment differentially decreases tumor burden in male and female Skh-1 mice in a model of UVB-induced cutaneous squamous cell carcinoma

    Science.gov (United States)

    Oberyszyn, Tatiana M.

    2013-01-01

    Ultraviolet B (UVB) light is the major environmental carcinogen contributing to non-melanoma skin cancer (NMSC) development. There are over 3.5 million NMSC diagnoses in two million patients annually, with men having a 3-fold greater incidence of squamous cell carcinoma (SCC) compared with women. Chronic inflammation has been linked to tumorigenesis, with a key role for the cyclooxygenase-2 (COX-2) enzyme. Diclofenac, a COX-2 inhibitor and non-steroidal anti-inflammatory drug, currently is prescribed to patients as a short-term therapeutic agent to induce SCC precursor lesion regression. However, its efficacy as a preventative agent in patients without evidence of precursor lesions but with significant UVB-induced cutaneous damage has not been explored. We previously demonstrated in a murine model of UVB-induced skin carcinogenesis that when exposed to equivalent UVB doses, male mice had lower levels of inflammation but developed increased tumor multiplicity, burden and grade compared with female mice. Because of the discrepancy in the degree of inflammation between male and female skin, we sought to determine if topical treatment of previously damaged skin with an anti-inflammatory COX-2 inhibitor would decrease tumor burden and if it would be equally effective in the sexes. Our results demonstrated that despite observed sex differences in the inflammatory response, prolonged topical diclofenac treatment of chronically UVB-damaged skin effectively reduced tumor multiplicity in both sexes. Unexpectedly, tumor burden was significantly decreased only in male mice. Our data suggest a new therapeutic use for currently available topical diclofenac as a preventative intervention for patients predisposed to cutaneous SCC development before lesions appear. PMID:23125227

  8. Designing a New Nano-Plant Composite of Cucurbita pepo for Wound Repair of Skin in Male Albino Mice: A New Nano Approach for Skin Repair

    Directory of Open Access Journals (Sweden)

    Nooshin Naghsh

    2013-06-01

    Full Text Available Background & Objective : The Cucurbita pepo is one of plants that are functional in traditional therapy. This plant has antioxidant and skin damage repair properties. This study investigated the effect of Cucurbita pepo nano silver as a new nano-plant composition in wound repair skin in male mice.   Materials & Methods: In this investigation, male albino mice were places in 8 groups, each containing 8 animals. Group I – VIII were treated with nano silver (500, 250, and 125 ppm concentrations and different concentrations of extracts [70%, 50%, and 25%] and the control group received a mixture of 25% Cucurbita pepo extract (125 ppm nano silver. The eighth group, as control, was treated with sterile deionizer water after the induction of wound skin. The average diameter of the wounds was measured 28 days after treatment in the control and treatment groups. These data were analyzed using the t-test and ANOVA statistical method.   Results: The results of this study showed that ethanol extraction (80% has its highest repair effect 28 days post treatment. The average diameter of the wounds in the control group was 1.16 ±. 0.46 cm, which was decreased to 0 cm and 0.12 ±. 0.23 cm in the ethanol extract (70% of the Cucurbita pepo and component groups, respectively (p value ≤ 0.01.   Conclusion: In this project, nano silver-Cucurbita pepo ethanol extraction for wound repair in albino male mice was more effective than single materials. These findings show that the repair synergic effects are between alcoholic extract and nano silver in this nano composite.

  9. The Potent Humanin Analogue (HNG) Protects Germ Cells and Leucocytes While Enhancing Chemotherapy-Induced Suppression of Cancer Metastases in Male Mice.

    Science.gov (United States)

    Lue, YanHe; Swerdloff, Ronald; Wan, Junxiang; Xiao, Jialin; French, Samuel; Atienza, Vince; Canela, Victor; Bruhn, Kevin W; Stone, Brian; Jia, Yue; Cohen, Pinchas; Wang, Christina

    2015-12-01

    Humanin is a peptide that is cytoprotective against stresses in many cell types. We investigated whether a potent humanin analogue S14G-humanin (HNG) would protect against chemotherapy-induced damage to normal cells without interfering with the chemotherapy-induced suppression of cancer cells. Young adult male mice were inoculated iv with murine melanoma cells. After 1 week, cancer-bearing mice were randomized to receive either: no treatment, daily ip injection of HNG, a single ip injection of cyclophosphamide (CP), or CP+HNG and killed at the end of 3 weeks. HNG rescued the CP-induced suppression of leucocytes and protected germ cell from CP-induced apoptosis. Lung metastases were suppressed by HNG or CP alone, and further suppressed by CP+HNG treatment. Plasma IGF-1 levels were suppressed by HNG with or without CP treatment. To investigate whether HNG maintains its protective effects on spermatogonial stem cells, sperm output, and peripheral leucocytes after repeated doses of CP, normal adult male mice received: no treatment, daily sc injection of HNG, 6 ip injections of CP at 5-day intervals, and the same regimens of CP+HNG and killed at the end of 4 weeks of treatment. Cauda epididymal sperm counts were elevated by HNG and suppressed by CP. HNG rescued the CP-induced suppression of spermatogonial stem cells, sperm count and peripheral leucocytes. We conclude that HNG 1) protects CP-induced loss of male germ cells and leucocytes, 2) enhances CP-induced suppression of cancer metastases, and 3) acts as a caloric-restriction mimetic by suppressing IGF-1 levels. Our findings suggest that humanin analogues may be promising adjuvants to chemotherapy.

  10. Sendai Virus Mucosal Vaccination Establishes Lung-Resident Memory CD8 T Cell Immunity and Boosts BCG-Primed Protection against TB in Mice.

    Science.gov (United States)

    Hu, Zhidong; Wong, Ka-Wing; Zhao, Hui-Min; Wen, Han-Li; Ji, Ping; Ma, Hui; Wu, Kang; Lu, Shui-Hua; Li, Feng; Li, Zhong-Ming; Shu, Tsugumine; Xu, Jian-Qing; Lowrie, Douglas B; Fan, Xiao-Yong

    2017-05-03

    Accumulating evidence has shown the protective role of CD8 + T cells in vaccine-induced immunity against Mycobacterium tuberculosis (Mtb) despite controversy over their role in natural immunity. However, the current vaccine BCG is unable to induce sufficient CD8 + T cell responses, especially in the lung. Sendai virus, a respiratory RNA virus, is here engineered firstly as a novel recombinant anti-TB vaccine (SeV85AB) that encodes Mtb immuno-dominant antigens, Ag85A and Ag85B. A single mucosal vaccination elicited potent antigen-specific T cell responses and a degree of protection against Mtb challenge similar to the effect of BCG in mice. Depletion of CD8 + T cells abrogated the protective immunity afforded by SeV85AB vaccination. Interestingly, only SeV85AB vaccination induced high levels of lung-resident memory CD8 + T (T RM ) cells, and this led to a rapid and strong recall of antigen-specific CD8 + T cell responses against Mtb challenge infection. Furthermore, when used in a BCG prime-SeV85AB boost strategy, SeV85AB vaccine significantly enhanced protection above that seen after BCG vaccination alone. Our findings suggest that CD8 + T RM cells that arise in lungs responding to this mucosal vaccination might help to protect against TB, and SeV85AB holds notable promise to improve BCG's protective efficacy in a prime-boost immunization regimen. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  11. Oestrogen at the neonatal stage is critical for the reproductive ability of male mice as revealed by supplementation with 17beta-oestradiol to aromatase gene (Cyp19) knockout mice.

    Science.gov (United States)

    Toda, K; Okada, T; Takeda, K; Akira, S; Saibara, T; Shiraishi, M; Onishi, S; Shizuta, Y

    2001-03-01

    Aromatase P450 (CYP19) is an enzyme responsible for the conversion of androgens to oestrogens. We generated CYP19 knockout (ArKO) mice by targeted disruption of Cyp19 and studied the role of oestrogens in male reproductive ability. Approximately 85% of ArKO males were unable to sire offspring. However, no obvious difference was found in testicular and epididymal weights, numbers of sperm in the epididymis or the ability of sperm to fertilize eggs in vitro between wild-type and ArKO males. An examination of mating behaviour demonstrated that ArKO males showed an impairment in mounting behaviour against sexually mature females. The inability of more than 90% of ArKO males to sire offspring was reversed by repeated subcutaneous injections of 17beta-oestradiol when initiated on the day of birth. The effects of 17beta-oestradiol on reproduction were concentration dependent and evident when supplementation was initiated on day 7, but not on day 15 after birth. These findings suggest that oestrogens acting during neonatal life are required for normal mating behaviour in adulthood.

  12. Chronic sleep fragmentation during the sleep period induces hypothalamic endoplasmic reticulum stress and PTP1b-mediated leptin resistance in male mice.

    Science.gov (United States)

    Hakim, Fahed; Wang, Yang; Carreras, Alba; Hirotsu, Camila; Zhang, Jing; Peris, Eduard; Gozal, David

    2015-01-01

    Sleep fragmentation (SF) is highly prevalent and may constitute an important contributing factor to excessive weight gain and the metabolic syndrome. Increased endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) leading to the attenuation of leptin receptor signaling in the hypothalamus leads to obesity and metabolic dysfunction. Mice were exposed to SF and sleep control (SC) for varying periods of time during which ingestive behaviors were monitored. UPR pathways and leptin receptor signaling were assessed in hypothalami. To further examine the mechanistic role of ER stress, changes in leptin receptor (ObR) signaling were also examined in wild-type mice treated with the ER chaperone tauroursodeoxycholic acid (TUDCA), as well as in CHOP-/+ transgenic mice. Fragmented sleep in male mice induced increased food intake starting day 3 and thereafter, which was preceded by increases in ER stress and activation of all three UPR pathways in the hypothalamus. Although ObR expression was unchanged, signal transducer and activator of transcription 3 (STAT3) phosphorylation was decreased, suggesting reduced ObR signaling. Unchanged suppressor of cytokine signaling-3 (SOCS3) expression and increases in protein-tyrosine phosphatase 1B (PTP1B) expression and activity emerged with SF, along with reduced p-STAT3 responses to exogenous leptin. SF-induced effects were reversed following TUDCA treatment and were absent in CHOP -/+ mice. SF induces hyperphagic behaviors and reduced leptin signaling in hypothalamus that are mediated by activation of ER stress, and ultimately lead to increased PTP1B activity. ER stress pathways are therefore potentially implicated in SF-induced weight gain and metabolic dysfunction, and may represent a viable therapeutic target. © 2014 Associated Professional Sleep Societies, LLC.

  13. The role of bile salt composition in liver pathology of mdr2 (-/-) mice: differences between males and females

    NARCIS (Netherlands)

    van Nieuwerk, C. M.; Groen, A. K.; Ottenhoff, R.; van Wijland, M.; van den Bergh Weerman, M. A.; Tytgat, G. N.; Offerhaus, Johan J. A.; Oude Elferink, R. P.

    1997-01-01

    BACKGROUND/AIMS: The mouse mdr2 gene encodes a P-glycoprotein expressed in the canalicular membrane of the hepatocyte. Mice in which this gene has been inactivated (mdr2 -/-) show a defect in biliary phospholipid and cholesterol secretion and develop non-suppurative cholangitis. We hypothesized that

  14. An improved procedure for integrated behavioral z-scoring illustrated with modified Hole Board behavior of male inbred laboratory mice

    NARCIS (Netherlands)

    Labots, M.|info:eu-repo/dai/nl/411290835; Laarakker, M.C.; Schetters, D.; Arndt, S.S.|info:eu-repo/dai/nl/30483615X; van Lith, H.A.|info:eu-repo/dai/nl/091342422

    2018-01-01

    Background: Guilloux et al. introduced: integrated behavioral z-scoring, a method for behavioral pheno-typing of mice. Using this method multiple ethological variables can be combined to show an overall description of a certain behavioral dimension or motivational system. However, a problem may

  15. THE EFFECT OF FICUS CARICA L. (ANJIR) LEAF EXTRACT ON GENTAMICIN INDUCED NEPHROTOXICITY IN ADULT MALE ALBINO MICE.

    Science.gov (United States)

    Ghaffar, Ammara; Tahir, Mohammad; Lone, Khalid Pervez; Faisal, Bushra; Latif, Waqas

    2015-01-01

    Gentamicin is an aminoglycoside isolated from Micromonospora purpurea known for its nephrotoxicity. Ficus carica L is known to treat many ailments. This study was designed to investigate the effects of Ficus carica L. (Anjir) leaf extract on renal oxidative stress induced by gentamicin in albino mice. In this laboratory based experimental study 30 mice were divided into three groups, containing 10 mice each. Group A being the control; groups B and C were experimental and treated with gentamicin 200 mg/kg/day intraperitoneally and, Ficus carica L. leaf extract 400 mg/kg/day orally with gentamicin 200 mg/kg/day intraperitoneally respectively for a period of 8 days. Blood samples were taken 24 hours after completion of the experimental period by cardiac puncture under anesthesia and kidneys of each mouse were taken out for microscopic examination. Gentamicin treatment increased serum urea and creatinine levels (group B). Ficus carica L. leaf extract treated animals showed significant reduction in biochemical markers of kidney functions in group C. The histopathological examination of group A showed normal renal structure which was deranged in group B treated with only gentamicin, whereas, group C exhibited marked improvement in histological structure. Ficus carica L. leaf extract is effective in preventing gentamicin induced functional and structural changes in kidney of albino mice.

  16. Genetic effects from radioactive isotopes. VI.Embryonal lethality in first progeny of male mice treated with phosphorus 32 in the premeiotic phase

    International Nuclear Information System (INIS)

    Baev, I.; Bajrakova, A.; Manchev, V.

    1975-01-01

    Sexually mature male mice of BAL B/C line were given by single intraperitoneal injection different activities (25, 50, 75 and 135 μCi) of phosghorus-32 as aqueous Na 2 HPO 4 solution. Ninety days after treatment each male was coupled for four weeks with five intact sexually mature females of C57BL line. Dissection of fecundated females was made, and the pre- and post-implantation mortality was estimated together with the overall loss in the first progeny and the incidence of induced dominant lethal mutations. Phosphorus-32 displayed mutagenic effectiveness for mouse spermatogonial cells. The degree of induced genetic injury differed depending on the incorporated activity; it was not demonstrable at 25 μCi/mouse, reached a maximum at 75 μCi/mouse and tended to decrease at 135 μCi/mouse. (Ch.K.)

  17. Anti-epileptogenic and antioxidant effect of Lavandula officinalis aerial part extract against pentylenetetrazol-induced kindling in male mice.

    Science.gov (United States)

    Rahmati, Batool; Khalili, Mohsen; Roghani, Mehrdad; Ahghari, Parisa

    2013-06-21

    Repeated application of Lavandula officinalis (L. officinalis) has been recommended for a long time in Iranian traditional medicine for some of nervous disorders like epilepsy and dementia. However, there is no available report for the effect of chronic administration of Lavandula extract in development (acquisition) of epilepsy. Therefore, this study was designed to investigate the anti-epileptogenic and antioxidant activity of repeated administration of Lavandula officinalis extract on pentylenetetrazol (PTZ) kindling seizures in mice model. Lavandula officinalis was tested for its ability (i) to suppress the seizure intensity and lethal effects of PTZ in kindled mice (anti-epileptogenic effect), (ii) to attenuate the PTZ-induced oxidative injury in the brain tissue (antioxidant effect) when given as a pretreatment prior to each PTZ injection during kindling development. Valproate (Val), a major antiepileptic drug, was also tested for comparison. Val and Lavandula officinalis extract showed anti-epileptogenic properties as they reduced seizure score of kindled mice and PTZ-induced mortality. In this regard, Lavandula officinalis was more effective than Val. Both Lavandula officinalis and Val suppressed brain nitric oxide (NO) level of kindled mice in comparison with the control and PTZ group. Meanwhile, Lavandula officinalis suppressed NO level more than Val and Lavandula officinalis also decreased brain MDA level relative to PTZ group. This is the first report to demonstrate NO suppressing and anti-epileptogenic effect of chronic administration of Lavandula officinalis extract on acquisition of epilepsy in PTZ kindling mice model. In this regard, Lavandula officinalis extract was more effective than Val, possibly and in part via brain NO suppression. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  18. Evaluation of buprenorphine hydrochloride Pluronic® gel formulation in male C57BL/6NCrl mice

    Science.gov (United States)

    Blankenship-Paris, Terry L.; Dutton, John W.; Goulding, David R.; McGee, Christopher A.; Kissling, Grace E.; Myers, Page H.

    2016-01-01

    Providing adequate analgesia while minimizing handling and stress post-surgery can be challenging. Recently, there have been commercial products made available for providing long acting analgesia in rodents. However, we find there are limitations for use in mice due to the viscosity of the product and the small dosing volumes needed. This project evaluated an in-house compounded formulation of buprenorphine easily made in the laboratory using pharmaceutical grade products. The release of buprenorphine was evaluated when compounded with two types of hydrogels (Pluronic® F-127 and F-68). Mice given buprenorphine in hydrogel (BP) demonstrated higher serum levels of buprenorphine for a longer period of time compared to mice given standard buprenorphine (Bup). However, the rate of decline in serum levels between the groups was similar; thus, it is more likely that the higher buprenorphine concentration seen in the BP group is due to the higher dose of buprenorphine given, rather than a slower release of product. Feed consumption was decreased in both groups one day after dosing; however, there was no difference in body weights. Increased activity in the open field was observed with both buprenorphine formulations, and lipemia was observed in mice given BP which persisted to at least 96 h. Based on our results, we conclude that this formulation did not sustain the release of buprenorphine or eliminate the increased activity commonly seen in mice given buprenorphine. In addition, the lipemia may confound research parameters, especially in cardiac studies and lipid metabolism studies. Therefore, we cannot recommend this formulation for use. PMID:27654688

  19. Evaluation of buprenorphine hydrochloride Pluronic(®) gel formulation in male C57BL/6NCrl mice.

    Science.gov (United States)

    Blankenship-Paris, Terry L; Dutton, John W; Goulding, David R; McGee, Christopher A; Kissling, Grace E; Myers, Page H

    2016-09-21

    Providing adequate analgesia while minimizing handling and stress post-surgery can be challenging. Recently, there have been commercial products made available for providing long acting analgesia in rodents. However, we find there are limitations for use in mice due to the viscosity of the product and the small dosing volumes needed. This project evaluated an in-house compounded formulation of buprenorphine easily made in the laboratory using pharmaceutical grade products. The release of buprenorphine was evaluated when compounded with two types of hydrogels (Pluronic(®) F-127 and F-68). Mice given buprenorphine in hydrogel (BP) demonstrated higher serum levels of buprenorphine for a longer period of time compared to mice given standard buprenorphine (Bup). However, the rate of decline in serum levels between the groups was similar; thus, it is more likely that the higher buprenorphine concentration seen in the BP group is due to the higher dose of buprenorphine given, rather than a slower release of product. Feed consumption was decreased in both groups one day after dosing; however, there was no difference in body weights. Increased activity in the open field was observed with both buprenorphine formulations, and lipemia was observed in mice given BP which persisted to at least 96 h. Based on our results, we conclude that this formulation did not sustain the release of buprenorphine or eliminate the increased activity commonly seen in mice given buprenorphine. In addition, the lipemia may confound research parameters, especially in cardiac studies and lipid metabolism studies. Therefore, we cannot recommend this formulation for use.

  20. L-arginine supplementation prevents increases in intestinal permeability and bacterial translocation in male Swiss mice subjected to physical exercise under environmental heat stress.

    Science.gov (United States)

    Costa, Kátia Anunciação; Soares, Anne Danieli Nascimento; Wanner, Samuel Penna; Santos, Rosana das Graças Carvalho dos; Fernandes, Simone Odília Antunes; Martins, Flaviano dos Santos; Nicoli, Jacques Robert; Coimbra, Cândido Celso; Cardoso, Valbert Nascimento

    2014-02-01

    Dietary supplementation with l-arginine has been shown to improve the intestinal barrier in many experimental models. This study investigated the effects of arginine supplementation on the intestinal permeability and bacterial translocation (BT) induced by prolonged physical exercise under heat stress. Under anesthesia, male Swiss mice (5-wk-old) were implanted with an abdominal sensor to record their core body temperature (T(core)). After recovering from surgery, the mice were divided into 3 groups: a non-supplemented group that was fed the standard diet formulated by the American Institute of Nutrition (AIN-93G; control), a non-supplemented group that was fed the AIN-93G diet and subjected to exertional hyperthermia (H-NS), and a group supplemented with l-arginine at 2% and subjected to exertional hyperthermia (H-Arg). After 7 d of treatment, the H-NS and H-Arg mice were forced to run on a treadmill (60 min, 8 m/min) in a warm environment (34°C). The control mice remained at 24°C. Thirty min before the exercise or control trials, the mice received a diethylenetriamine pentaacetic acid (DTPA) solution labeled with technetium-99m ((99m)Tc-DTPA) or (99m)Tc-Escherichia coli by gavage to assess intestinal permeability and BT, respectively. The H-NS mice terminated the exercise with T(core) values of ∼40°C, and, 4 h later, presented a 12-fold increase in the blood uptake of (99m)Tc-DTPA and higher bacterial contents in the blood and liver than the control mice. Although supplementation with arginine did not change the exercise-induced increase in T(core), it prevented the increases in intestinal permeability and BT caused by exertional hyperthermia. Our results indicate that dietary l-arginine supplementation preserves the integrity of the intestinal epithelium during exercise under heat stress, acting through mechanisms that are independent of T(core) regulation.

  1. Peak littering and the stud male in relation to virgin and remated female P(SD) mice.

    Science.gov (United States)

    Eveleigh, J R; Gunner, M; Haslam, F

    1979-01-01

    Peak littering occurred on the 22nd day after pairing. The percentage of pregnancies from virgin females increased as the stud males became more experienced; their success with remated females showed a more varied and lower response.

  2. Satisfaction among residents in ASHP-accredited pharmacy residency programs.

    Science.gov (United States)

    VanDenBerg, C; Murphy, J E

    1997-07-01

    The level of work satisfaction among pharmacists in ASHP-accredited residencies was studied. In March 1996 a questionnaire designed to measure residency satisfaction was mailed to 697 individuals in ASHP-accredited pharmacy practice and specialty practice residencies. Subjects responded to 16 statements relating to intrinsic and extrinsic determinants of work satisfaction on a scale of 1 to 5, where 1 = strongly disagree and 5 = strongly agree. Questionnaires were returned by 413 (59%) of the residents. The respondents were predominantly women (76%), and most (86%) had at least a Pharm. D. degree. Hospitals were the primary work setting (88%). Of the 413 residents, 305 were in pharmacy practice residencies and 108 were in specialized residencies. None of the mean scores indicated disagreement (scores 3) with the negatively worded statements. The median and mode were equal to 2 (disagree) for the three negatively worded items and 4 (agree) for all but three positively worded items. Only 8% of the residents indicated that they would not accept the residency again if given the chance. Specialized residents tended to rate positively worded statements higher and negatively worded statements lower than pharmacy practice residents. Female residents indicated greater satisfaction than male residents. Pay and benefits were rated slightly better than neutral. Pharmacy residents appeared generally satisfied with their residencies. Specialized pharmacy residents were more satisfied than pharmacy practice residents, and women were more satisfied than men.

  3. Role of miR-383 and miR-146b in different propensities to obesity in male mice.

    Science.gov (United States)

    Xia, Shu-Fang; Duan, Xiao-Mei; Cheng, Xiang-Rong; Chen, Li-Mei; Kang, Yan-Jun; Wang, Peng; Tang, Xue; Shi, Yong-Hui; Le, Guo-Wei

    2017-08-01

    The study was designed to investigate the possible mechanisms of hepatic microRNAs (miRs) in regulating local thyroid hormone (TH) action and ultimately different propensities to high-fat diet (HFD)-induced obesity. When obesity-prone (OP) and obesity-resistant (OR) mice were fed HFD for 7 weeks, OP mice showed apparent hepatic steatosis, with significantly higher body weight and lower hepatic TH receptor b (TRb) expression and type 1 deiodinase (DIO1) activity than OR mice. Next-generation sequencing technology revealed that 13 miRs in liver were dysregulated between the two phenotypes, of which 8 miRs were predicted to target on Dio1 or TRb When mice were fed for 17 weeks, OR mice had mild hepatic steatosis and increased Dio1 and TRb expression than OP mice, with downregulation of T3 target genes (including Srebp1c , Acc1 , Scd1 and Fasn ) and upregulation of Cpt1α , Atp5c1 , Cox7c and Cyp7a1 A stem-loop qRT-PCR analysis confirmed that the levels of miR-383, miR-34a and miR-146b were inversely correlated with those of DIO1 or TRb. Down-regulated expression of miR-383 or miR-146b by miR-383 inhibitor (anti-miR-383) or miR-146b inhibitor (anti-miR-146b) in free fatty acid-treated primary mouse hepatocytes led to increased DIO1 and TRb expressions, respectively, and subsequently decreased cellular lipid accumulation, while miR-34a inhibitor (anti-miR-34a) transfection had on effects on TRb expression. Luciferase reporter assay illustrated that miR-146b could directly target TRb 3'untranslated region (3'UTR). These findings suggested that miR-383 and miR-146b might play critical roles in different propensities to diet-induced obesity via targeting on Dio1 and TRb , respectively. © 2017 Society for Endocrinology.

  4. Hormonal and organ-specific dysfunction induced by the interaction between titanium dioxide nanoparticles and salicylic acid in male mice.

    Science.gov (United States)

    El-Shenawy, Nahla S; Al-Harbi, Mohammad S; Al Hamayani, Fatimah F E

    2016-06-01

    Nanomaterials coating gained much concern in orthopedic implants and cosmetics. Drug combination may be a promising strategy for treating multi-factorial diseases. Titanium dioxide (TDN) nanoparticles are being widely used in many industries as well as in medicine and pharmacology. Therefore, increased human and environmental exposure can be expected, which has put TDN under toxicological scrutiny, and it is necessary to address the potential health and safety implications of nanomaterials used in nanomedicine. The toxicity of titanium oxide nanoparticles (TDN) and salicylic acid (SA) separately or in combination was studied for 21 days. The liver and kidney biomarker were determined, and hormones and oxidative stress levels were detected in mice. The intraperitoneal (i.p.) injection of TDN and SA in combination had a potential toxicological effect on major organs and hormonal homeostasis of mice. TDN and SA could antagonistically interact to affect the liver and kidney functions. No synergistic damage was observed in the liver function of mice that were treated with both TDN and SA as compared to the SA group. TDN acted as a synergistic agent to SA in the case of total cholesterol and total proteins levels. SA acted as antagonistic to the effect of TDN when injected together in mice because the effect on kidney functions is less than that predicted on the basis of the additive. The effect of co-administration of SA and TDN on the following hormones; triiodothyronine, thyroxine, estradiol II and insulin various among additive, potentiation, antagonistic and no effect, respectively as compared to TDN group. The interaction of TDN and SA was also found to induce oxidative stress as indicated by the increase in lipid peroxidation (LPO) levels. The decrease in the level of the reduced glutathione in the co-treated group indicated that there were no synergistic damages. SA and TDN co-administration could induce a potential increase in LPO levels in liver, kidney, and

  5. Effectiveness of Changing the Application of Japanese Honey to a Hydrocolloid Dressing in Between the Inflammatory and Proliferative Phases on Cutaneous Wound Healing in Male Mice.

    Science.gov (United States)

    Mukai, Kanae; Komatsu, Emi; Yamanishi, Misa; Hutakuchi, Misako; Kanzaka, Kayo; Uno, Yuka; Yamazaki, Shizuka; Kato, Shizuka; Yamamoto, Tomomi; Hattori, Mayumi; Nakajima, Yukari; Urai, Tamae; Asano, Kimi; Murakado, Naoko; Okuwa, Mayumi; Nakatani, Toshio

    2017-01-01

    The aim of this study was to investigate the effects of changing the application of Japanese honey to a hydrocolloid dressing (HCD) in between the inflammatory and proliferative phases on cutaneous wound healing in 8-week-old, BALB/cCrSlc male mice. Mice were divided into 4 groups: acacia honey followed by a HCD, buckwheat flour honey followed by a HCD, Chinese milk vetch honey followed by a HCD, and a HCD alone (control group). All mice received 2 full-thickness wounds on both sides of the dorsum using a Disposable Biopsy Punch. The wounds of the control group were covered with a HCD, whereas wounds in the other groups were treated with 0.1 mL of the relevant type of honey until day 3 post-wound and then were covered with a HCD from days 4 to 14. In the experimental groups, the wound area ratio was significantly smaller in the inflammatory phase but significantly larger in the proliferative phase. Reepithelialization, collagen deposition, and wound contraction were significantly delayed compared with those in the control group. The re-expansion of the wounds in the proliferative phase could not be prevented, and reepithelialization, collagen deposition, and wound contraction were delayed compared with those upon the use of a HCD. The study's authors concluded that these methods do not promote cutaneous wound healing better than the use of a HCD alone.

  6. NOAEL-dose of a neonicotinoid pesticide, clothianidin, acutely induce anxiety-related behavior with human-audible vocalizations in male mice in a novel environment.

    Science.gov (United States)

    Hirano, Tetsushi; Yanai, Shogo; Takada, Tadashi; Yoneda, Naoki; Omotehara, Takuya; Kubota, Naoto; Minami, Kiichi; Yamamoto, Anzu; Mantani, Youhei; Yokoyama, Toshifumi; Kitagawa, Hiroshi; Hoshi, Nobuhiko

    2018-01-05

    Neonicotinoids are novel systemic pesticides acting as agonists on the nicotinic acetylcholine receptors (nAChRs) of insects. Experimental studies have revealed that neonicotinoids pose potential risks for the nervous systems of non-target species, but the brain regions responsible for their behavioral effects remain incompletely understood. This study aimed to assess the neurobehavioral effects of clothianidin (CTD), a later neonicotinoid developed in 2001 and widely used worldwide, and to explore the target regions of neonicotinoids in the mammalian brain. A single-administration of 5 or 50mg/kg CTD to male C57BL/6N mice at or below the no-observed-adverse-effect level (NOAEL) induced an acute increase in anxiety during the elevated plus-maze test. In addition, mice in the CTD-administered group spontaneously emitted human-audible vocalizations (4-16kHz), which are behavioral signs of aversive emotions, and showed increased numbers of c-fos immunoreactive cells in the paraventricular thalamic nucleus and dentate gyrus of the hippocampus. In conclusion, mice exposed to NOAEL-dose CTD would be rendered vulnerable to a novel environment via the activation of thalamic and hippocampal regions related to stress responses. These findings should provide critical insight into the neurobehavioral effects of neonicotinoids on mammals. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Susceptibility and morbidity between male and female Swiss mice infected with Angiostrongylus costaricensis: Susceptibilidade e morbidade entre camundongos Swiss machos e fêmeas infectados com Angiostrongylus costaricensis

    Directory of Open Access Journals (Sweden)

    Márcia B. Mentz

    2010-10-01

    Full Text Available The gender of vertebrate hosts may affect the outcome of parasitic infections. An experimental murine infection with Angiostrongylus costaricensis was followed with determinations of body weight, fecal larval elimination, number and length of adult worms, number of macroscopic intestinal lesions, and mortality. Groups of male and female Swiss mice were infected with 10 3rd-stage A. costaricensis larvae per animal. The results indicate there are no significant differences related to gender of the host, except for higher length of worms developed in male mice.O sexo dos hospedeiros vertebrados pode influenciar no resultado de infecções parasitárias. A infecção experimental de camundongos com Angiostrongylus costaricensis foi acompanhada com observação do peso corporal, eliminação de larvas nas fezes, número e comprimento dos vermes adultos, número de lesões macroscópicas nos intestinos e mortalidade. Grupos de camundongos Swiss machos e fêmeas foram infectados cada um com 10 larvas de terceiro estágio de A. costaricensis. Os resultados indicam que não há diferenças significativas relacionados ao sexo dos hospedeiros, exceto pelo maior comprimento dos vermes nos hospedeiros machos.

  8. Prenatal PPARα activation by clofibrate increases subcutaneous fat browning in male C57BL/6J mice fed a high-fat diet during adulthood.

    Science.gov (United States)

    Chen, Szu-Han; Chao, Pei-Min

    2017-01-01

    We tested the hypothesis that prenatal administration of PPARα agonist clofibrate may permanently increase browning capacity of developing white adipose tissue (WAT). Pregnant C57BL/6J mice were fed a basal diet, without (C) or with 0.5% clofibrate (CF, a PPARα agonist) throughout pregnancy. After parturition, only male offspring were used; all suckled their mothers (who were eating the C diet) and after weaning, they ate a standard chow diet for 4 wk, followed by a high-fat diet (HFD) for 5 wk. Administration of CF up-regulated serum concentrations and hepatic expression of FGF21 in fetuses, with a return to basal levels after CF withdrawal. At postnatal day 84 (P84), CF-offspring had significantly higher expression of thermogenic genes (Ucp1, Cidea, Ppara Ppargc1a, Cpt1b) and UCP1 protein levels in response to HFD in inguinal fat, but not in retroperitoneal (combined with perirenal) or epididymal fat. Based on UCP1 levels in inguinal fat on P7, P14, and P21, appearance of the transient brown-adipocyte phenotype seemed to be hastened by CF exposure. We concluded that giving CF to pregnant mice programmed greater HFD-induced WAT browning in subcutaneous, but not in visceral fat, in their male offspring at adulthood.

  9. Prenatal PPARα activation by clofibrate increases subcutaneous fat browning in male C57BL/6J mice fed a high-fat diet during adulthood.

    Directory of Open Access Journals (Sweden)

    Szu-Han Chen

    Full Text Available We tested the hypothesis that prenatal administration of PPARα agonist clofibrate may permanently increase browning capacity of developing white adipose tissue (WAT. Pregnant C57BL/6J mice were fed a basal diet, without (C or with 0.5% clofibrate (CF, a PPARα agonist throughout pregnancy. After parturition, only male offspring were used; all suckled their mothers (who were eating the C diet and after weaning, they ate a standard chow diet for 4 wk, followed by a high-fat diet (HFD for 5 wk. Administration of CF up-regulated serum concentrations and hepatic expression of FGF21 in fetuses, with a return to basal levels after CF withdrawal. At postnatal day 84 (P84, CF-offspring had significantly higher expression of thermogenic genes (Ucp1, Cidea, Ppara Ppargc1a, Cpt1b and UCP1 protein levels in response to HFD in inguinal fat, but not in retroperitoneal (combined with perirenal or epididymal fat. Based on UCP1 levels in inguinal fat on P7, P14, and P21, appearance of the transient brown-adipocyte phenotype seemed to be hastened by CF exposure. We concluded that giving CF to pregnant mice programmed greater HFD-induced WAT browning in subcutaneous, but not in visceral fat, in their male offspring at adulthood.

  10. Original Research: Metabolic alterations from early life thyroxine replacement therapy in male Ames dwarf mice are transient.

    Science.gov (United States)

    Darcy, Justin; Fang, Yimin; Hill, Cristal M; McFadden, Sam; Sun, Liou Y; Bartke, Andrzej

    2016-10-01

    Ames dwarf mice are exceptionally long-lived due to a Prop1 loss of function mutation resulting in deficiency of growth hormone, thyroid-stimulating hormone and prolactin. Deficiency in thyroid-stimulating hormone and growth hormone leads to greatly reduced levels of circulating thyroid hormones and insulin-like growth factor 1, as well as a reduction in insulin secretion. Early life growth hormone replacement therapy in Ames dwarf mice significantly shortens their longevity, while early life thyroxine (T4) replacement therapy does not. Possible mechanisms by which early life growth hormone replacement therapy shortens longevity include deleterious effects on glucose homeostasis and energy metabolism, which are long lasting. A mechanism explaining why early life T4 replacement therapy does not shorten longevity remains elusive. Here, we look for a possible explanation as to why early life T4 replacement therapy does not impact longevity of Ames dwarf mice. We found that early life T4 replacement therapy increased body weight and advanced the age of sexual maturation. We also find that early life T4 replacement therapy does not impact glucose tolerance or insulin sensitivity, and any deleterious effects on oxygen consumption, respiratory quotient and heat production are transient. Lastly, we find that early life T4 replacement therapy has long-lasting effects on bone mineral density and bone mineral content. We suggest that the transient effects on energy metabolism and lack of effects on glucose homeostasis are the reasons why there is no shortening of longevity after early life T4 replacement therapy in Ames dwarf mice. © 2016 by the Society for Experimental Biology and Medicine.

  11. Motor Deficits on a Ladder Rung Task in Male and Female Adolescent and Adult CGG Knock-in Mice

    OpenAIRE

    Hunsaker, Michael R.; von Leden, Ramona E.; Ta, Binh T.; Goodrich-Hunsaker, Naomi J.; Arque, Gloria; Kim, Kyoungmi; Willemsen, Rob; Berman, Robert F.

    2011-01-01

    The fragile X premutation is a tandem CGG trinucleotide repeat expansion on the FMR1 gene between 55 and 200 repeats in length. A CGG knock-in (CGG KI) mouse with CGG trinucleotide repeat lengths between 70 and 350 has been developed and used to model the histopathology and cognitive deficits reported in carriers of the fragile X premutation. Previous studies have shown that CGG KI mice show progressive deficits in processing spatial and temporal information. To characterize the motor deficit...

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

    Directory of Open Access Journals (Sweden)

    Kiran Chaudhari

    2014-09-01

    Conclusion: Exercise was the most effective treatment at improving cognitive function in both genotypes and sex, while antioxidants seemed to be effective only in the APOE4. In young adult mice only non-spatial learning and memory were improved. The combination of the two treatments did not yield further improvement in cognition, and there was no antagonistic action of the antioxidant supplementation on the beneficial effects of exercise.

  13. Relative Biological Effectiveness of Energetic Heavy Ions for Intestinal Tumorigenesis Shows Male Preponderance and Radiation Type and Energy Dependence in APC{sup 1638N/+} Mice

    Energy Technology Data Exchange (ETDEWEB)

    Suman, Shubhankar; Kumar, Santosh; Moon, Bo-Hyun; Strawn, Steve J.; Thakor, Hemang; Fan, Ziling [Department of Biochemistry and Molecular & Cellular Biology and Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia (United States); Shay, Jerry W. [Department of Cell Biology, UT Southwestern Medical Center, Dallas, Texas (United States); Fornace, Albert J. [Department of Biochemistry and Molecular & Cellular Biology and Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia (United States); Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah (Saudi Arabia); Datta, Kamal, E-mail: kd257@georgetown.edu [Department of Biochemistry and Molecular & Cellular Biology and Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia (United States)

    2016-05-01

    Purpose: There are uncertainties associated with the prediction of colorectal cancer (CRC) risk from highly energetic heavy ion (HZE) radiation. We undertook a comprehensive assessment of intestinal and colonic tumorigenesis induced after exposure to high linear energy transfer (high-LET) HZE radiation spanning a range of doses and LET in a CRC mouse model and compared the results with the effects of low-LET γ radiation. Methods and Materials: Male and female APC{sup 1638N/+} mice (n=20 mice per group) were whole-body exposed to sham-radiation, γ rays, {sup 12}C, {sup 28}Si, or {sup 56}Fe radiation. For the >1 Gy HZE dose, we used γ-ray equitoxic doses calculated using relative biological effectiveness (RBE) determined previously. The mice were euthanized 150 days after irradiation, and intestinal and colon tumor frequency was scored. Results: The highest number of tumors was observed after {sup 28}Si, followed by {sup 56}Fe and {sup 12}C radiation, and tumorigenesis showed a male preponderance, especially after {sup 28}Si. Analysis showed greater tumorigenesis per unit of radiation (per cGy) at lower doses, suggesting either radiation-induced elimination of target cells or tumorigenesis reaching a saturation point at higher doses. Calculation of RBE for intestinal and colon tumorigenesis showed the highest value with {sup 28}Si, and lower doses showed greater RBE relative to higher doses. Conclusions: We have demonstrated that the RBE of heavy ion radiation-induced intestinal and colon tumorigenesis is related to ion energy, LET, gender, and peak RBE is observed at an LET of 69 keV/μm. Our study has implications for understanding risk to astronauts undertaking long duration space missions.

  14. Dietary Manipulations That Induce Ketosis Activate the HPA Axis in Male Rats and Mice: A Potential Role for Fibroblast Growth Factor-21.

    Science.gov (United States)

    Ryan, Karen K; Packard, Amy E B; Larson, Karlton R; Stout, Jayna; Fourman, Sarah M; Thompson, Abigail M K; Ludwick, Kristen; Habegger, Kirk M; Stemmer, Kerstin; Itoh, Nobuyuki; Perez-Tilve, Diego; Tschöp, Matthias H; Seeley, Randy J; Ulrich-Lai, Yvonne M

    2018-01-01

    In response to an acute threat to homeostasis or well-being, the hypothalamic-pituitary-adrenocortical (HPA) axis is engaged. A major outcome of this HPA axis activation is the mobilization of stored energy, to fuel an appropriate behavioral and/or physiological response to the perceived threat. Importantly, the extent of HPA axis activity is thought to be modulated by an individual's nutritional environment. In this study, we report that nutritional manipulations signaling a relative depletion of dietary carbohydrates, thereby inducing nutritional ketosis, acutely and chronically activate the HPA axis. Male rats and mice maintained on a low-carbohydrate high-fat ketogenic diet (KD) exhibited canonical markers of chronic stress, including increased basal and stress-evoked plasma corticosterone, increased adrenal sensitivity to adrenocorticotropin hormone, increased stress-evoked c-Fos immunolabeling in the paraventricular nucleus of the hypothalamus, and thymic atrophy, an indicator of chronic glucocorticoid exposure. Moreover, acutely feeding medium-chain triglycerides (MCTs) to rapidly induce ketosis among chow-fed male rats and mice also acutely increased HPA axis activity. Lastly, and consistent with a growing literature that characterizes the hepatokine fibroblast growth factor-21 (FGF21) as both a marker of the ketotic state and as a key metabolic stress hormone, the HPA response to both KD and MCTs was significantly blunted among mice lacking FGF21. We conclude that dietary manipulations that induce ketosis lead to increased HPA axis tone, and that the hepatokine FGF21 may play an important role to facilitate this effect. Copyright © 2018 Endocrine Society.

  15. Relative Biological Effectiveness of Energetic Heavy Ions for Intestinal Tumorigenesis Shows Male Preponderance and Radiation Type and Energy Dependence in APC(1638N/+) Mice.

    Science.gov (United States)

    Suman, Shubhankar; Kumar, Santosh; Moon, Bo-Hyun; Strawn, Steve J; Thakor, Hemang; Fan, Ziling; Shay, Jerry W; Fornace, Albert J; Datta, Kamal

    2016-05-01

    There are uncertainties associated with the prediction of colorectal cancer (CRC) risk from highly energetic heavy ion (HZE) radiation. We undertook a comprehensive assessment of intestinal and colonic tumorigenesis induced after exposure to high linear energy transfer (high-LET) HZE radiation spanning a range of doses and LET in a CRC mouse model and compared the results with the effects of low-LET γ radiation. Male and female APC(1638N/+) mice (n=20 mice per group) were whole-body exposed to sham-radiation, γ rays, (12)C, (28)Si, or (56)Fe radiation. For the >1 Gy HZE dose, we used γ-ray equitoxic doses calculated using relative biological effectiveness (RBE) determined previously. The mice were euthanized 150 days after irradiation, and intestinal and colon tumor frequency was scored. The highest number of tumors was observed after (28)Si, followed by (56)Fe and (12)C radiation, and tumorigenesis showed a male preponderance, especially after (28)Si. Analysis showed greater tumorigenesis per unit of radiation (per cGy) at lower doses, suggesting either radiation-induced elimination of target cells or tumorigenesis reaching a saturation point at higher doses. Calculation of RBE for intestinal and colon tumorigenesis showed the highest value with (28)Si, and lower doses showed greater RBE relative to higher doses. We have demonstrated that the RBE of heavy ion radiation-induced intestinal and colon tumorigenesis is related to ion energy, LET, gender, and peak RBE is observed at an LET of 69 keV/μm. Our study has implications for understanding risk to astronauts undertaking long duration space missions. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Relative Biological Effectiveness of Energetic Heavy Ions for Intestinal Tumorigenesis Shows Male Preponderance and Radiation Type and Energy Dependence in APC1638N/+ Mice

    International Nuclear Information System (INIS)

    Suman, Shubhankar; Kumar, Santosh; Moon, Bo-Hyun; Strawn, Steve J.; Thakor, Hemang; Fan, Ziling; Shay, Jerry W.; Fornace, Albert J.; Datta, Kamal

    2016-01-01

    Purpose: There are uncertainties associated with the prediction of colorectal cancer (CRC) risk from highly energetic heavy ion (HZE) radiation. We undertook a comprehensive assessment of intestinal and colonic tumorigenesis induced after exposure to high linear energy transfer (high-LET) HZE radiation spanning a range of doses and LET in a CRC mouse model and compared the results with the effects of low-LET γ radiation. Methods and Materials: Male and female APC 1638N/+ mice (n=20 mice per group) were whole-body exposed to sham-radiation, γ rays, 12 C, 28 Si, or 56 Fe radiation. For the >1 Gy HZE dose, we used γ-ray equitoxic doses calculated using relative biological effectiveness (RBE) determined previously. The mice were euthanized 150 days after irradiation, and intestinal and colon tumor frequency was scored. Results: The highest number of tumors was observed after 28 Si, followed by 56 Fe and 12 C radiation, and tumorigenesis showed a male preponderance, especially after 28 Si. Analysis showed greater tumorigenesis per unit of radiation (per cGy) at lower doses, suggesting either radiation-induced elimination of target cells or tumorigenesis reaching a saturation point at higher doses. Calculation of RBE for intestinal and colon tumorigenesis showed the highest value with 28 Si, and lower doses showed greater RBE relative to higher doses. Conclusions: We have demonstrated that the RBE of heavy ion radiation-induced intestinal and colon tumorigenesis is related to ion energy, LET, gender, and peak RBE is observed at an LET of 69 keV/μm. Our study has implications for understanding risk to astronauts undertaking long duration space missions.

  17. Exposure to bisphenol-A during pregnancy partially mimics the effects of a high-fat diet altering glucose homeostasis and gene expression in adult male mice.

    Directory of Open Access Journals (Sweden)

    Marta García-Arevalo

    Full Text Available Bisphenol-A (BPA is one of the most widespread EDCs used as a base compound in the manufacture of polycarbonate plastics. The aim of our research has been to study how the exposure to BPA during pregnancy affects weight, glucose homeostasis, pancreatic β-cell function and gene expression in the major peripheral organs that control energy flux: white adipose tissue (WAT, the liver and skeletal muscle, in male offspring 17 and 28 weeks old. Pregnant mice were treated with a subcutaneous injection of 10 µg/kg/day of BPA or a vehicle from day 9 to 16 of pregnancy. One month old offspring were divided into four different groups: vehicle treated mice that ate a normal chow diet (Control group; BPA treated mice that also ate a normal chow diet (BPA; vehicle treated animals that had a high fat diet (HFD and BPA treated animals that were fed HFD (HFD-BPA. The BPA group started to gain weight at 18 weeks old and caught up to the HFD group before week 28. The BPA group as well as the HFD and HFD-BPA ones presented fasting hyperglycemia, glucose intolerance and high levels of non-esterified fatty acids (NEFA in plasma compared with the Control one. Glucose stimulated insulin release was disrupted, particularly in the HFD-BPA group. In WAT, the mRNA expression of the genes involved in fatty acid metabolism, Srebpc1, Pparα and Cpt1β was decreased by BPA to the same extent as with the HFD treatment. BPA treatment upregulated Pparγ and Prkaa1 genes in the liver; yet it diminished the expression of Cd36. Hepatic triglyceride levels were increased in all groups compared to control. In conclusion, male offspring from BPA-treated mothers presented symptoms of diabesity. This term refers to a form of diabetes which typically develops in later life and is associated with obesity.

  18. Exposure to Bisphenol-A during Pregnancy Partially Mimics the Effects of a High-Fat Diet Altering Glucose Homeostasis and Gene Expression in Adult Male Mice

    Science.gov (United States)

    García-Arevalo, Marta; Alonso-Magdalena, Paloma; Rebelo Dos Santos, Junia; Quesada, Ivan; Carneiro, Everardo M.; Nadal, Angel

    2014-01-01

    Bisphenol-A (BPA) is one of the most widespread EDCs used as a base compound in the manufacture of polycarbonate plastics. The aim of our research has been to study how the exposure to BPA during pregnancy affects weight, glucose homeostasis, pancreatic β-cell function and gene expression in the major peripheral organs that control energy flux: white adipose tissue (WAT), the liver and skeletal muscle, in male offspring 17 and 28 weeks old. Pregnant mice were treated with a subcutaneous injection of 10 µg/kg/day of BPA or a vehicle from day 9 to 16 of pregnancy. One month old offspring were divided into four different groups: vehicle treated mice that ate a normal chow diet (Control group); BPA treated mice that also ate a normal chow diet (BPA); vehicle treated animals that had a high fat diet (HFD) and BPA treated animals that were fed HFD (HFD-BPA). The BPA group started to gain weight at 18 weeks old and caught up to the HFD group before week 28. The BPA group as well as the HFD and HFD-BPA ones presented fasting hyperglycemia, glucose intolerance and high levels of non-esterified fatty acids (NEFA) in plasma compared with the Control one. Glucose stimulated insulin release was disrupted, particularly in the HFD-BPA group. In WAT, the mRNA expression of the genes involved in fatty acid metabolism, Srebpc1, Pparα and Cpt1β was decreased by BPA to the same extent as with the HFD treatment. BPA treatment upregulated Pparγ and Prkaa1 genes in the liver; yet it diminished the expression of Cd36. Hepatic triglyceride levels were increased in all groups compared to control. In conclusion, male offspring from BPA-treated mothers presented symptoms of diabesity. This term refers to a form of diabetes which typically develops in later life and is associated with obesity. PMID:24959901

  19. Effect of Withania somnifera supplementation on rotenone-induced oxidative damage in cerebellum and striatum of the male mice brain.

    Science.gov (United States)

    Manjunath, Mallaya Jayawanth; Muralidhara

    2013-03-01

    Withania somnifera (WS) an ayurvedic medicinal herb is widely known for its memory enhancing ability and improvement of brain function. In the present study, we tested the hypothesis that WS prophylaxis could offset neurotoxicant-induced oxidative dysfunctions in developing brain employing a rotenone (ROT) mouse model. Initially, we assessed the potential of WS oral supplements (100-400 mg/ kg b.w/ d, 4wks) to modulate the endogenous levels of oxidative markers in cerebellum (cb) and striatum (st) of prepubertal (PP) mice. Further, we assessed the induction of oxidative stress in cb and st of mice administered with ROT (i.p. 0.5 and 1mg/ kg b.w, 7d). ROT caused significant elevation in the levels of reactive oxygen species (ROS), malondialdehyde (MDA), hydroperoxides (HP) and nitric oxide (NO) levels in both brain regions. Furthe