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Sample records for adult offspring mice

  1. Maternal preconceptional nutrition leads to variable fat deposition and gut dimensions of adult offspring mice (C57BL/6JBom)

    DEFF Research Database (Denmark)

    Mortensen, Elna Louise Krogh; Wang, Tobias; Malte, H.; Raubenheimer, D; Mayntz, David

    2010-01-01

    Background:   Maternal nutrition during pregnancy or lactation may affect the chance of offspring becoming obese as adults, but little is known regarding the possible role of maternal nutrition before conception. In this study, we investigate how variable protein and carbohydrate content of the...... taken. Results:   Fat deposition of the offspring was significantly affected by preconceptional maternal nutrition and the effects differed between sexes. Male offspring deposited most fat when mothers were fed the LP diet, whereas female offspring deposited most fat when mothers were fed the ST diet....... The mass and length of the digestive organs were affected by preconceptional maternal nutrition. Total gut from pyloric sphincter to anus was significantly shorter and dry mass was heavier in mice whose mothers were fed LP diets compared with offspring of mothers fed ST diets or HP diets. There was no...

  2. Behavioural disturbances in adult CD-1 mice and absence of effects on their offspring upon SO{sub 2} exposure

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    Petruzzi, S. [Section of Behavioural Pathophysiology, Laboratorio di Fisiopatologia di Organo e di Sistema, Istituto Superiore di Sanita, Roma (Italy); Dell`Omo, G. [Section of Behavioural Pathophysiology, Laboratorio di Fisiopatologia di Organo e di Sistema, Istituto Superiore di Sanita, Roma (Italy); Fiore, M. [Section of Behavioural Pathophysiology, Laboratorio di Fisiopatologia di Organo e di Sistema, Istituto Superiore di Sanita, Roma (Italy); Chiarotti, F. [Section of Behavioural Pathophysiology, Laboratorio di Fisiopatologia di Organo e di Sistema, Istituto Superiore di Sanita, Roma (Italy); Bignami, G. [Section of Behavioural Pathophysiology, Laboratorio di Fisiopatologia di Organo e di Sistema, Istituto Superiore di Sanita, Roma (Italy); Alleva, E. [Section of Behavioural Pathophysiology, Laboratorio di Fisiopatologia di Organo e di Sistema, Istituto Superiore di Sanita, Roma (Italy)

    1996-09-01

    Adult male and female CD-1 mice were exposed to different SO{sub 2} concentrations (0, 5, 12, or 30 ppm) for 24 days, from 9 days before the formation of breeding pairs to pregnancy day 12-14. This exposure was near-continuous, covering about 80% of the total time. The offspring of exposed dams were cross-fostered shortly after birth to dams not previously exposed. Videorecordings of the adult subjects` activities during the first hour after the start of exposure showed marked, acute transient behavioural effects such as increase of rearing and social interactions, which were more pronounced in males than in females. Subsequent activity tests on exposure days 3, 6, and 9 showed subacute effects including a dose-dependent decrease of grooming and an increase of digging as well as changes in chamber crossing and wall-rearing which were not dose-dependent; most of these effects were more pronounced in females than in males. Food and water consumption and body weight declined in a dose-dependent fashion only after the formation of breeding pairs, when consummatory responses were enhanced in the controls. Reproductive performance as well as postnatal somatic and neurobehavioural development of the offspring (the latter assessed by an observational test battery including eight reflexes and responses) were not affected by SO{sub 2}. Passive avoidance acquisition and retention at the young adult stage (60 days) and response changes produced by repeated apparatus exposure in non-reinforced animals (habituation) were similarly unaffected. The data indicate that SO{sub 2} produces transient, acute behavioural disturbances and more subtle subacute response changes in adult mice which may be due, at least partly, to a functional interference with olfactory modulation of mouse behaviour. The absence of effects on reproductive performance and neurobehavioural development of the offspring suggests that the risk to the developing organism from gestational SO{sub 2} exposure is low.

  3. Prenatal nicotine exposure enhances Cx43 and Panx1 unopposed channel activity in brain cells of adult offspring mice fed a high-fat/cholesterol diet

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    Juan Andrés Orellana

    2014-12-01

    Full Text Available Nicotine, the most important neuroteratogen of tobacco smoke, can reproduce brain and cognitive disturbances per se when administered prenatally. However, it is still unknown if paracrine signaling among brain cells participates in prenatal nicotine-induced brain impairment of adult offspring. Paracrine signaling is partly mediated by unopposed channels formed by connexins (hemichannels and pannexins serving as aqueous pores permeable to ions and small signaling molecules, allowing exchange between the intra- and extracellular milieus. Our aim was to address whether prenatal nicotine exposure changes the activity of those channels in adult mice offspring under control conditions or subjected to a second challenge during young ages: high-fat/cholesterol (HFC diet. To induce prenatal exposure to nicotine, osmotic minipumps were implanted in CF1 pregnant mice at gestational day 5 to deliver nicotine bitartrate or saline (control solutions. After weaning, offspring of nicotine-treated or untreated pregnant mice were fed ad libitum with chow or HFC diets for 8 weeks. The functional state of Cx43 and Panx1 unopposed channels was evaluated by dye uptake experiments in hippocampal slices from 11-week-old mice. We found that prenatal nicotine increased the opening of Cx43 hemichannels in astrocytes, and Panx1 channels in microglia and neurons only if offspring mice were fed with HFC diet. Blockade of iNOS, COX2 and EP1, P2X7 and NMDA receptors, showed differential inhibition of prenatal nicotine-induced channel opening in glial cells and neurons. Importantly, inhibition of the above mentioned enzymes and receptors, or blockade of Cx43 and Panx1 unopposed channels greatly reduced ATP and glutamate release from hippocampal slices of prenatally nicotine-exposed offspring. We propose that unregulated gliotransmitter release through Cx43 and Panx1 unopposed channels may participate in brain alterations observed in offspring of mothers exposed to tobacco smoke

  4. Sleep fragmentation during late gestation induces metabolic perturbations and epigenetic changes in adiponectin gene expression in male adult offspring mice.

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    Khalyfa, Abdelnaby; Mutskov, Vesco; Carreras, Alba; Khalyfa, Ahamed A; Hakim, Fahed; Gozal, David

    2014-10-01

    Sleep fragmentation (SF) is a common condition among pregnant women, particularly during late gestation. Gestational perturbations promote the emergence of adiposity and metabolic disease risk in offspring, most likely through epigenetic modifications. Adiponectin (AdipoQ) expression inversely correlates with obesity and insulin resistance. The effects of SF during late gestation on metabolic function and AdipoQ expression in visceral white adipose tissue (VWAT) of offspring mice are unknown. Male offspring mice were assessed at 24 weeks after dams were exposed to SF or control sleep during late gestation. Increased food intake, body weight, VWAT mass, and insulin resistance, with reductions in AdipoQ expression in VWAT, emerged in SF offspring. Increased DNMT3a and -b and global DNA methylation and reduced histone acetyltransferase activity and TET1, -2, and -3 expression were detected in VWAT of SF offspring. Reductions in 5-hydroxymethylcytosine and H3K4m3 and an increase in DNA 5-methylcytosine and H3K9m2 in the promoter and enhancer regions of AdipoQ emerged in adipocytes from VWAT and correlated with AdipoQ expression. SF during late gestation induces epigenetic modifications in AdipoQ in male offspring mouse VWAT adipocytes along with a metabolic syndrome-like phenotype. Thus, altered gestational environments elicited by SF impose the emergence of adverse, long-lasting metabolic consequences in the next generation. PMID:24812424

  5. The scent of stress: environmental challenge in the peripartum environment of mice affects emotional behaviours of the adult offspring in a sex-specific manner.

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    Lerch, S; Dormann, C; Brandwein, C; Gass, P; Chourbaji, S

    2016-06-01

    Early adverse experiences are known to influence the risk of developing psychiatric disorders later. To shed further light on the development of laboratory mice, we systematically examined the influence of a prenatal or postnatal olfactory stressor, namely unfamiliar male mouse faeces, presented to pregnant or nursing mouse dams. Maternal and offspring behaviours were then examined. Maternal behaviours relative to controls revealed changes in nest building by the pregnant dams exposed to the unfamiliar faeces. There were no differences among groups on pup retrieval or exploration by the dams. Behavioural phenotyping of male and female offspring as adults included measures of exploration, anxiety, social and depressive-like behaviours. Additionally, serum corticosterone was assessed as a marker of physiological stress response. Group differences were dependent on the sex of the adult offspring. Males raised by dams that were stressed during pregnancy presented elevated emotionality as indicated by increased numbers of faecal boluses in the open field paradigm. Consistent with the effects of prenatal stress on the males only the prenatally stressed females had higher body weights than their respective controls. Indeed, males in both experimental groups had higher circulating corticosterone levels. By contrast, female offspring of dams exposed to the olfactory stressor after parturition were more anxious in the O-maze as indicated by increased latencies in entering the exposed areas of the maze. These findings emphasize the necessity for researchers to consider the pre- and postnatal environments, even of mice with almost identical genetic backgrounds, in designing experiments and interpreting their data. PMID:26408077

  6. Paternal exposure to radiation and offspring cancer in mice

    International Nuclear Information System (INIS)

    Parental exposure to radiation could induce various kinds of tumors in the next generation. In ICR mice, a large and significant increase of adult type tumor was observed in the F1 offspring after X-ray exposure at spermatozoa and spermatid stages, and less clear increase was observed after spermatogonial exposure. Mature oocytes were resistant up to 1 Gy, but very sensitive to tumor induction at higher doses. While there was no difference in the tumor incidence between acute and fractionated (0.36 Gy at 2 hr intervals) irradiation at post-gonial stages, a large reduction of tumor incidence was observed after spermatogonial and mature oocyte exposure, suggesting some repairs of X-ray damages in these germ cells. Acute lymphocytic leukemia was not induced in CCR and LT mice after spermatogonial exposure, while a larger increase of adult type cancers was observed in F1 offspring. However, 1.9-3.2 fold and 4.5-7.4 fold increases of leukemia incidence were observed in ICR and LT mice, when spermatozoa stage was treated with the X-ray doses of 0.36-5.04 Gy and 3.6-5.04 Gy, respectively, indicating the large difference in the sensitivity of developing germ cells to leukemia induction by radiation in the F1 offspring. In contrast to ICR and LT mice, N5 strain developed about 10 or 18 times higher incidence of leukemia in the offspring after spermatogonial or spermatozoa exposure to 5.04 Gy of X-rays, respectively, showing a marked difference in the sensitivity to the leukemia induction by radiation between mouse strains. These differential sensitivities between germ cell stages and also between mouse strains reconcile the difference between two population studies in Hiroshima/Nagasaki and Sellafield. However, there were large differences in the doubling doses for leukemia induction between the mouse experiments and Sellafield study in human. (author)

  7. Production of the first offspring from oocytes derived from fresh and cryopreserved pre-antral follicles of adult mice

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    Kagawa, Norika; Kuwayama, Masashige; Nakata, Kumiko;

    2007-01-01

    , as well as in women who wish to delay pregnancy and child raising until they are older. This study reports the birth of 10 healthy mouse pups derived from oocytes obtained from pre-antral follicles after adult ovary tissue cryopreservation and allotransplantation. High in-vitro maturation (55...

  8. Dietary early-life exposure to contaminated eels does not impair spatial cognitive performances in adult offspring mice as assessed in the Y-maze and the Morris water maze.

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    Dridi, Imen; Leroy, Delphine; Guignard, Cédric; Scholl, Georges; Bohn, Torsten; Landoulsi, Ahmed; Thomé, Jean-Pierre; Eppe, Gauthier; Soulimani, Rachid; Bouayed, Jaouad

    2014-12-01

    Many environmental contaminants are introduced via the diet and may act as neurotoxins and endocrine disrupters, especially influencing growing organisms in early life. The purpose of this study was to examine whether dietary exposure of dams to fish naturally contaminated with xenobiotics, especially with polychlorinated biphenyls (PCBs) and heavy metals (e.g., mercury and lead), resulted in cognitive function deficits in adult offspring mice. Daily, four groups of dams (n = 10/group) ingested standard diet plus paste with/without eels, during gestation and lactation, from gestational day (GD) six until post natal day (PND) 21 (weaning). Dams orally ingested a standardized amount of eel (0.8 mg kg(-1) d(-1)) containing the six non-dioxin-like (NDL) PCBs (Σ6 NDL-PCBs: 28, 52, 101, 138, 153, and 180) at 0, 85, 216, and 400 ng kg(-1) d(-1). Results showed that early-life exposure to contaminated eels did not (compared to non-exposed controls) impair immediate working memory in the Y-maze in the offspring assessed at PND 38. Furthermore, it did not significantly impact spatial learning and retention memory as measured in the Morris water maze in adult offspring mice (PND 120-123). Our results suggest that perinatal exposure to contaminated eels does not affect spatial cognitive performances, as assessed by the Y-maze and Morris water maze at adult age. Adverse effects of xenobiotics reported earlier might be camouflaged by beneficial eel constituents, such as n-3 fatty acids. However, additional studies are needed to differentiate between potential positive and negative effects following consumption of food items both rich in nutrients and contaminants. PMID:25476192

  9. Exercise during pregnancy protects adult mouse offspring from diet-induced obesity

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    Wasinski, F.; Bacurau, R.F.P.; Estrela, G.R.; Klempin, F.; Arakaki, A.M.; Batista, R.O.; Mafra, F.F.P.; do Nascimento, L.F.R.; M.I. Hiyane; L.A. Velloso; N.O.S. Camara; Araujo, R C

    2015-01-01

    Background Physical exercise induces positive alterations in gene expression involved in the metabolism of obesity. Maternal exercise provokes adaptations soon after birth in the offspring. Here, we investigated whether adult mouse offspring of swim-trained mothers is protected against the development of the deleterious effects of high fat diet (HFD). Methods Our study comprises two parts. First, female C57BL/6 mice were divided into one sedentary and one swim-trained group (before and during...

  10. Viable offspring obtained from Prm1-deficient sperm in mice

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    Takeda, Naoki; Yoshinaga, Kazuya; Furushima, Kenryo; Takamune, Kazufumi; Li, Zhenghua; Abe, Shin-ichi; Aizawa, Shin-ichi; Yamamura, Ken-ichi

    2016-01-01

    Protamines are expressed in the spermatid nucleus and allow denser packaging of DNA compared with histones. Disruption of the coding sequence of one allele of either protamine 1 (Prm1) or Prm2 results in failure to produce offspring, although sperm with disrupted Prm1 or Prm2 alleles are produced. Here, we produced Prm1-deficient female chimeric mice carrying Prm1-deficient oocytes. These mice successfully produced Prm1+/− male mice. Healthy Prm1+/− offspring were then produced by transferring blastocysts obtained via in vitro fertilization using zona-free oocytes and sperm from Prm1+/− mice. This result suggests that sperm lacking Prm1 can generate offspring despite being abnormally shaped and having destabilised DNA, decondensed chromatin and a reduction in mitochondrial membrane potential. Nevertheless, these mice showed little derangement of expression profiles. PMID:27250771

  11. Impact of hypericum (St.-John's-wort) given prenatally on cognition of mice offspring.

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    Rayburn, W F; Gonzalez, C L; Christensen, H D; Harkins, T L; Kupiec, T C

    2001-01-01

    This study investigated the cognitive impact of prenatal exposure to the herbal antidepressant hypericum in CD-1 mice. Hypericum (182 mg/kg/day) or a placebo was consumed in food bars for 2 weeks before mating and throughout gestation. The hypericin content in our hypericum formulation was in the middle range of standardized hypericum products. One offspring per gender from each litter (hypericum 13, placebo 12) was tested on each of the following tasks: juvenile runway with adult memory, adult Morris maze, adult passive avoidance, or adult straight water runway followed by a dry Cincinnati maze. Learning occurred in both genders in all tasks (Pmaze task (P<.05). Postlearning sessions did not show any significant differences. In conclusion, prenatal exposure to a therapeutic dose of hypericum did not have a major impact on certain cognitive tasks in mice offspring. PMID:11792531

  12. Distribution of 241Am in offspring from BALB/c mice injected with 241Am at 14 days of gestation: relation to calcium and iron metabolism and comparison with distribution of 241Am after injection of adults

    International Nuclear Information System (INIS)

    Pregnant mice were given intravenous injections of 241 Am citrate at 14 days of gestation. The fetal skeleton had a higher or similar uptake of 241Am per gram of fresh tissue than the liver. The liver in adults concentrated 5 to 20 times more 241 Am per gram of fresh tissue than the bones. Measurement of changes in calcium and iron content and concentration with time, showed that in developing mice intensive calcification of bones determined uptake of 241Am. The 241Am uptake was related to calcium concentration of the fetal bones, which was greater at 14 days of gestation in the anterior bones, mandibles and calvaria, than in ribs and femurs. Transfer of 241Am to pups via milk resulted in further accumulation of 241Am in skeleton and liver. The incorporation in the skeleton persisted after weaning and contributed to the lifetime body burden. The 241Am concentration decreased rapidly with time after injection in relation to growth of the organs. Radiation dose rates and cumulative radiation doses were calculated for liver and bones of contaminated offspring. (author)

  13. Cognitive function in adult offspring of women with Type 1 diabetes

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    Clausen, Tine Dalsgaard; Mortensen, E L; Schmidt, L;

    2011-01-01

    Maternal diabetes may affect offspring cognitive function. The objective of the study was to evaluate cognitive function and potential predictors hereof in adult offspring of women with Type 1 diabetes.......Maternal diabetes may affect offspring cognitive function. The objective of the study was to evaluate cognitive function and potential predictors hereof in adult offspring of women with Type 1 diabetes....

  14. Programming of stress-related behavior and epigenetic neural gene regulation in mice offspring through maternal exposure to predator odor

    Directory of Open Access Journals (Sweden)

    Sophie St-Cyr

    2015-06-01

    Full Text Available Perinatal stress mediated through the mother can lead to long-term alterations in stress-related phenotypes in offspring. The capacity for adaptation to adversity in early life depends in part of the life history of the animal. This study was designed to examine the behavioral and neural response in adult offspring to prenatal exposure to predator odor: an ethologically-relevant psychological stressor. Pregnant mice were exposed daily to predator odors or distilled water control over the second half of the pregnancy. Predator odor exposure lead to a transient decrease in maternal care in the mothers. As adults, the offspring of predator odor-exposed mothers showed increased anti-predator behavior and predator-odor induced decrease in activity, in female offspring, an increased corticosterone response to predator odor exposure. We found a highly specific response among stress-related genes within limbic brain regions. Transcript abundance of CRHR1 (Corticotropin-releasing hormone receptor 1 was elevated in the amygdala in female offspring of predator odor-exposed dams. In the hippocampus of adult female offspring, decreased BDNF (Brain-derived neurotrophic factor gene expression was correlated with a site-specific decrease in DNA methylation in the Bdnf exon IV, indicating the potential contribution of this epigenetic mechanism to maternal programming by prenatal predator odor exposure. These data indicate that prenatal predator odor exposure alone is sufficient to induce an altered stress-related phenotype in adulthood, with implications for anti-predator behavior in offspring.

  15. Effects of Prenatal Lipopolysaccharide Exposure on Reproductive Activities and Serum Concentrations of Pituitary-Gonadal Hormones in Mice Offspring

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    Jalal Solati

    2012-01-01

    Full Text Available Background: Maternal infection during pregnancy is a risk factor for some behavioralproblems with neurodevelopmental origin. This study aimed to evaluate the effects ofexposure of pregnant mice to the bacterial lipopolysaccharide (LPS on sexual behaviourand serum level of pituitary-gonadal hormones of offspring in adulthood.Materials and Methods: In this Expremental study, pregnant NMRI mice (n=7/groupwere treated with intra-peritoneal administration of LPS (1, 5 and 10 μg/kg at day 10of gestation. Induction of the pro-inflammatory cytokines, Tumor necrosis factor-alpha(TNF-α, interleukin-1beta (IL-1β and interleukin-6 (IL-6 were measured in maternalserum 2 hours following the maternal LPS challenge. Behavior in the adult male offspringreproductive activity was investigated using receptive female mice. Concentrationsof testosterone, luteinizing hormone (LH and follicle-stimulating hormone (FSHin adult offspring serum were measured using the enzyme-linked immunosorbent assay(ELISA method (at postnatal day 60, n=10/group.Results: One-way ANOVA showed that LPS administration induces a significant increasein TNF-α, IL-1β and IL-6 levels of maternal serum. Prenatal LPS exposure reduces sexualbehavior and serum concentration of LH and testosterone in adult male offspring.Conclusion: The overall results suggest that prenatal exposure to LPS increases proinflammatorycytokine levels, affects development of neuroendocrine systems and resultsin the inhibition of reproductive behaviors and reactivity of hypothalamic–pituitary-gonadal(HPG axis in adult male offspring.

  16. Immunoexpression of epidermal growth factor in odontogenesis of the offspring of alcoholic mice.

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    Hernández Guerrero, J C; Portilla Robertson, J; Ledezma Montes, C; Ponce-Bravo, S; Miranda Gómez, A; Arias Rivera, E M

    1996-01-01

    Several forms of cell perturbation have been associated with ethanol ingestion. Fetal alcohol syndrome (FAS) as well as diminished maxillofacial development and inhibition of cell regeneration in vitro and in vivo have been described. Epidermal growth factor (EGF) stimulates maxillofacial growth, DNA synthesis, and it is a potent mitogen for a number of various cell types. EGF exerts its effects on cells through binding to a specific cell surface receptor which leads to activation of a thyrosine kinase in the intracellular part of the receptor. The inhibitory effect of alcohol on EGF in the mouse dental follicle was studied in the offspring of alcoholic mothers using immunocytochemistry. Adult female mice were given 22% alcohol in their drinking water and fed a pelleted diet before and during pregnancy. Maternal blood alcohol levels were 262 +/- 1.3 mg/100 ml on gestation day 12.5. The offspring of the alcoholic and control mice were sacrificed on postnatal day 1.5, their mandibles were dissected, weighed and processed by routine immunocytochemistry with the following results. 1) Significant differences were found in mandible weight p alcoholism reduces EGF in the offspring. PMID:9369034

  17. Prenatal polycyclic aromatic hydrocarbon, adiposity, peroxisome proliferator-activated receptor (PPAR γ methylation in offspring, grand-offspring mice.

    Directory of Open Access Journals (Sweden)

    Zhonghai Yan

    Full Text Available RATIONALE: Greater levels of prenatal exposure to polycyclic aromatic hydrocarbon (PAH have been associated with childhood obesity in epidemiological studies. However, the underlying mechanisms are unclear. OBJECTIVES: We hypothesized that prenatal PAH over-exposure during gestation would lead to weight gain and increased fat mass in offspring and grand-offspring mice. Further, we hypothesized that altered adipose gene expression and DNA methylation in genes important to adipocyte differentiation would be affected. MATERIALS AND METHODS: Pregnant dams were exposed to a nebulized PAH mixture versus negative control aerosol 5 days a week, for 3 weeks. Body weight was recorded from postnatal day (PND 21 through PND60. Body composition, adipose cell size, gene expression of peroxisome proliferator-activated receptor (PPAR γ, CCAAT/enhancer-binding proteins (C/EBP α, cyclooxygenase (Cox-2, fatty acid synthase (FAS and adiponectin, and DNA methylation of PPAR γ, were assayed in both the offspring and grand-offspring adipose tissue. FINDINGS: Offspring of dams exposed to greater PAH during gestation had increased weight, fat mass, as well as higher gene expression of PPAR γ, C/EBP α, Cox2, FAS and adiponectin and lower DNA methylation of PPAR γ. Similar differences in phenotype and DNA methylation extended through the grand-offspring mice. CONCLUSIONS: Greater prenatal PAH exposure was associated with increased weight, fat mass, adipose gene expression and epigenetic changes in progeny.

  18. Mice age - Does the age of the mother predict offspring behaviour?

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    Lerch, Sandra; Brandwein, Christiane; Dormann, Christof; Gass, Peter; Chourbaji, Sabine

    2015-08-01

    Increasing paternal age is known to be associated with a great variety of psychiatric disorders such as schizophrenia or autism. Hence the factor "age" may be taken as strategic tool to analyse specific scientific hypotheses. Additionally, this finding also needs to be addressed in rather pragmatically performed breeding protocols of model organisms, since otherwise artefacts may challenge the validity of the results. Our study was performed to investigate influences of advanced age of mouse dams (30 vs. 16weeks) on maternal- and offspring behaviour. Adult offspring of both sexes was analysed in a test battery comprising paradigms for exploration, anxiety and depressive-like behaviours. Final blood sampling was conducted for stressphysiological analysis. Interestingly, advanced age of the mothers was associated with increased nest-building quality while maternal activity was unaffected. Moreover "maternal (mice) age" (MA) affected emotionality in the offspring, which became apparent in the dark-light box and the social recognition paradigm. These findings not only emphasize MA to model a potent risk factor with regard to emotional stability, but also underscore the vast necessity to include information about breeding protocols into the methods section of any animal study. PMID:25914174

  19. Effects of maternal exposure to nano-alumina during pregnancy on neurodevelopment in offspring mice

    Institute of Scientific and Technical Information of China (English)

    丁勇

    2013-01-01

    Objective To observe the effects of maternal exposure to nano-alumina during pregnancy on the neurodevelopment in offspring mice.Methods Female ICR mice were exposed to nano-alumina 10 d before mating,and the nano-alumina exposure lasted till offspring mice were born.All the female mice were randomly divided into 5groups:solvent control group (saline) ,nano-carbon group (11.76 mg/ml) ,microalumina group (50 mg/ml) ,50 nm alumina group (50 mg/ml) ,and 13 nm alumina group (50 mg/ml) .All the mice were treated by

  20. Maternal Age and Offspring Adult Health: Evidence From the Health and Retirement Study

    OpenAIRE

    Mikko Myrskylä; Andrew T. Fenelon

    2012-01-01

    Advanced maternal age is associated with negative offspring health outcomes. This interpretation often relies on physiological processes related to aging, such as decreasing oocyte quality. We use a large, population-based sample of American adults to analyze how selection and lifespan overlap between generations influence the maternal age–offspring adult health association. We find that offspring born to mothers younger than age 25 or older than 35 have worse outcomes with respect to mortali...

  1. Japanese macaque (Macaca fuscata) mothers huddle with their young offspring instead of adult females for thermoregulation.

    Science.gov (United States)

    Ueno, Masataka; Nakamichi, Masayuki

    2016-08-01

    It is unclear whom animals select to huddle with for thermoregulation. In this study, we investigated whom Japanese macaque (Macaca fuscata) mothers huddled with-their young offspring or other adult group members-when there is need for thermoregulation. We used a focal-animal sampling method, targeting 17 females at Katsuyama, Okayama Prefecture, Japan. A majority of huddling among adult females was recorded during winter season (December, January, and February). Females who had young (0- or 1-year-old) offspring huddled less frequently with other adult females compared to females who did not have young offspring in winter. However, including young offspring, the frequency of huddling with any other individuals did not differ by whether females had young offspring. Moreover, the females who did not have young offspring huddled with other adult females more often in cloudy than in sunny weather during winter season. In contrast, females who had young offspring increased huddling with their young offspring in cloudy than in sunny weather, but did not do so with other adult females. This study indicates that Japanese macaque mothers huddle with their young offspring instead of other adult females when there is need for thermoregulation. PMID:27262980

  2. Paternal alcohol exposure in mice alters brain NGF and BDNF and increases ethanol-elicited preference in male offspring.

    Science.gov (United States)

    Ceccanti, Mauro; Coccurello, Roberto; Carito, Valentina; Ciafrè, Stefania; Ferraguti, Giampiero; Giacovazzo, Giacomo; Mancinelli, Rosanna; Tirassa, Paola; Chaldakov, George N; Pascale, Esterina; Ceccanti, Marco; Codazzo, Claudia; Fiore, Marco

    2016-07-01

    Ethanol (EtOH) exposure during pregnancy induces cognitive and physiological deficits in the offspring. However, the role of paternal alcohol exposure (PAE) on offspring EtOH sensitivity and neurotrophins has not received much attention. The present study examined whether PAE may disrupt nerve growth factor (NGF) and/or brain-derived neurotrophic factor (BDNF) and affect EtOH preference/rewarding properties in the male offspring. CD1 sire mice were chronically addicted for EtOH or administered with sucrose. Their male offsprings when adult were assessed for EtOH preference by a conditioned place preference paradigm. NGF and BDNF, their receptors (p75(NTR) , TrkA and TrkB), dopamine active transporter (DAT), dopamine receptors D1 and D2, pro-NGF and pro-BDNF were also evaluated in brain areas. PAE affected NGF levels in frontal cortex, striatum, olfactory lobes, hippocampus and hypothalamus. BDNF alterations in frontal cortex, striatum and olfactory lobes were found. PAE induced a higher susceptibility to the EtOH rewarding effects mostly evident at the lower concentration (0.5 g/kg) that was ineffective in non-PAE offsprings. Moreover, higher ethanol concentrations (1.5 g/kg) produced an aversive response in PAE animals and a significant preference in non-PAE offspring. PAE affected also TrkA in the hippocampus and p75(NTR) in the frontal cortex. DAT was affected in the olfactory lobes in PAE animals treated with 0.5 g/kg of ethanol while no differences were found on D1/D2 receptors and for pro-NGF or pro-BDNF. In conclusion, this study shows that: PAE affects NGF and BDNF expression in the mouse brain; PAE may induce ethanol intake preference in the male offspring. PMID:25940002

  3. Altered engagement of autobiographical memory networks in adult offspring of postnatally depressed mothers

    OpenAIRE

    Macdonald, Birthe; Murray, Lynne; Moutsiana, Christina; Fearon, Pasco; Cooper, Peter J.; Halligan, Sarah L.; Johnstone, Tom

    2016-01-01

    Maternal depression is associated with increased risk for offspring mood and anxiety disorders. One possible impact of maternal depression during offspring development is on the emotional autobiographical memory system. We investigated the neural mechanisms of emotional autobiographical memory in adult offspring of mothers with postnatal depression (N = 16) compared to controls (N = 21). During fMRI, recordings of participants describing one pleasant and one unpleasant situation with their...

  4. Gestational Zinc Deficiency Impairs Humoral and Cellular Immune Responses to Hepatitis B Vaccination in Offspring Mice

    OpenAIRE

    Ning Zhao; Xuelian Wang; Ying Zhang; Qiuhong Gu; Fen Huang; Wei Zheng; Zhiwei Li

    2013-01-01

    BACKGROUND: Gestational zinc deficiency has been confirmed to impair the infant immune function. However, knowledge about effects of maternal mild zinc deficiency during pregnancy on hepatitis B vaccine responsiveness in offspring is limited. In this report, we aimed to examine how maternal zinc deficiency during pregnancy influences humoral and cellular immune responses to hepatitis B vaccination in offspring of BALB/c mice. METHODOLOGY/PRINCIPAL FINDINGS: From day 1 of pregnancy upon delive...

  5. The Effects of Parental Health Shocks on Adult Offspring Smoking Behavior and Self-Assessed Health.

    Science.gov (United States)

    Darden, Michael; Gilleskie, Donna

    2016-08-01

    An important avenue for smoking deterrence may be through familial ties if adult smokers respond to parental health shocks. In this paper, we merge the Original Cohort and the Offspring Cohort of the Framingham Heart Study to study how adult offspring smoking behavior and subjective health assessments vary with elder parent smoking behavior and health outcomes. These data allow us to model the smoking behavior of adult offspring over a 30-year period contemporaneously with parental behaviors and outcomes. We find strong 'like father, like son' and 'like mother, like daughter' correlations in smoking behavior. We find that adult offspring significantly curtail their own smoking following an own health shock; however, we find limited evidence that offspring smoking behavior is sensitive to parent health, with the notable exception that women significantly reduce both their smoking participation and intensity following a smoking-related cardiovascular event of a parent. We also model the subjective health assessment of adult offspring as a function of parent health, and we find that women report significantly worse health following the smoking-related death of a parent. Copyright © 2015 John Wiley & Sons, Ltd. PMID:25981179

  6. Antenatal Antioxidant Prevents Nicotine-Mediated Hypertensive Response in Rat Adult Offspring.

    Science.gov (United States)

    Xiao, DaLiao; Huang, Xiaohui; Li, Yong; Dasgupta, Chiranjib; Wang, Lei; Zhang, Lubo

    2015-09-01

    Previous studies have demonstrated that perinatal nicotine exposure increased blood pressure (BP) in adult offspring. However, the underlying mechanisms were unclear. The present study tested the hypothesis that perinatal nicotine-induced programming of hypertensive response is mediated by enhanced reactive oxygen species (ROS) in the vasculature. Nicotine was administered to pregnant rats via subcutaneous osmotic mini-pumps from Day 4 of gestation to Day 10 after birth, in the absence or presence of the ROS inhibitor N-acetyl-cysteine (NAC) in the drinking water. Experiments were conducted in 8-mo-old male offspring. Perinatal nicotine treatment resulted in a significant increase in arterial ROS production in offspring, which was abrogated by NAC. Angiotensin II (Ang II)-induced BP responses were significantly higher in nicotine-treated group than in saline-treated control group, and NAC treatment blocked the nicotine-induced increase in BP response. Consistent with that, the nicotine treatment significantly increased both Ang II-induced and phorbol [12, 13]-dibutyrate (PDBu, a Prkc activator)-induced arterial contractions in adult offspring, which were blocked by NAC treatment. In addition, perinatal nicotine treatment significantly attenuated acetylcholine-induced arterial relaxation in offspring, which was also inhibited by NAC treatment. Results demonstrate that inhibition of ROS blocks the nicotine-induced increase in arterial reactivity and BP response to vasoconstrictors in adult offspring, suggesting a key role for increased oxidative stress in nicotine-induced developmental programming of hypertensive phenotype in male offspring. PMID:26224008

  7. Alpha linolenic acid in maternal diet halts the lipid disarray due to saturated fatty acids in the liver of mice offspring at weaning

    OpenAIRE

    Shomonov-Wagner, Limor; Raz, Amiram; Leikin-Frenkel, Alicia

    2015-01-01

    Background Alpha linolenic acid (ALA, 18:3) in maternal diets has been shown to attenuate obesity associated insulin resistance (IR) in adult offspring in mice. The objective in the present study was to detect the early effects of maternal dietary saturated fatty acids (SFA) and their partial substitution with ω-3 ALA, docosa hexenoic acid (DHA,22:6) and eicosapentenoic acid 20:5 (EPA,20:5) on the HOMA index, liver lipids and fatty acid desaturases in the offspring at weaning. Methods 3 month...

  8. The Effect of Saffron Decoction Consumption on Pregnant Mice and Their Offspring

    OpenAIRE

    Oveisi; Anvari,; Nahang; Dashti-Rahmatabadi

    2012-01-01

    Introduction: In traditional medicine, saffron is used as a drug for treating many diseases. However there are many documents and evidences concerning its abortive and teratogenic effect especially in high doses. Aim: This study was conducted to evaluate the effect of saffron decoction consumption on pregnant mice and their offspring. Methods: In this study, 20 female mice after breeding and observation of vaginal plaque, randomly and equally divided into two groups. During pregnancy, animals...

  9. Parental Divorce, Maternal-Paternal Alcohol Problems, and Adult Offspring Lifetime Alcohol Dependence

    OpenAIRE

    Thompson, Ronald G.; ALONZO, DANA; Hasin, Deborah S.

    2013-01-01

    This study examined the influences of parental divorce and maternal-paternal histories of alcohol problems on adult offspring lifetime alcohol dependence using data from the 2001–2002 National Epidemiological Survey on Alcohol and Related Conditions (NESARC). Parental divorce and maternal-paternal alcohol problems interacted to differentially influence the likelihood of offspring lifetime alcohol dependence. Experiencing parental divorce and either maternal or paternal alcohol problems double...

  10. Physiological and behavioral responses in offspring mice following maternal exposure to sulfamonomethoxine during pregnancy.

    Science.gov (United States)

    Zhang, Qiang; Zhang, Dan; Ye, Kui; Liu, Kaiyong; Sheng, Jie; Liu, Yehao; Hu, Chunqiu; Ruan, Liang; Li, Li; Tao, Fangbiao

    2016-06-15

    Sulfamonomethoxine (SMM), a veterinary antibiotic, is widely used in China. However, the impacts of maternal SMM exposure on neurobehavioral development in early life remain little known. In this study, we investigated the effects of maternal SMM exposure during pregnancy on behavioral and physiological responses in offspring mice. Pregnant mice were randomly divided into three SMM-treated groups, namely low-(10mg/kg/day), medium-(50mg/kg/day), and high-dose (200mg/kg/day), and a control group. The pregnant mice in the SMM-treated groups received SMM by gavage daily from gestational day 1-18, whereas those in the control received normal saline. On postnatal day (PND) 50, spatial memory was assessed using the Morris water maze test, and anxiety was measured using the elevated plus-maze and open field tests. The results showed significantly increased blood glucose in pups whose mothers received a high SMM dose. In addition, maternal SMM exposure increased anxiety-related activities among the offspring; spatial learning and memory were impaired more severely in the male offspring. The contents of tetrahydrobiopterin (BH4) and brain-derived neurotrophic factors (BDNF) on PND 22 were significantly reduced in the male offspring of the high-dose group compared with the controls. These findings indicate that SMM may be identified as a risk factor for cognitive and behavioral development on the basis of gender and that it may be associated with diminished BH4 and BDNF levels early in life. PMID:27173165

  11. Parental Divorce and Interpersonal Trust in Adult Offspring.

    Science.gov (United States)

    King, Valarie

    2002-01-01

    Examines whether parental divorce is associated with offspring trust in parents, intimate partners, and others. Results reveal that although parental divorce is negatively associated with trust, these effects largely disappear once the quality of the past parent-teen relationship is taken into account. (Contains 48 references and 4 tables.) (GCP)

  12. Dominant cataract mutations detected in offspring of gamma-irradiated male mice

    International Nuclear Information System (INIS)

    The technique of biomicroscopic eye examination followed by breeding tests provides a new method for detection of dominant mutations in mice. A total of 11 cataract mutations were found among 17,436 offspring of irradiated male mice. No cataract mutations were observed in 8,174 offspring from the control group. All mutations were phenotypically different. Of the 11 cataract mutations, 3 were semilethal in heterozygous condition, 7 were lethal in homozygous condition, and one presumed mutant was sterile. Seven mutations had complete penetrance whereas penetrance of three mutations was reduced. The rate of dominant mutations affecting an organ system in mice is of main importance for the quantification of the overall genetic damage due to dominant mutations in man

  13. Effects of ethanol on offspring of C57BL/6J mice alcoholized during gestation

    Directory of Open Access Journals (Sweden)

    Grinfeld Hermann

    1999-01-01

    Full Text Available The effects of chronic alcohol consumption during pregnancy were analysed in the gestation and offspring of alcoholized mice. Female C57BL/6J mice were placed overnight with stud males and the presence of a sperm plug in the next morning indicated the onset of gestation. Pregnant mice were distributed in two weight-matched groups. In the alcoholized group, the mice received a high protein liquid diet ad libitum containing 27.5% of ethanol-derived calories (5.28% v/v from gestation day 5 to 19. The control group received the same volume of diet containing isocaloric amounts of maltose-dextrin substituted for ethanol. After postnatal day zero, the dams received food pellets and tap water ad libitum. On postnatal day 6 the pups were counted and weighed at variable intervals up to the 60th day of life. The majority of the pregnant dams that have received ethanol completed the gestational period, and the chronic consumption of alcohol did not interfere with the number of dams that gave birth. The alcoholized and control dams gained an equivalent weight and consumed an equivalent volume of diet throughout the gestation. The number of pups from alcohol diet dams was 46,26% smaller compared with the control group. There were less male than female pups in the offspring of alcoholized mice. Teratogeny like gastroschisis and limb malformation were present in the offspring of alcoholized dams. The body weight of the offspring of alcoholized mice increased from the 18th to the 36th postnatal day.

  14. Maternal exposure to cadmium during gestation perturbs the vascular system of the adult rat offspring

    International Nuclear Information System (INIS)

    Several cardiovascular diseases (CVD) observed in adulthood have been associated with environmental influences during fetal growth. Here, we show that maternal exposure to cadmium, a ubiquitously distributed heavy metal and main component of cigarette smoke is able to induce cardiovascular morpho-functional changes in the offspring at adult age. Heart morphology and vascular reactivity were evaluated in the adult offspring of rats exposed to 30 ppm of cadmium during pregnancy. Echocardiographic examination shows altered heart morphology characterized by a concentric left ventricular hypertrophy. Also, we observed a reduced endothelium-dependent reactivity in isolated aortic rings of adult offspring, while endothelium-independent reactivity remained unaltered. These effects were associated with an increase of hem-oxygenase 1 (HO-1) expression in the aortas of adult offspring. The expression of HO-1 was higher in females than males, a finding likely related to the sex-dependent expression of the vascular cell adhesion molecule 1 (VCAM-1), which was lower in the adult female. All these long-term consequences were observed along with normal birth weights and absence of detectable levels of cadmium in fetal and adult tissues of the offspring. In placental tissues however, cadmium levels were detected and correlated with increased NF-κB expression - a transcription factor sensitive to inflammation and oxidative stress - suggesting a placentary mechanism that affect genes related to the development of the cardiovascular system. Our results provide, for the first time, direct experimental evidence supporting that exposure to cadmium during pregnancy reprograms cardiovascular development of the offspring which in turn may conduce to a long term increased risk of CVD.

  15. Incretin and glucagon levels in adult offspring exposed to maternal diabetes in pregnancy

    DEFF Research Database (Denmark)

    Kelstrup, Louise; Clausen, Tine D; Mathiesen, Elisabeth R;

    2015-01-01

    CONTEXT: Fetal exposure to maternal diabetes is associated with increased risk of type 2 diabetes mellitus (T2DM) later in life. The pathogenesis of T2DM involves dysfunction of the incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), as well as...... hyperglucagonemia. OBJECTIVE: Our aim was to investigate circulating plasma levels of GLP-1, GIP, and glucagon during the oral glucose tolerance test (OGTT) in adult offspring of women with diabetes in pregnancy. DESIGN AND PARTICIPANTS: We conducted a follow-up study of 567 offspring, aged 18-27 years. We included...... two groups exposed to maternal diabetes in utero: offspring of women with diet-treated gestational diabetes mellitus (O-GDM; n = 163) or type 1 diabetes (O-T1DM; n = 146). Two reference groups were included: offspring of women with risk factors for GDM, but normoglycemia during pregnancy (O-NoGDM; n...

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

    Directory of Open Access Journals (Sweden)

    Fei Liang

    2015-01-01

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

  17. Maternal immune activation affects litter success, size and neuroendocrine responses related to behavior in adult offspring.

    Science.gov (United States)

    French, Susannah S; Chester, Emily M; Demas, Gregory E

    2013-07-01

    It is increasingly evident that influences other than genetics can contribute to offspring phenotype. In particular, maternal influences are an important contributing factor to offspring survival, development, physiology and behavior. Common environmental pathogens such as viral or bacterial microorganisms can induce maternal immune responses, which have the potential to alter the prenatal environment via multiple independent pathways. The effects of maternal immune activation on endocrine responses and behavior are less well studied and provide the basis for the current study. Our approach in the current study was two-pronged: 1) quantify sickness responses during pregnancy in adult female hamsters experiencing varying severity of immune responsiveness (i.e., differing doses of lipopolysaccharide [LPS]), and 2) assess the effects of maternal immune activation on offspring development, immunocompetence, hormone profiles, and social behavior during adulthood. Pregnancy success decreased with increasing doses of LPS, and litter size was reduced in LPS dams that managed to successfully reproduce. Unexpectedly, pregnant females treated with LPS showed a hypothermic response in addition to the more typical anorexic and body mass changes associated with sickness. Significant endocrine changes related to behavior were observed in the offspring of LPS-treated dams; these effects were apparent in adulthood. Specifically, offspring from LPS treated dams showed significantly greater cortisol responses to stressful resident-intruder encounters compared with offspring from control dams. Post-behavior cortisol was elevated in male LPS offspring relative to the offspring of control dams, and was positively correlated with the frequency of bites during agonistic interactions, and cortisol levels in both sexes were related to defensive behaviors, suggesting that changes in hypothalamo-pituitary-adrenal axis responsiveness may play a regulatory role in the observed behavioral

  18. Feeding Supplemental Iodine to Adult Mink;Effect on Thyroid Hormones in Adult and offspring

    Institute of Scientific and Technical Information of China (English)

    RossE.Jones; RichardJ.Aulerich; 等

    1993-01-01

    We fed adult mink diets containing supplemental iodine,from o 50 320ppm,for one or seven months prior to breeding.Bllod samples collected from the adults and their offspring(kits)at 4wk post-partum were assayed for total thyroxine(T4),triiodothyronine(T3),reverse T3(rT3),and T4-binding indices.As expected T4 concentrations of the adult and kit mink varied inversely with the level of supplemental iodine.In addition,T3 and r T3 concentrations decreased gradually in kits from the long-term experiment in response to the increased dietary iodine of the dams.T3 concentrations of kits from dams fed iodine short-term decreased markedly while r T3 concentrations were elevated greatly in response to increased dietary iodine of the dam.These decreases in hormone levels are due to serum odine blocking the thyroid uptake of iodine and subsequent decrease of hormone synthesis,Excess iodine may also block the effect of thyroid stimulating hormone.The T4-binding indices of the adults,in general,were depressed,while the T4-binding indices of the kits were more variable.These effects are probably due to fluctuations in thyroglobulin.

  19. Cognitive function in adult offspring of women with gestational diabetes-the role of glucose and other factors

    DEFF Research Database (Denmark)

    Clausen, Tine D; Mortensen, Erik Lykke; Schmidt, Lone;

    2013-01-01

    We aimed to evaluate cognitive function in adult offspring of women with diet-treated gestational diabetes and to study potential associations with maternal glucose values.......We aimed to evaluate cognitive function in adult offspring of women with diet-treated gestational diabetes and to study potential associations with maternal glucose values....

  20. Feeding probiotic Lactobacillus rhamnosus (MTCC 5897) fermented milk to suckling mothers alleviates ovalbumin-induced allergic sensitisation in mice offspring.

    Science.gov (United States)

    Saliganti, Vamshi; Kapila, Rajeev; Sharma, Rohit; Kapila, Suman

    2015-10-28

    The neonatal period is often polarised to T helper (Th2) response at the time of birth, predisposing offspring to allergic disorders. Passive immunity through the mother's milk is critical for immune system development of newborns. Probiotics have been proposed to harmonise Th1/Th2 imbalance in allergic conditions in adults. In the present study, the anti-allergic effects of feeding probiotic Lactobacillus rhamnosus-fermented milk (PFM) either to dams during the suckling period or to their offspring after weaning individually or else in successive periods against ovalbumin (OVA)-induced allergy in newborns was analysed. After allergen sensitisation, physical symptoms of allergy, gut immune response, humoral immune response and cell-mediated response through interleukins were detected. Consumption of PFM by mothers and offspring showed a reduction (P<0·01) in physical allergic symptoms in newborns with an increase (P<0·01) in the numbers of goblet and IgA+ cells in the small intestine. Similarly, considerable (P<0·001) decreases in OVA-specific antibodies (IgE, IgG, IgG1) and ratios of IgE/IgG2a and IgG1/IgG2a in the sera of newborn mice were recorded. A decrease in IL-4 and an increase in interferon-γ levels further confirmed the shift from Th2 to Th1 pathway in PFM-fed mice. It is logical to conclude that the timing of PFM intervention in alleviating allergic symptoms is critical, which was found to be most effective when mothers were fed during the suckling period. PMID:26330132

  1. Impact of maternal cigarette smoke exposure on brain inflammation and oxidative stress in male mice offspring

    OpenAIRE

    Chan, Yik Lung; Saad, Sonia; Pollock, Carol; Oliver, Brian; Al-Odat, Ibrahim; Zaky, Amgad A.; Jones, Nicole; Chen, Hui

    2016-01-01

    Maternal cigarette smoke exposure (SE) during gestation can cause lifelong adverse effects in the offspring’s brain. Several factors may contribute including inflammation, oxidative stress and hypoxia, whose changes in the developing brain are unknown. Female Balb/c mice were exposed to cigarette smoke prior to mating, during gestation and lactation. Male offspring were studied at postnatal day (P) 1, P20 and 13 weeks (W13). SE dams had reduced inflammatory mediators (IL-1β, IL-6 and toll lik...

  2. Gestational zinc deficiency impairs humoral and cellular immune responses to hepatitis B vaccination in offspring mice.

    Directory of Open Access Journals (Sweden)

    Ning Zhao

    Full Text Available BACKGROUND: Gestational zinc deficiency has been confirmed to impair the infant immune function. However, knowledge about effects of maternal mild zinc deficiency during pregnancy on hepatitis B vaccine responsiveness in offspring is limited. In this report, we aimed to examine how maternal zinc deficiency during pregnancy influences humoral and cellular immune responses to hepatitis B vaccination in offspring of BALB/c mice. METHODOLOGY/PRINCIPAL FINDINGS: From day 1 of pregnancy upon delivery, maternal mice were given a standard diet (30 mg/kg/day zinc, zinc deficient diet (8 mg/kg/day zinc, or combination of zinc deficient diet (8 mg/kg/day zinc in the first 2 weeks of gestation and zinc supplement diet (150 mg/kg/day zinc for the last week of pregnancy, respectively. Newborn pups of these maternal mice were immunized with hepatitis B vaccine at postnatal weeks 0, 2 and 4. Then, splenocytes and blood samples from the offspring mice were harvested for detection of serum zinc concentrations, humoral and cell-mediated immune responses, expression of cytokines using ELISA, CCK-8 and flow cytometric analysis. Results from the present study demonstrated that gestational zinc deficiency inhibited antibody responses, and decreased the proliferative capacity of T cells in offsprings immunized with hepatitis B vaccine. Additionally, HBsAg-specific cytokines analysis revealed that gestational zinc deficiency could inhibit secretion of IFN-γ from splenocytes, and decrease IFN-γ expression of CD4(+ and CD8(+ T cells. CONCLUSIONS/SIGNIFICANCE: Gestational zinc deficiency can weaken the humoral and cell-mediated immune responses to hepatitis B vaccine via decreasing B cell counts and hepatitis B virus-specific immunoglobulin G production, as well as reducing T cell proliferation, CD4(+/CD8(+ T cell ratio, and Th1-type immune responses.

  3. Effects of mother's dietary exposure to acesulfame-K in Pregnancy or lactation on the adult offspring's sweet preference.

    Science.gov (United States)

    Zhang, Gen-Hua; Chen, Meng-Ling; Liu, Si-Si; Zhan, Yue-Hua; Quan, Ying; Qin, Yu-Mei; Deng, Shao-Ping

    2011-11-01

    This study investigates whether mother's exposure to the artificial sweetener acesulfame-K (AK) during pregnancy or lactation affected her adult offspring's sweet preference. It was found that mother's dietary exposure to AK in pregnancy or lactation decreased the preference thresholds for AK and sucrose solutions in the adult offspring, whereas the preference pattern and the most preferred concentration for AK or sucrose solution were unchanged. Furthermore, the preference scores in the exposure groups were increased significantly when compared with the control group at a range of concentrations for AK or sucrose solution. The existence of AK and its dynamic changes within 24 h in amniotic fluid during pregnancy or in mother's milk during lactation after a single oral infusion of AK solution were revealed by the methods of reversed-phase high-performance liquid chromatography and mass spectrometry. Our data suggest that AK can be ingested by the prenatal or postnatal mice through their mother's amniotic fluid or breast milk, producing a long-dated function on the adult's sweet preference. PMID:21653241

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

    Science.gov (United States)

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

    2016-04-01

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

  5. Lethality and teratogenesis in F1 offspring mice following paternal fission neutron irradiation

    International Nuclear Information System (INIS)

    Studies were conducted to determine whether following genetic damage at germ cell stages induced by paternal exposure to 252Cf fission neutron could lead to teratogenesis in the offspring. Seven-week-old C3H male mice were irradiated with graded doses of 252Cf fission neutrons and then were mated with nine-week-old C57BL females two weeks after the exposure. Three weeks later, it was found that testis and epididymal weight losses as well as the proportions of caudal epididymal sperm abnormalities in irradiated males were significantly greater than those in non-irradiated groups. Pregnant dams were sacrificed on day 18 of gestation and their fetuses were examined for the number of resorptions, intrauterine deaths and teratogenesis in F1 surviving offspring. Embryo lethality among the F1 offspring was found to be significantly higher in the irradiated group than in the non-irradiated group (p 1 offspring significantly increased in the irradiated groups. These results suggest that the paternal radiation exposure may have caused genetic transmission of DNA damage and genetic instability, which is in line with findings that show increases in incidence of teratogenesis in B6C3F1. (author)

  6. Lethality and teratogenesis in F{sub 1} offspring mice following paternal fission neutron irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Shoji, Shuneki [Hiroshima Univ., Research Institute for Radiation Biology and Medicine, Hiroshima (Japan)

    2003-07-01

    Studies were conducted to determine whether following genetic damage at germ cell stages induced by paternal exposure to {sup 252}Cf fission neutron could lead to teratogenesis in the offspring. Seven-week-old C3H male mice were irradiated with graded doses of {sup 252}Cf fission neutrons and then were mated with nine-week-old C57BL females two weeks after the exposure. Three weeks later, it was found that testis and epididymal weight losses as well as the proportions of caudal epididymal sperm abnormalities in irradiated males were significantly greater than those in non-irradiated groups. Pregnant dams were sacrificed on day 18 of gestation and their fetuses were examined for the number of resorptions, intrauterine deaths and teratogenesis in F{sub 1} surviving offspring. Embryo lethality among the F{sub 1} offspring was found to be significantly higher in the irradiated group than in the non-irradiated group (p < 0.01), while the incidence of congenital malformations among the F{sub 1} offspring significantly increased in the irradiated groups. These results suggest that the paternal radiation exposure may have caused genetic transmission of DNA damage and genetic instability, which is in line with findings that show increases in incidence of teratogenesis in B{sub 6}C{sub 3}F{sub 1}. (author)

  7. Parents' Education and their Adult Offspring's Other-Regarding Behavior

    DEFF Research Database (Denmark)

    Nielsen, Ulrik Haagen

    among adults. This result is robust across age groups and genders. I provide two explanations for this. First, sociodemographic characteristics in general appear to be poor predictors of adults' other-regarding behavior. Second, by using Danish survey data, I find that Danish parents' educational...

  8. Cognitive Function in Adult Offspring of Women with Gestational Diabetes–The Role of Glucose and Other Factors

    OpenAIRE

    Clausen, Tine D.; Mortensen, Erik L.; Lone Schmidt; Mathiesen, Elisabeth R; Torben Hansen; Jensen, Dorte M.; Peter Damm

    2013-01-01

    OBJECTIVE: We aimed to evaluate cognitive function in adult offspring of women with diet-treated gestational diabetes and to study potential associations with maternal glucose values. MATERIALS AND METHODS: In 2003-2005 cognitive function was assessed in a cohort of 18-27 year old offspring of women with diet-treated gestational diabetes mellitus (n = 153) and offspring from the background population (n = 118). The main outcome measure was global cognitive score derived from Raven's Progressi...

  9. The maternal interleukin-17a pathway in mice promotes autism-like phenotypes in offspring.

    Science.gov (United States)

    Choi, Gloria B; Yim, Yeong S; Wong, Helen; Kim, Sangdoo; Kim, Hyunju; Kim, Sangwon V; Hoeffer, Charles A; Littman, Dan R; Huh, Jun R

    2016-02-26

    Viral infection during pregnancy has been correlated with increased frequency of autism spectrum disorder (ASD) in offspring. This observation has been modeled in rodents subjected to maternal immune activation (MIA). The immune cell populations critical in the MIA model have not been identified. Using both genetic mutants and blocking antibodies in mice, we show that retinoic acid receptor-related orphan nuclear receptor gamma t (RORγt)-dependent effector T lymphocytes [for example, T helper 17 (TH17) cells] and the effector cytokine interleukin-17a (IL-17a) are required in mothers for MIA-induced behavioral abnormalities in offspring. We find that MIA induces an abnormal cortical phenotype, which is also dependent on maternal IL-17a, in the fetal brain. Our data suggest that therapeutic targeting of TH17 cells in susceptible pregnant mothers may reduce the likelihood of bearing children with inflammation-induced ASD-like phenotypes. PMID:26822608

  10. Long-term effects of delayed fatherhood in mice on postnatal development and behavioral traits of offspring.

    Science.gov (United States)

    García-Palomares, Silvia; Pertusa, José F; Miñarro, José; García-Pérez, Miguel A; Hermenegildo, Carlos; Rausell, Francisco; Cano, Antonio; Tarín, Juan J

    2009-02-01

    This study aims to analyze, in mice, the long-term effects of delayed fatherhood on postnatal development, spontaneous motor activity, and learning capacity of offspring. Hybrid parental-generation (F(0)) males, at the age of 12, 70, 100, and 120 wk, were individually housed with a randomly selected 12-wk-old hybrid female. The resulting first-generation (F(1)) offspring were tested for several developmental and behavioral variables. Cumulative percentage of F(1) pups that attained immediate righting in the 120-wk group was lower than that found in the 12-, 70-, and 100-wk groups. Furthermore, the postnatal day of attaining immediate righting was higher in pups from the 120-wk group when compared to pups from the other age-groups. At the age of 20 wk, F(1) offspring from the 120-wk group displayed lower counts of motor activity than offspring from the 12-, 70-, and 100-wk groups. One week later, a higher percentage of offspring from the 100- and 120-wk groups entered the dark compartment during the retention trial of the passive-avoidance test when compared to offspring from the 12-wk group. Offspring from the 120-wk group exhibited also lower step-through latency in the retention trial than offspring from the 12-, 70-, and 100-wk groups. These results show that advanced paternal age at conception has long-term effects on preweaning development, spontaneous motor activity, and reduced passive-avoidance learning capacity of mouse offspring. PMID:18923158

  11. Giardia lamblia infections in adult mice.

    OpenAIRE

    Byrd, L G; Conrad, J T; Nash, T E

    1994-01-01

    An adult mouse-Giardia lamblia model was developed and used to study host-parasite interactions, including antigenic variation. The H7/1 clone of isolate GS infected mice consistently and produced infections in 14 mouse strains tested. Infection patterns were mouse strain and Giardia isolate dependent. Antigenic variation occurred in immunocompetent mice but not in mice with severe combined immunodeficiency.

  12. A search for transmission ratio distortions in offspring from crosses between inbred mice

    Indian Academy of Sciences (India)

    D. Purushothaman; R. W. Elliott; A. Ruvinsky

    2008-08-01

    Equal transmission of the two alleles at a locus from a heterozygote parent to the offspring is rarely violated. Beside the differential embryonic mortality, nondisjunction and gene conversion that are rather irregular forms of transmission–ratio distortion (TRD), there are two major forms of departure from Mendelian segregation. The first, found in females, based on the asymmetric nature of female meiosis, is usually referred to as meiotic drive, and has been well documented in a few cases. The second is segregation distortion found in males. There are several known male-related segregation distortion systems that are caused by different fertilizing capacity of sperm cells carrying alternative alleles at a particular locus. Observation of TRD effects requires a sufficient number of offspring produced by a parental pair. As individuals in a population most likely have different genotypes in TRD affecting loci, the total transmission ratio is close to the expected Mendelian ratio and masks potential TRD effects. Highly inbred strains of laboratory mice provide a very good model for studying this phenomenon, because comparing two mice strains is effectively similar as comparison of two individuals in a population. This study tests both forms of TRD in progeny of F1 hybrids from reciprocal crosses of inbred mice. Three previously unknown instances of TRD in females were observed. Therefore, this study concludes that some genes in females may carry alleles that can cause segregation distortion.

  13. Maternal Cocaine Administration in Mice Alters DNA Methylation and Gene Expression in Hippocampal Neurons of Neonatal and Prepubertal Offspring

    OpenAIRE

    Novikova, Svetlana I.; He, Fang; Bai, Jie; Cutrufello, Nicholas J.; Lidow, Michael S.; Undieh, Ashiwel S.

    2008-01-01

    Previous studies documented significant behavioral changes in the offspring of cocaine-exposed mothers. We now explore the hypothesis that maternal cocaine exposure could alter the fetal epigenetic machinery sufficiently to cause lasting neurochemical and functional changes in the offspring. Pregnant CD1 mice were administered either saline or 20 mg/kg cocaine twice daily on gestational days 8–19. Male pups from each of ten litters of the cocaine and control groups were analyzed at 3 (P3) or ...

  14. Gestational Exposure to a Viral Mimetic Poly(I:C Results in Long-Lasting Changes in Mitochondrial Function by Leucocytes in the Adult Offspring

    Directory of Open Access Journals (Sweden)

    Cecilia Giulivi

    2013-01-01

    Full Text Available Maternal immune activation (MIA is a potential risk factor for autism spectrum disorder (ASD and schizophrenia (SZ. In rodents, MIA results in changes in cytokine profiles and abnormal behaviors in the offspring that model these neuropsychiatric conditions. Given the central role that mitochondria have in immunity and other metabolic pathways, we hypothesized that MIA will result in a fetal imprinting that leads to postnatal deficits in the bioenergetics of immune cells. To this end, splenocytes from adult offspring exposed gestationally to the viral mimic poly(I:C were evaluated for mitochondrial outcomes. A significant decrease in mitochondrial ATP production was observed in poly(I:C-treated mice (45% of controls mainly attributed to a lower complex I activity. No differences were observed between the two groups in the coupling of electron transport to ATP synthesis, or the oxygen uptake under uncoupling conditions. Concanavalin A- (ConA- stimulated splenocytes from poly(I:C animals showed no statistically significant changes in cytokine levels compared to controls. The present study reports for the first time that MIA activation by poly(I:C at early gestation, which can lead to behavioral impairments in the offspring similar to SZ and ASD, leads to long-lasting effects in the bioenergetics of splenocytes of adult offspring.

  15. Associations between substance use disorders and major depression in parents and late adolescent-emerging adult offspring: an adoption study

    DEFF Research Database (Denmark)

    Marmorstein, N. R.; Iacono, W. G.; McGue, M.

    2012-01-01

    Aims To examine whether major depressive disorder (MDD) and substance use disorders [SUDs: specifically, nicotine dependence (ND), alcohol use disorders (AUDs), and cannabis use disorders (CUDs)] in parents predicted increased risk for these disorders in late adolescentemerging adult offspring and...

  16. Maternal exposure to airborne particulate matter causes postnatal immunological dysfunction in mice offspring

    International Nuclear Information System (INIS)

    Evidence suggests that prenatal exposure to air pollution affects the ontogeny and development of the fetal immune system. The aim of this study was to investigate the effect of maternal exposure to airborne particulate matter (PM) on immune function in postnatal offspring. Pregnant female ICR mice were intralaryngopharyngeally administered with 30 μl of phosphate buffered solution (the control group) or resuspended PM of Standard Reference Material 1649a at 0.09 (low), 0.28 (medium), 1.85 (high) or 6.92 (overdose) μg/μl once every three days from day 0 to 18 of pregnancy (n = 8–10). Offspring were sacrificed on postnatal day 30. Interleukin-4 and interferon-γ levels in plasma and splenocytes, splenic lymphocyte proliferation, and expressions of GATA-3 and T-bet mRNA in the spleen were tested. The spleen and thymus were histopathologically examined. The offspring of the medium, high and overdose PM-exposed dams showed significantly suppressed splenocyte proliferation. Decreased interferon-γ and increased interleukin-4 levels in the blood and splenocytes, and lowered T-bet and elevated GATA-3 mRNA expressions were found in the spleen in the medium, high and overdose groups when compared with the control or low dose group (P < 0.05). Histopathology revealed prominent tissue damage in the spleen and thymus in the overdose group. These results suggest that exposure of pregnant mice to PM modulates the fetal immune system, resulting in postnatal immune dysfunction by exacerbation of Thl/Th2 deviation. This deviation is associated with altered T-bet and GATA-3 gene expressions

  17. Older maternal age is associated with depression, anxiety, and stress symptoms in young adult female offspring.

    Science.gov (United States)

    Tearne, Jessica E; Robinson, Monique; Jacoby, Peter; Allen, Karina L; Cunningham, Nadia K; Li, Jianghong; McLean, Neil J

    2016-01-01

    The evidence regarding older parental age and incidence of mood disorder symptoms in offspring is limited, and that which exists is mixed. We sought to clarify these relationships by using data from the Western Australian Pregnancy Cohort (Raine) Study. The Raine Study provided comprehensive data from 2,900 pregnancies, resulting in 2,868 live born children. A total of 1,220 participants completed the short form of the Depression Anxiety Stress Scale (DASS-21) at the 20-year cohort follow-up. We used negative binomial regression analyses with log link and with adjustment for known perinatal risk factors to examine the extent to which maternal and paternal age at childbirth predicted continuous DASS-21 index scores. In the final multivariate models, a maternal age of 30-34 years was associated with significant increases in stress DASS-21 scores in female offspring relative to female offspring of 25- to 29-year-old mothers. A maternal age of 35 years and over was associated with increased scores on all DASS-21 scales in female offspring. Our results indicate that older maternal age is associated with depression, anxiety, and stress symptoms in young adult females. Further research into the mechanisms underpinning this relationship is needed. PMID:26569038

  18. Maternal protein restriction affects gene expression and enzyme activity of intestinal disaccharidases in adult rat offspring

    International Nuclear Information System (INIS)

    This study investigated the consequences of intrauterine protein restriction on the gastrointestinal tract and particularly on the gene expression and activity of intestinal disaccharidases in the adult offspring. Wistar rat dams were fed isocaloric diets containing 6% protein (restricted, n = 8) or 17% protein (control, n = 8) throughout gestation. Male offspring (n = 5-8 in each group) were evaluated at 3 or 16 weeks of age. Maternal protein restriction during pregnancy produced offspring with growth restriction from birth (5.7 ± 0.1 vs 6.3 ± 0.1 g; mean ± SE) to weaning (42.4 ± 1.3 vs 49.1 ± 1.6 g), although at 16 weeks of age their body weight was similar to control (421.7 ± 8.9 and 428.5 ± 8.5 g). Maternal protein restriction also increased lactase activity in the proximal (0.23 ± 0.02 vs 0.15 ± 0.02), medial (0.30 ± 0.06 vs 0.14 ± 0.01) and distal (0.43 ± 0.07 vs 0.07 ± 0.02 U·g-1·min-1) small intestine, and mRNA lactase abundance in the proximal intestine (7.96 ± 1.11 vs 2.38 ± 0.47 relative units) of 3-week-old offspring rats. In addition, maternal protein restriction increased sucrase activity (1.20 ± 0.02 vs 0.91 ± 0.02 U·g-1·min-1) and sucrase mRNA abundance (4.48 ± 0.51 vs 1.95 ± 0.17 relative units) in the duodenum of 16-week-old rats. In conclusion, the present study shows for the first time that intrauterine protein restriction affects gene expression of intestinal enzymes in offspring

  19. Maternal smoking during pregnancy predicts adult offspring cardiovascular risk factors - evidence from a community-based large birth cohort study.

    Directory of Open Access Journals (Sweden)

    Abdullah A Mamun

    Full Text Available BACKGROUND: Maternal smoking during pregnancy is associated with offspring obesity. However, little is known about whether maternal smoking in pregnancy predicts other offspring cardiovascular risk factors including waist circumference (WC, waist-hip-ratio (WHR, pulse rate (PR, systolic (SBP, and diastolic blood pressure (DBP. METHODS: We studied a sub-sample of 2038 (50% males young adults who were born in Brisbane, Australia to investigate the prospective association of maternal smoking during pregnancy with young adult cardiovascular risk factors. We compared offspring mean BMI, WC, WHR, SBP, DBP and PR and the risk of being overweight and obese at 21 years by three mutually exclusive categories of maternal smoking status defined as never smoked, smoked before and/or after pregnancy but not in pregnancy or smoked during pregnancy and other times. RESULTS: Offspring of mothers who smoked during pregnancy had greater mean BMI, WC, WHR and PR and they were at greater risk of being obese at 21 years compared to offspring of those mothers who never smoked. The mean of these risk factors among those adult offspring whose mothers stopped smoking during pregnancy, but who then smoked at other times in the child's life, were similar to those mothers who never smoked. These results were independent of a range of potential confounding factors. CONCLUSION: The findings of this study suggest a prospective association of maternal smoking during pregnancy and offspring obesity as well as PR in adulthood, and reinforce the need to persuade pregnant women not to smoke.

  20. The Effect of Saffron Decoction Consumption on Pregnant Mice and Their Offspring

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    Oveisi

    2012-02-01

    Full Text Available Introduction: In traditional medicine, saffron is used as a drug for treating many diseases. However there are many documents and evidences concerning its abortive and teratogenic effect especially in high doses. Aim: This study was conducted to evaluate the effect of saffron decoction consumption on pregnant mice and their offspring. Methods: In this study, 20 female mice after breeding and observation of vaginal plaque, randomly and equally divided into two groups. During pregnancy, animals were housed under the same environmental and nutritional condition while the test group received 0.5% saffron decoction as their drinks instead of tape water for control group. The pregnant mice were weighted during pregnancy and after delivery. Following the parturition, the number of live kids, their weight and sex and any pretended obvious abnormality were assigned. Results: The duration of pregnancy period and the number of live kids in test group were significantly less than control group while the mean infant’s weight in test group was more than control group. There was obvious one-eye blindness in 4 kids from saffron consumed group. In the case of mother's weight and sex ratio of live kids there was no significant difference between the two groups. Conclusion: This study indicated that saffron has a specific teratogenic effect on visual system and causes preterm labor and reduces the number of live infants which may be due to its abortive effect. Keywords: Saffron, Pregnancy, Infant, Teratogen, Mice

  1. Effects of fetal microwave radiation exposure on offspring behavior in mice

    International Nuclear Information System (INIS)

    The recent rapid development of electronic communication techniques is resulting in a marked increase in exposure of humans to electromagnetic fields (EMFs). This has raised public concerns about the health hazards of long-term environmental EMF exposure for fetuses and children. Some studies have suggested EMF exposure in children could induce nervous system disorders. However, gender-dependent effects of microwave radiation exposure on cognitive dysfunction have not previously been reported. Here we investigated whether in utero exposure to 9.417-GHz microwave throughout gestation (Days 3.5–18) affected behavior, using the open field test (OFT), elevated-plus maze (EPM), tail suspension test (TST), forced swimming test (FST) and Morris water maze (MWM). We found that mice showed less movement in the center of an open field (using the OFT) and in an open arm (using the EPM) after in utero exposure to 9.417-GHz radiation, which suggested that the mice had increased anxiety-related behavior. Mice demonstrated reduced immobility in TST and FST after in utero exposure to 9.417-GHz radiation, which suggested that the mice had decreased depression-related behavior. From the MWM test, we observed that male offspring demonstrated decreased learning and memory, while females were not affected in learning and memory, which suggested that microwaves had gender-dependent effects. In summary, we have provided the first experimental evidence of microwaves inducing gender-dependent effects. (author)

  2. Maternal allergen immunisation to prevent sensitisation in offspring: Th2-polarising adjuvants are more efficient than a Th1-polarising adjuvant in mice

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    Melkild Ingrid

    2010-03-01

    Full Text Available Abstract Background Allergy has been an increasing problem in several parts of the world. Prenatal exposure to allergen and microbial components may affect the development of allergies in childhood, as indicated by epidemiological and experimental studies. We investigated the capacity for allergic sensitisation in offspring after induction of a Th1- or a Th2-polarised immune response to the same allergen in mothers during pregnancy. Results During pregnancy, mice were immunised with ovalbumin (OVA given with either one of the Th2-adjuvants pertussis toxin (PT or Al(OH3 (aluminium hydroxide, or with the Th1 adjuvant CpG. Offspring were immunised with OVA in Al(OH3 as young adults. Serum and supernatants from ex vivo stimulated or non-stimulated spleen cells from mothers and offspring were analysed for OVA-specific antibodies and cytokines, respectively. Mothers immunised with OVA together with either Al(OH3 or PT had increased levels of OVA-specific IgE and IgG1 compared to naive mothers, whereas mothers immunised with OVA together with CpG had increased levels of OVA-specific IgG2a compared to naive mothers. In general the highest levels of IL-5, IL-10, and IFNγ were observed in spleen cells from mothers immunised with PT and OVA. Upon immunisation, offspring from mothers immunised with OVA and either PT or Al(OH3 showed reduced levels of OVA-specific IgE and IgG1 and increased levels of OVA-specific IgG2a antibodies compared to offspring from naive mothers. Maternal immunisation with CpG and OVA did not affect antibody responses in offspring. Conclusion Allergic sensitisation in the offspring was affected by the type of adjuvant used for immunisation of the mothers with the same allergen. Th2 polarisation of the immune response in the mothers was found to give reduced IgE levels upon sensitisation of the offspring, whereas no reduction was achieved with Th1 polarisation in the mothers.

  3. Insulin Resistance and Impaired Pancreatic β-Cell Function in Adult Offspring of Women With Diabetes in Pregnancy

    DEFF Research Database (Denmark)

    Kelstrup, Louise; Damm, Peter; Mathiesen, Elisabeth R;

    2013-01-01

    Context:Offspring of women with diabetes during pregnancy have increased risk of glucose intolerance in adulthood, but the underlying mechanisms are unknown.Objective:We aimed to investigate effects of intrauterine hyperglycemia on insulin secretion and - action in adult offspring of mothers...... reference groups were included: offspring of women with risk factors for GDM, but normo-glycemia during pregnancy (N=139) and offspring from the background population (N=128).Main outcome measures:Indices of insulin sensitivity and insulin release were calculated using insulin and glucose values from...... a standard oral glucose tolerance test (120 minutes, 75 gram glucose). Pancreatic beta-cell function taking the prevailing insulin sensitivity into account was estimated by disposition indices.Results:Both groups of offspring exposed during pregnancy to either maternal gestational diabetes or type 1 diabetes...

  4. Maternal Grand Multiparity and the Risk of Severe Mental Disorders in Adult Offspring.

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    Marius Lahti

    Full Text Available Previous studies have shown that maternal grand multiparity may predict an increased risk of mental disorders in young adult offspring, but whether such effects persist throughout adulthood remains unknown. The current study examined if maternal grand multiparity predicts the risks of severe mental disorders, suicides, suicide attempts and dementias throughout adult life.Our study sample comprised 13243 Helsinki Birth Cohort Study 1934-1944 participants (6905 men and 6338 women. According to hospital birth records, 341 offspring were born to grand multiparous mothers. From Finnish national hospital discharge and causes of death registers, we identified 1682 participants diagnosed with mental disorders during 1969-2010.Maternal grand multiparity predicted significantly increased risks of mood disorders (Hazard Ratio = 1.64, p = 0.03, non-psychotic mood disorders (Hazard Ratio = 2.02, p = 0.002, and suicide attempts (Hazard Ratio = 3.94, p = 0.01 in adult offspring. Furthermore, women born to grand multiparous mothers had significantly increased risks of any severe mental disorder (Hazard Ratio = 1.79, p = 0.01, non-psychotic substance use disorders (Hazard Ratio = 2.77, p = 0.02 schizophrenia, schizotypal and delusional disorders (Hazard Ratio = 2.40, p = 0.02, mood disorders (Hazard Ratio = 2.40, p = 0.002, non-psychotic mood disorders (Hazard Ratio = 2.91, p<0.001, and suicide attempts (Hazard Ratio = 5.05, p = 0.01 in adulthood. The effects of maternal grand multiparity on offspring psychopathology risk were independent of maternal age and body mass index at childbirth, and of year of birth, sex, childhood socioeconomic position, and birth weight of the offspring. In contrast, no significant effects were found among men.Women born to grand multiparous mothers are at an increased risk of severe mental disorders and suicide attempts across adulthood. Our findings may inform the

  5. Cognitive function in adult offspring of women with gestational diabetes--the role of glucose and other factors.

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    Tine D Clausen

    Full Text Available OBJECTIVE: We aimed to evaluate cognitive function in adult offspring of women with diet-treated gestational diabetes and to study potential associations with maternal glucose values. MATERIALS AND METHODS: In 2003-2005 cognitive function was assessed in a cohort of 18-27 year old offspring of women with diet-treated gestational diabetes mellitus (n = 153 and offspring from the background population (n = 118. The main outcome measure was global cognitive score derived from Raven's Progressive Matrices and three verbal subtests from the Weschler Adult Intelligence Scale. Maternal fasting- and 2-hour blood glucose values from the diagnostic oral glucose tolerance test were used as exposure variables. RESULTS: Offspring of women with gestational diabetes mellitus had a lower global cognitive score, than offspring from the background population (93.1 vs. 100.0, P<0.001. However, when adjusted for maternal age at delivery, parity, smoking during pregnancy, pre-pregnancy overweight, family social class, parental educational level, gender, birth weight, gestational age, perinatal complications and offspring age at follow-up, the difference was no longer statistically significant. Offspring global cognitive score decreased significantly with increasing maternal fasting glucose (β = -4.5, 95% CI -8.0 to -0.9, P = 0.01 and 2-hour glucose (β = -1.5, -2.9 to -0.2, P = 0.03 in univariate general linear models, but not when adjusted for family social class and parental educational level. CONCLUSIONS: Lower cognitive test scores in adult offspring of women with diet-treated gestational diabetes were explained by well known predictors of cognitive function, but not by maternal hyperglycaemia during pregnancy. We find it reassuring that mild intrauterine hyperglycaemia does not seem to have adverse effect on offspring cognitive function.

  6. GONADAL EFFECTS OF FETAL EXPOSURE TO THE AZO DYE CONGO RED IN MICE: INFERTILITY IN FEMALE BUT NOT MALE OFFSPRING

    Science.gov (United States)

    The present study describes the relationship between gonadal genesis and fertility in male and female mice exposed in utero to the diazo dye Congo red (CR). aternal CR treatment inhibited testicular and ovarian function in the offspring after oral administration of I or 0.5 g/kg/...

  7. Distribution of lead in lactating mice and suckling offspring with special emphasis on the mammary gland

    International Nuclear Information System (INIS)

    The distribution of lead in lactating mice and suckling offspring was studied with whole body autoradiography at 4 and 24 h after a single intravenous injection of 203Pb (50 mmol Pb/kg) to the dams. In the lactating mice on day 14 of lactation, the highest uptake of radioactivity at 4 h after administration was recorded in renal cortex, skeleton and liver. A high uptake was also evident in the mannary gland. At 24 h after administration, the radioactivity had decreased in most organs except in the skeleton. In the suckling pups, exposed to lead only via dams' milk for 24 h, the highest level of radioactivity was present in the intestinal mucosa and a much lower level of radioactivity was present in the skeleton. The mammary glands from mice given three daily intravenous injections of 240 μmol Pb/kg were examined with X-ray microanalysis. At 4 h after the last injection, lead was found associated with casein micelles both inside the alveolar cell and in the milk lumen, indicating that lead is excreted into the milk, bound to casein, via the Golgi secretory system. (orig.)

  8. Cognitive Function in Adult Offspring of Women with Gestational Diabetes–The Role of Glucose and Other Factors

    OpenAIRE

    Clausen, Tine D.; Mortensen, Erik L; Schmidt, Lone; Mathiesen, Elisabeth R.; Hansen, Torben; Jensen, Dorte M.; Damm, Peter

    2013-01-01

    Objective We aimed to evaluate cognitive function in adult offspring of women with diet-treated gestational diabetes and to study potential associations with maternal glucose values. Materials and Methods In 2003–2005 cognitive function was assessed in a cohort of 18–27 year old offspring of women with diet-treated gestational diabetes mellitus (n = 153) and offspring from the background population (n = 118). The main outcome measure was global cognitive score derived from Raven’s Progressive...

  9. Sex dependent effects of perinatal taurine exposure on the arterial pressure control in adult offspring

    OpenAIRE

    Roysommuti, Sanya; Suwanich, Atchariya; Lerdweeraphon, Wichaporn; Thaeomor, Atcharaporn; Jirakulsomchok, Dusit; Wyss, J. Michael

    2009-01-01

    The present study tests the sex-dependent effect of perinatal taurine exposure on arterial pressure control in adults. Female Sprague-Dawley rats were fed normal rat chow with 3% beta-alanine (taurine depletion, TD), 3% taurine (taurine supplementation, TS) or water alone (C) from conception to weaning. Their male and female offspring were then fed normal rat chow and tap water with 5% glucose (C with glucose, CG; TD with glucose, TDG; TS with glucose, TSG) or water alone (CW, TDW or TSW). At...

  10. Childhood maltreatment in adult offspring of Portuguese war veterans with and without PTSD

    Directory of Open Access Journals (Sweden)

    Aida Dias

    2014-02-01

    Full Text Available Background: The colonial war that Portugal was involved in between 1961 and 1974 had a significant impact on veterans and their families. However, it is unclear what the consequences of this war are, in particular with regard to levels of childhood maltreatment (CM in offspring. Objective: Our study aims to analyze the influences of fathers’ war exposure and posttraumatic stress disorder (PTSD on the offspring's CM and simultaneously test the hypothesis of the intergenerational transmission of father–child CM. Method: Cross-sectional data were collected, using the Childhood Trauma Questionnaire—Short Form, from 203 adult children and 117 fathers. Subjects were distributed according to three conditions based on the father's war exposure status: did not participate in war, or non-war-exposed (NW; participated in war, or war-exposed (W; and war-exposed with PTSD diagnosis (WP. The data were examined using correlations, variance/covariance, and regression analyses. Results: Children of war veterans with PTSD reported more emotional and physical neglect, while their fathers reported increased emotional and physical abuse exposure during their own childhood. Significant father–child CM correlations were found in the war veteran group but less in the war veteran with PTSD group. Father CM predicted 16% of offspring CM of children of war veterans. Conclusions: The father's war-related PTSD might be a risk factor for offspring neglect but potentially a protective one for the father–child abuse transmission. War-exposed fathers without PTSD did transmit their own CM experiences more often. Therefore, father's war exposure and father's war PTSD may each be important variables to take into account in the study of intergenerational transmission of CM.

  11. Maternal high fat diet during pregnancy and lactation alters hepatic expression of insulin like growth factor-2 and key microRNAs in the adult offspring

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    Lehnert Hendrik

    2009-10-01

    Full Text Available Abstract Background miRNAs play important roles in the regulation of gene functions. Maternal dietary modifications during pregnancy and gestation have long-term effects on the offspring, but it is not known whether a maternal high fat (HF diet during pregnancy and lactation alters expression of key miRNAs in the offspring. Results We studied the effects of maternal HF diet on the adult offspring by feeding mice with either a HF or a chow diet prior to conception, during pregnancy and lactation, and all offspring were weaned onto the same chow diet until adulthood. Maternal HF fed offspring had markedly increased hepatic mRNA levels of peroxisome proliferator activated receptor-alpha (ppar-alpha and carnitine palmitoyl transferase-1a (cpt-1a as well as insulin like growth factor-2 (Igf2. A HF diet induced up-regulation of ppar-alpha and cpt-1a expression in the wild type but not in Igf2 knock out mice. Furthermore, hepatic expression of let-7c was also reduced in maternal HF fed offspring. Among 579 miRNAs measured with microarray, ~23 miRNA levels were reduced by ~1.5-4.9-fold. Reduced expression of miR-709 (a highly expressed miRNA, miR-122, miR-192, miR-194, miR-26a, let-7a, let7b and let-7c, miR-494 and miR-483* (reduced by ~4.9 fold was validated by qPCR. We found that methyl-CpG binding protein 2 was the common predicted target for miR-709, miR-let7s, miR-122, miR-194 and miR-26a using our own purpose-built computer program. Conclusion Maternal HF feeding during pregnancy and lactation induced co-ordinated and long-lasting changes in expression of Igf2, fat metabolic genes and several important miRNAs in the offspring.

  12. Lymphoma and lung cancer in offspring born to pregnant mice dosed with dibenzo[a,l]pyrene: The importance of in utero vs. lactational exposure

    International Nuclear Information System (INIS)

    The fetus and neonate cannot be viewed as 'little adults'; they are highly sensitive to toxicity from environmental chemicals. This phenomenon contributes to the fetal basis of adult disease. One example is transplacental carcinogenesis. Animal models demonstrate that environmental chemicals, to which pregnant women are daily exposed, can increase susceptibility of the offspring to cancer. It is uncertain to what degree in utero vs. lactational exposure contributes to cancer, especially for hydrophobic chemicals such as polyhalogenated biphenyls, ethers, dioxins, furans, etc., which can partition into breast milk. We developed a pregnant mouse model in which exposure to the polycyclic aromatic hydrocarbon (PAH), dibenzo[a,l]pyrene (DBP), during late gestation, produces an aggressive T-cell lymphoma in offspring between 3 and 6 months of age. Survivors exhibit multiple lung and liver (males) tumors. Here, we adopt a cross-foster design with litters born to dams treated with DBP exchanged with those born to dams treated with vehicle. Exposure to DBP in utero (about 2 days) produced significantly greater mortality than residual DBP exposure only through breast milk (3 weeks of lactation). As previously observed pups in all groups with an ahrb-1/d ('responsive') genotype were more susceptible to lymphoma mortality than ahrd/d ('non-responsive') siblings. At termination of the study at 10 months, mice exposed in utero also had greater lung tumor multiplicity than mice exposed only during lactation. Our results demonstrate that short exposure to DBP during late gestation presents a greater risk to offspring than exposure to this very hydrophobic PAH following 3 weeks of nursing

  13. 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)

    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

  14. Adult and offspring size in the ocean over 17 orders of magnitude follows two life history strategies.

    Science.gov (United States)

    Neuheimer, A B; Hartvig, M; Heuschele, J; Hylander, S; Kiørboe, T; Olsson, K H; Sainmont, J; Andersen, K H

    2015-12-01

    Explaining variability in offspring vs. adult size among groups is a necessary step to determine the evolutionary and environmental constraints shaping variability in life history strategies. This is of particular interest for life in the ocean where a diversity of offspring development strategies is observed along with variability in physical and biological forcing factors in space and time. We compiled adult and offspring size for 407 pelagic marine species covering more than 17 orders of magnitude in body mass including Cephalopoda, Cnidaria, Crustaceans, Ctenophora, Elasmobranchii, Mammalia, Sagittoidea, and Teleost. We find marine life following one of two distinct strategies, with offspring size being either proportional to adult size (e.g., Crustaceans, Elasmobranchii, and Mammalia) or invariant with adult size (e.g., Cephalopoda, Cnidaria, Sagittoidea, Teleosts, and possibly Ctenophora). We discuss where these two strategies occur and how these patterns (along with the relative size of the offspring) may be shaped by physical and biological constraints in the organism's environment. This adaptive environment along with the evolutionary history of the different groups shape observed life history strategies and possible group-specific responses to changing environmental conditions (e.g., production and distribution). PMID:26909435

  15. Investigation of possible teratogenic effects in the offspring of mice exposed to methylphenidate during pregnancy.

    Science.gov (United States)

    Costa, Gabriel de Araújo; Galvão, Talita Cristina; Bacchi, André Demambre; Moreira, Estefânia Gastaldello; Salles, Maria José Sparça

    2016-02-01

    Methylphenidate (MPH) is a central nervous system stimulant drug that increases concentration and energy level. The safety of MPH use during pregnancy is not well established. Considering the high rate of unplanned pregnancy among young women, potential for accidental exposure to MPH in early pregnancy is high. This study aimed to investigate if MPH administered during pregnancy would induce maternotoxicity, teratogenicity in mice, or both. Pregnant Swiss mice were treated with MPH (5 mg/kg, subcutaneously) or 0.9% saline (control group) from the 5th to the 17th day of pregnancy. In the MPH-treated group, a significant increase in the total number of resorptions with a consequent increase in post-implantation loss and a decrease in fetal viability were detected (all P < 0.05). A total of 91.43% of resorptions were classified as early resorptions. The group treated with MPH presented significant external (polydactyly P < 0.01), skeletal (incomplete ossification of the skull P < 0.01) and visceral (dilated ventricles P < 0.05) malformations. Behavioural effects (motor activity, memory of habituation and anxiety) were not observed in both male and female offspring evaluated at postnatal days 22, 35 and 75. The results suggest that MPH is an embryotoxic and teratogenic drug. PMID:26687907

  16. Heterologous Infection of Pregnant Mice Induces Low Birth Weight and Modifies Offspring Susceptibility to Malaria

    Science.gov (United States)

    Sharma, Ankur; Conteh, Solomon; Langhorne, Jean; Duffy, Patrick E.

    2016-01-01

    Pregnancy malaria (PM) is associated with poor pregnancy outcomes, and can arise due to relapse, recrudescence or a re-infection with heterologous parasites. We have used the Plasmodium chabaudi model of pregnancy malaria in C57BL/6 mice to examine recrudescence and heterologous infection using CB and AS parasite strains. After an initial course of patent parasitemia and first recrudescence, CB but not AS parasites were observed to recrudesce again in most animals that became pregnant. Pregnancy exacerbated heterologous CB infection of AS-experienced mice, leading to mortality and impaired post-natal growth of pups. Parasites were detected in placental blood without evidence of sequestration, unlike P. falciparum but similar to other malaria species that infect pregnant women. Inflammatory cytokine levels were elevated in pregnant females during malaria, and associated with intensity of infection and with poor outcomes. Pups born to dams during heterologous infection were more resistant to malaria infections at 6–7 weeks of age, compared to pups born to malaria-experienced but uninfected dams or to malaria-naïve dams. In summary, our mouse model reproduces several features of human PM, including recrudescences, heterologous infections, poor pregnancy outcomes associated with inflammatory cytokines, and modulation of offspring susceptibility to malaria. This model should be further studied to explore mechanisms underlying PM pathogenesis. PMID:27467392

  17. Maternal protein restriction affects gene expression and enzyme activity of intestinal disaccharidases in adult rat offspring

    Energy Technology Data Exchange (ETDEWEB)

    Pinheiro, D.F.; Pacheco, P.D.G.; Alvarenga, P.V.; Buratini, J. Jr; Castilho, A.C.S.; Lima, P.F.; Sartori, D.R.S.; Vicentini-Paulino, M.L.M. [Departamento de Fisiologia, Instituto de Biociências, Universidade Estadual Paulista, Botucatu, SP (Brazil)

    2013-03-15

    This study investigated the consequences of intrauterine protein restriction on the gastrointestinal tract and particularly on the gene expression and activity of intestinal disaccharidases in the adult offspring. Wistar rat dams were fed isocaloric diets containing 6% protein (restricted, n = 8) or 17% protein (control, n = 8) throughout gestation. Male offspring (n = 5-8 in each group) were evaluated at 3 or 16 weeks of age. Maternal protein restriction during pregnancy produced offspring with growth restriction from birth (5.7 ± 0.1 vs 6.3 ± 0.1 g; mean ± SE) to weaning (42.4 ± 1.3 vs 49.1 ± 1.6 g), although at 16 weeks of age their body weight was similar to control (421.7 ± 8.9 and 428.5 ± 8.5 g). Maternal protein restriction also increased lactase activity in the proximal (0.23 ± 0.02 vs 0.15 ± 0.02), medial (0.30 ± 0.06 vs 0.14 ± 0.01) and distal (0.43 ± 0.07 vs 0.07 ± 0.02 U·g{sup -1}·min{sup -1}) small intestine, and mRNA lactase abundance in the proximal intestine (7.96 ± 1.11 vs 2.38 ± 0.47 relative units) of 3-week-old offspring rats. In addition, maternal protein restriction increased sucrase activity (1.20 ± 0.02 vs 0.91 ± 0.02 U·g{sup -1}·min{sup -1}) and sucrase mRNA abundance (4.48 ± 0.51 vs 1.95 ± 0.17 relative units) in the duodenum of 16-week-old rats. In conclusion, the present study shows for the first time that intrauterine protein restriction affects gene expression of intestinal enzymes in offspring.

  18. Effects of the use of assisted reproductive technologies and an obesogenic environment on resistance artery function and diabetes biomarkers in mice offspring.

    Directory of Open Access Journals (Sweden)

    Francisco I Ramirez-Perez

    Full Text Available Maternal obesity affects the incidence of cardiovascular disease and diabetes in offspring. Also the use of assisted reproductive technologies (ART has been associated with cardiovascular deficiencies in offspring. Obese women often suffer from infertility and use ART to achieve a pregnancy, but the combined effects of maternal obesity and ART on cardiovascular health and incidence of diabetes in the offspring is not known. Here, we report the effects of the use of ART within an obesogenic environment, consisting of feeding a western diet (WD to dams and offspring, on resistance artery function and presence of diabetes biomarkers in juvenile mice offspring. Our results indicate that WD and ART interacted to induce endothelial dysfunction in mesenteric resistance arteries isolated from 7-week-old mice offspring. This was determined by presence of a reduced acetylcholine-induced dilation compared to controls. The arteries from these WD-ART mice also had greater wall cross-sectional areas and wall to lumen ratios indicative of vascular hypertrophic remodeling. Of the diabetes biomarkers measured, only resistin was affected by a WD×ART interaction. Serum resistin was significantly greater in WD-ART offspring compared to controls. Diet and sex effects were observed in other diabetes biomarkers. Our conclusion is that in mice the use of ART within an obesogenic environment interacts to favor the development of endothelial dysfunction in the resistance arteries of juvenile offspring, while having marginal effects on diabetes biomarkers.

  19. Pathogenesis and epidemiology of Brucellosis in Yellowstone bison: serologic and culture results from adult females and their offspring

    Science.gov (United States)

    The objective of this prospective study was to follow the natural course of Brucella abortus infection in cohorts of seropositive and seronegative female bison and their offspring in Yellowstone National Park over a 5 year period. Specimens were collected from 53 adult, female bison at least once a...

  20. Adult and offspring size in the ocean over 17 orders of magnitude follows two life history strategies

    DEFF Research Database (Denmark)

    Neuheimer, Anna; Hartvig, Martin; Heuschele, Jan;

    2015-01-01

    is observed along with variability in physical and biological forcing factors in space and time. We compiled adult and offspring size for 407 pelagic marine species covering more than 17 orders of magnitude in body mass including Cephalopoda, Cnidaria, Crustaceans, Ctenophora, Elasmobranchii, Mammalia...... history strategies and possible group-specific responses to changing environmental conditions (e.g., production and distribution)....

  1. Maternal consumption of canola oil suppressed mammary gland tumorigenesis in C3(1) TAg mice offspring

    International Nuclear Information System (INIS)

    Maternal consumption of a diet high in omega 6 polyunsaturated fats (n-6 PUFA) has been shown to increase risk whereas a diet high in omega 3 polyunsaturated fats (n-3 PUFA) from fish oil has been shown to decrease risk for mammary gland cancer in female offspring of rats. The aim of this study was to determine whether increasing n-3 PUFA and reducing n-6 PUFA by using canola oil instead of corn oil in the maternal diet might reduce the risk for breast cancer in female offspring. Female SV 129 mice were divided into two groups and placed on diets containing either 10% w/w corn oil (which is 50% n-6 PUFA, control diet) or 10% w/w canola oil (which is 20% n-6 PUFA, 10% n-3 PUFA, test diet). After two weeks on the diets the females were bred with homozygous C3(1) TAg transgenic mice. Mother mice consumed the assigned diet throughout gestation and nursing of the offspring. After weaning, all female offspring were maintained on the control diet. Compared to offspring of mothers fed the corn oil diet (CO/CO group), offspring of mothers fed the canola oil diet (CA/CO group) had significantly fewer mammary glands with tumors throughout the experiment. At 130 days of age, the CA/CO group had significantly fewer tumors per mouse (multiplicity); the tumor incidence (fraction of mice with any tumor) and the total tumor weight (per mouse that developed tumor) was less than one half that of the CO/CO group. At 170 days of age, the total tumor weight per mouse was significantly less in the CA/CO group and if a tumor developed the rate of tumor growth rate was half that of CO/CO group. These results indicate that maternal consumption of canola oil was associated with delayed appearance of mammary gland tumors and slowed growth of the tumors that developed. Substituting canola oil for corn oil is an easy dietary change for people to make; such a change to the maternal diet may decrease risk for breast cancer in the daughter

  2. Maternal consumption of canola oil suppressed mammary gland tumorigenesis in C3(1 TAg mice offspring

    Directory of Open Access Journals (Sweden)

    Hardman W Elaine

    2010-03-01

    Full Text Available Abstract Background Maternal consumption of a diet high in omega 6 polyunsaturated fats (n-6 PUFA has been shown to increase risk whereas a diet high in omega 3 polyunsaturated fats (n-3 PUFA from fish oil has been shown to decrease risk for mammary gland cancer in female offspring of rats. The aim of this study was to determine whether increasing n-3 PUFA and reducing n-6 PUFA by using canola oil instead of corn oil in the maternal diet might reduce the risk for breast cancer in female offspring. Methods Female SV 129 mice were divided into two groups and placed on diets containing either 10% w/w corn oil (which is 50% n-6 PUFA, control diet or 10% w/w canola oil (which is 20% n-6 PUFA, 10% n-3 PUFA, test diet. After two weeks on the diets the females were bred with homozygous C3(1 TAg transgenic mice. Mother mice consumed the assigned diet throughout gestation and nursing of the offspring. After weaning, all female offspring were maintained on the control diet. Results Compared to offspring of mothers fed the corn oil diet (CO/CO group, offspring of mothers fed the canola oil diet (CA/CO group had significantly fewer mammary glands with tumors throughout the experiment. At 130 days of age, the CA/CO group had significantly fewer tumors per mouse (multiplicity; the tumor incidence (fraction of mice with any tumor and the total tumor weight (per mouse that developed tumor was less than one half that of the CO/CO group. At 170 days of age, the total tumor weight per mouse was significantly less in the CA/CO group and if a tumor developed the rate of tumor growth rate was half that of CO/CO group. These results indicate that maternal consumption of canola oil was associated with delayed appearance of mammary gland tumors and slowed growth of the tumors that developed. Conclusions Substituting canola oil for corn oil is an easy dietary change for people to make; such a change to the maternal diet may decrease risk for breast cancer in the daughter.

  3. Does physical activity during pregnancy adversely influence markers of the metabolic syndrome in adult offspring?

    DEFF Research Database (Denmark)

    Danielsen, Inge; Granström, Charlotta; Rytter, Dorte;

    2013-01-01

    It is unknown whether physical activity during pregnancy (PA) has long-term impact on the metabolic profile of the offspring. We investigated associations of PA with markers of the metabolic syndrome (MS) in 20y old offspring.......It is unknown whether physical activity during pregnancy (PA) has long-term impact on the metabolic profile of the offspring. We investigated associations of PA with markers of the metabolic syndrome (MS) in 20y old offspring....

  4. Maternal age at Holocaust exposure and maternal PTSD independently influence urinary cortisol levels in adult offspring

    OpenAIRE

    Bader, Heather N.; Linda M. Bierer; Amy eLehrner; Iouri eMakotkine; Daskalakis, Nikolaos P.; Rachel eYehuda

    2014-01-01

    Background: Parental traumatization has been associated with increased risk for the expression of psychopathology in offspring, and maternal PTSD appears to increase the risk for the development of offspring PTSD. In this study, Holocaust-related maternal age of exposure and PTSD were evaluated for their association with offspring ambient cortisol and PTSD-associated symptom expression. Method: 95 Holocaust offspring and Jewish comparison subjects received diagnostic and psychological evaluat...

  5. Maternal Age at Holocaust Exposure and Maternal PTSD Independently Influence Urinary Cortisol Levels in Adult Offspring

    OpenAIRE

    Bader, Heather N.; Linda M. Bierer; Lehrner, Amy; Makotkine, Iouri; Daskalakis, Nikolaos P.; Yehuda, Rachel

    2014-01-01

    Background: Parental traumatization has been associated with increased risk for the expression of psychopathology in offspring, and maternal posttraumatic stress disorder (PTSD) appears to increase the risk for the development of offspring PTSD. In this study, Holocaust-related maternal age of exposure and PTSD were evaluated for their association with offspring ambient cortisol and PTSD-associated symptom expression. Method: Ninety-five Holocaust offspring and Jewish comparison subjects r...

  6. A dose-response relationship between maternal smoking during late pregnancy and adult intelligence in male offspring.

    Science.gov (United States)

    Mortensen, Erik Lykke; Michaelsen, Kim Fleischer; Sanders, Stephanie A; Reinisch, June Machover

    2005-01-01

    An association between maternal smoking during pregnancy and cognitive and behavioural development has been observed in several studies, but potential effects of maternal smoking on offspring adult intelligence have not been investigated. The objective of the present study was to investigate a potential association between maternal smoking during pregnancy and offspring intelligence in young adulthood. Adult intelligence was assessed at the mean age of 18.7 years by a military draft board intelligence test (Borge Priens Prove) for 3044 singleton males from the Copenhagen Perinatal Cohort with information regarding maternal smoking during the third trimester coded into five categories (about 50% of the mothers were smokers). The following potential confounders were included as covariates in multivariable analyses: parental social status and education, single mother status, mother's height and age, number of pregnancies, and gestational age. In separate analyses, birthweight and length were also included as covariates. Maternal cigarette smoking during the third trimester, adjusted for the seven covariates, showed a negative association with offspring adult intelligence (P=0.0001). The mean difference between the no-smoking and the heaviest smoking category amounted to 0.41 standard deviation, corresponding to an IQ difference of 6.2 points [95% confidence interval 0.14, 0.68]. The association remained significant when further adjusted for birthweight and length (P=0.007). Both unadjusted and adjusted means suggested a dose-response relationship between maternal smoking during pregnancy and offspring adult intelligence. When subjects with missing data were excluded, essentially the same results were obtained in the reduced sample (n=1829). These results suggest that smoking during pregnancy may have long-term negative consequences on offspring adult intelligence. PMID:15670102

  7. Flow cytometric characterization of microglia in the offspring of PolyI:C treated mice.

    Science.gov (United States)

    Manitz, Marie Pierre; Plümper, Jennifer; Demir, Seray; Ahrens, Maike; Eßlinger, Manuela; Wachholz, Simone; Eisenacher, Martin; Juckel, Georg; Friebe, Astrid

    2016-04-01

    The neuropathology of schizophrenia has been reported to be closely associated with microglial activation. In a previous study, using the prenatal PolyI:C schizophrenia animal model, we showed an increase in cell numbers and a reduction in microglial branching in 30-day-old PolyI:C descendants, which suggests that there is microglial activation during adolescence. To provide more information about the activation state, we aimed to examine the expression levels of Iba1, which was reported to be up-regulated in activated microglia. We used a flow cytometric approach and investigated CD11b and CD45, two additional markers for the identification of microglial cells. We demonstrated that intracellular staining against Iba1 can be used as a reliable flow cytometric method for identification of microglial cells. Prenatal PolyI:C treatment had long-term effects on CD11b and CD45 expression. It also resulted in a trend towards increased Iba1 expression. Imbalance in CD11b, CD45, and Iba1 expression might contribute to impaired synaptic surveillance and enhanced activation/inflammatory activity of microglia in adult offspring. PMID:26872595

  8. Maternal age at Holocaust exposure and maternal PTSD independently influence urinary cortisol levels in adult offspring

    Directory of Open Access Journals (Sweden)

    Heather N Bader

    2014-07-01

    Full Text Available Background: Parental traumatization has been associated with increased risk for the expression of psychopathology in offspring, and maternal PTSD appears to increase the risk for the development of offspring PTSD. In this study, Holocaust-related maternal age of exposure and PTSD were evaluated for their association with offspring ambient cortisol and PTSD-associated symptom expression. Method: 95 Holocaust offspring and Jewish comparison subjects received diagnostic and psychological evaluations, and 24 hour urinary cortisol was assayed by RIA. Offspring completed the Parental PTSD Questionnaire to assess maternal PTSD status. Maternal Holocaust exposure was identified as having occurred in childhood, adolescence or adulthood and examined in relation to offspring psychobiology. Results: Urinary cortisol levels did not differ for Holocaust offspring and comparison subjects but differed significantly in offspring based on maternal age of exposure and maternal PTSD status. Increased maternal age of exposure and maternal PTSD were each associated with lower urinary cortisol in offspring, but did not exhibit a significant interaction. In addition, offspring PTSD-associated symptom severity increased with maternal age at exposure and PTSD diagnosis. A regression analysis of correlates of offspring cortisol indicated that both maternal age of exposure and maternal PTSD were significant predictors of lower offspring urinary cortisol, whereas childhood adversity and offspring PTSD symptoms were not. Conclusions: Offspring low cortisol and PTSD-associated symptom expression are related to maternal age of exposure, with the greatest effects associated with increased age at exposure. These effects are relatively independent of the negative consequences of being raised by a trauma survivor. These observations highlight the importance of maternal age of exposure in determining a psychobiology in offspring that is consistent with increased risk for stress

  9. Liquid fructose in pregnancy exacerbates fructose-induced dyslipidemia in adult female offspring.

    Science.gov (United States)

    Rodríguez, Lourdes; Panadero, María I; Rodrigo, Silvia; Roglans, Núria; Otero, Paola; Álvarez-Millán, Juan J; Laguna, Juan C; Bocos, Carlos

    2016-06-01

    Fructose intake from added sugars correlates with the epidemic rise in metabolic syndrome and related events. Nevertheless, consumption of beverages sweetened with fructose is not regulated in gestation. Previously, we found that maternal fructose intake produces in the progeny, when fetuses, impaired leptin signaling and hepatic steatosis and then impaired insulin signaling and hypoadiponectinemia in adult male rats. Interestingly, adult females from fructose-fed mothers did not exhibit any of these disturbances. However, we think that, actually, these animals keep a programmed phenotype hidden. Fed 240-day-old female progeny from control, fructose- and glucose-fed mothers were subjected for 3weeks to a fructose supplementation period (10% wt/vol in drinking water). Fructose intake provoked elevations in insulinemia and adiponectinemia in the female progeny independently of their maternal diet. In accordance, the hepatic mRNA levels of several insulin-responsive genes were similarly affected in the progeny after fructose intake. Interestingly, adult progeny of fructose-fed mothers displayed, in response to the fructose feeding, augmented plasma triglyceride and NEFA levels and hepatic steatosis versus the other two groups. In agreement, the expression and activity for carbohydrate response element binding protein (ChREBP), a lipogenic transcription factor, were higher after the fructose period in female descendants from fructose-fed mothers than in the other groups. Furthermore, liver fructokinase expression that has been indicated as one of those responsible for the deleterious effects of fructose ingestion was preferentially augmented in that group. Maternal fructose intake does influence the adult female offspring's response to liquid fructose and so exacerbates fructose-induced dyslipidemia and hepatic steatosis. PMID:27142744

  10. Prenatal inflammation-induced hypoferremia alters dopamine function in the adult offspring in rat: relevance for schizophrenia.

    Directory of Open Access Journals (Sweden)

    Argel Aguilar-Valles

    Full Text Available Maternal infection during pregnancy has been associated with increased incidence of schizophrenia in the adult offspring. Mechanistically, this has been partially attributed to neurodevelopmental disruption of the dopamine neurons, as a consequence of exacerbated maternal immunity. In the present study we sought to target hypoferremia, a cytokine-induced reduction of serum non-heme iron, which is common to all types of infections. Adequate iron supply to the fetus is fundamental for the development of the mesencephalic dopamine neurons and disruption of this following maternal infection can affect the offspring's dopamine function. Using a rat model of localized injury induced by turpentine, which triggers the innate immune response and inflammation, we investigated the effects of maternal iron supplementation on the offspring's dopamine function by assessing behavioral responses to acute and repeated administration of the dopamine indirect agonist, amphetamine. In addition we measured protein levels of tyrosine hydroxylase, and tissue levels of dopamine and its metabolites, in ventral tegmental area, susbtantia nigra, nucleus accumbens, dorsal striatum and medial prefrontal cortex. Offspring of turpentine-treated mothers exhibited greater responses to a single amphetamine injection and enhanced behavioral sensitization following repeated exposure to this drug, when compared to control offspring. These behavioral changes were accompanied by increased baseline levels of tyrosine hydroxylase, dopamine and its metabolites, selectively in the nucleus accumbens. Both, the behavioral and neurochemical changes were prevented by maternal iron supplementation. Localized prenatal inflammation induced a deregulation in iron homeostasis, which resulted in fundamental alterations in dopamine function and behavioral alterations in the adult offspring. These changes are characteristic of schizophrenia symptoms in humans.

  11. Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats

    International Nuclear Information System (INIS)

    Prenatal ethanol exposure (PEE) induces dyslipidemia and hyperglycemia in fetus and adult offspring. However, whether PEE increases the susceptibility to non-alcoholic fatty liver disease (NAFLD) in offspring and its underlying mechanism remain unknown. This study aimed to demonstrate an increased susceptibility to high-fat diet (HFD)-induced NAFLD and its intrauterine programming mechanisms in female rat offspring with PEE. Rat model of intrauterine growth retardation (IUGR) was established by PEE, the female fetus and adult offspring that fed normal diet (ND) or HFD were sacrificed. The results showed that, in PEE + ND group, serum corticosterone (CORT) slightly decreased and insulin-like growth factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE + HFD group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG) increased, with notable catch-up growth, higher metabolic status and NAFLD formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced expression of lipid output were accompanied in PEE + HFD group. In PEE fetus, serum CORT increased while IGF-1 decreased, with low body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1 expression as well as lipid output was down-regulated, while lipid synthesis significantly increased. Based on these findings, we propose a “two-programming” hypothesis for an increased susceptibility to HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine programming of liver glucose and lipid metabolic function is “the first programming”, and postnatal adaptive catch-up growth triggered by intrauterine programming of GC-IGF1 axis acts as “the second programming”. - Highlights: • Prenatal ethanol exposure increase the susceptibility of NAFLD in female offspring. • Prenatal ethanol exposure reprograms fetal liver’s glucose and lipid metabolism . • Prenatal ethanol exposure cause

  12. Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Lang; Liu, Zhongfen; Gong, Jun; Zhang, Li [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Wang, Linlong [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Magdalou, Jacques [UMR 7561 CNRS-Nancy Université, Faculté de Médicine, Vandoeuvre-lès-Nancy (France); Chen, Liaobin [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China)

    2014-01-15

    Prenatal ethanol exposure (PEE) induces dyslipidemia and hyperglycemia in fetus and adult offspring. However, whether PEE increases the susceptibility to non-alcoholic fatty liver disease (NAFLD) in offspring and its underlying mechanism remain unknown. This study aimed to demonstrate an increased susceptibility to high-fat diet (HFD)-induced NAFLD and its intrauterine programming mechanisms in female rat offspring with PEE. Rat model of intrauterine growth retardation (IUGR) was established by PEE, the female fetus and adult offspring that fed normal diet (ND) or HFD were sacrificed. The results showed that, in PEE + ND group, serum corticosterone (CORT) slightly decreased and insulin-like growth factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE + HFD group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG) increased, with notable catch-up growth, higher metabolic status and NAFLD formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced expression of lipid output were accompanied in PEE + HFD group. In PEE fetus, serum CORT increased while IGF-1 decreased, with low body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1 expression as well as lipid output was down-regulated, while lipid synthesis significantly increased. Based on these findings, we propose a “two-programming” hypothesis for an increased susceptibility to HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine programming of liver glucose and lipid metabolic function is “the first programming”, and postnatal adaptive catch-up growth triggered by intrauterine programming of GC-IGF1 axis acts as “the second programming”. - Highlights: • Prenatal ethanol exposure increase the susceptibility of NAFLD in female offspring. • Prenatal ethanol exposure reprograms fetal liver’s glucose and lipid metabolism . • Prenatal ethanol exposure cause

  13. [Tissue-specific Changes in the Polymorphism of Simple Repeats in DNA of the Offspring of Different Sex Born from Irradiated Male or Female Mice].

    Science.gov (United States)

    Lomaeva, M G; Fomenko, L A; Vasil'eva, G V; Bezlepkin, V G

    2016-01-01

    Evidence is presented indicating the differences in the polymorphism of microsatellite (MCS) repeats in DNA of somatic tissues in the offspring of BALB/c mice of different sex born from preconceptionally irradiated males or females. Brother-sister groups of the offspring born by non-irradiated parental pairs were compared with the offspring obtained after the irradiation of one parent in the same pairs. The number of MCS repeats in DNA of somatic tissues of the offspring from irradiated males or females was compared by a polymerase chain reaction using an arbitrary primer. It was found that changes in the polymorphism of the number of MCS repeats in the offspring from the males irradiated at a dose of 2 Gy was insignificant as compared with the offspring from control animals. In the offspring born by the females irradiated at a dose of 2 Gy (which does not impair the reproductive capacity), a statistically significant increase in the polymorphism was observed. Changes in the polymorphism were different in the offspring of different sex. A higher level of polymorphism was revealed in the female offspring born from the females of the F0 generation after their irradiation at a dose of 2 Gy. The increase in the polymorphism of the number of MCS repeats in DNA was more pronounced in postmitotic tissues compared with proliferating tissues. PMID:27534065

  14. Carbon black nanoparticle exposure during middle and late fetal development induces immune activation in male offspring mice

    International Nuclear Information System (INIS)

    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

  15. Hypoxia during pregnancy in rats leads to the changes of the cerebral white matter in adult offspring

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Lingxing; Cai, Ruowei [Department of Neurology, Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian (China); Lv, Guorong, E-mail: lxingwan502@gmail.com [Department of Ultrasound, Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian (China); Huang, Ziyang; Wang, Zhenhua [Department of Cardiology, Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian (China)

    2010-05-28

    The aim of the present study is to evaluate the effect of reduced fetal oxygen supply on cerebral white matter in the adult offspring and further assess its susceptibility to postnatal hypoxia and high-fat diet. Based on a 3 x 2 full factorial design consisting of three factors of maternal hypoxia, postnatal high-fat diet, and postnatal hypoxia, the ultrastructure of myelin, axon and capillaries were observed, and the expression of myelin basic protein (MBP), neurofilament-H+L(NF-H+L), and glial fibrillary acidic protein (GFAP) was analyzed in periventricular white matter of 16-month-old offspring. Demyelination, injured axon and damaged microvasculars were observed in maternal hypoxia offspring. The main effect of maternal hypoxia lead to decreased expression of MBP or NF-H+L, and increased expression of GFAP (all P < 0.05). Moreover, there was positive three-way interaction among maternal hypoxia, high-fat diet and postnatal hypoxia on MBP, NF-H+L or GFAP expression (all P < 0.05). In summary, our results indicated that maternal hypoxia during pregnancy in rats lead to changes of periventricular white matter in adult offspring, including demyelination, damaged axon and proliferated astroglia. This effect was amplified by high-fat diet and postnatal hypoxia.

  16. Hypoxia during pregnancy in rats leads to the changes of the cerebral white matter in adult offspring

    International Nuclear Information System (INIS)

    The aim of the present study is to evaluate the effect of reduced fetal oxygen supply on cerebral white matter in the adult offspring and further assess its susceptibility to postnatal hypoxia and high-fat diet. Based on a 3 x 2 full factorial design consisting of three factors of maternal hypoxia, postnatal high-fat diet, and postnatal hypoxia, the ultrastructure of myelin, axon and capillaries were observed, and the expression of myelin basic protein (MBP), neurofilament-H+L(NF-H+L), and glial fibrillary acidic protein (GFAP) was analyzed in periventricular white matter of 16-month-old offspring. Demyelination, injured axon and damaged microvasculars were observed in maternal hypoxia offspring. The main effect of maternal hypoxia lead to decreased expression of MBP or NF-H+L, and increased expression of GFAP (all P < 0.05). Moreover, there was positive three-way interaction among maternal hypoxia, high-fat diet and postnatal hypoxia on MBP, NF-H+L or GFAP expression (all P < 0.05). In summary, our results indicated that maternal hypoxia during pregnancy in rats lead to changes of periventricular white matter in adult offspring, including demyelination, damaged axon and proliferated astroglia. This effect was amplified by high-fat diet and postnatal hypoxia.

  17. Mortality in Adult Offspring of Immigrants: A Swedish National Cohort Study

    OpenAIRE

    Hélio Manhica; Susanna Toivanen; Anders Hjern; Mikael Rostila

    2015-01-01

    Background Higher risks of psychiatric disorders and lower-than-average subjective health in adulthood have been demonstrated in offspring of immigrants in Sweden compared with offspring of native Swedes, and linked to relative socioeconomic disadvantage. The present study investigated mortality rates in relation to this inequity from a gender perspective. Methods We used data from national registers covering the entire Swedish population aged 18-65 years. Offspring of foreign-born parents wh...

  18. Mortality in adult offspring of immigrants: a Swedish national cohort study.

    Directory of Open Access Journals (Sweden)

    Hélio Manhica

    Full Text Available Higher risks of psychiatric disorders and lower-than-average subjective health in adulthood have been demonstrated in offspring of immigrants in Sweden compared with offspring of native Swedes, and linked to relative socioeconomic disadvantage. The present study investigated mortality rates in relation to this inequity from a gender perspective.We used data from national registers covering the entire Swedish population aged 18-65 years. Offspring of foreign-born parents who were either Swedish born or had received residency in Sweden before school age (<7 years were defined as "offspring of immigrants." We used Cox regression models to examine the association between parental country of birth and mortality between 1990 and 2008, with adjustment for education, income, age and family type.Male offspring of immigrants from the Middle East (HR:2.00, CI:1.66-2.26, other non-European countries (HR:1.80, CI:1.36-2.36 and Finland (HR:1.56, CI:1.48-1.65 showed an age-adjusted excess mortality risk from all causes of death when compared to offspring with Swedish-born parents. Income, but not education, greatly attenuated these increased mortality risks. No excess mortality rates were found among female offspring of immigrants, with the exception of external cause of death among offspring of Finnish immigrants.The study demonstrates high mortality rates in male offspring of immigrants from Finland and non-European countries that are associated with economic, but not educational, disadvantage. No increased mortality rates were found among female offspring of immigrants. Future studies are needed to explain this gender differential and why income, but not education, predicts mortality in male offspring of immigrants.

  19. Elevated mutation rates in the germ line of first- and second-generation offspring of irradiated male mice

    OpenAIRE

    Barber, Ruth; Plumb, Mark A.; Boulton, Emma; Roux, Isabelle; Dubrova, Yuri E.

    2002-01-01

    Mutation rates at two expanded simple tandem repeat loci were studied in the germ line of first- and second-generation offspring of inbred male CBA/H, C57BL/6, and BALB/c mice exposed to either high linear energy transfer fission neutrons or low linear energy transfer x-rays. Paternal CBA/H exposure to either x-rays or fission neutrons resulted in increased mutation rates in the germ line of two subsequent generations. Comparable transgenerational effects were observed also in neutron-irradia...

  20. 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)

    By polymerase chain reaction with arbitrary primer (AP-PCR), the possibility of transmission of genome instability to somatic cells of the offspring (F1 generation) from male parents of mice exposed to chronic low-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

  1. Parental Midlife Body Shape and Association with Multiple Adult Offspring Obesity Measures: North West Adelaide Health Study.

    Directory of Open Access Journals (Sweden)

    Janet F Grant

    Full Text Available There is compelling evidence that parental weight is a strong determinant of offspring weight status. The study used cross-sectional self-reported and measured data from a longitudinal cohort of Australian adults (n = 2128 from Stage 3 (2008-10 of the North West Adelaide Health Study (1999-2003, baseline n = 4056 to investigate the association between midlife parental body shape and four indicators of obesity and fat distribution. The analysis used measured body mass index (BMI, waist circumference (WC, waist hip ratio (WHR and waist height ratio (WHtR of adult offspring, together with pictograms for recall of parental body shape. Compared to both parents being a healthy weight, offspring were more likely to be overweight or obese if both parents were an unhealthy weight at age 40 (OR 2.14, 95% CI 1.67-2.76 and further, those participants whose mother was an unhealthy weight were more likely to be overweight or obese themselves (OR 1.50, 95% CI 1.14-1.98. There were similar but lower results for those with an overweight/obese father (OR 1.44, 95% CI 1.08-1.93. The effect of one or both parents being overweight or obese tended to be stronger for daughters than for sons across BMI, WC and WHtR. BMI showed the strongest association with parental body shape (OR 2.14, followed by WC (OR 1.78, WHtR (OR 1.71 and WHR (OR 1.45. WHtR (42-45% and BMI (35-36% provided the highest positive predictive values for overweight/obesity from parental body shape. Parental obesity increases the risk of obesity for adult offspring, both for overall body shape and central adiposity, particularly for daughters. Pictograms could potentially be used as a screening tool in primary care settings to promote healthy weight among young adults.

  2. Discrepancy in Reports of Support Exchanges between Parents and Adult Offspring: Within- and Between-Family Differences

    OpenAIRE

    Kim, Kyungmin; Zarit, Steven H.; Birditt, Kira S.; Fingerman, Karen L.

    2014-01-01

    Using data from 929 parent-child dyads nested in 458 three-generation families (aged 76 for the oldest generation, 50 for the middle generation, and 24 for the youngest generation), this study investigated how discrepancies in reports of support that parents and their adult offspring exchanged with one another vary both within and between families, and what factors explain variations in dyadic discrepancies. We found substantial within- and between-family differences in dyadic discrepancies i...

  3. Aerobic exercise training reduces cardiac function in adult male offspring exposed to prenatal hypoxia.

    Science.gov (United States)

    Reyes, Laura M; Kirschenman, Raven; Quon, Anita; Morton, Jude S; Shah, Amin; Davidge, Sandra T

    2015-09-01

    Intrauterine growth restriction (IUGR) has been associated with increased susceptibility to myocardial ischemia-reperfusion (I/R) injury. Exercise is an effective preventive intervention for cardiovascular diseases; however, it may be detrimental in conditions of compromised health. The aim of this study was to determine whether exercise training can improve cardiac performance after I/R injury in IUGR offspring. We used a hypoxia-induced IUGR model by exposing pregnant Sprague-Dawley rats to 21% oxygen (control) or hypoxic (11% oxygen; IUGR) conditions from gestational day 15 to 21. At 10 wk of age, offspring were randomized to a sedentary group or to a 6-wk exercise protocol. Transthoracic echocardiography assessments were performed after 6 wk. Twenty-four hours after the last bout of exercise, ex vivo cardiac function was determined using a working heart preparation. With exercise training, there was improved baseline cardiac performance in male control offspring but a reduced baseline cardiac performance in male IUGR exercised offspring (P exercise decreased superoxide generation in control offspring, while in IUGR offspring, it had the polar opposite effect (interaction P ≤ 0.05). There was no effect of IUGR or exercise on cardiac function in female offspring. In conclusion, in male IUGR offspring, exercise may be a secondary stressor on cardiac function. A reduction in cardiac performance along with an increase in superoxide production in response to exercise was observed in this susceptible group. PMID:26157059

  4. Epigenetics: Behavioral Influences on Gene Function, Part I: Maternal Behavior Permanently Affects Adult Behavior in Offspring

    Science.gov (United States)

    Ogren, Marilee P.; Lombroso, Paul J.

    2008-01-01

    The article highlights the field of epigenetics and its relevance in determining the effects of maternal nurturing on behavioral patterns in offsprings. Results concluded that maternal behavior influences the offspring's behavior to stress in adulthood and the effects are transgenerational through epigenetic mechanisms.

  5. Pre-weaning growth hormone treatment reverses hypertension and endothelial dysfunction in adult male offspring of mothers undernourished during pregnancy.

    Directory of Open Access Journals (Sweden)

    Clint Gray

    Full Text Available Maternal undernutrition results in elevated blood pressure (BP and endothelial dysfunction in adult offspring. However, few studies have investigated interventions during early life to ameliorate the programming of hypertension and vascular disorders. We have utilised a model of maternal undernutrition to examine the effects of pre-weaning growth hormone (GH treatment on BP and vascular function in adulthood. Female Sprague-Dawley rats were fed either a standard control diet (CON or 50% of CON intake throughout pregnancy (UN. From neonatal day 3 until weaning (day 21, CON and UN pups received either saline (CON-S, UN-S or GH (2.5 ug/g/day(CON-GH, UN-GH. All dams were fed ad libitum throughout lactation. Male offspring were fed a standard diet until the end of the study. Systolic blood pressure (SBP was measured at day 150 by tail cuff plethysmography. At day 160, intact mesenteric vessels mounted on a pressure myograph. Responses to pressure, agonist-induced constriction and endothelium-dependent vasodilators were investigated to determine vascular function. SBP was increased in UN-S groups and normalised in UN-GH groups (CON-S 121±2 mmHg, CON-GH 115±3, UN-S 146±3, UN-GH 127±2. Pressure mediated dilation was reduced in UN-S offspring and normalised in UN-GH groups. Vessels from UN-S offspring demonstrated a reduced constrictor response to phenylephrine and reduced vasodilator response to acetylcholine (ACh. Furthermore, UN-S offspring vessels displayed a reduced vasodilator response in the presence of L-NG-Nitroarginine Methyl Ester (L-NAME, carbenoxolone (CBX, L-NAME and CBX, Tram-34 and Apamin. UN-GH vessels showed little difference in responses when compared to CON and significantly increased vasodilator responses when compared to UN-S offspring. Pre-weaning GH treatment reverses the negative effects of maternal UN on SBP and vasomotor function in adult offspring. These data suggest that developmental cardiovascular programming is

  6. 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)

    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

  7. Maternal exercise before and during pregnancy does not impact offspring exercise or body composition in mice

    OpenAIRE

    Kelly, Scott A.; Hua, Kunjie; Wallace, Jennifer N.; Wells, Sarah E.; Nehrenberg, Derrick L.; Pomp, Daniel

    2015-01-01

    Background The genome, the environment, and their interactions simultaneously regulate complex traits such as body composition and voluntary exercise levels. One such environmental influence is the maternal milieu (i.e., in utero environment or maternal care). Variability in the maternal environment may directly impact the mother, and simultaneously has the potential to influence the physiology and/or behavior of offspring in utero, post birth, and into adulthood. Here, we utilized a murine m...

  8. Low functional programming of renal AT{sub 2}R mediates the developmental origin of glomerulosclerosis in adult offspring induced by prenatal caffeine exposure

    Energy Technology Data Exchange (ETDEWEB)

    Ao, Ying [Department of Pharmacology, School of Basic Medical Science of Wuhan University, Wuhan 430071 (China); Hubei Provincial Key Laboratory of Developmentally Originated Disorder, Wuhan 430071 (China); Sun, Zhaoxia; Hu, Shuangshuang; Zuo, Na [Department of Pharmacology, School of Basic Medical Science of Wuhan University, Wuhan 430071 (China); Li, Bin [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Yang, Shuailong; Xia, Liping; Wu, Yong [Department of Pharmacology, School of Basic Medical Science of Wuhan University, Wuhan 430071 (China); Wang, Linlong [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); He, Zheng [Department of Pharmacology, School of Basic Medical Science of Wuhan University, Wuhan 430071 (China); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, School of Basic Medical Science of Wuhan University, Wuhan 430071 (China); Hubei Provincial Key Laboratory of Developmentally Originated Disorder, Wuhan 430071 (China)

    2015-09-01

    Our previous study has indicated that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR) of offspring. Recent research suggested that IUGR is a risk factor for glomerulosclerosis. However, whether PCE could induce glomerulosclerosis and its underlying mechanisms remain unknown. This study aimed to demonstrate the induction to glomerulosclerosis in adult offspring by PCE and its intrauterine programming mechanisms. A rat model of IUGR was established by PCE, male fetuses and adult offspring at the age of postnatal week 24 were euthanized. The results revealed that the adult offspring kidneys in the PCE group exhibited glomerulosclerosis as well as interstitial fibrosis, accompanied by elevated levels of serum creatinine and urine protein. Renal angiotensin II receptor type 2 (AT{sub 2}R) gene expression in adult offspring was reduced by PCE, whereas the renal angiotensin II receptor type 1a (AT{sub 1a}R)/AT{sub 2}R expression ratio was increased. The fetal kidneys in the PCE group displayed an enlarged Bowman's space and a shrunken glomerular tuft, accompanied by a reduced cortex width and an increase in the nephrogenic zone/cortical zone ratio. Observation by electronic microscope revealed structural damage of podocytes; the reduced expression level of podocyte marker genes, nephrin and podocin, was also detected by q-PCR. Moreover, AT{sub 2}R gene and protein expressions in fetal kidneys were inhibited by PCE, associated with the repression of the gene expression of glial-cell-line-derived neurotrophic factor (GDNF)/tyrosine kinase receptor (c-Ret) signaling pathway. These results demonstrated that PCE could induce dysplasia of fetal kidneys as well as glomerulosclerosis of adult offspring, and the low functional programming of renal AT{sub 2}R might mediate the developmental origin of adult glomerulosclerosis. - Highlights: • Prenatal caffeine exposure induces glomerulosclerosis in adult offspring. • Prenatal caffeine

  9. Low functional programming of renal AT2R mediates the developmental origin of glomerulosclerosis in adult offspring induced by prenatal caffeine exposure

    International Nuclear Information System (INIS)

    Our previous study has indicated that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR) of offspring. Recent research suggested that IUGR is a risk factor for glomerulosclerosis. However, whether PCE could induce glomerulosclerosis and its underlying mechanisms remain unknown. This study aimed to demonstrate the induction to glomerulosclerosis in adult offspring by PCE and its intrauterine programming mechanisms. A rat model of IUGR was established by PCE, male fetuses and adult offspring at the age of postnatal week 24 were euthanized. The results revealed that the adult offspring kidneys in the PCE group exhibited glomerulosclerosis as well as interstitial fibrosis, accompanied by elevated levels of serum creatinine and urine protein. Renal angiotensin II receptor type 2 (AT2R) gene expression in adult offspring was reduced by PCE, whereas the renal angiotensin II receptor type 1a (AT1aR)/AT2R expression ratio was increased. The fetal kidneys in the PCE group displayed an enlarged Bowman's space and a shrunken glomerular tuft, accompanied by a reduced cortex width and an increase in the nephrogenic zone/cortical zone ratio. Observation by electronic microscope revealed structural damage of podocytes; the reduced expression level of podocyte marker genes, nephrin and podocin, was also detected by q-PCR. Moreover, AT2R gene and protein expressions in fetal kidneys were inhibited by PCE, associated with the repression of the gene expression of glial-cell-line-derived neurotrophic factor (GDNF)/tyrosine kinase receptor (c-Ret) signaling pathway. These results demonstrated that PCE could induce dysplasia of fetal kidneys as well as glomerulosclerosis of adult offspring, and the low functional programming of renal AT2R might mediate the developmental origin of adult glomerulosclerosis. - Highlights: • Prenatal caffeine exposure induces glomerulosclerosis in adult offspring. • Prenatal caffeine exposure inhibits fetal kidney

  10. Discrepancy in reports of support exchanges between parents and adult offspring: within- and between-family differences.

    Science.gov (United States)

    Kim, Kyungmin; Zarit, Steven H; Birditt, Kira S; Fingerman, Karen L

    2014-04-01

    Using data from 929 parent-child dyads nested in 458 three-generation families (aged 76 for the oldest generation, 50 for the middle generation, and 24 for the youngest generation), this study investigated how discrepancies in reports of support that parents and their adult offspring exchanged with one another vary both within and between families, and what factors explain variations in dyadic discrepancies. We found substantial within- and between-family differences in dyadic discrepancies in reports of support exchanges. For downward exchanges (from parents to offspring), both dyad-specific characteristics within a family (e.g., gender composition, relative levels of relationship quality, and family obligation) and shared family characteristics (e.g., average levels of relationship quality) showed significant effects on dyadic discrepancies. For upward exchanges (from offspring to parents), however, only dyad-specific characteristics (e.g., gender composition, coresidence, relative levels of positive relationship quality, and family obligation) were significantly associated with discrepancies. Discrepancies in support exchanges were mainly associated with dyad-specific characteristics, but they also appeared to be influenced by family emotional environments. The use of multiple informants revealed that families differ in discrepancies in reports of exchanges, which has implications for quality of family life as well as future exchanges. PMID:24548009

  11. Maternal dietary loads of alpha-tocopherol increase synapse density and glial synaptic coverage in the hippocampus of adult offspring

    Directory of Open Access Journals (Sweden)

    S. Salucci

    2014-05-01

    Full Text Available An increased intake of the antioxidant α-Tocopherol (vitamin E is recommended in complicated pregnancies, to prevent free radical damage to mother and fetus. However, the anti-PKC and antimitotic activity of α-Tocopherol raises concerns about its potential effects on brain development. Recently, we found that maternal dietary loads of α-Tocopherol through pregnancy and lactation cause developmental deficit in hippocampal synaptic plasticity in rat offspring. The defect persisted into adulthood, with behavioral alterations in hippocampus-dependent learning. Here, using the same rat model of maternal supplementation, ultrastructural morphometric studies were carried out to provide mechanistic interpretation to such a functional impairment in adult offspring by the occurrence of long-term changes in density and morphological features of hippocampal synapses. Higher density of axo-spinous synapses was found in CA1 stratum radiatum of α-Tocopherol-exposed rats compared to controls, pointing to a reduced synapse pruning. No morphometric changes were found in synaptic ultrastructural features, i.e., perimeter of axon terminals, length of synaptic specializations, extension of bouton-spine contact. Glia-synapse anatomical relationship was also affected. Heavier astrocytic coverage of synapses was observed in Tocopherol-treated offspring, notably surrounding axon terminals; moreover, the percentage of synapses contacted by astrocytic endfeet at bouton-spine interface (tripartite synapses was increased. These findings indicate that gestational and neonatal exposure to supranutritional tocopherol intake can result in anatomical changes of offspring hippocampus that last through adulthood. These include a surplus of axo-spinous synapses and an aberrant glia-synapse relationship, which may represent the morphological signature of previously described alterations in synaptic plasticity and hippocampus-dependent learning.

  12. Maternal Dietary Loads of Alpha-Tocopherol Increase Synapse Density and Glial Synaptic Coverage in the Hippocampus of Adult Offspring

    Science.gov (United States)

    Salucci, S.; Ambrogini, P.; Lattanzi, D.; Betti, M.; Gobbi, P.; Galati, C.; Galli, F.; Cuppini, R.; Minelli, A.

    2014-01-01

    An increased intake of the antioxidant α-Tocopherol (vitamin E) is recommended in complicated pregnancies, to prevent free radical damage to mother and fetus. However, the anti-PKC and antimitotic activity of α-Tocopherol raises concerns about its potential effects on brain development. Recently, we found that maternal dietary loads of α-Tocopherol through pregnancy and lactation cause developmental deficit in hippocampal synaptic plasticity in rat offspring. The defect persisted into adulthood, with behavioral alterations in hippocampus-dependent learning. Here, using the same rat model of maternal supplementation, ultrastructural morphometric studies were carried out to provide mechanistic interpretation to such a functional impairment in adult offspring by the occurrence of long-term changes in density and morphological features of hippocampal synapses. Higher density of axo-spinous synapses was found in CA1 stratum radiatum of α-Tocopherol-exposed rats compared to controls, pointing to a reduced synapse pruning. No morphometric changes were found in synaptic ultrastructural features, i.e., perimeter of axon terminals, length of synaptic specializations, extension of bouton-spine contact. Gliasynapse anatomical relationship was also affected. Heavier astrocytic coverage of synapses was observed in Tocopherol-treated offspring, notably surrounding axon terminals; moreover, the percentage of synapses contacted by astrocytic endfeet at bouton-spine interface (tripartite synapses) was increased. These findings indicate that gestational and neonatal exposure to supranutritional Tocopherol intake can result in anatomical changes of offspring hippocampus that last through adulthood. These include a surplus of axo-spinous synapses and an aberrant gliasynapse relationship, which may represent the morphological signature of previously described alterations in synaptic plasticity and hippocampus-dependent learning. PMID:24998923

  13. Perinatal exposure to bisphenol-A inhibits synaptogenesis and affects the synaptic morphological development in offspring male mice.

    Science.gov (United States)

    Xu, Xiaohong; Xie, Lingdan; Hong, Xing; Ruan, Qin; Lu, Hongfei; Zhang, Qin; Zhang, Guangxia; Liu, Xingyi

    2013-05-01

    Our previous study indicated that perinatal exposure to low-dose BPA, one of the most common environmental endocrine disrupters, alters behavioral development in offspring mice. Given that synaptic structure of the hippocampus is closely related to behaviors, in the present study, we examined the effects of perinatal exposure to BPA (0.04, 0.4, and 4.0 mg kg(-1) day(-1)) on the synaptic density and the synaptic structural modification of pyramidal cells in hippocampus region CA1 and the expressions of synaptic proteins such as synapsin I and PSD-95 and glutamate NMDA and AMPA receptors in male offspring mice on postnatal day (PND) 14, 21, and 56. The results of electron microscope measurement showed that BPA significantly reduced the numeric synaptic density and altered the structural modification of synaptic interface of pyramidal cells with the enlarged synaptic cleft, the shortened active zone, and the thinned postsynaptic density (PSD) on PND 14, 21, and 56 and the increased curvature of synaptic interface on PND 14 and 21. Further analyses of Western blot indicated that BPA markedly reduced the levels of synapsin I and PSD-95 on PND 14, 21, and 56 and down-regulated NMDA receptor subunit NR1 and AMPA receptor subunit GluR1 during development and young adulthood. These results suggest that perinatal exposure to low level of BPA inhibits synaptogenesis and affects synaptic structural modification after birth. The reduced expressions of synaptic proteins synapsin I and PSD-95 and glutamate NMDA and AMPA receptors may be involved in the negative changes in the synaptic plasticity. PMID:23490186

  14. Childhood maltreatment in adult offspring of Portuguese war veterans with and without PTSD.

    NARCIS (Netherlands)

    Dos Santos Dias, Aida; Sales, L.; Cardoso, R. M.; Kleber, Rolf

    2014-01-01

    BACKGROUND: The colonial war that Portugal was involved in between 1961 and 1974 had a significant impact on veterans and their families. However, it is unclear what the consequences of this war are, in particular with regard to levels of childhood maltreatment (CM) in offspring. OBJECTIVE: Our stud

  15. Maternal Nutritional Imbalance between Linoleic Acid and Alpha-Linolenic Acid Increases Offspring's Anxious Behavior with a Sex-Dependent Manner in Mice.

    Science.gov (United States)

    Sakayori, Nobuyuki; Tokuda, Hisanori; Yoshizaki, Kaichi; Kawashima, Hiroshi; Innis, Sheila M; Shibata, Hiroshi; Osumi, Noriko

    2016-01-01

    Omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFAs) are essential nutrients for normal brain development. The principal dietary n-6 and n-3 PUFAs are linoleic acid (LA) and α-linolenic acid (ALA), respectively, We have previously shown that maternal dietary imbalance between these PUFAs, i.e., rich in LA and poor in ALA, affected brain development and increased anxiety-related behavior in the mouse offspring. Here we further addressed sex difference in anxiety-related behavior in the offspring exposed to maternal LA:ALA imbalance. We fed pregnant mice a LA excess/ALA deficient (LA(ex)/ALA(def)) diet, and raised their offspring on a well-balanced LA:ALA diet from an early lactation period. When the offspring were grown to adulthood, they were subjected to behavioral and biochemical analyses. We found that both male and female offspring exposed to the LA(ex)/ALA(def) diet showed increased anxiety-related behavior compared to those exposed to the control diet, which was differently observed between the sexes. The female offspring also exhibited hyperactivity by maternal intake of the LA(ex)/ALA(def) diet. On the other hand, abnormal depressive behavior was undetected in both sexes. We also found that the ratio of n-6 to n-3 PUFAs in the brain was unaffected regardless of maternal diet or offspring's sex. Since the n-6/n-3 ratio is known to influence emotional behavior, it is reasonable to assume that LA:ALA imbalance exposed during brain development is the key for causing enhanced anxiety in adulthood. The present study indicates that maternal dietary imbalance between LA and ALA increases offspring's anxiety-related behavior with a sex-dependent manner. PMID:27558477

  16. Maternal immune activation differentially impacts mature and adult-born hippocampal neurons in male mice.

    Science.gov (United States)

    Zhang, Zhi; van Praag, Henriette

    2015-03-01

    Schizophrenia is associated with deficits in the hippocampus, a brain area important for learning and memory. The dentate gyrus (DG) of the hippocampus develops both before and after birth. To study the relative contribution of mature and adult-born DG granule cells to disease etiology, we compared both cell populations in a mouse model of psychiatric illness resulting from maternal immune activation. Polyriboinosinic-polyribocytidilic acid (PolyIC, 5mg/kg) or saline was given on gestation day 15 to pregnant female C57Bl/6 mice. Male offspring (n=105), was administered systemic bromodeoxyuridine (BrdU, 50mg/kg) (n=52) or intracerebral retroviral injection into the DG (n=53), to label dividing cells at one month of age. Two months later behavioral tests were performed to evaluate disease phenotype. Immunohistochemistry and whole-cell patch clamping were used to assess morphological and physiological characteristics of DG cells. Three-month-old PolyIC exposed male offspring exhibited deficient pre-pulse inhibition, spatial maze performance and motor coordination, as well as increased depression-like behavior. Histological analysis showed reduced DG volume and parvalbumin positive interneuron number. Both mature and new hippocampal neurons showed modifications in intrinsic properties such as increased input resistance and lower current threshold, and decreased action potential number. Reduced GABAergic inhibitory transmission was observed only in mature DG neurons. Differential impairments in mature DG cells and adult-born new neurons may have implications for behavioral deficits associated with maternal immune activation. PMID:25449671

  17. Sexual Dimorphism in Offspring Glucose-Sensitive Hypothalamic Gene Expression and Physiological Responses to Maternal High-Fat Diet Feeding

    OpenAIRE

    Dearden, Laura; Balthasar, Nina

    2014-01-01

    A wealth of animal and human studies demonstrate that early life environment significantly influences adult metabolic balance, however the etiology for offspring metabolic misprogramming remains incompletely understood. Here, we determine the effect of maternal diet per se on offspring sex-specific outcomes in metabolic health and hypothalamic transcriptome regulation in mice. Furthermore, to define developmental periods of maternal diet misprogramming aspects of offspring metabolic balance, ...

  18. Gestational protein restriction in mice has pronounced effects on gene expression in newborn offspring's liver and skeletal muscle; protective effect of taurine

    DEFF Research Database (Denmark)

    Mortensen, Ole Hartvig; Olsen, Hanne Lodberg; Frandsen, Lis;

    2010-01-01

    We examined gene expression changes in liver and skeletal muscle of newborn mice subjected to a maternal low protein (LP) or normal protein (NP) diet during pregnancy, with or without taurine supplementation in the drinking water. LP offspring had a 40% lower birthweight than NP offspring, whereas...... in genes concerned with fatty acid metabolism in liver and with oxidative phoshorylation and tri carboxylic acid (TCA) cycle in skeletal muscle. Conclusion: Gestational protein restriction resulted in lower birthweight associated with significant gene expression changes, which was different in liver...

  19. Overweight and the metabolic syndrome in adult offspring of women with diet-treated gestational diabetes mellitus or type 1 diabetes

    DEFF Research Database (Denmark)

    Clausen, Tine D; Mathiesen, Elisabeth R; Hansen, Torben;

    2009-01-01

    Overweight and the metabolic syndrome in adult offspring of women with diet-treated gestational diabetes mellitus or type 1 diabetes Context: In animal studies exposure to intrauterine hyperglycemia increases the risk of cardiovascular disease through only partly understood epigenetic mechanisms....... Human long-term follow-up studies on the same topic are few. Objective: To study the risk of overweight and the metabolic syndrome in adult offspring of women with diet-treated gestational diabetes mellitus (GDM) or type 1 diabetes, and additionally to study associations between estimates of maternal...... syndrome increased significantly with increasing maternal fasting blood glucose as well as 2-h blood glucose (during OGTT). Conclusions: Adult offspring of women with diet-treated GDM or type 1 diabetes are risk groups for overweight and the metabolic syndrome. Intrauterine hyperglycemia may in addition to...

  20. Maternal Exercise during Pregnancy Increases BDNF Levels and Cell Numbers in the Hippocampal Formation but Not in the Cerebral Cortex of Adult Rat Offspring.

    Directory of Open Access Journals (Sweden)

    Sérgio Gomes da Silva

    Full Text Available Clinical evidence has shown that physical exercise during pregnancy may alter brain development and improve cognitive function of offspring. However, the mechanisms through which maternal exercise might promote such effects are not well understood. The present study examined levels of brain-derived neurotrophic factor (BDNF and absolute cell numbers in the hippocampal formation and cerebral cortex of rat pups born from mothers exercised during pregnancy. Additionally, we evaluated the cognitive abilities of adult offspring in different behavioral paradigms (exploratory activity and habituation in open field tests, spatial memory in a water maze test, and aversive memory in a step-down inhibitory avoidance task. Results showed that maternal exercise during pregnancy increased BDNF levels and absolute numbers of neuronal and non-neuronal cells in the hippocampal formation of offspring. No differences in BDNF levels or cell numbers were detected in the cerebral cortex. It was also observed that offspring from exercised mothers exhibited better cognitive performance in nonassociative (habituation and associative (spatial learning mnemonic tasks than did offspring from sedentary mothers. Our findings indicate that maternal exercise during pregnancy enhances offspring cognitive function (habituation behavior and spatial learning and increases BDNF levels and cell numbers in the hippocampal formation of offspring.

  1. Cytomegalovirus infection of adipose tissues induces steatitis in adult mice.

    OpenAIRE

    Price, P; Eddy, K. S.; Papadimitriou, J M; Robertson, T. A.; Shellam, G R

    1990-01-01

    Young adult mice infected with MCMV were shown to develop inflammatory lesions in the peripancreatic and salivary gland adipose tissues. MCMV replication was detected by immunoperoxidase staining and electron microscopy in adipocytes, fibroblasts, endothelial cells and pericytes in brown and white adipose tissues. More infected cells were detected in C3H mice than in BALB/c, BALB.B, BALB.K or C57BL/6 mice. Peripancreatic steatitis consisted of a monocytic infiltrate surrounding focal necrosis...

  2. The neuropsychopharmacological effects of Catha edulis in mice offspring born to mothers exposed during pregnancy and lactation.

    Science.gov (United States)

    Bedada, Worku; Engidawork, Ephrem

    2010-02-01

    Chewing fresh leaves of the khat plant (Catha edulis Forsk) is a deep rooted and widespread habit in East Africa and the Middle East. Although a body of knowledge exists about the adverse effects of khat during pregnancy, data are sparse with regard to the consequences of long-term exposure during pregnancy and lactation. The present work, therefore, was initiated to evaluate the neuropsychopharmacological effects of Catha edulis exposure during pregnancy and lactation in mice at postnatal day 28. To this effect, a lyophilized extract of khat (100 mg/kg, K100 and 200 mg/kg, K200), amphetamine (1 mg/kg, positive control, AMP), and a similar volume of 2% v/v Tween-80 in distilled water (negative control, CONT) were administered daily to pregnant mice from gestational day 6 until weaning. Neuropsychopharmacological measurements were done by making use of a battery of neurobehavioural and cognitive tests. Moreover, toxicity to liver and kidney was also evaluated by determining biochemical markers for possible tissue damage. K200 produced significant motor in-coordination and emotional instability; as revealed by impairment in both cliff avoidance (p effect only on grip strength where a decrement was noted (p effects during pregnancy and lactation which might pose a serious impediment to the physical and mental development of the offspring. PMID:19585482

  3. Fish oil supplementation during pregnancy and allergic respiratory disease in the adult offspring

    DEFF Research Database (Denmark)

    Hansen, Susanne; Strøm, Marin; Maslova, Ekaterina;

    2016-01-01

    BACKGROUND: Maternal supplementation with long-chain n-3 polyunsaturated fatty acids can have immunologic effects on the developing fetus through several anti-inflammatory pathways. However, there is limited knowledge of the long-term programming effects. OBJECTIVE: In a randomized controlled trial...... from 1990 with 24 years of follow-up, our aim was to determine whether supplementation with 2.7 g of long-chain n-3 polyunsaturated fatty acids in pregnancy can reduce the risk of asthma in offspring and allergic respiratory disease. METHODS: The randomized controlled trial included 533 women who were...... randomly assigned to receive fish oil during the third trimester of pregnancy, olive oil, or no oil in the ratio 2:1:1. The offspring were followed in a mandatory national prescription register, with complete follow-up for prescriptions related to the treatment of asthma and allergic rhinitis as primary...

  4. 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.

  5. Vertical transmission of Zika virus targeting the radial glial cells affects cortex development of offspring mice.

    Science.gov (United States)

    Wu, Kong-Yan; Zuo, Guo-Long; Li, Xiao-Feng; Ye, Qing; Deng, Yong-Qiang; Huang, Xing-Yao; Cao, Wu-Chun; Qin, Cheng-Feng; Luo, Zhen-Ge

    2016-06-01

    The recent Zika virus (ZIKV) epidemic in Latin America coincided with a marked increase in microcephaly in newborns. However, the causal link between maternal ZIKV infection and malformation of the fetal brain has not been firmly established. Here we show a vertical transmission of ZIKV in mice and a marked effect on fetal brain development. We found that intraperitoneal (i.p.) injection of a contemporary ZIKV strain in pregnant mice led to the infection of radial glia cells (RGs) of dorsal ventricular zone of the fetuses, the primary neural progenitors responsible for cortex development, and caused a marked reduction of these cortex founder cells in the fetuses. Interestingly, the infected fetal mice exhibited a reduced cavity of lateral ventricles and a discernable decrease in surface areas of the cortex. This study thus supports the conclusion that vertically transmitted ZIKV affects fetal brain development and provides a valuable animal model for the evaluation of potential therapeutic or preventative strategies. PMID:27174054

  6. Vertical transmission of Zika virus targeting the radial glial cells affects cortex development of offspring mice

    Science.gov (United States)

    Wu, Kong-Yan; Zuo, Guo-Long; Li, Xiao-Feng; Ye, Qing; Deng, Yong-Qiang; Huang, Xing-Yao; Cao, Wu-Chun; Qin, Cheng-Feng; Luo, Zhen-Ge

    2016-01-01

    The recent Zika virus (ZIKV) epidemic in Latin America coincided with a marked increase in microcephaly in newborns. However, the causal link between maternal ZIKV infection and malformation of the fetal brain has not been firmly established. Here we show a vertical transmission of ZIKV in mice and a marked effect on fetal brain development. We found that intraperitoneal (i.p.) injection of a contemporary ZIKV strain in pregnant mice led to the infection of radial glia cells (RGs) of dorsal ventricular zone of the fetuses, the primary neural progenitors responsible for cortex development, and caused a marked reduction of these cortex founder cells in the fetuses. Interestingly, the infected fetal mice exhibited a reduced cavity of lateral ventricles and a discernable decrease in surface areas of the cortex. This study thus supports the conclusion that vertically transmitted ZIKV affects fetal brain development and provides a valuable animal model for the evaluation of potential therapeutic or preventative strategies. PMID:27174054

  7. Maternal in utero exposure to the endocrine disruptor di-(2-ethylhexyl) phthalate affects the blood pressure of adult male offspring

    Energy Technology Data Exchange (ETDEWEB)

    Martinez–Arguelles, D.B. [The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada H3G 1A4 (Canada); Department of Medicine, McGill University, Montreal, Quebec, Canada H3G 1A4 (Canada); McIntosh, M.; Rohlicek, C.V. [The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada H3G 1A4 (Canada); Department of Pediatrics, McGill University, Montreal, Quebec, Canada H3G 1A4 (Canada); Culty, M. [The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada H3G 1A4 (Canada); Department of Medicine, McGill University, Montreal, Quebec, Canada H3G 1A4 (Canada); Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada H3G 1A4 (Canada); Zirkin, B.R. [Department of Biochemistry and Molecular Biology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205 (United States); Papadopoulos, V., E-mail: vassilios.papadopoulos@mcgill.ca [The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada H3G 1A4 (Canada); Department of Medicine, McGill University, Montreal, Quebec, Canada H3G 1A4 (Canada); Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada H3G 1A4 (Canada); Department of Biochemistry and Molecular Biology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205 (United States)

    2013-01-01

    Di-(2-ethylhexyl) phthalate (DEHP) is used industrially to add flexibility to polyvinyl chloride (PVC) polymers and is ubiquitously found in the environment, with evidence of prenatal, perinatal and early infant exposure in humans. In utero exposure to DEHP decreases circulating testosterone levels in the adult rat. In addition, DEHP reduces the expression of the angiotensin II receptors in the adrenal gland, resulting in decreased circulating aldosterone levels. The latter may have important effects on water and electrolyte balance as well as systemic arterial blood pressure. Therefore, we determined the effects of in utero exposure to DEHP on systemic arterial blood pressure in the young (2 month-old) and older (6.5 month-old) adult rats. Sprague-Dawley pregnant dams were exposed from gestational day 14 until birth to 300 mg DEHP/kg/day. Blood pressure, heart rate, and activity data were collected using an intra-aortal transmitter in the male offspring at postnatal day (PND) 60 and PND200. A low (0.01%) and high-salt (8%) diet was used to challenge the animals at PND200. In utero exposure to DEHP resulted in reduced activity at PND60. At PND200, systolic and diastolic systemic arterial pressures as well as activity were reduced in response to DEHP exposure. This is the first evidence showing that in utero exposure to DEHP has cardiovascular and behavioral effects in the adult male offspring. Highlights: ► In utero exposure to 300 mg DEHP/kg/day decreases activity at postnatal day 60. ► In utero exposure to DEHP decreases aldosterone levels at postnatal day 200. ► In utero exposure to DEHP decreases systolic blood pressure at postnatal day 200. ► An 8% salt diet recovers the decreased blood pressure at postnatal day 200.

  8. Adult neurogenesis in the four-striped mice (Rhabdomys pumilio)

    OpenAIRE

    Olaleye, Olatunbosun O.; Ihunwo, Amadi O.

    2014-01-01

    In this study, we investigated non-captive four-striped mice (Rhabdomys pumilio) for evidence that adult neurogenesis occurs in the adult brain of animal models in natural environment. Ki-67 (a marker for cell proliferation) and doublecortin (a marker for immature neurons) immunostaining confirmed that adult neurogenesis occurs in the active sites of subventricular zone of the lateral ventricle with the migratory stream to the olfactory bulb, and the subgranular zone of the dentate gyrus of t...

  9. High prevalence of type 2 diabetes and pre-diabetes in adult offspring of women with gestational diabetes mellitus or type 1 diabetes: the role of intrauterine hyperglycemia

    DEFF Research Database (Denmark)

    Clausen, Tine D; Mathiesen, Elisabeth R; Hansen, Torben;

    2008-01-01

    OBJECTIVE: The role of intrauterine hyperglycemia and future risk of type 2 diabetes in human offspring is debated. We studied glucose tolerance in adult offspring of women with either gestational diabetes mellitus (GDM) or type 1 diabetes, taking the impact of both intrauterine hyperglycemia and...... intrauterine environment appears to be involved in the pathogenesis of type 2 diabetes/pre-diabetes in adult offspring of primarily Caucasian women with either diet-treated GDM or type 1 diabetes during pregnancy....... genetic predisposition to type 2 diabetes into account. RESEARCH DESIGN AND METHODS: The glucose tolerance status following a 2-h 75-g oral glucose tolerance test (OGTT) was evaluated in 597 subjects, primarily Caucasians, aged 18-27 years. They were subdivided into four groups according to maternal...

  10. Transmission of cultural values among Mexican-origin parents and their adolescent and emerging adult offspring.

    Science.gov (United States)

    Perez-Brena, Norma J; Updegraff, Kimberly A; Umaña-Taylor, Adriana J

    2015-06-01

    The integration of the U.S. and Mexican culture is an important process associated with Mexican-origin youths' adjustment and family dynamics. The current study examined the reciprocal associations in parents' and two offspring's cultural values (i.e., familism and respect) in 246 Mexican-origin families. Overall, mothers' values were associated with increases in youths' values 5 years later. In contrast, youths' familism values were associated with increases in fathers' familism values 5 years later. In addition, developmental differences emerged where parent-to-offspring effects were more consistent for youth transitioning from early to late adolescence than for youth transitioning from middle adolescence to emerging adulthood. Finally, moderation by immigrant status revealed a youth-to-parent effect for mother-youth immigrant dyads, but not for dyads where youth were U.S.-raised. Our findings highlight the reciprocal nature of parent-youth value socialization and provide a nuanced understanding of these processes through the consideration of familism and respect values. As Mexican-origin youth represent a large and rapidly growing segment of the U.S. population, research that advances our understanding of how these youth develop values that foster family cohesion and support is crucial. PMID:25470657

  11. Hepatic peroxisome proliferator-activated receptor α may have an important role in the toxic effects of di(2-ethylhexyl)phthalate on offspring of mice

    International Nuclear Information System (INIS)

    Maternal exposure to di(2-ethylhexyl)phthalate (DEHP) is associated with adverse effects on offspring, and the metabolites are agonists of peroxisome proliferator-activated receptor (PPAR) α, which exhibits species differences in expression and function. This study aimed to clarify the mechanism of DEHP-induced adverse effects on offspring in relation to maternal mouse and human PPARα. Male and female Sv/129 wild-type (mPPARα), Pparα-null and humanized PPARα (hPPARα) mice were treated with diets containing 0%, 0.01%, 0.05% (medium) or 0.1% (high) DEHP. After 4 weeks, males and females were mated. Dams were killed on gestational day 18 and postnatal day (PND) 2. High-dose DEHP decreased the number of total and live fetuses, and increased resorptions in mPPARα mice. In hPPARα mice, resorptions were increased above the medium dose, and the number of births was decreased at the high dose. The number of live pups on PND2 was decreased over the medium dose in mPPARα and at the high dose in hPPARα mice. No such findings were observed in Pparα-null mice. High-dose DEHP decreased plasma triglyceride in pregnant mPPARα mice, but not in Pparα-null and hPPARα ones. Above the medium dose in mPPARα mice significantly reduced hepatic microsomal triglyceride transfer protein (MTP) expression. Medium- and/or high-dose DEHP increased the levels of maternal PPARα target genes in mPPARα and hPPARα mice. Taken together, PPARα expression is required for the toxicity of DEHP in fetuses and pups and altered plasma triglyceride levels, through regulation of MTP may be important in mPPARα mice and not in hPPARα mice.

  12. Maternal exposure to diets containing high fructose and saturated fats, low B vitamins, or their combination programs growth, adiposity, and insulin sensitivity in adult offspring

    Science.gov (United States)

    Early exposure to unfavorable nutrition programs increases risk of adult-onset diseases. In this rat study, we investigate morphological, metabolic and endocrinal phenotypes of offspring born to dams consuming isocaloric diets containing 30% fructose, 9.9% coconut fat and 0.5% cholesterol (F+SFA), m...

  13. Dexamethasone treatment alters insulin, leptin, and adiponectin levels in male mice as observed in DIO but does not lead to alterations of metabolic phenotypes in the offspring

    OpenAIRE

    Bönisch, Clemens; Irmler, Martin; Brachthäuser, Laura; Neff, Frauke; Bamberger, Mareike T.; Marschall, Susan; Hrabě de Angelis, Martin; Beckers, Johannes

    2015-01-01

    Epigenetic inheritance (EI) of metabolic phenotypes via the paternal lineage has been shown in rodent models of diet-induced obesity (DIO). However, the factors involved in soma-to-germline information transfer remain elusive. Here, we address the role of alterations in insulin, leptin, and adiponectin levels for EI of metabolic phenotypes by treating C57BL/6NTac male mice (F0) with the synthetic glucocorticoid dexamethasone and generating offspring (F1) either by in vitro fertilization or by...

  14. Moderate exercise during pregnancy in Wistar rats alters bone and body composition of the adult offspring in a sex-dependent manner.

    Directory of Open Access Journals (Sweden)

    Brielle V Rosa

    Full Text Available Exercise during pregnancy may have long-lasting effects on offspring health. Musculoskeletal growth and development, metabolism, and later-life disease risk can all be impacted by the maternal environment during pregnancy. The skeleton influences glucose handling through the actions of the bone-derived hormone osteocalcin. The purpose of this study was to test the effects of moderate maternal exercise during pregnancy on the bone and body composition of the offspring in adult life, and to investigate the role of osteocalcin in these effects. Groups of pregnant Wistar rats either performed bipedal standing exercise to obtain food/water throughout gestation but not lactation, or were fed conventionally. Litters were reduced to 8/dam and pups were raised to maturity under control conditions. Whole body dual-energy x-ray absorptiometry, and ex vivo peripheral quantitative computed tomography scans of the right tibia were performed. At study termination blood and tissue samples were collected. Serum concentrations of fully and undercarboxylated osteocalcin were measured, and the relative expression levels of osteocalcin, insulin receptor, Forkhead box transcription factor O1, and osteotesticular protein tyrosine phosphatase mRNA were quantified. Body mass did not differ between the offspring of exercised and control dams, but the male offspring of exercised dams had a greater % fat and lower % lean than controls (p=0.001 and p=0.0008, respectively. At the mid-tibial diaphysis, offspring of exercised dams had a lower volumetric bone mineral density than controls (p=0.01 and in the male offspring of exercised dams the bone: muscle relationship was fundamentally altered. Serum concentrations of undercarboxylated osteocalcin were significantly greater in the male offspring of exercised dams than in controls (p=0.02; however, the relative expression of the measured genes did not differ between groups. These results suggest that moderate exercise during

  15. Subclinical inflammation during third trimester of pregnancy was not associated with markers of the metabolic syndrome in young adult offspring

    DEFF Research Database (Denmark)

    Danielsen, Inge; Granström, Charlotta; Rytter, Dorte;

    2013-01-01

    for maternal smoking during pregnancy, height, prepregnancy body mass index (BMI), education, and offspring's sex. Offspring MS markers included waist circumference, BMI, blood pressure, HOMA insulin resistance, and plasma levels of fasting glucose, triglycerides, cholesterol fractions, insulin, and leptin...

  16. Small Glutamine-Rich Tetratricopeptide Repeat-Containing Protein Alpha (SGTA) Ablation Limits Offspring Viability and Growth in Mice.

    Science.gov (United States)

    Philp, Lisa K; Day, Tanya K; Butler, Miriam S; Laven-Law, Geraldine; Jindal, Shalini; Hickey, Theresa E; Scher, Howard I; Butler, Lisa M; Tilley, Wayne D

    2016-01-01

    Small glutamine-rich tetratricopeptide repeat-containing protein α (SGTA) has been implicated as a co-chaperone and regulator of androgen and growth hormone receptor (AR, GHR) signalling. We investigated the functional consequences of partial and full Sgta ablation in vivo using Cre-lox Sgta-null mice. Sgta(+/-) breeders generated viable Sgta(-/-) offspring, but at less than Mendelian expectancy. Sgta(-/-) breeders were subfertile with small litters and higher neonatal death (P penis and preputial size, and testis descent, were greater in Sgta(-/-). Expression of AR and its targets remained largely unchanged, although AR localisation was genotype- and tissue-dependent. Generally expression of other TPR-containing proteins was unchanged. In conclusion, this thorough investigation of SGTA-null mutation reports a mild phenotype of reduced body size. The model's full potential likely will be realised by genetic crosses with other models to interrogate the role of SGTA in the many diseases in which it has been implicated. PMID:27358191

  17. Evaluation of possible toxic effects of spearmint (Mentha spicata) on the reproductive system, fertility and number of offspring in adult male rats

    OpenAIRE

    Fatemeh Nozhat; Sanaz Alaee; Khodabakhsh Behzadi; Najmeh Azadi Chegini

    2014-01-01

    Objective: In this study we investigated the effects of spearmint (Mentha spicata Labiatae) on the reproductive system, fertility and number of offspring in adult male rats. Materials and Methods: Adult Wistar male rats in one control (C) and three experimental groups (I, II and III) received 0, 10, 20 and 40 mg/kg spearmint extract orally for 45 days, respectively.  Following this treatment, the animals’ weights, and the standard weight of reproductive tissues, sperm count, sperm motility an...

  18. On the evolution of intergenerational division of labor, menopause and transfers among adults and offspring

    OpenAIRE

    C.Y. Cyrus Chu; Ronald D. Lee

    2013-01-01

    We explain how upward transfers from adult children to their elderly parents might evolve as an interrelated feature of a deepening intergenerational division of labor. Humans have a particularly long period of juvenile dependence requiring both food and care time provided mainly by younger and older adults. We suggest that the division of labor evolves to exploit comparative advantage between young and old adults in fertility, childcare and foraging. Eventually the evolving division of labor...

  19. Perinatal exposure to methoxychlor enhances adult cognitive responses and hippocampal neurogenesis in mice.

    Directory of Open Access Journals (Sweden)

    Mariangela eMartini

    2014-06-01

    Full Text Available During perinatal life, sex steroids, such as estradiol, have marked effects on the development and function of the nervous system. Environmental estrogens or xenoestrogens are man-made chemicals, which animal and human population encounter in the environment and which are able to disrupt the functioning of the endocrine system. Scientific interest in the effects of exposure to xenoestrogens has focused more on fertility and reproductive behaviors, while the effects on cognitive behaviors have received less attention. Therefore, the present study explored whether the organochlorine insecticide Methoxychlor (MXC, with known xenoestrogens properties, administered during the perinatal period (from gestational day 11 to postnatal day 8 to pregnant-lactating females, at an environmentally relevant dose (20µg/kg (body weight/day, would also affect learning and memory functions depending on the hippocampus of male and female offspring mice in adulthood. When tested in adulthood, MXC perinatal exposure led to an increase in anxiety-like behavior and in short-term spatial working memory in both sexes. Emotional learning was also assessed using a contextual fear paradigm and MXC treated male and female mice showed an enhanced freezing behavior compared to controls. These results were correlated with an increased survival of adult generated cells in the adult hippocampus. In conclusion, our results show that perinatal exposure to an environmentally relevant dose of MXC has an organizational effect on hippocampus-dependent memory and emotional behaviors.

  20. Paternal fenvalerate exposure influences reproductive functions in the offspring.

    Science.gov (United States)

    Xia, Dong; Parvizi, Nahid; Zhou, Yuchuan; Xu, Kesi; Jiang, Hui; Li, Rongjie; Hang, Yiqiong; Lu, Yang

    2013-11-01

    Fenvalerate (Fen), a synthetic pyrethroid insecticide, has been shown to have adverse effects on male reproductive system. Thus, the aim of the present study was to elucidate whether these adverse effects are passed from exposed male mice to their offspring. Adult male mice received Fen (10 mg/kg) daily for 30 days and mated with untreated females to produce offspring. Fenvalerate significantly changed the methylation status of angiotensin I-converting enzyme (Ace), forkhead box O3 (Foxo3a), huntingtin-associated protein 1 (Hap1), nuclear receptor subfamily 3 (Nr3c2), promyelocytic leukemia (Pml), and Prostaglandin F2 receptor negative regulator (Ptgfrn) genes in paternal mice sperm genomic DNA. Further, Fen significantly increased sperm abnormalities; serum testosterone and estradiol-17ß level in adult male (F0) and their male offspring (F1). Further, paternal Fen treatment significantly increased the length of estrous cycle, serum estradiol-17ß concentration in estrus, and progesterone levels in diestrus in female offspring (F1). These findings suggest that adverse effects of paternal Fen exposure on reproductive functions can be seen not only in treated males (F0) but also in their offsprings. PMID:23548413

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

    Science.gov (United States)

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

    2016-03-11

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

  2. Influence of paternal 252Cf neutron exposure on abnormal sperm, embryonal lethality, and liver tumorigenesis in the F1 offspring of mice

    International Nuclear Information System (INIS)

    Experiments were conducted to determine whether neutron-induced genetic damage in parental germline cells can lead to the development of cancer in the offspring. Seven-week-old C3H male mice were irradiated with 252Cf neutrons at a dose of 0, 50, 100, or 200 cGy. Two weeks or 3 months after irradiation, the male mice were mated with virgin 9-week-old C57BL females. Two weeks after irradiation, the irradiated male mice showed an increased incidence of sperm abnormalities, which led to embryo lethalities in a dose-dependent manner when they were mated with unirradiated female mice. Furthermore, liver tumors in male offspring of male mice in the 50 cGy group were significantly increased in 19 of 44 (43.2%) animals, in clear contrast to the unirradiated group (1 of 31; 3.2%) (P1 generation may be caused by genetic transmission of hepatoma-associated trait (s) induced by 252Cf neutron irradiation. (author)

  3. Maternal choline supplementation differentially alters the basal forebrain cholinergic system of young-adult Ts65Dn and disomic mice

    Science.gov (United States)

    Kelley, Christy M.; Powers, Brian E.; Velazquez, Ramon; Ash, Jessica A.; Ginsberg, Stephen D.; Strupp, Barbara J.; Mufson, Elliott J.

    2014-01-01

    Down syndrome (DS), trisomy 21, is a multifaceted condition marked by intellectual disability and early presentation of Alzheimer’s disease (AD) neuropathological lesions including degeneration of the basal forebrain cholinergic neuron (BFCN) system. While DS is diagnosable during gestation, there is no treatment option for expectant mothers or DS individuals. Using the Ts65Dn mouse model of DS that displays age-related degeneration of the BFCN system, we investigated the effects of maternal choline supplementation on the BFCN system in adult Ts65Dn mice and disomic (2N) littermates at 4.3–7.5 mos of age. Ts65Dn dams were maintained on a choline supplemented diet (5.1 g/kg choline chloride) or a control, unsupplemented diet with adequate amounts of choline (1 g/kg choline chloride) from conception until weaning of offspring; postweaning, offspring were fed the control diet. Mice were transcardially perfused with paraformaldehyde, brains were sectioned, and immunolabeled for choline acetyltransferase (ChAT) or p75-neurotrophin receptor (p75NTR). BFCN number and size, the area of the regions, and the intensity of hippocampal labeling were determined. Ts65Dn unsupplemented mice displayed region- and immunolabel-dependent increased BFCN number, larger areas, smaller BFCNs, and overall increased hippocampal ChAT intensity compared with 2N unsupplemented mice. These effects were partially normalized by maternal choline supplementation. Taken together, the results suggest a developmental imbalance in the Ts65Dn BFCN system. Early maternal-diet choline supplementation attenuates some of the genotype-dependent alterations in the BFCN system, suggesting this naturally occurring nutrient as a treatment option for pregnant mothers with knowledge that their offspring is trisomy 21. PMID:24178831

  4. Maternal smoking promotes chronic obstructive lung disease in the offspring as adults

    Directory of Open Access Journals (Sweden)

    Beyer D

    2009-12-01

    Full Text Available Abstract Introduction In utero and/or childhood environmental tobacco smoke exposure is well known to adversely affect lung function and to depreciate child's health in many ways. Fewer studies have assessed the long-term effects on COPD development and disease severity in later adulthood. Methods COPD patients were interviewed using a structured questionnaire regarding their personal as well as the smoking habits of their parents. Data were compared with the disease history, e.g. COPD exacerbation rate, and their lung function data. Results Between 2003 and 2004 COPD patients were recruited a in a private practice specialized in pulmonary medicine (n = 133 and b in a hospital (n = 158. 75% of their fathers and only 15.4 of all mothers smoked regularly. COPD patients from smoking mothers had lower FEV1 predicted than those raised in household without maternal smoking exposure: 39.4 ± 9.5% vs. 51.9 ± 6.0% (P = 0.037. Fathers had no effect on FEV1 regardless if they are smokers or non-smokers. Rate of severe exacerbations requiring hospitalization remained unaffected by parental second hand smoke exposure. Conclusion Maternal smoking negatively affects lung function of their offspring even in late adulthood when they develop COPD. It even aggravates the cumulative effect of active cigarette consumption. Clinical course of the COPD remained unaffected.

  5. Heart regeneration in adult MRL mice

    Science.gov (United States)

    Leferovich, John M.; Bedelbaeva, Khamilia; Samulewicz, Stefan; Zhang, Xiang-Ming; Zwas, Donna; Lankford, Edward B.; Heber-Katz, Ellen

    2001-08-01

    The reaction of cardiac tissue to acute injury involves interacting cascades of cellular and molecular responses that encompass inflammation, hormonal signaling, extracellular matrix remodeling, and compensatory adaptation of myocytes. Myocardial regeneration is observed in amphibians, whereas scar formation characterizes cardiac ventricular wound healing in a variety of mammalian injury models. We have previously shown that the MRL mouse strain has an extraordinary capacity to heal surgical wounds, a complex trait that maps to at least seven genetic loci. Here, we extend these studies to cardiac wounds and demonstrate that a severe transmural, cryogenically induced infarction of the right ventricle heals extensively within 60 days, with the restoration of normal myocardium and function. Scarring is markedly reduced in MRL mice compared with C57BL/6 mice, consistent with both the reduced hydroxyproline levels seen after injury and an elevated cardiomyocyte mitotic index of 10-20% for the MRL compared with 1-3% for the C57BL/6. The myocardial response to injury observed in these mice resembles the regenerative process seen in amphibians.

  6. Exposure to Low Dose of Cinnabar (a Naturally Occurring Mercuric Sulfide (HgS Caused Neurotoxicological Effects in Offspring Mice

    Directory of Open Access Journals (Sweden)

    Chun-Fa Huang

    2012-01-01

    Full Text Available Cinnabar, a naturally occurring mercuric sulfide (HgS, has long been used in Chinese mineral medicine for more than 2000 years. Although mercury is well-known for its toxicity, whether cinnabar induces neurotoxicity, especially in infants and children, is unknown. The purpose of this study was to explore the neurotoxic effects of low-dose of cinnabar (10 mg/kg/day on developing mice. The results revealed neurobehavioral defects in F1-C-Cin group, which were associated with Hg accumulation, increased NOx levels in whole blood, and Na+/K+-ATPase activities in brain tissues. F1- and F2-Cin-V groups were found to increase brain Hg contents and prominent neurobehavioral defects compared with F1-C-V group, suggesting that the fetal brain was more susceptible to irreversible effects for cinnabar-induced damage. Moreover, F1- and F2-Cin-Cin groups had severely neurobehavioral dysfunctions, closely correlated with the further alteration of NOx levels and Na+/K+-ATPase activities than F1- and F2-C-Cin groups. Effects in F2-Cin-Cin group were more significant than those in F1-Cin-Cin group. In conclusion, this study demonstrates that exposure to low-dose of cinnabar during the perinatal and developmental stages results in irreversible and severe injuries of the neurotoxicity in offspring, and NOx and Na+/K+-ATPase activities may exist potential and useful biomarkers for neurotoxicity-induced by low-doses of mercuric compounds.

  7. 241Am distribution and retention in pregnant mice, in their offspring and in non-pregnant mice: comparison between continuous Am administration and single injection

    International Nuclear Information System (INIS)

    Pregnant BALB/c mice and age and sex matched nulliparous controls were contaminated with 241Am (13 kBq per mouse). Five days after the termination of contamination, 241Am incorporation was measured in the tissues of adults and in the liver an the femur of newborn and one-month-old mice. Pregnancy resulted in higher 241Am concentrations in bone but lower concentrations in the liver of the mothers. Protracted administration of 241Am compared to a single injection resulted in a lower concentration of 241Am in the livers of pregnant mice, their nulliparous controls and from newborn mice. The higher 241Am concentration in the femur at birth after protected exposure before 14 days of gestation compared to protracted exposure after 14 days of gestation could reflect the increased placental transfer of 241Am with advancing gestational age. Radiation doses to the femur were estimated between 4 and 20 mGy. Haemopoietic changes were noticed at these dose levels in all groups until at least 6 months after birth. (author)

  8. Perinatal caffeine, acting on maternal adenosine A(1 receptors, causes long-lasting behavioral changes in mouse offspring.

    Directory of Open Access Journals (Sweden)

    Olga Björklund

    Full Text Available BACKGROUND: There are lingering concerns about caffeine consumption during pregnancy or the early postnatal period, partly because there may be long-lasting behavioral changes after caffeine exposure early in life. METHODOLOGY/PRINCIPAL FINDINGS: We show that pregnant wild type (WT mice given modest doses of caffeine (0.3 g/l in drinking water gave birth to offspring that as adults exhibited increased locomotor activity in an open field. The offspring also responded to cocaine challenge with greater locomotor activity than mice not perinatally exposed to caffeine. We performed the same behavioral experiments on mice heterozygous for adenosine A(1 receptor gene (A(1RHz. In these mice signaling via adenosine A(1 receptors is reduced to about the same degree as after modest consumption of caffeine. A(1RHz mice had a behavioral profile similar to WT mice perinatally exposed to caffeine. Furthermore, it appeared that the mother's genotype, not offspring's, was critical for behavioral changes in adult offspring. Thus, if the mother partially lacked A(1 receptors the offspring displayed more hyperactivity and responded more strongly to cocaine stimulation as adults than did mice of a WT mother, regardless of their genotype. This indicates that long-term behavioral alterations in the offspring result from the maternal effect of caffeine, and not a direct effect on fetus. WT offspring from WT mother but having a A(1R Hz grandmother preserved higher locomotor response to cocaine. CONCLUSIONS/SIGNIFICANCE: We suggest that perinatal caffeine, by acting on adenosine A(1 receptors in the mother, causes long-lasting behavioral changes in the offspring that even manifest themselves in the second generation.

  9. Opiate addiction in adult offspring through possible imprinting after obstetric treatment.

    OpenAIRE

    Jacobson, B; Nyberg, K; Grönbladh, L; Eklund, G; Bygdeman, M; Rydberg, U

    1990-01-01

    OBJECTIVE--To test the hypothesis that opiate addiction in adults might stem partly from an imprinting process during birth when certain drugs are given to the mother. DESIGN--Retrospective study by logistic regression of opiate addicts with siblings as controls. SETTING--Stockholm, Sweden. SUBJECTS--200 Opiate addicts born in Stockholm during 1945-66, comprising 41 identified during interviews of probands for an earlier study; 75 patients whose death from opiate addiction had been confirmed ...

  10. Embryonic caffeine exposure acts via A1 adenosine receptors to alter adult cardiac function and DNA methylation in mice.

    Directory of Open Access Journals (Sweden)

    Daniela L Buscariollo

    Full Text Available Evidence indicates that disruption of normal prenatal development influences an individual's risk of developing obesity and cardiovascular disease as an adult. Thus, understanding how in utero exposure to chemical agents leads to increased susceptibility to adult diseases is a critical health related issue. Our aim was to determine whether adenosine A1 receptors (A1ARs mediate the long-term effects of in utero caffeine exposure on cardiac function and whether these long-term effects are the result of changes in DNA methylation patterns in adult hearts. Pregnant A1AR knockout mice were treated with caffeine (20 mg/kg or vehicle (0.09% NaCl i.p. at embryonic day 8.5. This caffeine treatment results in serum levels equivalent to the consumption of 2-4 cups of coffee in humans. After dams gave birth, offspring were examined at 8-10 weeks of age. A1AR+/+ offspring treated in utero with caffeine were 10% heavier than vehicle controls. Using echocardiography, we observed altered cardiac function and morphology in adult mice exposed to caffeine in utero. Caffeine treatment decreased cardiac output by 11% and increased left ventricular wall thickness by 29% during diastole. Using DNA methylation arrays, we identified altered DNA methylation patterns in A1AR+/+ caffeine treated hearts, including 7719 differentially methylated regions (DMRs within the genome and an overall decrease in DNA methylation of 26%. Analysis of genes associated with DMRs revealed that many are associated with cardiac hypertrophy. These data demonstrate that A1ARs mediate in utero caffeine effects on cardiac function and growth and that caffeine exposure leads to changes in DNA methylation.

  11. Too risky to settle: avian community structure changes in response to perceived predation risk on adults and offspring

    Science.gov (United States)

    Hua, Fangyuan; Fletcher, Robert J.; Sieving, Kathryn E.; Dorazio, Robert M.

    2013-01-01

    Predation risk is widely hypothesized as an important force structuring communities, but this potential force is rarely tested experimentally, particularly in terrestrial vertebrate communities. How animals respond to predation risk is generally considered predictable from species life-history and natural-history traits, but rigorous tests of these predictions remain scarce. We report on a large-scale playback experiment with a forest bird community that addresses two questions: (i) does perceived predation risk shape the richness and composition of a breeding bird community? And (ii) can species life-history and natural-history traits predict prey community responses to different types of predation risk? On 9 ha plots, we manipulated cues of three avian predators that preferentially prey on either adult birds or offspring, or both, throughout the breeding season. We found that increased perception of predation risk led to generally negative responses in the abundance, occurrence and/or detection probability of most prey species, which in turn reduced the species richness and shifted the composition of the breeding bird community. Species-level responses were largely predicted from the key natural-history trait of body size, but we did not find support for the life-history theory prediction of the relationship between species' slow/fast life-history strategy and their response to predation risk.

  12. Gestation and breastfeeding in schistosomotic mothers differently modulate the immune response of adult offspring to postnatal Schistosoma mansoni infection.

    Science.gov (United States)

    Santos, Patrícia d'Emery Alves; Lorena, Virgínia Maria Barros de; Fernandes, Érica de Souza; Sales, Iana Rafaela Fernandes; Nascimento, Wheverton Ricardo Correia do; Gomes, Yara de Miranda; Albuquerque, Mônica Camelo Pessoa de Azevedo; Costa, Vlaudia Maria Assis; Souza, Valdênia Maria Oliveira de

    2016-02-01

    Schistosoma mansoni antigens in the early life alter homologous and heterologous immunity during postnatal infections. We evaluate the immunity to parasite antigens and ovalbumin (OA) in adult mice born/suckled by schistosomotic mothers. Newborns were divided into: born (BIM), suckled (SIM) or born/suckled (BSIM) in schistosomotic mothers, and animals from noninfected mothers (control). When adults, the mice were infected and compared the hepatic granuloma size and cellularity. Some animals were OA + adjuvant immunised. We evaluated hypersensitivity reactions (HR), antibodies levels (IgG1/IgG2a) anti-soluble egg antigen and anti-soluble worm antigen preparation, and anti-OA, cytokine production, and CD4+FoxP3+T-cells by splenocytes. Compared to control group, BIM mice showed a greater quantity of granulomas and collagen deposition, whereas SIM and BSIM presented smaller granulomas. BSIM group exhibited the lowest levels of anti-parasite antibodies. For anti-OA immunity, immediate HR was suppressed in all groups, with greater intensity in SIM mice accompanied of the remarkable level of basal CD4+FoxP3+T-cells. BIM and SIM groups produced less interleukin (IL)-4 and interferon (IFN)-g. In BSIM, there was higher production of IL-10 and IFN-g, but lower levels of IL-4 and CD4+FoxP3+T-cells. Thus, pregnancy in schistosomotic mothers intensified hepatic fibrosis, whereas breastfeeding diminished granulomas in descendants. Separately, pregnancy and breastfeeding could suppress heterologous immunity; however, when combined, the responses could be partially restored in infected descendants. PMID:26872339

  13. The Association of Maternal Socialization in Childhood and Adolescence with Adult Offsprings' Sympathy/Caring

    Science.gov (United States)

    Eisenberg, Nancy; VanSchyndel, Sarah K.; Hofer, Claire

    2015-01-01

    The purpose of the study was to examine associations between mothers' socialization practices in childhood and adolescence and offsprings' (N = 32, 16 female) sympathy/concern in early adulthood. Mothers reported on their socialization practices and beliefs a total of 6 times using a Q-sort during their offsprings' childhood…

  14. Maternal High-Fat Diet-Induced Loss of Fetal Oocytes Is Associated with Compromised Follicle Growth in Adult Rat Offspring.

    Science.gov (United States)

    Tsoulis, Michael W; Chang, Pauline E; Moore, Caroline J; Chan, Kaitlyn A; Gohir, Wajiha; Petrik, James J; Vickers, Mark H; Connor, Kristin L; Sloboda, Deborah M

    2016-04-01

    Maternal obesity predisposes offspring to metabolic and reproductive dysfunction. We have shown previously that female rat offspring born to mothers fed a high-fat (HF) diet throughout pregnancy and lactation enter puberty early and display aberrant reproductive cyclicity. The mechanisms driving this reproductive phenotype are currently unknown thus we investigated whether changes in ovarian function were involved. Wistar rats were mated and randomized to: dams fed a control diet (CON) or dams fed a HF diet from conception until the end of lactation (HF). Ovaries were collected from fetuses at Embryonic Day (E) 20, and neonatal ovaries at Day 4 (P4), prepubertal ovaries at P27 and adult ovaries at P120. In a subset of offspring, the effects of a HF diet fed postweaning were evaluated. The present study shows that fetuses of mothers fed a HF diet had significantly fewer oocytes at E20, and in neonates, have reduced AMH signaling that may facilitate an increased number of assembled primordial follicles. Both prepubertally and in adulthood, ovaries show increased follicular atresia. As adults, offspring have reduced FSH responsiveness, low expression levels of estrogen receptor alpha (Eralpha), the oocyte-secreted factor, Gdf9, oocyte-specific RNA binding protein, Dazl, and high expression levels of the granulosa-cell derived factor, AMH, in antral follicles. Together, these data suggest that ovarian compromise in offspring born to HF-fed mothers may arise from changes already observable in the fetus and neonate and in the long term, associated with increased follicular atresia through adulthood. PMID:26962114

  15. Pulmonary exposure to carbon black by inhalation or instillation in pregnant mice: Effects on liver DNA strand breaks in dams and offspring

    OpenAIRE

    Jackson, Petra; Hougaard, Karin Sørig; Boisen, Anne Mette Z; Jacobsen, Nicklas Raun; Jensen, Keld Alstrup; Møller, Peter; Brunborg, Gunnar; Gutzkow, Kristine Bjerve; Andersen, Ole; Loft, Steffen; Vogel, Ulla; Wallin, Håkan

    2012-01-01

    Effects of maternal pulmonary exposure to carbon black (Printex 90) on gestation, lactation and DNA strand breaks were evaluated. Time-mated C57BL/6BomTac mice were exposed by inhalation to 42 mg/m3 Printex 90 for 1 h/day on gestation days (GD) 8-18, or by four intratracheal instillations on GD 7, 10, 15 and 18, with total doses of 11, 54 and 268 (μg/animal. Dams were monitored until weaning and some offspring until adolescence. Inflammation was assessed in maternal bronchoalveolar lavage (BA...

  16. Combined effects of perfluorooctane sulfonate (PFOS) and maternal restraint stress on hypothalamus adrenal axis (HPA) function in the offspring of mice

    International Nuclear Information System (INIS)

    Although it is known that prenatal exposure to perfluorooctane sulfonate (PFOS) can cause developmental adverse effects in mammals, the disruptive effects of this compound on hormonal systems are still controversial. Information concerning the effects of PFOS on hypothalamus adrenal (HPA) axis response to stress and corticosterone levels is not currently available. On the other hand, it is well established that stress can enhance the developmental toxicity of some chemicals. In the present study, we assessed the combined effects of maternal restraint stress and PFOS on HPA axis function in the offspring of mice. Twenty plug-positive female mice were divided in two groups. Animals were given by gavage 0 and 6 mg PFOS/kg/day on gestation days 12-18. One half of the animals in each group were also subjected to restraint stress (30 min/session, 3 sessions/day) during the same period. Five plug-positive females were also included as non-manipulated controls. At 3 months of age, activity in an open-field and the stress response were evaluated in male and female mice by exposing them to 30 min of restraint stress. Male and female offspring were subsequently sacrificed and blood samples were collected to measure changes in corticosterone levels at four different moments related to stress exposure conditions: before stress exposure, immediately after 30 min of stress exposure, and recuperation levels at 60 and 90 min after stress exposure. Results indicate corticosterone levels were lower in mice prenatally exposed to restraint. In general terms, PFOS exposure decreased corticosterone levels, although this effect was only significant in females. The recuperation pattern of corticosterone was mainly affected by prenatal stress. Interactive effects between PFOS and maternal stress were sex dependent. The current results suggest that prenatal PFOS exposure induced long-lasting effects in mice.

  17. Effect of vitamin B deprivation during pregnancy and lactation on homocysteine metabolism and related metabolites in brain and plasma of mice offspring.

    Directory of Open Access Journals (Sweden)

    Vanessa Cavalcante da Silva

    Full Text Available Epidemiological and experimental studies indicate that the altered fetal and neonatal environment influences physiological functions and may increase the risk of developing chronic diseases in adulthood. Because homocysteine (Hcy metabolic imbalance is considered a risk factor for neurodegenerative diseases, we investigated whether maternal Vitamin B deficiency during early development alters the offspring's methionine-homocysteine metabolism in their brain. To this end, the dams were submitted to experimental diet one month before and during pregnancy or pregnancy/lactation. After birth, the offspring were organized into the following groups: control (CT, deficient diet during pregnancy and lactation (DPL and deficient diet during pregnancy (DP. The mice were euthanized at various stages of development. Hcy, cysteine, glutathione (GSH, S-adenosylmethionine (SAM, S-adenosylhomocysteine (SAH, folate and cobalamin concentrations were measured in the plasma and/or brain. At postnatal day (PND 0, total brain of female and male offspring exhibited decreased SAM/SAH ratios. Moreover, at PND 28, we observed decreased GSH/GSSG ratios in both females and males in the DPL group. Exposure to a Vitamin B-deficient diet during the ontogenic plasticity period had a negative impact on plasma folate and brain cortex SAM concentrations in aged DPL males. We also observed decreased plasma GSH concentrations in both DP and DPL males (PND 210. Additionally, this manipulation seemed to affect the female and male offspring differently. The decreased plasma GSH concentration may reflect redox changes in tissues and the decreased brain cortex SAM may be involved in changes of gene expression, which could contribute to neurodegenerative diseases over the long term.

  18. Effect of vitamin B deprivation during pregnancy and lactation on homocysteine metabolism and related metabolites in brain and plasma of mice offspring.

    Science.gov (United States)

    da Silva, Vanessa Cavalcante; Fernandes, Leandro; Haseyama, Eduardo Jun; Agamme, Ana Luiza Dias Abdo; Guerra Shinohara, Elvira Maria; Muniz, Maria Tereza Cartaxo; D'Almeida, Vânia

    2014-01-01

    Epidemiological and experimental studies indicate that the altered fetal and neonatal environment influences physiological functions and may increase the risk of developing chronic diseases in adulthood. Because homocysteine (Hcy) metabolic imbalance is considered a risk factor for neurodegenerative diseases, we investigated whether maternal Vitamin B deficiency during early development alters the offspring's methionine-homocysteine metabolism in their brain. To this end, the dams were submitted to experimental diet one month before and during pregnancy or pregnancy/lactation. After birth, the offspring were organized into the following groups: control (CT), deficient diet during pregnancy and lactation (DPL) and deficient diet during pregnancy (DP). The mice were euthanized at various stages of development. Hcy, cysteine, glutathione (GSH), S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), folate and cobalamin concentrations were measured in the plasma and/or brain. At postnatal day (PND) 0, total brain of female and male offspring exhibited decreased SAM/SAH ratios. Moreover, at PND 28, we observed decreased GSH/GSSG ratios in both females and males in the DPL group. Exposure to a Vitamin B-deficient diet during the ontogenic plasticity period had a negative impact on plasma folate and brain cortex SAM concentrations in aged DPL males. We also observed decreased plasma GSH concentrations in both DP and DPL males (PND 210). Additionally, this manipulation seemed to affect the female and male offspring differently. The decreased plasma GSH concentration may reflect redox changes in tissues and the decreased brain cortex SAM may be involved in changes of gene expression, which could contribute to neurodegenerative diseases over the long term. PMID:24695104

  19. Peroxisome proliferator-activated receptors-alpha and gamma are targets to treat offspring from maternal diet-induced obesity in mice.

    Directory of Open Access Journals (Sweden)

    D'Angelo Carlo Magliano

    Full Text Available AIM: The aim of the present study was to evaluate whether activation of peroxisome proliferator-activated receptor (PPARalpha and PPARgamma by Bezafibrate (BZ could attenuate hepatic and white adipose tissue (WAT abnormalities in male offspring from diet-induced obese dams. MATERIALS AND METHODS: C57BL/6 female mice were fed a standard chow (SC; 10% lipids diet or a high-fat (HF; 49% lipids diet for 8 weeks before mating and during gestation and lactation periods. Male offspring received SC diet at weaning and were subdivided into four groups: SC, SC/BZ, HF and HF/BZ. Treatment with BZ (100 mg/Kg diet started at 12 weeks of age and was maintained for three weeks. RESULTS: The HF diet resulted in an overweight phenotype and an increase in oral glucose intolerance and fasting glucose of dams. The HF offspring showed increased body mass, higher levels of plasmatic and hepatic triglycerides, higher levels of pro-inflammatory and lower levels of anti-inflammatory adipokines, impairment of glucose metabolism, abnormal fat pad mass distribution, higher number of larger adipocytes, hepatic steatosis, higher expression of lipogenic proteins concomitant to decreased expression of PPARalpha and carnitine palmitoyltransferase I (CPT-1 in liver, and diminished expression of PPARgamma and adiponectin in WAT. Treatment with BZ ameliorated the hepatic and WAT abnormalities generated by diet-induced maternal obesity, with improvements observed in the structural, biochemical and molecular characteristics of the animals' livers and epididymal fat. CONCLUSION: Diet-induced maternal obesity lead to alterations in metabolism, hepatic lipotoxicity and adverse liver and WAT remodeling in the offspring. Targeting PPAR with Bezafibrate has beneficial effects reducing the alterations, mainly through reduction of WAT inflammatory state through PPARgamma activation and enhanced hepatic beta-oxidation due to increased PPARalpha/PPARgamma ratio in liver.

  20. Toluene Induces Depression-Like Behaviors in Adult Mice

    OpenAIRE

    Yang, Miyoung; Kim, Sung-Ho; Kim, Jong-Choon; Shin, Taekyun; Moon, Changjong

    2010-01-01

    It has been clinically reported that toluene causes mental depression in humans. However, the detrimental effects of toluene exposure on brain function and the relation between features of mental depression and toluene exposure are poorly understood. This study evaluated depression-like behaviors in adult C57BL/6 mice after administration of toluene, and elucidated the effects of classical antidepressants on the depression-like behaviors. For the estimation of depression-like behaviors, tail ...

  1. Increased cardiovascular reactivity to acute stress and salt-loading in adult male offspring of fat fed non-obese rats.

    Directory of Open Access Journals (Sweden)

    Olena Rudyk

    Full Text Available Diet-induced obesity in rat pregnancy has been shown previously to be associated with consistently raised blood pressure in the offspring, attributed to sympathetic over-activation, but the relative contributions to this phenotype of maternal obesity versus raised dietary fat is unknown. Sprague-Dawley female rats were fed either a control (4.3% fat, n = 11 or lard-enriched (23.6% fat, n = 16 chow 10 days prior to mating, throughout pregnancy and lactation. In conscious adult (9-month-old offspring cardiovascular parameters were measured (radiotelemetry. The short period of fat-feeding did not increase maternal weight versus controls and the baseline blood pressure was similar in offspring of fat fed dams (OF and controls (OC. However, adult male OF showed heightened cardiovascular reactivity to acute restraint stress (p<0.01; Δ systolic blood pressure (SBP and Δheart rate (HR with a prolonged recovery time compared to male OC. α1/β-adrenergic receptor blockade normalised the response. Also, after dietary salt-loading (8%-NaCl ad libitum for 1 week male OF demonstrated higher SBP (p<0.05 in the awake phase (night-time and increased low/high frequency ratio of power spectral density of HR variability versus OC. Baroreflex gain and basal power spectral density components of the heart rate or blood pressure were similar in male OF and OC. Minor abnormalities were evident in female OF. Fat feeding in the absence of maternal obesity in pregnant rats leads to altered sympathetic control of cardiovascular function in adult male offspring, and hypertension in response to stressor stimuli.

  2. Evaluation of possible toxic effects of spearmint (Mentha spicata on the reproductive system, fertility and number of offspring in adult male rats

    Directory of Open Access Journals (Sweden)

    Fatemeh Nozhat

    2014-11-01

    Full Text Available Objective: In this study we investigated the effects of spearmint (Mentha spicata Labiatae on the reproductive system, fertility and number of offspring in adult male rats. Materials and Methods: Adult Wistar male rats in one control (C and three experimental groups (I, II and III received 0, 10, 20 and 40 mg/kg spearmint extract orally for 45 days, respectively.  Following this treatment, the animals’ weights, and the standard weight of reproductive tissues, sperm count, sperm motility and serum testosterone concentration were measured, and reproductive tissues were examined histopathologically. To evaluate the effects of spearmint on fertility of male rats and growth of their offspring, male rats of the control and experimental groups mated with untreated female rats. Results: Results showed that spearmint did not affect the rats’ body and reproductive tissue weights. The sperm count, fast and slow progressive motility of sperm and serum testosterone concentration decreased while number of non-progressive sperm and immotile sperm increased in the experimental groups compared to the control group, but none of these changes were statistically significant. Histopathological studies showed no severe changes in reproductive tissues between control and experimental groups. Number and growth of offspring born from mating of male rats with untreated female rats showed no difference. Conclusion: We concluded that spearmint has no significant toxic effect on the reproductive system, fertility and number of offspring in adult male rats at the above  mentioned dose levels. However high levels of this extract may have adverse effects on male fertility.

  3. Adaptation of enterovirus 71 to adult interferon deficient mice.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Caine

    Full Text Available Non-polio enteroviruses, including enterovirus 71 (EV71, have caused severe and fatal cases of hand, foot and mouth disease (HFMD in the Asia-Pacific region. The development of a vaccine or antiviral against these pathogens has been hampered by the lack of a reliable small animal model. In this study, a mouse adapted EV71 strain was produced by conducting serial passages through A129 (α/β interferon (IFN receptor deficient and AG129 (α/β, γ IFN receptor deficient mice. A B2 sub genotype of EV71 was inoculated intraperitoneally (i.p. into neonatal AG129 mice and brain-harvested virus was subsequently passaged through 12 and 15 day-old A129 mice. When tested in 10 week-old AG129 mice, this adapted strain produced 100% lethality with clinical signs including limb paralysis, eye irritation, loss of balance, and death. This virus caused only 17% mortality in same age A129 mice, confirming that in the absence of a functional IFN response, adult AG129 mice are susceptible to infection by adapted EV71 isolates. Subsequent studies in adult AG129 and young A129 mice with the adapted EV71 virus examined the efficacy of an inactivated EV71 candidate vaccine and determined the role of humoral immunity in protection. Passive transfer of rabbit immune sera raised against the EV71 vaccine provided protection in a dose dependent manner in 15 day-old A129 mice. Intramuscular injections (i.m. in five week-old AG129 mice with the alum adjuvanted vaccine also provided protection against the mouse adapted homologous strain. No clinical signs of disease or mortality were observed in vaccinated animals, which received a prime-and-boost, whereas 71% of control animals were euthanized after exhibiting systemic clinical signs (P<0.05. The development of this animal model will facilitate studies on EV71 pathogenesis, antiviral testing, the evaluation of immunogenicity and efficacy of vaccine candidates, and has the potential to establish correlates of protection

  4. Postnatal high-fat diet leads to spatial deficit, obesity, and central and peripheral inflammation in prenatal dexamethasone adult offspring rats.

    Science.gov (United States)

    Hsieh, Chih-Sung; Li, Shih-Wen; Sheen, Jiunn-Ming; Yu, Hong-Ren; Tiao, Mao-Meng; Tain, You-Lin; Su, Chung-Hao; Huang, Li-Tung

    2016-08-01

    Synthetic glucocorticoids are frequently used in clinical practice for treating pregnant women at risk of preterm delivery, but their long-term effects on the infant brain are largely unknown. Pregnant Sprague-Dawley rats were administered vehicle or dexamethasone between gestational days 14 and 21. Male offspring were then weaned onto either a standard chow or a high-fat diet. The postnatal levels of insulin-like growth factor I (IGF-1), tumor necrosis factor-α (TNF-α), and asymmetric dimethylarginine (ADMA) in the plasma, liver, and brain were examined, as well as the possible effects of prenatal dexamethasone on cognition. We found that a postnatal high-fat diet led to spatial deficits detected by the Morris water maze in adult offspring administered dexamethasone prenatally. The spatial deficit was accompanied by decreased IGF-1 mRNA and increased ADMA levels in the dorsal hippocampus. In peripheral systems, a postnatal high-fat diet resulted in decreased plasma IGF-1, increased plasma corticosterone, increased concentrations of transaminases, TNF-α mRNA, and ADMA in the liver, and associated obesity in adult offspring administered prenatal dexamethasone. In conclusion, a postnatal high-fat diet led to spatial deficits, obesity, and altered levels of IGF-1, TNF-α, and ADMA in the plasma, liver, or brain. PMID:27272689

  5. Maternal dietary loads of α-tocopherol depress protein kinase C signaling and synaptic plasticity in rat postnatal developing hippocampus and promote permanent deficits in adult offspring.

    Science.gov (United States)

    Betti, Michele; Ambrogini, Patrizia; Minelli, Andrea; Floridi, Alessandro; Lattanzi, Davide; Ciuffoli, Stefano; Bucherelli, Corrado; Prospero, Emilia; Frontini, Andrea; Santarelli, Lory; Baldi, Elisabetta; Benetti, Fernando; Galli, Francesco; Cuppini, Riccardo

    2011-01-01

    Vitamin E (α-tocopherol) supplementation has been tested as prophylaxis against gestational disorders associated with oxidative damage. However, recent evidence showing that high maternal α-tocopherol intake can adversely affect offspring development raises concerns on the safety of vitamin E extradosages during pregnancy. Besides acting as an antioxidant, α-tocopherol depresses cell proliferation and modulates cell signaling through inhibiting protein kinase C (PKC), a kinase that is deeply involved in neural maturation and plasticity. Possible effects of α-tocopherol loads in the maturing brain, where PKC dysregulation is associated to developmental dysfunctions, are poorly known. Here, supranutritional doses of α-tocopherol were fed to pregnant and lactating dams to evaluate the effects on PKC signaling and morphofunctional maturation in offspring hippocampus. Results showed that maternal supplementation potentiates hippocampal α-tocopherol incorporation in offspring and leads to marked decrease of PKC phosphorylation throughout postnatal maturation, accompanied by reduced phosphorylation of growth-associated protein-43 and myristoylated alanine-rich C kinase substrate, two PKC substrates involved in neural development and plasticity. Although processes of neuronal maturation, synapse formation and targeting appeared unaffected, offspring of supplemented mothers displayed a marked reduction of long-term synaptic plasticity in juvenile hippocampus. Interestingly, this impairment persisted in adulthood, when a deficit in hippocampus-dependent, long-lasting spatial memory was also revealed. In conclusion, maternal supplementation with elevated doses of α-tocopherol can influence cell signaling and synaptic plasticity in developing hippocampus and promotes permanent adverse effects in adult offspring. The present results emphasize the need to evaluate the safety of supranutritional maternal intake of α-tocopherol in humans. PMID:20382010

  6. Adult neurogenesis in the four-striped mice (Rhabdomys pumilio)

    Institute of Scientific and Technical Information of China (English)

    Olatunbosun O Olaleye; Amadi O Ihunwo

    2014-01-01

    In this study, we investigated non-captive four-striped mice (Rhabdomys pumilio) for evidence that adult neurogenesis occurs in the adult brain of animal models in natural environment. Ki-67 (a marker for cell proliferation) and doublecortin (a marker for immature neurons) immunos-taining conifrmed that adult neurogenesis occurs in the active sites of subventricular zone of the lateral ventricle with the migratory stream to the olfactory bulb, and the subgranular zone of the dentate gyrus of the hippocampus. No Ki-67 proliferating cells were observed in the striatum substantia nigra, amygdala, cerebral cortex or dorsal vagal complex. Doublecortin-immunore-active cells were observed in the striatum, third ventricle, cerebral cortex, amygdala, olfactory bulb and along the rostral migratory stream but absent in the substantia nigra and dorsal vagal complex. The potential neurogenic sites in the four-striped mouse species could invariably lead to increased neural plasticity.

  7. Adult neurogenesis in the four-striped mice (Rhabdomys pumilio).

    Science.gov (United States)

    Olaleye, Olatunbosun O; Ihunwo, Amadi O

    2014-11-01

    In this study, we investigated non-captive four-striped mice (Rhabdomys pumilio) for evidence that adult neurogenesis occurs in the adult brain of animal models in natural environment. Ki-67 (a marker for cell proliferation) and doublecortin (a marker for immature neurons) immunostaining confirmed that adult neurogenesis occurs in the active sites of subventricular zone of the lateral ventricle with the migratory stream to the olfactory bulb, and the subgranular zone of the dentate gyrus of the hippocampus. No Ki-67 proliferating cells were observed in the striatum substantia nigra, amygdala, cerebral cortex or dorsal vagal complex. Doublecortin-immunoreactive cells were observed in the striatum, third ventricle, cerebral cortex, amygdala, olfactory bulb and along the rostral migratory stream but absent in the substantia nigra and dorsal vagal complex. The potential neurogenic sites in the four-striped mouse species could invariably lead to increased neural plasticity. PMID:25558241

  8. The association between parental history of diagnosed mood/anxiety disorders and psychiatric symptoms and disorders in young adult offspring

    OpenAIRE

    Low Nancy CP; Dugas Erika; Constantin Evelyn; Karp Igor; Rodriguez Daniel; O’Loughlin Jennifer

    2012-01-01

    Abstract Background Parental history of mood or anxiety disorders is one of the strongest and most consistent risk factors for the development of these disorders in offspring. Gaps remain however in our knowledge of whether maternal or paternal disorders are more strongly associated with offspring disorders, and whether the association exists in non-clinical samples. This study uses a large population-based sample to test if maternal or paternal history of mood and/or anxiety disorders increa...

  9. 出生前后DEHP暴露对小鼠神经行为的影响❋%Effects of utero and lactational exposure to di-(2-ethylhexyl) phthalate on neurobehavior of offspring mice

    Institute of Scientific and Technical Information of China (English)

    徐晓虹; 竹庆杰; 杨艳玲; 阮琴

    2015-01-01

    The present study investigated the effects of utero and lactational exposure to DEHP (10, 50, and 200 mg/( kg·d) ) from gestation day 7 through postnatal day 21 on the behavior of offspring mice at age of 6 and 12 weeks. The results showed that DEHP exposure significantly inhibited locomotion but increased anxie-ty-like state of pubertal offspring mice of both sexes, and permanently influenced anxiety-like state of females in adulthood. Utero and lactational exposure to DEHP impaired spatial learning and memory function in puber-tal male mice, but not in pubertal females and adult mice of both sexes. These results suggested that develop-mental DEHP exposure sex specifically influenced a variety of neurobehavior, and anxiety and memory of pu-berty were more susceptible to DEHP.%研究了增塑剂邻苯二甲酸二(2-乙基)己酯(di-(2-ethyl hexyl)phthalate,DEHP)围生期母体暴露对青春期(6周龄)和成年后部(12周龄)子代小鼠行为的影响。母鼠从妊娠第7天至断乳前(产后21 d)灌胃染毒DEHP(10,50和200 mg/(kg·d)),同时设空白对照组及溶媒对照组。出生后第6和第12周时分别检测仔鼠的活动性、焦虑、空间记忆等行为。结果显示:DEHP暴露显著抑制了青春期雌、雄仔鼠的活动性,增加了其焦虑状态,且加剧的焦虑状态可延续到成年后的雌鼠;损伤青春期雄鼠的空间学习记忆能力,但对青春期雌鼠和成年后雌、雄仔鼠的空间记忆能力没有影响。以上结果提示,发育期DEHP暴露性别特异性地影响仔鼠的多种神经行为,青春期的情感和记忆能力更容易受影响。

  10. Sex-specific Effects of Exercise Ancestry on Metabolic, Morphological, and Gene Expression Phenotypes in Multiple Generations of Mouse Offspring

    OpenAIRE

    Guth, Lisa M.; Andrew T. Ludlow; Witkowski, Sarah; Marshall, Mallory R.; Lima, Laila C. J.; Venezia, Andrew C.; Xiao, Tao; Lee, Mei-Ling Ting; Spangenburg, Espen E.; Roth, Stephen M.

    2013-01-01

    Early life and pre-conception environmental stimuli can affect adult health-related phenotypes. Exercise training is an environmental stimulus affecting many systems throughout the body and appears to alter offspring phenotypes. The aim of this study was to examine the influence of parental exercise training, or “exercise ancestry,” on morphological and metabolic phenotypes in two generations of mouse offspring. F0 C57BL/6 mice were exposed to voluntary exercise or sedentary lifestyle and bre...

  11. Changes in Liver Antioxidant Status of Offspring Mice Induced by Maternal Fluoride Exposure During Gestation and Lactation.

    Science.gov (United States)

    Niu, Ruiyan; Han, Haijun; Zhang, Yuliang; Wang, Jinming; Zhang, Jianhai; Yin, Wei; Yin, Xiufang; Sun, Zilong; Wang, Jundong

    2016-07-01

    Excessive fluoride intake for a long time has been demonstrated to provoke hepatic oxidative stress in adults. However, the response to fluoride toxicity of liver in newborns exposed to fluoride during embryonic and suckling stages remains unclear. In this study, female Kunming mice were administrated with 25, 50, and 100 mg/L sodium fluoride (NaF) from prenatal day 0 to day 21 after delivery, and the antioxidative status in the liver of their pups at postnatal day 21 was evaluated. The results showed that compared with the control group, NaF significantly increased malondialdehyde (MDA) level and reduced catalase (CAT) activity, while no statistical difference was observed in activities and mRNA expressions of superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR). Notably, with comparison to the controls, the protein level of CAT was significantly reduced in medium- and high-fluoride groups, while its relative mRNA abundance was enhanced which could result from the encouragement of the lowered CAT protein expression. These findings suggested that CAT was more susceptible to low-fluoride exposure in early life. PMID:26613789

  12. A Maternal Gluten-Free Diet Reduces Inflammation and Diabetes Incidence in the Offspring of NOD Mice

    DEFF Research Database (Denmark)

    Hansen, Camilla Hartmann Friis; Krych, Lukasz; Buschard, Karsten;

    2014-01-01

    pronounced difference between both mothers and their offspring on different diets, characterized by increased numbers of Akkermansia, Proteobacteria, and TM7 in the GF diet group. In addition, pancreatic forkhead box P3 regulatory T cells were increased in GF-fed offspring, as were M2 macrophage gene markers...... and tight junction-related genes in the gut, while intestinal gene expression of proinflammatory cytokines was reduced. An increased proportion of T cells in the pancreas expressing the mucosal integrin alpha 4 beta 7 suggests that the mechanism involves increased trafficking of gut-primed immune...... cells to the pancreas. In conclusion, a GF diet during fetal and early postnatal life reduces the incidence of diabetes. The mechanism may involve changes in gut microbiota and shifts to a less proinflammatory immunological milieu in the gut and pancreas....

  13. Growth Hormone Inhibits Hepatic De Novo Lipogenesis in Adult Mice.

    Science.gov (United States)

    Cordoba-Chacon, Jose; Majumdar, Neena; List, Edward O; Diaz-Ruiz, Alberto; Frank, Stuart J; Manzano, Anna; Bartrons, Ramon; Puchowicz, Michelle; Kopchick, John J; Kineman, Rhonda D

    2015-09-01

    Patients with nonalcoholic fatty liver disease (NAFLD) are reported to have low growth hormone (GH) production and/or hepatic GH resistance. GH replacement can resolve the fatty liver condition in diet-induced obese rodents and in GH-deficient patients. However, it remains to be determined whether this inhibitory action of GH is due to direct regulation of hepatic lipid metabolism. Therefore, an adult-onset, hepatocyte-specific, GH receptor (GHR) knockdown (aLivGHRkd) mouse was developed to model hepatic GH resistance in humans that may occur after sexual maturation. Just 7 days after aLivGHRkd, hepatic de novo lipogenesis (DNL) was increased in male and female chow-fed mice, compared with GHR-intact littermate controls. However, hepatosteatosis developed only in male and ovariectomized female aLivGHRkd mice. The increase in DNL observed in aLivGHRkd mice was not associated with hyperactivation of the pathway by which insulin is classically considered to regulate DNL. However, glucokinase mRNA and protein levels as well as fructose-2,6-bisphosphate levels were increased in aLivGHRkd mice, suggesting that enhanced glycolysis drives DNL in the GH-resistant liver. These results demonstrate that hepatic GH actions normally serve to inhibit DNL, where loss of this inhibitory signal may explain, in part, the inappropriate increase in hepatic DNL observed in NAFLD patients. PMID:26015548

  14. The association between parental history of diagnosed mood/anxiety disorders and psychiatric symptoms and disorders in young adult offspring

    Directory of Open Access Journals (Sweden)

    Low Nancy CP

    2012-11-01

    Full Text Available Abstract Background Parental history of mood or anxiety disorders is one of the strongest and most consistent risk factors for the development of these disorders in offspring. Gaps remain however in our knowledge of whether maternal or paternal disorders are more strongly associated with offspring disorders, and whether the association exists in non-clinical samples. This study uses a large population-based sample to test if maternal or paternal history of mood and/or anxiety disorders increases the risk of mood and/or anxiety disorders, or symptoms of specific anxiety disorders, in offspring. Methods Data were drawn from the Nicotine Dependence in Teens Study, a prospective cohort investigation of 1293 grade 7 students. Data on mental health outcomes were collected in mailed self-report questionnaires when participants were aged 20.4 (0.7 years on average. Parental data were collected in mailed self-report questionnaires. This current analysis pertains to 564 participants with maternal and/or paternal data. The association between maternal and paternal history and each of diagnosed anxiety disorder, diagnosed mood disorder, and symptoms of specific anxiety disorders in offspring was studied in multivariate logistic regression. Results A higher proportion of mothers than fathers had a diagnosed mood/anxiety disorder (23% versus 12%. Similarly, 14% of female offspring had a diagnosed mood/anxiety disorder, compared to 6% of male offspring. The adjusted odds ratio (95% confidence interval for maternal history was 2.2 (1.1, 4.5 for diagnosed mood disorders, 4.0 (2.1, 7.8 for diagnosed anxiety disorders, and 2.2 (1.2, 4.0 for social phobia symptoms. Paternal history was not associated with any of the mental health outcomes in offspring. Conclusion Maternal, but not paternal mood/anxiety disorders were associated with diagnosed psychiatric disorders, as well as symptoms of specific anxiety disorders, in offspring. Efforts to detect mood and anxiety

  15. Paternal High Fat Diet in Rats Leads to Renal Accumulation of Lipid and Tubular Changes in Adult Offspring

    Directory of Open Access Journals (Sweden)

    Sabiha S. Chowdhury

    2016-08-01

    Full Text Available Along with diabetes and obesity, chronic kidney disease (CKD is increasing across the globe. Although some data support an effect of maternal obesity on offspring kidney, the impact of paternal obesity is unknown; thus, we have studied the effect of paternal obesity prior to conception. Male Sprague Dawley rats were fed chow diet or high fat diet (HFD for 13–14 weeks before mating with chow-fed females. Male offspring were weaned onto chow and killed at 27 weeks for renal gene expression and histology. Fathers on HFD were 30% heavier than Controls at mating. At 27 weeks of age offspring of obese fathers weighed 10% less; kidney triglyceride content was significantly increased (5.35 ± 0.84 vs. 2.99 ± 0.47 μg/mg, p < 0.05, n = 8 litters per group. Histological analysis of the kidney demonstrated signs of tubule damage, with significantly greater loss of brush border, and increased cell sloughing in offspring of obese compared to Control fathers. Acat1, involved in entry of fatty acid for beta-oxidation, was significantly upregulated, possibly to counteract increased triglyceride storage. However other genes involved in lipid metabolism, inflammation and kidney injury showed no changes. Paternal obesity was associated with renal triglyceride accumulation and histological changes in tubules, suggesting a mild renal insult in offspring, who may be at risk of developing CKD.

  16. Paternal High Fat Diet in Rats Leads to Renal Accumulation of Lipid and Tubular Changes in Adult Offspring.

    Science.gov (United States)

    Chowdhury, Sabiha S; Lecomte, Virginie; Erlich, Jonathan H; Maloney, Christopher A; Morris, Margaret J

    2016-01-01

    Along with diabetes and obesity, chronic kidney disease (CKD) is increasing across the globe. Although some data support an effect of maternal obesity on offspring kidney, the impact of paternal obesity is unknown; thus, we have studied the effect of paternal obesity prior to conception. Male Sprague Dawley rats were fed chow diet or high fat diet (HFD) for 13-14 weeks before mating with chow-fed females. Male offspring were weaned onto chow and killed at 27 weeks for renal gene expression and histology. Fathers on HFD were 30% heavier than Controls at mating. At 27 weeks of age offspring of obese fathers weighed 10% less; kidney triglyceride content was significantly increased (5.35 ± 0.84 vs. 2.99 ± 0.47 μg/mg, p kidney demonstrated signs of tubule damage, with significantly greater loss of brush border, and increased cell sloughing in offspring of obese compared to Control fathers. Acat1, involved in entry of fatty acid for beta-oxidation, was significantly upregulated, possibly to counteract increased triglyceride storage. However other genes involved in lipid metabolism, inflammation and kidney injury showed no changes. Paternal obesity was associated with renal triglyceride accumulation and histological changes in tubules, suggesting a mild renal insult in offspring, who may be at risk of developing CKD. PMID:27563922

  17. Role of cannabinoidergic mechanisms in ethanol self-administration and ethanol seeking in rat adult offspring following perinatal exposure to Δ9-tetrahydrocannabinol

    International Nuclear Information System (INIS)

    The present study evaluated the consequences of perinatal Δ9-tetrahydrocannabinol (Δ9-THC) treatment (5 mg/kg/day by gavage), either alone or combined with ethanol (3% v/v as the only fluid available), on ethanol self-administration and alcohol-seeking behavior in rat adult offspring. Furthermore, the effect of the selective cannabinoid CB1 receptor antagonist, SR-141716A, on ethanol self-administration and on reinstatement of ethanol-seeking behavior induced either by stress or conditioned drug-paired cues was evaluated in adult offspring of rats exposed to the same perinatal treatment. Lastly, microarray experiments were conducted to evaluate if perinatal treatment with Δ9-tetrahydrocannabinol, ethanol or their combination causes long-term changes in brain gene expression profile in rats. The results of microarray data analysis showed that 139, 112 and 170 genes were differentially expressed in the EtOH, Δ9-THC, or EtOH + Δ9-THC group, respectively. No differences in alcohol self-administration and alcohol seeking were observed between rat groups. Intraperitoneal (IP) administration of SR-141716A (0.3-3.0 mg/kg) significantly reduced lever pressing for ethanol and blocked conditioned reinstatement of alcohol seeking. At the same doses SR-141716A failed to block foot-shock stress-induced reinstatement of alcohol seeking. The results reveal that perinatal exposure to Δ9-THC ethanol or their combination results in evident changes in gene expression patterns. However, these treatments do not significantly affect vulnerability to ethanol abuse in adult offspring. On the other hand, the results obtained with SR-141716A emphasize that endocannabinoid mechanisms play a major role in ethanol self-administration, as well as in the reinstatement of ethanol-seeking behavior induced by conditioned cues, supporting the idea that cannabinoid CB1 receptor antagonists may represent interesting agents for the pharmacotherapy of alcoholism

  18. Maternal consumption of canola oil suppressed mammary gland tumorigenesis in C3(1) TAg mice offspring

    OpenAIRE

    Hardman W Elaine; Akinsete Juliana A; Ion Gabriela

    2010-01-01

    Abstract Background Maternal consumption of a diet high in omega 6 polyunsaturated fats (n-6 PUFA) has been shown to increase risk whereas a diet high in omega 3 polyunsaturated fats (n-3 PUFA) from fish oil has been shown to decrease risk for mammary gland cancer in female offspring of rats. The aim of this study was to determine whether increasing n-3 PUFA and reducing n-6 PUFA by using canola oil instead of corn oil in the maternal diet might reduce the risk for breast cancer in female off...

  19. Bone status of adult female butyrylcholinesterase gene-deficient mice.

    Science.gov (United States)

    Haupt, Malte; Kauschke, Vivien; Sender, Jonas; Kampschulte, Marian; Kovtun, Anna; Dürselen, Lutz; Heiss, Christian; Lips, Katrin Susanne

    2015-11-01

    Butyrylcholinesterase (BChE) degrades acetylcholine in addition to acetylcholinesterase (AChE) which is involved in embryonic development of limbs. Since BChE is expressed by osteoblast-like cells we asked whether it is functional in adult bone remodeling. We addressed this issue by analyzing BChE gene-deficient mice (BChE-KO). Bones were extracted from 16-week old female BChE-KO and corresponding wild type mice (WT). Femoral bones were used for biomechanical testing and μCT evaluation of cancellous and cortical bone. Also vertebrae Th12 and L1 were investigated with μCT while L3 was used for tartrate-resistant acidic phosphatase (TRAP) histomorphometry and Th10 for gene expression analysis by means of real-time RT-PCR. BChE-KO did not reveal significant differences in biomechanical bone strength and bone mineral density determined by μCT. Microarchitecture of cancellous and cortical bone showed an increase in μCT parameters like trabecular thickness, trabecular separation, and relative cortical bone area of femoral BChE-KO bone compared to WT. In vertebrae no changes of microstructure and mRNA expression were detected. However, osteoclast histomorphometry with TRAP stained sections demonstrated a significant increase in relative osteoclast number. In conclusion, in adult murine bone the role of BChE is limited to bone specific changes in microarchitecture and to an increase in relative number of bone resorbing osteoclasts whereas the main collagen resorbing enzyme Cathepsin-K (CtsK) was stably expressed. Besides, AChE might be able to compensate the lack of BChE. Thus, further analyses using bone tissue specific AChE BChE cre-lox double knockout mice would be helpful. PMID:26138460

  20. In Utero exposure to genistein enhanced intranasal house dust mite allergen-induced respiratory sensitization in young adult B6C3F1 mice.

    Science.gov (United States)

    Guo, Tai L; Meng, Andrew H

    2016-06-24

    Despite many hypothesized benefits of dietary isoflavone genistein (GEN) deriving from soy-based products, questions surrounding GEN's developmental immunotoxic effects are increasing. To understand how in utero GEN exposure may modulate postnatal respiratory sensitization, we conducted a time course study using a common household allergen (house dust mites: HDM; 10μg/mouse) following intranasal instillation, a physiological route of allergen exposure. GEN was administered to dams by gavage from gestational day 14 to parturition at a physiologically relevant dose (20mg/kg bw). Female and male offspring were sensitized with HDM allergens beginning about one month prior to sacrifice followed by challenges with three weekly doses of HDM extracts, and they were euthanized at day 3 following the final HDM exposure at four different time points (postnatal day (PND) 80, 120, 160, and 200). In utero GEN combined with postnatal HDM exposures (GEN+HDM) increased total IgE production in both young female and male B6C3F1 offspring (e.g., PND 80 in females and PND 120 in males). Increased antigen-specific IgG1, IgG2a and IgG2b levels were also observed at various time points in both female and male offspring. In addition, increases in macrophage number in bronchoalveolar lavage fluid of both female and male GEN+HDM offspring at PND 80 and PND 120, respectively, were observed when compared to the vehicle group. For T cells, an increase over the vehicle in female GEN+HDM offspring was observed at PND 80. Due to similar patterns of increases, it seems likely that GEN+HDM-induced increases in total IgE and macrophages are related. Overall, in utero GEN plus later-life HDM exposures exert increases in total IgE and HDM-specific IgG production as well as macrophage recruitments to the lung in young adult mice. PMID:27113705

  1. Protein Restriction During the Last Third of Pregnancy Malprograms the Neuroendocrine Axes to Induce Metabolic Syndrome in Adult Male Rat Offspring.

    Science.gov (United States)

    de Oliveira, Júlio Cezar; Gomes, Rodrigo Mello; Miranda, Rosiane Aparecida; Barella, Luiz Felipe; Malta, Ananda; Martins, Isabela Peixoto; Franco, Claudinéia Conationi da Silva; Pavanello, Audrei; Torrezan, Rosana; Natali, Maria Raquel Marçal; Lisboa, Patrícia Cristina; Mathias, Paulo Cezar de Freitas; de Moura, Egberto Gaspar

    2016-05-01

    Metabolic malprogramming has been associated with low birth weight; however, the interplay between insulin secretion disruption and adrenal function upon lipid metabolism is unclear in adult offspring from protein-malnourished mothers during the last third of gestation. Thus, we aimed to study the effects of a maternal low-protein diet during the last third of pregnancy on adult offspring metabolism, including pancreatic islet function and morphophysiological aspects of the liver, adrenal gland, white adipose tissue, and pancreas. Virgin female Wistar rats (age 70 d) were mated and fed a protein-restricted diet (4%, intrauterine protein restricted [IUPR]) from day 14 of pregnancy until delivery, whereas control dams were fed a 20.5% protein diet. At age 91 d, their body composition, glucose-insulin homeostasis, ACTH, corticosterone, leptin, adiponectin, lipid profile, pancreatic islet function and liver, adrenal gland, and pancreas morphology were assessed. The birth weights of the IUPR rats were 20% lower than the control rats (P rats were heavier, hyperphagic, hyperglycemic, hyperinsulinemic, hyperleptinemic, and hypercorticosteronemic (P rats (P < .05). Maternal undernutrition during the last third of gestation disrupts the pancreatic islet insulinotropic response and induces obesity-associated complications. Such alterations lead to a high risk of metabolic syndrome, characterized by insulin resistance, visceral obesity, and lower high-density lipoprotein cholesterol. PMID:27007071

  2. 妊娠期和哺乳期双酚A暴露对幼年子代小鼠焦虑和抑郁行为的影响%Gestational and Lactational Exposure to Bisphenol A Affects Anxiety- and Depression-Behaviors in Young Offspring Mice

    Institute of Scientific and Technical Information of China (English)

    杨宇杰; 徐晓虹; 洪星; 谢灵丹; 余奇静; 田栋

    2012-01-01

    Bisphenol A (BPA) is an environmental estrogenic disrupter widely used in the production of plastics, and ubiquitous human exposure to this chemical has been proposed to be a potential risk to public health. There has been a growing concern about the effect of early-life exposure to low doses of BPA. This study was to investigate the behavior difference of mice which exposed to BPA in gestation period or lactation period separately. After acclimatization for one week, adult female ICR mice were placed with males (two females : one male) and vaginal smears were examined daily. A sperm-positive smear determined gestational day (GD) 1. Pregnant mice were divided into 2 groups randomly. One group was orally exposed to BPA dissolved in peanut oil (0.4 or 4 mg/kg ·d) or only peanut oil as vehicle control from GD8 until offspring mice born. The other group was exposed to BPA with the same method from offspring mice born to postnatal day (PND) 14. At PND21 of age, open field, dark/light transition, mirror chamber, elevated plus-maze, forced swim and step-down were respectively used to test spontaneous activity, exploratory behavior, anxiety, depression, and passive avoidance memory in offspring mice. The results showed that gestational or lactational exposure to BPA differently affects behaviors in offspring mice. Gestational exposure to BPA weakened anxiety and increased spontaneous activity of young offspring, as well as enhanced exploratory behavior of male offspring and passive avoidance memory of female offspring. Lactational exposure to BPA decreased the spontaneous activity of young offspring, but no significant effect on anxiety was found in offspring mice. Both gestational and lactational exposure to BPA strengthened depression in male and female offspring mice. These results suggested that non-reproductive behaviors in offspring mice, such as anxiety, depression, passive avoidance memory, were affected by both gestational and lactational exposure to BPA, while

  3. Pulmonary exposure to carbon black by inhalation or instillation in pregnant mice: Effects on liver DNA strand breaks in dams and offspring

    DEFF Research Database (Denmark)

    Jackson, Petra; Hougaard, Karin Sørig; Boisen, Anne Mette Zenner;

    2011-01-01

    cells and liver, and in offspring liver. Persistent lung inflammation was observed in exposed mothers. Inhalation exposure induced more DNA strand breaks in the liver of mothers and their offspring, whereas intratracheal instillation did not. Neither inhalation nor instillation affected gestation and...... lactation. Maternal inhalation exposure to Printex 90-induced liver DNA damage in the mothers and the in utero exposed offspring....

  4. Delayed expulsion of adult Trichinella spiralis by mast cell-deficient W/Wv mice.

    OpenAIRE

    Ha, T. Y.; Reed, N D; Crowle, P K

    1983-01-01

    Mast cell-deficient W/Wv mice and their mast cell-sufficient littermates were given infections of Trichinella spiralis. W/Wv mice were slower than their littermates to expel adult T. spiralis. Repair of the mast cell deficiency of W/Wv mice by bone marrow grafting was accompanied by accelerated expulsion of T. spiralis.

  5. Neurotoxicity of perfluorooctane sulfonate to hippocampal cells in adult mice.

    Directory of Open Access Journals (Sweden)

    Yan Long

    Full Text Available Perfluorooctane sulfonate (PFOS is a ubiquitous pollutant and found in the environment and in biota. The neurotoxicity of PFOS has received much concern among its various toxic effects when given during developing period of brain. However, little is known about the neurotoxic effects and potential mechanisms of PFOS in the mature brain. Our study demonstrated the neurotoxicity and the potential mechanisms of PFOS in the hippocampus of adult mice for the first time. The impairments of spatial learning and memory were observed by water maze studies after exposure to PFOS for three months. Significant apoptosis was found in hippocampal cells after PFOS exposure, accompanied with a increase of glutamate in the hippocampus and decreases of dopamine (DA and 3,4-dihydrophenylacetic acid (DOPAC in Caudate Putamen in the 10.75 mg/kg PFOS group. By two-dimensional fluorescence difference in gel electrophoresis (2D-DIGE analysis, seven related proteins in the hippocampus that responded to PFOS exposure were identified, among which, Mib1 protein (an E3 ubiquitin-protein ligase, Herc5 (hect domain and RLD 5 isoform 2 and Tyro3 (TYRO3 protein tyrosine kinase 3 were found down-regulated, while Sdha (Succinate dehydrogenase flavoprotein subunit, Gzma (Isoform HF1 of Granzyme A precursor, Plau (Urokinase-type plasminogen activator precursor and Lig4 (DNA ligase 4 were found up-regulated in the 10.75 mg/kg PFOS-treated group compare with control group. Furthermore, we also found that (i increased expression of caspase-3 protein and decreased expression of Bcl-2, Bcl-XL and survivin proteins, (ii the increased glutamate release in the hippocampus. All these might contribute to the dysfunction of hippocampus which finally account for the impairments of spatial learning and memory in adult mice.

  6. Spatial Cognition in Adult and Aged Mice Exposed to High-Fat Diet.

    Science.gov (United States)

    Kesby, James P; Kim, Jane J; Scadeng, Miriam; Woods, Gina; Kado, Deborah M; Olefsky, Jerrold M; Jeste, Dilip V; Achim, Cristian L; Semenova, Svetlana

    2015-01-01

    Aging is associated with a decline in multiple aspects of cognitive function, with spatial cognition being particularly sensitive to age-related decline. Environmental stressors, such as high-fat diet (HFD) exposure, that produce a diabetic phenotype and metabolic dysfunction may indirectly lead to exacerbated brain aging and promote the development of cognitive deficits. The present work investigated whether exposure to HFD exacerbates age-related cognitive deficits in adult versus aged mice. Adult (5 months old) and aged (15 months old) mice were exposed to control diet or HFD for three months prior to, and throughout, behavioral testing. Anxiety-like behavior in the light-dark box test, discrimination learning and memory in the novel object/place recognition tests, and spatial learning and memory in the Barnes maze test were assessed. HFD resulted in significant gains in body weight and fat mass content with adult mice gaining significantly more weight and adipose tissue due to HFD than aged mice. Weight gain was attributed to food calories sourced from fat, but not total calorie intake. HFD increased fasting insulin levels in all mice, but adult mice showed a greater increase relative to aged mice. Behaviorally, HFD increased anxiety-like behavior in adult but not aged mice without significantly affecting spatial cognition. In contrast, aged mice fed either control or HFD diet displayed deficits in novel place discrimination and spatial learning. Our results suggest that adult mice are more susceptible to the physiological and anxiety-like effects of HFD consumption than aged mice, while aged mice displayed deficits in spatial cognition regardless of dietary influence. We conclude that although HFD induces systemic metabolic dysfunction in both adult and aged mice, overall cognitive function was not adversely affected under the current experimental conditions. PMID:26448649

  7. Spatial Cognition in Adult and Aged Mice Exposed to High-Fat Diet.

    Directory of Open Access Journals (Sweden)

    James P Kesby

    Full Text Available Aging is associated with a decline in multiple aspects of cognitive function, with spatial cognition being particularly sensitive to age-related decline. Environmental stressors, such as high-fat diet (HFD exposure, that produce a diabetic phenotype and metabolic dysfunction may indirectly lead to exacerbated brain aging and promote the development of cognitive deficits. The present work investigated whether exposure to HFD exacerbates age-related cognitive deficits in adult versus aged mice. Adult (5 months old and aged (15 months old mice were exposed to control diet or HFD for three months prior to, and throughout, behavioral testing. Anxiety-like behavior in the light-dark box test, discrimination learning and memory in the novel object/place recognition tests, and spatial learning and memory in the Barnes maze test were assessed. HFD resulted in significant gains in body weight and fat mass content with adult mice gaining significantly more weight and adipose tissue due to HFD than aged mice. Weight gain was attributed to food calories sourced from fat, but not total calorie intake. HFD increased fasting insulin levels in all mice, but adult mice showed a greater increase relative to aged mice. Behaviorally, HFD increased anxiety-like behavior in adult but not aged mice without significantly affecting spatial cognition. In contrast, aged mice fed either control or HFD diet displayed deficits in novel place discrimination and spatial learning. Our results suggest that adult mice are more susceptible to the physiological and anxiety-like effects of HFD consumption than aged mice, while aged mice displayed deficits in spatial cognition regardless of dietary influence. We conclude that although HFD induces systemic metabolic dysfunction in both adult and aged mice, overall cognitive function was not adversely affected under the current experimental conditions.

  8. Both food restriction and high-fat diet during gestation induce low birth weight and altered physical activity in adult rat offspring: the "Similarities in the Inequalities" model.

    Directory of Open Access Journals (Sweden)

    Fábio da Silva Cunha

    Full Text Available We have previously described a theoretical model in humans, called "Similarities in the Inequalities", in which extremely unequal social backgrounds coexist in a complex scenario promoting similar health outcomes in adulthood. Based on the potential applicability of and to further explore the "similarities in the inequalities" phenomenon, this study used a rat model to investigate the effect of different nutritional backgrounds during gestation on the willingness of offspring to engage in physical activity in adulthood. Sprague-Dawley rats were time mated and randomly allocated to one of three dietary groups: Control (Adlib, receiving standard laboratory chow ad libitum; 50% food restricted (FR, receiving 50% of the ad libitum-fed dam's habitual intake; or high-fat diet (HF, receiving a diet containing 23% fat. The diets were provided from day 10 of pregnancy until weaning. Within 24 hours of birth, pups were cross-fostered to other dams, forming the following groups: Adlib_Adlib, FR_Adlib, and HF_Adlib. Maternal chow consumption and weight gain, and offspring birth weight, growth, physical activity (one week of free exercise in running wheels, abdominal adiposity and biochemical data were evaluated. Western blot was performed to assess D2 receptors in the dorsal striatum. The "similarities in the inequalities" effect was observed on birth weight (both FR and HF groups were smaller than the Adlib group at birth and physical activity (both FR_Adlib and HF_Adlib groups were different from the Adlib_Adlib group, with less active males and more active females. Our findings contribute to the view that health inequalities in fetal life may program the health outcomes manifested in offspring adult life (such as altered physical activity and metabolic parameters, probably through different biological mechanisms.

  9. Young offspring at genetic risk of adult psychoses: the form of the trajectory of IQ or memory may orient to the right dysfunction at the right time.

    Directory of Open Access Journals (Sweden)

    Michel Maziade

    Full Text Available OBJECTIVE: Neurocognitive dysfunctions analogous to those of adult patients have been detected in children at risk of schizophrenia and bipolar disorder. This led to the following developmental question: Do IQ and memory impairments exhibit different developmental courses from childhood to young adulthood in terms of stability or fluctuations? METHODS: In a high risk sample, we used a step by step sampling approach to narrow-down the early disease mechanisms. Upstream, we started with a 20-year follow-up of 48 densely affected multigenerational kindreds, including 1500 clinically characterized adult members. We then identified 400 adult members affected by a DSM-IV schizophrenia or bipolar disorder. Downstream, we finally focused on 65 offspring (of an affected parent aged 7 to 22, who were administered a neuropsychological battery. We then constructed cross-sectional trajectories that were compared to those of controls. RESULTS: The childhood IQ deficit displayed a stability until young adulthood. The delay in visual memory exhibited a non-linear two-stage trajectory: a lagging period during childhood followed by a recuperation period from adolescence until adulthood, as supported by a significant Group x Age Periods interaction. No data suggested deterioration between 7 and 22. CONCLUSION: In these offspring at genetic risk, the developmental trajectory of global IQ impairment may not apply to specific domains of cognition such as episodic memory. Different cognitive dysfunctions would mark different developmental courses. The shape of the trajectories might itself have a meaning and provide empirical leads for targeting the right dysfunction at the right time in future prevention research.

  10. Incorporation and metabolism of tritium in pregnant mice and their offspring after feeding organically labelled tritiated milk powder during pregnancy

    International Nuclear Information System (INIS)

    Food mixed from equal amounts of organically labelled tritiated milk powder and normal food pellets was given to mice during pregnancy and lactation. At birth, some new-born were swapped with those from non-exposed mothers to compare separately accumulation and metabolism during pregnancy and lactation. Young mice were sacrificed at different time after birth, and tritium activity in different organs was determined. Tritium activity was also determined in maternal organs at various times during and after the 42 days feeding period. The activity per g in some tissues of the young, particularly in fat, exceeded that of the food given, probably as a result of the high activity and low metabolic dilution of the fats in the food. Young mice contaminated during lactation and pregnancy contained still detectible activity at an age of 2 months. Activity was nearly the same in mice receiving tritium only during lactation as in those receiving it also during pregnancy. Dilution was more marked due to rapid growth when tritium application was discontinued at birth. Tritium water was replaced most rapidly, organic tritium in brain turned over most slowly with and additional metabolic component of a half life in the order of 1 month. Organic tritium in liver displayed an intermediate half life. (author)

  11. Transplacental Arsenic Carcinogenesis in Mice

    OpenAIRE

    Waalkes, Michael P.; Liu, Jie; Diwan, Bhalchandra A.

    2007-01-01

    Our work has focused on the carcinogenic effects of in utero arsenic exposure in mice. Our data show a short period of maternal exposure to inorganic arsenic in the drinking water is an effective, multi-tissue carcinogen in the adult offspring. These studies have been reproduced in three temporally separate studies using two different mouse strains. In these studies pregnant mice were treated with drinking water containing sodium arsenite at up to 85 ppm arsenic from day 8 to 18 of gestation,...

  12. Myogenin regulates exercise capacity but is dispensable for skeletal muscle regeneration in adult mdx mice.

    Directory of Open Access Journals (Sweden)

    Eric Meadows

    Full Text Available Duchenne muscular dystrophy (DMD is the most prevalent inherited childhood muscle disorder in humans. mdx mice exhibit a similar pathophysiology to the human disorder allowing for an in-depth investigation of DMD. Myogenin, a myogenic regulatory factor, is best known for its role in embryonic myogenesis, but its role in adult muscle maintenance and regeneration is still poorly understood. Here, we generated an mdx:Myog(flox/flox mouse harboring a tamoxifen-inducible Cre recombinase transgene, which was used to conditionally delete Myog during adult life. After tamoxifen treatment, three groups of mice were created to study the effects of Myog deletion: mdx:Myog(flox/flox mice (mdx, Myog(flox/flox mice (wild-type, and mdx:Myog(floxΔ/floxΔ:Cre-ER mice (mdx:Myog-deleted. mdx:Myog-deleted mice exhibited no adverse phenotype and behaved normally. When run to exhaustion, mdx:Myog-deleted mice demonstrated an enhanced capacity for exercise compared to mdx mice, running nearly as far as wild-type mice. Moreover, these mice showed the same signature characteristics of muscle regeneration as mdx mice. Unexpectedly, we found that myogenin was dispensable for muscle regeneration. Factors associated with muscle fatigue, metabolism, and proteolysis were significantly altered in mdx:Myog-deleted mice, and this might contribute to their increased exercise capacity. Our results reveal novel functions for myogenin in adult muscle and suggest that reducing Myog expression in other muscle disease models may partially restore muscle function.

  13. Gene expression and DNA methylation of PPARGC1A in Muscle and Adipose Tissue from Adult Offspring of Women with Diabetes in Pregnancy

    DEFF Research Database (Denmark)

    Kelstrup, Louise; Hjort, Line; Houshmand-Oeregaard, Azadeh;

    2016-01-01

    clinical examination, oral glucose tolerance test, gene expression and DNA methylation of PPARGC1A in skeletal muscle and SAT.Plasma glucose was significantly higher for both O-GDM and O-T1DM compared to O-BP (p...Prenatal exposure to maternal hyperglycemia is associated with increased risk of later adverse metabolic health. Changes in regulation of peroxisome proliferator-activated receptor-γ coactivator-1α (PPARGC1A) in skeletal muscle and subcutaneous adipose tissue (SAT) is suggested to play a role...... in developmental programming of dysmetabolism based on studies in human subjects exposed to abnormal intrauterine environment e.g. low birth weight individuals.We studied 206 adult offspring of women with gestational diabetes (O-GDM), type 1 diabetes (O-T1DM) and from the background population (O-BP) including...

  14. Lipopolysaccharide exposure during late embryogenesis results in diminished locomotor activity and amphetamine response in females and spatial cognition impairment in males in adult, but not adolescent rat offspring.

    Science.gov (United States)

    Batinić, Bojan; Santrač, Anja; Divović, Branka; Timić, Tamara; Stanković, Tamara; Obradović, Aleksandar Lj; Joksimović, Srđan; Savić, Miroslav M

    2016-02-15

    Numerous basic and epidemiological studies have connected prenatal maternal immune activation with the occurrence of schizophrenia and/or autism. Depending on subtle differences in protocols of the used animal model, a variety of behavioral abnormalities has been reported. This study investigated behavioral differences in Wistar rat offspring of both genders, exposed to the 100 μg/kg per day dose of lipopolysaccharide (LPS) in late embryogenesis (embryonic days 15 and 16), while tested at their adolescent and young adult age (postnatal days 40 and 60, respectively). Immune activation was confirmed by detecting high levels of TNF-α and IL-6 in dam blood withdrawn 2h after the first dose of LPS. The animals were assessed in three consecutive trials of locomotor activity (novelty exploration, response to i.p. saline injection and challenge with 0.5mg/kg amphetamine), Morris water maze and social interaction tests. Overt behavioral dysfunction was perceived in adult rats only, and these changes were gender-distinctive. When compared with control rats, LPS females displayed baseline hypolocomotion and a decreased reactivity to amphetamine, while LPS males exhibited spatial learning (acquisition trials) and memory (probe trial) impairments. Prenatal treatment did not affect the time spent in social interaction. As maternal exposure to LPS in late gestation resulted in behavioral changes in offspring in early adulthood, it may model schizophrenia-like, but not autism-like endophenotypes. However, lack of a potentiated response to amphetamine testified that this model could not mimic positive symptoms, but rather certain traits of cognitive dysfunction and deficit symptoms, in males and females, respectively. PMID:26620494

  15. Hemopoietic precursor-cells in radiation chimeras restored by bone marrow of adult thymectomized mice

    International Nuclear Information System (INIS)

    Radioprotective capacity of bone marrow CFUs of adult thymectomized mice was studied. Lethaly irradiated mice were inoculated with bone marrow of mice thymectomized 8-11 months before. The colony forming capacity and proliferative rate of CFUs were studied 1-7.5 months after obtaining the radiation chimeras. It has been shown that proliferative capacity of bone marrow of adult thymectomized mice was reduced in comparison with that of normal animals. We also found that the content of CFUs in bone of those chimeras was reduced later - after 7.5 months. In this period (1-7.5 months) the cellularity of bone marrow did not change

  16. A new and fast technique to generate offspring after germ cells transplantation in adult fish: the Nile tilapia (Oreochromis niloticus model.

    Directory of Open Access Journals (Sweden)

    Samyra M S N Lacerda

    Full Text Available BACKGROUND: Germ cell transplantation results in fertile recipients and is the only available approach to functionally investigate the spermatogonial stem cell biology in mammals and probably in other vertebrates. In the current study, we describe a novel non-surgical methodology for efficient spermatogonial transplantation into the testes of adult tilapia (O. niloticus, in which endogenous spermatogenesis had been depleted with the cytostatic drug busulfan. METHODOLOGY/PRINCIPAL FINDINGS: Using two different tilapia strains, the production of fertile spermatozoa with donor characteristics was demonstrated in adult recipient, which also sired progeny with the donor genotype. Also, after cryopreservation tilapia spermatogonial cells were able to differentiate to spermatozoa in the testes of recipient fishes. These findings indicate that injecting germ cells directly into adult testis facilitates and enable fast generation of donor spermatogenesis and offspring compared to previously described methods. CONCLUSION: Therefore, a new suitable methodology for biotechnological investigations in aquaculture was established, with a high potential to improve the production of commercially valuable fish, generate transgenic animals and preserve endangered fish species.

  17. A maternal high fat diet programmes endothelial function and cardiovascular status in adult male offspring independent of body weight, which is reversed by maternal conjugated linoleic acid (CLA supplementation.

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    Clint Gray

    Full Text Available Maternal high fat intake during pregnancy and lactation can result in obesity and adverse cardio-metabolic status in offspring independent of postnatal diet. While it is clear that maternal high fat intake can cause hypertension in adult offspring, there is little evidence regarding the role of dietary interventions in terms of reversing these adverse effects. Conjugated linoleic acid (CLA is an omega 6 fatty acid with beneficial effects in obesity and metabolic status. However, the impact of CLA supplementation in the context of pregnancy disorders and high fat diet-induced developmental programming of offspring cardio-metabolic dysfunction has not been investigated. We have utilised a model of maternal overnutrition to examine the effects of CLA supplementation on programmed endothelial dysfunction during adulthood. Female Sprague-Dawley rats were fed either a purified control diet (CON or purified control diet supplemented with 1% CLA (of total fat, a purified high fat (HF diet (45%kcal from fat and a purified HF diet supplemented with 1% CLA (of total fat (HFCLA. All dams were fed ad libitum throughout pregnancy and lactation. Offspring were fed a standard chow diet from weaning (day 21 until the end of the study (day 150. Systolic blood pressure (SBP was measured at day 85 and 130 by tail cuff plethysmography. At day 150, offspring mesenteric vessels were mounted on a pressure myograph and vascular responses to agonist-induced constriction and endothelium-dependent vasodilators were investigated. SBP was increased at day 85 and 130 in HF and HFCLA adult male offspring compared to CON and CLA groups with no effect of CLA supplementation. An overall effect of a maternal HF diet was observed in adult male vessels with a reduced vasoconstrictor response to phenylephrine and blunted vasodilatory response to acetylcholine (ACh. Furthermore, HF and HFCLA offspring displayed a reduction in nitric oxide pathway function and an increased compensatory

  18. Synergistic induction of tumors in NMRI mice by combined fetal X-irradiation with low doses and ethylnitrosourea administered to juvenile offspring

    Energy Technology Data Exchange (ETDEWEB)

    Schmahl, W.

    1988-08-01

    Mice were X-irradiated on day 15 of gestation with 0.2, 0.4, 0.8 or 1.6 Gy. Offspring were reared by their mothers and divided into two subgroups at an age of 21 days, one subgroup receiving a single dose (45 mg/kg) of ethylnitrosourea (ENU). All animals were kept ultimately until 22 months to register the long-term tumor pattern. The carcinogenic effects of ENU alone were also studied in two separate experiments. Prenatal X-irradiation with 1.6 Gy mostly abolished the carcinogenic late effects of ENU, with the exception of an almost constant leucosis incidence and an unchanged lung tumor frequency. Lowering the prenatal X-ray dose to 0.8 Gy resulted in a significantly increased rate of liver tumors and ovary tumors. Synergistic effects on various tissues were observed after both 0.4- and 0.2-Gy fetal X-irradiation treatment in combination with postnatal application of ENU. These effects mainly involved a significant increase in the frequency of leucosis and of tumors of the liver, intestine, uterus and ovaries. The greater-than-additive effect in the case of these tumors suggests that low-level prenatal X-irradiation leads to a lasting sensitivity of some tissues towards a subsequent carcinogenic stimulus.

  19. Synergistic induction of tumours in NMRI mice by combined foetal X-irradiation with low doses and ethylnitrosourea administered to juvenile offspring

    International Nuclear Information System (INIS)

    Mice were X-irradiated on day 15 of gestation with 0.2, 0.4, 0.8 or 1.6 Gy. Offspring were reared by their mothers and divided into two subgroups at an age of 21 days, one subgroup receiving a single dose (45 mg/kg) of ethylnitrosourea (ENU). All animals were kept ultimately until 22 months to register the long-term tumour pattern. The carcinogenic effects of ENU alone were also studied in two separate experiments. Prenatal X-irradiation with 1.6 Gy mostly abolished the carcinogenic late effects of ENU, with the exception of an almost constant leucosis incidence and an unchanged lung tumour frequency. Lowering the prenatal X-ray dose to 0.8 Gy resulted in a significantly increased rate of liver tumours and ovary tumours. Synergistic effects on various tissues were observed after both 0.4- and 0.2-Gy foetal X-irradiation treatment in combination with postnatal application of ENU. These effects mainly involved a significant increase in the frequency of leucosis and of tumours of the liver, intestine, uterus and ovaries. The greater-than-additive effect in the case of these tumours suggests that low-level prenatal X-irradiation leads to a lasting sensitivity of some tissues towards a subsequent carcinogenic stimulus. (author)

  20. Toxicity of benzyl alcohol in adult and neonatal mice

    International Nuclear Information System (INIS)

    Benzyl alcohol (BA) is an aromatic alcohol, which is used as a bacteriostat in a variety of parenteral preparations. In 1982, it was implicated as the agent responsible for precipitating The Gasping Syndrome in premature neonates. The investigate further this toxicity, BA was administered, intraperiotoneally, to adult and neonatal CD-1 male mice. Gross behavioral changes were monitored. Low doses produced minimal toxic effects within an initial 4 hour observation period. At the end of this time, the LD50 was determined to be 1000 mg/kg for both age groups. Death was due to respiratory arrest in all cases. Rapid absorption and conversion of BA to its primary metabolite, benzaldehyde, was demonstrated by gas chromatographic analysis of plasma from both experimental groups. The conversion of BA to benzaldehyde was confirmed in in vitro by using both horse-liver and mouse liver ADH. The inhibition of alcohol dehydrogenase (ADH) by pyrazole was similarly demonstrated in both enzyme systems. 14C-labelled BA was utilized to determine the distribution of BA and its metabolites in the body, and to possibly pinpoint a target organ of toxicity

  1. Hemopoietic support capacity of adult mouse liver. Studies in 89Sr marrow-ablated mice

    International Nuclear Information System (INIS)

    The capacity of normal livers in adult mice to support proliferation of pluripotent hemopoietic stem cells (CFU-S) was studied. We assayed CFU-S of the blood and livers of mice with intact marrows and of mice whose marrows had been ablated with 89Sr (4 μCi/g) either before or after removal of their spleens, the major hemopoietic organ in marrow-ablated mice. Splenectomy alone resulted in an increase in the numbers of blood and hepatic CFU-S; since the spleen is an efficient trapper of CFU-S released from the marrow, in the splenectomized mice more CFU-S were available for trapping by the liver. Mice splenectomized 3 days prior to 89Sr injection had virtually no blood or liver CFU-S by the tenth day after 89Sr injection. Fourteen days after injection of 89Sr there were supranormal numbers of CFU-S in both blood and liver of intact mice. One week after such mice were splenectomized, however, CFU-S were virtually absent from both blood and liver. This study suggests that normal livers in adult mice cannot support detectable proliferation of normal CFU-S even if the animal is subjected to severe and relatively prolonged hemopoietic stress. In addition, the results of our studies demonstrate that normal livers of adult mice have the capacity to trap large numbers of CFU-S

  2. Zika Kills Vital Nervous System Cells in Adult Mice, Study Finds

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_160505.html Zika Kills Vital Nervous System Cells in Adult Mice, ... 2016 THURSDAY, Aug. 18, 2016 (HealthDay News) -- The Zika virus kills neural stem cells in the brains ...

  3. Endogenous CNTF mediates stroke-induced adult CNS neurogenesis in mice

    OpenAIRE

    Kang, Seong Su; Keasey, Matthew P.; Arnold, Sheila A.; Reid, Rollie; Geralds, Justin; Hagg, Theo

    2012-01-01

    Focal brain ischemia in adult rats rapidly and robustly induces neurogenesis in the subventricular zone (SVZ) but there are few and inconsistent reports in mice, presenting a hurdle to genetically investigate the endogenous neurogenic regulators such as ciliary neurotrophic factor (CNTF). Here, we first provide a platform for further studies by showing that middle cerebral artery occlusion in adult male C57BL/6 mice robustly enhances neurogenesis in the SVZ only under very specific conditions...

  4. Interaction of recalled parental ADHD symptoms and rearing behavior with current attachment and emotional dysfunction in adult offspring with ADHD.

    Science.gov (United States)

    Edel, Marc-Andreas; Juckel, Georg; Brüne, Martin

    2010-06-30

    Research into attachment and emotion regulation has shown that children with ADHD are at risk of developing attachment disorders and emotion regulation disturbances, which in part may be due to the rearing style of their parents. No such data exists for adults with persistent ADHD. We hypothesized that current attachment style and emotion processing of adult patients with ADHD may be influenced by the presence of parental ADHD symptoms when the now adult patients were children, assuming that ADHD symptoms of parents have an impact on their parenting style. We examined recalled parental ADHD symptoms and rearing style as well as current attachment and emotion regulation abilities in a sample of 73 adults with ADHD using several self-rating instruments. Recalled prevalence of ADHD symptoms in the mother, and less so in the father, of adult patients with ADHD was significantly associated with partly adverse parental rearing styles, current attachment problems in romantic partnerships and emotion regulation disturbances compared with adult ADHD patients without possibly affected parent. ADHD symptoms in parents of children with ADHD may present a risk factor for attachment problems and poor emotion regulation when ADHD children are grown. PMID:20452044

  5. Effect of Benzene on Proliferation and Apoptosis of Splenic Lymphocytes in Mother Generation and Offspring Mice%苯对母鼠和子鼠脾淋巴细胞的增殖与凋亡影响

    Institute of Scientific and Technical Information of China (English)

    旷亦乐; 李纯颖; 杨双波; 李紫; 吴成秋

    2011-01-01

    Objective To explore the effect of benzene on proliferation and apoptceis of splenic lymphocytes in mother generation and offspring mice. Methods Forty pregnant mice were divided averagely into 4 groups at random. From the 7th day after pregnancy, each of group was exposed to benzene vapour until to parturition (0.0, 5.0, 10.0 and 15.0 mg/m3,respectively), 2 hours par day. At the 1st and 7th days after parturition, 5 mother generation mice end 5 offspring mice of each group were killed to detect the proliferation, cell cycle and apoptosis of splenic lymphocytes in mother generation and offspring mice by MTT assay and flow cytometric analysis. Results During the 1st day and 7th day after parturition, the proliferation of splenic lymphocytes of mother generation and offspring mice in the middle - and high - concentration of benzene groups was inhibited significantly in a concentration-dependent manner (P<O. 05). The cell cycle of splenic lymphocytes of mother generation and offspring mice was blocked in G0/G1 phase in the middle - and high - concentration of benzene groups. The quantity of splenic lymphocytes apoptosis was increased significantly in a concentration- dependent manner in each benzene group (P < 0.05). Conclusion Benzene exposure during pregnancy can damage the immunological function of mother generation mice and offspring mice.%目的 探讨妊娠期接触苯对母鼠及其子鼠免疫功能的影响.方法 40只孕鼠被随机等分为空气对照组和5.0、10.0、15.0 mg/m3三个不同浓度的苯染毒组,各组从孕7 d开始,连续染毒至分娩,每天染毒2 h.分别在分娩后的1 d及7 d,每组取5只母鼠和5只子鼠处死,取脾制备脾淋巴细胞;检测母鼠和子鼠脾淋巴细胞增殖力、细胞周期及细胞凋亡.结果 在分娩后1 d及7 d,中、高浓度苯染毒组母鼠及子鼠的脾淋巴细胞增殖力均低于对照组(P<0.05),并有明显的剂量-效应关系(P<0.05);子鼠与母鼠的淋巴细胞增殖抑制

  6. Impact of Diet Composition in Adult Offspring is Dependent on Maternal Diet during Pregnancy and Lactation in Rats

    Directory of Open Access Journals (Sweden)

    Megan C. Hallam

    2016-01-01

    Full Text Available The Thrifty Phenotype Hypothesis proposes that the fetus takes cues from the maternal environment to predict its postnatal environment. A mismatch between the predicted and actual environments precipitates an increased risk of chronic disease. Our objective was to determine if, following a high fat, high sucrose (HFS diet challenge in adulthood, re-matching offspring to their maternal gestational diet would improve metabolic health more so than if there was no previous exposure to that diet. Animals re-matched to a high prebiotic fiber diet (HF had lower body weight and adiposity than animals re-matched to a high protein (HP or control (C diet and also had increased levels of the satiety hormones GLP-1 and PYY (p < 0.05. Control animals, whether maintained throughout the study on AIN-93M, or continued on HFS rather than reverting back to AIN-93M, did not differ from each other in body weight or adiposity. Overall, the HF diet was associated with the most beneficial metabolic phenotype (body fat, glucose control, satiety hormones. The HP diet, as per our previous work, had detrimental effects on body weight and adiposity. Findings in control rats suggest that the obesogenic potential of the powdered AIN-93 diet warrants investigation.

  7. Simvastatin and artesunate impact the structural organization of adult Schistosoma mansoni in hypercholesterolemic mice.

    Science.gov (United States)

    Alencar, Alba Cristina Miranda de Barros; Santos, Thais da Silva; Neves, Renata Heisler; Lopes Torres, Eduardo José; Nogueira-Neto, José Firmino; Machado-Silva, José Roberto

    2016-08-01

    Experimental data have shown that simvastatin and artesunate possess activity against Schistosoma mansoni worms in mice fed standard chow. However, little is known regarding the roles of these drugs in mice fed high-fat chow. We have extended past studies by measuring the effects of these drugs on the structural organization of adult schistosomes in hypercholesterolemic mice. For this purpose, mice were gavaged with either simvastatin or artesunate at nine weeks post-infection and were euthanized by cervical dislocation at two weeks post-treatment. Adult worms were then collected and examined by conventional light microscopy, morphometry and confocal laser scanning microscopy. Plasma total cholesterol and worm reduction rates were significantly increased in mice fed high-fat chow compared with their respective control groups. Simvastatin and artesunate caused changes in the tegument, tubercles, and reproductive system (testicular lobes, vitelline glands and ovarian cells), particularly when administered to mice fed high-fat chow. In particular, the tegument and tubercles were significantly thinner in artesunate-treated worms in mice fed high-fat chow compared with mice fed standard chow. This study thus demonstrated that simvastatin and artesunate have several novel effects on the structural organization of adult worms. Together, these results show, for the first time, that simvastatin and artesunate display antischistosomal activity in hypercholesterolemic mice. PMID:27228897

  8. Auto-mobilized adult hematopoietic stem cells advance neovasculature in diabetic retinopathy of mice

    Institute of Scientific and Technical Information of China (English)

    TIAN Bei; LI Xiao-xin; SHEN Li; ZHAO Min; YU Wen-zhen

    2010-01-01

    Background Hematopoietic stem cells (HSCs) can be used to deliver functionally active angiostatic molecules to the retinal vasculature by targeting active astrocytes and may be useful in targeting pre-angiogenic retinal lesions. We sought to determine whether HSC mobilization can ameliorate early diabetic retinopathy in mice.Methods Mice were devided into four groups: normal mice control group, normal mice HSC-mobilized group, diabetic mice control group and diabetic mice HSC mobilized group. Murine stem cell growth factor (murine SCF) and recombined human granulocyte colony stimulating factor (rhG-csf) were administered to the mice with diabetes and without diabetes for continuous 5 days to induce autologous HSCs mobilization, and subcutaneous injection of physiological saline was used as control. Immunohistochemical double staining was conducted with anti-mouse rat CD31 monoclonal antibody and anti-BrdU rat antibody.Results Marked HSCs clearly increased after SCF plus G-csf-mobilization. Non-mobilized diabetic mice showed more HSCs than normal mice (P=0.032), and peripheral blood significantly increased in both diabetic and normal mice (P=0.000).Diabetic mice showed more CD31 positive capillary vessels (P=0.000) and accelerated endothelial cell regeneration. Only diabetic HSC-mobilized mice expressed both BrdU and CD31 antigens in the endothelial cells of new capillaries.Conclusion Auto-mobilized adult hematopoietic stem cells advance neovasculature in diabetic retinopathy of mice.

  9. Gender-dependent effects of maternal immune activation on the behavior of mouse offspring.

    Directory of Open Access Journals (Sweden)

    Ingrid C Y Xuan

    Full Text Available Autism spectrum disorders are neurodevelopmental disorders characterized by two core symptoms; impaired social interactions and communication, and ritualistic or repetitive behaviors. Both epidemiological and biochemical evidence suggests that a subpopulation of autistics may be linked to immune perturbations that occurred during fetal development. These findings have given rise to an animal model, called the "maternal immune activation" model, whereby the offspring from female rodents who were subjected to an immune stimulus during early or mid-pregnancy are studied. Here, C57BL/6 mouse dams were treated mid-gestation with saline, lipopolysaccharide (LPS to mimic a bacterial infection, or polyinosinic:polycytidylic acid (Poly IC to mimic a viral infection. Autism-associated behaviors were examined in the adult offspring of the treated dams. Behavioral tests were conducted to assess motor activity, exploration in a novel environment, sociability, and repetitive behaviors, and data analyses were carried independently on male and female mice. We observed a main treatment effect whereby male offspring from Poly IC-treated dams showed reduced motor activity. In the marble burying test of repetitive behavior, male offspring but not female offspring from both LPS and Poly IC-treated mothers showed increased marble burying. Our findings indicate that offspring from mothers subjected to immune stimulation during gestation show a gender-specific increase in stereotyped repetitive behavior.

  10. Carbohydrate-related dietary factors and plasma adiponectin levels in healthy adults in the Framingham Offspring Cohort

    Science.gov (United States)

    Diet may influence circulating adiponectin levels by improving insulin sensitivity. We examined the associations between carbohydrate-related dietary factors and plasma adiponectin levels in healthy adults aged 26–81 y (n= 979 men and 1227 women). Dietary intakes were assessed using a FFQ. Fasting...

  11. Mice cloned from embryonic stem cells

    OpenAIRE

    Wakayama, Teruhiko; Rodriguez, Ivan; Perry, Anthony C F; Yanagimachi, Ryuzo; Mombaerts, Peter

    1999-01-01

    Cloning allows the asexual reproduction of selected individuals such that the offspring have an essentially identical nuclear genome. Cloning by nuclear transfer thus far has been reported only with freshly isolated cells and cells from primary cultures. We previously reported a method of cloning mice from adult somatic cells after nuclear transfer by microinjection. Here, we apply this method to clone mice from widely available, established embryonic stem (ES) cell ...

  12. Maternal High-Fat Diet Modulates Hepatic Glucose, Lipid Homeostasis and Gene Expression in the PPAR Pathway in the Early Life of Offspring

    Directory of Open Access Journals (Sweden)

    Jia Zheng

    2014-08-01

    Full Text Available Maternal dietary modifications determine the susceptibility to metabolic diseases in adult life. However, whether maternal high-fat feeding can modulate glucose and lipid metabolism in the early life of offspring is less understood. Furthermore, we explored the underlying mechanisms that influence the phenotype. Using C57BL/6J mice, we examined the effects on the offspring at weaning from dams fed with a high-fat diet or normal chow diet throughout pregnancy and lactation. Gene array experiments and quantitative real-time PCR were performed in the liver tissues of the offspring mice. The offspring of the dams fed the high-fat diet had a heavier body weight, impaired glucose tolerance, decreased insulin sensitivity, increased serum cholesterol and hepatic steatosis at weaning. Bioinformatic analyses indicated that all differentially expressed genes of the offspring between the two groups were mapped to nine pathways. Genes in the peroxisome proliferator-activated receptor (PPAR signaling pathway were verified by quantitative real-time PCR and these genes were significantly up-regulated in the high-fat diet offspring. A maternal high-fat diet during pregnancy and lactation can modulate hepatic glucose, lipid homeostasis, and gene expression in the PPAR signaling in the early life of offspring, and our results suggested that potential mechanisms that influences this phenotype may be related partially to up-regulate some gene expression in the PPAR signalling pathway.

  13. CpG Improves Influenza Vaccine Efficacy in Young Adult but Not Aged Mice.

    Science.gov (United States)

    Ramirez, Alejandro; Co, Mary; Mathew, Anuja

    2016-01-01

    Several studies have shown a reduced efficacy of influenza vaccines in the elderly compared to young adults. In this study, we evaluated the immunogenicity and protective efficacy of a commercially available inactivated influenza vaccine (Fluzone®) in young adult and aged mice. C57/BL6 mice were administered a single or double immunization of Fluzone® with or without CpG and challenged intranasally with H1N1 A/California/09 virus. A double immunization of Fluzone® adjuvanted with CpG elicited the highest level of protection in young adult mice which was associated with increases in influenza specific IgG, elevated HAI titres, reduced viral titres and lung inflammation. In contrast, the vaccine schedule which provided fully protective immunity in young adult mice conferred limited protection in aged mice. Antigen presenting cells from aged mice were found to be less responsive to in vitro stimulation by Fluzone and CpG which may partially explain this result. Our data are supportive of studies that have shown limited effectiveness of influenza vaccines in the elderly and provide important information relevant to the design of more immunogenic vaccines in this age group. PMID:26934728

  14. Adult hematopoietic progenitors are pluripotent in chimeric mice

    OpenAIRE

    Pessac, Bernard; K. Nimmagadda, Vamshi; Makar, Tapas; S. Fishman, Paul; T. Bever Jr., Christopher; Trisler, David

    2012-01-01

    18 pages, 7 figures. Embryonic stem cells (ESCs) and adult somatic cells, induced to pluripotency (iPSCs) by genetic manipulation, display high self-­‐renewal potential and the capacity to differentiate into multiple cell lineages. We asked whether there are in adult mammals natural stem cells that are pluripotent. We previously reported that normal adult mammalian bone marrow contains a sub-­‐population of CD34+ cells, that naturally expresses genes characteristic of ESCs and those requir...

  15. A Simplified Method for Three-Dimensional (3-D Ovarian Tissue Culture Yielding Oocytes Competent to Produce Full-Term Offspring in Mice.

    Directory of Open Access Journals (Sweden)

    Carolyn M Higuchi

    Full Text Available In vitro growth of follicles is a promising technology to generate large quantities of competent oocytes from immature follicles and could expand the potential of assisted reproductive technologies (ART. Isolated follicle culture is currently the primary method used to develop and mature follicles in vitro. However, this procedure typically requires complicated, time-consuming procedures, as well as destruction of the normal ovarian microenvironment. Here we describe a simplified 3-D ovarian culture system that can be used to mature multilayered secondary follicles into antral follicles, generating developmentally competent oocytes in vitro. Ovaries recovered from mice at 14 days of age were cut into 8 pieces and placed onto a thick Matrigel drop (3-D culture for 10 days of culture. As a control, ovarian pieces were cultured on a membrane filter without any Matrigel drop (Membrane culture. We also evaluated the effect of activin A treatment on follicle growth within the ovarian pieces with or without Matrigel support. Thus we tested four different culture conditions: C (Membrane/activin-, A (Membrane/activin+, M (Matrigel/activin-, and M+A (Matrigel/activin+. We found that the cultured follicles and oocytes steadily increased in size regardless of the culture condition used. However, antral cavity formation occurred only in the follicles grown in the 3-D culture system (M, M+A. Following ovarian tissue culture, full-grown GV oocytes were isolated from the larger follicles to evaluate their developmental competence by subjecting them to in vitro maturation (IVM and in vitro fertilization (IVF. Maturation and fertilization rates were higher using oocytes grown in 3-D culture (M, M+A than with those grown in membrane culture (C, A. In particular, activin A treatment further improved 3-D culture (M+A success. Following IVF, two-cell embryos were transferred to recipients to generate full-term offspring. In summary, this simple and easy 3-D ovarian

  16. The programming effects of nutrition-induced catch-up growth on gut microbiota and metabolic diseases in adult mice.

    Science.gov (United States)

    Zheng, Jia; Xiao, Xinhua; Zhang, Qian; Yu, Miao; Xu, Jianping; Qi, Cuijuan; Wang, Tong

    2016-04-01

    Substantial evidence indicated that catch-up growth could increase the susceptibility to obesity, insulin resistance, and type 2 diabetes mellitus in adulthood. However, investigations into the "programming" effects of catch-up growth on gut microbiota in the offspring are limited. C57/BL6 mice were fed on either low protein (LP) or normal chow (NC) diet throughout gestation and lactation. Then, the offspring were randomly weaned to either NC or high fat (HF) diet until 32 weeks of age, generating four experimental groups: NC-NC, NC-HF, LP-NC, and LP-HF. Metabolic parameters and gut microbiota were examined in the offspring. It showed that the NC-HF and LP-HF offspring displayed higher body weight (P percentage was negatively associated with blood glucose concentrations of intraperitoneal glucose tolerance test (r = -0.886, P = 0.019). In conclusion, catch-up growth predisposes the offspring to gut microbiota perturbation, obesity, impaired glucose tolerance, insulin resistance, and dyslipidemia. Our study is novel in showing the "programming" effects of nutrition-induced catch-up growth on gut microbiota and metabolic diseases in later life. PMID:26749443

  17. Mechanism of infectivity of a murine leukemia virus in adult mice

    International Nuclear Information System (INIS)

    Infection of adult BALB/c mice with murine leukemia virus (MuLV) induces typical thymic lymphomas. Expression of virus was measured by using a radioimmunoassay for murine P-30, a virion core protein. Nineteen days after injection of MuLV-S into adult mice, there were 0.3μg P-30/ml of serum. X-irradiation permitted the early expression of high levels of viremia, when given before or after MuLV-S administration, and it also hastened the development of lymphomas. Seventeen to 21 days after injection of MuLV-S into x-irradiated (600 rads) adult mice, there were 2.7 μg of P-30/ml of serum. The virus produced by infected adult mice was infectious and oncogenic when given to newborn mice. Several lines of evidence are presented that suggest the mechanism by which x-irradiation permits early expession of virion proteins and lymphomas is not immunosuppression

  18. Sex-specific attentional deficits in adult vitamin D deficient BALB/c mice.

    Science.gov (United States)

    Groves, Natalie J; Burne, Thomas H J

    2016-04-01

    Epidemiological studies have shown an association between vitamin D deficiency and cognitive impairment. However, there is a paucity of preclinical data showing that vitamin D deficiency is a causal factor for impaired cognitive processing. The aim of this study was to assess two cognitive tasks, the 5 choice-serial reaction task and the 5 choice-continuous performance task in adult vitamin D (AVD) deficient BALB/c mice. Ten-week old male and female BALB/c mice were fed a control or vitamin D deficient diet for 10 weeks prior to, and during behavioural testing. We found sex-dependent impairments in attentional processing and showed that male AVD-deficient mice were less accurate, took longer to respond when making a correct choice and were more likely to make an omission, without a change in the motivation to collect reward. By contrast, female AVD-deficient mice had a reduced latency to collect reward, but no changes on any other measures compared to controls. Therefore, we have shown that in otherwise healthy adult mice, vitamin D deficiency led to mild cognitive impairment in male but not female mice and therefore this model will be useful for future investigations into unravelling the mechanism by which vitamin D affects the adult brain and cognitive function. PMID:26836278

  19. The influence of parental history of diabetes and offspring birthweight on offspring glucose metabolism in adulthood

    DEFF Research Database (Denmark)

    Lauenborg, Jeannet; Jørgensen, Mie Kw; Damm, Peter;

    2011-01-01

    Background. Links are well established between both family history of diabetes and reduced birthweight and increased risk of diabetes in adulthood. Objectives. 1) To investigate the influence of parental history of type 2 diabetes (T2DM) on offspring birthweight and adult offspring glucose...... tolerance status in non-diabetic offspring of patients with T2DM and 2) to study the associations of birthweight with measures of pancreatic beta-cell function and insulin sensitivity. Design. Family cohort study. Population. Offspring of patients with verified T2DM diagnosed after age 40 years with a...... spouse without known diabetes. Methods. Oral glucose tolerance tests and frequently sampled intravenous glucose tolerance tests (FSIGT) in non-diabetic offspring. Birthweight and length obtained from birth records. Results. Among 122 offspring with maternal history of T2DM, 14.8% had diabetes compared to...

  20. Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer

    OpenAIRE

    Bernardes de Jesus, Bruno; Vera, Elsa; Schneeberger, Kerstin; Tejera, Agueda M.; Ayuso, Eduard; Bosch, Fatima; Blasco, Maria A.

    2012-01-01

    A major goal in aging research is to improve health during aging. In the case of mice, genetic manipulations that shorten or lengthen telomeres result, respectively, in decreased or increased longevity. Based on this, we have tested the effects of a telomerase gene therapy in adult (1 year of age) and old (2 years of age) mice. Treatment of 1- and 2-year old mice with an adeno associated virus (AAV) of wide tropism expressing mouse TERT had remarkable beneficial effects on health and fitness,...

  1. Imidacloprid-treated seed ingestion has lethal effect on adult partridges and reduces both breeding investment and offspring immunity.

    Science.gov (United States)

    Lopez-Antia, Ana; Ortiz-Santaliestra, Manuel E; Mougeot, François; Mateo, Rafael

    2015-01-01

    The ingestion of imidacloprid treated seeds by farmland birds may result in exposure to toxic amounts of this insecticide. Here we report on the effects that the exposure to the recommended application rate and to 20% of that rate may produce on birds feeding on treated seeds. Experimental exposure to imidacloprid treated seeds was performed on red-legged partridges (Alectoris rufa) (n=15 pairs per treatment group: control, 20% or 100% of the recommended application rate) during two periods that corresponded to the autumn (duration of exposure: 25 days) and late winter (10 days) cereal sowing times in Spanish farmlands. We studied effects on the survival, body condition, oxidative stress biomarkers, plasma biochemistry, carotenoid-based coloration, T-cell mediated immune response and reproduction of exposed adult partridges, and on the survival and T-cell immune response of their chicks. The high dose (recommended application rate) killed all partridges, with mortality occurring faster in females than in males. The low dose (20% the recommended application rate) had no effect on mortality, but reduced levels of plasma biochemistry parameters (glucose, magnesium and lactate dehydrogenase), increased blood superoxide dismutase activity, produced changes in carotenoid-based integument coloration, reduced the clutch size, delayed the first egg lay date, increased egg yolk vitamins and carotenoids and depressed T-cell immune response of chicks. Moreover, the analysis of the livers of dead partridges revealed an accumulation of imidacloprid during exposure time. Despite the moratorium on the use of neonicotinoids in the European Union, birds may still be at high risk of poisoning by these pesticides through direct sources of exposure to coated seeds in autumn and winter. PMID:25460626

  2. Gestational Hypothyroidism Improves the Ability of the Female Offspring to Clear Streptococcus pneumoniae Infection and to Recover From Pneumococcal Pneumonia.

    Science.gov (United States)

    Nieto, Pamela A; Peñaloza, Hernán F; Salazar-Echegarai, Francisco J; Castellanos, Raquel M; Opazo, Maria Cecilia; Venegas, Luis; Padilla, Oslando; Kalergis, Alexis M; Riedel, Claudia A; Bueno, Susan M

    2016-06-01

    Maternal thyroid hormones are essential for proper fetal development. A deficit of these hormones during gestation has enduring consequences in the central nervous system of the offspring, including detrimental learning and impaired memory. Few studies have shown that thyroid hormone deficiency has a transient effect in the number of T and B cells in the offspring gestated under hypothyroidism; however, there are no studies showing whether maternal hypothyroidism during gestation impacts the response of the offspring to infections. In this study, we have evaluated whether adult mice gestated in hypothyroid mothers have an altered response to pneumococcal pneumonia. We observed that female mice gestated in hypothyroidism have increased survival rate and less bacterial dissemination to blood and brain after an intranasal challenge with Streptococcus pneumoniae. Further, these mice had higher amounts of inflammatory cells in the lungs and reduced production of cytokines characteristic of sepsis in spleen, blood, and brain at 48 hours after infection. Interestingly, mice gestated in hypothyroid mothers had basally increased vascular permeability in the lungs. These observations suggest that gestational hypothyroidism alters the immune response and the physiology of lungs in the offspring, increasing the resistance to respiratory bacterial infections. PMID:27035652

  3. Effect of chronic social defeat stress on behaviors and dopamine receptor in adult mice.

    Science.gov (United States)

    Huang, Guang-Biao; Zhao, Tong; Gao, Xiao-Lei; Zhang, Hong-Xing; Xu, Yu-Ming; Li, Hao; Lv, Lu-Xian

    2016-04-01

    Victims of bullying often undergo depression, low self-esteem, high anxiety and post-traumatic stress disorder symptoms. The social defeat model has become widely accepted for studying experimental animal behavior changes associated with bullying; however, differences in the effects in susceptible and unsusceptible individuals have not been well studied. The present study investigated the effects of social defeat stress on behavior and the expression of dopamine receptors D1 and D2 in the brains of adult mice. Adult mice were divided into susceptible and unsusceptible groups after 10days of social defeat stress. Behavioral tests were conducted, and protein levels in the brains were assessed by Western blotting. The results indicate that all mice undergo decreased locomotion and increased anxiety behavior. However, decreased social interaction and impaired memory performance were only observed in susceptible mice. A significantly decreased expression of D1 was observed in the prefrontal cortex and amygdala of susceptible mice only. No significant differences in D2 expression were shown between control and defeated mice in any area studied. These data indicate that depression-like behavior and cognition impairment caused by social defeat stress in susceptible mice may be related to changes in the dopamine receptor D1. PMID:26655446

  4. Early postnatal motor experience shapes the motor properties of C57BL/6J adult mice.

    Science.gov (United States)

    Serradj, Nadjet; Picquet, Florence; Jamon, Marc

    2013-11-01

    This study aimed to evaluate the long-term consequences of early motor training on the muscle phenotype and motor output of middle-aged C57BL/6J mice. Neonatal mice were subjected to a variety of motor training procedures, for 3 weeks during the period of acquisition of locomotion. These procedures are widely used for motor training in adults; they include enriched environment, forced treadmill, chronic centrifugation, and hindlimb suspension. At 9 months, the mice reared in the enriched environment showed a slower type of fibre in slow muscles and a faster type in fast muscles, improved performance in motor tests, and a modified gait and body posture while walking. The proportion of fibres in the postural muscles of centrifuged mice did not change, but these mice showed improved resistance to fatigue. The suspended mice showed increased persistence of immature hybrid fibres in the tibialis, with a slower shift in the load-bearing soleus, without any behavioural changes. The forced treadmill was very stressful for the mice, but had limited effects on motor output, although a slower profile was observed in the tibialis. These results support the hypothesis that motor experience during a critical period of motor development shapes muscle phenotype and motor output. The different impacts of the various training procedures suggest that motor performance in adults can be optimized by appropriate training during a defined period of motor development. PMID:23869740

  5. Study on mechanisms of hypertension in rat adult offspring following prenatal exposure to immuno-inflammatory stimulants

    Institute of Scientific and Technical Information of China (English)

    ZHOU Jian-zhi; LI Xiao-hui

    2008-01-01

    Objective Essential hypertension (EH) is one of the most common cardiovascular disease and the main causes of human fatility. Recently significant progress has been made in our lab, it was found that exterior stimulation during pregnancy may play a key role in chronicle adult disease. However, what factors affect the growth of fetus after those exterior stimulation and why has not been reported. Based on our previous finding, this study intends to investigate how immuno-inflammatory stimulation affect the development of embryo. Methods 1. Sprague-Dawley (SD) rats, dams in each group received i.p. injections of 0.79 mg· kg-1 LPS, 8 mg·kg-1 zymosan or sterile saline respectively on their gestational days 8, 10, and 12.2. The serums were collected in tail nick at 2 h after the last injection, and the amniotic fluid was mixed at 2, 12, 24,48 h after the last injection. TNF-α and IL-6 levels of serum and amniotic fluid were measured by RIA method. 3. TNF-α and IL-6 mRNA levels were quantitated in amnion, placenta, amniotic fluid, Embryo and maerophage by real-time fluorescent quantitative-PCR. Results 1. The serum level of TNF-α and IL-6 in LPS group and zymosan group was higher than that in control group (P<0.01). It showed that there was immuno-imflammatory response after LPS or zymosan injection in rats. The mRNA levels of TNF-α and IL-6 was very higher in macrophage than in other organization. 2. In embryo, the mRNA level of IL-6 was more than other organization, but the mRNA level of TNF-α was lower than other organization. However, the IL-6 mRNA level of LPS group and zymosan group was higher several dozens times than control group on 24 h and 48 h. Conclusions It suggested that IL-6 was important in the model that prenatalexposure to immuno-inflammatory stimulant results in increases of blood pressure and body weight in rats.

  6. Drebrin A regulates hippocampal LTP and hippocampus-dependent fear learning in adult mice.

    Science.gov (United States)

    Kojima, N; Yasuda, H; Hanamura, K; Ishizuka, Y; Sekino, Y; Shirao, T

    2016-06-01

    Structural plasticity of dendritic spines, which underlies higher brain functions including learning and memory, is dynamically regulated by the actin cytoskeleton and its associated proteins. Drebrin A is an F-actin-binding protein preferentially expressed in the brain and localized in the dendritic spines of mature neurons. Isoform conversion from drebrin E to drebrin A and accumulation of the latter in dendritic spines occurs during synapse maturation. We have previously demonstrated that drebrin A plays a pivotal role in spine morphogenesis and plasticity. However, it is unclear whether drebrin A plays a specific role in processes required for structural plasticity, and whether drebrin E can substitute in this role. To answer these questions, we analyzed mutant mice (named DAKO mice), in which isoform conversion from drebrin E to drebrin A is disrupted. In DAKO mouse brain, drebrin E continues to be expressed throughout life instead of drebrin A. Electrophysiological studies using hippocampal slices revealed that long-term potentiation of CA1 synapses was impaired in adult DAKO mice, but not in adolescents. In parallel with this age-dependent impairment, DAKO mice exhibited impaired hippocampus-dependent fear learning in an age-dependent manner; the impairment was evident in adult mice, but not in adolescents. In addition, histological investigation revealed that the spine length of the apical dendrite of CA1 pyramidal cells was significantly longer in adult DAKO mice than in wild-type mice. Our data indicate that the roles of drebrin E and drebrin A in brain function are different from each other, that the isoform conversion of drebrin is critical, and that drebrin A is indispensable for normal synaptic plasticity and hippocampus-dependent fear memory in the adult brain. PMID:26970584

  7. Allogenic inhibition of the stem hemopoietic cells in the bone marrow and embryonic liver in adult mice

    International Nuclear Information System (INIS)

    The maternal effect was shown to influence the degree of allogenic inhibition of stem hemopoietic cells of the embryonic liver and adult bone marrow in CBA and C57Bl/6 mice. The display of allogenic inhibition of stem cells of the embryonic liver and adult bone marrow proved to be similar in C57Bl/6 mice and dissimilar in CBA

  8. Chronic Sleep Fragmentation Promotes Obesity in Young Adult Mice

    OpenAIRE

    Wang, Yang; Carreras, Alba; Lee, Seunghoon; Hakim, Fahed; Zhang, Shelley X.; Nair, Deepti; Ye, Honggang; Gozal, David

    2013-01-01

    Objectives Short sleep confers a higher risk of obesity in humans. Restricted sleep increases appetite, promotes higher calorie intake from fat and carbohydrate sources, and induces insulin resistance. However, the effects of fragmented sleep (SF), such as occurs in sleep apnea, on body weight, metabolic rates, and adipose tissue distribution are unknown. Design and Methods C57BL/6 mice were exposed to SF for 8 weeks. Their body weight, food consumption, and metabolic expenditure were monitor...

  9. Effect of acetylsalicylic acid on spermatogenesis in adult albino mice

    International Nuclear Information System (INIS)

    Spermatogenesis in male albino mice. Study Design: Laboratory based randomized controlled trial. Place and Duration of Study: Department of Anatomy University of Health Sciences, Lahore from Apr, 2012 to Dec, 2012. Material and Methods: Thirty nine male albino mice, 6-8 weeks old weighing 30 - 5 gm, were used; these were randomly divided into three groups having thirteen mice in each using random numbers table. Group A served as a control and was given distilled water orally via oral gavage 10 ml per kg for 30 days. Group B was given acetylsalicylic acid 100 mg/kg dissolved in 10 ml distilled orally for a period of 30 days. Group C was given acetylsalicylic acid 25 mg/kg dissolved in 2.5 ml distilled orally for a period of 30 days. Animals were sacrificed 24 hours after the last dose and the testes were removed, fixed in Bouin's fixative for 48 hours. Five microns thick sections of processed tissue were stained with H and E and PAS for calculation of Johnsen score and diameter of seminiferous tubules. Serum testosterone level was measured by testosterone enzyme immunoassay test kits. Results: Microscopic examination demonstrated that ASA treatment lead to statistically significant increase in the mean Johnsen score and mean diameter of seminiferous tubules. Conclusion: It was concluded from the current study that ASA treatment enhances spermatogenesis. (author)

  10. Metals and kidney markers in adult offspring of endemic nephropathy patients and controls: a two-year follow-up study

    Directory of Open Access Journals (Sweden)

    Tsolova Svetla

    2008-04-01

    Full Text Available Abstract Background The etiology of Balkan Endemic Nephropathy, (BEN, a tubulointerstitial kidney disease, is unknown. Although this disease is endemic in rural areas of Bosnia, Bulgaria, Croatia, Romania, and Serbia, similar manifestations are reported to occur in other regions, for instance Tunisia and Sri Lanka. A number of explanations have been stated including lignites, aristolochic acid, ochratoxin A, metals, and metalloids. Etiologic claims are often based on one or a few studies without sound scientific evidence. In this systematic study, we tested whether exposures to metals (cadmium and lead and metalloids (arsenic and selenium are related to Balkan Endemic Nephropathy. Methods In 2003/04 we recruited 102 adults whose parents had BEN and who resided in one of three communities (Vratza, Bistretz, or Beli Izvor, Bulgaria. A control group comprised of 99 adults having non-BEN hospitalized parents was enrolled in the study during the same time. We conducted face-to-face interviews, ultrasound kidney measurements, and determined kidney function in two consecutive investigations (2003/04 and 2004/05. Metals and metalloids were measured in urine and blood samples. To assess the agreement between these consecutive measurements, we calculated intraclass correlation coefficients. Repeated measurement data were analyzed using mixed models. Results We found that cadmium and arsenic were associated with neither kidney size nor function. Lead had a significant but negligible effect on creatinine clearance. Selenium showed a weak but significant negative association with two of the four kidney parameters, namely creatinine clearance and β2-microglobulin. It was positively related to kidney length. These associations were not restricted to the offspring of BEN patients. Adding credence to these findings are reports showing comparable kidney effects in animals exposed to selenium. Conclusion The findings of this 2-year follow-up study indicate that

  11. Acute Multiple Organ Failure in Adult Mice Deleted for the Developmental Regulator Wt1

    Science.gov (United States)

    Chau, You-Ying; Brownstein, David; Mjoseng, Heidi; Lee, Wen-Chin; Buza-Vidas, Natalija; Nerlov, Claus; Jacobsen, Sten Eirik; Perry, Paul; Berry, Rachel; Thornburn, Anna; Sexton, David; Morton, Nik; Hohenstein, Peter; Freyer, Elisabeth; Samuel, Kay; van't Hof, Rob; Hastie, Nicholas

    2011-01-01

    There is much interest in the mechanisms that regulate adult tissue homeostasis and their relationship to processes governing foetal development. Mice deleted for the Wilms' tumour gene, Wt1, lack kidneys, gonads, and spleen and die at mid-gestation due to defective coronary vasculature. Wt1 is vital for maintaining the mesenchymal–epithelial balance in these tissues and is required for the epithelial-to-mesenchyme transition (EMT) that generates coronary vascular progenitors. Although Wt1 is only expressed in rare cell populations in adults including glomerular podocytes, 1% of bone marrow cells, and mesothelium, we hypothesised that this might be important for homeostasis of adult tissues; hence, we deleted the gene ubiquitously in young and adult mice. Within just a few days, the mice suffered glomerulosclerosis, atrophy of the exocrine pancreas and spleen, severe reduction in bone and fat, and failure of erythropoiesis. FACS and culture experiments showed that Wt1 has an intrinsic role in both haematopoietic and mesenchymal stem cell lineages and suggest that defects within these contribute to the phenotypes we observe. We propose that glomerulosclerosis arises in part through down regulation of nephrin, a known Wt1 target gene. Protein profiling in mutant serum showed that there was no systemic inflammatory or nutritional response in the mutant mice. However, there was a dramatic reduction in circulating IGF-1 levels, which is likely to contribute to the bone and fat phenotypes. The reduction of IGF-1 did not result from a decrease in circulating GH, and there is no apparent pathology of the pituitary and adrenal glands. These findings 1) suggest that Wt1 is a major regulator of the homeostasis of some adult tissues, through both local and systemic actions; 2) highlight the differences between foetal and adult tissue regulation; 3) point to the importance of adult mesenchyme in tissue turnover. PMID:22216009

  12. Nonhematopoietic Nrf2 dominantly impedes adult progression of sickle cell anemia in mice

    Science.gov (United States)

    Ghosh, Samit; Ihunnah, Chibueze A.; Hazra, Rimi; Walker, Aisha L.; Hansen, Jason M.; Archer, David R.; Owusu-Ansah, Amma T.; Ofori-Acquah, Solomon F.

    2016-01-01

    The prevention of organ damage and early death in young adults is a major clinical concern in sickle cell disease (SCD). However, mechanisms that control adult progression of SCD during the transition from adolescence are poorly defined with no cognate prophylaxis. Here, we demonstrate in a longitudinal cohort of homozygous SCD (SS) mice a link between intravascular hemolysis, vascular inflammation, lung injury, and early death. Prophylactic Nrf2 activation in young SS mice stabilized intravascular hemolysis, reversed vascular inflammation, and attenuated lung edema in adulthood. Enhanced Nrf2 activation in endothelial cells in vitro concurred with the dramatic effect on vascular inflammation in the mice. BM chimeric SS mice lacking Nrf2 expression in nonhematopoietic tissues were created to dissect the role of nonerythroid Nrf2 in SCD progression. The SS chimeras developed severe intravascular hemolysis despite having erythroid Nrf2. In addition, they developed premature vascular inflammation and pulmonary edema and died younger than donor littermates with intact nonhematopoietic Nrf2. Our results reveal a dominant protective role for nonhematopoietic Nrf2 against tissue damage in both erythroid and nonerythroid tissues in SCD. Furthermore, we show that prophylactic augmentation of Nrf2-coordinated cytoprotection effectively impedes onset of the severe adult phenotype of SCD in mice. PMID:27158670

  13. Reduced white fat mass in adult mice bearing a truncated Patched 1

    Directory of Open Access Journals (Sweden)

    Zili Li, Heng Zhang, Leslie A. Denhard, Lan-Hsin Liu, Huaxin Zhou, Zi-Jian Lan

    2008-01-01

    Full Text Available Hedgehog (Hh signaling emerges as a potential pathway contributing to fat formation during postnatal development. In this report, we found that Patched 1 (Ptc1, a negative regulator of Hh signaling, was expressed in the epididymal fat pad of adult mice. Reduced total white fat mass and epididymal adipocyte cell size were observed in naturally occurring spontaneous mesenchymal dysplasia (mes adult mice (Ptc1mes/mes, which carry a deletion of Ptc1 at the carboxyl-terminal cytoplasmic region. Increased expression of truncated Ptc1, Ptc2 and Gli1, the indicators of ectopic activation of Hh signaling, was observed in epididymal fat pads of adult Ptc1mes/mes mice. In contrast, expression of peroxisome proliferator-activated receptor gamma, CCAAT/enhancer binding protein alpha, adipocyte P2 and adipsin were reduced in epididymal fat pads of adult Ptc1mes/mes mice. Taken together, our results indicate that deletion of carboxyl-terminal tail of Ptc1 can lead to the reduction of white fat mass during postnatal development.

  14. Leptin-independent programming of adult body weight and adiposity in mice.

    Science.gov (United States)

    Cottrell, Elizabeth C; Martin-Gronert, Malgorzata S; Fernandez-Twinn, Denise S; Luan, Jian'an; Berends, Lindsey M; Ozanne, Susan E

    2011-02-01

    Low birth weight and rapid postnatal weight gain are independent and additive risk factors for the subsequent development of metabolic disease. Despite an abundance of evidence for these associations, mechanistic data are lacking. The hormone leptin has received significant interest as a potential programming factor, because differences in the profile of leptin in early life have been associated with altered susceptibility to obesity. Whether leptin alone is a critical factor for programming obesity has, until now, remained unclear. Using the leptin-deficient ob/ob mouse, we show that low birth weight followed by rapid catch-up growth during lactation (recuperated offspring) leads to a persistent increase in body weight in adult life, both in wild-type and ob/ob animals. Furthermore, recuperated offspring are hyperphagic and epididymal fat pad weights are significantly increased, reflecting greater adiposity. These results show definitively that factors other than leptin are crucial in the programming of energy homeostasis in this model and are powerful enough to alter adiposity in a genetically obese strain. PMID:21209019

  15. Nutritional intervention restores muscle but not kidney phenotypes in adult calcineurin aα null mice

    DEFF Research Database (Denmark)

    Madsen, Kirsten; Reddy, Ramesh N; Price, S Russ;

    2013-01-01

    Mice lacking the α isoform of the catalytic subunit of calcineurin (CnAα) were first reported in 1996 and have been an important model to understand the role of calcineurin in the brain, immune system, bones, muscle, and kidney. Research using the mice has been limited, however, by failure to...... deprivation is known to significantly alter development, it is imperative that previous conclusions based on CnAα-/- mice are revisited to determine which aspects of the phenotype were attributable to caloric restriction versus a direct role for CnAα. In this study, we find that defects in renal development......, loss of CnAα likely alters insulin response due to a reduction in insulin receptor substrate-2 (IRS2) expression and signaling in muscle. This study illustrates the importance of re-examining the phenotypes of CnAα-/- mice and the advances that are now possible with the use of adult, rescued knockout...

  16. Effect of Vitamin B Deprivation during Pregnancy and Lactation on Homocysteine Metabolism and Related Metabolites in Brain and Plasma of Mice Offspring

    OpenAIRE

    da Silva, Vanessa Cavalcante; Fernandes, Leandro; Haseyama, Eduardo Jun; Agamme, Ana Luiza Dias Abdo; Shinohara, Elvira Maria Guerra; Muniz, Maria Tereza Cartaxo; D'Almeida, Vânia

    2014-01-01

    Epidemiological and experimental studies indicate that the altered fetal and neonatal environment influences physiological functions and may increase the risk of developing chronic diseases in adulthood. Because homocysteine (Hcy) metabolic imbalance is considered a risk factor for neurodegenerative diseases, we investigated whether maternal Vitamin B deficiency during early development alters the offspring's methionine-homocysteine metabolism in their brain. To this end, the dams were submit...

  17. Fetal and neonatal exposure to nicotine leads to augmented hepatic and circulating triglycerides in adult male offspring due to increased expression of fatty acid synthase

    International Nuclear Information System (INIS)

    While nicotine replacement therapy is assumed to be a safer alternative to smoking during pregnancy, the long-term consequences for the offspring remain elusive. Animal studies now suggest that maternal nicotine exposure during perinatal life leads to a wide range of adverse outcomes for the offspring including increased adiposity. The focus of this study was to investigate if nicotine exposure during pregnancy and lactation leads to alterations in hepatic triglyceride synthesis. Female Wistar rats were randomly assigned to receive daily subcutaneous injections of saline (vehicle) or nicotine bitartrate (1 mg/kg/day) for two weeks prior to mating until weaning. At postnatal day 180 (PND 180), nicotine exposed offspring exhibited significantly elevated levels of circulating and hepatic triglycerides in the male offspring. This was concomitant with increased expression of fatty acid synthase (FAS), the critical hepatic enzyme in de novo triglyceride synthesis. Given that FAS is regulated by the nuclear receptor Liver X receptor (LXRα), we measured LXRα expression in both control and nicotine-exposed offspring. Nicotine exposure during pregnancy and lactation led to an increase in hepatic LXRα protein expression and enriched binding to the putative LXRE element on the FAS promoter in PND 180 male offspring. This was also associated with significantly enhanced acetylation of histone H3 [K9,14] surrounding the FAS promoter, a hallmark of chromatin activation. Collectively, these findings suggest that nicotine exposure during pregnancy and lactation leads to an increase in circulating and hepatic triglycerides long-term via changes in the transcriptional and epigenetic regulation of the hepatic lipogenic pathway. - Highlights: • Our data reveals the links nicotine exposure in utero and long-term hypertriglyceridemia. • It is due to nicotine-induced augmented expression of hepatic FAS and LXRα activity. • Moreover, this involves nicotine-induced enhanced

  18. Fetal and neonatal exposure to nicotine leads to augmented hepatic and circulating triglycerides in adult male offspring due to increased expression of fatty acid synthase

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Noelle [Department of Physiology and Pharmacology, The University of Western Ontario (Canada); Department of Obstetrics and Gynecology, The University of Western Ontario (Canada); The Lawson Health Research Institute, The University of Western Ontario (Canada); Nicholson, Catherine J. [Department of Obstetrics and Gynecology, McMaster University (Canada); Wong, Michael [Department of Physiology and Pharmacology, The University of Western Ontario (Canada); Department of Obstetrics and Gynecology, The University of Western Ontario (Canada); The Lawson Health Research Institute, The University of Western Ontario (Canada); Holloway, Alison C. [Department of Obstetrics and Gynecology, McMaster University (Canada); Hardy, Daniel B., E-mail: Daniel.Hardy@schulich.uwo.ca [Department of Physiology and Pharmacology, The University of Western Ontario (Canada); Department of Obstetrics and Gynecology, The University of Western Ontario (Canada); The Children' s Health Research Institute, The University of Western Ontario (Canada); The Lawson Health Research Institute, The University of Western Ontario (Canada)

    2014-02-15

    While nicotine replacement therapy is assumed to be a safer alternative to smoking during pregnancy, the long-term consequences for the offspring remain elusive. Animal studies now suggest that maternal nicotine exposure during perinatal life leads to a wide range of adverse outcomes for the offspring including increased adiposity. The focus of this study was to investigate if nicotine exposure during pregnancy and lactation leads to alterations in hepatic triglyceride synthesis. Female Wistar rats were randomly assigned to receive daily subcutaneous injections of saline (vehicle) or nicotine bitartrate (1 mg/kg/day) for two weeks prior to mating until weaning. At postnatal day 180 (PND 180), nicotine exposed offspring exhibited significantly elevated levels of circulating and hepatic triglycerides in the male offspring. This was concomitant with increased expression of fatty acid synthase (FAS), the critical hepatic enzyme in de novo triglyceride synthesis. Given that FAS is regulated by the nuclear receptor Liver X receptor (LXRα), we measured LXRα expression in both control and nicotine-exposed offspring. Nicotine exposure during pregnancy and lactation led to an increase in hepatic LXRα protein expression and enriched binding to the putative LXRE element on the FAS promoter in PND 180 male offspring. This was also associated with significantly enhanced acetylation of histone H3 [K9,14] surrounding the FAS promoter, a hallmark of chromatin activation. Collectively, these findings suggest that nicotine exposure during pregnancy and lactation leads to an increase in circulating and hepatic triglycerides long-term via changes in the transcriptional and epigenetic regulation of the hepatic lipogenic pathway. - Highlights: • Our data reveals the links nicotine exposure in utero and long-term hypertriglyceridemia. • It is due to nicotine-induced augmented expression of hepatic FAS and LXRα activity. • Moreover, this involves nicotine-induced enhanced

  19. Morphometric study of Schistosoma mansoni adult worms recovered from undernourished infected mice

    Directory of Open Access Journals (Sweden)

    Sheilla A Oliveira

    2003-07-01

    Full Text Available Some unfavourable effects of malnutrition of the host on Schistosoma mansoni worm biology and structure have been reported based upon brigthfield microscopy. This paper aims to study by morphometric techniques, some morphological parameters in male and female adult worms recovered from undernourished albino mice in comparison with parasites recovered from well-fed infected mice. Undernourished animals were fed a multideficient and essentially low protein diet (RBD diet and compared to well-fed control mice fed with the commercial diet NUVILAB. Seventy-five days post-infection with 80 cercarie (BL strain animals were sacrificed. All adult worms were fixed in 10% formalin and stained with carmine chloride. One hundred male and 60 female specimens from each group (undernourished and control were examined using an image system analysis Leica Quantimet 500C and the Sigma Scan Measurement System. The following morphometrical parameters were studied: body length and width, oral and ventral suckers, number and area of testicular lobes, length and width of ovary and uterine egg. For statistical analysis, the Student's t test for unpaired samples was applied. Significant differences (p < 0.05 were detected in body length and width, in parameters of suckers, uterine egg width, ovary length and area of testicular lobes, with lower values for specimens from undernourished mice. The nutritional status of the host has negative influence on S. mansoni adult worms, probably through unavailability of essential nutrients to the parasites.

  20. Human-derived neural progenitors functionally replace astrocytes in adult mice

    Science.gov (United States)

    Chen, Hong; Qian, Kun; Chen, Wei; Hu, Baoyang; Blackbourn, Lisle W.; Du, Zhongwei; Ma, Lixiang; Liu, Huisheng; Knobel, Karla M.; Ayala, Melvin; Zhang, Su-Chun

    2015-01-01

    Astrocytes are integral components of the homeostatic neural network as well as active participants in pathogenesis of and recovery from nearly all neurological conditions. Evolutionarily, compared with lower vertebrates and nonhuman primates, humans have an increased astrocyte-to-neuron ratio; however, a lack of effective models has hindered the study of the complex roles of human astrocytes in intact adult animals. Here, we demonstrated that after transplantation into the cervical spinal cords of adult mice with severe combined immunodeficiency (SCID), human pluripotent stem cell–derived (PSC-derived) neural progenitors migrate a long distance and differentiate to astrocytes that nearly replace their mouse counterparts over a 9-month period. The human PSC-derived astrocytes formed networks through their processes, encircled endogenous neurons, and extended end feet that wrapped around blood vessels without altering locomotion behaviors, suggesting structural, and potentially functional, integration into the adult mouse spinal cord. Furthermore, in SCID mice transplanted with neural progenitors derived from induced PSCs from patients with ALS, astrocytes were generated and distributed to a similar degree as that seen in mice transplanted with healthy progenitors; however, these mice exhibited motor deficit, highlighting functional integration of the human-derived astrocytes. Together, these results indicate that this chimeric animal model has potential for further investigating the roles of human astrocytes in disease pathogenesis and repair. PMID:25642771

  1. Global gene expression patterns in the post-pneumonectomy lung of adult mice

    Directory of Open Access Journals (Sweden)

    Ingenito Edward P

    2009-10-01

    Full Text Available Abstract Background Adult mice have a remarkable capacity to regenerate functional alveoli following either lung resection or injury that exceeds the regenerative capacity observed in larger adult mammals. The molecular basis for this unique capability in mice is largely unknown. We examined the transcriptomic responses to single lung pneumonectomy in adult mice in order to elucidate prospective molecular signaling mechanisms used in this species during lung regeneration. Methods Unilateral left pneumonectomy or sham thoracotomy was performed under general anesthesia (n = 8 mice per group for each of the four time points. Total RNA was isolated from the remaining lung tissue at four time points post-surgery (6 hours, 1 day, 3 days, 7 days and analyzed using microarray technology. Results The observed transcriptomic patterns revealed mesenchymal cell signaling, including up-regulation of genes previously associated with activated fibroblasts (Tnfrsf12a, Tnc, Eln, Col3A1, as well as modulation of Igf1-mediated signaling. The data set also revealed early down-regulation of pro-inflammatory cytokine transcripts and up-regulation of genes involved in T cell development/function, but few similarities to transcriptomic patterns observed during embryonic or post-natal lung development. Immunohistochemical analysis suggests that early fibroblast but not myofibroblast proliferation is important during lung regeneration and may explain the preponderance of mesenchymal-associated genes that are over-expressed in this model. This again appears to differ from embryonic alveologenesis. Conclusion These data suggest that modulation of mesenchymal cell transcriptome patterns and proliferation of S100A4 positive mesenchymal cells, as well as modulation of pro-inflammatory transcriptome patterns, are important during post-pneumonectomy lung regeneration in adult mice.

  2. Lepidium meyenii (Maca increases litter size in normal adult female mice

    Directory of Open Access Journals (Sweden)

    Gasco Manuel

    2005-05-01

    Full Text Available Abstract Background Lepidium meyenii, known as Maca, grows exclusively in the Peruvian Andes over 4000 m altitude. It has been used traditionally to increase fertility. Previous scientific studies have demonstrated that Maca increases spermatogenesis and epididymal sperm count. The present study was aimed to investigate the effects of Maca on several fertility parameters of female mice at reproductive age. Methods Adult female Balb/C mice were divided at random into three main groups: i Reproductive indexes group, ii Implantation sites group and iii Assessment of uterine weight in ovariectomized mice. Animals received an aqueous extract of lyophilized Yellow Maca (1 g/Kg BW or vehicle orally as treatment. In the fertility indexes study, animals received the treatment before, during and after gestation. The fertility index, gestation index, post-natal viability index, weaning viability index and sex ratio were calculated. Sexual maturation was evaluated in the female pups by the vaginal opening (VO day. In the implantation study, females were checked for implantation sites at gestation day 7 and the embryos were counted. In ovariectomized mice, the uterine weight was recorded at the end of treatment. Results Implantation sites were similar in mice treated with Maca and in controls. All reproductive indexes were similar in both groups of treatment. The number of pups per dam at birth and at postnatal day 4 was significantly higher in the group treated with Maca. VO day occurred earlier as litter size was smaller. Maca did not affect VO day. In ovariectomized mice, the treatment with Maca increased significantly the uterine weights in comparison to their respective control group. Conclusion Administration of aqueous extract of Yellow Maca to adult female mice increases the litter size. Moreover, this treatment increases the uterine weight in ovariectomized animals. Our study confirms for the first time some of the traditional uses of Maca to

  3. Cellulose supplementation early in life ameliorates colitis in adult mice.

    Directory of Open Access Journals (Sweden)

    Dorottya Nagy-Szakal

    Full Text Available Decreased consumption of dietary fibers, such as cellulose, has been proposed to promote the emergence of inflammatory bowel diseases (IBD: Crohn disease [CD] and ulcerative colitis [UC] where intestinal microbes are recognized to play an etiologic role. However, it is not known if transient fiber consumption during critical developmental periods may prevent consecutive intestinal inflammation. The incidence of IBD peaks in young adulthood indicating that pediatric environmental exposures may be important in the etiology of this disease group. We studied the effects of transient dietary cellulose supplementation on dextran sulfate sodium (DSS colitis susceptibility during the pediatric period in mice. Cellulose supplementation stimulated substantial shifts in the colonic mucosal microbiome. Several bacterial taxa decreased in relative abundance (e.g., Coriobacteriaceae [p = 0.001], and other taxa increased in abundance (e.g., Peptostreptococcaceae [p = 0.008] and Clostridiaceae [p = 0.048]. Some of these shifts persisted for 10 days following the cessation of cellulose supplementation. The changes in the gut microbiome were associated with transient trophic and anticolitic effects 10 days following the cessation of a cellulose-enriched diet, but these changes diminished by 40 days following reversal to a low cellulose diet. These findings emphasize the transient protective effect of dietary cellulose in the mammalian large bowel and highlight the potential role of dietary fibers in amelioration of intestinal inflammation.

  4. Effects of prenatal exposure to surface-coated nanosized titanium dioxide (UV-Titan). A study in mice

    DEFF Research Database (Denmark)

    Hougaard, Karin S.; Jackson, Petra; Jensen, Keld A.;

    2010-01-01

    ; offspring neurofunction and fertility. Physicochemical particle properties were determined to provide information on specific exposure and deposition. Results: Particles consisted of mainly elongated rutile titanium dioxide (TiO2) with an average crystallite size of 21 nm, modified with Al, Si and Zr, and...... coated with polyalcohols. In exposed adult mice, 38 mg Ti/kg was detected in the lungs on day 5 and differential cell counts of bronchoalveolar lavage fluid revealed lung inflammation 5 and 26-27 days following exposure termination, relative to control mice. As young adults, prenatally exposed offspring...

  5. Maternal Exercise during Pregnancy Increases BDNF Levels and Cell Numbers in the Hippocampal Formation but Not in the Cerebral Cortex of Adult Rat Offspring

    Science.gov (United States)

    Gomes da Silva, Sérgio; de Almeida, Alexandre Aparecido; Fernandes, Jansen; Lopim, Glauber Menezes; Cabral, Francisco Romero; Scerni, Débora Amado; de Oliveira-Pinto, Ana Virgínia; Lent, Roberto; Arida, Ricardo Mario

    2016-01-01

    Clinical evidence has shown that physical exercise during pregnancy may alter brain development and improve cognitive function of offspring. However, the mechanisms through which maternal exercise might promote such effects are not well understood. The present study examined levels of brain-derived neurotrophic factor (BDNF) and absolute cell…

  6. Paternal B Vitamin Intake Is a Determinant of Growth, Hepatic Lipid Metabolism and Intestinal Tumor Volume in Female Apc1638N Mouse Offspring.

    Directory of Open Access Journals (Sweden)

    Julia A Sabet

    Full Text Available The importance of maternal nutrition to offspring health and risk of disease is well established. Emerging evidence suggests paternal diet may affect offspring health as well.In the current study we sought to determine whether modulating pre-conception paternal B vitamin intake alters intestinal tumor formation in offspring. Additionally, we sought to identify potential mechanisms for the observed weight differential among offspring by profiling hepatic gene expression and lipid content.Male Apc1638N mice (prone to intestinal tumor formation were fed diets containing replete (control, CTRL, mildly deficient (DEF, or supplemental (SUPP quantities of vitamins B2, B6, B12, and folate for 8 weeks before mating with control-fed wild type females. Wild type offspring were euthanized at weaning and hepatic gene expression profiled. Apc1638N offspring were fed a replete diet and euthanized at 28 weeks of age to assess tumor burden.No differences in intestinal tumor incidence or burden were found between male Apc1638N offspring of different paternal diet groups. Although in female Apc1638N offspring there were no differences in tumor incidence or multiplicity, a stepwise increase in tumor volume with increasing paternal B vitamin intake was observed. Interestingly, female offspring of SUPP and DEF fathers had a significantly lower body weight than those of CTRL fed fathers. Moreover, hepatic trigylcerides and cholesterol were elevated 3-fold in adult female offspring of SUPP fathers. Weanling offspring of the same fathers displayed altered expression of several key lipid-metabolism genes. Hundreds of differentially methylated regions were identified in the paternal sperm in response to DEF and SUPP diets. Aside from a few genes including Igf2, there was a striking lack of overlap between these genes differentially methylated in sperm and differentially expressed in offspring.In this animal model, modulation of paternal B vitamin intake prior to mating

  7. Round and Round and Round We Go: Behavior of Adult Female Mice on the ISS

    Science.gov (United States)

    Ronca, April E.

    2016-01-01

    The NASA Decadal Survey (2011) emphasized the importance of long duration rodent experiments on the International Space Station (ISS). To accomplish this objective, flight hardware and science capabilities supporting mouse studies in space were developed at Ames Research Center. Here we present a video-based behavioral analysis of ten C57BL6 female adult mice exposed to a total of 37 days in space compared with identically housed Ground Controls. Flight and Control mice exhibited the same range of behaviors, including feeding, drinking, exploratory behavior, grooming, and social interactions. Mice propelled themselves freely and actively throughout the Habitat using their forelimbs to push off or by floating from one cage area to another. Overall activity was greater in Flt as compared to GC mice. Spontaneous, organized circling or race-tracking behavior emerged within the first few days of flight and encompassed the primary dark cycle activity for the remainder of the experiment. I will summarize qualitative observations and quantitative comparisons of mice in microgravity and 1g conditions. Behavioral phenotyping revealed important insights into the overall health and adaptation of mice to the space environment, and identified unique behaviors that can guide future habitat development and research on rodents in space.

  8. Establishment of a tamoxifen-inducible Cre-driver mouse strain for widespread and temporal genetic modification in adult mice.

    Science.gov (United States)

    Ichise, Hirotake; Hori, Akiko; Shiozawa, Seiji; Kondo, Saki; Kanegae, Yumi; Saito, Izumu; Ichise, Taeko; Yoshida, Nobuaki

    2016-07-29

    Temporal genetic modification of mice using the ligand-inducible Cre/loxP system is an important technique that allows the bypass of embryonic lethal phenotypes and access to adult phenotypes. In this study, we generated a tamoxifen-inducible Cre-driver mouse strain for the purpose of widespread and temporal Cre recombination. The new line, named CM32, expresses the GFPneo-fusion gene in a wide variety of tissues before FLP recombination and tamoxifen-inducible Cre after FLP recombination. Using FLP-recombined CM32 mice (CM32Δ mice) and Cre reporter mouse lines, we evaluated the efficiency of Cre recombination with and without tamoxifen administration to adult mice, and found tamoxifen-dependent induction of Cre recombination in a variety of adult tissues. In addition, we demonstrated that conditional activation of an oncogene could be achieved in adults using CM32Δ mice. CM32Δ;T26 mice, which harbored a Cre recombination-driven, SV40 large T antigen-expressing transgene, were viable and fertile. No overt phenotype was found in the mice up to 3 months after birth. Although they displayed pineoblastomas (pinealoblastomas) and/or thymic enlargement due to background Cre recombination by 6 months after birth, they developed epidermal hyperplasia when administered tamoxifen. Collectively, our results suggest that the CM32Δ transgenic mouse line can be applied to the assessment of adult phenotypes in mice with loxP-flanked transgenes. PMID:26923756

  9. Maternal lipopolysaccharide treatment differentially affects 5-HT(2A) and mGlu2/3 receptor function in the adult male and female rat offspring.

    Science.gov (United States)

    Wischhof, Lena; Irrsack, Ellen; Dietz, Frank; Koch, Michael

    2015-10-01

    Maternal infection during pregnancy increases the risk for the offspring to develop schizophrenia. However, it is still not fully understood which biochemical mechanisms are responsible for the emergence of neuropsychiatric symptoms following prenatal immune activation. The serotonin (5-hydroxytryptamine, 5-HT) and glutamate system have prominently been associated with the schizophrenia pathophysiology but also with the mechanism of antipsychotic drug actions. Here, we investigated the behavioral and cellular response to 5-HT2A and metabotropic glutamate (mGlu)2/3 receptor stimulation in male and female offspring born to lipopolysaccharide (LPS)-treated mothers. Additionally, we assessed protein expression levels of prefrontal 5-HT2A and mGlu2 receptors. Prenatally LPS-exposed male and female offspring showed locomotor hyperactivity and increased head-twitch behavior in response to the 5-HT2A receptor agonist DOI. In LPS-exposed male offspring, the mGlu2/3 receptor agonist LY379268 failed to reduce DOI-induced prepulse inhibition deficits. In LPS-males, the behavioral changes were further accompanied by enhanced DOI-induced c-Fos protein expression and an up-regulation of prefrontal 5-HT2A receptors. No changes in either 5-HT2A or mGlu2 receptor protein levels were found in female offspring. Our data support the hypothesis of an involvement of maternal infection during pregnancy contributing, at least partially, to the pathology of schizophrenia. Identifying biochemical alterations that parallel the behavioral deficits may help to improve therapeutic strategies in the treatment of this mental illness. Since most studies in rodents almost exclusively include male subjects, our data further contribute to elucidating possible gender differences in the effects of prenatal infection on 5-HT2A and mGlu2/3 receptor function. PMID:26051401

  10. Pannexin 1 regulates bidirectional hippocampal synaptic plasticity in adult mice

    Science.gov (United States)

    Ardiles, Alvaro O.; Flores-Muñoz, Carolina; Toro-Ayala, Gabriela; Cárdenas, Ana M.; Palacios, Adrian G.; Muñoz, Pablo; Fuenzalida, Marco; Sáez, Juan C.; Martínez, Agustín D.

    2014-01-01

    The threshold for bidirectional modification of synaptic plasticity is known to be controlled by several factors, including the balance between protein phosphorylation and dephosphorylation, postsynaptic free Ca2+ concentration and NMDA receptor (NMDAR) composition of GluN2 subunits. Pannexin 1 (Panx1), a member of the integral membrane protein family, has been shown to form non-selective channels and to regulate the induction of synaptic plasticity as well as hippocampal-dependent learning. Although Panx1 channels have been suggested to play a role in excitatory long-term potentiation (LTP), it remains unknown whether these channels also modulate long-term depression (LTD) or the balance between both types of synaptic plasticity. To study how Panx1 contributes to excitatory synaptic efficacy, we examined the age-dependent effects of eliminating or blocking Panx1 channels on excitatory synaptic plasticity within the CA1 region of the mouse hippocampus. By using different protocols to induce bidirectional synaptic plasticity, Panx1 channel blockade or lack of Panx1 were found to enhance LTP, whereas both conditions precluded the induction of LTD in adults, but not in young animals. These findings suggest that Panx1 channels restrain the sliding threshold for the induction of synaptic plasticity and underlying brain mechanisms of learning and memory. PMID:25360084

  11. Increased adult hippocampal neurogenesis is not necessary for wheel running to abolish conditioned place preference for cocaine in mice.

    Science.gov (United States)

    Mustroph, M L; Merritt, J R; Holloway, A L; Pinardo, H; Miller, D S; Kilby, C N; Bucko, P; Wyer, A; Rhodes, J S

    2015-01-01

    Recent evidence suggests that wheel running can abolish conditioned place preference (CPP) for cocaine in mice. Running significantly increases the number of new neurons in the hippocampus, and new neurons have been hypothesised to enhance plasticity and behavioral flexibility. Therefore, we tested the hypothesis that increased neurogenesis was necessary for exercise to abolish cocaine CPP. Male nestin-thymidine kinase transgenic mice were conditioned with cocaine, and then housed with or without running wheels for 32 days. Half of the mice were fed chow containing valganciclovir to induce apoptosis in newly divided neurons, and the other half were fed standard chow. For the first 10 days, mice received daily injections of bromodeoxyuridine (BrdU) to label dividing cells. On the last 4 days, mice were tested for CPP, and then euthanized for measurement of adult hippocampal neurogenesis by counting the number of BrdU-positive neurons in the dentate gyrus. Levels of running were similar in mice fed valganciclovir-containing chow and normal chow. Valganciclovir significantly reduced the numbers of neurons (BrdU-positive/NeuN-positive) in the dentate gyrus of both sedentary mice and runner mice. Valganciclovir-fed runner mice showed similar levels of neurogenesis as sedentary, normal-fed controls. However, valganciclovir-fed runner mice showed the same abolishment of CPP as runner mice with intact neurogenesis. The results demonstrate that elevated adult hippocampal neurogenesis resulting from running is not necessary for running to abolish cocaine CPP in mice. PMID:25393660

  12. How does long-term odor deprivation affect the olfactory capacity of adult mice?

    Directory of Open Access Journals (Sweden)

    Coppola David M

    2010-05-01

    Full Text Available Abstract Background Unilateral naris occlusion (UNO has been the most common method of effecting stimulus deprivation in studies of olfactory plasticity. However, despite the large corpus on the effects of this manipulation, dating back to the 19th century, little is known about its behavioral sequela. Here we report the results of standard olfactory habituation and discrimination studies on adult mice that had undergone perinatal UNO followed by adult contralateral olfactory bulbectomy (bulb-x. Methods The olfactory performance of UNO mice was compared to matched controls that had unilateral bulb-x but open nares. Both habituation and discrimination (operant experiments employed a protocol in which after successful dishabituation or discrimination to dilute individual odors (A = 0.01% isoamyl acetate; B = 0.01% ethyl butyrate; each v/v in mineral oil, mice were challenged with a single odor versus a mixture comparison (A vs. A + B. In a series of tests the volume portion of Odor B in the mixture was systematically decreased until dishabituation or discrimination thresholds were reached. Results For the habituation experiment, UNOs (n = 10 and controls (n = 9 dishabituated to a 10% mixture of Odor B in Odor A after being habituated to A alone, while both groups failed to show differential responding to a 2% mixture of B in A. However, the UNO group's increased investigation durations for the 2% mixture approached significance (p Conclusions Adult mice relying on an olfactory system deprived of odor by naris occlusion from near the time of birth display enhanced olfactory capacity compared to control mice. This counterintuitive result suggests that UNO is neither an absolute method of deprivation nor does it diminish olfactory capabilities. Enhanced olfactory capacity, as observed in the current study, that is a consequence of deprivation, is consistent with recent molecular and physiological evidence that stimulus deprivation triggers

  13. Neonatal colon insult alters growth factor expression and TRPA1 responses in adult mice.

    Science.gov (United States)

    Christianson, Julie A; Bielefeldt, Klaus; Malin, Sacha A; Davis, Brian M

    2010-11-01

    Inflammation or pain during neonatal development can result in long-term structural and functional alterations of nociceptive pathways, ultimately altering pain perception in adulthood. We have developed a mouse model of neonatal colon irritation (NCI) to investigate the plasticity of pain processing within the viscerosensory system. Mouse pups received an intracolonic administration of 2% mustard oil (MO) on postnatal days 8 and 10. Distal colons were processed at subsequent timepoints for myeloperoxidase (MPO) activity and growth factor expression. Adult mice were assessed for visceral hypersensitivity by measuring the visceromotor response during colorectal distension. Dorsal root ganglion (DRG) neurons from adult mice were retrogradely labeled from the distal colon and calcium imaging was used to measure transient receptor potential vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1) responses to acute application of capsaicin and MO, respectively. Despite the absence of inflammation (as indicated by MPO activity), neonatal exposure to intracolonic MO transiently maintained a higher expression level of growth factor messenger RNA (mRNA). Adult NCI mice displayed significant visceral hypersensitivity, as well as increased sensitivity to mechanical stimulation of the hindpaw, compared to control mice. The percentage of TRPA1-expressing colon afferents was significantly increased in NCI mice, however they displayed no increase in the percentage of TRPV1-immunopositive or capsaicin-sensitive colon DRG neurons. These results suggest that early neonatal colon injury results in a long-lasting visceral hypersensitivity, possibly driven by an early increase in growth factor expression and maintained by permanent changes in TRPA1 function. PMID:20850221

  14. Risk of emotional disorder in offspring of depressed parents : Gender differences in the effect of a second emotionally affected parent

    NARCIS (Netherlands)

    Landman-Peeters, K.M.; Ormel, J.; van Sonderen, E.L.; den Boer, J.A.; Minderaa, R.B.; Hartman, C.A.

    2008-01-01

    In offspring of depressed parents a second parent with emotional problems is likely to increase risk of emotional disorder. This effect may however differ between sons and daughters and between offspring of depressed fathers and offspring of depressed mothers. In adolescent and young-adult offspring

  15. Cellular origins of cold-induced brown adipocytes in adult mice

    OpenAIRE

    Lee, Yun-Hee; Petkova, Anelia P.; Konkar, Anish A.; Granneman, James G.

    2014-01-01

    This work investigated how cold stress induces the appearance of brown adipocytes (BAs) in brown and white adipose tissues (WATs) of adult mice. In interscapular brown adipose tissue (iBAT), cold exposure increased proliferation of endothelial cells and interstitial cells expressing platelet-derived growth factor receptor, α polypeptide (PDGFRα) by 3- to 4-fold. Surprisingly, brown adipogenesis and angiogenesis were largely restricted to the dorsal edge of iBAT. Although cold stress did not i...

  16. Behavioral responses to and brain distribution of morphine in mature adult and aged mice

    International Nuclear Information System (INIS)

    Mature adult (3-6 mo old) and aged (2 yr old) male ICR mice were injected with 10 to 100 mg/kg morphine, s.c. The ED50 values for running behavior (as measured using Stoelting activity monitors and having each mouse serve as its own control) representing 5 times control activity was approximately 7.5 mg/kg for aged mice and approximately 17.5 mg/kg for the mature adults. The ED50 values for analgesia 1 hr after morphine administration using the tail-flick method (max. response time = 8 sec) were approx. 70 mg/kg for the aged mice and 15 mg/kg for the mature adults. One hour after injecting 3H-morphine at doses of 30 and 100 mg/kg, 0.13 and 0.14% of the doses appeared in brains of aged and mature adult mice, respectively. Regional distribution of the morphine was the same for both age groups. Expressed as percent of total brain morphine, it was as follows: cortex, 30%; midbrain, 18%; cerebellum, 17%; medulla, 12%; pons, 9%; striatum, 8% and periaqueductal gray, 6%. Expressed as g morphine/g tissue for the 2 doses, the distribution was; periaqueductal gray, 30 and 80; striatum, 9 and 34; medulla, 6 and 20 pons; 5 and 19; cerebellum, 4 and 13; midbrain 2.5 and 8.5 and cortex, 2 and 8. These results suggest that the differences in response to morphine by the two age groups were due to age-related differences in opioid receptor populations and/or affinities

  17. Behavioral responses to and brain distribution of morphine in mature adult and aged mice

    Energy Technology Data Exchange (ETDEWEB)

    Burton, C.K.; Ho, I.K.; Hoskins, B.

    1986-03-01

    Mature adult (3-6 mo old) and aged (2 yr old) male ICR mice were injected with 10 to 100 mg/kg morphine, s.c. The ED50 values for running behavior (as measured using Stoelting activity monitors and having each mouse serve as its own control) representing 5 times control activity was approximately 7.5 mg/kg for aged mice and approximately 17.5 mg/kg for the mature adults. The ED50 values for analgesia 1 hr after morphine administration using the tail-flick method (max. response time = 8 sec) were approx. 70 mg/kg for the aged mice and 15 mg/kg for the mature adults. One hour after injecting /sup 3/H-morphine at doses of 30 and 100 mg/kg, 0.13 and 0.14% of the doses appeared in brains of aged and mature adult mice, respectively. Regional distribution of the morphine was the same for both age groups. Expressed as percent of total brain morphine, it was as follows: cortex, 30%; midbrain, 18%; cerebellum, 17%; medulla, 12%; pons, 9%; striatum, 8% and periaqueductal gray, 6%. Expressed as g morphine/g tissue for the 2 doses, the distribution was; periaqueductal gray, 30 and 80; striatum, 9 and 34; medulla, 6 and 20 pons; 5 and 19; cerebellum, 4 and 13; midbrain 2.5 and 8.5 and cortex, 2 and 8. These results suggest that the differences in response to morphine by the two age groups were due to age-related differences in opioid receptor populations and/or affinities.

  18. Neonatal oxygen adversely affects lung function in adult mice without altering surfactant composition or activity

    OpenAIRE

    Yee, Min; Chess, Patricia R.; McGrath-Morrow, Sharon A.; Wang, Zhengdong; Gelein, Robert; Zhou, Rui; Dean, David A.; Notter, Robert H.; O'Reilly, Michael A.

    2009-01-01

    Despite its potentially adverse effects on lung development and function, supplemental oxygen is often used to treat premature infants in respiratory distress. To understand how neonatal hyperoxia can permanently disrupt lung development, we previously reported increased lung compliance, greater alveolar simplification, and disrupted epithelial development in adult mice exposed to 100% inspired oxygen fraction between postnatal days 1 and 4. Here, we investigate whether oxygen-induced changes...

  19. Repeated inhalation of crack-cocaine affects spermatogenesis in young and adult mice.

    Science.gov (United States)

    Pires, A; Pieri, P; Hage, M; Santos, A B G; Medeiros, M C R; Garcia, R C T; Yonamine, M; Hallak, J; Saldiva, P H N; Zorzetto, J C; Bueno, H M S

    2012-06-01

    To investigate the effects of repeated crack-cocaine inhalation on spermatogenesis of pubertal and mature Balb/c mice, ten young (Y(ex)) and ten adult (A(ex)) Balb/c mice were exposed to the smoke from 5 g of crack with 57.7% of pure cocaine in an inhalation chamber, 5 days/week for 2 months. The young (Y(c)) and adult (A(c)) control animals (n = 10) were kept in a specially built and controlled animal house facility. The morphologic analysis of both testes of all animals included the analysis of quantitative and qualitative histologic parameters to assess the effect of crack-cocaine on spermatogenesis and Leydig cells. Apoptosis was determined by immunolabeling with caspase-3 antibodies. Compared to the Y(c) animals, Y(ex) animals showed a significant reduction in the number of stage VII tubules per testis (p = 0.02), Sertoli cells (p cocaine smoke inhalation induced spermatogenesis disruption in chronically exposed mice, particularly in pubertal mice. PMID:22642293

  20. Theory of hantavirus infection spread incorporating localized adult and itinerant juvenile mice

    Science.gov (United States)

    Kenkre, V. M.; Giuggioli, L.; Abramson, G.; Camelo-Neto, G.

    2007-02-01

    A generalized model of the spread of the Hantavirus in mice populations is presented on the basis of recent observational findings concerning the movement characteristics of the mice that carry the infection. The factual information behind the generalization is based on mark-recapture observations reported in Giuggioli et al. [Bull. Math. Biol. 67, 1135 (2005)] that have necessitated the introduction of home ranges in the simple model of Hantavirus spread presented by Abramson and Kenkre [Phys. Rev. E 66, 11912 (2002)]. The essential feature of the model presented here is the existence of adult mice that remain largely confined to locations near their home ranges, and itinerant juvenile mice that are not so confined, and, during their search for their own homes, move and infect both other juveniles and adults that they meet during their movement. The model is presented at three levels of description: mean field, kinetic and configuration. Results of calculations are shown explicitly from the mean field equations and the simulation rules, and are found to agree in some respects and to differ in others. The origin of the differences is shown to lie in spatial correlations. It is indicated how mark-recapture observations in the field may be employed to verify the applicability of the theory.

  1. Flt3 Ligand Regulates the Development of Innate Lymphoid Cells in Fetal and Adult Mice.

    Science.gov (United States)

    Baerenwaldt, Anne; von Burg, Nicole; Kreuzaler, Matthias; Sitte, Selina; Horvath, Edit; Peter, Annick; Voehringer, David; Rolink, Antonius G; Finke, Daniela

    2016-03-15

    Flt3 ligand (Flt3L) promotes survival of lymphoid progenitors in the bone marrow and differentiation of dendritic cells (DCs), but its role in regulating innate lymphoid cells (ILCs) during fetal and adult life is not understood. By using Flt3L knockout and transgenic mice, we demonstrate that Flt3L controls ILC numbers by regulating the pool of α4β7(-) and α4β7(+) lymphoid tissue inducer cell progenitors in the fetal liver and common lymphoid progenitors in the bone marrow. Deletion of flt3l severely reduced the number of fetal liver progenitors and lymphoid tissue inducer cells in the neonatal intestine, resulting in impaired development of Peyer's patches. In the adult intestine, NK cells and group 2 and 3 ILCs were severely reduced. This effect occurred independently of DCs as ILC numbers were normal in mice in which DCs were constitutively deleted. Finally, we could show that administration of Flt3L increased the number of NKp46(-) group 3 ILCs in wild-type and even in Il7(-/-) mice, which generally have reduced numbers of ILCs. Taken together, Flt3L significantly contributes to ILC and Peyer's patches development by targeting lymphoid progenitor cells during fetal and adult life. PMID:26851220

  2. Urinary bladder hypersensitivity and dysfunction in female mice following early life and adult stress.

    Science.gov (United States)

    Pierce, Angela N; Di Silvestro, Elizabeth R; Eller, Olivia C; Wang, Ruipeng; Ryals, Janelle M; Christianson, Julie A

    2016-05-15

    Early adverse events have been shown to increase the incidence of interstitial cystitis/painful bladder syndrome in adulthood. Despite high clinical relevance and reports of stress-related symptom exacerbation, animal models investigating the contribution of early life stress to female urological pain are lacking. We examined the impact of neonatal maternal separation (NMS) on bladder sensitivity and visceral neuroimmune status both prior-to, and following, water avoidance stress (WAS) in adult female mice. The visceromotor response to urinary bladder distension was increased at baseline and 8d post-WAS in NMS mice, while colorectal sensitivity was transiently increased 1d post-WAS only in naïve mice. Bladder micturition rate and output, but not fecal output, were also significantly increased following WAS in NMS mice. Changes in gene expression involved in regulating the stress response system were observed at baseline and following WAS in NMS mice, and WAS reduced serum corticosterone levels. Cytokine and growth factor mRNA levels in the bladder, and to a lesser extent in the colon, were significantly impacted by NMS and WAS. Peripheral mRNA levels of stress-responsive receptors were differentially influenced by early life and adult stress in bladder, but not colon, of naïve and NMS mice. Histological evidence of mast cell degranulation was increased in NMS bladder, while protein levels of protease activated receptor 2 (PAR2) and transient receptor potential ankyrin 1 (TRPA1) were increased by WAS. Together, this study provides new insight into mechanisms contributing to stress associated symptom onset or exacerbation in patients exposed to early life stress. PMID:26940840

  3. Effects of Kerack used in addict Iranian people on fertility of adult mice

    Directory of Open Access Journals (Sweden)

    Mehdi Amini

    2013-08-01

    Full Text Available Background: Infertility is one of the most serious social problems. Illicit drug use can be an important cause of male factor infertility. Kerack which its use is rising up in Iran refers to a high purity street-level heroin (heroin Kerack. Heroin Kerack used in Iran is an opioid and has harmful effects on body organs. The aim of this study is to investigate the effects of Kerack used in Iran on fertility adult mice.Methods: In this study, 25 male mice were divided into five groups (control, sham and three experimental. Experimental groups of Kerack-dependent mice (received ascend-ing dose of Kerack for seven days were divided into three categories, experimental I, II and III. Experimental I was given Kerack at a dose of 5 mg/kg, experimental II 35 mg/kg and experimental III 70 mg/kg, intraperitoneally twice a day for a period of 35 days. The sham group received normal saline and lemon juice (2.6 µl/ml whilst the control group just received water and food. Mice were then scarified and sperm removed from cauda epididymis were analyzed for sperm count, motility, morphology (normal/abnormal and viability. Testes were also removed, weighed and processed for light microscopic studies.Results: The results showed that fertility were significantly decreased in addicted mice compared with control groups (P≤0.05. Epididymal sperm parameters and thickness of seminiferous epithelium were significantly decreased in experimental groups (dose-dependent compared with sham and control groups (P≤0.05. Gonadosomatic index was significantly reduced with high dose Kerack injected (70 mg/kg in comparison with control testes (P≤0.05.Conclusion: This study has shown the deleterious effects of Kerack used in addicted Iranian people on fertility for the first time. This effect is especially on epididymal sperm parameters in adult mice.

  4. Developmental Exposure to Xenoestrogens at Low Doses Alters Femur Length and Tensile Strength in Adult Mice1

    OpenAIRE

    Pelch, Katherine E.; Carleton, Stephanie M.; Phillips, Charlotte L.; Nagel, Susan C.

    2011-01-01

    Developmental exposure to high doses of the synthetic xenoestrogen diethylstilbestrol (DES) has been reported to alter femur length and strength in adult mice. However, it is not known if developmental exposure to low, environmentally relevant doses of xenoestrogens alters adult bone geometry and strength. In this study we investigated the effects of developmental exposure to low doses of DES, bisphenol A (BPA), or ethinyl estradiol (EE2) on bone geometry and torsional strength. C57BL/6 mice ...

  5. Glutamate neurotransmission is affected in prenatally stressed offspring

    DEFF Research Database (Denmark)

    Adrover, Ezequiela; Pallarés, Maria Eugenia; Baier, Carlos Javier;

    2015-01-01

    Previous studies from our laboratory have shown that male adult offspring of stressed mothers exhibited higher levels of ionotropic and metabotropic glutamate receptors than control rats. These offspring also showed long-lasting astroglial hypertrophy and a reduced dendritic arborization with syn...

  6. Complex life cycles and offspring provisioning in marine invertebrates.

    Science.gov (United States)

    Marshall, Dustin J; Keough, Michael J

    2006-10-01

    Offspring size can have pervasive effects throughout an organism's life history. Mothers can make either a few large or many small offspring, and the balance between these extremes is determined by the relationship between offspring size and performance. This relationship in turn is thought to be determined by the offspring's environment. Recently, it has become clear that events in one life-history stage can strongly affect performance in another. Given these strong carryover effects, we asked whether events in the larval phase can change the relationship between offspring size and performance in the adult phase. We manipulated the length of the larval period in the bryozoan Bugula neritina and then examined the relationship between offspring size and various parameters of adult performance under field conditions. We found that despite the adult stage being outplanted into identical conditions, different offspring sizes were predicted to be optimal, depending on the experience of those adults as larvae. This work highlights the fact that the strong phenotypic links between life-history stages may result in optimal offspring size being highly unpredictable for organisms with complex life cycles. PMID:21672775

  7. Sex-specific positive and negative consequences of avoidance training during childhood on adult active avoidance learning in mice

    Directory of Open Access Journals (Sweden)

    Almuth Spröwitz

    2013-10-01

    The experiments revealed a clear sex difference in the group of late-adolescent mice: female mice showed better avoidance learning during late adolescence compared to males, and the beneficial impact of late-adolescent pretraining on adult learning was more pronounced in females compared to males.

  8. The effects of co-administration of opium and morphine with nicotine during pregnancy on spatial learning and memory of adult male offspring rats

    OpenAIRE

    Gholamreza Sepehri; Shahrnaz Parsania; Mousa‐Al‐Reza Hajzadeh; Tahereh Haghpanah; Vahid Sheibani; Kouros Divsalar; Shahnaz Shekarforoush; Mohammad Reza Afarinesh

    2014-01-01

    Objective(s): Smoking opium/cigarette is a global health concern. The aim of this study was to examine learning and memory of rat male offsprings whose mothers had been exposed to either opium or morphine with nicotine during pregnancy. Materials and Methods: Wistar rats were used for the experiments. In the female rats, opium, morphine and nicotine dependencies were induced by daily injections of drug solution for 10 days before mating. Spatial memory was tested by Morris water maze test in ...

  9. Early life stress differentially modulates distinct forms of brain plasticity in young and adult mice.

    Directory of Open Access Journals (Sweden)

    Inga Herpfer

    Full Text Available BACKGROUND: Early life trauma is an important risk factor for many psychiatric and somatic disorders in adulthood. As a growing body of evidence suggests that brain plasticity is disturbed in affective disorders, we examined the short-term and remote effects of early life stress on different forms of brain plasticity. METHODOLOGY/PRINCIPAL FINDINGS: Mice were subjected to early deprivation by individually separating pups from their dam in the first two weeks after birth. Distinct forms of brain plasticity were assessed in the hippocampus by longitudinal MR volumetry, immunohistochemistry of neurogenesis, and whole-cell patch-clamp measurements of synaptic plasticity. Depression-related behavior was assessed by the forced swimming test in adult animals. Neuropeptides and their receptors were determined by real-time PCR and immunoassay. Early maternal deprivation caused a loss of hippocampal volume, which returned to normal in adulthood. Adult neurogenesis was unaffected by early life stress. Long-term synaptic potentiation, however, was normal immediately after the end of the stress protocol but was impaired in adult animals. In the forced swimming test, adult animals that had been subjected to early life stress showed increased immobility time. Levels of substance P were increased both in young and adult animals after early deprivation. CONCLUSION: Hippocampal volume was affected by early life stress but recovered in adulthood which corresponded to normal adult neurogenesis. Synaptic plasticity, however, exhibited a delayed impairment. The modulation of synaptic plasticity by early life stress might contribute to affective dysfunction in adulthood.

  10. Excretory/secretory products from Trichinella spiralis adult worms ameliorate DSS-induced colitis in mice.

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    Xiaodi Yang

    Full Text Available BACKGROUND: Many evidences show the inverse correlation between helminth infection and allergic or autoimmune diseases. Identification and characterization of the active helminth-derived products responsible for the beneficial effects on allergic or inflammatory diseases will provide another feasible approach to treat these diseases. METHODS AND FINDINGS: Colitis was induced in C57BL/6 mice by giving 3% DSS orally for 7 days. During this period, the mice were treated daily with the excretory/secretory products from T. spiralis adult worms (AES intraperitoneally. The severity of colitis was monitored by measuring body weight, stool consistency or bleeding, colon length and inflammation. To determine the T. spiralis AES product-induced immunological response, Th1, Th2, Th17 and regulatory cytokine profiles were measured in lymphocytes isolated from colon, mesenteric lymph nodes (MLN, and the spleen of treated mice. The CD4+ CD25+ FOXP3+ regulatory T cells (Tregs were also measured in the spleens and MLN of treated mice. Mice treated with AES significantly ameliorated the severity of the DSS-induced colitis indicated by the reduced disease manifestations, improved macroscopic and microscopic inflammation correlated with the up-regulation of Treg response (increased regulatory cytokines IL-10, TGF-beta and regulatory T cells and down-regulation of pro-inflammatory cytokines (IFN-gamma, IL-6 and IL-17 in the spleens, MLN and colon of treated mice. CONCLUSIONS: Our results provide direct evidences that T. spiralis AES have a therapeutic potential for alleviating inflammatory colitis in mice. This effect is possibly mediated by the immunomodulation of regulatory T cells to produce regulatory and anti-inflammatory cytokines and inhibit pro-inflammatory cytokines.

  11. Re-expression of IGF-II is important for beta cell regeneration in adult mice.

    Directory of Open Access Journals (Sweden)

    Luxian Zhou

    Full Text Available BACKGROUND: The key factors which support re-expansion of beta cell numbers after injury are largely unknown. Insulin-like growth factor II (IGF-II plays a critical role in supporting cell division and differentiation during ontogeny but its role in the adult is not known. In this study we investigated the effect of IGF-II on beta cell regeneration. METHODOLOGY/PRINCIPAL FINDINGS: We employed an in vivo model of 'switchable' c-Myc-induced beta cell ablation, pIns-c-MycER(TAM, in which 90% of beta cells are lost following 11 days of c-Myc (Myc activation in vivo. Importantly, such ablation is normally followed by beta cell regeneration once Myc is deactivated, enabling functional studies of beta cell regeneration in vivo. IGF-II was shown to be re-expressed in the adult pancreas of pIns-c-MycER(TAM/IGF-II(+/+ (MIG mice, following beta cell injury. As expected in the presence of IGF-II beta cell mass and numbers recover rapidly after ablation. In contrast, in pIns-c-MycER(TAM/IGF-II(+/- (MIGKO mice, which express no IGF-II, recovery of beta cell mass and numbers were delayed and impaired. Despite failure of beta cell number increase, MIGKO mice recovered from hyperglycaemia, although this was delayed. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that beta cell regeneration in adult mice depends on re-expression of IGF-II, and supports the utility of using such ablation-recovery models for identifying other potential factors critical for underpinning successful beta cell regeneration in vivo. The potential therapeutic benefits of manipulating the IGF-II signaling systems merit further exploration.

  12. Effect of voluntary running on adult hippocampal neurogenesis in cholinergic lesioned mice

    Directory of Open Access Journals (Sweden)

    Dawe Gavin S

    2009-06-01

    Full Text Available Abstract Background Cholinergic neuronal dysfunction of the basal forebrain is observed in patients with Alzheimer's disease and dementia, and has been linked to decreased neurogenesis in the hippocampus, a region involved in learning and memory. Running is a robust inducer of adult hippocampal neurogenesis. This study aims to address the effect of running on hippocampal neurogenesis in lesioned mice, where septohippocampal cholinergic neurones have been selectively eliminated in the medial septum and diagonal band of Broca of the basal forebrain by infusion of mu-p75-saporin immunotoxin. Results Running increased the number of newborn cells in the dentate gyrus of the hippocampus in cholinergic denervated mice compared to non-lesioned mice 24 hours after injection of bromodeoxyuridine (BrdU. Although similar levels of surviving cells were present in cholinergic depleted animals and their respective controls four weeks after injection of BrdU, the majority of progenitors that proliferate in response to the initial period of running were not able to survive beyond one month without cholinergic input. Despite this, the running-induced increase in the number of surviving neurones was not affected by cholinergic depletion. Conclusion The lesion paradigm used here models aspects of the cholinergic deficits associated with Alzheimer's Disease and aging. We showed that running still increased the number of newborn cells in the adult hippocampal dentate gyrus in this model of neurodegenerative disease.

  13. Constrained tibial vibration does not produce an anabolic bone response in adult mice.

    Science.gov (United States)

    Christiansen, Blaine A; Kotiya, Akhilesh A; Silva, Matthew J

    2009-10-01

    and exposure to anesthesia was associated with significant loss of trabecular and cortical bone. We conclude that direct vibrational loading of bone in anesthetized, adult mice is not anabolic. PMID:19576309

  14. Abnormal motor phenotype at adult stages in mice lacking type 2 deiodinase.

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    Soledad Bárez-López

    Full Text Available BACKGROUND: Thyroid hormones have a key role in both the developing and adult central nervous system and skeletal muscle. The thyroid gland produces mainly thyroxine (T4 but the intracellular concentrations of 3,5,3'-triiodothyronine (T3; the transcriptionally active hormone in the central nervous system and skeletal muscle are modulated by the activity of type 2 deiodinase (D2. To date no neurological syndrome has been associated with mutations in the DIO2 gene and previous studies in young and juvenile D2-knockout mice (D2KO did not find gross neurological alterations, possibly due to compensatory mechanisms. AIM: This study aims to analyze the motor phenotype of 3-and-6-month-old D2KO mice to evaluate the role of D2 on the motor system at adult stages in which compensatory mechanisms could have failed. RESULTS: Motor abilities were explored by validated tests. In the footprint test, D2KO showed an altered global gait pattern (mice walked slower, with shorter strides and with a hindlimb wider base of support than wild-type mice. No differences were detected in the balance beam test. However, a reduced latency to fall was found in the rotarod, coat-hanger and four limb hanging wire tests indicating impairment on coordination and prehensile reflex and a reduction of muscle strength. In histological analyses of cerebellum and skeletal muscle, D2KO mice did not present gross structural abnormalities. Thyroid hormones levels and deiodinases activities were also determined. In D2KO mice, despite euthyroid T3 and high T4 plasma levels, T3 levels were significantly reduced in cerebral cortex (48% reduction and skeletal muscle (33% reduction, but not in the cerebellum where other deiodinase (type 1 is expressed. CONCLUSIONS: The motor alterations observed in D2KO mice indicate an important role for D2 in T3 availability to maintain motor function and muscle strength. Our results suggest a possible implication of D2 in motor disorders.

  15. Comparison of catalase immunoreactivity in the hippocampus between young, adult and aged mice and rats.

    Science.gov (United States)

    Ahn, Ji Hyeon; Chen, Bai Hui; Shin, Bich-Na; Lee, Tae-Kyeong; Cho, Jeong Hwi; Kim, In Hye; Park, Joon Ha; Lee, Jae-Chul; Tae, Hyun-Jin; Lee, Choong-Hyun; Won, Moo-Ho; Lee, Yun Lyul; Choi, Soo Young; Hong, Seongkweon

    2016-07-01

    Catalase (CAT) is an important antioxidant enzyme and is crucial in modulating synaptic plasticity in the brain. In this study, CAT expression as well as neuronal distribution was compared in the hippocampus among young, adult and aged mice and rats. Male ICR mice and Sprague Dawley rats were used at postnatal month (PM) 1, PM 6 and PM 24 as the young, adult and aged groups, respectively (n=14/group). CAT expression was examined by immunohistochemistry and western blot analysis. In addition, neuronal distribution was examined by NeuN immunohistochemistry. In the present study, the mean number of NeuN‑immunoreactive neurons was marginally decreased in mouse and rat hippocampi during aging, although this change was not identified to be significantly different. However, CAT immunoreactivity was significantly increased in pyramidal and granule neurons in the adult mouse and rat hippocampi and was significantly decreased in the aged mouse and rat hippocampi compared with that in the young animals. CAT protein levels in the hippocampus were also lowest in the aged mouse and rat hippocampus. These results indicate that CAT expression is significantly decreased in the hippocampi of aged animals and decreased CAT expression may be closely associated with aging. PMID:27221506

  16. The Effect of the Postnatal Environment on Altered Fetal Programming of Adult Vascular Function in Mice Lacking Endothelial Nitic Oxide Synthase

    Science.gov (United States)

    Clark, Shannon M.; Makhlouf, Michel; Hankins, Gary D.V.; Anderson, Garland D.; Saade, George R.; Longo, Monica

    2007-01-01

    Objective: To investigate vascular reactivity in heterozygous and homozygous offspring with a genetic predisposition for hypertension after postnatal cross fostering to mothers with the opposite genetic inheritance of the NOS3 knockout allele. Study design: Homozygous NOS3 knockout (C57BL/6J-NOS3−/−KO) and wild-type mice (NOS3+/+WT) were bred to obtain heterozygous litters with a paternally-derived (NOS3+/−pat) or maternally-derived (NOS3+/−mat) knockout allele. After delivery, heterozygous and homozygous litters were cross fostered to a mother with the opposite NOS3 gene status. Carotid arteries were placed in a wire myograph for isometric tension recording using contractile and relaxant agents. Statistical analysis with One-Way ANOVA and Neuman-Keuls post-hoc testing was performed. Results: Increased sensitivity to phenylephrine and absent relaxation to acetycholine in NOS3+/−mat was reversed with cross-fostering and vasorelaxation to isoproteronol was increased. Contraction to calcium was increased in the cross fostered paternally-derived and wild-type litters. Conclusion: Postnatal interventions may favorably alter the adult vascular profile resulting from an abnormal intrauterine environment. PMID:17403420

  17. Risk of emotional disorder in offspring of depressed parents: Gender differences in the effect of a second emotionally affected parent

    OpenAIRE

    Landman-Peeters, K.M.; Ormel, J.; van Sonderen, E.L.; Den Boer, J A; Minderaa, R. B.; Hartman, C.A.

    2008-01-01

    In offspring of depressed parents a second parent with emotional problems is likely to increase risk of emotional disorder. This effect may however differ between sons and daughters and between offspring of depressed fathers and offspring of depressed mothers. In adolescent and young-adult offspring of parents with major depressive disorder, this study examined the effects of a second affected parent, offspring gender, gender of the depressed parent and their interactions on risk of depressio...

  18. Effects of postnatal alcohol exposure on hippocampal gene expression and learning in adult mice.

    Science.gov (United States)

    Lee, Dong Hoon; Moon, Jihye; Ryu, Jinhyun; Jeong, Joo Yeon; Roh, Gu Seob; Kim, Hyun Joon; Cho, Gyeong Jae; Choi, Wan Sung; Kang, Sang Soo

    2016-04-28

    Fetal alcohol syndrome (FAS) is a condition resulting from excessive drinking by pregnant women. Symptoms of FAS include abnormal facial features, stunted growth, intellectual deficits and attentional dysfunction. Many studies have investigated FAS, but its underlying mechanisms remain unknown. This study evaluated the relationship between alcohol exposure during the synaptogenesis period in postnatal mice and subsequent cognitive function in adult mice. We delivered two injections, separated by 2 h, of ethanol (3 g/kg, ethanol/saline, 20% v/v) to ICR mice on postnatal day 7. After 10 weeks, we conducted a behavioral test, sacrificed the animals, harvested brain tissue and analyzed hippocampal gene expression using a microarray. In ethanol-treated mice, there was a reduction in brain size and decreased neuronal cell number in the cortex, and also cognitive impairment. cDNA microarray results indicated that 1,548 genes showed a > 2-fold decrease in expression relative to control, whereas 974 genes showed a > 2-fold increase in expression relative to control. Many of these genes were related to signal transduction, synaptogenesis and cell membrane formation, which are highlighted in our findings. PMID:26960969

  19. Development of the adult neurogenic niche in the hippocampus of mice

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    Zeina eNicola

    2015-05-01

    Full Text Available When does adult hippocampal neurogenesis begin? We describe the development of the neurogenic niche in the subgranular zone (SGZ of the hippocampal dentate gyrus. We did so from the perspective of the situation in the adult.Ontogeny of the dentate gyrus is complex and results in an ectopic neurogenic niche that lifelong generates new granule cells. Neurogenesis during the fetal and early postnatal periods builds the dentate gyrus and gives way to activity-dependent adult neurogenesis. We used markers most relevant to adult neurogenesis research to describe this transition: Nestin, Sox2, BLBP, GFAP, Tbr2, Doublecortin (DCX, NeuroD1 and Prox1. We found that massive changes and a local condensation of proliferating precursor cells occurs between postnatal day 7 (P7, near the peak in proliferation, and P14. Before and around P7, the spatial distribution of cells and the co-localization of markers were distinct from the situation in the adult. Unlike the adult SGZ, the marker pair Nestin/Sox2 and the radial glial marker BLBP were not overlapping during embryonic development, presumably indicating different types of radial glia-like cells. Before P7 GFAP-positive cells in the hilus lacked the radial orientation that is characteristic of the adult type-1 cells. DCX, which is concentrated in type-2b and type-3 progenitor cells and early postmitotic neurons in the adult, showed diffuse expression before P7. Intermediate progenitor cell marker Tbr2 became restricted to the SGZ but was found in the granule cell layer and hilus before. Lineage markers NeuroD1 and Prox1 confirmed this pattern.We conclude that the neurogenic niche of adult neurogenesis is in place well before true adulthood. This might indicate that consistent with the hypothesized function of adult neurogenesis in activity-dependent plasticity, the early transition from postnatal neurogenesis to adult neurogenesis coincides with the time, when the young mice start to become active themselves.

  20. Dermal dysplasia, hypotrichosis, and dorsal skin ulcers in adult NMRI-mice after X-irradiation in utero

    International Nuclear Information System (INIS)

    Prenatal X-irradiation in mice leads to a marked incidence of hypotrichosis and alopecia in offspring, when irradiation occurs during the stage of late organogenesis (day 11-13 p.c.). In addition, severe ulcerative dermatitis occurs in offspring starting at 2 months of age, with marked preference for those animals which have been irradiated at least during days 11-13 p.c. This occurs without any dose dependence; application of doses between 2.4 Gy and 7.2 Gy results in approximately similar incidence rates of skin ulcers (range between 39.1 and 48.0%). There is no sex preference and no dependence on housing. At autopsy no special abnormalities were found in the internal organs with the exception of frequent signs of amyloidosis. This disease pattern could also be produced in germ-free animals. The intracutanous administration of skin extracts from affected animals into unirradiated mice leads to a marked infiltration of leukocytes. It is therefore suggested that prenatal X-irradiation induces a distinct dysplasia of the epidermis, which is followed by an endogenous leukotactic activity. (orig.)

  1. Evaluation of antioxidant effects of crocin on sperm quality in cyclophosphamide treated adult mice

    OpenAIRE

    Bakhtiary, Zahra; Shahrooz, Rasoul; Ahmadi, Abbas; Zarei, Leila

    2014-01-01

    Cyclophosphamide (CP) is one of the anti-neoplastic drugs. Despite its numerous clinical applications, it has devastating effects on the testicles and declines the sperm quality in treated patients. This study was aimed to investigate the protective effect of crocin in improving the toxicity induced by CP in reproductive system. In this study, 24 male adult mice (6 to 8 weeks) were randomly divided into three groups, control group received normal saline (0.1 mL, IP, daily), the CP group recei...

  2. Distinct Effects of Chronic Dopaminergic Stimulation on Hippocampal Neurogenesis and Striatal Doublecortin Expression in Adult Mice

    Science.gov (United States)

    Salvi, Rachele; Steigleder, Tobias; Schlachetzki, Johannes C. M.; Waldmann, Elisabeth; Schwab, Stefan; Winner, Beate; Winkler, Jürgen; Kohl, Zacharias

    2016-01-01

    While adult neurogenesis is considered to be restricted to the hippocampal dentate gyrus (DG) and the subventricular zone (SVZ), recent studies in humans and rodents provide evidence for newly generated neurons in regions generally considered as non-neurogenic, e.g., the striatum. Stimulating dopaminergic neurotransmission has the potential to enhance adult neurogenesis in the SVZ and the DG most likely via D2/D3 dopamine (DA) receptors. Here, we investigated the effect of two distinct preferential D2/D3 DA agonists, Pramipexole (PPX), and Ropinirole (ROP), on adult neurogenesis in the hippocampus and striatum of adult naïve mice. To determine newly generated cells in the DG incorporating 5-bromo-2′-deoxyuridine (BrdU) a proliferation paradigm was performed in which two BrdU injections (100 mg/kg) were applied intraperitoneally within 12 h after a 14-days-DA agonist treatment. Interestingly, PPX, but not ROP significantly enhanced the proliferation in the DG by 42% compared to phosphate buffered saline (PBS)-injected control mice. To analyze the proportion of newly generated cells differentiating into mature neurons, we quantified cells co-expressing BrdU and Neuronal Nuclei (NeuN) 32 days after the last of five BrdU injections (50 mg/kg) applied at the beginning of 14-days DA agonist or PBS administration. Again, PPX only enhanced neurogenesis in the DG significantly compared to ROP- and PBS-injected mice. Moreover, we explored the pro-neurogenic effect of both DA agonists in the striatum by quantifying neuroblasts expressing doublecortin (DCX) in the entire striatum, as well as in the dorsal and ventral sub-regions separately. We observed a significantly higher number of DCX+ neuroblasts in the dorsal compared to the ventral sub-region of the striatum in PPX-injected mice. These results suggest that the stimulation of hippocampal and dorsal striatal neurogenesis may be up-regulated by PPX. The increased generation of neural cells, both in constitutively active

  3. Distinct effects of chronic dopaminergic stimulation on hippocampal neurogenesis and striatal doublecortin expression in adult mice

    Directory of Open Access Journals (Sweden)

    Rachele eSalvi

    2016-03-01

    Full Text Available While adult neurogenesis is considered to be restricted to the hippocampal dentate gyrus (DG and the subventricular zone (SVZ, recent studies in humans and rodents provide evidence for newly generated neurons in regions generally considered as non-neurogenic, e.g. the striatum. Stimulating dopaminergic neurotransmission has the potential to enhance adult neurogenesis in the SVZ and the DG most likely via D2/D3 dopamine (DA receptors. Here, we investigated the effect of two distinct preferential D2/D3 DA agonists, Pramipexole (PPX and Ropinirole (ROP, on adult neurogenesis in the hippocampus and striatum of adult naïve mice. To determine newly generated cells in the DG incorporating 5-bromo-2'-deoxyuridine (BrdU a proliferation paradigm was performed in which two BrdU injections (100 mg/kg were applied intraperitoneally within 12 hours after a 14-day-DA agonist treatment. Interestingly, PPX, but not ROP significantly enhanced the proliferation in the DG by 42% compared to phosphate buffered saline (PBS-injected control mice. To analyze the proportion of newly generated cells differentiating into mature neurons, we quantified cells co-expressing BrdU and NeuN 32 days after the last of five BrdU injections (50 mg/kg applied at the beginning of 14-day DA agonist or PBS administration. Again, PPX only enhanced neurogenesis in the DG significantly compared to ROP- and PBS-injected mice. Moreover, we explored the pro-neurogenic effect of both DA agonists in the striatum by quantifying neuroblasts expressing doublecortin (DCX in the entire striatum, as well as in the dorsal and ventral sub-regions separately. We observed a significantly higher number of DCX+ neuroblasts in the dorsal compared to the ventral sub-region of the striatum in PPX-injected mice. These results suggest that the stimulation of hippocampal and dorsal striatal neurogenesis may be up-regulated by PPX. The increased generation of neural cells, both in constitutively active and

  4. Distinct Effects of Chronic Dopaminergic Stimulation on Hippocampal Neurogenesis and Striatal Doublecortin Expression in Adult Mice.

    Science.gov (United States)

    Salvi, Rachele; Steigleder, Tobias; Schlachetzki, Johannes C M; Waldmann, Elisabeth; Schwab, Stefan; Winner, Beate; Winkler, Jürgen; Kohl, Zacharias

    2016-01-01

    While adult neurogenesis is considered to be restricted to the hippocampal dentate gyrus (DG) and the subventricular zone (SVZ), recent studies in humans and rodents provide evidence for newly generated neurons in regions generally considered as non-neurogenic, e.g., the striatum. Stimulating dopaminergic neurotransmission has the potential to enhance adult neurogenesis in the SVZ and the DG most likely via D2/D3 dopamine (DA) receptors. Here, we investigated the effect of two distinct preferential D2/D3 DA agonists, Pramipexole (PPX), and Ropinirole (ROP), on adult neurogenesis in the hippocampus and striatum of adult naïve mice. To determine newly generated cells in the DG incorporating 5-bromo-2'-deoxyuridine (BrdU) a proliferation paradigm was performed in which two BrdU injections (100 mg/kg) were applied intraperitoneally within 12 h after a 14-days-DA agonist treatment. Interestingly, PPX, but not ROP significantly enhanced the proliferation in the DG by 42% compared to phosphate buffered saline (PBS)-injected control mice. To analyze the proportion of newly generated cells differentiating into mature neurons, we quantified cells co-expressing BrdU and Neuronal Nuclei (NeuN) 32 days after the last of five BrdU injections (50 mg/kg) applied at the beginning of 14-days DA agonist or PBS administration. Again, PPX only enhanced neurogenesis in the DG significantly compared to ROP- and PBS-injected mice. Moreover, we explored the pro-neurogenic effect of both DA agonists in the striatum by quantifying neuroblasts expressing doublecortin (DCX) in the entire striatum, as well as in the dorsal and ventral sub-regions separately. We observed a significantly higher number of DCX(+) neuroblasts in the dorsal compared to the ventral sub-region of the striatum in PPX-injected mice. These results suggest that the stimulation of hippocampal and dorsal striatal neurogenesis may be up-regulated by PPX. The increased generation of neural cells, both in constitutively active

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

    OpenAIRE

    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. Adu...

  6. Regulation of plasma lipid homeostasis by hepatic lipoprotein lipase in adult mice.

    Science.gov (United States)

    Liu, Gan; Xu, Jun-Nan; Liu, Dong; Ding, Qingli; Liu, Meng-Na; Chen, Rong; Fan, Mengdi; Zhang, Ye; Zheng, Chao; Zou, Da-Jin; Lyu, Jianxin; Zhang, Weiping J

    2016-07-01

    LPL is a pivotal rate-limiting enzyme to catalyze the hydrolysis of TG in circulation, and plays a critical role in regulating lipid metabolism. However, little attention has been paid to LPL in the adult liver due to its relatively low expression. Here we show that endogenous hepatic LPL plays an important physiological role in plasma lipid homeostasis in adult mice. We generated a mouse model with the Lpl gene specifically ablated in hepatocytes with the Cre/LoxP approach, and found that specific deletion of hepatic Lpl resulted in a significant decrease in plasma LPL contents and activity. As a result, the postprandial TG clearance was markedly impaired, and plasma TG and cholesterol levels were significantly elevated. However, deficiency of hepatic Lpl did not change the liver TG and cholesterol contents or glucose homeostasis. Taken together, our study reveals that hepatic LPL is involved in the regulation of plasma LPL activity and lipid homeostasis. PMID:27234787

  7. Maternal inheritance of severe hypertriglyceridemia impairs glucose metabolism in offspring

    Institute of Scientific and Technical Information of China (English)

    Ya-Hong Ma; Caiguo Yu; Abudurexiti Kayoumu; Xin Guo; Zhili Ji; George Liu

    2015-01-01

    Maternally inherited familial hypercholesterolemia (FH) impairs glucose metabolism and increases cardiovascular risks in the offspring to a greater degree than paternal inherited FH.However,it remains unknown whether hypertriglyceridemia affects glucose metabolism via inheritance.In this study,we sought to compare the impact of maternally and paternally inherited hypertriglyceridemia on glucose and lipid metabolism in mice.ApoCⅢ transgenic mice with severe hypertriglyceridemia were mated with non-transgenic control mice to obtain 4 types of offspring:maternal non-transgenic control and maternal transgenic offspring,and paternal control and paternal transgenic offspring.Plasma triglycerides (TG),total cholesterol (TC),fasting plasma glucose (FPG) and fasting insulin (FINS) were measured.ApoCⅢ overexpression caused severe hypertriglyceridemia,but the transgenic female mice had unaltered fertility with normal pregnancy and birth of pups.The 4 groups of offspring had similar birth weight and growth rate.The plasma TG of maternal and paternal transgenic offspring were nearly 40-fold higher than maternal and paternal control mice,but there was no difference in plasma TG between maternal and paternal transgenic offspring.Although the FPG of the 4 groups of animals had no difference,the maternal transgenic mice showed impaired glucose tolerance,increased FINS levels and higher homeostasis model assessment insulin resistance index (HOMA-IR) than the other 3 groups.In conclusion,maternally inherited hypertriglyceridemia in ApoCⅢ transgenic mice displayed impaired glucose tolerance,hyperinsulinemia and increased HOMA-R,while paternally inherited hypertriglyceridemia did not have such impacts.

  8. Developmental minocycline treatment reverses the effects of neonatal immune activation on anxiety- and depression-like behaviors, hippocampal inflammation, and HPA axis activity in adult mice.

    Science.gov (United States)

    Majidi, Jafar; Kosari-Nasab, Morteza; Salari, Ali-Akbar

    2016-01-01

    Neonatal infection is associated with increased lifetime risk for neuropsychiatric disorders including anxiety and depression, with evidence showing that dysregulation of the hypothalamic-pituitary-adrenal-(HPA)-axis system may be partly responsible. Preclinical and clinical studies demonstrate that minocycline exhibits antidepressant effects through inhibition of microglial activation and anti-inflammatory actions, and of interest is that recent studies suggest that minocycline alleviates the behavioral abnormalities induced by early-life insults. The current study was designed to determine if developmental minocycline treatment attenuates the neonatal immune activation-induced anxiety- and depression-like symptoms and HPA-axis-dysregulation later in life. To this end, neonatal mice were treated to either lipopolysaccharide or saline on postnatal days (PND) 3-5, then dams during lactation (PND 6-20) and male offspring during adolescence (PND 21-40) received oral administration of minocycline or water via regular drinking bottles. Anxiety- and depression-like behaviors, HPA-axis-reactivity (corticosterone), and hippocampal inflammation (TNF-α and IL-1β) after exposure to stress were evaluated. The results indicated that neonatal immune activation resulted in increased anxiety and depression-like symptoms, HPA-axis-hyperactivity, and elevated the levels of TNF-α and IL-1β in the hippocampus in response to stress in adulthood. Interestingly, developmental minocycline treatment significantly reduced the abnormalities induced by neonatal inflammation in adult mice. In addition, minocycline, regardless of postnatal inflammation, did not have any detrimental effects on the above measured parameters. Considering that minocycline is currently under exploration as an alternative or adjunctive therapy for reducing the symptoms of neurological disorders, our findings suggest that minocycline during development can decrease the behavioral abnormalities induced by early

  9. Evidence for physiological function of epidermal growth factor: pregestational sialoadenectomy of mice decreases milk production and increases offspring mortality during lactation period.

    OpenAIRE

    S. Okamoto; Oka, T

    1984-01-01

    Female virgin mice, whose submandibular glands were removed, underwent normal pregnancy and delivery. During the nursing period, however, a substantial number of pups born to and nursed by sialoadenectomized mothers died within 5 days of birth, whereas this did not occur among pups born to normal mothers. Cross-foster nursing experiments indicated that the cause of death of pups was to be found in sialoadenectomized mothers, not in the pups. The capacity of the sialoadenectomized mothers to n...

  10. Parental legacy in insects: variation of transgenerational immune priming during offspring development.

    Directory of Open Access Journals (Sweden)

    Ute Trauer

    Full Text Available In insects, a parental immune challenge can prepare and enhance offspring immune activity. Previous studies of such transgenerational immune priming (TGIP mainly focused on a single offspring life stage. However, different developmental stages may be exposed to different risks and show different susceptibility to parental immune priming. Here we addressed the question (i whether TGIP effects on the immunity of Manduca sexta offspring vary among the different developmental offspring stages. We differentiated between unchallenged and immunochallenged offspring; for the latter type of offspring, we further investigated (ii whether TGIP has an impact on the time that enhanced immune levels persist after offspring immune challenge. Finally, we determined (iii whether TGIP effects on offspring performance depend on the offspring stage. Our results show that TGIP effects on phenoloxidase (PO activity, but not on antibacterial activity, vary among unchallenged offspring stages. In contrast, TGIP effects on PO and antibacterial activity did not vary among immunochallenged offspring stages. The persistence of enhanced immune levels in immunochallenged offspring was dependent on the parental immune state. Antibacterial (but not PO activity in offspring of immunochallenged parents decreased over five days after pupal immune challenge, whereas no significant change over time was detectable in offspring of control parents. Finally, TGIP effects on the developmental time of unchallenged offspring varied among stages; young larvae of immunochallenged parents developed faster and gained more weight than larvae of control parents. However, offspring females of immunochallenged parents laid fewer eggs than females derived from control parents. These findings suggest that the benefits which the offspring gains from TGIP during juvenile development are paid by the adults with reduced reproductive power. Our study shows that TGIP effects vary among offspring stages

  11. Redox proteomic analysis of the gastrocnemius muscle from adult and old mice.

    Science.gov (United States)

    McDonagh, Brian; Sakellariou, Giorgos K; Smith, Neil T; Brownridge, Philip; Jackson, Malcolm J

    2015-09-01

    The data provides information in support of the research article, "Differential Cysteine Labeling and Global Label-Free Proteomics Reveals an Altered Metabolic State in Skeletal Muscle Aging", Journal of Proteome Research, 2014, 13 (11), 2008-21 [1]. Raw data is available from ProteomeXchange [2] with identifier PDX001054. The proteome of gastrocnemius muscle from adult and old mice was analyzed by global label-free proteomics and the relative quantification of specific reduced and reversibly oxidized Cysteine (Cys) residues was performed using Skyline [3]. Briefly, reduced Cysteine (Cys) containing peptides was alkylated using N-ethylmalemide (d0-NEM). Samples were desalted and reversibly oxidized Cys residues were reduced using tris(2-carboxyethyl)phosphine (TCEP) and the newly formed reduced Cys residues were labeled with heavy NEM( d5-NEM). Label-free analysis of the global proteome of adult (n=5) and old (n=4) gastrocnemius muscles was performed using Peaks7™ mass spectrometry data analysis software [4]. Relative quantification of Cys containing peptides that were identified as reduced (d(0) NEM labeled) and reversibly oxidized d(5)-NEM labeled was performed using the intensity of their precursor ions in Skyline. Results indicate that muscles from old mice show reduced redox flexibility particularly in proteins involved in the generation of precursor metabolites and energy metabolism, indicating a loss in the flexibility of the redox energy response. PMID:26217813

  12. The impact of Ly6Clow monocytes after cerebral hypoxia-ischemia in adult mice

    Science.gov (United States)

    Michaud, Jean-Philippe; Pimentel-Coelho, Pedro Moreno; Tremblay, Yannick; Rivest, Serge

    2014-01-01

    After an ischemic stroke, mononuclear phagocytic cells such as microglia, macrophages, and monocytes migrate to the lesion site and coordinate an immune response. Monocytes, which are recruited from the bloodstream after ischemic brain injury, can be categorized into two subsets in mice: inflammatory and patrolling monocytes. Although inflammatory monocytes (Ly6Chi) seem to have a protective role in stroke progression, the impact of patrolling monocytes (Ly6Clow) is unknown. To address the role of Ly6Clow monocytes in stroke, we generated bone marrow chimeric mice in which their hematopoietic system was replaced by Nr4a1−/− cells, allowing the complete and permanent ablation of Ly6Clow monocytes without affecting the Ly6Chi subset. We then subjected adult mice to cerebral hypoxia-ischemia using the Levine/Vannucci model. Functional outcomes after stroke such as body weight change, neurologic score, motor functions and spatial learning were not affected. Moreover, depletion in Ly6Clow monocytes did not change significantly the total infarct size, cell loss, atrophy, the number, or the activation state of microglia/macrophages at the lesion site. These data suggest that Ly6Clow patrolling monocytes are redundant in the progression and recovery of ischemic stroke. PMID:24780898

  13. Pregnancy rates, prenatal and postnatal survival of offspring, and litter sizes after reciprocal embryo transfer in DBA/2JHd, C3H/HeNCrl and NMRI mice.

    Science.gov (United States)

    Rose, C; Schwegler, H; Hanke, J; Yilmazer-Hanke, D M

    2012-06-01

    Success of embryo transfer is often a limiting factor in transgenic procedures and rederivation efforts, and depends on the genetic background of the donor and recipient strains used. Here we show that embryo transfer to DBA/2J females is possible, and present data on pre- and postnatal success rates after reciprocal embryo transfer using the inbred DBA/2J and C3H/HeN, and outbred NMRI strains. The highest embryo yield was achieved in outbred NMRI females, but embryo yields were similar in DBA/2J and C3H/HeN mice following superovulation despite poor estrus cycle synchronization in DBA/2J females. In-strain transfer of DBA/2J blastocysts (transfer of embryos to recipients from the same strain) resulted in pregnancy rates (57.1%) similar to those obtained following in-strain transfer of C3H/HeN (60.0%) and NMRI mice (83.3%), although the prenatal survival rate of blastocysts was low. Moreover, from the pups born only half survived the postnatal period after transfer of DBA/2J and C3H/HeN blastocysts to DBA/2J recipients. These problems were not observed when transferring NMRI-blastocysts to C3H/HeN and DBA/2J mothers. The number of blastocysts transferred also had a positive effect on the success of embryo transfer. In conclusion, C3H/HeN and DBA/2J females can be used as recipients for embryo transfer procedures for certain donor strains like NMRI, as one major determinant seems to be the genetic background of the embryos transferred. We also recommend to increase the number of DBA/2J blastocysts transferred, and to foster the DBA/2J pups to other DBA/2J mothers postnatally for in-strain transfer of DBA/2J mice. PMID:22401828

  14. Characteristics of Multi-Organ Lymphangiectasia Resulting from Temporal Deletion of Calcitonin Receptor-Like Receptor in Adult Mice

    OpenAIRE

    Hoopes, Samantha L.; Willcockson, Helen H.; Caron, Kathleen M.

    2012-01-01

    Adrenomedullin (AM) and its receptor complexes, calcitonin receptor-like receptor (Calcrl) and receptor activity modifying protein 2/3, are highly expressed in lymphatic endothelial cells and are required for embryonic lymphatic development. To determine the role of Calcrl in adulthood, we used an inducible Cre-loxP system to temporally and ubiquitously delete Calcrl in adult mice. Following tamoxifen injection, Calcrlfl/fl/CAGGCre-ER™ mice rapidly developed corneal edema and inflammation tha...

  15. Delayed and transient increase of adult hippocampal neurogenesis by physical exercise in DBA/2 mice.

    Directory of Open Access Journals (Sweden)

    Rupert W Overall

    Full Text Available This study builds on the findings that physical activity, such as wheel running in mice, enhances cell proliferation and neurogenesis in the adult hippocampus of the common mouse strain C57BL/6, and that the baseline level of neurogenesis varies by strain, being considerably lower in DBA/2. Because C57BL/6 and DBA/2 are important as the parental strains of the BXD recombinant inbred cross which allows the detection of genetic loci regulating phenotypes such as adult neurogenesis, we performed the current study to investigate the gene x environment interactions regulating neurogenesis. At equal distances and times run DBA/2J mice lacked the acute increase in precursor cell proliferation known from C57BL/6. In DBA/2J proliferation even negatively correlated with the distance run. This was neither due to a stress response (to running itself or single housing nor differences in estrous cycle. DBA/2 animals exhibited a delayed and weaker pro-neurogenic response with a significant increase in numbers of proliferating cells first detectable after more than a week of wheel running. The proliferative response to running was transient in both strains, the effect being undetectable by 6 weeks. There was also a small transient increase in the production of new neurons in DBA/2J, although these extra cells did not survive. These findings indicate that the comparison between C57BL/6 and DBA/2, and by extension the BXD genetic reference population derived from these strains, should provide a powerful tool for uncovering the complex network of modifier genes affecting the activity-dependent regulation of adult hippocampal neurogenesis. More generally, our findings also describe how the external physical environment interacts with the internal genetic environment to produce different responses to the same behavioral stimuli.

  16. Immunohistochemical localization of keratin 5 in the submandibular gland in adult and postnatal developing mice.

    Science.gov (United States)

    Yamamoto, Miyuki; Nakata, Hiroki; Kumchantuek, Tewarat; Sakulsak, Natthiya; Iseki, Shoichi

    2016-03-01

    Keratin 5 (K5) is a marker of basal progenitor cells in the epithelia of a number of organs. During prenatal development of the submandibular gland (SMG) in mice, K5(+) progenitor cells in the developing epithelia play important roles in its organogenesis. Although K5(+) cells are also present in the adult mouse SMG and may function in tissue regeneration, their histological localization has not yet investigated in detail. In the present study, we examined the immunohistochemical localization of K5 in the SMG in adult and postnatal developing mice. At birth, K5 immunoreactivity was detected in the entire duct system, in which it was localized in the basal cells of a double-layered epithelium, but was not detected in the terminal tubule or myoepithelial cells. At postnatal weeks 1-3, with the development of intercalated ducts (ID), striated ducts (SD), and excretory ducts (ED), K5-immunoreactive basal cells were gradually restricted to the ED and the proximal double-layered portions of the ID connecting to the SD. At the same time, K5 immunoreactivity appeared in myoepithelial cells, in which its positive ratio gradually increased. In adults, K5 immunoreactivity was localized to most myoepithelial cells, most basal cells in the ED, and a small number of ID cells at the boundary between the ID and SD in the female SMG or between the ID and granular convoluted tubules in the male SMG. These results suggest that K5 is a marker of differentiated myoepithelial cells and duct progenitor cells in the mouse SMG. PMID:26671786

  17. Adolescent mice are less sensitive to the effects of acute nicotine on context pre-exposure than adults.

    Science.gov (United States)

    Kutlu, Munir Gunes; Braak, David C; Tumolo, Jessica M; Gould, Thomas J

    2016-07-01

    Adolescence is a critical developmental period associated with both increased vulnerability to substance abuse and maturation of certain brain regions important for learning and memory such as the hippocampus. In this study, we employed a hippocampus-dependent learning context pre-exposure facilitation effect (CPFE) paradigm in order to test the effects of acute nicotine on contextual processing during adolescence (post-natal day (PND) 38) and adulthood (PND 53). In Experiment 1, adolescent or adult C57BL6/J mice received either saline or one of three nicotine doses (0.09, 0.18, and 0.36mg/kg) prior to contextual pre-exposure and testing. Our results demonstrated that both adolescent and adult mice showed CPFE in the saline groups. However, adolescent mice only showed acute nicotine enhancement of CPFE with the highest nicotine dose whereas adult mice showed the enhancing effects of acute nicotine with all three doses. In Experiment 2, to determine if the lack of nicotine's effects on CPFE shown by adolescent mice is specific to the age when they are tested, mice were either given contextual pre-exposure during adolescence or adulthood and received immediate shock and testing during adulthood after a 15day delay. We found that both adolescent and adult mice showed CPFE in the saline groups when tested during adulthood. However, like Experiment 1, mice that received contextual pre-exposure during adolescence did not show acute nicotine enhancement except at the highest dose (0.36mg/kg) whereas both low (0.09mg/kg) and high (0.36mg/kg) doses enhanced CPFE in adult mice. Finally, we showed that the enhanced freezing response found with 0.36mg/kg nicotine in the 15-day experiment may be a result of decreased locomotor activity as mice that received this dose of nicotine traveled shorter distances in an open field paradigm. Overall, our results indicate that while adolescent mice showed normal contextual processing when tested both during adolescence and adulthood, they

  18. Transcription factors FOXA1 and FOXA2 maintain dopaminergic neuronal properties and control feeding behavior in adult mice

    OpenAIRE

    Pristerà, A; Lin, W.; Kaufmann, AK; Brimblecombe, KR; Threlfell, S.; Dodson, PD; Magill, PJ; Fernandes, C; Cragg, SJ; Ang, SL

    2015-01-01

    Midbrain dopaminergic (mDA) neurons are implicated in cognitive functions, neuropsychiatric disorders, and pathological conditions; hence understanding genes regulating their homeostasis has medical relevance. Transcription factors FOXA1 and FOXA2 (FOXA1/2) are key determinants of mDA neuronal identity during development, but their roles in adult mDA neurons are unknown. We used a conditional knockout strategy to specifically ablate FOXA1/2 in mDA neurons of adult mice. We show that deletion ...

  19. Transcription factors FOXA1 and FOXA2 maintain dopaminergic neuronal properties and control feeding behavior in adult mice.

    OpenAIRE

    Pristerà, A; Lin, W.; Kaufmann, AK; Brimblecombe, KR; Threlfell, S.; Dodson, PD; Magill, PJ; Fernandes, C; Cragg, SJ; Ang, SL

    2015-01-01

    Midbrain dopaminergic (mDA) neurons are implicated in cognitive functions, neuropsychiatric disorders, and pathological conditions; hence understanding genes regulating their homeostasis has medical relevance. Transcription factors FOXA1 and FOXA2 (FOXA1/2) are key determinants of mDA neuronal identity during development, but their roles in adult mDA neurons are unknown. We used a conditional knockout strategy to specifically ablate FOXA1/2 in mDA neurons of adult mice. We show that deletion ...

  20. Cross-sectional association of dietary patterns with insulin-resistant phenotypes among adults without diabetes in the Framingham Offspring Study.

    Science.gov (United States)

    Liu, Enju; McKeown, Nicola M; Newby, P K; Meigs, James B; Vasan, Ramachandran S; Quatromoni, Paula A; D'Agostino, Ralph B; Jacques, Paul F

    2009-08-01

    Cluster analysis is a valuable tool for exploring the health consequences of consuming different dietary patterns. We used this approach to examine the cross-sectional relationship between dietary patterns and insulin-resistant phenotypes, including waist circumference, BMI, fasting insulin, 2 h post-challenge insulin, insulin sensitivity index (ISI0,120), HDL-cholesterol, TAG and blood pressure, using data from the fifth examination cycle of the Framingham Offspring Study. Among 2875 participants without diabetes, we identified four dietary patterns based on the predominant sources of energy: 'Fruits, Reduced Fat Dairy and Whole Grains', 'Refined Grains and Sweets', 'Beer' and 'Soda'. After adjusting for multiple comparisons and potential confounders, compared with the 'Fruits, Reduced Fat Dairy and Whole Grains' pattern, the 'Refined Grains and Sweets' pattern had significantly higher mean waist circumference (92.4 v. 90.5 cm; P = 0.008) and BMI (27.3 v. 26.6 kg/m2; P = 0.02); the 'Soda' pattern had significantly higher mean fasting insulin concentration (31.3 v. 28.0 microU/ml; P refined grains, high-fat dairy, sweet baked foods, candy and sugar-sweetened soda may promote insulin-resistant phenotypes. PMID:19216828

  1. Skeletal myofiber VEGF regulates contraction-induced perfusion and exercise capacity but not muscle capillarity in adult mice.

    Science.gov (United States)

    Knapp, Amy E; Goldberg, Daniel; Delavar, Hamid; Trisko, Breanna M; Tang, Kechun; Hogan, Michael C; Wagner, Peter D; Breen, Ellen C

    2016-07-01

    A single bout of exhaustive exercise signals expression of vascular endothelial growth factor (VEGF) in the exercising muscle. Previous studies have reported that mice with life-long deletion of skeletal myofiber VEGF have fewer capillaries and a severe reduction in endurance exercise. However, in adult mice, VEGF gene deletion conditionally targeted to skeletal myofibers limits exercise capacity without evidence of capillary regression. To explain this, we hypothesized that adult skeletal myofiber VEGF acutely regulates skeletal muscle perfusion during muscle contraction. A tamoxifen-inducible skeletal myofiber-specific VEGF gene deletion mouse (skmVEGF-/-) was used to reduce skeletal muscle VEGF protein by 90% in adult mice. Three weeks after inducing deletion of the skeletal myofiber VEGF gene, skmVEGF-/- mice exhibited diminished maximum running speed (-10%, P < 0.05) and endurance capacity (-47%; P < 0.05), which did not persist after 8 wk. In skmVEGF-/- mice, gastrocnemius complex time to fatigue measured in situ was 71% lower than control mice. Contraction-induced perfusion measured by optical imaging during a period of electrically stimulated muscle contraction was 85% lower in skmVEGF-/- than control mice. No evidence of capillary rarefication was detected in the soleus, gastrocnemius, and extensor digitorum longus (EDL) up to 8 wk after tamoxifen-induced VEGF ablation, and contractility and fatigue resistance of the soleus measured ex vivo were also unchanged. The force-frequency of the EDL showed a small right shift, but fatigue resistance did not differ between EDL from control and skmVEGF-/- mice. These data suggest myofiber VEGF is required for regulating perfusion during periods of contraction and may in this manner affect endurance capacity. PMID:27225953

  2. Dispase rapidly and effectively purifies Schwann cells from newborn mice and adult rats

    Institute of Scientific and Technical Information of China (English)

    Jiaxue Zhu; Jinbao Qin; Zunli Shen; James D. Kretlow; Xiaopan Wang; Zhangyin Liu; Yuqing Jin

    2012-01-01

    In the present study, Schwann cells were isolated from the sciatic nerve of neonatal mice and purified using dispase and collagenase. Results showed that after the first round of purification with dispase, most of the Schwann cells appeared round in shape and floated in culture solution after 15 minutes. In addition, cell yield and cell purity were higher when compared to the collagenase group. After the second round of purification, the final cell yield for the dispase group was higher than that for the collagenase group, but no significant difference was found in cell purity. Moreover, similar results in cell quantity and purity were observed in adult Sprague-Dawley rats. These findings indicate that purification with dispase can result in the rapid isolation of Schwann cells with a high yield and purity.

  3. Experimental evidence for offspring learning in parent-offspring communication.

    OpenAIRE

    Kedar, H; Rodríguez-Gironés, M A; Yedvab, S; Winkler, D.W.; Lotem, A

    2000-01-01

    The offspring of birds and mammals solicit food from their parents by a combination of movements and vocalizations that have come to be known collectively as 'begging'. Recently, begging has most often been viewed as an honest signal of offspring need. Yet, if offspring learn to adjust their begging efforts to the level that rewards them most, begging intensities may also reflect offsprings' past experience rather than their precise current needs. Here we show that bird nestlings with equal l...

  4. Memory-enhancing effects of Cuscuta japonica Choisy via enhancement of adult hippocampal neurogenesis in mice.

    Science.gov (United States)

    Moon, Minho; Jeong, Hyun Uk; Choi, Jin Gyu; Jeon, Seong Gak; Song, Eun Ji; Hong, Seon-Pyo; Oh, Myung Sook

    2016-09-15

    It is generally accepted that functional and structural changes within the hippocampus are involved in learning and memory and that adult neurogenesis in this region may modulate cognition. The extract of Cuscuta japonica Choisy (CJ) is a well-known traditional Chinese herbal medicine that has been used since ancient times as a rejuvenation remedy. The systemic effects of this herb are widely known and can be applied for the treatment of a number of physiological diseases, but there is a lack of evidence describing its effects on brain function. Thus, the present study investigated whether CJ would enhance memory function and/or increase hippocampal neurogenesis using mice orally administered with CJ water extract or vehicle for 21days. Performance on the novel object recognition and passive avoidance tests revealed that treatment with CJ dose-dependently improved the cognitive function of mice. Additionally, CJ increased the Ki-67-positive proliferating cells and the number of doublecortin-stained neuroblasts in the dentate gyrus (DG) of the hippocampus, and double labeling with 5-bromo-2-deoxyuridine and neuronal specific nuclear protein showed that CJ increased the number of mature neurons in the DG. Finally, CJ resulted in the upregulated expression of neurogenic differentiation factor, which is essential for the maturation and differentiation of granule cells in the hippocampus. Taken together, the present findings indicate that CJ stimulated neuronal cell proliferation, differentiation, and maturation, which are all processes associated with neurogenesis. Additionally, these findings suggest that CJ may improve learning and memory via the enhancement of adult hippocampal neurogenesis. PMID:27185736

  5. Dynamics of cell proliferation in the adult dentate gyrus of two inbred strains of mice

    Science.gov (United States)

    Hayes, N. L.; Nowakowski, R. S.

    2002-01-01

    The output potential of proliferating populations in either the developing or the adult nervous system is critically dependent on the length of the cell cycle (T(c)) and the size of the proliferating population. We developed a new approach for analyzing the cell cycle, the 'Saturate and Survive Method' (SSM), that also reveals the dynamic behaviors in the proliferative population and estimates of the size of the proliferating population. We used this method to analyze the proliferating population of the adult dentate gyrus in 60 day old mice of two inbred strains, C57BL/6J and BALB/cByJ. The results show that the number of cells labeled by exposure to BUdR changes dramatically with time as a function of the number of proliferating cells in the population, the length of the S-phase, cell division, the length of the cell cycle, dilution of the S-phase label, and cell death. The major difference between C57BL/6J and BALB/cByJ mice is the size of the proliferating population, which differs by a factor of two; the lengths of the cell cycle and the S-phase and the probability that a newly produced cell will die within the first 10 days do not differ in these two strains. This indicates that genetic regulation of the size of the proliferating population is independent of the genetic regulation of cell death among those newly produced cells. The dynamic changes in the number of labeled cells as revealed by the SSM protocol also indicate that neither single nor repeated daily injections of BUdR accurately measure 'proliferation.'.

  6. Adult but Not Aged C57BL/6 Male Mice Are Capable of Using Geometry for Orientation

    Science.gov (United States)

    Schachner, Melitta; Morellini, Fabio; Fellini, Laetitia

    2006-01-01

    Geometry, e.g., the shape of the environment, can be used by numerous animal species to orientate, but data concerning the mouse are lacking. We addressed the question of whether mice are capable of using geometry for navigating. To test whether aging could affect searching strategies, we compared adult (3- to 5-mo old) and aged (20- to 21-mo old)…

  7. Efficiency of AUY922 in mice with adult T-cell leukemia/lymphoma

    Science.gov (United States)

    ISHIKAWA, CHIE; SENBA, MASACHIKA; MORI, NAOKI

    2016-01-01

    Adult T-cell leukemia/lymphoma (ATLL) is an aggressive malignancy caused by human T-cell leukemia virus type 1 (HTLV-1). ATLL is associated with poor prognosis mainly due to resistance to chemotherapy, which highlights the requirement for alternative therapies. The chaperone heat shock protein (HSP) 90 assist proteins involved in the onset and progression of ATLL. In the present study, the efficacy of a second generation HSP90 inhibitor termed AUY922 was investigated in ATLL. In vitro, AUY922 induced marked inhibition of cell viability in the HTLV-1-infected T-cell lines HUT-102 and MT-4. In immunodeficient mice bearing HUT-102 xenotransplants, AUY922 markedly retarded tumor growth, compared with the control group. Apoptosis was evident in hematoxylin and eosin stained- and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling-labeled tissue sections from AUY922-treated mice. In addition, AUY922 significantly reduced the serum levels of the surrogate tumor markers soluble interleukin-2 receptor and soluble cluster of differentiation 30. Overall, the present results demonstrate that AUY922 has potent anti-ATLL activity, thus providing a rationale for continuing the clinical development of HSP90 inhibitors in clinical trials for the treatment of patients with ATLL. PMID:27347156

  8. Dopaminergic Modulation of Excitatory Transmission in the Anterior Cingulate Cortex of Adult Mice.

    Science.gov (United States)

    Darvish-Ghane, Soroush; Yamanaka, Manabu; Zhuo, Min

    2016-01-01

    Dopamine (DA) possesses potent neuromodulatory properties in the central nervous system. In the anterior cingulate cortex, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPAR) are key ion channels in mediating nerve injury induced long-term potentiation (LTP) and chronic pain phenotype. In the present study, we reported the effects of DA on glutamate mediated excitatory post-synaptic currents (EPSCs) in pyramidal neurons of layer II/III of the ACC in adult mice. Bath application of DA (50 μM) caused a significant, rapid and reversible inhibition of evoked EPSCs (eEPSC). This inhibitory effect is dose-related and was absent in lower concentration of DA (5 μM). Furthermore, selective postsynaptic application of GDP-β-S (1.6 mM) in the internal solution completely abolished the inhibitory effects of DA (50 μM). We also investigated modulation of spontaneous EPSCs (sEPSCs) and TTX sensitive, miniature EPSCs (mEPSCs) by DA. Our results indicated mixed effects of potentiation and inhibition of frequency and amplitude for sEPSCs and mEPSCs. Furthermore, high doses of SCH23390 (100 μM) and sulpiride (100 μM) revealed that, inhibition of eEPSCs is mediated by postsynaptic D2-receptors (D2R). Our finding posits a pre- and postsynaptic mode of pyramidal neuron EPSC modulation in mice ACC by DA. PMID:27317578

  9. Cellular origins of cold-induced brown adipocytes in adult mice.

    Science.gov (United States)

    Lee, Yun-Hee; Petkova, Anelia P; Konkar, Anish A; Granneman, James G

    2015-01-01

    This work investigated how cold stress induces the appearance of brown adipocytes (BAs) in brown and white adipose tissues (WATs) of adult mice. In interscapular brown adipose tissue (iBAT), cold exposure increased proliferation of endothelial cells and interstitial cells expressing platelet-derived growth factor receptor, α polypeptide (PDGFRα) by 3- to 4-fold. Surprisingly, brown adipogenesis and angiogenesis were largely restricted to the dorsal edge of iBAT. Although cold stress did not increase proliferation in inguinal white adipose tissue (ingWAT), the percentage of BAs, defined as multilocular adipocytes that express uncoupling protein 1, rose from undetectable to 30% of total adipocytes. To trace the origins of cold-induced BAs, we genetically tagged PDGFRα(+) cells and adipocytes prior to cold exposure, using Pdgfra-Cre recombinase estrogen receptor T2 fusion protein (CreER(T2)) and adiponectin-CreER(T2), respectively. In iBAT, cold stress triggered the proliferation and differentiation of PDGFRα(+) cells into BAs. In contrast, all newly observed BAs in ingWAT (5207 out of 5207) were derived from unilocular adipocytes tagged by adiponectin-CreER(T2)-mediated recombination. Surgical denervation of iBAT reduced cold-induced brown adipogenesis by >85%, whereas infusion of norepinephrine (NE) mimicked the effects of cold in warm-adapted mice. NE-induced de novo brown adipogenesis in iBAT was eliminated in mice lacking β1-adrenergic receptors. These observations identify a novel tissue niche for brown adipogenesis in iBAT and further define depot-specific mechanisms of BA recruitment. PMID:25392270

  10. An inducible hepatocellular carcinoma model for preclinical evaluation of antiangiogenic therapy in adult mice.

    Science.gov (United States)

    Runge, Anja; Hu, Junhao; Wieland, Matthias; Bergeest, Jan-Philip; Mogler, Carolin; Neumann, André; Géraud, Cyrill; Arnold, Bernd; Rohr, Karl; Komljenovic, Dorde; Schirmacher, Peter; Goerdt, Sergij; Augustin, Hellmut G

    2014-08-01

    The limited availability of experimental tumor models that faithfully mimic the progression of human tumors and their response to therapy remains a major bottleneck to the clinical translation and application of novel therapeutic principles. To address this challenge in hepatocellular carcinoma (HCC), one of the deadliest and most common cancers in the world, we developed and validated an inducible model of hepatocarcinogenesis in adult mice. Tumorigenesis was triggered by intravenous adenoviral delivery of Cre recombinase in transgenic mice expressing the hepatocyte-specific albumin promoter, a loxP-flanked stop cassette, and the SV40 large T-antigen (iAST). Cre recombinase-mediated excision of the stop cassette led to a transient viral hepatitis and resulted in multinodular tumorigenesis within 5 to 8 weeks. Tumor nodules with histologic characteristics of human HCC established a functional vasculature by cooption, remodeling, and angiogenic expansion of the preexisting sinusoidal liver vasculature with increasing signs of vascular immaturity during tumor progression. Treatment of mice with sorafenib rapidly resulted in the induction of vascular regression, inhibition of tumor growth, and enhanced overall survival. Vascular regression was characterized by loss of endothelial cells leaving behind avascular type IV collagen-positive empty sleeves with remaining pericytes. Sorafenib treatment led to transcriptional changes of Igf1, Id1, and cMet over time, which may reflect the emergence of potential escape mechanisms. Taken together, our results established the iAST model of inducible hepatocarcinogenesis as a robust and versatile preclinical model to study HCC progression and validate novel therapies. PMID:24906623

  11. 哺乳期母体接触氯氰菊酯对子代雌鼠学习记忆的损害效应%Effects of maternal cypermethrin exposure during lactation on learning and memory ability in adult female offspring

    Institute of Scientific and Technical Information of China (English)

    章恒; 王华; 徐德祥

    2012-01-01

    目的 研究哺乳期母鼠接触氯氰菊酯对子代成年雌鼠学习记忆能力的损害作用及其可能机制.方法 12只ICR母鼠随机分成对照组、6.25和25.00 mg/kg染毒组(每组4只母鼠,每窝10只仔鼠,雌雄各半,即每组20只雌鼠),于子代雌鼠出生后第1~21天(PNDl~ PND21),每天经口灌胃给予母鼠氯氰菊酯(6.25和25.00 mg/kg)染毒1次,对照组母鼠给予玉米油.染毒后39d,采用六臂放射状水迷 宫检测PND60雌鼠的学习记忆能力.检试结束后,称体重,处死动物取脑称重并分离海马组织,用蛋白质免疫印迹(Western blotting)法检测海马中N-甲基-D-门冬氨酸(NMDA)受体NR1亚单位蛋白表达水平.结果 各组子代雌鼠体重和脑重的差异无统计学意义(P>0.05).经重复测量资料方差分析显示,在学习期,25.00 mg/kg染毒组子代雌鼠潜伏期[(31.3±17.0)s]长于对照组[(21.0±14.0)s];在记忆期,25.00 mg/kg染毒组子代雌鼠潜伏期[(24.6±21.1)s]较对照组[(14.1±16.3)s]延长,差异均有统计学意义(P<0.05).各组子代雌鼠在学习期和记忆期的错误数比较,差异均无统计学(P>0.05).与对照组相比,25.0 mg/kg染毒组子代雌鼠海马组织NR1蛋白表达水平明显降低,差异有统计学意义(P<0.01).结论 哺乳期母鼠接触氯氰菊酯在一定程度上损伤子代成年雌鼠学习记忆能力,可能与海马组织中NR1亚单位蛋白表达水平下降有关.%Objective To explore the effect of maternal cypermethrin exposure during lactation on learning and memory ability in adult female offspring,as well as the possible mechanism.Methods Twelve maternal mice were randomly divided into 6.25 mg/kg cypermethrin,25.0 mg/kg cypermethrin and control groups (four dams each group,ten pups each dam,half male half female,twenty female pups each group).Maternal mice were orally administered with different doses of cypermethrin (6.25 and 25 mg/kg/d) once daily from postnatal day 1 (PND1) to PND21.Maternal

  12. Taste Bud Labeling in Whole Tongue Epithelial Sheet in Adult Mice.

    Science.gov (United States)

    Venkatesan, Nandakumar; Boggs, Kristin; Liu, Hong-Xiang

    2016-04-01

    Molecular labeling in whole-mount tissues provides an efficient way to obtain general information about the formation, maintenance, degeneration, and regeneration of many organs and tissues. However, labeling of lingual taste buds in whole tongue tissues in adult mice has been problematic because of the strong permeability barrier of the tongue epithelium. In this study, we present a simple method for labeling taste buds in the intact tongue epithelial sheet of an adult mouse. Following intralingual protease injection and incubation, immediate fixation of the tongue on mandible in 4% paraformaldehyde enabled the in situ shape of the tongue epithelium to be well maintained after peeling. The peeled epithelium was accessible to taste bud labeling with a pan-taste cell marker, keratin 8, and a type II taste cell marker, α-gustducin, in all three types of taste papillae, that is, fungiform, foliate, and circumvallate. Overnight incubation of tongue epithelial sheets with primary and secondary antibodies was sufficient for intense labeling of taste buds with both fluorescent and DAB visualizations. Labeled individual taste buds were easy to identify and quantify. This protocol provides an efficient way for phenotypic analyses of taste buds, especially regarding distribution pattern and number. PMID:26701416

  13. Successful small intestine colonization of adult mice by Vibrio cholerae requires ketamine anesthesia and accessory toxins.

    Directory of Open Access Journals (Sweden)

    Verena Olivier

    Full Text Available Vibrio cholerae colonizes the small intestine of adult C57BL/6 mice. In this study, the physical and genetic parameters that facilitate this colonization were investigated. Successful colonization was found to depend upon anesthesia with ketamine-xylazine and neutralization of stomach acid with sodium bicarbonate, but not streptomycin treatment. A variety of common mouse strains were colonized by O1, O139, and non-O1/non-O139 strains. All combinations of mutants in the genes for hemolysin, the multifunctional, autoprocessing RTX toxin (MARTX, and hemagglutinin/protease were assessed, and it was found that hemolysin and MARTX are each sufficient for colonization after a low dose infection. Overall, this study suggests that, after intragastric inoculation, V. cholerae encounters barriers to infection including an acidic environment and an immediate immune response that is circumvented by sodium bicarbonate and the anti-inflammatory effects of ketamine-xylazine. After initial adherence in the small intestine, the bacteria are subjected to additional clearance mechanisms that are evaded by the independent toxic action of hemolysin or MARTX. Once colonization is established, it is suggested that, in humans, these now persisting bacteria initiate synthesis of the major virulence factors to cause cholera disease. This adult mouse model of intestinal V. cholerae infection, now well-characterized and fully optimized, should serve as a valuable tool for studies of pathogenesis and testing vaccine efficacy.

  14. Maternal Exercise and Cognitive Functions of the Offspring

    OpenAIRE

    Robinson, Andrea M.; Bucci, David J.

    2012-01-01

    Substantial research has established that exercise can improve mental health and cognitive function in both human and non-human animals. Exercise has been shown to improve learning and memory in both adult and juvenile animals, with larger and more durable effects associated with exercising during development. Exercise during the gestational period has also been shown to improve cognition in the offspring. Several recent studies indicate that the offspring of mothers that exercised during pre...

  15. Effects of paternal age and offspring cognitive ability in early adulthood on the risk of schizophrenia and related disorders

    DEFF Research Database (Denmark)

    Sørensen, Holger J; Pedersen, Carsten B; Nordentoft, Merete;

    2014-01-01

    Advanced paternal age (APA) and intelligence quotient (IQ) are both associated with the risk of schizophrenia spectrum disorder (SSD) in young adult offspring. We hypothesized that the offspring SSD risk gradient associated with paternal age is mediated by offspring IQ. We investigated joint and ...

  16. Production of transgenic mice by random recombination of targeted genes in female germline stem cells

    Institute of Scientific and Technical Information of China (English)

    Yong Zhang; Ji Xiong; Jie Xiang; Ji Wu; Zhaojuan Yang; Yunze Yang; Shuzeng Wang; Lingjun Shi; Wenhai Xie; Kejing Sun; Kang Zou; Lei Wang

    2011-01-01

    Oocyte production in most mammalian species is believed to cease before birth. However, this idea has been challenged with the finding that postnatal mouse ovaries possess mitotically active germ cells. A recent study showed that female germline stem cells (FGSCs) from adult mice were isolated, cultured long term and produced oocytes and progeny after transplantation into infertile mice. Here, we demonstrate the successful generation of transgenic or gene knock-down mice using FGSCs. The FGSCs from ovaries of 5-day-old and adult mice were isolated and either infected with recombinant viruses carrying green fluorescent protein, Oocyte-G1 or the mouse dynein axonemal intermediate chain 2 gene, or transfected with the Oocyte-G1 specific shRNA expression vector (pRS shOocyte-G1 vector), and then transplanted into infertile mice. Transplanted cells in the ovaries underwent oogenesis and produced heterozygous offspring after mating with wild-type male mice. The offspring were genetically characterized and the biological functions of the transferred or knock-down genes were investigated. Efficiency of genetransfer or gene knock-down was 29%-37% and it took 2 months to produce transgenic offspring. Gene manipulation of FGSCs is a rapid and efficient method of animal transgenesis and may serve as a powerful tool for biomedical science and biotechnology.

  17. Microbial Reconstitution Reverses Maternal Diet-Induced Social and Synaptic Deficits in Offspring.

    Science.gov (United States)

    Buffington, Shelly A; Di Prisco, Gonzalo Viana; Auchtung, Thomas A; Ajami, Nadim J; Petrosino, Joseph F; Costa-Mattioli, Mauro

    2016-06-16

    Maternal obesity during pregnancy has been associated with increased risk of neurodevelopmental disorders, including autism spectrum disorder (ASD), in offspring. Here, we report that maternal high-fat diet (MHFD) induces a shift in microbial ecology that negatively impacts offspring social behavior. Social deficits and gut microbiota dysbiosis in MHFD offspring are prevented by co-housing with offspring of mothers on a regular diet (MRD) and transferable to germ-free mice. In addition, social interaction induces synaptic potentiation (LTP) in the ventral tegmental area (VTA) of MRD, but not MHFD offspring. Moreover, MHFD offspring had fewer oxytocin immunoreactive neurons in the hypothalamus. Using metagenomics and precision microbiota reconstitution, we identified a single commensal strain that corrects oxytocin levels, LTP, and social deficits in MHFD offspring. Our findings causally link maternal diet, gut microbial imbalance, VTA plasticity, and behavior and suggest that probiotic treatment may relieve specific behavioral abnormalities associated with neurodevelopmental disorders. VIDEO ABSTRACT. PMID:27315483

  18. Decreased ovarian reserve, dysregulation of mitochondrial biogenesis, and increased lipid peroxidation in female mouse offspring exposed to an obesogenic maternal diet.

    Science.gov (United States)

    Aiken, Catherine E; Tarry-Adkins, Jane L; Penfold, Naomi C; Dearden, Laura; Ozanne, Susan E

    2016-04-01

    Maternal diet during pregnancy influences the later life reproductive potential of female offspring. We investigate the molecular mechanisms underlying the depletion of ovarian follicular reserve in young adult females following exposure to obesogenic diet in early life. Furthermore, we explore the interaction between adverse maternal diet and postweaning diet in generating reduced ovarian reserve. Female mice were exposed to either maternal obesogenic (high fat/high sugar) or maternal control dietin uteroand during lactation, then weaned onto either obesogenic or control diet. At 12 wk of age, the offspring ovarian reserve was depleted following exposure to maternal obesogenic diet (Pcopy numberPcopper/zinc superoxide dismutasePcentral role in determining follicular reserve in adult female offspring. Our observations suggest that lipid peroxidation and mitochondrial biogenesis are the key intracellular pathways involved in programming of ovarian reserve.-Aiken, C. E., Tarry-Adkins, J. L., Penfold, N. C., Dearden, L., Ozanne, S. E. Decreased ovarian reserve, dysregulation of mitochondrial biogenesis, and increased lipid peroxidation in female mouse offspring exposed to an obesogenic maternal diet. PMID:26700734

  19. Gestational lead exposure selectively decreases retinal dopamine amacrine cells and dopamine content in adult mice

    International Nuclear Information System (INIS)

    Gestational lead exposure (GLE) produces supernormal scotopic electroretinograms (ERG) in children, monkeys and rats, and a novel retinal phenotype characterized by an increased number of rod photoreceptors and bipolar cells in adult mice and rats. Since the loss of dopaminergic amacrine cells (DA ACs) in GLE monkeys and rats contributes to supernormal ERGs, the retinal DA system was analyzed in mice following GLE. C57BL/6 female mice were exposed to low (27 ppm), moderate (55 ppm) or high (109 ppm) lead throughout gestation and until postnatal day 10 (PN10). Blood [Pb] in control, low-, moderate- and high-dose GLE was ≤ 1, ≤ 10, ∼ 25 and ∼ 40 μg/dL, respectively, on PN10 and by PN30 all were ≤ 1 μg/dL. At PN60, confocal-stereology studies used vertical sections and wholemounts to characterize tyrosine hydroxylase (TH) expression and the number of DA and other ACs. GLE dose-dependently and selectively decreased the number of TH-immunoreactive (IR) DA ACs and their synaptic plexus without affecting GABAergic, glycinergic or cholinergic ACs. Immunoblots and confocal revealed dose-dependent decreases in retinal TH protein expression and content, although monoamine oxidase-A protein and gene expression were unchanged. High-pressure liquid chromatography showed that GLE dose-dependently decreased retinal DA content, its metabolites and DA utilization/release. The mechanism of DA selective vulnerability is unknown. However, a GLE-induced loss/dysfunction of DA ACs during development could increase the number of rods and bipolar cells since DA helps regulate neuronal proliferation, whereas during adulthood it could produce ERG supernormality as well as altered circadian rhythms, dark/light adaptation and spatial contrast sensitivity. -- Highlights: ► Peak [BPb] in control, low-, moderate- and high-dose newborn mice with gestational lead exposure: ≤ 1, ≤ 10, 25 and 40 μg/dL ► Gestational lead exposure dose-dependently decreased the number of TH

  20. Gestational lead exposure selectively decreases retinal dopamine amacrine cells and dopamine content in adult mice

    Energy Technology Data Exchange (ETDEWEB)

    Fox, Donald A., E-mail: dafox@uh.edu [College of Optometry, University of Houston, Houston, TX (United States); Department of Biology and Biochemistry, University of Houston, Houston, TX (United States); Department of Pharmacology and Pharmaceutical Sciences, University of Houston, Houston, TX (United States); Hamilton, W. Ryan [Department of Biology and Biochemistry, University of Houston, Houston, TX (United States); Johnson, Jerry E. [Department of Natural Sciences, University of Houston-Downtown, Houston, TX (United States); Xiao, Weimin [College of Optometry, University of Houston, Houston, TX (United States); Chaney, Shawntay; Mukherjee, Shradha [Department of Biology and Biochemistry, University of Houston, Houston, TX (United States); Miller, Diane B.; O' Callaghan, James P. [Toxicology and Molecular Biology Branch, Health Effects Research Laboratory, Centers for Disease Control and Prevention-NIOSH, Morgantown, WV USA (United States)

    2011-11-15

    Gestational lead exposure (GLE) produces supernormal scotopic electroretinograms (ERG) in children, monkeys and rats, and a novel retinal phenotype characterized by an increased number of rod photoreceptors and bipolar cells in adult mice and rats. Since the loss of dopaminergic amacrine cells (DA ACs) in GLE monkeys and rats contributes to supernormal ERGs, the retinal DA system was analyzed in mice following GLE. C57BL/6 female mice were exposed to low (27 ppm), moderate (55 ppm) or high (109 ppm) lead throughout gestation and until postnatal day 10 (PN10). Blood [Pb] in control, low-, moderate- and high-dose GLE was {<=} 1, {<=} 10, {approx} 25 and {approx} 40 {mu}g/dL, respectively, on PN10 and by PN30 all were {<=} 1 {mu}g/dL. At PN60, confocal-stereology studies used vertical sections and wholemounts to characterize tyrosine hydroxylase (TH) expression and the number of DA and other ACs. GLE dose-dependently and selectively decreased the number of TH-immunoreactive (IR) DA ACs and their synaptic plexus without affecting GABAergic, glycinergic or cholinergic ACs. Immunoblots and confocal revealed dose-dependent decreases in retinal TH protein expression and content, although monoamine oxidase-A protein and gene expression were unchanged. High-pressure liquid chromatography showed that GLE dose-dependently decreased retinal DA content, its metabolites and DA utilization/release. The mechanism of DA selective vulnerability is unknown. However, a GLE-induced loss/dysfunction of DA ACs during development could increase the number of rods and bipolar cells since DA helps regulate neuronal proliferation, whereas during adulthood it could produce ERG supernormality as well as altered circadian rhythms, dark/light adaptation and spatial contrast sensitivity. -- Highlights: Black-Right-Pointing-Pointer Peak [BPb] in control, low-, moderate- and high-dose newborn mice with gestational lead exposure: {<=} 1, {<=} 10, 25 and 40 {mu}g/dL Black

  1. Long-Term Intermittent Hypoxia Elevates Cobalt Levels in the Brain and Injures White Matter in Adult Mice

    Science.gov (United States)

    Veasey, Sigrid C.; Lear, Jessica; Zhu, Yan; Grinspan, Judith B.; Hare, Dominic J.; Wang, SiHe; Bunch, Dustin; Doble, Philip A.; Robinson, Stephen R.

    2013-01-01

    Study Objectives: Exposure to the variable oxygenation patterns in obstructive sleep apnea (OSA) causes oxidative stress within the brain. We hypothesized that this stress is associated with increased levels of redox-active metals and white matter injury. Design: Participants were randomly allocated to a control or experimental group (single independent variable). Setting: University animal house. Participants: Adult male C57BL/6J mice. Interventions: To model OSA, mice were exposed to long-term intermittent hypoxia (LTIH) for 10 hours/day for 8 weeks or sham intermittent hypoxia (SIH). Measurements and Results: Laser ablation-inductively coupled plasma-mass spectrometry was used to quantitatively map the distribution of the trace elements cobalt, copper, iron, and zinc in forebrain sections. Control mice contained 62 ± 7 ng cobalt/g wet weight, whereas LTIH mice contained 5600 ± 600 ng cobalt/g wet weight (P < 0.0001). Other elements were unchanged between conditions. Cobalt was concentrated within white matter regions of the brain, including the corpus callosum. Compared to that of control mice, the corpus callosum of LTIH mice had significantly more endoplasmic reticulum stress, fewer myelin-associated proteins, disorganized myelin sheaths, and more degenerated axon profiles. Because cobalt is an essential component of vitamin B12, serum methylmalonic acid (MMA) levels were measured. LTIH mice had low MMA levels (P < 0.0001), indicative of increased B12 activity. Conclusions: Long-term intermittent hypoxia increases brain cobalt, predominantly in the white matter. The increased cobalt is associated with endoplasmic reticulum stress, myelin loss, and axonal injury. Low plasma methylmalonic acid levels are associated with white matter injury in long-term intermittent hypoxia and possibly in obstructive sleep apnea. Citation: Veasey SC; Lear J; Zhu Y; Grinspan JB; Hare DJ; Wang S; Bunch D; Doble PA; Robinson SR. Long-term intermittent hypoxia elevates cobalt

  2. Ablation of huntingtin in adult neurons is nondeleterious but its depletion in young mice causes acute pancreatitis.

    Science.gov (United States)

    Wang, Guohao; Liu, Xudong; Gaertig, Marta A; Li, Shihua; Li, Xiao-Jiang

    2016-03-22

    The Huntington's disease (HD) protein, huntingtin (HTT), is essential for early development. Because suppressing the expression of mutantHTTis an important approach to treat the disease, we must first understand the normal function of Htt in adults versus younger animals. Using inducibleHttknockout mice, we found thatHttdepletion does not lead to adult neurodegeneration or animal death at >4 mo of age, which was also verified by selectively depletingHttin neurons. On the other hand, young Htt KO mice die at 2 mo of age of acute pancreatitis due to the degeneration of pancreatic acinar cells. Importantly, Htt interacts with the trypsin inhibitor, serine protease inhibitor Kazal-type 3 (Spink3), to inhibit activation of digestive enzymes in acinar cells in young mice, and transgenicHTTcan rescue the early death of Htt KO mice. These findings point out age- and cell type-dependent vital functions of Htt and the safety of knocking down neuronal Htt expression in adult brains as a treatment. PMID:26951659

  3. Immunosuppression in early postnatal days induces persistent and allergen-specific immune tolerance to asthma in adult mice.

    Science.gov (United States)

    Chen, Yan; Zhang, Jin; Lu, Yong; Wang, Libo

    2015-01-01

    Bronchial asthma is a chronic airway inflammatory condition with high morbidity, and effective treatments for asthma are limited. Allergen-specific immunotherapy can only induce peripheral immune tolerance and is not sustainable. Exploring new therapeutic strategies is of great clinical importance. Recombinant adenovirus (rAdV) was used as a vector to make cells expressing cytotoxic T lymphocyte-associated antigen-4-immunoglobulin (CTLA4Ig) a soluble CTLA4 immunoglobulin fusion protein. Dendritic cells (DCs) were modified using the rAdVs together with allergens. Then these modified DCs were transplanted to mice before allergen sensitization. The persistence and specificity of immune tolerance were evaluated in mice challenged with asthma allergens at 3 and 7 months. DCs modified by CTLA4Ig showed increased IL-10 secretion, decreased IL-12 secretion, and T cell stimulation in vitro. Mice treated with these DCs in the early neonatal period developed tolerance against the allergens that were used to induce asthma in the adult stage. Asthma symptoms, lung damage, airway reactivity, and inflammatory response all improved. Humoral immunity indices showed that this therapeutic strategy strongly suppressed mice immune responses and was maintained for as long as 7 months. Furthermore, allergen cross-sensitization and challenge experiments demonstrated that this immune tolerance was allergen-specific. Treatment with CTLA4Ig modified DCs in the early neonatal period, inducing persistent and allergen-specific immune tolerance to asthma in adult mice. Our results suggest that it may be possible to develop a vaccine for asthma. PMID:25860995

  4. Transcription factors FOXA1 and FOXA2 maintain dopaminergic neuronal properties and control feeding behavior in adult mice.

    Science.gov (United States)

    Pristerà, Alessandro; Lin, Wei; Kaufmann, Anna-Kristin; Brimblecombe, Katherine R; Threlfell, Sarah; Dodson, Paul D; Magill, Peter J; Fernandes, Cathy; Cragg, Stephanie J; Ang, Siew-Lan

    2015-09-01

    Midbrain dopaminergic (mDA) neurons are implicated in cognitive functions, neuropsychiatric disorders, and pathological conditions; hence understanding genes regulating their homeostasis has medical relevance. Transcription factors FOXA1 and FOXA2 (FOXA1/2) are key determinants of mDA neuronal identity during development, but their roles in adult mDA neurons are unknown. We used a conditional knockout strategy to specifically ablate FOXA1/2 in mDA neurons of adult mice. We show that deletion of Foxa1/2 results in down-regulation of tyrosine hydroxylase, the rate-limiting enzyme of dopamine (DA) biosynthesis, specifically in dopaminergic neurons of the substantia nigra pars compacta (SNc). In addition, DA synthesis and striatal DA transmission were reduced after Foxa1/2 deletion. Furthermore, the burst-firing activity characteristic of SNc mDA neurons was drastically reduced in the absence of FOXA1/2. These molecular and functional alterations lead to a severe feeding deficit in adult Foxa1/2 mutant mice, independently of motor control, which could be rescued by L-DOPA treatment. FOXA1/2 therefore control the maintenance of molecular and physiological properties of SNc mDA neurons and impact on feeding behavior in adult mice. PMID:26283356

  5. Sex and laterality differences in medial amygdala neurons and astrocytes of adult mice.

    Science.gov (United States)

    Pfau, Daniel R; Hobbs, Nicholas J; Breedlove, S Marc; Jordan, Cynthia L

    2016-08-15

    The posterodorsal aspect of the medial amygdala (MePD) in rats is sexually dimorphic, being larger and containing more and larger neurons in males than in females. It is also highly lateralized, with the right MePD larger than the left in both sexes, but with the smaller left MePD actually containing more and larger neurons than the larger right. Astrocytes are also strikingly sexually differentiated, with male-biased numbers and lateralized favoring the right in the rat MePD. However, comparable information is scant for mice where genetic tools offer greater experimental power. Hence, we examined the MePD from adult male and female C57Bl/6(J) mice. We now report that the MePD is larger in males than in females, with the MePD in males containing more astrocytes and neurons than in females. However, we did not find sex differences in astrocyte complexity or overall glial number nor effects of laterality in either measure. While the mouse MePD is generally less lateralized than in rats, we did find that the sex difference in astrocyte number is only on the right because of a significant lateralization in females, with significantly fewer astrocytes on the right than the left but only in females. A sex difference in neuronal soma size favoring males was also evident, but only on the left. Sex differences in the number of neurons and astrocytes common to both rodent species may represent core morphological features that critically underlie the expression of sex-specific behaviors that depend on the MePD. J. Comp. Neurol. 524:2492-2502, 2016. © 2016 Wiley Periodicals, Inc. PMID:26780286

  6. Pharmacological reduction of adult hippocampal neurogenesis modifies functional brain circuits in mice exposed to a cocaine conditioned place preference paradigm.

    Science.gov (United States)

    Castilla-Ortega, Estela; Blanco, Eduardo; Serrano, Antonia; Ladrón de Guevara-Miranda, David; Pedraz, María; Estivill-Torrús, Guillermo; Pavón, Francisco Javier; Rodríguez de Fonseca, Fernando; Santín, Luis J

    2016-05-01

    We investigated the role of adult hippocampal neurogenesis in cocaine-induced conditioned place preference (CPP) behaviour and the functional brain circuitry involved. Adult hippocampal neurogenesis was pharmacologically reduced with temozolomide (TMZ), and mice were tested for cocaine-induced CPP to study c-Fos expression in the hippocampus and in extrahippocampal addiction-related areas. Correlational and multivariate analysis revealed that, under normal conditions, the hippocampus showed widespread functional connectivity with other brain areas and strongly contributed to the functional brain module associated with CPP expression. However, the neurogenesis-reduced mice showed normal CPP acquisition but engaged an alternate brain circuit where the functional connectivity of the dentate gyrus was notably reduced and other areas (the medial prefrontal cortex, accumbens and paraventricular hypothalamic nucleus) were recruited instead of the hippocampus. A second experiment unveiled that mice acquiring the cocaine-induced CPP under neurogenesis-reduced conditions were delayed in extinguishing their drug-seeking behaviour. But if the inhibited neurons were generated after CPP acquisition, extinction was not affected but an enhanced long-term CPP retention was found, suggesting that some roles of the adult-born neurons may differ depending on whether they are generated before or after drug-contextual associations are established. Importantly, cocaine-induced reinstatement of CPP behaviour was increased in the TMZ mice, regardless of the time of neurogenesis inhibition. The results show that adult hippocampal neurogenesis sculpts the addiction-related functional brain circuits, and reduction of the adult-born hippocampal neurons increases cocaine seeking in the CPP model. PMID:25870909

  7. Protective effects of vitamin E and Cornus mas fruit extract on methotrexate-induced cytotoxicity in sperms of adult mice

    OpenAIRE

    Zarei, Leila; Sadrkhanlou, Rajabali; Shahrooz, Rasoul; Malekinejad, Hassan; Eilkhanizadeh, Behroz; Ahmadi, Abbas

    2014-01-01

    This study was aimed to assess the protective effects of Cornus mas fruit extract (CMFE) and vitamin E (Vit E) on sperm quality parameters in the methotrexate (MTX)-treated mice. Forty-eight young adult male mice (8-12 weeks) were randomly divided into six groups including control and test groups. The control group received normal saline orally , and the test groups were treated MTX (20 mg kg-1, ip, once weekly), MTX + CMFE (250 mg kg-1), MTX + CMFE (500 mg kg-1), MTX + CMFE (1000 mg kg-1), a...

  8. Behavioral disturbances in adult mice following neonatal virus infection or kynurenine treatment--role of brain kynurenic acid.

    Science.gov (United States)

    Liu, Xi-Cong; Holtze, Maria; Powell, Susan B; Terrando, Niccolò; Larsson, Markus K; Persson, Anna; Olsson, Sara K; Orhan, Funda; Kegel, Magdalena; Asp, Linnea; Goiny, Michel; Schwieler, Lilly; Engberg, Göran; Karlsson, Håkan; Erhardt, Sophie

    2014-02-01

    Exposure to infections in early life is considered a risk-factor for developing schizophrenia. Recently we reported that a neonatal CNS infection with influenza A virus in mice resulted in a transient induction of the brain kynurenine pathway, and subsequent behavioral disturbances in immune-deficient adult mice. The aim of the present study was to investigate a potential role in this regard of kynurenic acid (KYNA), an endogenous antagonist at the glycine site of the N-methyl-D-aspartic acid (NMDA) receptor and at the cholinergic α7 nicotinic receptor. C57BL/6 mice were injected i.p. with neurotropic influenza A/WSN/33 virus (2400 plaque-forming units) at postnatal day (P) 3 or with L-kynurenine (2×200 mg/kg/day) at P7-16. In mice neonatally treated with L-kynurenine prepulse inhibition of the acoustic startle, anxiety, and learning and memory were also assessed. Neonatally infected mice showed enhanced sensitivity to D-amphetamine-induced (5 mg/kg i.p.) increase in locomotor activity as adults. Neonatally L-kynurenine treated mice showed enhanced sensitivity to D-amphetamine-induced (5 mg/kg i.p.) increase in locomotor activity as well as mild impairments in prepulse inhibition and memory. Also, D-amphetamine tended to potentiate dopamine release in the striatum in kynurenine-treated mice. These long-lasting behavioral and neurochemical alterations suggest that the kynurenine pathway can link early-life infection with the development of neuropsychiatric disturbances in adulthood. PMID:24140727

  9. Effects of prenatal exposure to surface-coated nanosized titanium dioxide (UV-Titan). A study in mice

    DEFF Research Database (Denmark)

    Hougaard, Karin S.; Jackson, Petra; Jensen, Keld A.;

    2010-01-01

    Background: Engineered nanoparticles are smaller than 100 nm and designed to improve or achieve new physicochemical properties. Consequently, also toxicological properties may change compared to the parent compound. We examined developmental and neurobehavioral effects following maternal exposure...... coated with polyalcohols. In exposed adult mice, 38 mg Ti/kg was detected in the lungs on day 5 and differential cell counts of bronchoalveolar lavage fluid revealed lung inflammation 5 and 26-27 days following exposure termination, relative to control mice. As young adults, prenatally exposed offspring...... mice. Gestationally exposed offspring displayed moderate neurobehavioral alterations. The results are discussed in the light of the observed particle size distribution in the exposure atmosphere and the potential pathways by which nanoparticles may impart changes in fetal development....

  10. Effects of prenatal stress on male offspring sexual maturity

    Directory of Open Access Journals (Sweden)

    Nancy Rodríguez

    2007-04-01

    Full Text Available Prenatal stimulations have been shown to have long-term effects on at reproductive activity. We evaluated the influence of the prenatal stress on the hypothalamic-pituitary-gonad (HPG axis in male off­springs from mothers with high number of offsprings per litter (HNL and low number of offsprings per litter (LNL after hypothesizing that the number of offsprings per litter may modify the effect of the prenatal stress on the HPG of adult offsprings. Pregnant Wistar rats were used for this study. Immobilization (IMO stress was used, 30 min, 3 times per week, from the 5th to 21st day of pregnancy. The weight of adrenal and gonads, and the corticosterone (COR, testosterone (TES and luteinizing hormone (LH plasmatic levels were analyzed in the male offspring at 30, 45 and 70 days of age. The offspring males coming from LNL showed a decrease in testicle weight and TES levels, without changes in the plasmatic LH levels. However, the offspring of HNL showed a decrease of LH levels. It is possible to conclude that in LNL prenatal stress would produce alterations to gonadal level, while in HNL the effect of stress would be evident at pituitary level.

  11. Maternal exposure to low levels of corticosterone during lactation protects against experimental inflammatory colitis-induced damage in adult rat offspring.

    Directory of Open Access Journals (Sweden)

    Carla Petrella

    Full Text Available Opposing emotional events (negative/trauma or positive/maternal care during the postnatal period may differentially influence vulnerability to the effects of stress later in life. The development and course of intestinal disorders such as inflammatory bowel disease are negatively affected by persistent stress, but to date the role of positive life events on these pathologies has been entirely unknown. In the present study, the effect of early life beneficial experiences in the development of intestinal dysfunctions, where inflammation and stress stimuli play a primary role, was investigated. As a "positive" experimental model we used adult male rat progeny nursed by mothers whose drinking water was supplemented with moderate doses of corticosterone (CORT (0.2 mg/ml during the lactation period. Such animals have been generally shown to cope better with different environmental situations during life. The susceptibility to inflammatory experimental colitis induced by intracolonic infusion of TNBS (2,4,6-trinitrobenzenesulphonic acid was investigated in CORT-nursed rats in comparison with control rats. This mild increase in maternal corticosterone during lactation induced, in CORT-nursed rats, a long lasting protective effect on TNBS-colitis, characterized by improvements in some indices of the disease (increased colonic myeloperoxidase activity, loss of body weight and food intake and by the involvement of endogenous peripheral pathways known to participate in intestinal disorder development (lower plasma corticosterone levels and colonic mast cell degranulation, alterations in the colonic expression of both corticotrophin releasing factor/CRF and its receptor/CRH-1R. All these findings contribute to suggesting that the reduced vulnerability to TNBS-colitis in CORT-nursed rats is due to recovery from the colonic mucosal barrier dysfunction. Such long lasting changes induced by mild hormonal manipulation during lactation, making the adult also

  12. The protein kinase KIS impacts gene expression during development and fear conditioning in adult mice.

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    Valérie Manceau

    Full Text Available The brain-enriched protein kinase KIS (product of the gene UHMK1 has been shown to phosphorylate the human splicing factor SF1 in vitro. This phosphorylation in turn favors the formation of a U2AF(65-SF1-RNA complex which occurs at the 3' end of introns at an early stage of spliceosome assembly. Here, we analyzed the effects of KIS knockout on mouse SF1 phosphorylation, physiology, adult behavior, and gene expression in the neonate brain. We found SF1 isoforms are differently expressed in KIS-ko mouse brains and fibroblasts. Re-expression of KIS in fibroblasts restores a wild type distribution of SF1 isoforms, confirming the link between KIS and SF1. Microarray analysis of transcripts in the neonate brain revealed a subtle down-regulation of brain specific genes including cys-loop ligand-gated ion channels and metabolic enzymes. Q-PCR analyses confirmed these defects and point to an increase of pre-mRNA over mRNA ratios, likely due to changes in splicing efficiency. While performing similarly in prepulse inhibition and most other behavioral tests, KIS-ko mice differ in spontaneous activity and contextual fear conditioning. This difference suggests that disregulation of gene expression due to KIS inactivation affects specific brain functions.

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

    International Nuclear Information System (INIS)

    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

  14. MicroRNA-210 promotes sensory axon regeneration of adult mice in vivo and in vitro.

    Science.gov (United States)

    Hu, Yi-Wen; Jiang, Jing-Jing; Yan-Gao; Wang, Rui-Ying; Tu, Guan-Jun

    2016-05-27

    Axon regeneration as a critical step in nerve repairing and remodeling after peripheral nerve injury relies on regulation of gene expression. MicroRNAs are emerging to be important epigenetic regulators of gene expression to control axon regeneration. Here we used a novel in vivo electroporation approach to transfect microRNA-210 (miR-210) or siRNAs to adult mice dorsal root ganglion (DRG) neurons, measured the axon length 3days after sciatic nerve crush or dissociated DRG cultures in vitro to detect the effect of miR-210 in sensory axon regeneration. Importantly, we found that miR-210 overexpression could promote sensory axon regeneration and inhibit apoptsosis by ephrin-A3 (EFNA3). In addition, inhibition of endogenous miR-210 in DRG neurons impaired axon regeneration in vitro and in vivo, the regulatory effect of miR-210 was mediated by increased expression of EFNA3 because downregulation of EFNA3 fully rescued axon regeneration. We thus demonstrate that miR-210 is a new physiological regulator of sensory axon regeneration, and EFNA3 may be the functional target of miR-210. We conclude that miR-210 may play an important role in sensory axon regeneration. PMID:27102143

  15. Mass mortality of adult male subantarctic fur seals: are alien mice the culprits?

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    P J Nico de Bruyn

    Full Text Available BACKGROUND: Mass mortalities of marine mammals due to infectious agents are increasingly reported. However, in contrast to previous die-offs, which were indiscriminate with respect to sex and age, here we report a land-based mass mortality of Subantarctic fur seals with apparent exclusivity to adult males. An infectious agent with a male-predilection is the most plausible explanation for this die-off. Although pathogens with gender-biased transmission and pathologies are unusual, rodents are known sources of male-biased infectious agents and the invasive Mus musculus house mouse, occurs in seal rookeries. METHODOLOGY/ PRINCIPAL FINDINGS: Molecular screening for male-biased pathogens in this potential rodent reservoir host revealed the absence of Cardiovirus and Leptospirosis genomes in heart and kidney samples, respectively, but identified a novel Streptococcus species with 30% prevalence in mouse kidneys. CONCLUSIONS/ SIGNIFICANCE: Inter-species transmission through environmental contamination with this novel bacterium, whose congenerics display male-bias and have links to infirmity in seals and terrestrial mammals (including humans, highlights the need to further evaluate disease risks posed by alien invasive mice to native species, on this and other islands.

  16. TNF-like weak inducer of apoptosis (TWEAK promotes beta cell neogenesis from pancreatic ductal epithelium in adult mice.

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    Fei Wu

    Full Text Available AIM/HYPOTHESIS: The adult mammalian pancreas has limited ability to regenerate in order to restore adequate insulin production from multipotent progenitors, the identity and function of which remain poorly understood. Here we test whether the TNF family member TWEAK (TNF-like weak inducer of apoptosis promotes β-cell neogenesis from proliferating pancreatic ductal epithelium in adult mice. METHODS: C57Bl/6J mice were treated with Fc-TWEAK and pancreas harvested at different time points for analysis by histology and immunohistochemistry. For lineage tracing, 4 week old double transgenic mice CAII-CreER(TM: R26R-eYFP were implanted with tamoxifen pellet, injected with Fc-TWEAK or control Ig twice weekly and analyzed at day 18 for TWEAK-induced duct cell progeny by costaining for insulin and YFP. The effect of TWEAK on pancreatic regeneration was determined by pancytokeratin immunostaining of paraffin embedded sections from wildtype and TWEAK receptor (Fn14 deficient mice after Px. RESULTS: TWEAK stimulates proliferation of ductal epithelial cells through its receptor Fn14, while it has no mitogenic effect on pancreatic α- or β-cells or acinar cells. Importantly, TWEAK induces transient expression of endogenous Ngn3, a master regulator of endocrine cell development, and induces focal ductal structures with characteristics of regeneration foci. In addition, we identify by lineage tracing TWEAK-induced pancreatic β-cells derived from pancreatic duct epithelial cells. Conversely, we show that Fn14 deficiency delays formation of regenerating foci after Px and limits their expansion. CONCLUSIONS/INTERPRETATION: We conclude that TWEAK is a novel factor mediating pancreatic β-cell neogenesis from ductal epithelium in normal adult mice.

  17. Neonatal Whisker Trimming Impairs Fear/Anxiety-Related Emotional Systems of the Amygdala and Social Behaviors in Adult Mice.

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    Hitomi Soumiya

    Full Text Available Abnormalities in tactile perception, such as sensory defensiveness, are common features in autism spectrum disorder (ASD. While not a diagnostic criterion for ASD, deficits in tactile perception contribute to the observed lack of social communication skills. However, the influence of tactile perception deficits on the development of social behaviors remains uncertain, as do the effects on neuronal circuits related to the emotional regulation of social interactions. In neonatal rodents, whiskers are the most important tactile apparatus, so bilateral whisker trimming is used as a model of early tactile deprivation. To address the influence of tactile deprivation on adult behavior, we performed bilateral whisker trimming in mice for 10 days after birth (BWT10 mice and examined social behaviors, tactile discrimination, and c-Fos expression, a marker of neural activation, in adults after full whisker regrowth. Adult BWT10 mice exhibited significantly shorter crossable distances in the gap-crossing test than age-matched controls, indicating persistent deficits in whisker-dependent tactile perception. In contrast to controls, BWT10 mice exhibited no preference for the social compartment containing a conspecific in the three-chamber test. Furthermore, the development of amygdala circuitry was severely affected in BWT10 mice. Based on the c-Fos expression pattern, hyperactivity was found in BWT10 amygdala circuits for processing fear/anxiety-related responses to height stress but not in circuits for processing reward stimuli during whisker-dependent cued learning. These results demonstrate that neonatal whisker trimming and concomitant whisker-dependent tactile discrimination impairment severely disturbs the development of amygdala-dependent emotional regulation.

  18. Neonatal Whisker Trimming Impairs Fear/Anxiety-Related Emotional Systems of the Amygdala and Social Behaviors in Adult Mice

    Science.gov (United States)

    Soumiya, Hitomi; Godai, Ayumi; Araiso, Hiromi; Mori, Shingo; Furukawa, Shoei; Fukumitsu, Hidefumi

    2016-01-01

    Abnormalities in tactile perception, such as sensory defensiveness, are common features in autism spectrum disorder (ASD). While not a diagnostic criterion for ASD, deficits in tactile perception contribute to the observed lack of social communication skills. However, the influence of tactile perception deficits on the development of social behaviors remains uncertain, as do the effects on neuronal circuits related to the emotional regulation of social interactions. In neonatal rodents, whiskers are the most important tactile apparatus, so bilateral whisker trimming is used as a model of early tactile deprivation. To address the influence of tactile deprivation on adult behavior, we performed bilateral whisker trimming in mice for 10 days after birth (BWT10 mice) and examined social behaviors, tactile discrimination, and c-Fos expression, a marker of neural activation, in adults after full whisker regrowth. Adult BWT10 mice exhibited significantly shorter crossable distances in the gap-crossing test than age-matched controls, indicating persistent deficits in whisker-dependent tactile perception. In contrast to controls, BWT10 mice exhibited no preference for the social compartment containing a conspecific in the three-chamber test. Furthermore, the development of amygdala circuitry was severely affected in BWT10 mice. Based on the c-Fos expression pattern, hyperactivity was found in BWT10 amygdala circuits for processing fear/anxiety-related responses to height stress but not in circuits for processing reward stimuli during whisker-dependent cued learning. These results demonstrate that neonatal whisker trimming and concomitant whisker-dependent tactile discrimination impairment severely disturbs the development of amygdala-dependent emotional regulation. PMID:27362655

  19. Male CD81 Knockout Genotype Disrupts Mendelian Distribution of Offspring

    OpenAIRE

    Mordica, Whitney J.; Gallagher, Ryan J; Kennedy, Jenna L; Chapes, Stephen K.

    2010-01-01

    CD81 is an integral membrane protein in the tetraspanin superfamily that serves as an adaptor protein. CD81 is also a maternally imprinted gene that is found in a regulated cluster of genes on mouse chromosome 7. Among offspring produced from heterozygous breeding pairs, CD81null/null mice grew at the same rate as CD81+/+ and CD81+/null mice. Because of an inhibition in sperm–egg fusion, CD81null/null female mice are much less fertile than CD81+/+ and CD81+/null mice. However, no published st...

  20. Activity of Artemether and Mefloquine against Juvenile and Adult Schistosoma mansoni in Athymic and Immunocompetent NMRI Mice

    OpenAIRE

    Keiser, Jennifer; Vargas, Mireille; Doenhoff, Michael J.

    2010-01-01

    Immune effector mechanisms can enhance the activity of antischistosomal drugs. We examined the in vivo effect of single oral doses of the antimalarials artemether (400 mg/kg) and mefloquine (200 mg/kg), recently described to have promising antischistosomal properties, against juvenile and adult Schistosoma mansoni in T cell-deficient and in comparably infected age- and sex-matched immunologically intact control mice. Artemether and mefloquine are equally effective in athymic and immunocompete...

  1. Functional Analysis of Neurovascular Adaptations to Exercise in the Dentate Gyrus of Young Adult Mice Associated With Cognitive Gain

    OpenAIRE

    Clark, Peter J.; Brzezinska, Weronika J.; Puchalski, Emily K.; Krone, David A.; Rhodes, Justin S.

    2009-01-01

    The discovery that aerobic exercise increases adult hippocampal neurogenesis and can enhance cognitive performance holds promise as a model for regenerative medicine. This study adds two new pieces of information to the rapidly growing field. First, we tested whether exercise increases vascular density in the granular layer of the dentate gyrus, whole hippocampus, and striatum in C57BL/6J mice known to display procognitive effects of exercise. Second, we determined the extent to which new neu...

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

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    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.

  3. An autoradiographic study of new fat cell formation in adipose tissue in adult mice during malnutrition and refeeding

    International Nuclear Information System (INIS)

    The renewal of adipose cells in adult mice has been autoradiographically studied. The number of adipose cells was diminished by eighty percent during malnutrition and the same number of adipose cells proliferated during the refeeding stage. The results of our study showed that adipose tissue, which had previously been believed to be stable in cell number, has the capacity for cell proliferation according to changes in nutritional status. (author)

  4. Chronic hemodynamic unloading regulates the morphologic development of newborn mouse hearts transplanted into the ear of isogeneic adult mice.

    OpenAIRE

    Rossi, M. A.

    1992-01-01

    The morphologic development of newborn mouse hearts transplanted into the pinna of the ears of isogeneic adult mice was assessed in comparison to in situ ventricular myocardium of recipients. The grafted hearts became vascularized from the auricular artery at the base of the ear, and although these preparations appeared not to be intrinsically innervated, most of them showed grossly visible pulsatile activity. Since they were not subjected to hemodynamic load due to working against a pressure...

  5. Paternal irradiation perturbs the expression of circadian genes in offspring

    Energy Technology Data Exchange (ETDEWEB)

    Gomes, Andre M.G.F.; Barber, Ruth C.; Dubrova, Yuri E., E-mail: yed2@le.ac.uk

    2015-05-15

    Highlights: • We have analysed gene expression in the offspring of irradiated male mice. • CBA/Ca and BALB/c male mice were used in our study. • The pattern of gene expression was established in four tissues. • Expression of genes in involved in rhythmic process/circadian rhythm is compromised. • Our data may explain the phenomenon of transgenerational genomic instability. - Abstract: The circadian system represents a complex network which influences the timing of many biological processes. Recent studies have established that circadian alterations play an important role in the susceptibility to many human diseases, including cancer. Here we report that paternal irradiation in mice significantly affects the expression of genes involved in rhythmic processes in their first-generation offspring. Using microarrays, the patterns of gene expression were established for brain, kidney, liver and spleen samples from the non-exposed offspring of irradiated CBA/Ca and BALB/c male mice. The most over-represented categories among the genes differentially expressed in the offspring of control and irradiated males were those involved in rhythmic process, circadian rhythm and DNA-dependent regulation of transcription. The results of our study therefore provide a plausible explanation for the transgenerational effects of paternal irradiation, including increased transgenerational carcinogenesis described in other studies.

  6. Paternal irradiation perturbs the expression of circadian genes in offspring

    International Nuclear Information System (INIS)

    Highlights: • We have analysed gene expression in the offspring of irradiated male mice. • CBA/Ca and BALB/c male mice were used in our study. • The pattern of gene expression was established in four tissues. • Expression of genes in involved in rhythmic process/circadian rhythm is compromised. • Our data may explain the phenomenon of transgenerational genomic instability. - Abstract: The circadian system represents a complex network which influences the timing of many biological processes. Recent studies have established that circadian alterations play an important role in the susceptibility to many human diseases, including cancer. Here we report that paternal irradiation in mice significantly affects the expression of genes involved in rhythmic processes in their first-generation offspring. Using microarrays, the patterns of gene expression were established for brain, kidney, liver and spleen samples from the non-exposed offspring of irradiated CBA/Ca and BALB/c male mice. The most over-represented categories among the genes differentially expressed in the offspring of control and irradiated males were those involved in rhythmic process, circadian rhythm and DNA-dependent regulation of transcription. The results of our study therefore provide a plausible explanation for the transgenerational effects of paternal irradiation, including increased transgenerational carcinogenesis described in other studies

  7. Gastrointestinal absorption of plutonium and uranium in fed and fasted adult baboons and mice: application to humans

    International Nuclear Information System (INIS)

    Gastrointestinal (GI) absorption values of plutonium and uranium were determined in fed and fasted adult baboons and mice. For both baboons and mice, the GI absorptions of plutonium and uranium were 10 to 20 times higher in 24 h fasted animals than in fed ones. For plutonium, GI absorption values in baboons were almost identical to those in mice for both fed and fasted conditions, and values for fed animals agreed with estimates for humans. For uranium, GI absorption values in fed and fasted baboons were 6 to 7 times higher than those in mice, and agreed well with those fed and fasted humans. For one baboon that was not given its morning meal, plutonium absorption 2 h after the start of the active phase was the same as that in the 24 h fasted animals. In contrast, for baboons that received a morning meal, plutonium absorption did not rise to the value of 24 h fasted baboons even 8 h after the meal. We conclude that GI absorption values for plutonium and uranium in adult baboons are good estimates of the values in humans and that the values for the fasted condition should be used to set standards for oral exposure of persons in the workplace. (author)

  8. Maternal inheritance of severe hypertriglyceridemia impairs glucose metabolism in offspring

    OpenAIRE

    Ma, Ya-Hong; Yu, Caiguo; Kayoumu, Abudurexiti; Guo, Xin; Ji, Zhili; Liu, George

    2015-01-01

    Abstract Maternally inherited familial hypercholesterolemia (FH) impairs glucose metabolism and increases cardiovascular risks in the offspring to a greater degree than paternal inherited FH. However, it remains unknown whether hypertriglyceridemia affects glucose metabolism via inheritance. In this study, we sought to compare the impact of maternally and paternally inherited hypertriglyceridemia on glucose and lipid metabolism in mice. ApoCIII transgenic mice with severe hypertriglyceridemia...

  9. Impaired Memory in OT-II Transgenic Mice Is Associated with Decreased Adult Hippocampal Neurogenesis Possibly Induced by Alteration in Th2 Cytokine Levels.

    Science.gov (United States)

    Jeon, Seong Gak; Kim, Kyoung Ah; Chung, Hyunju; Choi, Junghyun; Song, Eun Ji; Han, Seung-Yun; Oh, Myung Sook; Park, Jong Hwan; Kim, Jin-Il; Moon, Minho

    2016-08-31

    Recently, an increasing number of studies have focused on the effects of CD4+ T cell on cognitive function. However, the changes of Th2 cytokines in restricted CD4+ T cell receptor (TCR) repertoire model and their effects on the adult hippocampal neurogenesis and memory are not fully understood. Here, we investigated whether and how the mice with restricted CD4+ repertoire TCR exhibit learning and memory impairment by using OT-II mice. OT-II mice showed decreased adult neurogenesis in hippocampus and short- and long- term memory impairment. Moreover, Th2 cytokines in OT-II mice are significantly increased in peripheral organs and IL-4 is significantly increased in brain. Finally, IL-4 treatment significantly inhibited the proliferation of cultured adult rat hippocampal neural stem cells. Taken together, abnormal level of Th2 cytokines can lead memory dysfunction via impaired adult neurogenesis in OT-II transgenic. PMID:27432189

  10. Maternal immune activation leads to selective functional deficits in offspring parvalbumin interneurons.

    Science.gov (United States)

    Canetta, S; Bolkan, S; Padilla-Coreano, N; Song, L J; Sahn, R; Harrison, N L; Gordon, J A; Brown, A; Kellendonk, C

    2016-07-01

    Abnormalities in prefrontal gamma aminobutyric acid (GABA)ergic transmission, particularly in fast-spiking interneurons that express parvalbumin (PV), are hypothesized to contribute to the pathophysiology of multiple psychiatric disorders, including schizophrenia, bipolar disorder, anxiety disorders and depression. While primarily histological abnormalities have been observed in patients and in animal models of psychiatric disease, evidence for abnormalities in functional neurotransmission at the level of specific interneuron populations has been lacking in animal models and is difficult to establish in human patients. Using an animal model of a psychiatric disease risk factor, prenatal maternal immune activation (MIA), we found reduced functional GABAergic transmission in the medial prefrontal cortex (mPFC) of adult MIA offspring. Decreased transmission was selective for interneurons expressing PV, resulted from a decrease in release probability and was not observed in calretinin-expressing neurons. This deficit in PV function in MIA offspring was associated with increased anxiety-like behavior and impairments in attentional set shifting, but did not affect working memory. Furthermore, cell-type specific optogenetic inhibition of mPFC PV interneurons was sufficient to impair attentional set shifting and enhance anxiety levels. Finally, we found that in vivo mPFC gamma oscillations, which are supported by PV interneuron function, were linearly correlated with the degree of anxiety displayed in adult mice, and that this correlation was disrupted in MIA offspring. These results demonstrate a selective functional vulnerability of PV interneurons to MIA, leading to affective and cognitive symptoms that have high relevance for schizophrenia and other psychiatric disorders. PMID:26830140

  11. Suckling a protein-restricted rat dam leads to diminished albuminuria in her male offspring in adult life: a longitudinal study

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    James Lynwen A

    2006-09-01

    Full Text Available Abstract Background Previous studies have shown that in male rats, exposure to maternal protein restriction either in utero or whilst suckling can have profound effects on both longevity and kidney telomere lengths. This study monitored albuminuria longitudinally in male rats whose mothers had been protein restricted either during pregnancy or lactation. Methods Pregnant Wistar rats were fed either a 20% ('control' or an 8% protein ('low protein' diet. At two days of age some of the pups were cross-fostered to dams fed the diet that was not given to their biological mothers. At weaning all pups were fed standard chow. Urine samples were collected for the measurement of albumin and creatinine at monthly intervals from two months-of-age. Longitudinal analysis was then performed using repeated measures analysis of variance. Results Overall estimated marginal geometric mean (95 % confidence interval urine albumin to creatinine ratios were: control animals 79.5 (57.2~110.6 g/mol (n = 6 litters, 24 animals in total, those exposed in utero to maternal protein restriction 71.0 (47.4~106.5 (n = 4 litters, 16 animals in total, those exposed to maternal protein restriction whilst suckling 21.2 (14.7~30.4 (n = 5 litters, 20 animals in total (p Conclusion Animals exposed to maternal protein restriction whilst suckling exhibited lower urine albumin excretions during much of adult life. As urine albumin can be nephrotoxic, these rats therefore appeared to be relatively protected against future nephron damage like that previously observed in animals exposed to maternal protein restriction in utero.

  12. Effect of Infection Duration on Habitat Selection and Morphology of Adult Echinostoma caproni (Digenea: Echinostomatidae) in ICR Mice.

    Science.gov (United States)

    Platt, Thomas R; Zelmer, Derek A

    2016-02-01

    The course of infection of Echinostoma caproni was followed in female ICR mice, a permissive laboratory host, from infection to natural termination. Twenty-one mice were infected with 20 metacercariae via oral intubation and housed 3 per cage. Three mice from a randomly selected cage were necropsied at 1 mo intervals. A second group of 15 mice was infected approximately 1 yr later to replace mice negative at necropsy in the first group. Mice in the second group were examined weekly for the presence of eggs in the feces. Mice negative for eggs on consecutive days were killed and necropsied. The location of individual worms and worm clusters were located in 20 segments of the small intestine. Adult worms were killed and fixed in hot formalin, stained, and prepared as whole mounts. Standard measurements were taken using a compound microscope fitted with an ocular micrometer. The infection spontaneously resolved in 10 mice from 7 to 32 wk PI, indicating the host response is highly variable and extending the maximum recorded length of E. caproni infections in ICR mice to 31 wk. A moribund worm was found in the feces of an animal that continued to pass eggs for an additional 2 mo indicating individual variation in worm responses. Worms located preferentially in the ileum (segments 11-13) during the first 3 mo of the infection but shifted to the jejunum (segments 8-9) during weeks 4-6. Morphologically, worms of different ages clustered together in multivariate space, with substantial overlap between the 3- and 4-mo-old infrapopulations and between the 5- and 6-mo-old infrapopulations. Muscular structures increased in size throughout the experiment, while the gonads increased in size for the first 3 mo and then declined during the last 3 mo. The relationship between E. caproni and ICR mice is more nuanced than previously reported. The reduction in gonad size and the shift from the ileum to the jejunum in the last 3 mo likely are related. These changes might be attributable

  13. Effect of prenatal stress on the expression of Parvalbuminand Calretinin in adult female rat offspring%孕期应激对子代雌鼠成年后钙结合蛋白Parvalbumin和Calretinin表达的影响

    Institute of Scientific and Technical Information of China (English)

    伍校琼; 王岐本; 蔡维君; 罗明英

    2015-01-01

    目的:探讨孕期应激对子代雌鼠成年后钙结合蛋白阳性神经元表达的影响。方法6只SD孕鼠随机分为孕期应激组(PS组)和对照组(CON组)。PS组孕鼠在妊娠晚期接受限制性应激,CON组不给予孕期应激。子代成年后,PS组和CON组雌性子代随机分别又分为PS-S组,PS-NS组,CON-S组和CON-NS组(n均=6)。PS-S组和CON-S组动物先后接受限制性应激和冰水应激。动物在接受应激后均给与水和酒精喂养,用Western blot检测海马钙结合蛋白Parvalbumin(PV)和Calretinin(CR)蛋白的表达,进一步结合共聚焦免疫荧光组织化学方法检测PV和CR在海马CA1、CA3区和齿状回(dentate gyrus, DG)的表达。结果与CON-NS组相比,海马区PV和CR的蛋白表达在CON-S,PS-NS和PS-S组下降,以PS-S组表达最低。PV在海马CA1、CA3区和DG的免疫荧光结果与PV的蛋白表达呈一致性,免疫阳性细胞明显减少;而CR的表达除了在海马CA1区的PS-NS组略有升高外,在其余各组的表达均较减少。与CON-NS组相比,PV和CR在其它各组的蛋白表达和免疫阳性细胞计数差异有统计学意义,其中以PS-S组的表达降低最为有统计学意义(P<0.05)。结论孕期应激可影响子代雌鼠成年后海马结构钙结合蛋白PV和CR的表达。%Objective To observe the effect of prenatal stress on the expression of Parvalbumin(PV) and Calretinin(CR)in adult female rat offspring. Methods Six pregnant SD rats were randomly divided into a prenatal stress (PS) group and a control group (CON). Rats in PS group were subjected to restraint stress during the late gestational periods, while rats in the control group were not given prenatal stress. The adult female offspring were randomly divided into PS plus stress group (PS-S) and PS without stress group (PS-NS), CON plus stress group (CON-S) and CON plus no stress group (CON-NS). The rats in PS-S and CON-S were subjected to

  14. 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.

  15. Cerebral cell renewal in adult mice controls the onset of obesity.

    Directory of Open Access Journals (Sweden)

    Alexandra Gouazé

    Full Text Available The hypothalamus plays a crucial role in the control of the energy balance and also retains neurogenic potential into adulthood. Recent studies have reported the severe alteration of the cell turn-over in the hypothalamus of obese animals and it has been proposed that a neurogenic deficiency in the hypothalamus could be involved in the development of obesity. To explore this possibility, we examined hypothalamic cell renewal during the homeostatic response to dietary fat in mice, i.e., at the onset of diet-induced obesity. We found that switching to high-fat diet (HFD accelerated cell renewal in the hypothalamus through a local, rapid and transient increase in cell proliferation, peaking three days after introducing the HFD. Blocking HFD-induced cell proliferation by central delivery of an antimitotic drug prevented the food intake normalization observed after HFD introduction and accelerated the onset of obesity. This result showed that HFD-induced dividing brain cells supported an adaptive anorectic function. In addition, we found that the percentage of newly generated neurons adopting a POMC-phenotype in the arcuate nucleus was increased by HFD. This observation suggested that the maturation of neurons in feeding circuits was nutritionally regulated to adjust future energy intake. Taken together, these results showed that adult cerebral cell renewal was remarkably responsive to nutritional conditions. This constituted a physiological trait required to prevent severe weight gain under HFD. Hence this report highlighted the amazing plasticity of feeding circuits and brought new insights into our understanding of the nutritional regulation of the energy balance.

  16. 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

    OpenAIRE

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

    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 injec...

  17. Genetic pharmacotherapy as an early CNS drug development strategy: testing glutaminase inhibition for schizophrenia treatment in adult mice

    Directory of Open Access Journals (Sweden)

    Susana eMingote

    2016-01-01

    Full Text Available Genetic pharmacotherapy is an early drug development strategy for the identification of novel CNS targets in mouse models prior to the development of specific ligands. Here for the first time, we have implemented this strategy to address the potential therapeutic value of a glutamate-based pharmacotherapy for schizophrenia involving inhibition of the glutamate recycling enzyme phosphate-activated glutaminase. Mice constitutively heterozygous for GLS1, the gene encoding glutaminase, manifest a schizophrenia resilience phenotype, a key dimension of which is an attenuated locomotor response to propsychotic amphetamine challenge. If resilience is due to glutaminase deficiency in adulthood, then glutaminase inhibitors should have therapeutic potential. However, this has been difficult to test given the dearth of neuroactive glutaminase inhibitors. So, we used genetic pharmacotherapy to test the therapeutic potential of glutaminase inhibition. We specifically asked whether adult induction of GLS1 heterozygosity would attenuate amphetamine responsiveness. We generated conditional floxGLS1 mice and crossed them with global CAG ERT2 cre/+ mice to produce GLS1 iHET mice, susceptible to tamoxifen induction of GLS1 heterozygosity. One month after tamoxifen treatment of adult GLS1 iHET mice, we found a 50% reduction in GLS1 allelic abundance and glutaminase mRNA levels in the brain. While GLS1 iHET mice showed some recombination prior to tamoxifen, there was no impact on mRNA levels. We then asked whether induction of GLS heterozygosity would attenuate the locomotor response to propsychotic amphetamine challenge. Before tamoxifen, control and GLS1 iHET mice did not differ in their response to amphetamine. One month after tamoxifen treatment, amphetamine-induced hyperlocomotion was blocked in GLS1 iHET mice. The block was largely maintained after 5 months. Thus, a genetically induced glutaminase reduction — mimicking pharmacological inhibition — strongly

  18. Natural suppressor (NS) cells found in the spleen of neonatal mice and adult mice given total lymphoid irradiation (TLI) express the null surface phenotype

    International Nuclear Information System (INIS)

    The authors studied the surface markers of suppressor cells of the mixed leukocyte reaction (MLR) that are transiently present in the spleens of neonatal mice after birth and of adult mice after total lymphoid irradiation (TLI). Approximately 80% of the mononuclear cells in the spleen, within the first few days after birth or after TLI, express neither the Thy-1 antigen nor surface immunoglobulin (Ig). After 30 days, less than 20% of mononuclear cells bear this null phenotype. With the use of the panning technique, they showed that the suppressors of the MLR are confined to the null cell population. The null suppressor cells are not macrophages because they did not carry macrophage markers identified by the monoclonal antibodies anti-MAC-1 and F4/80. In addition, the suppressor cells did not stain for nonspecific esterase and did not adhere firmly to plastic or glass. Spleen cells from TLI-treated mice maintained their suppressive capacity after culture in vitro for 6 to 8 wk. The cultured suppressor cells did not develop mature T cell, B cell, or macrophage markers during this time interval. Thus, the suppressor cells did not appear to be precursors of the latter cells. The suppressor cells are similar to NK cells in that both are found in the absence of antigenic challenge, lack antigen specificity, and bear the null surface phenotype. Thus, they have termed the former cells natural suppressor (NS) cells

  19. Methionine restriction restores a younger metabolic phenotype in adult mice with alterations in fibroblast growth factor 21.

    Science.gov (United States)

    Lees, Emma K; Król, Elżbieta; Grant, Louise; Shearer, Kirsty; Wyse, Cathy; Moncur, Eleanor; Bykowska, Aleksandra S; Mody, Nimesh; Gettys, Thomas W; Delibegovic, Mirela

    2014-10-01

    Methionine restriction (MR) decreases body weight and adiposity and improves glucose homeostasis in rodents. Similar to caloric restriction, MR extends lifespan, but is accompanied by increased food intake and energy expenditure. Most studies have examined MR in young animals; therefore, the aim of this study was to investigate the ability of MR to reverse age-induced obesity and insulin resistance in adult animals. Male C57BL/6J mice aged 2 and 12 months old were fed MR (0.172% methionine) or control diet (0.86% methionine) for 8 weeks or 48 h. Food intake and whole-body physiology were assessed and serum/tissues analyzed biochemically. Methionine restriction in 12-month-old mice completely reversed age-induced alterations in body weight, adiposity, physical activity, and glucose tolerance to the levels measured in healthy 2-month-old control-fed mice. This was despite a significant increase in food intake in 12-month-old MR-fed mice. Methionine restriction decreased hepatic lipogenic gene expression and caused a remodeling of lipid metabolism in white adipose tissue, alongside increased insulin-induced phosphorylation of the insulin receptor (IR) and Akt in peripheral tissues. Mice restricted of methionine exhibited increased circulating and hepatic gene expression levels of FGF21, phosphorylation of eIF2a, and expression of ATF4, with a concomitant decrease in IRE1α phosphorylation. Short-term 48-h MR treatment increased hepatic FGF21 expression/secretion and insulin signaling and improved whole-body glucose homeostasis without affecting body weight. Our findings suggest that MR feeding can reverse the negative effects of aging on body mass, adiposity, and insulin resistance through an FGF21 mechanism. These findings implicate MR dietary intervention as a viable therapy for age-induced metabolic syndrome in adult humans. PMID:24935677

  20. Presynaptic size of associational/commissural CA3 synapses is controlled by fibroblast growth factor 22 in adult mice.

    Science.gov (United States)

    Pasaoglu, Taliha; Schikorski, Thomas

    2016-02-01

    Associational/commissural CA3-CA3 synapses define the recurrent CA3 network that generates the input to CA1 pyramidal neurons. We quantified the fine structure of excitatory synapses in the stratum radiatum of the CA3d area in adult wild type (WT) and fibroblast growth factor 22 knock-out (FGF22KO) mice by using serial 3D electron microscopy. WT excitatory CA3 synapses are rather small yet range 10 fold in size. Spine size, however, was small and uniform and did not correlate with the size of the synaptic junction. To reveal mechanisms that regulate presynaptic structure, we investigated the role of FGF22, a target-derived signal specific for the distal part of area CA3 (CA3d). In adult FGF22KO mice, postsynaptic properties of associational CA3 synapses were unaltered. Presynaptically, the number of synaptic vesicles (SVs), the bouton volume, and the number of vesicles in axonal regions (the super pool) were reduced. This concurrent decrease suggests concerted control by FGF22 of presynaptic size. This hypothesis is supported by the finding that WT presynapses in the proximal part of area CA3 (CA3p) that do not receive FGF22 signaling in WT mice were smaller than presynapses in CA3d in WT but of comparable size in CA3d of FGF22KO mice. Docked SV density was decreased in CA1, CA3d, and CA3p in FGF22KO mice. Because CA1 and CA3p are not directly affected by the loss of FGF22, the smaller docked SV density may be an adaptation to activity changes in the CA3 network. Thus, docked SV density potentially is a long-term regulator for the synaptic release probability and/or the strength of short-term depression in vivo. PMID:26222899

  1. Immunosuppression in early postnatal days induces persistent and allergen-specific immune tolerance to asthma in adult mice.

    Directory of Open Access Journals (Sweden)

    Yan Chen

    Full Text Available Bronchial asthma is a chronic airway inflammatory condition with high morbidity, and effective treatments for asthma are limited. Allergen-specific immunotherapy can only induce peripheral immune tolerance and is not sustainable. Exploring new therapeutic strategies is of great clinical importance. Recombinant adenovirus (rAdV was used as a vector to make cells expressing cytotoxic T lymphocyte-associated antigen-4-immunoglobulin (CTLA4Ig a soluble CTLA4 immunoglobulin fusion protein. Dendritic cells (DCs were modified using the rAdVs together with allergens. Then these modified DCs were transplanted to mice before allergen sensitization. The persistence and specificity of immune tolerance were evaluated in mice challenged with asthma allergens at 3 and 7 months. DCs modified by CTLA4Ig showed increased IL-10 secretion, decreased IL-12 secretion, and T cell stimulation in vitro. Mice treated with these DCs in the early neonatal period developed tolerance against the allergens that were used to induce asthma in the adult stage. Asthma symptoms, lung damage, airway reactivity, and inflammatory response all improved. Humoral immunity indices showed that this therapeutic strategy strongly suppressed mice immune responses and was maintained for as long as 7 months. Furthermore, allergen cross-sensitization and challenge experiments demonstrated that this immune tolerance was allergen-specific. Treatment with CTLA4Ig modified DCs in the early neonatal period, inducing persistent and allergen-specific immune tolerance to asthma in adult mice. Our results suggest that it may be possible to develop a vaccine for asthma.

  2. Environmental Enrichment Reduces the Likelihood of Alopecia in Adult C57BL/6J Mice

    OpenAIRE

    Bechard, Allison; Meagher, Rebecca; Mason, Georgia

    2011-01-01

    Barbering (incessant grooming) is an abnormal behavior causing alopecia and commonly affects various strains of laboratory mice, including C57BL/6J. Barbering-induced alopecia is a potential symptom of brain impairment and can indicate a stressful environment. We compared alopecia prevalence and severity in mice housed in enriched or standard cages. Providing an enriched environment delayed the onset and reduced the prevalence and overall severity of alopecia in C57BL/6J mice. Husbandry metho...

  3. Neonatal Bacillus Calmette-Guérin vaccination alleviates lipopolysaccharide-induced neurobehavioral impairments and neuroinflammation in adult mice.

    Science.gov (United States)

    Yang, Junhua; Qi, Fangfang; Yao, Zhibin

    2016-08-01

    The Bacillus Calmette-Guérin (BCG) vaccine is routinely administered to human neonates worldwide. BCG has recently been identified as a neuroprotective immune mediator in several neuropathological conditions, exerting neuroprotection in a mouse model of Parkinson's disease and slowing the progression of clinically isolated syndrome in patients with multiple sclerosis. The immune system is significantly involved in brain development, and several types of neonatal immune activations exert influences on the brain and behavior following a secondary immune challenge in adulthood. However, whether the neonatal BCG vaccination affects the brain in adulthood remains to be elucidated. In the present study, newborn C57BL/6 mice were injected subcutaneously with BCG (105 colony forming units) or phosphate‑buffered saline (PBS). A total of 12 weeks later, the mice were injected intraperitoneally with 330 µg/kg lipopolysaccharide (LPS) or PBS. The present study reported that the neonatal BCG vaccination alleviated sickness, anxiety and depression‑like behavior, lessened the impairments in hippocampal cell proliferation and downregulated the proinflammatory responses in the serum and brain that were induced by the adult LPS challenge. However, BCG vaccination alone had no evident influence on the brain and behavior in adulthood. In conclusion, the neonatal BCG vaccination alleviated the neurobehavioral impairments and neuroinflammation induced by LPS exposure in adult mice, suggesting a potential neuroprotective role of the neonatal BCG vaccination in adulthood. PMID:27357155

  4. Blocking glucocorticoid receptors at adolescent age prevents enhanced freezing between repeated cue-exposures after conditioned fear in adult mice raised under chronic early life stress.

    Science.gov (United States)

    Arp, J Marit; Ter Horst, Judith P; Loi, Manila; den Blaauwen, Jan; Bangert, Eline; Fernández, Guillén; Joëls, Marian; Oitzl, Melly S; Krugers, Harm J

    2016-09-01

    Early life adversity can have long-lasting impact on learning and memory processes and increase the risk to develop stress-related psychopathologies later in life. In this study we investigated (i) how chronic early life stress (ELS) - elicited by limited nesting and bedding material from postnatal day 2 to 9 - affects conditioned fear in adult mice and (ii) whether these effects can be prevented by blocking glucocorticoid receptors (GRs) at adolescent age. In adult male and female mice, ELS did not affect freezing behavior to the first tone 24h after training in an auditory fear-conditioning paradigm. Exposure to repeated tones 24h after training also resulted in comparable freezing behavior in ELS and control mice, both in males and females. However, male (but not female) ELS compared to control mice showed significantly more freezing behavior between the tone-exposures, i.e. during the cue-off periods. Intraperitoneal administration of the GR antagonist RU38486 during adolescence (on postnatal days 28-30) fully prevented enhanced freezing behavior during the cue-off period in adult ELS males. Western blot analysis revealed no effects of ELS on hippocampal expression of glucocorticoid receptors, neither at postnatal day 28 nor at adult age, when mice were behaviorally tested. We conclude that ELS enhances freezing behavior in adult mice in a potentially safe context after cue-exposure, which can be normalized by brief blockade of glucocorticoid receptors during the critical developmental window of adolescence. PMID:27246249

  5. Linking adult olfactory neurogenesis to social behavior

    Directory of Open Access Journals (Sweden)

    Claudia E Feierstein

    2012-11-01

    Full Text Available In the adult brain, new neurons are added to two brain areas: the olfactory bulb and the hippocampus. Newly-generated neurons integrate into the preexisting circuits, bringing a set of unique properties, such as increased plasticity and responsiveness to stimuli. However, the functional implications of the constant addition of these neurons remain unclear, although they are believed to be important for learning and memory. The levels of neurogenesis are regulated by a variety of environmental factors, as well as during learning, suggesting that new neurons could be important for coping with changing environmental demands. Notably, neurogenesis has been shown to be physiologically regulated in relation to reproductive behavior: neurogenesis increases in female mice upon exposure to cues of the mating partners, during pregnancy and lactation, and in male mice upon exposure to their offspring. In this scenario, and because of the key contribution of olfaction to maternal behavior, we sought to investigate the contribution of adult-generated neurons in the olfactory system to maternal behavior and offspring recognition. To do so, we selectively disrupted neurogenesis in the olfactory pathway of female mice using focal irradiation. Disruption of adult neurogenesis in the olfactory bulb did not affect maternal behavior, or the ability of female mice to discriminate familiar from unfamiliar pups. However, reduction of olfactory neurogenesis resulted in abnormal social interaction of female mice, specifically with male conspecifics. Because the olfactory system is crucial for sex recognition, we suggest that the abnormal interaction with males could result from the inability to detect or discriminate male-specific odors and could therefore have implications for the recognition of potential mating partners. Here, I review the results of this and other studies, and discuss their implications for our understanding of the function of adult neurogenesis.

  6. Circadian cycle-dependent EEG biomarkers of pathogenicity in adult mice following prenatal exposure to in utero inflammation.

    Science.gov (United States)

    Adler, D A; Ammanuel, S; Lei, J; Dada, T; Borbiev, T; Johnston, M V; Kadam, S D; Burd, I

    2014-09-01

    Intrauterine infection or inflammation in preterm neonates is a known risk for adverse neurological outcomes, including cognitive, motor and behavioral disabilities. Our previous data suggest that there is acute fetal brain inflammation in a mouse model of intrauterine exposure to lipopolysaccharides (LPS). We hypothesized that the in utero inflammation induced by LPS produces long-term electroencephalogram (EEG) biomarkers of neurodegeneration in the exposed mice that could be determined by using continuous quantitative video/EEG/electromyogram (EMG) analyses. A single LPS injection at E17 was performed in pregnant CD1 dams. Control dams were injected with same volumes of saline (LPS n=10, Control n=8). At postnatal age of P90-100, 24-h synchronous video/EEG/EMG recordings were done using a tethered recording system and implanted subdural electrodes. Behavioral state scoring was performed blind to treatment group, on each 10s EEG epoch using synchronous video, EMG and EEG trace signatures to generate individual hypnograms. Automated EEG power spectrums were analyzed for delta and theta-beta power ratios during wake vs. sleep cycles. Both control and LPS hypnograms showed an ultradian wake/sleep cycling. Since rodents are nocturnal animals, control mice showed the expected diurnal variation with significantly longer time spent in wake states during the dark cycle phase. In contrast, the LPS-treated mice lost this circadian rhythm. Sleep microstructure also showed significant alteration in the LPS mice specifically during the dark cycle, caused by significantly longer average non-rapid eye movement (NREM) cycle durations. No significance was found between treatment groups for the delta power data; however, significant activity-dependent changes in theta-beta power ratios seen in controls were absent in the LPS-exposed mice. In conclusion, exposure to in utero inflammation in CD1 mice resulted in significantly altered sleep architecture as adults that were circadian

  7. Maternal overweight programs insulin and adiponectin signaling in the offspring

    Science.gov (United States)

    Gestational exposure to maternal overweight (OW) influences the risk of obesity in adult-life. Male offspring from OW dams gain greater body weight, fat mass and develop insulin resistance when fed high fat diets (45 percent fat). In this report we identify molecular targets of maternal OW-induced p...

  8. Effect of insulin supplementation on in vitro maturation of pre-antral follicles from adult and pre-pubertal mice.

    Science.gov (United States)

    Nath, Amar; Hakim, Bilal Ahmad; Rajender, Singh; Singh, Kavita; Sachdev, Monika; Konwar, Rituraj

    2016-05-01

    This study was aimed to determine the impact of insulin concentrations on in vitro pre-antral follicle growth, survival, antrum formation rate, and retrieval of mature oocytes in mice. Mice pre-antral follicle growth were recorded on days 2, 4, 6, 8, 10, and 12 in α-modified essential media (α-MEM) supplemented with insulin concentrations of 6, 8, and 10 μg/ml along with 10% FBS, 100 mIU/ml follicle stimulating hormone, 10 mIU/ml luteinizing hormone, 100 μg/ml penicillin, and 50 μg/ml streptomycin. After 12 d of growth in vitro, follicles were allowed to mature for 16-18 h in α-MEM supplemented with 1.5 IU/ml human chorionic gonadotrophin (hCG) and 5 ng/ml epidermal growth factor (EGF). The initial diameter (54.86 ± 2.5 μm) of mice oocyte progressively increased in all the three insulin concentration groups and attained a maximum size on day 12 (71.90 ± 2.8 μm). Supplementation with higher concentrations of insulin (both 8 and 10 μg/ml) significantly enhanced antrum formation without effecting the oocyte diameter and percent retrieval of mature oocyte in all the three concentration groups. Both in vitro cultured as well as in vivo collected follicles and oocytes showed similar localization and expression of oocyte maturation markers SAS1B and GDF9. Insulin concentration of 8 μg/ml was found to be optimal for in vitro follicle culture of adult mice (42-49 d). Optimized follicle culture conditions were also assessed successfully with pre-pubertal mice (12-14 d); however, adult mice showed higher follicle survival, antrum formation, and more mature oocytes production in comparison to pre-pubertal mice. PMID:26956357

  9. Chronic early postnatal scream sound stress induces learning deficits and NMDA receptor changes in the hippocampus of adult mice.

    Science.gov (United States)

    Hu, Lili; Han, Bo; Zhao, Xiaoge; Mi, Lihua; Song, Qiang; Wang, Jue; Song, Tusheng; Huang, Chen

    2016-04-13

    Chronic scream sounds during adulthood affect spatial learning and memory, both of which are sexually dimorphic. The long-term effects of chronic early postnatal scream sound stress (SSS) during postnatal days 1-21 (P1-P21) on spatial learning and memory in adult mice as well as whether or not these effects are sexually dimorphic are unknown. Therefore, the present study examines the performance of adult male and female mice in the Morris water maze following exposure to chronic early postnatal SSS. Hippocampal NR2A and NR2B levels as well as NR2A/NR2B subunit ratios were tested using immunohistochemistry. In the Morris water maze, stress males showed greater impairment in spatial learning and memory than background males; by contrast, stress and background females performed equally well. NR2B levels in CA1 and CA3 were upregulated, whereas NR2A/NR2B ratios were downregulated in stressed males, but not in females. These data suggest that chronic early postnatal SSS influences spatial learning and memory ability, levels of hippocampal NR2B, and NR2A/NR2B ratios in adult males. Moreover, chronic early stress-induced alterations exert long-lasting effects and appear to affect performance in a sex-specific manner. PMID:27015584

  10. High frequency of transmission of murine AIDS virus in C57BL/10 mice via mother's milk.

    OpenAIRE

    Okada, Y; Suzuki, K; Komuro, K; Mizuochi, T

    1992-01-01

    Maternal transmission of a murine leukemia virus (MuLV) mixture named LP-BM5 MuLV, which is knwon to induce murine AIDS (MAIDS), was investigated. Adult female C57BL/10 mice were inoculated intraperitoneally with LP-BM5 MuLV. When the virus-inoculated female mice developed splenomegaly or lymphadenopathy, they were mated with normal C57BL/10 male mice. Of 56 offspring born to MAIDS mothers, 14 appeared to develop MAIDS, as assessed by the occurrence of splenomegaly or lymphadenopathy as well ...

  11. Maternal antibiotic-induced early changes in microbial colonization selectively modulate colonic permeability and inducible heat shock proteins, and digesta concentrations of alkaline phosphatase and TLR-stimulants in swine offspring.

    Directory of Open Access Journals (Sweden)

    Marie-Edith Arnal

    Full Text Available Elevated intake of high energy diets is a risk factor for the development of metabolic diseases and obesity. High fat diets cause alterations in colonic microbiota composition and increase gut permeability to bacterial lipopolysaccharide, and subsequent low-grade chronic inflammation in mice. Chronic inflammatory bowel diseases are increasing worldwide and may involve alterations in microbiota-host dialog. Metabolic disorders appearing in later life are also suspected to reflect changes in early programming. However, how the latter affects the colon remains poorly studied. Here, we hypothesized that various components of colonic physiology, including permeability, ion exchange and protective inducible heat shock proteins (HSP are influenced in the short- and long-terms by early disturbances in microbial colonization. The hypothesis was tested in a swine model. Offspring were born to control mothers (n = 12 or mothers treated with the antibiotic (ATB amoxicillin around parturition (n = 11. Offspring were slaughtered between 14 and 42 days of age to study short-term effects. For long-term effects, young adult offspring from the same litters consumed a normal or a palm oil-enriched diet for 4 weeks between 140 and 169 days of age. ATB treatment transiently modified maternal fecal microbiota although the minor differences observed for offspring colonic microbiota were nonsignificant. In the short-term, consistently higher HSP27 and HSP70 levels and transiently increased horseradish peroxidase permeability in ATB offspring colon were observed. Importantly, long-term consequences included reduced colonic horseradish peroxidase permeability, and increased colonic digesta alkaline phosphatase (AP and TLR2- and TLR4-stimulant concentrations in rectal digesta in adult ATB offspring. Inducible HSP27 and HSP70 did not change. Interactions between early ATB treatment and later diet were noted for paracellular permeability and concentrations of colonic

  12. Transient Treg-cell depletion in adult mice results in persistent self-reactive CD4(+) T-cell responses.

    Science.gov (United States)

    Nyström, Sofia N; Bourges, Dorothée; Garry, Sarah; Ross, Ellen M; van Driel, Ian R; Gleeson, Paul A

    2014-12-01

    Depletion of Foxp3(+) CD4(+) regulatory T cells (Treg) in adults results in chronic inflammation and autoimmune disease. However, the impact of transient Treg-cell depletion on self-reactive responses is poorly defined. Here, we studied the effect of transient depletion of Treg cells on CD4(+) T-cell responses to endogenous self-antigens. Short-term ablation of Treg cells in mice resulted in rapid activation of CD4(+) T cells, increased percentage of IFN-γ(+) and Th17 cells in lymphoid organs, and development of autoimmune gastritis. To track self-reactive responses, we analyzed the activation of naïve gastric-specific CD4(+) T cells. There was a dramatic increase in proliferation and acquisition of effector function of gastric-specific T cells in the stomach draining LNs of Treg-cell-depleted mice, compared with untreated mice, either during Treg-cell depletion or after Treg-cell reconstitution. Moreover, the hyperproliferation of gastric-specific T cells in the Treg-cell-ablated mice was predominantly antigen-dependent. Transient depletion of Treg cells resulted in a shift in the ratio of peripheral:thymic Treg cells in the reemerged Treg-cell population, indicating an altered composition of Treg cells. These findings indicate that transient Treg-cell depletion results in ongoing antigen-driven self-reactive T-cell responses and emphasize the continual requirement for an intact Treg-cell population. PMID:25231532

  13. Chronic social defeat stress increases dopamine D2 receptor dimerization in the prefrontal cortex of adult mice.

    Science.gov (United States)

    Bagalkot, T R; Jin, H-M; Prabhu, V V; Muna, S S; Cui, Y; Yadav, B K; Chae, H-J; Chung, Y-C

    2015-12-17

    The present study aimed to examine the effects of chronic social defeat stress on the dopamine receptors and proteins involved in post-endocytic trafficking pathways. Adult mice were divided into susceptible and unsusceptible groups after 10 days of social defeat stress. Western blot analysis was used to measure the protein expression levels of dopamine D2 receptors (D2Rs), a short (D2S) and a long form (D2L) and, D2R monomers and dimers, dopamine D1 receptors (D1Rs), neuronal calcium sensor-1 (NCS-1) and G protein-coupled receptor-associated sorting protein-1 (GASP-1), and reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the mRNA expression levels of D2S, D2L, D2R monomers and dimers, and D1Rs in different brain areas. We observed increased expression of D2S, D2L and D2Rs dimers in the prefrontal cortex (PFC) of susceptible and/or unsusceptible mice compared with controls. The only significant findings with regard to mRNA expression levels were lower expression of D2S mRNA in the amygdala (AMYG) of susceptible and unsusceptible mice compared with controls. The present study demonstrated that chronic social defeat stress induced increased expression of D2S, D2L, and D2R dimers in the PFC of susceptible and/or unsusceptible mice. PMID:26484605

  14. Pubertal exposure to di-(2-ethylhexyl) phthalate influences social behavior and dopamine receptor D2 of adult female mice.

    Science.gov (United States)

    Wang, Ran; Xu, Xiaohong; Zhu, Qingjie

    2016-02-01

    DEHP, one of the most commonly phthalates used in plastics and many other products, is an environmental endocrine disruptor (EED). Puberty is another critical period for the brain development besides the neonatal period and is sensitive to EEDs. Social behavior is organized during puberty, so the present study is to investigate whether pubertal exposure to DEHP influenced social behavior of adult female mice. The results showed that pubertal exposure to DEHP for 2 weeks did not change the serum level of 17β-estradiol and the weight of uterus of adult females, but decreased the number of grid crossings and the frequency of rearing, and increased grooming in open field. DEHP reduced the open arm entries and the time spent in open arms in the elevated plus maze. DEHP reduced mutual sniffing and grooming between unfamiliar conspecifics in social play task and reduced the right chamber (containing unfamiliar female mouse) entries and the frequency of sniffing unfamiliar female mouse. DEHP at 1 mg kg(-1) d(-1) reduced the time spent in right chamber. Furthermore, Western blot analyses showed that DEHP decreased the levels of estrogen receptor β (ERβ), dopamine receptor D2, and the phosphorylation of ERKs in striatum. These results suggest that pubertal exposure to DEHP impaired social investigation and sociability and influenced anxiety-like state of adult female mice. The decreased activity of ERK1/2, and the down-regulated D2 and ERβ in striatum may be associated with the DEHP-induced changes of emotional and social behavior in mice. PMID:26524146

  15. Unusual Repertoire of Vocalizations in Adult BTBR T+tf/J Mice During Three Types of Social Encounters

    Science.gov (United States)

    Scattoni, Maria Luisa; Ricceri, Laura; Crawley, Jacqueline N.

    2010-01-01

    BTBR T+tf/J (BTBR) is an inbred mouse strain that displays social deficits and repetitive behaviors analogous to the first and third diagnostic symptoms of autism. We previously reported an unusual pattern of ultrasonic vocalizations in BTBR pups that may represent a behavioral homologue to the second diagnostic symptom of autism, impaired communication. The present study investigated the social and vocal repertoire in adult BTBR mice, to evaluate the role of ultrasonic vocalizations in multiple social situations at the adult stage of development. Three different social contexts were considered: male-female, male-male (resident-intruder) and female-female interactions. Behavioral responses and ultrasonic vocalizations were recorded for BTBR and for the highly social control strain C57BL/6J (B6). No episodes of overt fighting or mating were observed during the short durations of the three different experimental encounters. BTBR displayed lower levels of vocalizations and social investigation in all three social contexts as compared to B6. In addition, the correlation analyses between social investigation and USVs emission rate revealed that in B6 mice the two variables were positively correlated in all the three different social settings, whereas in BTBR mice the positive correlation was significant only in the male-female interactions. These findings strongly support the value of simultaneously recording two aspects of the mouse social repertoire, social motivation and bioacoustic communication. Moreover, our findings in adults are consistent with previous results in pups, showing an unusual vocal repertoire in BTBR as compared to B6. PMID:20618443

  16. Moderate neonatal stress decreases within-group variation in behavioral, immune and HPA responses in adult mice.

    Directory of Open Access Journals (Sweden)

    Simone Macrì

    Full Text Available BACKGROUND: The significance of behavioral neuroscience and the validity of its animal models of human pathology largely depend on the possibility to replicate a given finding across different laboratories. Under the present test and housing conditions, this axiom fails to resist the challenge of experimental validation. When several mouse strains are tested on highly standardized behavioral test batteries in different laboratories, significant strain x lab interactions are often detected. This limitation, predominantly due to elevated within-group variability observed in control subjects, increases the number of animals needed to address fine experimental questions. Laboratory rodents display abnormal stress and fear reactions to experimental testing, which might depend on the discrepancy between the stability of the neonatal environment and the challenging nature of the adult test and housing conditions. METHODOLOGY/PRINCIPAL FINDINGS: Stimulating neonatal environments (e.g. brief maternal separations, increased foraging demands or maternal corticosterone supplementation reduce stress and fear responses in adulthood. Here we tested whether reduced fearfulness associated with experimental testing would also reduce inter-individual variation. In line with our predictions, we show that a moderate elevation in neonatal corticosterone through maternal milk significantly reduces fear responses and inter-individual variability (average 44% in adult mouse offspring. CONCLUSIONS/SIGNIFICANCE: We observed reduced variation in pain perception, novelty preference, hormonal stress response and resistance to pathogen infection. This suggests that the results of this study may apply to a relatively broad spectrum of neuro-behavioral domains. Present findings encourage a reconsideration of the basic principles of neonatal housing systems to improve the validity of experimental models and reduce the number of animals used.

  17. Selective Life-Long Skeletal Myofiber-Targeted VEGF Gene Ablation Impairs Exercise Capacity in Adult Mice.

    Science.gov (United States)

    Tang, Kechun; Gu, Yusu; Dalton, Nancy D; Wagner, Harrieth; Peterson, Kirk L; Wagner, Peter D; Breen, Ellen C

    2016-02-01

    Exercise is dependent on adequate oxygen supply for mitochondrial respiration in both cardiac and locomotor muscle. To determine whether skeletal myofiber VEGF is critical for regulating exercise capacity, independent of VEGF function in the heart, ablation of the VEGF gene was targeted to skeletal myofibers (skmVEGF-/-) during embryogenesis (∼ E9.5), leaving intact VEGF expression by all other cells in muscle. In adult mice, VEGF levels were decreased in the soleus (by 65%), plantaris (94%), gastrocnemius (74%), EDL (99%) and diaphragm (64%) (P exercise capacity. PMID:26201683

  18. Long-term exposure to decabrominated diphenyl ether impairs CD8 T-cell function in adult mice

    OpenAIRE

    Zeng, Weihong; Wang, Ying; Liu, Zhicui; Khanniche, Asma; Hu, Qingliang; Feng, Yan; Ye, Weiyi; Yang, Jianglong; Wang, Shujun; Zhou, Lin; Shen, Hao; Wang, Yan

    2014-01-01

    Polybrominated diphenyl ethers (PBDEs) are ubiquitous environmental pollutants that accumulate to high levels in human populations that are subject to occupational or regional industry exposure. PBDEs have been shown to affect human neuronal, endocrine and reproductive systems, but their effect on the immune system is not well understood. In this study, experimental adult mice were intragastrically administered 2,2′,3,3′,4,4′,5,5′,6,6′-decabromodiphenyl ether (BDE-209) at doses of 8, 80 or 80...

  19. Methionine restriction restores a younger metabolic phenotype in adult mice with alterations in fibroblast growth factor 21

    OpenAIRE

    Lees, Emma K.; Król, Elżbieta; Grant, Louise; Shearer, Kirsty; Wyse, Cathy; Moncur, Eleanor; Bykowska, Aleksandra S; Mody, Nimesh; Gettys, Thomas W.; Delibegovic, Mirela

    2014-01-01

    Methionine restriction (MR) decreases body weight and adiposity and improves glucose homeostasis in rodents. Similar to caloric restriction, MR extends lifespan, but is accompanied by increased food intake and energy expenditure. Most studies have examined MR in young animals; therefore, the aim of this study was to investigate the ability of MR to reverse age-induced obesity and insulin resistance in adult animals. Male C57BL/6J mice aged 2 and 12 months old were fed MR (0.172% methionine) o...

  20. Molecular Mechanisms Mediating a Deficit in Recall of Fear Extinction in Adult Mice Exposed to Cocaine In Utero

    OpenAIRE

    Kabir, Zeeba D.; Katzman, Aaron C.; Kosofsky, Barry E.

    2013-01-01

    Prenatal cocaine exposure has been shown to alter cognitive processes of exposed individuals, presumed to be a result of long-lasting molecular alterations in the brain. In adult prenatal cocaine exposed (PCOC) mice we have identified a deficit in recall of fear extinction, a behavior that is dependent on the medial prefrontal cortex (mPFC) and the hippocampus. While we observed no change in the constitutive expression of brain derived neurotrophic factor (BDNF) protein and mRNA in the mPFC a...

  1. EFFECT OF MORPHINE ADDICTION AND WITHDRAWAL IN PARENTS PRIOR TO MATING ON FORAGING BEHAVIOR IN ADULT OFFSPRING RATS%大鼠配对前经历吗啡成瘾及戒断对子代掠食行为的影响

    Institute of Scientific and Technical Information of China (English)

    姚亚丽; 曹文字; 徐杨; 钟小林; 罗雁威; 刘丹; 李芳; 张建一; 李昌琪

    2011-01-01

    目的:探讨亲代大鼠配对前经历吗啡成瘾及戒断对子代掠食行为的影响及机制.方法:选用8周龄Sprague -Dawley大鼠40只建立吗啡依赖模型,自然戒断21 d后配对分组合笼,子鼠8周龄时进行掠食行为观察,采用Golgi-Cox染色观察子鼠前扣带皮质内神经元树突形态情况.结果:吗啡成瘾组子代掠食量均低于对照组(P<0.001);吗啡成瘾组子代前扣带皮质内神经元顶树突分枝数、分枝总长度和树突棘密度均低于对照组(P<0.05).结论:亲代经历吗啡成瘾戒断会导致子代掠食行为障碍,其机制可能与前扣带皮质内神经元树突发育不良有关.%Objective: To investigate the effects and possible mechanisms of morphine addiction and withdrawal in parents prior to mating on the foraging behavior in adult offspring rats. Methods: Eight -week healthy adult Sprague - Dawleyda (SD) rats were used to eatabilish morphine - addiction model (re = 40). Male and female rats were mated 21 days after morphine withdrawal. The foraging behavior tests were assessed when the offsprings were 8 weeks old. Golgi staining was conducted in order to analyze the neuronal morphology of anterior cingulate cortex. Results: Much fewer food was foraged by offsprings of morphine - addicted group compared with control group ( P < 0. 001) ; the numbers of apical dendrites branches, the total length of apical dendrites branch and apical dendritic spine density in anterior cingulate cortex neurons of offsprings from morphine - addicted group were all lower than those from control group(P <0. 05). Conclusion: The experience of morphine addiction and withdrawal prior to mating will lead to food foraging function deficit in the offspring, which might be related to dysplasia of dendritic morphology in anterior cingulate cortex neurons.

  2. Transplantation of adult mouse iPS cell-derived photoreceptor precursors restores retinal structure and function in degenerative mice.

    Directory of Open Access Journals (Sweden)

    Budd A Tucker

    Full Text Available This study was designed to determine whether adult mouse induced pluripotent stem cells (iPSCs, could be used to produce retinal precursors and subsequently photoreceptor cells for retinal transplantation to restore retinal function in degenerative hosts. iPSCs were generated using adult dsRed mouse dermal fibroblasts via retroviral induction of the transcription factors Oct4, Sox2, KLF4 and c-Myc. As with normal mouse ES cells, adult dsRed iPSCs expressed the pluripotency genes SSEA1, Oct4, Sox2, KLF4, c-Myc and Nanog. Following transplantation into the eye of immune-compromised retinal degenerative mice these cells proceeded to form teratomas containing tissue comprising all three germ layers. At 33 days post-differentiation a large proportion of the cells expressed the retinal progenitor cell marker Pax6 and went on to express the photoreceptor markers, CRX, recoverin, and rhodopsin. When tested using calcium imaging these cells were shown to exhibit characteristics of normal retinal physiology, responding to delivery of neurotransmitters. Following subretinal transplantation into degenerative hosts differentiated iPSCs took up residence in the retinal outer nuclear layer and gave rise to increased electro retinal function as determined by ERG and functional anatomy. As such, adult fibroblast-derived iPSCs provide a viable source for the production of retinal precursors to be used for transplantation and treatment of retinal degenerative disease.

  3. Protocol to isolate a large amount of functional oligodendrocyte precursor cells from the cerebral cortex of adult mice and humans.

    Directory of Open Access Journals (Sweden)

    Eva María Medina-Rodríguez

    Full Text Available During development, oligodendrocytes are generated from oligodendrocyte precursor cells (OPCs, a cell type that is a significant proportion of the total cells (3-8% in the adult central nervous system (CNS of both rodents and humans. Adult OPCs are responsible for the spontaneous remyelination that occurs in demyelinating diseases like Multiple Sclerosis (MS and they constitute an interesting source of cells for regenerative therapy in such conditions. However, there is little data regarding the neurobiology of adult OPCs isolated from mice since an efficient method to isolate them has yet to be established. We have designed a protocol to obtain viable adult OPCs from the cerebral cortex of different mouse strains and we have compared its efficiency with other well-known methods. In addition, we show that this protocol is also useful to isolate functional OPCs from human brain biopsies. Using this method we can isolate primary cortical OPCs in sufficient quantities so as to be able to study their survival, maturation and function, and to facilitate an evaluation of their utility in myelin repair.

  4. Periostin Deficiency Increases Bone Damage and Impairs Injury Response to Fatigue Loading in Adult Mice

    OpenAIRE

    Bonnet, Nicolas; Gineyts, Evelyne; Ammann, Patrick; Conway, Simon J; Garnero, Patrick; Ferrari, Serge Livio

    2013-01-01

    Bone damage removal and callus formation in response to fatigue loading are essential to prevent fractures. Periostin (Postn) is a matricellular protein that mediates adaptive response of cortical bone to loading. Whether and how periostin influences damage and the injury response to fatigue remains unknown. We investigated the skeletal response of Postn -/- and Postn +/+ mice after fatigue stimulus by axial compression of their tibia. In Postn +/+ mice, cracks number and surface (CsNb, CsS) ...

  5. Long-term voluntary running improves diet-induced adiposity in young adult mice

    Science.gov (United States)

    The present study investigated the effects of long-term voluntary running on diet-induced adiposity in male C57BL/6 mice. Four-week old mice (n = 15 per group) were fed the AIN93G diet or a 45% high-fat diet (% kcal.) with or without access to in-cage activity wheels for 14 weeks. The high-fat die...

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

    OpenAIRE

    Motoi Tamura; Chigusa Hoshi; Sachiko Hori

    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....

  7. Parents bereaved by offspring suicide

    DEFF Research Database (Denmark)

    Bolton, James M; Au, Wendy; Leslie, William D;

    2013-01-01

    CONTEXT Suicide bereavement remains understudied and poorly understood. OBJECTIVES To examine outcomes of parents bereaved by the suicide death of their offspring and to compare these with both nonbereaved parent controls and parents who had offspring die in a motor vehicle crash (MVC). DESIGN...... Population-based case-control study. Suicide-bereaved parents were compared with nonbereaved matched control parents in the general population (n = 1415) and with MVC-bereaved parents (n = 1132) on the rates of physician-diagnosed mental and physical disorders, social factors, and treatment use in the 2...... years after death of the offspring. Adjusted relative rates (ARRs) were generated by generalized estimating equation models and adjusted for confounding factors. SETTING Manitoba, Canada. PARTICIPANTS All identifiable parents who had an offspring die by suicide between 1996 and 2007 (n = 1415). MAIN...

  8. Prenatal stress causes alterations in the morphology of microglia and the inflammatory response of the hippocampus of adult female mice

    Directory of Open Access Journals (Sweden)

    Diz-Chaves Yolanda

    2012-04-01

    Full Text Available Abstract Background Stress during fetal life increases the risk of affective and immune disorders later in life. The altered peripheral immune response caused by prenatal stress may impact on brain function by the modification of local inflammation. In this study we have explored whether prenatal stress results in alterations in the immune response in the hippocampus of female mice during adult life. Methods Pregnant C57BL/6 mice were subjected three times/day during 45 minutes to restraint stress from gestational Day 12 to delivery. Control non-stressed pregnant mice remained undisturbed. At four months of age, non-stressed and prenatally stressed females were ovariectomized. Fifteen days after surgery, mice received an i.p. injection of vehicle or of 5 mg/kg of lipopolysaccharide (LPS. Mice were sacrificed 20 hours later by decapitation and the brains were removed. Levels of interleukin-1β (IL1β, interleukin-6 (IL-6, tumor necrosis factor α (TNF-α, interferon γ-inducible protein 10 (IP10, and toll-like receptor 4 mRNA were assessed in the hippocampus by quantitative real-time polymerase chain reaction. Iba1 immunoreactivity was assessed by immunocytochemistry. Statistical significance was determined by one-way or two-way analysis of variance. Results Prenatal stress, per se, increased IL1β mRNA levels in the hippocampus, increased the total number of Iba1-immunoreactive microglial cells and increased the proportion of microglial cells with large somas and retracted cellular processes. In addition, prenatally stressed and non-stressed animals showed different responses to peripheral inflammation induced by systemic administration of LPS. LPS induced a significant increase in mRNA levels of IL-6, TNF-α and IP10 in the hippocampus of prenatally stressed mice but not of non-stressed animals. In addition, after LPS treatment, prenatally stressed animals showed a higher proportion of Iba1-immunoreactive cells in the hippocampus with

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

    Energy Technology Data Exchange (ETDEWEB)

    Haddad, Rami, E-mail: rami.haddad@mail.mcgill.ca [Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 chemin Cote Ste Catherine, Montréal, Québec, Canada H3T 1E2 (Canada); Division of Experimental Medicine, Department of Medicine, McGill University, 850 Sherbrooke Street, Montréal, Québec, Canada H3A 1A2 (Canada); Kasneci, Amanda, E-mail: amanda.kasneci@mail.mcgill.ca [Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 chemin Cote Ste Catherine, Montréal, Québec, Canada H3T 1E2 (Canada); Mepham, Kathryn, E-mail: katherine.mepham@mail.mcgill.ca [Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 chemin Cote Ste Catherine, Montréal, Québec, Canada H3T 1E2 (Canada); Division of Experimental Medicine, Department of Medicine, McGill University, 850 Sherbrooke Street, Montréal, Québec, Canada H3A 1A2 (Canada); Sebag, Igal A., E-mail: igal.sebag@mcgill.ca [Division of Cardiology, Jewish General Hospital, 3755 chemin Cote Ste Catherine, Montréal, Québec, Canada H3T 1E2 (Canada); and others

    2013-01-01

    Pregnant women, and thus their fetuses, are exposed to many endocrine disruptor compounds (EDCs). Fetal cardiomyocytes express sex hormone receptors making them potentially susceptible to re-programming by estrogenizing EDCs. Diethylstilbestrol (DES) is a proto-typical, non-steroidal estrogen. We hypothesized that changes in adult cardiac structure/function after gestational exposure to the test compound DES would be a proof in principle for the possibility of estrogenizing environmental EDCs to also alter the fetal heart. Vehicle (peanut oil) or DES (0.1, 1.0 and 10.0 μg/kg/da.) was orally delivered to pregnant C57bl/6n dams on gestation days 11.5–14.5. At 3 months, male progeny were left sedentary or were swim trained for 4 weeks. Echocardiography of isoflurane anesthetized mice revealed similar cardiac structure/function in all sedentary mice, but evidence of systolic dysfunction and increased diastolic relaxation after swim training at higher DES doses. The calcium homeostasis proteins, SERCA2a, phospholamban, phospho-serine 16 phospholamban and calsequestrin 2, are important for cardiac contraction and relaxation. Immunoblot analyses of ventricle homogenates showed increased expression of SERCA2a and calsequestrin 2 in DES mice and greater molecular remodeling of these proteins and phospho-serine 16 phospholamban in swim trained DES mice. DES increased cardiac DNA methyltransferase 3a expression and DNA methylation in the CpG island within the calsequestrin 2 promoter in heart. Thus, gestational DES epigenetically altered ventricular DNA, altered cardiac function and expression, and reduced the ability of adult progeny to cardiac remodel when physically challenged. We conclude that gestational exposure to estrogenizing EDCs may impact cardiac structure/function in adult males. -- Highlights: ► Gestational DES changes cardiac SERCA2a and CASQ2 expression. ► Echocardiography identified systolic dysfunction and increased diastolic relaxation. ► DES

  10. The Effect of Orally Administered L-carnitine on Testis Tissue Sperm Parameters and Daily Sperm Production in Adult Mice

    Directory of Open Access Journals (Sweden)

    Zohre Zare

    2010-01-01

    Full Text Available Introduction: The purpose of this study was to evaluate body and testis weight, testis tissue,counts, motility, viability, morphology, and chromatin quality of epididymal sperm, aswell as the testicular spermatid number (TSN per gram of testis, and daily sperm production(DSP in L-carnitine treated mice.Materials and Methods: In the present study, adult male NMRI mice (mean age of 4weeks were administered L-carnitine by gavage for two weeks. The experimental groupsreceived 1mg L-carnitine/100 μl deionized water and 10 mg L-carnitine/100 μl deionizedwater, respectively. The control group did not receive L-carnitine. All samples were assessedaccording to World Health Organization (WHO criteria. Sperm morphology wasassessed with papanicula staining. Sperm chromatin quality was assessed using anilinebluestaining.The left testes were fixed in Bouins solution for histological examination and the end sliceswere stained with hematoxilin and eosin (H&E. The right testis was homogenized, andTSN and DSP were calculated with an improved neubauer haemocytometer and respectiveformula.Results: Administration of L-carnitine induced significant reduction in body weight (p<0.05and an increase in tchromatine quality (p<0.05. Amongst the other parameters no significantdifferences were observed in all groups.Conclusion: These results show that oral administration of L-carnitine to mice with normalspermatogenesis does not have any significant effect on the reproductive systems.Thus, L-carnitine seems to be ineffective in normospermic animals.

  11. Chronic treatment with fluoxetine for more than 6 weeks decreases neurogenesis in the subventricular zone of adult mice

    Directory of Open Access Journals (Sweden)

    Ohira Koji

    2011-03-01

    Full Text Available Abstract Background Recent studies indicate that chronic treatment with serotonergic antidepressants upregulates adult neurogenesis of the dentate gyrus (DG. In contrast, some studies claimed that there was very little alteration of neurogenesis in the subventricular zone (SVZ by the antidepressants. Since almost all of those studies treated animals with drugs for 2 to 4 weeks as chronic treatment models of antidepressants, it is possible that antidepressant treatments for longer periods would affect adult neurogenesis in the SVZ. Results In the present study, we examined the effects of long-term (up to 9 weeks administration of fluoxetine (FLX, a selective serotonin reuptake inhibitor, on cell proliferation and survival in the DG and the SVZ of adult mice. As reported previously, in the DG of mice treated with FLX for 3, 6, or 9 weeks that were also injected with 5-bromodeoxyuridine (BrdU in the last 3 days before perfusion, the numbers of Ki67- and BrdU-positive cells, which are cell proliferation markers, were significantly upregulated even at 3 weeks after the onset of the FLX treatments, and these increases were sustained in mice treated with FLX for 9 weeks. On the other hand, in the SVZ, we found a small, insignificant decrease in the numbers of Ki67- and BrdU-positive cells at 3 weeks, followed by highly significant decreases in the numbers of Ki67- and BrdU-positive cells at both 6 and 9 weeks. Furthermore, among olfactory newly generated cells that survived for 3 weeks after BrdU injection, the number of new cells was decreased at 9 weeks of FLX treatment. Conclusions These results demonstrate that long-term (more than 6 weeks treatment with FLX has the opposite effect on neurogenesis in the SVZ than it does in the DG. The results also suggest that the decrease in neurogenesis in the SVZ might be involved in some aspects of the drugs' therapeutic effects on depression. In addition, our findings raise the possibility that some of the

  12. Changes in adult olfactory bulb neurogenesis in mice expressing the A30P mutant form of alpha-synuclein.

    Science.gov (United States)

    Marxreiter, Franz; Nuber, Silke; Kandasamy, Mahesh; Klucken, Jochen; Aigner, Robert; Burgmayer, Ralf; Couillard-Despres, Sebastien; Riess, Olaf; Winkler, Jürgen; Winner, Beate

    2009-03-01

    In familial and sporadic forms of Parkinson's disease (PD), alpha-synuclein pathology is present in the brain stem nuclei and olfactory bulb (OB) long before Lewy bodies are detected in the substantia nigra. The OB is an active region of adult neurogenesis, where newly generated neurons physiologically integrate. While accumulation of wild-type alpha-synuclein is one of the pathogenic hallmarks of non-genetic forms of PD, the A30P alpha-synuclein mutation results in an earlier disease onset and a severe clinical phenotype. Here, we study the regulation of adult neurogenesis in the subventricular zone (SVZ)/OB system in a tetracycline-suppressive (tet-off) transgenic model of synucleinopathies, expressing human mutant A30P alpha-synuclein under the control of the calcium/calmodulin-dependent protein kinase II alpha (CaMK) promoter. In A30P transgenic mice alpha-synuclein was abundant at the site of integration in the glomerular cell layer of the OB. Without changes in proliferation in the SVZ, significantly fewer newly generated neurons were observed in the OB granule cell and glomerular layers of A30P transgenic mice than in controls, most probably due to increased cell death. By tetracycline-dependent abrogation of A30P alpha-synuclein expression, OB neurogenesis and programmed cell death was restored to control levels. Our results indicate that, using A30P conditional (tet-off) mice, A30P alpha-synuclein has a negative impact on olfactory neurogenesis and suppression of A30P alpha-synuclein enhances survival of newly generated neurons. This finding suggests that interfering with alpha-synuclein pathology can rescue newly generated neurons, possibly leading to new targets for therapeutic interventions in synucleinopathies. PMID:19291219

  13. Apple pectin affects the efficacy of epigallocatechin gallate on oral sucrose tolerance test in adult mice.

    Science.gov (United States)

    Tamura, M; Hori, S

    2011-11-01

    Epigallocatechin gallate (EGCg), a dietary polyphenol and a major tea catechin, is a known sucrase inhibitor. Since dietary pectin is known to modulate some of the functions of the gastrointestinal tract, we investigated whether it could specifically affect the efficacy of EGCg on an oral sucrose tolerance test in mice. Male Crj:CD-1 (ICR) mice (seven weeks old) were randomly divided into two groups and fed a 5 % apple pectin (PE) or 5 % cellulose (CE) diet (control diet) for 28 days. After the experimental diet period, all mice were fasted overnight. A volume of 0.2 mL EGCg (20 mg/mL) was orally administered to all the mice by stainless steel feeding needle via injection syringe and a sucrose tolerance test was performed. The blood glucose levels were measured in blood collected from the tail vein using the OneTouch® Ultra® blood glucose monitoring system. Blood glucose levels at 30 minutes and 60 minutes after sucrose loading in the PE group were significantly higher than initial blood glucose levels. However, blood glucose levels at 30 minutes, 60 minutes, and 120 minutes after sucrose loading in the CE group were not significantly higher than initial blood glucose levels. After laparotomy, plasma lipids were also measured. Plasma triglyceride concentrations were significantly greater in the PE group than in the CE (control) group. This demonstrates that dietary pectin can affect the efficacy of EGCg on the oral sucrose tolerance test in mice. PMID:22673921

  14. Maternal obesity, lipotoxicity and cardiovascular diseases in offspring.

    Science.gov (United States)

    Dong, Maolong; Zheng, Qijun; Ford, Stephen P; Nathanielsz, Peter W; Ren, Jun

    2013-02-01

    Maternal obesity has risen dramatically over the past 20 years, by nearly 42% in African-Americans and 29% in Caucasians. Maternal obesity is afflicted with many maternal obstetric complications in the offspring including high blood pressure, obesity, gestational diabetes and increased perinatal morbidity. Maternal nutritional environment plays a rather important role in the programming of the health set-points in the offspring such as glucose and insulin metabolism, energy balance and predisposition to metabolic disorders. In particular, maternal obesity is associated with elevated prevalence of cardiovascular diseases in the offspring. Evidence from human and experimental studies including rodents and nonhuman primates has indicated that maternal obesity or overnutrition programs offspring for an increased risk of adult obesity. Maternal obesity or fat diet exposure predisposes the onset and development of obesity, insulin resistance, cardiac hypertrophy and myocardial contractile anomalies in the offspring. A number of mechanisms including elevated hormones (leptin, insulin), nutrients (fatty acids, triglycerides and glucose) and inflammatory cytokines have been postulated to play a key role in maternal obesity-induced postnatal cardiovascular sequelae. In addition, lipotoxicity (accumulation of lipid metabolites) resulting from maternal obesity is capable of activating a number of stress signaling cascades including pro-inflammatory cytokines and oxidative stress to exacerbate maternal obesity-induced cardiovascular complications later on in adult life. This mini-review summarizes the recent knowledge with regard to the role of lipotoxicity in maternal obesity-induced change in cardiovascular function in the offspring. This article is part of a Special Issue entitled "Focus on Cardiac Metabolism". PMID:22982026

  15. Sex roles in nest keeping - how information asymmetry contributes to parent-offspring co-adaptation.

    Science.gov (United States)

    Lucass, Carsten; Fresneau, Nolwenn; Eens, Marcel; Müller, Wendt

    2016-03-01

    Parental food provisioning and offspring begging influence each other reciprocally. This makes both traits agents and targets of selection, which may ultimately lead to co-adaptation. The latter may reflect co-adapted parent and offspring genotypes or could be due to maternal effects. Maternal effects are in turn likely to facilitate in particular mother-offspring co-adaptation, further emphasized by the possibility that mothers are sometimes found to be more responsive to offspring need. However, parents may not only differ in their sensitivity, but often play different roles in postnatal care. This potentially impinges on the access to information about offspring need. We here manipulated the information on offspring need as perceived by parents by playing back begging calls at a constant frequency in the nest-box of blue tits (Cyanistes caeruleus). We measured the parental response in provisioning to our treatment, paying particular attention to sex differences in parental roles and whether such differences alter the perception of the intensity of our manipulation. This enabled us to investigate whether an information asymmetry about offspring need exists between parents and how such an asymmetry relates to co-adaptation between parental provisioning and offspring begging. Our results show that parents indeed differed in the frequency how often they perceived the playback due to the fact that females spent more time with their offspring in the nest box. Correcting for the effective exposure of an adult to the playback, the parental response in provisioning covaried more strongly (positive) with offspring begging intensity, independent of the parental sex, indicating coadaptation on the phenotypic level. Females were not more sensitive to experimentally increased offspring need than males, but they were exposed to more broadcasted begging calls. Therefore, sex differences in access to information about offspring need, due to different parental roles, have the

  16. The p38α MAPK function in osteoprecursors is required for bone formation and bone homeostasis in adult mice.

    Directory of Open Access Journals (Sweden)

    Edgardo Rodríguez-Carballo

    Full Text Available p38 MAPK activity plays an important role in several steps of the osteoblast lineage progression through activation of osteoblast-specific transcription factors and it is also essential for the acquisition of the osteoblast phenotype in early development. Although reports indicate p38 signalling plays a role in early skeletal development, its specific contributions to adult bone remodelling are still to be clarified.We evaluated osteoblast-specific deletion of p38α to determine its significance in early skeletogenesis, as well as for bone homeostasis in adult skeleton. Early p38α deletion resulted in defective intramembranous and endochondral ossification in both calvaria and long bones. Mutant mice showed reduction of trabecular bone volume in distal femurs, associated with low trabecular thickness. In addition, knockout mice also displayed decreased femoral cortical bone volume and thickness. Deletion of p38α did not affect osteoclast function. Yet it impaired osteoblastogenesis and osteoblast maturation and activity through decreased expression of osteoblast-specific transcription factors and their targets. Furthermore, the inducible Cre system allowed us to control the onset of p38α disruption after birth by removal of doxycycline. Deletion of p38α at three or eight weeks postnatally led to significantly lower trabecular and cortical bone volume after 6 or 12 months.Our data demonstrates that, in addition to early skeletogenesis, p38α is essential for osteoblasts to maintain their function in mineralized adult bone, as bone anabolism should be sustained throughout life. Moreover, our data also emphasizes that clinical development of p38 inhibitors should take into account their potential bone effects.

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

    Science.gov (United States)

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

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

  18. The Nuclear Progesterone Receptor Reduces Post-Sigh Apneas during Sleep and Increases the Ventilatory Response to Hypercapnia in Adult Female Mice

    OpenAIRE

    Marcouiller, François; Boukari, Ryma; Laouafa, Sofien; Lavoie, Raphaël; Joseph, Vincent

    2014-01-01

    We tested the hypothesis that the nuclear progesterone receptor (nPR) is involved in respiratory control and mediates the respiratory stimulant effect of progesterone. Adult female mice carrying a mutation in the nPR gene (PRKO mice) and wild-type controls (WT) were implanted with an osmotic pump delivering vehicle or progesterone (4 mg/kg/day). The mice were instrumented with EEG and neck EMG electrodes connected to a telemetry transmitter. The animals were placed in a whole body plethysmogr...

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

    International Nuclear Information System (INIS)

    Aggressive behavior (AB) in first generation (F1) 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)

  20. Neurexin Dysfunction in Adult Neurons Results in Autistic-like Behavior in Mice

    Directory of Open Access Journals (Sweden)

    Luis G. Rabaneda

    2014-07-01

    Full Text Available Autism spectrum disorders (ASDs comprise a group of clinical phenotypes characterized by repetitive behavior and social and communication deficits. Autism is generally viewed as a neurodevelopmental disorder where insults during embryonic or early postnatal periods result in aberrant wiring and function of neuronal circuits. Neurexins are synaptic proteins associated with autism. Here, we generated transgenic βNrx1ΔC mice in which neurexin function is selectively impaired during late postnatal stages. Whole-cell recordings in cortical neurons show an impairment of glutamatergic synaptic transmission in the βNrx1ΔC mice. Importantly, mutant mice exhibit autism-related symptoms, such as increased self-grooming, deficits in social interactions, and altered interaction for nonsocial olfactory cues. The autistic-like phenotype of βNrx1ΔC mice can be reversed after removing the mutant protein in aged animals. The defects resulting from disruption of neurexin function after the completion of embryonic and early postnatal development suggest that functional impairment of mature circuits can trigger autism-related phenotypes.

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

    Science.gov (United States)

    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 (P<0.001). Monitoring the results of individual mice 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 (P<0.001) than in the others (P<0.05). These results suggest that the corticosterone levels in saliva 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

  2. Periostin deficiency increases bone damage and impairs injury response to fatigue loading in adult mice.

    Science.gov (United States)

    Bonnet, Nicolas; Gineyts, Evelyne; Ammann, Patrick; Conway, Simon J; Garnero, Patrick; Ferrari, Serge

    2013-01-01

    Bone damage removal and callus formation in response to fatigue loading are essential to prevent fractures. Periostin (Postn) is a matricellular protein that mediates adaptive response of cortical bone to loading. Whether and how periostin influences damage and the injury response to fatigue remains unknown. We investigated the skeletal response of Postn(-/-) and Postn(+/+) mice after fatigue stimulus by axial compression of their tibia. In Postn(+/+) mice, cracks number and surface (CsNb, CsS) increased 1h after fatigue, with a decrease in strength compared to non-fatigued tibia. At 15 days, CsNb had started to decline, while CtTV and CtBV increased in fatigued vs non-fatigued tibia, reflecting a woven bone response that was present in 75% of the fatigued bones. Cortical porosity and remodelling also prominently increased in the fatigued tibia of Postn(+/+) mice. At 30 days, paralleling a continuous removal of cortical damage, strength of the fatigued tibia was similar to the non-fatigue tibia. In Postn(-/-) mice, cracks were detectable even in the absence of fatigue, while the amount of collagen crosslinks and tissue hardness was decreased compared to Postn(+/+). Fatigue significantly increased CsNb and CsS in Postn(-/-), but was not associated with changes in CtTV and CtBV, as only 16% of the fatigued bones formed some woven bone. Cortical porosity and remodelling did not increase either after fatigue in Postn(-/-), and the level of damage remained high even after 30 days. As a result, strength remained compromised in Postn(-/-) mice. Contrary to Postn(+/+), which osteocytic lacunae showed a change in the degree of anisotropy (DA) after fatigue, Postn(-/-) showed no DA change. Hence periostin appears to influence bone materials properties, damage accumulation and repair, including local modeling/remodeling processes in response to fatigue. These observations suggest that the level of periostin expression could influence the propensity to fatigue fractures. PMID

  3. Periostin deficiency increases bone damage and impairs injury response to fatigue loading in adult mice.

    Directory of Open Access Journals (Sweden)

    Nicolas Bonnet

    Full Text Available Bone damage removal and callus formation in response to fatigue loading are essential to prevent fractures. Periostin (Postn is a matricellular protein that mediates adaptive response of cortical bone to loading. Whether and how periostin influences damage and the injury response to fatigue remains unknown. We investigated the skeletal response of Postn(-/- and Postn(+/+ mice after fatigue stimulus by axial compression of their tibia. In Postn(+/+ mice, cracks number and surface (CsNb, CsS increased 1h after fatigue, with a decrease in strength compared to non-fatigued tibia. At 15 days, CsNb had started to decline, while CtTV and CtBV increased in fatigued vs non-fatigued tibia, reflecting a woven bone response that was present in 75% of the fatigued bones. Cortical porosity and remodelling also prominently increased in the fatigued tibia of Postn(+/+ mice. At 30 days, paralleling a continuous removal of cortical damage, strength of the fatigued tibia was similar to the non-fatigue tibia. In Postn(-/- mice, cracks were detectable even in the absence of fatigue, while the amount of collagen crosslinks and tissue hardness was decreased compared to Postn(+/+. Fatigue significantly increased CsNb and CsS in Postn(-/-, but was not associated with changes in CtTV and CtBV, as only 16% of the fatigued bones formed some woven bone. Cortical porosity and remodelling did not increase either after fatigue in Postn(-/-, and the level of damage remained high even after 30 days. As a result, strength remained compromised in Postn(-/- mice. Contrary to Postn(+/+, which osteocytic lacunae showed a change in the degree of anisotropy (DA after fatigue, Postn(-/- showed no DA change. Hence periostin appears to influence bone materials properties, damage accumulation and repair, including local modeling/remodeling processes in response to fatigue. These observations suggest that the level of periostin expression could influence the propensity to fatigue fractures.

  4. Effects of aluminum sulfate on delta-aminolevulinate dehydratase from kidney, brain, and liver of adult mice

    Directory of Open Access Journals (Sweden)

    Schetinger M.R.C.

    1999-01-01

    Full Text Available The purpose of the present study was to investigate the in vitro and in vivo effects of aluminum sulfate on delta-aminolevulinic acid dehydratase (ALA-D activity from the brain, liver and kidney of adult mice (Swiss albine. In vitro experiments showed that the aluminum sulfate concentration needed to inhibit the enzyme activity was 1.0-5.0 mM (N = 3 in brain, 4.0-5.0 mM (N = 3 in liver and 0.0-5.0 mM (N = 3 in kidney. The in vivo experiments were performed on three groups for one month: 1 control animals (N = 8; 2 animals treated with 1 g% (34 mM sodium citrate (N = 8 and 3 animals treated with 1 g% (34 mM sodium citrate plus 3.3 g% (49.5 mM aluminum sulfate (N = 8. Exposure to aluminum sulfate in drinking water inhibited ALA-D activity in kidney (23.3 ± 3.7%, mean ± SEM, P<0.05 compared to control, but enhanced it in liver (31.2 ± 15.0%, mean ± SEM, P<0.05. The concentrations of aluminum in the brain, liver and kidney of adult mice were determined by graphite furnace atomic absorption spectrometry. The aluminum concentrations increased significantly in the liver (527 ± 3.9%, mean ± SEM, P<0.05 and kidney (283 ± 1.7%, mean ± SEM, P<0.05 but did not change in the brain of aluminum-exposed mice. One of the most important and striking observations was the increase in hepatic aluminum concentration in the mice treated only with 1 g% sodium citrate (34 mM (217 ± 1.5%, mean ± SEM, P<0.05 compared to control. These results show that aluminum interferes with delta-aminolevulinate dehydratase activity in vitro and in vivo. The accumulation of this element was in the order: liver > kidney > brain. Furthermore, aluminum had only inhibitory properties in vitro, while in vivo it inhibited or stimulated the enzyme depending on the organ studied.

  5. Effects of prenatal exposure to surface-coated nanosized titanium dioxide (UV-Titan. A study in mice

    Directory of Open Access Journals (Sweden)

    Vibenholt Anni

    2010-06-01

    Full Text Available Abstract Background Engineered nanoparticles are smaller than 100 nm and designed to improve or achieve new physico-chemical properties. Consequently, also toxicological properties may change compared to the parent compound. We examined developmental and neurobehavioral effects following maternal exposure to a nanoparticulate UV-filter (UV-titan L181. Methods Time-mated mice (C57BL/6BomTac were exposed by inhalation 1h/day to 42 mg/m3 aerosolized powder (1.7·106 n/cm3; peak-size: 97 nm on gestation days 8-18. Endpoints included: maternal lung inflammation; gestational and litter parameters; offspring neurofunction and fertility. Physicochemical particle properties were determined to provide information on specific exposure and deposition. Results Particles consisted of mainly elongated rutile titanium dioxide (TiO2 with an average crystallite size of 21 nm, modified with Al, Si and Zr, and coated with polyalcohols. In exposed adult mice, 38 mg Ti/kg was detected in the lungs on day 5 and differential cell counts of bronchoalveolar lavage fluid revealed lung inflammation 5 and 26-27 days following exposure termination, relative to control mice. As young adults, prenatally exposed offspring tended to avoid the central zone of the open field and exposed female offspring displayed enhanced prepulse inhibition. Cognitive function was unaffected (Morris water maze test. Conclusion Inhalation exposure to nano-sized UV Titan dusts induced long term lung inflammation in time-mated adult female mice. Gestationally exposed offspring displayed moderate neurobehavioral alterations. The results are discussed in the light of the observed particle size distribution in the exposure atmosphere and the potential pathways by which nanoparticles may impart changes in fetal development.

  6. ATP differentially upregulates fibroblast growth factor 2 and transforming growth factor α in neonatal and adult mice: effect on neuroproliferation.

    Science.gov (United States)

    Jia, C; Cussen, A R; Hegg, C C

    2011-03-17

    Multiple neurotrophic factors play a role in proliferation, differentiation and survival in the olfactory epithelium (OE); however, the signaling cascade has not been fully elucidated. We tested the hypotheses that ATP induces the synthesis and secretion of two neurotrophic factors, fibroblast growth factor 2 (FGF2) and transforming growth factor alpha (TGFα), and that these neurotrophic factors have a role in inducing proliferation. Protein levels of FGF2 and TGFα were increased 20 h post-intranasal instillation of ATP compared to vehicle control in adult Swiss Webster mice. Pre-intranasal treatment with purinergic receptor antagonist pyridoxal-phosphate-6-azophenyl-20,40-disulfonic acid (PPADS) significantly blocked this ATP-induced increase, indicating that upregulation of FGF2 and TGFα expression is mediated by purinergic receptor activation. However, in neonatal mouse, intranasal instillation of ATP significantly increased the protein levels of FGF2, but not TGFα. Likewise, ATP evoked the secretion of FGF2, but not TGFα, from neonatal mouse olfactory epithelial slices and PPADS significantly blocked ATP-evoked FGF2 release. To determine the role of FGF2 and TGFα in inducing proliferation, 5-bromo-2-deoxyuridine (BrdU) incorporation was examined in adult olfactory epithelium. Intranasal treatment with FGF receptor inhibitor PD173074 or epidermal growth factor receptor inhibitor AG1478 following ATP instillation significantly blocked ATP-induced BrdU incorporation. Collectively, these data demonstrate that ATP induces proliferation in adult mouse olfactory epithelium by promoting FGF2 and TGFα synthesis and activation of their receptors. These data suggest that different mechanisms regulate neurogenesis in neonatal and adult OE, and FGF2 and TGFα may have different roles throughout development. PMID:21187124

  7. ATP differentially upregulates growth factors FGF2 and TGFα in neonatal and adult mice: Effect on neuroproliferation

    Science.gov (United States)

    Jia, Cuihong; Cussen, Amber R.; Hegg, Colleen Cosgrove

    2011-01-01

    Multiple neurotrophic factors play a role in proliferation, differentiation and survival in the olfactory epithelium; however, the signaling cascade has not been fully elucidated. We tested the hypotheses that ATP induces the synthesis and secretion of two neurotrophic factors, fibroblast growth factor 2 (FGF2) and transforming growth factor alpha (TGFα), and that these neurotrophic factors have a role in inducing proliferation. Protein levels of FGF2 and TGFα were increased 20 h post-intranasal instillation of ATP compared to vehicle control in adult Swiss Webster mice. Pre-intranasal treatment with purinergic receptor antagonist pyridoxalphosphate-6-azophenyl-20,40-disulfonic acid (PPADS) significantly blocked this ATP-induced increase, indicating that upregulation of FGF2 and TGFα expression is mediated by purinergic receptor activation. However, in neonatal mouse, intranasal instillation of ATP significantly increased the protein levels of FGF2, but not TGFα. Likewise, ATP evoked the secretion of FGF2, but not TGFα, from neonatal mouse olfactory epithelial slices and PPADS significantly blocked ATP-evoked FGF2 release. To determine the role of FGF2 and TGFα in inducing proliferation, 5-bromo-2-deoxyuridine (BrdU) incorporation was examined in adult olfactory epithelium. Intranasal treatment with FGF receptor inhibitor PD173074 or epidermal growth factor receptor inhibitor AG1478 following ATP instillation significantly blocked ATP-induced BrdU incorporation. Collectively, these data demonstrate that ATP induces proliferation in adult mouse olfactory epithelium by promoting FGF2 and TGFα synthesis and activation of their receptors. These data suggest that different mechanisms regulate neurogenesis in neonatal and adult OE, and FGF2 and TGFα may have different roles throughout development. PMID:21187124

  8. Properties of doublecortin-(DCX-expressing cells in the piriform cortex compared to the neurogenic dentate gyrus of adult mice.

    Directory of Open Access Journals (Sweden)

    Friederike Klempin

    Full Text Available The piriform cortex receives input from the olfactory bulb and (via the entorhinal cortex sends efferents to the hippocampus, thereby connecting the two canonical neurogenic regions of the adult rodent brain. Doublecortin (DCX is a cytoskeleton-associated protein that is expressed transiently in the course of adult neurogenesis. Interestingly, the adult piriform cortex, which is usually considered non-neurogenic (even though some reports exist that state otherwise, also contains an abundant population of DCX-positive cells. We asked how similar these cells would be to DCX-positive cells in the course of adult hippocampal neurogenesis. Using BAC-generated transgenic mice that express GFP under the DCX promoter, we studied DCX-expression and electrophysiological properties of DCX-positive cells in the mouse piriform cortex in comparison with the dentate gyrus. While one class of cells in the piriform cortex indeed showed features similar to newly generated immature granule neurons, the majority of DCX cells in the piriform cortex was mature and revealed large Na+ currents and multiple action potentials. Furthermore, when proliferative activity was assessed, we found that all DCX-expressing cells in the piriform cortex were strictly postmitotic, suggesting that no DCX-positive "neuroblasts" exist here as they do in the dentate gyrus. We conclude that DCX in the piriform cortex marks a unique population of postmitotic neurons with a subpopulation that retains immature characteristics associated with synaptic plasticity. DCX is thus, per se, no marker of neurogenesis but might be associated more broadly with plasticity.

  9. The Effect of Parents' Attitudes toward Divorce on Offspring's Attitudes: Gender and Parental Divorce as Mediating Factors

    Science.gov (United States)

    Kapinus, Carolyn A.

    2004-01-01

    This study addresses three questions: (a) What influence do parents' attitudes toward divorce have on offspring's attitudes? (b) How are offspring's attitudes toward divorce influenced by parental divorce, and do the effects vary depending on the gender of the child? and (c) How do conditions surrounding parental divorce influence young adults'…

  10. β-Cells Are Not Generated in Pancreatic Duct Ligation–Induced Injury in Adult Mice

    OpenAIRE

    Rankin, Matthew M.; Wilbur, Christopher J.; Rak, Kimberly; Shields, Emily J.; Granger, Anne; Kushner, Jake A.

    2013-01-01

    The existence of adult β-cell progenitors remains the most controversial developmental biology topic in diabetes research. It has been reported that β-cell progenitors can be activated by ductal ligation–induced injury of adult mouse pancreas and apparently act in a cell-autonomous manner to double the functional β-cell mass within a week by differentiation and proliferation. Here, we demonstrate that pancreatic duct ligation (PDL) does not activate progenitors to contribute to β-cell mass ex...

  11. Elevated paternal glucocorticoid exposure alters the small noncoding RNA profile in sperm and modifies anxiety and depressive phenotypes in the offspring.

    Science.gov (United States)

    Short, A K; Fennell, K A; Perreau, V M; Fox, A; O'Bryan, M K; Kim, J H; Bredy, T W; Pang, T Y; Hannan, A J

    2016-01-01

    Recent studies have suggested that physiological and behavioral traits may be transgenerationally inherited through the paternal lineage, possibly via non-genomic signals derived from the sperm. To investigate how paternal stress might influence offspring behavioral phenotypes, a model of hypothalamic-pituitary-adrenal (HPA) axis dysregulation was used. Male breeders were administered water supplemented with corticosterone (CORT) for 4 weeks before mating with untreated female mice. Female, but not male, F1 offspring of CORT-treated fathers displayed altered fear extinction at 2 weeks of age. Only male F1 offspring exhibited altered patterns of ultrasonic vocalization at postnatal day 3 and, as adults, showed decreased time in open on the elevated-plus maze and time in light on the light-dark apparatus, suggesting a hyperanxiety-like behavioral phenotype due to paternal CORT treatment. Interestingly, expression of the paternally imprinted gene Igf2 was increased in the hippocampus of F1 male offspring but downregulated in female offspring. Male and female F2 offspring displayed increased time spent in the open arm of the elevated-plus maze, suggesting lower levels of anxiety compared with control animals. Only male F2 offspring showed increased immobility time on the forced-swim test and increased latency to feed on the novelty-supressed feeding test, suggesting a depression-like phenotype in these animals. Collectively, these data provide evidence that paternal CORT treatment alters anxiety and depression-related behaviors across multiple generations. Analysis of the small RNA profile in sperm from CORT-treated males revealed marked effects on the expression of small noncoding RNAs. Sperm from CORT-treated males contained elevated levels of three microRNAs, miR-98, miR-144 and miR-190b, which are predicted to interact with multiple growth factors, including Igf2 and Bdnf. Sustained elevation of glucocorticoids is therefore involved in the transmission of paternal

  12. Postanesthetic Effects of Isoflurane on Behavioral Phenotypes of Adult Male C57BL/6J Mice

    OpenAIRE

    Yonezaki, Kumiko; Uchimoto, Kazuhiro; Miyazaki, Tomoyuki; Asakura, Ayako; Kobayashi, Ayako; Takase, Kenkichi; Goto, Takahisa

    2015-01-01

    Isoflurane was previously the major clinical anesthetic agent but is now mainly used for veterinary anesthesia. Studies have reported widespread sites of action of isoflurane, suggesting a wide array of side effects besides sedation. In the present study, we phenotyped isoflurane-treated mice to investigate the postanesthetic behavioral effects of isoflurane. We applied comprehensive behavioral test batteries comprising sensory test battery, motor test battery, anxiety test battery, depressio...

  13. Harvesting the maximum length of sciatic nerve from adult mice: a step-by-step approach

    OpenAIRE

    Bala, Usman; Tan, Kai-Leng; Ling, King-Hwa; Cheah, Pike-See

    2014-01-01

    Background Over the past several decades, many studies concerning peripheral nerve damage or regeneration have been performed. Mice have been widely used for many of these studies, with the sciatic nerve being the most targeted and preferred nerve. Therefore, techniques for harvesting mouse sciatic nerves of a maximum length that is sufficient for different analyses will be highly valuable. Here we describe a simple step-by-step guide for harvesting the maximum length of mouse sciatic nerve a...

  14. Aberrant Neural Stem Cell Proliferation and Increased Adult Neurogenesis in Mice Lacking Chromatin Protein HMGB2

    OpenAIRE

    Abraham, Ariel B; Robert Bronstein; Avanish S Reddy; Mirjana Maletic-Savatic; Adan Aguirre; Tsirka, Stella E.

    2013-01-01

    Neural stem and progenitor cells (NSCs/NPCs) are distinct groups of cells found in the mammalian central nervous system (CNS). Previously we determined that members of the High Mobility Group (HMG) B family of chromatin structural proteins modulate NSC proliferation and self-renewal. Among them HMGB2 was found to be dynamically expressed in proliferating and differentiating NSCs, suggesting that it may regulate NSC maintenance. We report now that Hmgb2(-/-) mice exhibit SVZ hyperproliferation...

  15. Ethyl Pyruvate Ameliorates The Damage Induced by Cyclophosphamide on Adult Mice Testes

    OpenAIRE

    Zahra Bakhtiary; Rasoul Shahrooz; Abbas Ahmadiooz; Farhad Soltanalinejad

    2016-01-01

    Background: Cyclophosphamide (CP) is a chemotherapy drug which causes deleterious effects on testicular tissue and increases free radicals in the body. The aim of this study is to investigate the protective effects of ethyl pyruvate (EP) on testicular improvement in CP treated animals. Materials and Methods: In this experimental study, 15 male mice (6-8 weeks) were divided into 3 groups. The control group received normal saline (0.1 ml/day), intraperitoneal (IP), CP group re...

  16. Repopulation of adult and neonatal mice with human hepatocytes: A chimeric animal model

    OpenAIRE

    Bissig, Karl-Dimiter; Le, Tam T.; Woods, Niels-Bjarne; Verma, Inder M.

    2007-01-01

    We report the successful transplantation of human hepatocytes in immunodeficient, fumarylacetoacetate hydrolase-deficient (fah−/−) mice. Engraftment occurs over the entire liver acinus upon transplantation. A few weeks after transplantation, increasing concentrations of human proteins (e.g., human albumin and human C3a) can be measured in the blood of the recipient mouse. No fusion between mouse and human hepatocytes can be detected. Three months after transplantation, up to 20% of the mouse ...

  17. Neurexin Dysfunction in Adult Neurons Results in Autistic-like Behavior in Mice

    OpenAIRE

    Luis G. Rabaneda; Estefanía Robles-Lanuza; José Luis Nieto-González; Francisco G. Scholl

    2014-01-01

    Autism spectrum disorders (ASDs) comprise a group of clinical phenotypes characterized by repetitive behavior and social and communication deficits. Autism is generally viewed as a neurodevelopmental disorder where insults during embryonic or early postnatal periods result in aberrant wiring and function of neuronal circuits. Neurexins are synaptic proteins associated with autism. Here, we generated transgenic βNrx1ΔC mice in which neurexin function is selectively impaired during late postnat...

  18. CDKL5 knockout leads to altered inhibitory transmission in the cerebellum of adult mice.

    Science.gov (United States)

    Sivilia, S; Mangano, C; Beggiato, S; Giuliani, A; Torricella, R; Baldassarro, V A; Fernandez, M; Lorenzini, L; Giardino, L; Borelli, A C; Ferraro, L; Calzà, L

    2016-06-01

    Mutations in the X-linked cyclin-dependent kinase-like 5 gene (CDKL5) are associated to severe neurodevelopmental alterations including motor symptoms. In order to elucidate the neurobiological substrate of motor symptoms in CDKL5 syndrome, we investigated the motor function, GABA and glutamate pathways in the cerebellum of CDKL5 knockout female mice. Behavioural data indicate that CDKL5-KO mice displayed impaired motor coordination on the Rotarod test, and altered steps, as measured by the gait analysis using the CatWalk test. A higher reduction in spontaneous GABA efflux, than that in glutamate, was observed in CDKL5-KO mouse cerebellar synaptosomes, leading to a significant increase of spontaneous glutamate/GABA efflux ratio in these animals. On the contrary, there were no differences between groups in K(+) -evoked GABA and glutamate efflux. The anatomical analysis of cerebellar excitatory and inhibitory pathways showed a selective defect of the GABA-related marker GAD67 in the molecular layer in CDKL5-KO mice, while the glutamatergic marker VGLUT1 was unchanged in the same area. Fine cerebellar structural abnormalities such as a reduction of the inhibitory basket 'net' estimated volume and an increase of the pinceau estimated volume were also observed in CDKL5-KO mice. Finally, the BDNF mRNA expression level in the cerebellum, but not in the hippocampus, was reduced compared with WT animals. These data suggest that CDKL5 deletion during development more markedly impairs the establishment of a correct GABAergic cerebellar network than that of glutamatergic one, leading to the behavioural symptoms associated with CDKL5 mutation. PMID:27108663

  19. Subchronic phencyclidine treatment in adult mice increases GABAergic transmission and LTP threshold in the hippocampus.

    Science.gov (United States)

    Nomura, Toshihiro; Oyamada, Yoshihiro; Fernandes, Herman B; Remmers, Christine L; Xu, Jian; Meltzer, Herbert Y; Contractor, Anis

    2016-01-01

    Repeated administration of non-competitive N-methyl-d-aspartate (NMDA) receptor antagonists such as phencyclidine (PCP) to rodents causes long-lasting deficits in cognition and memory, and has effects on behaviors that have been suggested to be models of the cognitive impairment associated with schizophrenia (CIAS). Despite this being a widely studied animal model, little is known about the long lasting changes in synapses and circuits that underlie the altered behaviors. Here we examined synaptic transmission ex-vivo in the hippocampus of mice after a subchronic PCP (scPCP) administration regime. We found that after at least one week of drug free washout period when mice have impaired cognitive function, the threshold for long-term potentiation (LTP) of CA1 excitatory synapses was elevated. This elevated LTP threshold was directly related to increased inhibitory input to CA1 pyramidal cells through increased activity of GABAergic neurons. These results suggest repeated PCP administration causes a long-lasting metaplastic change in the inhibitory circuits in the hippocampus that results in impaired LTP, and could contribute to the deficits in hippocampal-dependent memory in PCP-treated mice. Changes in GABA signaling have been described in patients with schizophrenia, therefore our results support using scPCP as a model of CIAS. This article is part of the Special Issue entitled 'Synaptopathy--from Biology to Therapy'. PMID:25937215

  20. Ah receptor expression in cardiomyocytes protects adult female mice from heart dysfunction induced by TCDD exposure.

    Science.gov (United States)

    Kurita, Hisaka; Carreira, Vinicius S; Fan, Yunxia; Jiang, Min; Naticchioni, Mindi; Koch, Sheryl; Rubinstein, Jack; Puga, Alvaro

    2016-04-29

    Epidemiological studies in humans and experimental work in rodents suggest that exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a persistent environmental toxicant, is associated with incidence of heart disease. Although TCDD toxicity depends by and large on the aryl hydrocarbon receptor (AHR), the role of the cardiac AHR in TCDD induced cardiovascular disease is not well defined. To determine whether the Ahr gene mediates disruption of heart function by TCDD, we generated a cardiomyocyte-specific Ahr knockout mouse by crossing Ahr(fx/fx) mice with βMhc:cre/+ mice, in which expression of Cre recombinase is driven by the promoter of the βMhc (myosin heavy chain-beta) gene. Starting at three months of age, mice with cardiomyocyte-specific Ahr ablation were exposed to 1μg/kg/week of TCDD or control vehicle by oral gavage for an additional three months. Relative to unexposed controls, TCDD-exposure induced cardiomyocyte Ahr-independent changes in males but not females, including a significant increase in body weight, blood pressure, and cardiac hypertrophy and a decrease in cardiac ejection fraction. TCDD exposure also induced cardiomyocyte Ahr-dependent changes in fibrosis and calcium signaling gene expression in both males and females. TCDD exposure appears to cause sexually dimorphic effects on heart function and induce fibrosis and changes in calcium signaling in both males and females through activation of the cardiomyocyte-specific Ahr. PMID:27163630

  1. Desensitization and Incomplete Recovery of Hepatic Target Genes After Chronic Thyroid Hormone Treatment and Withdrawal in Male Adult Mice.

    Science.gov (United States)

    Ohba, Kenji; Leow, Melvin Khee-Shing; Singh, Brijesh Kumar; Sinha, Rohit Anthony; Lesmana, Ronny; Liao, Xiao-Hui; Ghosh, Sujoy; Refetoff, Samuel; Sng, Judy Chia Ghee; Yen, Paul Michael

    2016-04-01

    Clinical symptoms may vary and not necessarily reflect serum thyroid hormone (TH) levels during acute and chronic hyperthyroidism as well as recovery from hyperthyroidism. We thus examined changes in hepatic gene expression and serum TH/TSH levels in adult male mice treated either with a single T3 (20 μg per 100 g body weight) injection (acute T3) or daily injections for 14 days (chronic T3) followed by 10 days of withdrawal. Gene expression arrays from livers harvested at these time points showed that among positively-regulated target genes, 320 were stimulated acutely and 429 chronically by T3. Surprisingly, only 69 of 680 genes (10.1%) were induced during both periods, suggesting desensitization of the majority of acutely stimulated target genes. About 90% of positively regulated target genes returned to baseline expression levels after 10 days of withdrawal; however, 67 of 680 (9.9%) did not return to baseline despite normalization of serum TH/TSH levels. Similar findings also were observed for negatively regulated target genes. Chromatin immunoprecipitation analysis of representative positively regulated target genes suggested that acetylation of H3K9/K14 was associated with acute stimulation, whereas trimethylation of H3K4 was associated with chronic stimulation. In an in vivo model of chronic intrahepatic hyperthyroidism since birth, adult male monocarboxylate transporter-8 knockout mice also demonstrated desensitization of most acutely stimulated target genes that were examined. In summary, we have identified transcriptional desensitization and incomplete recovery of gene expression during chronic hyperthyroidism and recovery. Our findings may be a potential reason for discordance between clinical symptoms and serum TH levels observed in these conditions. PMID:26866609

  2. Physiological and neuroendocrine responses to chronic variable stress in male California mice (Peromyscus californicus): influence of social environment and paternal state

    OpenAIRE

    De Jong, TR; Harris, BN; Perea-Rodriguez, JP; Saltzman, W

    2013-01-01

    Social environment and parental state affect stress responses in mammals, but their impact may depend on the social and reproductive strategy of the species. The influences of cohabitation with a male or female conspecific, and the birth of offspring, on the physiological and endocrine responses to chronic variable stress were studied in the monogamous and biparental California mouse (Peromyscus californicus). Adult male California mice were housed either with a male cage ma...

  3. Prophylactic Role of Oral Melatonin Administration on Neurogenesis in Adult Balb/C Mice during REM Sleep Deprivation.

    Science.gov (United States)

    López-Armas, Gabriela; Flores-Soto, Mario Eduardo; Chaparro-Huerta, Verónica; Jave-Suarez, Luis Felipe; Soto-Rodríguez, Sofía; Rusanova, Iryna; Acuña-Castroviejo, Dario; González-Perez, Oscar; González-Castañeda, Rocío Elizabeth

    2016-01-01

    Purpose. The aim of this study was to assess the effect of melatonin in the proliferation of neural progenitors, melatonin concentration, and antiapoptotic proteins in the hippocampus of adult mice exposed to 96 h REM sleep deprivation (REMSD) prophylactic administration of melatonin for 14 days. Material and Methods. Five groups of Balb/C mice were used: (1) control, (2) REMSD, (3) melatonin (10 mg/kg) plus REMSD, (4) melatonin and intraperitoneal luzindole (once a day at 5 mg/kg) plus REMSD, and (5) luzindole plus REMSD. To measure melatonin content in hippocampal tissue we used HPLC. Bcl-2 and Bcl-xL proteins were measured by Western Blot and neurogenesis was determined by injecting 5-bromo-2-deoxyuridine (BrdU) and BrdU/nestin expressing cells in the subgranular zone of the dentate gyrus were quantified by epifluorescence. Results. The melatonin-treated REMSD group showed an increased neural precursor in 44% with respect to the REMSD group and in 28% when contrasted with the control group (P expression of Bcl-2 and Bcl-xL as compared to the rest of the groups. Conclusion. The exogenous administration of melatonin restores the tissue levels of sleep-deprived group and appears to be an efficient neuroprotective agent against the deleterious effects of REMSD. PMID:27579149

  4. Prophylactic Role of Oral Melatonin Administration on Neurogenesis in Adult Balb/C Mice during REM Sleep Deprivation

    Science.gov (United States)

    Flores-Soto, Mario Eduardo; Chaparro-Huerta, Verónica; Soto-Rodríguez, Sofía; González-Perez, Oscar

    2016-01-01

    Purpose. The aim of this study was to assess the effect of melatonin in the proliferation of neural progenitors, melatonin concentration, and antiapoptotic proteins in the hippocampus of adult mice exposed to 96 h REM sleep deprivation (REMSD) prophylactic administration of melatonin for 14 days. Material and Methods. Five groups of Balb/C mice were used: (1) control, (2) REMSD, (3) melatonin (10 mg/kg) plus REMSD, (4) melatonin and intraperitoneal luzindole (once a day at 5 mg/kg) plus REMSD, and (5) luzindole plus REMSD. To measure melatonin content in hippocampal tissue we used HPLC. Bcl-2 and Bcl-xL proteins were measured by Western Blot and neurogenesis was determined by injecting 5-bromo-2-deoxyuridine (BrdU) and BrdU/nestin expressing cells in the subgranular zone of the dentate gyrus were quantified by epifluorescence. Results. The melatonin-treated REMSD group showed an increased neural precursor in 44% with respect to the REMSD group and in 28% when contrasted with the control group (P < 0.021). The melatonin-treated REMSD group also showed the highest expression of Bcl-2 and Bcl-xL as compared to the rest of the groups. Conclusion. The exogenous administration of melatonin restores the tissue levels of sleep-deprived group and appears to be an efficient neuroprotective agent against the deleterious effects of REMSD.

  5. Proliferation of Estrogen Receptor alpha Positive Mammary Epithelial Cells is Restrained by TGFbeta1 in Adult Mice

    Energy Technology Data Exchange (ETDEWEB)

    Ewan, Kenneth B.R.; Oketch-Rabah, Hellen A.; Ravani, Shraddha A.; Shyamala, G.; Moses, Harold L.; Barcellos-Hoff, Mary Helen

    2005-03-03

    Transforming growth factor {beta}1 (TGF{beta}1) is a potent inhibitor of mammary epithelial proliferation. In human breast, estrogen receptor {alpha} (ER{alpha}) cells rarely co-localize with markers of proliferation, but their increased frequency correlates with breast cancer risk. To determine whether TGF{beta}1 is necessary for the quiescence of ER{alpha}-positive population, we examined mouse mammary epithelial gland at estrus. Approximately 35% of cells showed TGF{beta}1 activation, which co-localized with nuclear receptor-phosphorylated Smad 2/3, indicating that TGF{beta} signaling is autocrine. Furthermore, nuclear Smad co-localized with nuclear ER{alpha}. To test whether TGF{beta} was functional, we examined genetically engineered mice with different levels of TGF{beta}1. ER{alpha} co-localization with markers of proliferation (i.e. Ki-67 or BrdU) at estrus was significantly increased in the mammary glands of Tgf{beta}1 C57/bl/129SV heterozygote mice. This relationship was maintained following pregnancy, but was absent at puberty. Conversely, mammary epithelial expression of constitutively active TGF{beta}1 via the MMTV promoter suppressed proliferation of ER{alpha} positive cells. Thus, TGF{beta}1 activation functionally restrains ER{alpha} positive cells from proliferating in adult mammary gland. Accordingly, we propose that TGF{beta}1 dysregulation may promote proliferation of ER{alpha} positive cells associated with breast cancer risk in humans.

  6. Influence of 90Sr, adult thymectomy and antilymphocyteglobulin on haematopoietic tissues and peripheral blood leucocytes in CBA mice

    International Nuclear Information System (INIS)

    The role or long-time immune suppression in carcinogenesis induced by the long-lived internal emitter 90Sr, is investigated in an ongoing study. The experimental design is based on the assumption that impaired immune responsiveness, by other means than 90Sr, might increase the neoplastic response in exposed individuals, and thus reflect a protective function, if existing. Intercomparison is made of the tumour yield in mice exposed to different single doses of 90Sr and simultaneously subjected or not to long-term immune suppression by adult thymectomy (ATx) and/or antilymphocyteglobulin (ALG) treatment. Information on the general condition and responsiveness of the immune system, in the respective models, during tumour expectancy time, is essential for a conclusive evaluation of the results. To meet theses demands the present paper reports on histopathologic alternations in immune organs and changes in white blood cell counts, induced by the different combinations of 90Sr, ATx + ALG treatment. The results confirm the prediction, that ATx + ALG is an efficient and, with respect to the purpose of the study, suitable treatment for additive long-term depression of the immune system in 90Sr irradiated mice, evidenced in particular by increased depletion of monomorphonuclear cells (MNC) in lymphoid organs and peripheral blood. Subsequent reports will deal with functional immune parameters. (orig.)

  7. Does radioadaptive response also apply to the case of heavy-ion irradiations in fetal and adult mice?

    International Nuclear Information System (INIS)

    Possible induction of adaptive response (AR) by the high linear energy transfer (LET) accelerated heavy ion irradiations (HI) is being attempted both in young adult female mice and in fetal mice of C57BL/6J Jms strain, using growth delay, hematopoietic damage and reduced survival in vivo, prenatal growth delay, malformation and death in utero as endpoints. In this fiscal year, using carbon, silicon, neon, and iron ion irradiations and X-rays, we demonstrated that 1) in the in utero studies, the priming low dose X-irradiations could induce protective effects against the detrimental effects from the high LET heavy-ion challenging irradiations from neon but not from iron beams; 2) in the in vivo studies, the priming low dose X-irradiations could induce protective effects against the detrimental effects from the high LET heavy-ion challenging irradiations from neon beams; 3) also in the in vivo studies, priming low dose of high LET iron ions did not show any protective effects against challenging dose from X-rays while priming low dose of high LET carbon ions could induce protective effects against the detrimental effects from the high LET heavy-ion challenging irradiations from neon beams. (author)

  8. Effect of intermittent exposure to ethanol and MDMA during adolescence on learning and memory in adult mice

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    Vidal-Infer Antonio

    2012-06-01

    Full Text Available Abstract Background Heavy binge drinking is increasingly frequent among adolescents, and consumption of 3,4-methylenedioxymethamphetamine (MDMA is often combined with ethanol (EtOH. The long-lasting effects of intermittent exposure to EtOH and MDMA during adolescence on learning and memory were evaluated in adult mice using the Hebb-Williams maze. Methods Adolescent OF1 mice were exposed to EtOH (1.25 g/kg on two consecutive days at 48-h intervals over a 14-day period (from PD 29 to 42. MDMA (10 or 20 mg/kg was injected twice daily at 4-h intervals over two consecutive days, and this schedule was repeated six days later (PD 33, 34, 41 and 42, resulting in a total of eight injections. Animals were initiated in the Hebb-Williams maze on PND 64. The concentration of brain monoamines in the striatum and hippocampus was then measured. Results At the doses employed, both EtOH and MDMA, administered alone or together, impaired learning in the Hebb-Williams maze, as treated animals required more time to reach the goal than their saline-treated counterparts. The groups treated during adolescence with EtOH, alone or plus MDMA, also presented longer latency scores and needed more trials to reach the acquisition criterion score. MDMA induced a decrease in striatal DA concentration, an effect that was augmented by the co-administration of EtOH. All the treatment groups displayed an imbalance in the interaction DA/serotonin. Conclusions The present findings indicate that the developing brain is highly vulnerable to the damaging effects of EtOH and/or MDMA, since mice receiving these drugs in a binge pattern during adolescence exhibit impaired learning and memory in adulthood.

  9. Increased adipogenesis in cultured embryonic chondrocytes and in adult bone marrow of dominant negative Erg transgenic mice.

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    Sébastien Flajollet

    Full Text Available In monolayer culture, primary articular chondrocytes have an intrinsic tendency to lose their phenotype during expansion. The molecular events underlying this chondrocyte dedifferentiation are still largely unknown. Several transcription factors are important for chondrocyte differentiation. The Ets transcription factor family may be involved in skeletal development. One family member, the Erg gene, is mainly expressed during cartilage formation. To further investigate the potential role of Erg in the maintenance of the chondrocyte phenotype, we isolated and cultured chondrocytes from the rib cartilage of embryos of transgenic mice that express a dominant negative form of Erg (DN-Erg during cartilage formation. DN-Erg expression in chondrocytes cultured for up to 20 days did not affect the early dedifferentiation usually observed in cultured chondrocytes. However, lipid droplets accumulated in DN-Erg chondrocytes, suggesting adipocyte emergence. Transcriptomic analysis using a DNA microarray, validated by quantitative RT-PCR, revealed strong differential gene expression, with a decrease in chondrogenesis-related markers and an increase in adipogenesis-related gene expression in cultured DN-Erg chondrocytes. These results indicate that Erg is involved in either maintaining the chondrogenic phenotype in vitro or in cell fate orientation. Along with the in vitro studies, we compared adipocyte presence in wild-type and transgenic mice skeletons. Histological investigations revealed an increase in the number of adipocytes in the bone marrow of adult DN-Erg mice even though no adipocytes were detected in embryonic cartilage or bone. These findings suggest that the Ets transcription factor family may contribute to the homeostatic balance in skeleton cell plasticity.

  10. Bi-parental care contributes to sexually dimorphic neural cell genesis in the adult mammalian brain.

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    Gloria K Mak

    Full Text Available Early life events can modulate brain development to produce persistent physiological and behavioural phenotypes that are transmissible across generations. However, whether neural precursor cells are altered by early life events, to produce persistent and transmissible behavioural changes, is unknown. Here, we show that bi-parental care, in early life, increases neural cell genesis in the adult rodent brain in a sexually dimorphic manner. Bi-parentally raised male mice display enhanced adult dentate gyrus neurogenesis, which improves hippocampal neurogenesis-dependent learning and memory. Female mice display enhanced adult white matter oligodendrocyte production, which increases proficiency in bilateral motor coordination and preference for social investigation. Surprisingly, single parent-raised male and female offspring, whose fathers and mothers received bi-parental care, respectively, display a similar enhancement in adult neural cell genesis and phenotypic behaviour. Therefore, neural plasticity and behavioural effects due to bi-parental care persist throughout life and are transmitted to the next generation.

  11. Multiple phenotypes in adult mice following inactivation of the Coxsackievirus and Adenovirus Receptor (Car gene.

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    Ahmad Pazirandeh

    Full Text Available To determine the normal function of the Coxsackievirus and Adenovirus Receptor (CAR, a protein found in tight junctions and other intercellular complexes, we constructed a mouse line in which the CAR gene could be disrupted at any chosen time point in a broad spectrum of cell types and tissues. All knockouts examined displayed a dilated intestinal tract and atrophy of the exocrine pancreas with appearance of tubular complexes characteristic of acinar-to-ductal metaplasia. The mice also exhibited a complete atrio-ventricular block and abnormal thymopoiesis. These results demonstrate that CAR exerts important functions in the physiology of several organs in vivo.

  12. Cytogenetic damage in adult and newborn mice exposed to Elf magnetic fields

    Energy Technology Data Exchange (ETDEWEB)

    Ieradi, L.A. [Istituto per lo Studio degli Ecosistemi, CNR, Rome (Italy); Udroiu, I.; Chiuchiarelli, G.; Migliorini, D.; Cristaldi, M. [Universite La Sapienza, Dipt. di Biologia Animale e dell' Uomo, Rome (Italy); Tanzarella, C. [Roma Univ., Dipt. di Biologia (Italy)

    2006-07-01

    Data obtained in newborn mice show that the chronic exposure during intra-uterine life to a 50 Hz, 650 {mu}T E.L.F. magnetic field induce a genetic damage. Nevertheless, the increase of DNA strand break in brain and in micronuclei frequency in peripheral blood and liver disagree with the data obtained by Abramsson-Zetterberg and Grawe (13) which did not find any genetic alterations in mice exposed to extremely low frequency (E.L.F.) magnetic field. In any case, along with other dissimilarities in the experimental design, the intensity of the field (14 {mu}T) and the time of sampling (35 days) were different. It is important to underline the four-fold increase in C.R.E.S.T.+ micronuclei frequency in circulating erythrocytes in the exposed group in comparison with the control group. Even though this value is quite low, it could indicate that E.L.F. magnetic fields may have different properties to damage the genome integrity. This stresses the need for further investigation on the possible link between electromagnetic fields and aneuploidy in order to elucidate the relationship with carcinogenesis. Preliminary data obtained with sperm abnormality assay show a significant increase of sperm abnormalities in mice exposed to E.L.F. magnetic fields and suggest a possible alteration to the spermatogenic process after exposure. This data agrees with data obtained by Tablado et al. (1998), in mice exposed continually for 35 days to a field of 1 T. Regarding the palatal ridges alterations assay, the results obtained show that the development of the secondary palate is not affected by E.L.F. magnetic field (50 Hz, 0,65 T). Nevertheless further studies at different frequency and intensity should be carried out to detect the possible epigenetic damage induced by E.L.F. exposure (Migliorini, 2005). With regard to the mechanism of action, it is generally believed that the damage induced by the magnetic field is an oxidative damage and that free radicals are involved. Some authors

  13. Cytogenetic damage in adult and newborn mice exposed to Elf magnetic fields

    International Nuclear Information System (INIS)

    Data obtained in newborn mice show that the chronic exposure during intra-uterine life to a 50 Hz, 650 μT E.L.F. magnetic field induce a genetic damage. Nevertheless, the increase of DNA strand break in brain and in micronuclei frequency in peripheral blood and liver disagree with the data obtained by Abramsson-Zetterberg and Grawe (13) which did not find any genetic alterations in mice exposed to extremely low frequency (E.L.F.) magnetic field. In any case, along with other dissimilarities in the experimental design, the intensity of the field (14 μT) and the time of sampling (35 days) were different. It is important to underline the four-fold increase in C.R.E.S.T.+ micronuclei frequency in circulating erythrocytes in the exposed group in comparison with the control group. Even though this value is quite low, it could indicate that E.L.F. magnetic fields may have different properties to damage the genome integrity. This stresses the need for further investigation on the possible link between electromagnetic fields and aneuploidy in order to elucidate the relationship with carcinogenesis. Preliminary data obtained with sperm abnormality assay show a significant increase of sperm abnormalities in mice exposed to E.L.F. magnetic fields and suggest a possible alteration to the spermatogenic process after exposure. This data agrees with data obtained by Tablado et al. (1998), in mice exposed continually for 35 days to a field of 1 T. Regarding the palatal ridges alterations assay, the results obtained show that the development of the secondary palate is not affected by E.L.F. magnetic field (50 Hz, 0,65 T). Nevertheless further studies at different frequency and intensity should be carried out to detect the possible epigenetic damage induced by E.L.F. exposure (Migliorini, 2005). With regard to the mechanism of action, it is generally believed that the damage induced by the magnetic field is an oxidative damage and that free radicals are involved. Some authors

  14. Haematologic changes in young adult Swiss albino mice after tritiated water administration

    International Nuclear Information System (INIS)

    Tritiated water (HTO) injected intraperitoneally to Swiss albino mice at the rate of 370 kBq (10 μCi)/g body weight has been found to cause certain alterations in blood parameters 1, 5, 7 and 15 days post injectionem. Leukocyte count dropped significantly post treatment. Differential leukocyte counting showed lymphocytes to be most affected which were reduced by 38.29% on 5th day p.i. Erythrocyte count, haemoglobin and haematocrit values though showed no significant changes at early intervals, these values were significantly lower at later intervals than those of control. (author)

  15. Drug treatment of malaria infections can reduce levels of protection transferred to offspring via maternal immunity

    OpenAIRE

    Staszewski, Vincent; Reece, Sarah E; O'Donnell, Aidan J.; Cunningham, Emma J. A.

    2012-01-01

    Maternally transferred immunity can have a fundamental effect on the ability of offspring to deal with infection. However, levels of antibodies in adults can vary both quantitatively and qualitatively between individuals and during the course of infection. How infection dynamics and their modification by drug treatment might affect the protection transferred to offspring remains poorly understood. Using the rodent malaria parasite Plasmodium chabaudi, we demonstrate that curing dams part way ...

  16. Growing Up with a Parent having Schizophrenia: Experiences and Resilience in the Offsprings

    OpenAIRE

    Herbert, Hesi S.; Manjula, M.; Mariamma Philip

    2013-01-01

    Background: Parental mental illness has been found to have an impact on offsprings in their emotional, social, and behavioral aspects of life. Aims: To examine the experiences of offsprings of a parent having schizophrenia and to study their resilience. Materials and Methods: A sample of 45 adults with one parent diagnosed with schizophrenia was selected using purposive sampling. Subjects were assessed using socio-demographic data sheet, semi-structured interview schedule, and Connor-Davidson...

  17. Human-derived neural progenitors functionally replace astrocytes in adult mice

    OpenAIRE

    Chen, Hong; Qian, Kun; Chen, Wei; Hu, Baoyang; Blackbourn, Lisle W.; Du, Zhongwei; Ma, Lixiang; Liu, Huisheng; Knobel, Karla M.; Ayala, Melvin; Zhang, Su-Chun

    2015-01-01

    Astrocytes are integral components of the homeostatic neural network as well as active participants in pathogenesis of and recovery from nearly all neurological conditions. Evolutionarily, compared with lower vertebrates and nonhuman primates, humans have an increased astrocyte-to-neuron ratio; however, a lack of effective models has hindered the study of the complex roles of human astrocytes in intact adult animals. Here, we demonstrated that after transplantation into the cervical spinal co...

  18. Maternal antioxidant blocks programmed cardiovascular and behavioural stress responses in adult mice

    OpenAIRE

    Roghair, Robert D.; Wemmie, John A.; Volk, Kenneth A.; Scholz, Thomas D.; Lamb, Fred S.; Jeffrey L. Segar

    2011-01-01

    Intra-uterine growth restriction is an independent risk factor for adult psychiatric and cardiovascular diseases. In humans, intra-uterine growth restriction is associated with increased placental and fetal oxidative stress, as well as down-regulation of placental 11β-HSD (11β-hydroxysteroid dehydrogenase). Decreased placental 11β-HSD activity increases fetal exposure to maternal glucocorticoids, further increasing fetal oxidative stress. To explore the developmental origins of co-morbid hype...

  19. Skin-derived neural precursors competitively generate functional myelin in adult demyelinated mice

    OpenAIRE

    Mozafari, Sabah; Laterza, Cecilia; Roussel, Delphine; Bachelin, Corinne; Marteyn, Antoine; Deboux, Cyrille; Martino, Gianvito; Evercooren, Anne Baron-Van

    2015-01-01

    Induced pluripotent stem cell–derived (iPS-derived) neural precursor cells may represent the ideal autologous cell source for cell-based therapy to promote remyelination and neuroprotection in myelin diseases. So far, the therapeutic potential of reprogrammed cells has been evaluated in neonatal demyelinating models. However, the repair efficacy and safety of these cells has not been well addressed in the demyelinated adult CNS, which has decreased cell plasticity and scarring. Moreover, it i...

  20. Enhanced dopamine D1 and BDNF signaling in the adult dorsal striatum but not nucleus accumbens of prenatal cocaine treated mice

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    Thomas F. Tropea

    2011-12-01

    Full Text Available Previous work from our group and others utilizing animal models have demonstrated long lasting structural and functional alterations in the meso-cortico-striatal dopamine pathway following prenatal cocaine treatment. We have shown that prenatal cocaine treatment results in augmented D1 -induced cyclic AMP (cAMP and cocaine-induced immediate-early gene expression in the striatum of adult mice. In this study we further examined basal as well as cocaine or D1-induced activation of a set of molecules known to be mediators of neuronal plasticity following psychostimulant treatment, with emphasis in the dorsal striatum (Str and nucleus accumbens (NAc of adult mice exposed to cocaine in utero. Basally, in the striatum of prenatal cocaine treated (PCOC mice there were significantly higher levels of a number of the transcription factors studied. Following acute administration of cocaine (15 mg/kg, i.p. or D1 agonist (SKF 82958; 1 mg/kg, i.p. there were significantly higher levels of Ser133 P-CREB, Thr34 P-DARPP-32, and Thr202/Tyr204 P-ERK2 in the Str, that were significantly augmented in PCOC mice. In sharp contrast, in the NAc of those mice, we found increased P-CREB and P-ERK2 in PSAL mice, a response that was not evident in PCOC mice. Examination of Ser 845 P-GluA1 revealed increased levels in PSAL mice, but significantly decreased levels in PCOC mice in both the Str and NAc following acute administration of cocaine or D1 agonist. We also found significantly higher levels of the BDNF precursor, pro-BDNF and one of its receptors, TrkB in the Str of PCOC mice. These results suggest a persistent up-regulation of molecules critical to D1 and BDNF signaling in the Str of adult mice exposed to cocaine in utero. These molecular adaptations may underlie components of the behavioral deficits evident in exposed animals and a subset of exposed humans, and may represent a therapeutic target for ameliorating aspects of the prenatal cocaine-induced phenotype.

  1. Impaired Maternal Behavior in Usp46 Mutant Mice: A Model for Trans-Generational Transmission of Maternal Care.

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    Shoya Umemura

    Full Text Available Usp46 mutant mice (congenic strain on a B6 genetic background; MT mice have a low weaning rate and display poor maternal behavior compared to C57BL/6J mice (B6 mice. Based on these observations, we examined how maternal behavior is shaped by cross-fostering and in-fostering MT and B6 mice. The experiments consisted of six groups: B6 mice fostered by their biological mother (B6-CO; MT mice fostered by their biological mother (MT-CO; B6 mice fostered by a different B6 mother (B6-IF; MT mice fostered by a different MT mother (MT-IF; B6 mice fostered by an MT mother (B6-CF; and MT mice fostered by a B6 mother (MT-CF. Maternal behavior was assessed using the pup-retrieval test in adult female offspring, and four parameters, time nursing pups in the nest, time sniffing or licking pups, rearing behavior, and latency to retrieve pups, were measured. Cross-fostering significantly reduced time spent nursing and sniffing/licking pup, and increased the number of instances of rearing in the B6-CF group, and improved three parameters of maternal behaviors (nursing, rearing and latency in the MT-CF group. These results indicate that the level of maternal care is transmitted to their pups and proper maternal behaviors can be shaped if adequate postpartum maternal care is given, even in genetically vulnerable mice. However, the offspring's genotype may also influence the development of maternal behaviors in adulthood. Thus, MT mice may prove useful as a model for trans-generational transmission of maternal care, and these findings may provide insight into the mechanisms of maltreating behaviors in human child abuse.

  2. 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 < 0.05). Urinary amounts of equol were significantly higher in the XD group than in the CD group (p < 0.05). The fecal lipid contents (% dry weight) were significantly greater in the XD group than in the CD group (p < 0.01). The cecal microbiota differed between the two dietary groups. The occupation ratios of Bacteroides were significantly greater in the CD than in the XD group (p < 0.05). This study suggests that xylitol has the potential to affect the metabolism of daidzein by altering the metabolic activity of the intestinal microbiota and/or gut environment. Given that equol affects bone health, dietary xylitol plus isoflavonoids may exert a favorable effect on bone health. PMID:24336061

  3. Chronic minocycline treatment improves social recognition memory in adult male Fmr1 knockout mice.

    Science.gov (United States)

    Yau, Suk Yu; Chiu, Christine; Vetrici, Mariana; Christie, Brian R

    2016-10-01

    Fragile X syndrome (FXS) is caused by a mutation in the Fmr1 gene that leads to silencing of the gene and a loss of its gene product, Fragile X mental retardation protein (FMRP). Some of the key behavioral phenotypes for FXS include abnormal social anxiety and sociability. Here we show that Fmr1 knock-out (KO) mice exhibit impaired social recognition when presented with a novel mouse, and they display normal social interactions in other sociability tests. Administering minocycline to Fmr1 KO mice throughout critical stages of neural development improved social recognition memory in the novel mouse recognition task. To determine if synaptic changes in the prefrontal cortex (PFC) could have played a role in this improvement, we examined PSD-95, a member of the membrane-associated guanylate kinase family, and signaling molecules (ERK1/2, and Akt) linked to synaptic plasticity in the PFC. Our analyses indicated that while minocycline treatment can enhance behavioral performance, it does not enhance expression of PSD-95, ERK1/2 or Akt in the PFC. PMID:27291517

  4. 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.

  5. Newly generated cells are increased in hippocampus of adult mice lacking a serine protease inhibitor

    Directory of Open Access Journals (Sweden)

    Sticker Melanie

    2010-06-01

    Full Text Available Abstract Background Neurogenesis in the hippocampal dentate gyrus and the subventricular zone occurs throughout the life of mammals and newly generated neurons can integrate functionally into established neuronal circuits. Neurogenesis levels in the dentate gyrus are modulated by changes in the environment (enrichment, exercise, hippocampal-dependent tasks, NMDA receptor (NMDAR activity, sonic hedgehog (SHH and/or other factors. Results previously, we showed that Protease Nexin-1 (PN-1, a potent serine protease inhibitor, regulates the NMDAR availability and activity as well as SHH signaling. Compared with wild-type (WT, we detected a significant increase in BrdU-labeled cells in the dentate gyrus of mice lacking PN-1 (PN-1 -/- both in controls and after running exercise. Patched homologue 1 (Ptc1 and Gli1 mRNA levels were higher and Gli3 down-regulated in mutant mice under standard conditions and to a lesser extent after running exercise. However, the number of surviving BrdU-positive cells did not differ between WT and PN-1 -/- animals. NMDAR availability was altered in the hippocampus of mutant animals after exercise. Conclusion All together our results indicate that PN-1 controls progenitors proliferation through an effect on the SHH pathway and suggest an influence of the serpin on the survival of newly generated neurons through modulation of NMDAR availability.

  6. Aniracetam does not alter cognitive and affective behavior in adult C57BL/6J mice.

    Directory of Open Access Journals (Sweden)

    Thomas W Elston

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

  7. Aniracetam does not alter cognitive and affective behavior in adult C57BL/6J mice.

    Science.gov (United States)

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

    2014-01-01

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

  8. Pre-birth world and the development of the immune system: mum's diet affects our adult health: new insight on how the diet during pregnancy permanently influences offspring health and immune fitness.

    Science.gov (United States)

    Ferreira, Manuela; Veiga-Fernandes, Henrique

    2014-12-01

    Secondary lymphoid organs form in utero through an inherited and well-established developmental program. However, maternal non-heritable features can have a major impact on the gene expression of the embryo, hence influencing the future health of the offspring. Recently, maternal retinoids were shown to regulate the formation of immune structures, shedding light on the role of maternal nutrition in the genetic signature of emergent immune cells. Here we highlight evidence showing how the maternal diet influences the establishment of the immune system, and we also discuss how unbalanced maternal diets may set the response to infection and vaccination in the progeny. PMID:25382781

  9. Effects of prenatal exposure to low dose beta radiation from tritiated water on postnatal growth and neurobehavior of mice

    International Nuclear Information System (INIS)

    Pregnant adult C57BL/6J mice were randomly assigned to 4 groups and 3 of them were irradiated with beta-rays from tritiated water (HTO) by a single intraperitoneal injection on the 12.5 th day of gestation. Their offsprings received cumulative dose of 0.036, 0.071 and 0.213 Gy, respectively. Offspring of mice were observed for postnatal growth (body weight), the appearance of four physiologic makers (eye opening, pinna detachment, testes decent, vaginal opening), the age of acquisition of two reflexes (cloff avoidance, air righting) and sensuous functions (auditory startle, pain threshold), movement and coordination functions and activity (pivoting, foot splay, continuous corridor activity), and learning and memory (electric avoidance reflex in Y-maze, conditioning reflex). It was found that results for the parameters in 0.036 or 0.071 Gy group were differed significantly from those for the controls, and for most parameters, a dose dependent effect was found

  10. The nuclear progesterone receptor reduces post-sigh apneas during sleep and increases the ventilatory response to hypercapnia in adult female mice.

    Science.gov (United States)

    Marcouiller, François; Boukari, Ryma; Laouafa, Sofien; Lavoie, Raphaël; Joseph, Vincent

    2014-01-01

    We tested the hypothesis that the nuclear progesterone receptor (nPR) is involved in respiratory control and mediates the respiratory stimulant effect of progesterone. Adult female mice carrying a mutation in the nPR gene (PRKO mice) and wild-type controls (WT) were implanted with an osmotic pump delivering vehicle or progesterone (4 mg/kg/day). The mice were instrumented with EEG and neck EMG electrodes connected to a telemetry transmitter. The animals were placed in a whole body plethysmograph 7 days after surgery to record ventilation, metabolic rate, EEG and neck EMGs for 4 consecutive hours. The animals were exposed to hypercapnia (5% CO2), hypoxia (12% O2) and hypoxic-hypercapnia (5% CO2+12% O2-5 min each) to assess chemoreflex responses. EEG and EMG signals were used to characterize vigilance states (e.g., wake, non-REM, and REM sleep). PRKO mice exhibited similar levels of minute ventilation during non-REM and REM sleep, and higher frequencies of sighs and post-sigh apneas during non-REM sleep compared to WT. Progesterone treatment increased minute ventilation and metabolic rate in WT and PRKO mice during non-REM sleep. In WT mice, but not in PRKO mice, the ventilation under hypercapnia and hypoxic hypercapnia was enhanced after progesterone treatment. We conclude that the nPR reduces apnea frequency during non-REM sleep and enhances chemoreflex responses to hypercapnia after progesterone treatment. These results also suggest that mechanisms other than nPR activation increase metabolic rate in response to progesterone treatment in adult female mice. PMID:24945655

  11. Additive effects of physical exercise and environmental enrichment on adult hippocampal neurogenesis in mice

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    Klaus Fabel

    2009-11-01

    Full Text Available Voluntary physical exercise (wheel running, RUN and environmental enrichment (ENR both stimulate adult hippocampal neurogenesis but do so by different mechanisms. RUN induces precursor cell proliferation, whereas ENR exerts a survival-promoting effect on newborn cells. In addition, continued RUN prevented the physiologically occurring age-related decline in precursor cell in the dentate gyrus but did not lead to a corresponding increase in net neurogenesis. We hypothesized that in the absence of appropriate cognitive stimuli the potential for neurogenesis could not be realized but that an increased potential by proliferating precursor cells due to RUN could actually lead to more adult neurogenesis if an appropriate survival-promoting stimulus follows the exercise. We thus asked whether a sequential combination of RUN and ENR (RUNENR would show additive effects that are distinct from the application of either paradigm alone. We found that the effects of 10 days of RUN followed by 35 days of ENR were additive in that the combined stimulation yielded an approximately 30% greater increase in new neurons than either stimulus alone, which also increased neurogenesis. Surprisingly, this result indicates that although overall the amount of proliferating cells in the dentate gyrus is poorly predictive of net adult neurogenesis, an increased neurogenic potential nevertheless provides the basis for a greater efficiency of the same survival-promoting stimulus. We thus propose that physical activity can “prime” the neurogenic region of the dentate gyrus for increased neurogenesis in the case the animal is exposed to an additional cognitive stimulus, here represented by the enrichment paradigm.

  12. Glutathione restores the mechanism of synaptic plasticity in aged mice to that of the adult.

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    Julie M Robillard

    Full Text Available Glutathione (GSH, the major endogenous antioxidant produced by cells, can modulate the activity of N-methyl-D-aspartate receptors (NMDARs through its reducing functions. During aging, an increase in oxidative stress leads to decreased levels of GSH in the brain. Concurrently, aging is characterized by calcium dysregulation, thought to underlie impairments in hippocampal NMDAR-dependent long-term potentiation (LTP, a form of synaptic plasticity thought to represent a cellular model for memory. Here we show that orally supplementing aged mice with N-acetylcysteine, a precursor for the formation of glutathione, reverses the L-type calcium channel-dependent LTP seen in aged animals to NMDAR-dependent LTP. In addition, introducing glutathione in the intrapipette solution during whole-cell recordings restores LTP obtained in whole-cell conditions in the aged hippocampus. We conclude that aging leads to a reduced redox potential in hippocampal neurons, triggering impairments in LTP.

  13. Evidence of oxidative shielding of offspring in a wild mammal

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    Emma I.K. Vitikainen

    2016-05-01

    Full Text Available Oxidative damage has been proposed as a potential mechanism underlying a life history tradeoff between survival and reproduction. However, evidence that reproduction is associated with increased oxidative damage is equivocal, and some studies have found that breeding females exhibit reduced, rather than elevated, levels of oxidative damage compared to equivalent non-breeders. Recently it was hypothesised that oxidative damage could have negative impacts on developing offspring, and that mothers might down-regulate oxidative damage during reproduction to shield their offspring from such damage. We tested this hypothesis through a longitudinal study of adult survival, reproduction, and oxidative damage in wild banded mongooses (Mungos mungo in Uganda. High levels of oxidative damage as measured by malondialdehyde (MDA were associated with reduced survival in both sexes. Levels of protein carbonyls were not linked to survival. Mothers showed reduced levels of MDA during pregnancy, and individuals with higher MDA levels gestated fewer offspring and had lower pup survival. These results suggest that maternal oxidative damage has transgenerational costs, and are consistent with the idea that mothers may attempt to shield their offspring from particularly harmful types of oxidative damage during pregnancy. Further advance in understanding of life history variation would benefit from theory and tests of the potential transgenerational impacts of the mechanisms underlying life history trade-offs.

  14. Bone marrow from Balb/c mice radiocontaminated with 241Am in utero shows a deficient in vitro haemopoiesis

    International Nuclear Information System (INIS)

    Radiation damage from 241Am to bone marrow cells was manifest in long-term bone marrow cultures (LTC) from offspring of mice radiocontaminated at 14th day of gestation (119, 479, 803, 1754 kBq 241Am kg). Offspring were reared by their own contaminated mother for 3 weeks postnatal. LTC from these offspring were less able to support in vitro CFC proliferation than control LTC. This radiation damage persisted 71 weeks after radiocontamination in utero. Damage was observed at lower doses if 241Am contamination occurred at foetal rather than adult ages. Radiation damage was observed only using LTC. After culturing LTC in 25% FCS and recharging the stromal adherent layer with bone marrow cell suspensions originating either from control offspring or from offspring contaminated with 241Am in utero evidence was found that the proliferation capacity of haemopoietic cells was diminished. However, the nature of effects on the stromal elements is currently somewhat equivocal. Following in utero contamination stromal adherent cells appeared to support better production of in vitro CFC. (author)

  15. The study of susceptibility to carbon tetrachloride and benzene in offspring of expanded simple tandem repeats mutation mice exposed to formaldehyde%甲醛致扩张性简单串联重复序列突变小鼠子代对四氯化碳和苯暴露易感性研究

    Institute of Scientific and Technical Information of China (English)

    王超; 刘云儒; 周印; 李爱萍; 周建伟

    2011-01-01

    为5.88‰±4.55‰,F10代为8.25‰±2.06‰;C组1000 mg/kg苯染毒组:F5代为7.50‰±6.99‰,F10代为10.67‰±1.16‰;H组500 mg/kg苯染毒组:F5代为7.88‰±3.09‰,F10代为9.20‰±1.30‰;H组1000 mg/kg苯染毒组:F5代为9.63‰±4.34‰,F10代为13.33‰±2.08‰)随苯剂量的增加而增加,与溶剂对照组(C组F5代为1.13‰±0.35‰,F10代为1.20‰±0.82‰;H组F5代为1.25‰±0.46‰,F10代为1.33‰±1.03‰)的差异均有统计学意义(P<0.05,P<0.01).结论 甲醛暴露引起的基因组ESTR突变可改变子代小鼠对CCl4和苯的易感性.ESTR突变可能是影响机体对化学物易感性的生物学标志,其分子机制有待进一步阐明.%Objective To investigate the susceptibility to carbon tetrachloride and benzene in offspring of expanded simple tandem repeats (ESTR) mutation mice exposed to formaldehyde (FA). Methods F5 and F10 offspring (200 mg/m3 ×2 hours) served as H group and ICR mice were used as control group(group C). The F5 and F10 offspring were exposed to 10 ml/kg carbon tetrachloride at the doses of 0.05%, 0.50% or 5.00% for 24 hours, respectively or 500 or 1000 mg/kg benzene for 24 hours, respectively by intraperitoneal injection. Serum alanine transaminase (ALT), aspartate transaminase (AST) and the hepatic superoxide dismutase (SOD) or malondialdehyde (MDA) were detected; also the hepatic pathological changes were observed under light microscope; the micronucleus in sternum bone marrow cells as the biomarker of benzene blood toxicity were measured. Results ALT and AST activities in group C of F5 mice exposed to 0.50% and 5.00% CCl4, ALT in groups C and H of F10 mice exposed to 0.05%, 0.50%, 5.00% CCl4, AST in groups C and H of F10 mice exposed to 0.50% and 5.00% CCl4 were significantly higher than those in controls, respectively (P<0.05); as compared to the control, hepatic SOD activities in group C of F5 and F10 mice exposed to 0.50% and 5.00% CCl4, in group H of F5 mice exposed to 0.50% and 5.00% CCl4, and

  16. Does radioadaptive response also apply to the case of heavy-ion irradiations in fetal and adult mice?

    International Nuclear Information System (INIS)

    Possible induction of adaptive response (AR) by the high LET accelerated heavy ion irradiations (HI) is being attempted both in young adult female mice and in fetal mice of C57BL/6J Jms strain, using growth delay, hematopoietic damage and reduced survival in utero, prenatal growth delay, malformation and death in utero as endpoints. Investigations are to verify if priming dose from low LET X-irradiation could induce an AR against the detrimental effects from the high challenging dose of HI, if priming dose from HI could induce an AR against the high challenging dose from low LET X-irradiations, and if an AR could be induced when both priming and challenging doses are from HI. Three kinds of HI are being examined: carbon, silicon and iron, with the LET values of about 15, 55, and 200 keV/micrometer, respectively. Results show, at whole body level for the first time, that priming dose of low LET X-irradiations could induce AR both in vivo and in utero against the challenging dose from high LET HI, and priming dose from high LET HI could induce AR against the challenging dose from low LET X-irradiations in vivo. The remaining questions that if priming dose from HI could induce an AR against the challenging dose from low LET X-irradiations in ulero, if an AR could be induced both in vivo and in utero when both priming and challenging doses are from HI, and if there is any LET dependency in AR induction at whole body level, are still to be answered by further intensive investigations. (author)

  17. Does radioadaptive response also apply to the case of heavy-ion irradiations in fetal and adult mice?

    International Nuclear Information System (INIS)

    Possible induction of adaptive response (AR) by the high linear energy transfer (LET) accelerated heavy ion irradiations (HI) is being attempted both in young adult female mice and in fetal mice of C57BL/6J Jms strain, using growth delay, hematopoietic damage and reduced survival in vivo, prenatal growth delay, malformation and death in utero as endpoints. Investigations are to verify if priming dose from low LET X-irradiation could induce an AR against the detrimental effects from the high challenging dose of HI, if priming dose from HI could induce an AR against the high challenging dose from low LET X-irradiations, and if an AR could be induced when both priming and challenging doses are from HI. Four kinds of HI are being examined: carbon, neon, silicon and iron, with the LET values of about 15, 30, 55, and 200 keV/micrometer, respectively. Results show that the priming low dose X-irradiations could induce AR against high LET heavy-ion challenging irradiations from carbon and silicon beams in vivo and in utero, but not iron ions in vivo; the priming low dose carbon-ion irradiations could induce AR against the high challenging irradiations in vivo from X-rays or carbon ions, but not silicon and iron ions; priming dose from carbon, silicon or iron ions could not induce any AR against challenging dose from X-rays in utero. It seems that AR induction at whole body level is radiation quality-related event. Further investigations are needed to answer if this event is of LET- or/and nuclide-dependency. (author)

  18. Parental age and characteristics of the offspring.

    Science.gov (United States)

    Liu, Yongsheng; Zhi, Mingxing; Li, Xiuju

    2011-01-01

    The relations of an offspring to its parents are complex, and the ways in which a parent may influence the characteristics of its offspring are many. This review focuses on the relations of parental age to intelligence, health outcomes, longevity and other characteristics of offspring. Many researchers have demonstrated that children of older parents tend to be more intelligent than do children of younger parents, although there are also some negative findings. Either teenage or advanced parental age is associated with risk of birth and health outcomes in offspring. Parental age at birth displays a negative association with offspring longevity. Parental age can also influence dominant characters, sex ratio, personality and development process of the offspring. To fully analyze the influence of parental age on the offspring is of great significance in deciding the optimal age for parenthood. PMID:20887815

  19. Temporal and spatial patterns of transgene expression in aging adult mice provide insights about the origins, organization, and differentiation of the intestinal epithelium.

    OpenAIRE

    Cohn, S. M.; Roth, K A; Birkenmeier, E H; Gordon, J I

    1991-01-01

    We have used liver fatty acid-binding protein/human growth hormone (L-FABP/hGH) fusion genes to explore the temporal and spatial differentiation of intestinal epithelial cells in 1- to 12-month-old transgenic mice. The intact, endogenous L-FABP gene (Fabpl) was not expressed in the colon at any time. Young adult transgenic mice containing nucleotides -596 to +21 of the rat L-FABP gene linked to the hGH gene (minus its 5' nontranscribed domain) demonstrated inappropriate expression of hGH in e...

  20. Seipin knockout in mice impairs stem cell proliferation and progenitor cell differentiation in the adult hippocampal dentate gyrus via reduced levels of PPARγ

    Directory of Open Access Journals (Sweden)

    Guoxi Li

    2015-12-01

    Full Text Available The seipin gene (BSCL2 was originally identified in humans as a loss-of-function gene associated with congenital generalized lipodystrophy type 2 (CGL2. Neuronal seipin-knockout (seipin-nKO mice display a depression-like phenotype with a reduced level of hippocampal peroxisome proliferator-activated receptor gamma (PPARγ. The present study investigated the influence of seipin deficiency on adult neurogenesis in the hippocampal dentate gyrus (DG and the underlying mechanisms of the effects. We show that the proliferative capability of stem cells in seipin-nKO mice was substantially reduced compared to in wild-type (WT mice, and that this could be rescued by the PPARγ agonist rosiglitazone (rosi. In seipin-nKO mice, neuronal differentiation of progenitor cells was inhibited, with the enhancement of astrogliogenesis; both of these effects were recovered by rosi treatment during early stages of progenitor cell differentiation. In addition, rosi treatment could correct the decline in hippocampal ERK2 phosphorylation and cyclin A mRNA level in seipin-nKO mice. The MEK inhibitor U0126 abolished the rosi-rescued cell proliferation and cyclin A expression in seipin-nKO mice. In seipin-nKO mice, the hippocampal Wnt3 protein level was less than that in WT mice, and there was a reduction of neurogenin 1 (Neurog1 and neurogenic differentiation 1 (NeuroD1 mRNA, levels of which were corrected by rosi treatment. STAT3 phosphorylation (Tyr705 was enhanced in seipin-nKO mice, and was further elevated by rosi treatment. Finally, rosi treatment for 10 days could alleviate the depression-like phenotype in seipin-nKO mice, and this alleviation was blocked by the MEK inhibitor U0126. The results indicate that, by reducing PPARγ, seipin deficiency impairs proliferation and differentiation of neural stem and progenitor cells, respectively, in the adult DG, which might be responsible for the production of the depression-like phenotype in seipin-nKO mice.

  1. High Fetal Estrogen Concentrations: Correlation with Increased Adult Sexual Activity and Decreased Aggression in Male Mice

    Science.gov (United States)

    Vom Saal, Frederick S.; Grant, William M.; McMullen, Carol W.; Laves, Kurt S.

    1983-06-01

    In the house mouse (Mus musculus), fetuses may develop in utero next to siblings of the same or opposite sex. The amniotic fluid of the female fetuses contains higher concentrations of estradiol than that of male fetuses. Male fetuses that developed in utero between female fetuses had higher concentrations of estradiol in their amniotic fluid than males that were located between other male fetusesw during intrauterine development. They were also more sexually active as adults, less aggressive, and had smaller seminal vesicles than males that had developed between other male fetuses in utero. These findings raise the possibility that during fetal life circulating estrogens may interact with circulating androgens both in regulating the development of sex differences between males and females and in producing variation in phenotype among males and among females.

  2. Protective effects of crocin on testes of adult cyclophosphamide treated mice

    Directory of Open Access Journals (Sweden)

    2014-04-01

    Full Text Available Background & aim: The side effect of cyclophosphamide is to reduce fertility or even sterility in men treated with these medications. This study was performed to improve these side effects. Methods: In the present experimental study, 15 male mice (20-25 g were divided into three groups. The control group was treated with 0.1cc of saline daily. The sham group received 15 mg/kg cyclophosphamide once a week and the experimental group was treated with 200 mg/kg Crocin intraperitoneally along with cyclophosphamide. Five weeks after injection total antioxidant capacity of serum was measured. The testes were studied for histological and morphometric parameters. The collected data was analyzed by ANOVA. Results: Histomorphometrical study indicated that epithelial thickness, diameter of seminiferous tubules and Leydig cells of experimental group was significantly greater than sham controls (p<0.05. Mean distribution of mast cells in the sham group compared to the experimental group showed a significant increase (p<0.05. Additionally, positive PAS reaction, alkaline phosphatase and vegetable fat in the cytoplasm of Leydig cells of sham control were observed, whereas in the other groups not seen. In addition, total antioxidant capacity of sham group decreased significantly compared to the control and experimental groups with the sham control and experimental groups ((p<0.05. Conclusion: in general Crocin could significantly prevent the side effects of cyclophosphamide therapy.

  3. Congenital and nursing effects on the evolution of Schistosoma mansoni infection in mice

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    J. A. Lenzi

    1987-01-01

    Full Text Available Modification of the immune response to schistosomal infection in children or offspring born to mother R infected with Schistosoma mansoni has been demonstrated in human and in experimental schistosomiasis. One of the hypothesis to explain this fact could be the transfer of circulating antigens and antibodies from mother to foetus through the placenta or from mother to child by milk. The results of this spontaneous transference are controversial in the literature. In an attempt to investigate these questions, we studied one hundred and twenty offspring (Swiss mice, sixty born to infected-mothers (group A and sixty born to non-infected mothers (group B. These were percutaneously infected with 50 cercariae/mouse, and divided in six sub-groups (20 mice/sub-group, according to the following schedule: after birth (sub-groups A.I and B.I, 10 days old (sub-groups A.II and B.II and 21 days old (sub-groups A.III and B.III. After the exposure period, the young mice returned to their own mothers for nursing. Six weeks later, the mice were killed. We obtained the following results: 1 There is transference of antibody to cercariae (CAP, adult worms (SWAP and egg antigens (SEA from the infected mothers to the offspring, probably through placenta and milk; 2 Offspring born to infected mothers exhibit much less coagulative hepatic necrosis and show a lower number of eggs in the small intestine and a less intense and predominant exsudative stage of the hepatic granulomas when compared with the exsudative-productive stage of the control groups. The findings suggest that congenital and nursing factors can interfere on the development of the schistosomiasis infection, causing an hyporesponse to the eggs.

  4. Maternal cypermethrin exposure during the perinatal period impairs testicular development in C57BL male offspring.

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    Chaobin Huang

    Full Text Available Numerous studies have demonstrated that endocrine-disrupting compounds (EDC are a possible cause of male reproductive organ malfunction and malformation. Cypermethrin (CYP is a widely used synthetic pyrethroid and a potential EDC. This study aimed to examine the effects of perinatal exposure to low-dose CYP on the development and function of the offspring testes. Pregnant mice were intragastrically administered 0.12 to 12 mg/kg/day CYP from embryonic day 0.5 (E0.5 to weaning (PD21.5, postnatal day 21.5. Maternal exposure to 0.12, 1.2, and 12 mg/kg/day CYP affected the body and organ weight of the offspring. Exposure of CYP led to a dose-dependent decrease in the male-to-female sex ratio. A histopathological analysis revealed a thinner seminiferous epithelium layer at PD21.5, interstitial hyperplasia at PD45.5, and germ cell vacuolization at PD90.5 in the 12 mg/kg/day CYP group. The TUNEL assay results revealed increased germ cell apoptosis in the 12 mg/kg/day CYP group. The serum testosterone (T level decreased, whereas the estradiol level increased with age in the 1.2 and 12 mg/kg/day CYP groups. The RT-PCR analysis demonstrated decreased expression of T production-related, mitosis-related, and meiosis-related genes in the 1.2 and 12 mg/kg/day CYP groups. The in vitro experimental results demonstrated reduced expression of steroidogenesis genes and decreased T levels. It is concluded that perinatal exposure to low-dose CYP affects testes development and function in adults.

  5. Maternal cypermethrin exposure during the perinatal period impairs testicular development in C57BL male offspring.

    Science.gov (United States)

    Huang, Chaobin; Li, Xiangdong

    2014-01-01

    Numerous studies have demonstrated that endocrine-disrupting compounds (EDC) are a possible cause of male reproductive organ malfunction and malformation. Cypermethrin (CYP) is a widely used synthetic pyrethroid and a potential EDC. This study aimed to examine the effects of perinatal exposure to low-dose CYP on the development and function of the offspring testes. Pregnant mice were intragastrically administered 0.12 to 12 mg/kg/day CYP from embryonic day 0.5 (E0.5) to weaning (PD21.5, postnatal day 21.5). Maternal exposure to 0.12, 1.2, and 12 mg/kg/day CYP affected the body and organ weight of the offspring. Exposure of CYP led to a dose-dependent decrease in the male-to-female sex ratio. A histopathological analysis revealed a thinner seminiferous epithelium layer at PD21.5, interstitial hyperplasia at PD45.5, and germ cell vacuolization at PD90.5 in the 12 mg/kg/day CYP group. The TUNEL assay results revealed increased germ cell apoptosis in the 12 mg/kg/day CYP group. The serum testosterone (T) level decreased, whereas the estradiol level increased with age in the 1.2 and 12 mg/kg/day CYP groups. The RT-PCR analysis demonstrated decreased expression of T production-related, mitosis-related, and meiosis-related genes in the 1.2 and 12 mg/kg/day CYP groups. The in vitro experimental results demonstrated reduced expression of steroidogenesis genes and decreased T levels. It is concluded that perinatal exposure to low-dose CYP affects testes development and function in adults. PMID:24810582

  6. Early postnatal treatment with soluble epoxide hydrolase inhibitor or 15-deoxy-Δ(12,14)-prostagandin J2 prevents prenatal dexamethasone and postnatal high saturated fat diet induced programmed hypertension in adult rat offspring.

    Science.gov (United States)

    Lu, Pei-Chen; Sheen, Jiunn-Ming; Yu, Hong-Ren; Lin, Yu-Ju; Chen, Chih-Cheng; Tiao, Mao-Meng; Tsai, Ching-Chou; Huang, Li-Tung; Tain, You-Lin

    2016-07-01

    Prenatal dexamethasone (DEX) exposure, postnatal high-fat (HF) intake, and arachidonic acid pathway are closely related to hypertension. We tested whether a soluble epoxide hydrolase (SEH) inhibitor, 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) or 15-deoxy-Δ(12,14)-prostagandin J2 (15dPGJ2) therapy can rescue programmed hypertension in the DEX+HF two-hit model. Four groups of Sprague Dawley rats were studied: control, DEX+HF, AUDA, and 15dPGJ2. Dexamethasone (0.1mg/kg body weight) was intraperitoneally administered to pregnant rats from gestational day 16-22. Male offspring received high-fat diet (D12331, Research Diets) from weaning to 4 months of age. In AUDA group, mother rats received 25mg/L in drinking water during lactation. In the 15dPGJ2 group, male offspring received 15dPGJ2 1.5mg/kg BW by subcutaneous injection once daily for 1 week after birth. We found postnatal HF diet aggravated prenatal DEX-induced programmed hypertension, which was similarly prevented by early treatment with AUDA or 15dPGJ2. The beneficial effects of AUDA and 15d-PGJ2 therapy include inhibition of SEH, increases of renal angiotensin converting enzyme-2 (ACE2) and angiotensin II type 2 receptor (AT2R) protein levels, and restoration of nitric oxide bioavailability. Better understanding of the impact of arachidonic acid pathway in the two-hit model will help prevent programmed hypertension in children exposed to corticosteroids and postnatal HF intake. PMID:27210044

  7. Expression profiling reveals novel hypoxic biomarkers in peripheral blood of adult mice exposed to chronic hypoxia.

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    Matias Mosqueira

    Full Text Available Hypoxia induces a myriad of changes including an increase in hematocrit due to erythropoietin (EPO mediated erythropoiesis. While hypoxia is of importance physiologically and clinically, lacunae exist in our knowledge of the systemic and temporal changes in gene expression occurring in blood during the exposure and recovery from hypoxia. To identify these changes expression profiling was conducted on blood obtained from cohorts of C57Bl-10 wild type mice that were maintained at normoxia (NX, exposed for two weeks to normobaric chronic hypoxia (CH or two weeks of CH followed by two weeks of normoxic recovery (REC. Using stringent bioinformatic cut-offs (0% FDR, 2 fold change cut-off, 230 genes were identified and separated into four distinct temporal categories. Class I contained 1 transcript up-regulated in both CH and REC; Class II contained 202 transcripts up-regulated in CH but down-regulated after REC; Class III contained 9 transcripts down-regulated both in CH and REC; Class IV contained 18 transcripts down-regulated after CH exposure but up-regulated after REC. Profiling was independently validated and extended by analyzing expression levels of selected genes as novel biomarkers from our profile (e.g. spectrin alpha-1, ubiquitin domain family-1 and pyrroline-5-carboxylate reductase-1 by performing qPCR at 7 different time points during CH and REC. Our identification and characterization of these genes define transcriptome level changes occurring during chronic hypoxia and normoxic recovery as well as novel blood biomarkers that may be useful in monitoring a variety of physiological and pathological conditions associated with hypoxia.

  8. Risk of emotional disorder in offspring of depressed parents: gender differences in the effect of a second emotionally affected parent.

    Science.gov (United States)

    Landman-Peeters, Karlien M C; Ormel, Johan; Van Sonderen, Eric L P; Den Boer, Johan A; Minderaa, Ruud B; Hartman, Catharina A

    2008-01-01

    In offspring of depressed parents a second parent with emotional problems is likely to increase risk of emotional disorder. This effect may however differ between sons and daughters and between offspring of depressed fathers and offspring of depressed mothers. In adolescent and young-adult offspring of parents with major depressive disorder, this study examined the effects of a second affected parent, offspring gender, gender of the depressed parent and their interactions on risk of depression and anxiety disorder. We found that daughters had a higher risk of depression and anxiety than sons and that offspring of depressed mothers had a higher risk of anxiety than offspring of depressed fathers. In addition to these main effects, we found an interaction between parent and offspring gender inasmuch that sons of depressed fathers had the lowest risk of depression and anxiety relative to the other groups. A second affected parent tended to increase risk of depression and significantly increased risk of anxiety. However, this effect of a second affected parent on offspring anxiety was most prominent in daughters when the second affected parent was the father, whereas risk in sons did not increase if the father was affected as well. Our results indicate that paternal and maternal depression similarly and additively increase daughters' risk of emotional disorder, but that sons' risk only increases with maternal depression. Intergenerational transmission of emotional disorder seems strongest when the female gender is involved, either in the form of a daughter or a depressed mother. PMID:17941098

  9. Impact of Environmental Microbes on the Composition of the Gut Microbiota of Adult BALB/c Mice

    Science.gov (United States)

    Li, Na; Bai, Zhiyu; Zhang, Liling; Xue, Zhencheng; Jiang, Haitao; Song, Yuan; Zhou, Dongrui

    2016-01-01

    To investigate the impact of microbes within the living environment on the gut microbiota of adults, we raised three groups of BALB/c mice from 3–4 weeks age in the same specific-pathogen-free animal room for 8 weeks. The control group lived in cages with sterilized bedding (pelletized cardboard), the probiotics group had three probiotics added to the sterilized bedding, and the intestinal microbes (IM) group had the intestinal microbes of a healthy goat added to the bedding. All other variables such as diet, age, genetic background, physiological status, original gut microbiota, and living room were controlled. Using high-throughput sequencing of the 16S rRNA gene, we observed that the control and probiotics groups had similar diversity and richness of gut microbiota. The two groups had significantly lower diversity than the IM group. We also observed that the IM group had a specific structure of gut microbial community compared with the control and probiotics groups. However, the dominate bacteria changed slightly upon exposure to intestinal microbes, and the abundance of the non-dominate species changed significantly. In addition, exposure to intestinal microbes inhibited DNFB-induced elevation of serum IgE levels. Our results provide new evidence in support of the microflora and hygiene hypotheses. PMID:27518814

  10. Increases in the numerical density of GAT-1 positive puncta in the barrel cortex of adult mice after fear conditioning.

    Directory of Open Access Journals (Sweden)

    Ewa Siucinska

    Full Text Available Three days of fear conditioning that combines tactile stimulation of a row of facial vibrissae (conditioned stimulus, CS with a tail shock (unconditioned stimulus, UCS expands the representation of "trained" vibrissae, which can be demonstrated by labeling with 2-deoxyglucose in layer IV of the barrel cortex. We have also shown that functional reorganization of the primary somatosensory cortex (S1 increases GABAergic markers in the hollows of "trained" barrels of the adult mouse. This study investigated how whisker-shock conditioning (CS+UCS affected the expression of puncta of a high-affinity GABA plasma membrane transporter GAT-1 in the barrel cortex of mice 24 h after associative learning paradigm. We found that whisker-shock conditioning (CS+UCS led to increase expression of neuronal and astroglial GAT-1 puncta in the "trained" row compared to controls: Pseudoconditioned, CS-only, UCS-only and Naïve animals. These findings suggest that fear conditioning specifically induces activation of systems regulating cellular levels of the inhibitory neurotransmitter GABA.

  11. Impact of Environmental Microbes on the Composition of the Gut Microbiota of Adult BALB/c Mice.

    Science.gov (United States)

    Bai, Zhimao; Zhang, Honglin; Li, Na; Bai, Zhiyu; Zhang, Liling; Xue, Zhencheng; Jiang, Haitao; Song, Yuan; Zhou, Dongrui

    2016-01-01

    To investigate the impact of microbes within the living environment on the gut microbiota of adults, we raised three groups of BALB/c mice from 3-4 weeks age in the same specific-pathogen-free animal room for 8 weeks. The control group lived in cages with sterilized bedding (pelletized cardboard), the probiotics group had three probiotics added to the sterilized bedding, and the intestinal microbes (IM) group had the intestinal microbes of a healthy goat added to the bedding. All other variables such as diet, age, genetic background, physiological status, original gut microbiota, and living room were controlled. Using high-throughput sequencing of the 16S rRNA gene, we observed that the control and probiotics groups had similar diversity and richness of gut microbiota. The two groups had significantly lower diversity than the IM group. We also observed that the IM group had a specific structure of gut microbial community compared with the control and probiotics groups. However, the dominate bacteria changed slightly upon exposure to intestinal microbes, and the abundance of the non-dominate species changed significantly. In addition, exposure to intestinal microbes inhibited DNFB-induced elevation of serum IgE levels. Our results provide new evidence in support of the microflora and hygiene hypotheses. PMID:27518814

  12. [Reinnervation of central visual areas and recovery of visual functions following optic nerve regeneration in adult mice].

    Science.gov (United States)

    Koriyama, Yoshiki; Kurimoto, Takuji; de Lima, Silmara; Benowitz, Larry

    2014-03-01

    The optic nerve has been widely studied in search for insights into mechanisms that suppress or promote axon regeneration after injury. Like other CNS neurons, adult retinal ganglion cells (RGCs) normally fail to regenerate their axons after optic nerve injury. Recent studies have identified molecular pathways able to allow partial regeneration of damaged RGCs axons in mature rodents; however, it is still unknown, whether regrowing optic axons can re-enter the brain in large numbers, innervate the correct target areas, and thus restore vision. We investigated these questions by using three manipulations that synergistically increase regeneration far above the level induced by any of the three used alone. Oncomodulin is a calcium-binding protein secreted by activated macrophages and neutrophils and stimulates RGCs to regenerate axons. Its ability to bind to RGCs and activate a downstream response is enhanced by elevating intracellular cAMP. Studies were carried out in mice with a conditional deletion of the gene encoding PTEN, a phosphatase and tensin homolog that suppresses signaling through the Akt/mTOR/S6K pathway. Our results showed that intraocular inflammation, deletion of the PTEN gene and elevation of intracellular cAMP exert synergistic effects that enable RGCs to regenerate the full length of axons, form synapses, and restore simple visual functions. These results demonstrate the feasibility of reconstructing central circuitry for vision after optic nerve damage in mature mammals. PMID:24607951

  13. Activation of the Wnt/β-catenin signaling pathway is associated with glial proliferation in the adult spinal cord of ALS transgenic mice

    International Nuclear Information System (INIS)

    Highlights: ► Wnt3a and Cyclin D1 were upregulated in the spinal cord of the ALS mice. ► β-catenin translocated from the cell membrane to the nucleus in the ALS mice. ► Wnt3a, β-catenin and Cyclin D1 co-localized for astrocytes were all increased. ► BrdU/Cyclin D1 double-positive cells were increased in the spinal cord of ALS mice. ► BrdU/Cyclin D1/GFAP triple-positive cells were detected in the ALS mice. -- Abstract: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive and fatal loss of motor neurons. In ALS, there is a significant cell proliferation in response to neurodegeneration; however, the exact molecular mechanisms of cell proliferation and differentiation are unclear. The Wnt signaling pathway has been shown to be involved in neurodegenerative processes. Wnt3a, β-catenin, and Cyclin D1 are three key signaling molecules of the Wnt/β-catenin signaling pathway. We determined the expression of Wnt3a, β-catenin, and Cyclin D1 in the adult spinal cord of SOD1G93A ALS transgenic mice at different stages by RT-PCR, Western blot, and immunofluorescence labeling techniques. We found that the mRNA and protein of Wnt3a and Cyclin D1 in the spinal cord of the ALS mice were upregulated compared to those in wild-type mice. In addition, β-catenin translocated from the cell membrane to the nucleus and subsequently activated transcription of the target gene, Cyclin D1. BrdU and Cyclin D1 double-positive cells were increased in the spinal cord of these mice. Moreover, Wnt3a, β-catenin, and Cyclin D1 were also expressed in both neurons and astrocytes. The expression of Wnt3a, β-catenin or Cyclin D1 in mature GFAP+ astrocytes increased. Moreover, BrdU/Cyclin D1/GFAP triple-positive cells were detected in the ALS mice. Our findings suggest that neurodegeneration activates the Wnt/β-catenin signaling pathway, which is associated with glial proliferation in the adult spinal cord of ALS transgenic mice. This

  14. Activation of the Wnt/{beta}-catenin signaling pathway is associated with glial proliferation in the adult spinal cord of ALS transgenic mice

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yanchun [Department of Histology and Embryology, Weifang Medical University, Weifang, Shandong (China); Department of Histology and Embryology, Shandong University School of Medicine, Jinan, Shandong (China); Guan, Yingjun, E-mail: guanyj@wfmc.edu.cn [Department of Histology and Embryology, Weifang Medical University, Weifang, Shandong (China); Department of Histology and Embryology, Shandong University School of Medicine, Jinan, Shandong (China); Liu, Huancai [Department of Orthopedic, Affiliated Hospital, Weifang Medical University, Weifang, Shandong (China); Wu, Xin; Yu, Li; Wang, Shanshan; Zhao, Chunyan; Du, Hongmei [Department of Histology and Embryology, Weifang Medical University, Weifang, Shandong (China); Wang, Xin, E-mail: xwang@rics.bwh.harvard.edu [Department of Neurosurgery, Brigham and Women' s Hospital, Harvard Medical School, Boston, MA (United States)

    2012-04-06

    Highlights: Black-Right-Pointing-Pointer Wnt3a and Cyclin D1 were upregulated in the spinal cord of the ALS mice. Black-Right-Pointing-Pointer {beta}-catenin translocated from the cell membrane to the nucleus in the ALS mice. Black-Right-Pointing-Pointer Wnt3a, {beta}-catenin and Cyclin D1 co-localized for astrocytes were all increased. Black-Right-Pointing-Pointer BrdU/Cyclin D1 double-positive cells were increased in the spinal cord of ALS mice. Black-Right-Pointing-Pointer BrdU/Cyclin D1/GFAP triple-positive cells were detected in the ALS mice. -- Abstract: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive and fatal loss of motor neurons. In ALS, there is a significant cell proliferation in response to neurodegeneration; however, the exact molecular mechanisms of cell proliferation and differentiation are unclear. The Wnt signaling pathway has been shown to be involved in neurodegenerative processes. Wnt3a, {beta}-catenin, and Cyclin D1 are three key signaling molecules of the Wnt/{beta}-catenin signaling pathway. We determined the expression of Wnt3a, {beta}-catenin, and Cyclin D1 in the adult spinal cord of SOD1{sup G93A} ALS transgenic mice at different stages by RT-PCR, Western blot, and immunofluorescence labeling techniques. We found that the mRNA and protein of Wnt3a and Cyclin D1 in the spinal cord of the ALS mice were upregulated compared to those in wild-type mice. In addition, {beta}-catenin translocated from the cell membrane to the nucleus and subsequently activated transcription of the target gene, Cyclin D1. BrdU and Cyclin D1 double-positive cells were increased in the spinal cord of these mice. Moreover, Wnt3a, {beta}-catenin, and Cyclin D1 were also expressed in both neurons and astrocytes. The expression of Wnt3a, {beta}-catenin or Cyclin D1 in mature GFAP{sup +} astrocytes increased. Moreover, BrdU/Cyclin D1/GFAP triple-positive cells were detected in the ALS mice. Our findings suggest that

  15. Exercise prevents high-fat diet-induced impairment of flexible memory expression in the water maze and modulates adult hippocampal neurogenesis in mice.

    Science.gov (United States)

    Klein, C; Jonas, W; Iggena, D; Empl, L; Rivalan, M; Wiedmer, P; Spranger, J; Hellweg, R; Winter, Y; Steiner, B

    2016-05-01

    Obesity is currently one of the most serious threats to human health in the western civilization. A growing body of evidence suggests that obesity is associated with cognitive dysfunction. Physical exercise not only improves fitness but it has also been shown in human and animal studies to increase hippocampus-dependent learning and memory. High-fat diet (HFD)-induced obesity and physical exercise both modulate adult hippocampal neurogenesis. Adult neurogenesis has been demonstrated to play a role in hippocampus-dependent learning and memory, particularly flexible memory expression. Here, we investigated the effects of twelve weeks of HFD vs. control diet (CD) and voluntary physical activity (wheel running; -R) vs. inactivity (sedentary; -S) on hippocampal neurogenesis and spatial learning and flexible memory function in female C57Bl/6 mice assessed in the Morris water maze. HFD was initiated either in adolescent mice combined with long-term concurrent exercise (preventive approach) or in young adult mice with 14days of subsequent exercise (therapeutic approach). HFD resulted in impaired flexible memory expression only when initiated in adolescent (HFD-S) but not in young adult mice, which was successfully prevented by concurrent exercise (HFD-R). Histological analysis revealed a reduction of immature neurons in the hippocampus of the memory-impaired HFD-S mice of the preventive approach. Long-term physical exercise also led to accelerated spatial learning during the acquisition period, which was accompanied by increased numbers of newborn mature neurons (HFD-R and CD-R). Short-term exercise of 14days in the therapeutic group was not effective in improving spatial learning or memory. We show that (1) alterations in learning and flexible memory expression are accompanied by changes in the number of neuronal cells at different maturation stages; (2) these neuronal cells are in turn differently affected by HFD; (3) adolescent mice are specifically susceptible to the

  16. Voluntary Running in Young Adult Mice Reduces Anxiety-Like Behavior and Increases the Accumulation of Bioactive Lipids in the Cerebral Cortex

    OpenAIRE

    Santos-Soto, Iván J.; Chorna, Nataliya; Carballeira, Néstor M.; Vélez-Bartolomei, José G.; Méndez-Merced, Ana T.; Chornyy, Anatoliy P.; de Ortiz, Sandra Peña

    2013-01-01

    Combinatorial therapies using voluntary exercise and diet supplementation with polyunsaturated fatty acids have synergistic effects benefiting brain function and behavior. Here, we assessed the effects of voluntary exercise on anxiety-like behavior and on total FA accumulation within three brain regions: cortex, hippocampus, and cerebellum of running versus sedentary young adult male C57/BL6J mice. The running group was subjected to one month of voluntary exercise in their home cages, while t...

  17. Altered gene expression and spine density in nucleus accumbens of adolescent and adult male mice exposed to emotional and physical stress.

    Science.gov (United States)

    Warren, Brandon L; Sial, Omar K; Alcantara, Lyonna F; Greenwood, Maria A; Brewer, Jacob S; Rozofsky, John P; Parise, Eric M; Bolaños-Guzmán, Carlos A

    2014-01-01

    Stressful early life experiences are implicated in lifelong health. However, little is known about the consequences of emotional stress (ES) or physical stress (PS) on neurobiology. Therefore, the following set of experiments was designed to assess changes in transcription and translation of key proteins within the nucleus accumbens (NAc). Male adolescent (postnatal day 35) or adult (8-week-old) mice were exposed to ES or PS using a witness social defeat paradigm. Then, 24 h after the last stress session, we measured levels of specific mRNAs and proteins within the NAc. Spine density was also assessed in separate groups of mice. Exposure to ES or PS disrupted extracellular signal-related kinase 2 (ERK2), reduced transcription of ΔFosB and had no effect on cAMP response element-binding protein (CREB) mRNA. Western blots revealed that exposure to ES or PS decreased ERK2 phosphorylation in adolescents, whereas the same stress regimen increased ERK2 phosphorylation in adults. Exposure to ES or PS had no effect on ΔFosB or CREB phosphorylation. ES and PS increased spine density in the NAc of adolescent exposed mice, but only exposure to PS increased spine density in adults. Together, these findings demonstrate that exposure to ES or PS is a potent stressor in adolescent and adult mice and can disturb the integrity of the NAc by altering transcription and translation of important signaling molecules in an age-dependent manner. Furthermore, exposure to ES and PS induces substantial synaptic plasticity of the NAc. PMID:24943326

  18. Protective Effects of Royal Jelly and Vitamin C against Experimental Hemolytic Anemia on Sex Hormones and Histochemical Testicle Tissue Histochemistry of Adult Mice

    OpenAIRE

    H Anbara; R Shahrooz; H Malekinejad; S Saadati

    2016-01-01

    Introduction: Phenylhydrazine (PHZ) is a well-known hemolytic compound inducing intoxication in erythrocytes. Therefore, the present study aimed to evaluate the protective effects of royal jelly and vitamin C against phenylhydrazine-induced damages in mouse testicles. Methods: In this study, 64 adult male mice were randomly and equally assigned to eight groups. The first group received normal saline (0.1ml) intraperitoneally. The second group received PHZ (6 mg/100 gr) intraperitoneally i...

  19. Epigallocatechin-3-gallate rescues LPS-impaired adult hippocampal neurogenesis through suppressing the TLR4-NF-κB signaling pathway in mice.

    Science.gov (United States)

    Seong, Kyung-Joo; L