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Sample records for rats exposed prenatally

  1. Immunotoxic effects of iodine-131 in prenatally exposed rats

    International Nuclear Information System (INIS)

    Cole, D.A.; Stevens, R.H.; Lindholm, P.A.; Cheng, H.F.

    1985-01-01

    Present results suggest that offspring exposed in utero to radioactive iodine-131 develop a measureable cell-mediated immune (CMI) response. Regnant Fischer F344 inbred rats were exposed to 370 kBg to 3.7 MBg (10 to 100 μCi) Na 131I on 16 to 18 days of gestation and evaluated for CMI responsiveness 2 to 3 months post exposure using an 125I radiolabeled membrane release assay. Current data suggest that not only the F1, but also the F2 pups develop a measureable CMI response. In order to determine whether other immune functions are altered studies have been initiated to evaluate the immunotoxic effect of prenatal exposure to 131I. These studies include the evaluation of the delayed hypersensitivity response and the blastogenic responses to phytoheemagglutinin, concanavalin A, and lipopolysaccharide

  2. Brain plasticity of rats exposed to prenatal immobilization stress

    Directory of Open Access Journals (Sweden)

    Badalyan B. Yu.

    2011-10-01

    Full Text Available Aim. This histochemical and immunohistochemical study was aimed at examining the brain cellular structures of newborn rats exposed to prenatal immobilization (IMO stress. Methods. Histochemical method on detection of Ca2+-dependent acid phosphatase activity and ABC immunohistochemical technique. Results. Cell structures with radial astrocytes marker GFAP, neuroepithelial stem cell marker gene nestin, stem-cells marker and the hypothalamic neuroprotective proline-rich polypeptide PRP-1 (Galarmin, a natural cytokine of a common precursor to neurophysin vasopressin associated glycoprotein have been revealed in several brain regions. Conclusions. Our findings indicate the process of generation of new neurons in response to IMO and PRP-1 involvement in this recovery mechanism, as PRP-1-Ir was detected in the above mentioned cell structures, as well as in the neurons and nerve fibers.

  3. Effect of Amphetamine on Adult Male and Female Rats Prenatally Exposed to Methamphetamine

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    Romana Šlamberová

    2014-01-01

    Full Text Available The aim of the present study was to examine the cross-sensitization induced by prenatal methamphetamine (MA exposure to adult amphetamine (AMP treatment in male and female rats. Rat mothers received a daily injection of MA (5 mg/kg or saline throughout the gestation period. Adult male and female offspring (prenatally MA- or saline-exposed were administered with AMP (5 mg/kg or saline (1 ml/kg in adulthood. Behaviour in unknown environment was examined in open field test (Laboras, active drug-seeking behaviour in conditioned place preference test (CPP, spatial memory in the Morris water maze (MWM, and levels of corticosterone (CORT were analyzed by enzyme immunoassay (EIA. Our data demonstrate that in Laboras test, AMP treatment in adulthood increased general locomotion (time and distance travelled regardless of the prenatal exposure and sex, while AMP increased exploratory activity (rearing only in prenatally MA-exposed animals. AMP induced sensitization only in male rats, but not in females when tested drug-seeking behaviour in the CPP test. In the spatial memory MWM test, AMP worsened the performance only in females, but not in males. On the other hand, males swam faster after chronic AMP treatment regardless of the prenatal drug exposure. EIA analysis of CORT levels demonstrated higher level in females in all measurement settings. In males, prenatal MA exposure and chronic adult AMP treatment decreased CORT levels. Thus, our data demonstrated that adult AMP treatment affects behaviour of adult rats, their spatial memory and stress response in sex-specific manner. The effect is also influenced by prenatal drug exposure.

  4. Prenatal zinc reduces stress response in adult rat offspring exposed to lipopolysaccharide during gestation.

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    Galvão, Marcella C; Chaves-Kirsten, Gabriela P; Queiroz-Hazarbassanov, Nicolle; Carvalho, Virgínia M; Bernardi, Maria M; Kirsten, Thiago B

    2015-01-01

    Previous investigations by our group have shown that prenatal treatment with lipopolysaccharide (LPS; 100 μg/kg, intraperitoneally) on gestation day (GD) 9.5 in rats, which mimics infections by Gram-negative bacteria, induces short- and long-term behavioral and neuroimmune changes in the offspring. Because LPS induces hypozincemia, dams were treated with zinc after LPS in an attempt to prevent or ameliorate the impairments induced by prenatal LPS exposure. LPS can also interfere with hypothalamic-pituitary-adrenal (HPA) axis development; thus, behavioral and neuroendocrine parameters linked to HPA axis were evaluated in adult offspring after a restraint stress session. We prenatally exposed Wistar rats to LPS (100 μg/kg, intraperitoneally, on GD 9.5). One hour later they received zinc (ZnSO4, 2 mg/kg, subcutaneously). Adult female offspring that were in metestrus/diestrus were submitted to a 2 h restraint stress session. Immediately after the stressor, 22 kHz ultrasonic vocalizations, open field behavior, serum corticosterone and brain-derived neurotrophic factor (BDNF) levels, and striatal and hypothalamic neurotransmitter and metabolite levels were assessed. Offspring that received prenatal zinc after LPS presented longer periods in silence, increased locomotion, and reduced serum corticosterone and striatal norepinephrine turnover compared with rats treated with LPS and saline. Prenatal zinc reduced acute restraint stress response in adult rats prenatally exposed to LPS. Our findings suggest a potential beneficial effect of prenatal zinc, in which the stress response was reduced in offspring that were stricken with infectious/inflammatory processes during gestation. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Responsiveness of cerebral and hepatic cytochrome P450s in rat offspring prenatally exposed to lindane

    International Nuclear Information System (INIS)

    Johri, Ashu; Yadav, Sanjay; Dhawan, Alok; Parmar, Devendra

    2008-01-01

    ABSTRACT: Prenatal exposure to low doses of lindane has been shown to affect the ontogeny of xenobiotic metabolizing cytochrome P450s (CYPs), involved in the metabolism and neurobehavioral toxicity of lindane. Attempts were made in the present study to investigate the responsiveness of CYPs in offspring prenatally exposed to lindane (0.25 mg/kg b. wt.; 1/350th of LD 50 ; p. o. to mother) when challenged with 3-methylcholanthrene (MC) or phenobarbital (PB), inducers of CYP1A and 2B families or a sub-convulsant dose of lindane (30 mg/kg b. wt., p. o.) later in life. Prenatal exposure to lindane was found to produce an increase in the mRNA and protein expression of CYP1A1, 1A2, 2B1, 2B2 isoforms in brain and liver of the offspring at postnatal day 50. The increased expression of the CYPs in the offspring suggests the sensitivity of the CYPs during postnatal development, possibly, to low levels of lindane, which may partition into mother's milk. A higher increase in expression of CYP1A and 2B isoenzymes and their catalytic activity was observed in animals pretreated prenatally with lindane and challenged with MC (30 mg/kg, i. p. x 5 days) or PB (80 mg/kg, i. p. x 5 days) when young at age (approx. 7 weeks) compared to animals exposed to MC or PB alone. Further, challenge of the control and prenatally exposed offspring with a single sub-convulsant dose of lindane resulted in an earlier onset and increased incidence of convulsions in the offspring prenatally exposed to lindane have demonstrated sensitivity of the CYPs in the prenatally exposed offspring. Our data assume significance as the subtle changes in the expression profiles of hepatic and cerebral CYPs in rat offspring during postnatal development could modify the adult response to a later exposure to xenobiotics

  6. Effect of honey on the reproductive system of male rat offspring exposed to prenatal restraint stress.

    Science.gov (United States)

    Haron, M N; Mohamed, M

    2016-06-01

    Exposure to prenatal stress is associated with impaired reproductive function in male rat offspring. Honey is traditionally used by the Malays for enhancement of fertility. The aim of this study was to determine the effect of honey on reproductive system of male rat offspring exposed to prenatal restraint stress. Dams were divided into four groups (n = 10/group): control, honey, stress and honey + stress groups. Dams from honey and honey + stress groups received oral honey (1.2 g kg(-1) body weight) daily from day 1 of pregnancy, meanwhile dams from stress and honey + stress groups were subjected to restraint stress (three times per day) from day 11 of pregnancy until delivery. At 10 weeks old, each male rat offspring was mated with a regular oestrus cycle female. Male sexual behaviour and reproductive performance were evaluated. Then, male rats were euthanised for assessment on reproductive parameters. Honey supplementation during prenatal restraint stress significantly increased testis and epididymis weights as well as improved the percentages of abnormal spermatozoa and sperm motility in male rat offspring. In conclusion, this study might suggest that supplementation of honey during pregnancy seems to reduce the adverse effects of restraint stress on reproductive organs weight and sperm parameters in male rat offspring. © 2015 Blackwell Verlag GmbH.

  7. Changes in markers of oxidative stress and membrane properties in synaptosomes from rats exposed prenatally to toluene

    DEFF Research Database (Denmark)

    Edelfors, Sven; Hass, Ulla; Hougaard, Karin S.

    2002-01-01

    for the experiments, Synaptosomes from rats exposed prenatally to toluene exhibited an increased level of oxidative stress when incubated with toluene in vitro compared to synaptosomes from unexposed offspring. Also the cell membrane was affected, as the calcium leakage was more increased from exposed synaptosomes...

  8. Developmental disruption of amygdala transcriptome and socioemotional behavior in rats exposed to valproic acid prenatally.

    Science.gov (United States)

    Barrett, Catherine E; Hennessey, Thomas M; Gordon, Katelyn M; Ryan, Steve J; McNair, Morgan L; Ressler, Kerry J; Rainnie, Donald G

    2017-01-01

    The amygdala controls socioemotional behavior and has consistently been implicated in the etiology of autism spectrum disorder (ASD). Precocious amygdala development is commonly reported in ASD youth with the degree of overgrowth positively correlated to the severity of ASD symptoms. Prenatal exposure to VPA leads to an ASD phenotype in both humans and rats and has become a commonly used tool to model the complexity of ASD symptoms in the laboratory. Here, we examined abnormalities in gene expression in the amygdala and socioemotional behavior across development in the valproic acid (VPA) rat model of ASD. Rat dams received oral gavage of VPA (500 mg/kg) or saline daily between E11 and 13. Socioemotional behavior was tracked across development in both sexes. RNA sequencing and proteomics were performed on amygdala samples from male rats across development. Effects of VPA on time spent in social proximity and anxiety-like behavior were sex dependent, with social abnormalities presenting in males and heightened anxiety in females. Across time VPA stunted developmental and immune, but enhanced cellular death and disorder, pathways in the amygdala relative to saline controls. At postnatal day 10, gene pathways involved in nervous system and cellular development displayed predicted activations in prenatally exposed VPA amygdala samples. By juvenile age, however, transcriptomic and proteomic pathways displayed reductions in cellular growth and neural development. Alterations in immune pathways, calcium signaling, Rho GTPases, and protein kinase A signaling were also observed. As behavioral, developmental, and genomic alterations are similar to those reported in ASD, these results lend support to prenatal exposure to VPA as a useful tool for understanding how developmental insults to molecular pathways in the amygdala give rise to ASD-related syndromes.

  9. Transfer of tritium to prenatal and neonatal rats from their mothers exposed to tritiated compounds

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    Takeda, H.; Nishimura, Y.; Inaba, J. (National Inst. of Radiological Sciences, Chiba (Japan))

    1994-01-01

    The transfer of tritium through the placenta or milk was investigated to estimate the radiation dose to the fetus and newborn. Female rats at gestational stages or after delivery were exposed to tritium in the form of water, thymidine and lysine by a single oral administration and radioactivity in tissues including conceptuses (placenta, fetal membrane and fetus) and in the newborn was determined at various times after administration. In all cases of the investigated triated compounds, there was no significant difference between the tritium concentration in the fetus and that in the maternal tissues, suggesting that the placenta has no effect in preventing or accelerating the placental transfer of tritium. The time course of tritium concentration and tritium content in the fetus and newborn were, however, dependent on the chemical form of tritium and on the prenatal or neonatal stages at the time of ingestion. In general, the tritium concentration and tritium content after the ingestion of [sup 3]H-lysine were higher than that after the ingestion of tritiated water or [sup 3]H-thymidine. The result of dose estimation showed that [sup 3]H-lysine gave higher prenatal and neonatal doses than tritiated water or [sup 3]H-thymidine by a factor of 1.5 to 6.0. (author).

  10. Histological investigations on thymus of male rats prenatally exposed to bisphenol A.

    Science.gov (United States)

    Aydemir, Işıl; Kum, Şadiye; Tuğlu, Mehmet İbrahim

    2018-04-27

    Bisphenol A is called as a endocrine-distrupting chemical because of the its steroid-like activity and it used in the construction of plastic containing materials. It is indicated that bisphenol A can pass the human serum, urine, follicular fluid, placenta and umblical cord as a result of the use of substances containing this agent. In this study, we aimed to investigate the effects of bisphenol A on the development of the thymus, a primary lymphoid organ which plays an important role in the specific immunity. The adult pregnant female rats were administered orally with bisphenol A (for 21 days) and postnatal thymus samples were obtained on day 21, 45 and 90 and were performed for histochemical and immunohistochemical staining for CD3, CD4, CD8 and CD79a and TUNEL assay for the apoptotic cells. Evaluation of all groups, CD3, CD4, CD8 and CD79a stainings were decreased in the experimental groups compared with control group. The apoptotic cells were determined in the all groups on day 90 as a result of the thymus involution. It is noted that there was not any histological and morphological damages in the rats prenatally exposed the bisphenol A. The effect of the bisphenol A is unknown in the future, but there is no problem in the adult rats. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. Intrauterine programming mechanism for hypercholesterolemia in prenatal caffeine-exposed female adult rat offspring.

    Science.gov (United States)

    Xu, Dan; Luo, Hanwen W; Hu, Wen; Hu, Shuwei W; Yuan, Chao; Wang, Guihua H; Zhang, Li; Yu, Hong; Magdalou, Jacques; Chen, Liaobin B; Wang, Hui

    2018-05-02

    ac and H3K14ac) and expression of HMGCR. This GC-dependent cholesterol metabolism programming effect was sustained through adulthood, leading to the occurrence of hypercholesterolemia.-Xu, D., Luo, H. W., Hu, W., Hu, S. W., Yuan, C., Wang, G. H., Zhang, L., Yu, H., Magdalou, J., Chen, L. B., Wang, H. Intrauterine programming mechanism for hypercholesterolemia in prenatal caffeine-exposed female adult rat offspring.

  12. Postnatal Administration of Allopregnanolone Modifies Glutamate Release but Not BDNF Content in Striatum Samples of Rats Prenatally Exposed to Ethanol

    Directory of Open Access Journals (Sweden)

    Roberto Yunes

    2015-01-01

    Full Text Available Ethanol consumption during pregnancy may induce profound changes in fetal CNS development. We postulate that some of the effects of ethanol on striatal glutamatergic transmission and neurotrophin expression could be modulated by allopregnanolone, a neurosteroid modulator of GABAA receptor activity. We describe the acute pharmacological effect of allopregnanolone (65 μg/kg, s.c. administered to juvenile male rats (day 21 of age on the corticostriatal glutamatergic pathway, in both control and prenatally ethanol-exposed rats (two ip injections of 2.9 g/kg in 24% v/v saline solution on gestational day 8. Prenatal ethanol administration decreased the K+-induced release of glutamate regarding the control group. Interestingly, this effect was reverted by allopregnanolone. Regarding BDNF, allopregnanolone decreases the content of this neurotrophic factor in the striatum of control groups. However, both ethanol alone and ethanol plus allopregnanolone treated animals did not show any change regarding control values. We suggest that prenatal ethanol exposure may produce an alteration of GABAA receptors which blocks the GABA agonist-like effect of allopregnanolone on rapid glutamate release, thus disturbing normal neural transmission. Furthermore, the reciprocal interactions found between GABAergic neurosteroids and BDNF could underlie mechanisms operating during the neuronal plasticity of fetal development.

  13. The effects of in vitro exposure to white spirit on [Ca2+] in synaptosomes from rats exposed prenatally to white spirit

    DEFF Research Database (Denmark)

    Edelfors, S.; Hass, Ulla; Ravn-Jonsen, A.

    1999-01-01

    Female rats were exposed to white spirit (400 and 800 ppm for 6 hr/day) at day 7-20 during pregnancy. Thirty-five days after birth all female offspring were sacrificed, the brains removed, and the synaptosomal fractions prepared for in vitro studies. The cytosolic calcium concentration was measured...... using the FURA-2 technique. The results show that cytosolic calcium was increased in synaptosomes from rats exposed to white spirit prenatally compared to synaptosomes from unexposed rats. When synaptosomes were exposed to white spirit in vitro, the cytosolic calcium concentration changes were identical...... in all groups of rats. The membrane leakage measured as FURA-2 leakage from the synaptosomes identical in all three groups of animals. The results suggest that prenatal exposure to white spirit induces long-lasting and possibly irreversible changes in calcium homeostasis in the rat nervous system....

  14. Brain manganese, catecholamine turnover, and the development of startle in rats prenatally exposed to manganese

    International Nuclear Information System (INIS)

    Kontur, P.J.; Fechter, L.D.

    1985-01-01

    Manganese (Mn) can be neurotoxic when present in high concentrations. Neonatal animals show differential absorption, accumulation, and excretion of Mn relative to adults. If similar kinetic differences exist during gestation, then fetal animals may be susceptible to Mn neurotoxicity. The objective of this study was to examine maternal-fetal Mn transfer and the susceptibility of prenatal animals to Mn neurotoxicity. This was approached by studying the ability of Mn to cross the placenta and reach the fetal central nervous system using radiotracer and atomic absorption spectroscopy techniques. Manganese is thought to disrupt catecholamine neurotransmission in the central nervous system. This was examined in newborn rats by alpha-methyl-para-tyrosine induced catecholamine turnover and the development of the acoustic startle response. The results suggest that there are limits on fetal Mn accumulation under conditions of both normal and excessive dietary Mn levels. Manganese accumulation in the fetal brain after exposure to increased dietary Mn does not alter either dopamine or norepinephrine turnover or the development of the acoustic startle response. Excess Mn does not appear to be neurotoxic to fetal rats in spite of its limited accumulation in nervous tissue after gestational exposure

  15. Prenatal effects by exposing to amoxicillin on dental enamel in Wistar rats.

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    Gottberg, Beatriz; Berné, Jeanily; Quiñónez, Belkis; Solórzano, Eduvigis

    2014-01-01

    Amoxicillin is an antibiotic widely prescribed; its most frequent side effects are gastrointestinal disorders and hypersensitivity reactions. Over the last 10 years studies have been published which suggest that amoxicillin may cause dental alterations similar to dental fluorosis. Never the less, the results are not conclusive, this is why it was planned the need to make controlled studies on test animals. The purpose of this study was to determine the effect produced by amoxicillin prenatal administration on dental enamel in Wistar rats. 12 pregnant adult rats were used distributed into five different groups: witness control (n=2) didn't get any treatment; negative control (n=2) they were prescribed with saline solution; positive control (n=3) they were prescribed with tetracycline 130 mg/kg, and two groups (n=3 and n=2) treated with amoxicillin doses of 50 and 100 mg/kg respectively. The treatments were daily administered by mouth, from the 6th gestation day to the end of gestation. Twenty five days after they were born, the offspring were sacrificed with a sodium pentobarbital overdose, the mandible was dissected and the first lower molars were gotten. The samples were fixed in 10% formaldehyde solution and clinically and histologically observed to determine any enamel disorders. hypomineralization was observed in every single sample of the tetracyclic and amoxicillin treated group 100 mg/kg, meanwhile only 50% from the group administered with 50 mg/kg amoxicillin showed this histological disorder. the side effect caused by amoxicillin on dental enamel was doses dependent.

  16. Transfer of 14C to prenatal and neonatal rats from their mothers exposed to 14C compounds by ingestion

    International Nuclear Information System (INIS)

    Takeda, H.; Fuma, S.; Miyamoto, K.; Kuroda, N.; Inaba, J.

    2003-01-01

    The transfer of 14 C through placenta or milk was investigated and the radiation dose to fetal and newborn rats was estimated. Female rats at gestational stages or after delivery were exposed to 14 C in the form of sodium bicarbonate, thymidine and lysine by a single ingestion. Radioactivity in maternal tissues and conceptuses (placenta, fetal membrane and fetus) and in the newborn was determined at various times after ingestion. After exposure to these 14 C compounds, there was no significant difference between the 14 C concentration in the fetus and that in the maternal tissues, suggesting that the placenta has no effect in preventing or accelerating the placental transfer of 14 C. The concentration and content of 14 C in the fetus and newborn were, however, dependent on the chemical form of 14 C and on the prenatal or neonatal stage at the time of ingestion. The result of the dose estimation showed that 14 C-lysine gave significantly higher prenatal and neonatal doses than 14 C-sodium bicarbonate or 14 C-thymidine. (author)

  17. Toxicological assessments of rats exposed prenatally to inhaled vapors of gasoline and gasoline-ethanol blends.

    Science.gov (United States)

    Bushnell, Philip J; Beasley, Tracey E; Evansky, Paul A; Martin, Sheppard A; McDaniel, Katherine L; Moser, Virginia C; Luebke, Robert W; Norwood, Joel; Copeland, Carey B; Kleindienst, Tadeusz E; Lonneman, William A; Rogers, John M

    2015-01-01

    The primary alternative to petroleum-based fuels is ethanol, which may be blended with gasoline in the United States at concentrations up to 15% for most automobiles. Efforts to increase the amount of ethanol in gasoline have prompted concerns about the potential toxicity of inhaled ethanol vapors from these fuels. The well-known sensitivity of the developing nervous and immune systems to ingested ethanol and the lack of information about the neurodevelopmental toxicity of ethanol-blended fuels prompted the present work. Pregnant Long-Evans rats were exposed for 6.5h/day on days 9-20 of gestation to clean air or vapors of gasoline containing no ethanol (E0) or gasoline blended with 15% ethanol (E15) or 85% ethanol (E85) at nominal concentrations of 3000, 6000, or 9000 ppm. Estimated maternal peak blood ethanol concentrations were less than 5mg/dL for all exposures. No overt toxicity in the dams was observed, although pregnant dams exposed to 9000 ppm of E0 or E85 gained more weight per gram of food consumed during the 12 days of exposure than did controls. Fuel vapors did not affect litter size or weight, or postnatal weight gain in the offspring. Tests of motor activity and a functional observational battery (FOB) administered to the offspring between post-natal day (PND) 27-29 and PND 56-63 revealed an increase in vertical activity counts in the 3000- and 9000-ppm groups in the E85 experiment on PND 63 and a few small changes in sensorimotor responses in the FOB that were not monotonically related to exposure concentration in any experiment. Neither cell-mediated nor humoral immunity were affected in a concentration-related manner by exposure to any of the vapors in 6-week-old male or female offspring. Systematic concentration-related differences in systolic blood pressure were not observed in rats tested at 3 and 6 months of age in any experiment. No systematic differences were observed in serum glucose or glycated hemoglobin A1c (a marker of long-term glucose

  18. Behavioral changes in preweaning and adult rats exposed prenatally to low ionizing radiation

    International Nuclear Information System (INIS)

    Norton, S.

    1986-01-01

    Seven behavioral tests were used to evaluate the postnatal behavior of rats after exposure on gestational Day 15 to 0, 25, 50, 75, or 125 r, whole body irradiation of the pregnant rat. Three tests were administered in the first 2 postnatal weeks (righting reflex, negative geotaxis, and reflex suspension); three tests were administered on postnatal Day 21 (modified open field, spatial maze, and continuous corridor). As adults, the rats were retested with the same tests as at 21 days and also in the running wheel. Dose-response decreases in body weight were greater in the younger rats. Some behavioral tests were not altered by irradiation, while others showed clear dose-response relationships, starting as low as 25 r. The early changes were characterized by light body weight, delays in behavioral development and hypoactivity, followed by recovery of some parameters with maturation. Eventually hyperactivity developed in adult rats after gestational irradiation. However, it cannot be concluded that either morphological or behavioral tests are more sensitive than neonatal body weight change for detection of damage from gestational irradiation

  19. Study on the ultrastructure of brain in rats prenatally exposed to tritiated water

    International Nuclear Information System (INIS)

    Yang Zhiyuan; Guo Yuefen; Lai Chixiang

    1993-01-01

    At 11th day of gestation, rats were intraperitoneally injected with HTO, the activity of which were 5.55 x 10 6 Bq/mL of body water and 5.55 x 10 5 Bq/mL of body water. In these conditions, the cumulative doses for 1-day-old and 18-day-old young rats were estimated to be 1.6-1.7 Gy and 0.16-0.17 Gy, respectively. Under the above-mentioned conditions, some significant injuries in the ultrastructure of the nucleus of neutron and of the cell apparatuses in the cytoplasm of the cerebral and cerebellar cortexes can be seen on the 1-day-old and 18-day-old young rats. When young rats were 90 days old, these injuries of ultrastructure in brain cells had not be observed but it was observed that the processes of neutroglia cells replenished the crevices in injured neutropilem of the cerebral and cerebellar cortex

  20. Effects of sex and housing on social, spatial, and motor behavior in adult rats exposed to moderate levels of alcohol during prenatal development.

    Science.gov (United States)

    Rodriguez, Carlos I; Magcalas, Christy M; Barto, Daniel; Fink, Brandi C; Rice, James P; Bird, Clark W; Davies, Suzy; Pentkowski, Nathan S; Savage, Daniel D; Hamilton, Derek A

    2016-10-15

    Persistent deficits in social behavior, motor behavior, and behavioral flexibility are among the major negative consequences associated with exposure to ethanol during prenatal development. Prior work from our laboratory has linked moderate prenatal alcohol exposure (PAE) in the rat to deficits in these behavioral domains, which depend upon the ventrolateral frontal cortex (Hamilton et al., 2014) [20]. Manipulations of the social environment cause modifications of dendritic morphology and experience-dependent immediate early gene expression in ventrolateral frontal cortex (Hamilton et al., 2010) [19], and may yield positive behavioral outcomes following PAE. In the present study we evaluated the effects of housing PAE rats with non-exposed control rats on adult behavior. Rats of both sexes were either paired with a partner from the same prenatal treatment condition (ethanol or saccharin) or from the opposite condition (mixed housing condition). At four months of age (∼3 months after the housing manipulation commenced), social behavior, tongue protrusion, and behavioral flexibility in the Morris water task were measured as in (Hamilton et al., 2014) [20]. The behavioral effects of moderate PAE were primarily limited to males and were not ameliorated by housing with a non-ethanol exposed partner. Unexpectedly, social behavior, motor behavior, and spatial flexibility were adversely affected in control rats housed with a PAE rat (i.e., in mixed housing), indicating that housing with a PAE rat has broad behavioral consequences beyond the social domain. These observations provide further evidence that moderate PAE negatively affects social behavior, and underscore the importance of considering potential negative effects of housing with PAE animals on the behavior of critical comparison groups. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Decreased duration of pentobarbital-induced narcosis in immature and adult female rats prenatally exposed to cimetidine

    International Nuclear Information System (INIS)

    Donnelly, D.A.; Iba, M.M.

    1986-01-01

    The effect of prenatal cimetidine exposure (PreCM) on the duration of pentobarbital-induced narcosis (DPN) was assessed in immature (14- and 28-day old) and adult (50-60-day old) male and female rats. PreCM exposure was accomplished by treating mothers with cimetidine (CM) (20 mg/kg, ip) daily for the last two days of gestation and then (0.01% in drinking water) throughout lactation. Pregnant mothers of untreated offspring (Con) received saline. PreCM decreased DPN to 505 +/- 33 min (from 611 +/- 23 min in Con) and 393 +/- 190 min (from 686 +/- 44 min in Con) in 14-day old male and female rats, respectively. Similarly, PreCM decreased DPN to 88 +/- 15 min (from 134 +/- 3 min in Con) and 102 +/- 19 min (from 171 +/- 44 min in Con) in 28-day old male and female rats, respectively. At 21 days, PreCM did not alter DPN in either sex. At 50-60 days, however, it decreased DPN to 144 +/- 41 min (from 238 +/- 7 min in Con) in females but had no effect in males; PreCM also increased the plasma clearance of administered 14 C-pentobarbital more in females than in males. The effects of PreCM, particularly the long-term effects, were most prominent in female rats and were the opposite of those of postnatal treatment with CM. The results together with those of studies with hepatic microsomes suggest that PreCM may have resulted in the induction of hepatic drug-metabolizing enzymes during the perinatal period

  2. Transfer of {sup 14}C to prenatal and neonatal rats from their mothers exposed to {sup 14}C compounds by ingestion

    Energy Technology Data Exchange (ETDEWEB)

    Takeda, H.; Fuma, S.; Miyamoto, K.; Kuroda, N.; Inaba, J

    2003-07-01

    The transfer of {sup 14}C through placenta or milk was investigated and the radiation dose to fetal and newborn rats was estimated. Female rats at gestational stages or after delivery were exposed to {sup 14}C in the form of sodium bicarbonate, thymidine and lysine by a single ingestion. Radioactivity in maternal tissues and conceptuses (placenta, fetal membrane and fetus) and in the newborn was determined at various times after ingestion. After exposure to these {sup 14}C compounds, there was no significant difference between the {sup 14}C concentration in the fetus and that in the maternal tissues, suggesting that the placenta has no effect in preventing or accelerating the placental transfer of {sup 14}C. The concentration and content of {sup 14}C in the fetus and newborn were, however, dependent on the chemical form of {sup 14}C and on the prenatal or neonatal stage at the time of ingestion. The result of the dose estimation showed that {sup 14}C-lysine gave significantly higher prenatal and neonatal doses than {sup 14}C-sodium bicarbonate or {sup 14}C-thymidine. (author)

  3. Maternal glucocorticoid elevation and associated blood metabonome changes might be involved in metabolic programming of intrauterine growth retardation in rats exposed to caffeine prenatally

    International Nuclear Information System (INIS)

    Kou, Hao; Liu, Yansong; Liang, Gai; Huang, Jing; Hu, Jieqiong; Yan, You-e; Li, Xiaojun; Yu, Hong; He, Xiaohua; Zhang, Baifang; Zhang, Yuanzhen; Feng, Jianghua; Wang, Hui

    2014-01-01

    Our previous studies demonstrated that prenatal caffeine exposure causes intrauterine growth retardation (IUGR), fetuses are over-exposed to high levels of maternal glucocorticoids (GC), and intrauterine metabolic programming and associated metabonome alteration that may be GC-mediated. However, whether maternal metabonomes would be altered and relevant metabolite variations might mediate the development of IUGR remained unknown. In the present studies, we examined the dose- and time-effects of caffeine on maternal metabonome, and tried to clarify the potential roles of maternal GCs and metabonome changes in the metabolic programming of caffeine-induced IUGR. Pregnant rats were treated with caffeine (0, 20, 60 or 180 mg/kg · d) from gestational days (GD) 11 to 20, or 180 mg/kg · d caffeine from GD9. Metabonomes of maternal plasma on GD20 in the dose–effect study and on GD11, 14 and 17 in the time–course study were analyzed by 1 H nuclear magnetic resonance spectroscopy, respectively. Caffeine administration reduced maternal weight gains and elevated both maternal and fetal corticosterone (CORT) levels. A negative correlation between maternal/fetal CORT levels and fetal bodyweight was observed. The maternal metabonome alterations included attenuated metabolism of carbohydrates, enhanced lipolysis and protein breakdown, and amino acid accumulation, suggesting GC-associated metabolic effects. GC-associated metabolite variations (α/β-glucoses, high density lipoprotein-cholesterol, β-hydroxybutyrate) were observed early following caffeine administration. In conclusion, prenatal caffeine exposure induced maternal GC elevation and metabonome alteration, and maternal GC and relevant discriminatory metabolites might be involved in the metabolic programming of caffeine-induced IUGR. - Highlights: • Prenatal caffeine exposure elevated maternal blood glucocorticoid levels. • Prenatal caffeine exposure altered maternal blood metabonomes. • Maternal metabonome

  4. Maternal glucocorticoid elevation and associated blood metabonome changes might be involved in metabolic programming of intrauterine growth retardation in rats exposed to caffeine prenatally

    Energy Technology Data Exchange (ETDEWEB)

    Kou, Hao; Liu, Yansong; Liang, Gai; Huang, Jing; Hu, Jieqiong; Yan, You-e; Li, Xiaojun [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Yu, Hong; He, Xiaohua; Zhang, Baifang [Hubei Provincial Key Laboratory of Developmentally Originated Diseases, Wuhan 430071 (China); Zhang, Yuanzhen [Hubei Provincial Key Laboratory of Developmentally Originated Diseases, Wuhan 430071 (China); Center for Reproductive Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Feng, Jianghua, E-mail: jianghua.feng@xmu.edu.cn [Department of Electronic Science, Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance, Xiamen University, Xiamen 361005 (China); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Hubei Provincial Key Laboratory of Developmentally Originated Diseases, Wuhan 430071 (China)

    2014-03-01

    Our previous studies demonstrated that prenatal caffeine exposure causes intrauterine growth retardation (IUGR), fetuses are over-exposed to high levels of maternal glucocorticoids (GC), and intrauterine metabolic programming and associated metabonome alteration that may be GC-mediated. However, whether maternal metabonomes would be altered and relevant metabolite variations might mediate the development of IUGR remained unknown. In the present studies, we examined the dose- and time-effects of caffeine on maternal metabonome, and tried to clarify the potential roles of maternal GCs and metabonome changes in the metabolic programming of caffeine-induced IUGR. Pregnant rats were treated with caffeine (0, 20, 60 or 180 mg/kg · d) from gestational days (GD) 11 to 20, or 180 mg/kg · d caffeine from GD9. Metabonomes of maternal plasma on GD20 in the dose–effect study and on GD11, 14 and 17 in the time–course study were analyzed by {sup 1}H nuclear magnetic resonance spectroscopy, respectively. Caffeine administration reduced maternal weight gains and elevated both maternal and fetal corticosterone (CORT) levels. A negative correlation between maternal/fetal CORT levels and fetal bodyweight was observed. The maternal metabonome alterations included attenuated metabolism of carbohydrates, enhanced lipolysis and protein breakdown, and amino acid accumulation, suggesting GC-associated metabolic effects. GC-associated metabolite variations (α/β-glucoses, high density lipoprotein-cholesterol, β-hydroxybutyrate) were observed early following caffeine administration. In conclusion, prenatal caffeine exposure induced maternal GC elevation and metabonome alteration, and maternal GC and relevant discriminatory metabolites might be involved in the metabolic programming of caffeine-induced IUGR. - Highlights: • Prenatal caffeine exposure elevated maternal blood glucocorticoid levels. • Prenatal caffeine exposure altered maternal blood metabonomes. • Maternal

  5. Maternal age as a factor in determining the reproductive and behavioral outcome of rats prenatally exposed to ethanol.

    Science.gov (United States)

    Vorhees, C V

    1988-01-01

    Nulliparous Long-Evans rats were bred at one of four different ages and assigned to one of three treatment groups within each age condition. Maternal ages were 9, 18, 32, and 36 weeks. Treatment groups were ethanol (E), administered by gavage as 8 g/kg in two divided doses on days 10-14 of gestation, pair-fed (PF) controls, administered as an isocaloric sucrose solution by gavage on days 10-14 of gestation, and ad lib fed controls (C). All offspring were surrogate fostered shortly after delivery to untreated recently parturient dams. Litter sizes were standardized to 8 on the day of birth. Offspring were assessed longitudinally for growth, mortality, and behavior (olfaction, locomotor activity, maze learning, avoidance acquisition and startle). Approximately 85% of the 36 week old dams did not produce viable litters. In the remaining maternal age conditions, ethanol delayed offspring olfactory orientation and increased locomotor activity, the latter dissipating after 50-60 days of age. These ethanol-related effects occurred independent of maternal age condition. Maternal age, independent of ethanol, was a factor which reduced litter size and offspring weight up to 50 days, but produced few effects on behavior. The combination of maternal age and prenatal ethanol interacted to increase pregnancy loss (oldest maternal age), reduce offspring weight up to day 99 (oldest and middle maternal age), alter olfactory orientation performance (oldest and middle maternal age), reverse the typical ethanol-induced increase in activity for males in the figure-8 test (oldest maternal age group), shift the pattern of open-field activity, and change errors in a complex water maze. Not all of these interactions turned out to be specific to the ethanol X old maternal age condition. Several of the interactions occurred in both the old and middle maternal age conditions. The only effect of old maternal age that interacted strongly with ethanol was in their combined effects on

  6. Maternal glucocorticoid elevation and associated blood metabonome changes might be involved in metabolic programming of intrauterine growth retardation in rats exposed to caffeine prenatally.

    Science.gov (United States)

    Kou, Hao; Liu, Yansong; Liang, Gai; Huang, Jing; Hu, Jieqiong; Yan, You-e; Li, Xiaojun; Yu, Hong; He, Xiaohua; Zhang, Baifang; Zhang, Yuanzhen; Feng, Jianghua; Wang, Hui

    2014-03-01

    Our previous studies demonstrated that prenatal caffeine exposure causes intrauterine growth retardation (IUGR), fetuses are over-exposed to high levels of maternal glucocorticoids (GC), and intrauterine metabolic programming and associated metabonome alteration that may be GC-mediated. However, whether maternal metabonomes would be altered and relevant metabolite variations might mediate the development of IUGR remained unknown. In the present studies, we examined the dose- and time-effects of caffeine on maternal metabonome, and tried to clarify the potential roles of maternal GCs and metabonome changes in the metabolic programming of caffeine-induced IUGR. Pregnant rats were treated with caffeine (0, 20, 60 or 180 mg/kg·d) from gestational days (GD) 11 to 20, or 180 mg/kg·d caffeine from GD9. Metabonomes of maternal plasma on GD20 in the dose-effect study and on GD11, 14 and 17 in the time-course study were analyzed by ¹H nuclear magnetic resonance spectroscopy, respectively. Caffeine administration reduced maternal weight gains and elevated both maternal and fetal corticosterone (CORT) levels. A negative correlation between maternal/fetal CORT levels and fetal bodyweight was observed. The maternal metabonome alterations included attenuated metabolism of carbohydrates, enhanced lipolysis and protein breakdown, and amino acid accumulation, suggesting GC-associated metabolic effects. GC-associated metabolite variations (α/β-glucoses, high density lipoprotein-cholesterol, β-hydroxybutyrate) were observed early following caffeine administration. In conclusion, prenatal caffeine exposure induced maternal GC elevation and metabonome alteration, and maternal GC and relevant discriminatory metabolites might be involved in the metabolic programming of caffeine-induced IUGR. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Targeting anandamide metabolism rescues core and associated autistic-like symptoms in rats prenatally exposed to valproic acid

    OpenAIRE

    Servadio, M; Melancia, F; Manduca, A; di Masi, A; Schiavi, S; Cartocci, V; Pallottini, V; Campolongo, P; Ascenzi, P; Trezza, V

    2016-01-01

    Autism spectrum disorders (ASD) are characterized by altered sociability, compromised communication and stereotyped/repetitive behaviors, for which no specific treatments are currently available. Prenatal exposure to valproic acid (VPA) is a known, although still underestimated, environmental risk factor for ASD. Altered endocannabinoid activity has been observed in autistic patients, and endocannabinoids are known to modulate behavioral traits that are typically affected in ASD. On this basi...

  8. Development of the central nervous system functions in rat pups prenatally exposed to alcohol (study on the behavioural teratology of ethanol in CFY rat pups).

    Science.gov (United States)

    Lehotzky, K; Ungváry, G; Szeberényi, J M; Kiss, A

    1988-01-01

    As a model of fetal alcohol syndrome (FAS) the rate of the maturation of the functions of the central nervous system was studied in the offspring of pregnant CFY rats receiving (from the 7th-15th day of gestation) either oral ethanol treatment or liquid diet containing ethanol. Both types of exposure caused numerous behavioural impairments, besides high perinatal mortality also the opening of the eyes and ears, and the appearance of postural reflexes were delayed. The newborn rats could be characterized by hyperactivity and weak motor coordination. The learning capacity, the avoidance conditioned reflexes was the poorest in the case of the offspring of mothers kept on liquid diet, containing alcohol, the latency of the conditioned response was significantly lenghtened. During reconditioning, in the case of the sexually already mature pups, the weakest performance was observed in the offspring of mothers having received oral alcohol treatment. This findings indicated, on one hand, that the retardation ceased and, on the other, that the learning and memory impairments caused by oral alcohol exposure was persistent. Following prenatal alcohol exposure carried out by different methods the neurotoxic effect, the retardation of the rate of maturation of the central nervous functions, and the adaptive mechanisms were all affected to different extent. Besides alcohol exposure also other factors (relative protein insufficiency, malnutrition) may be involved in the pathomechanism of the above mentioned phenomena.

  9. Report of final results regarding brain and heart tumors in Sprague-Dawley rats exposed from prenatal life until natural death to mobile phone radiofrequency field representative of a 1.8 GHz GSM base station environmental emission.

    Science.gov (United States)

    Falcioni, L; Bua, L; Tibaldi, E; Lauriola, M; De Angelis, L; Gnudi, F; Mandrioli, D; Manservigi, M; Manservisi, F; Manzoli, I; Menghetti, I; Montella, R; Panzacchi, S; Sgargi, D; Strollo, V; Vornoli, A; Belpoggi, F

    2018-08-01

    In 2011, IARC classified radiofrequency radiation (RFR) as possible human carcinogen (Group 2B). According to IARC, animals studies, as well as epidemiological ones, showed limited evidence of carcinogenicity. In 2016, the NTP published the first results of its long-term bioassays on near field RFR, reporting increased incidence of malignant glial tumors of the brain and heart Schwannoma in rats exposed to GSM - and CDMA - modulated cell phone RFR. The tumors observed in the NTP study are of the type similar to the ones observed in some epidemiological studies of cell phone users. The Ramazzini Institute (RI) performed a life-span carcinogenic study on Sprague-Dawley rats to evaluate the carcinogenic effects of RFR in the situation of far field, reproducing the environmental exposure to RFR generated by 1.8 GHz GSM antenna of the radio base stations of mobile phone. This is the largest long-term study ever performed in rats on the health effects of RFR, including 2448 animals. In this article, we reported the final results regarding brain and heart tumors. Male and female Sprague-Dawley rats were exposed from prenatal life until natural death to a 1.8 GHz GSM far field of 0, 5, 25, 50 V/m with a whole-body exposure for 19 h/day. A statistically significant increase in the incidence of heart Schwannomas was observed in treated male rats at the highest dose (50 V/m). Furthermore, an increase in the incidence of heart Schwann cells hyperplasia was observed in treated male and female rats at the highest dose (50 V/m), although this was not statistically significant. An increase in the incidence of malignant glial tumors was observed in treated female rats at the highest dose (50 V/m), although not statistically significant. The RI findings on far field exposure to RFR are consistent with and reinforce the results of the NTP study on near field exposure, as both reported an increase in the incidence of tumors of the brain and heart in RFR-exposed Sprague

  10. Prenatal choline supplementation mitigates behavioral alterations associated with prenatal alcohol exposure in rats.

    Science.gov (United States)

    Thomas, Jennifer D; Idrus, Nirelia M; Monk, Bradley R; Dominguez, Hector D

    2010-10-01

    Prenatal alcohol exposure can alter physical and behavioral development, leading to a range of fetal alcohol spectrum disorders. Despite warning labels, pregnant women continue to drink alcohol, creating a need to identify effective interventions to reduce the severity of alcohol's teratogenic effects. Choline is an essential nutrient that influences brain and behavioral development. Recent studies indicate that choline supplementation can reduce the teratogenic effects of developmental alcohol exposure. The present study examined whether choline supplementation during prenatal ethanol treatment could mitigate the adverse effects of ethanol on behavioral development. Pregnant Sprague-Dawley rats were intubated with 6 g/kg/day ethanol in a binge-like manner from gestational days 5-20; pair-fed and ad libitum chow controls were included. During treatment, subjects from each group were intubated with either 250 mg/kg/day choline chloride or vehicle. Spontaneous alternation, parallel bar motor coordination, Morris water maze, and spatial working memory were assessed in male and female offspring. Subjects prenatally exposed to alcohol exhibited delayed development of spontaneous alternation behavior and deficits on the working memory version of the Morris water maze during adulthood, effects that were mitigated with prenatal choline supplementation. Neither alcohol nor choline influenced performance on the motor coordination task. These data indicate that choline supplementation during prenatal alcohol exposure may reduce the severity of fetal alcohol effects, particularly on alterations in tasks that require behavioral flexibility. These findings have important implications for children of women who drink alcohol during pregnancy. © 2010 Wiley-Liss, Inc.

  11. Cytokine mRNA profiles in pigs exposed prenatally and postnatally to Schistosoma japonicum

    DEFF Research Database (Denmark)

    Techau, Michala E.; Johansen, Maria V.; Aasted, Bent

    2007-01-01

    of septal fibrosis were significantly higher in the postnatal group compared to the prenatal group (P prenatally infected animals compared to the control...... group (P prenatal group showed higher levels of TGF-beta 1 in the liver compared with the postnatally infected group (P control group (P prenatally exposed pigs.......The pig is a natural host for Schistosoma japonicum and a useful animal model of human infection. The aim of the present study was to assess the differences between the cytokine profiles in prenatally or postnatally S. japonicum exposed pigs. Seven prenatally exposed pigs, 7 postnatally exposed...

  12. Brain damage among the prenatally exposed

    International Nuclear Information System (INIS)

    Otake, Masanori; Schull, W.J.; Yoshimaru, Hiroshi.

    1991-01-01

    Significant effects on the developing brain of exposure to ionizing radiation are seen among those individuals exposed in the 8th through the 25th week after fertilization. These effects, particularly in the most sensitive period, 8-15 weeks after fertilization, manifest themselves as an increased frequency of severe mental retardation (SMR), a diminution in IQ score and in school performance, and an increase in the occurrence of seizures. Of 30 SMR cases, 18 (60%) had small heads. About 10% of the individuals with small head sizes observed among the in utero clinical sample were mentally retarded. When all of the cases of mental retardation are included in the analysis, a linear dose-response model fits the data adequately and no evidence of a threshold emerges; however, if the two probable nonradiation-related cases of Down's syndrome are excluded from the 19 SMR cases exposed 8-15 weeks after fertilization, the evidence of a threshold is stronger. The 95% lower bound of the threshold based on the new dosimetry system appears to be in the range of 0.12-0.23 Gy. In the 16-25 week period, the 95% lower bound of the threshold is 0.21 Gy both with and without inclusion of two probable nonradiation-related retarded cases. In a regression analysis of IQ scores and school performance data, a greater linearity is suggested with the new dosimetry (DS86) than with the old (T65DR), but the mean IQ score and the mean school performance of those exposed in utero to doses under 0.10 Gy are similar, and not statistically different from the means in the control group. The risk ratios for unprovoked seizures, following exposure during the 8th through the 15th week after fertilization, are 4.4 (90% confidence interval: 0.5-40.9) after 0.10-0.49 Gy and 24.9 (4.1-191.6) after 0.50 Gy or more when the mentally retarded are included and 4.4 (0.5-40.9) and 14.5 (0.4-199.6), respectively, when they are excluded. (author)

  13. Effects of prenatal exposure to xylene on postnatal development and behavior in rats

    DEFF Research Database (Denmark)

    Hass, Ulla; Lund, S. P.; Simonsen, L.

    1995-01-01

    The effects of prenatal exposure to the organic solvent xylene (dimethylbenzene, GAS-no 1330-20-7) on postnatal development and behavior in rats were studied. Pregnant rats (Mol:WIST) were exposed to 500 ppm technical xylene 6 h per day on gestation days 7-20. The dose level was selected so as no...

  14. Effects of prenatal exposure to toluene on postnatal development and behavior in rats

    DEFF Research Database (Denmark)

    Hougaard, K. S.; Hass, Ulla; Lund, S. P.

    1999-01-01

    Development and neurobehavioral effects of prenatal exposure to toluene (CAS 108-88-3) were studied after exposing pregnant rats (Mol:WIST) to 1800 ppm of the solvent for 6 h daily on days 7-20 of gestation. Body weights of exposed offspring were lower until day 10 after parturition. Neurobehavio...

  15. The effect of prenatal methamphetamine exposure on recognition memory in adult rats.

    Science.gov (United States)

    Fialová, Markéta; Šírová, Jana; Bubeníková-Valešová, Věra; Šlamberová, Romana

    2015-01-01

    The use of methamphetamine (MA) among pregnant women is an increasing world-wide health problem. Prenatal MA exposure may cause changes in foetus but the exact effects have remained unclear. The aim of this study is to present the effect of prenatal MA exposure on recognition memory in adult rats. Adult female Wistar rats were injected daily with D-methamphetamine HCl (MA; 5 mg/kg, s.c.) during the entire gestation period. Control females were treated with saline in the same regime. Adult male offspring was administrated acutely by MA (1 mg/kg i.p.) or saline 30 minutes before beginning of an experiment. For testing recognition memory two tasks were chosen: Novel Object Recognition Test (NORT) and Object Location Test (OLT). Our results demonstrate that prenatally MA-exposed animals were worse in NORT independently on an acute administration of MA in adulthood. Prenatally MA-exposed rats did not deteriorate in OLT, but after acute administration of MA in adulthood, there was significant worsening compared to appropriate control. Prenatally saline-exposed offspring did not deteriorate in any test even after acute administration of MA. Our data suggest that prenatal MA exposure in rats cause impairment in recognition memory in adult offspring, but not in spatial memory. In addition, acute administration of MA to controls did not deteriorate either recognition or spatial memory.

  16. Deficits in response inhibition in male rats prenatally exposed to vapor condensates made from gasoline containing ethanol at 0% and 15%, but not 85%

    Science.gov (United States)

    The impact of developmental exposure to inhaled ethanol-gasoline fuel blends is a potential public health concern. We previously reported that rats whose mothers inhaled ethanol (21,000 ppm) during pregnancy had increased levels of anticipatory responding on a choice reaction tim...

  17. Prenatal cocaine exposure alters alpha2 receptor expression in adolescent rats

    Directory of Open Access Journals (Sweden)

    Silvers Janelle M

    2006-04-01

    Full Text Available Abstract Background Prenatal cocaine exposure produces attentional deficits which to persist through early childhood. Given the role of norepinephrine (NE in attentional processes, we examined the forebrain NE systems from prenatal cocaine exposed rats. Cocaine was administered during pregnancy via the clinically relevant intravenous route of administration. Specifically, we measured α2-adrenergic receptor (α2-AR density in adolescent (35-days-old rats, using [3H]RX821002 (5 nM. Results Sex-specific alterations of α2-AR were found in the hippocampus and amygdala of the cocaine-exposed animals, as well as an upregulation of α2-AR in parietal cortex. Conclusion These data suggest that prenatal cocaine exposure results in a persistent alteration in forebrain NE systems as indicated by alterations in receptor density. These neurochemical changes may underlie behavioral abnormalities observed in offspring attentional processes following prenatal exposure to cocaine.

  18. Psychopharmacologic treatment of children prenatally exposed to drugs of abuse.

    Science.gov (United States)

    Hulvershorn, Leslie A; Schroeder, Kristen M; Wink, Logan K; Erickson, Craig A; McDougle, Christopher J

    2015-05-01

    This pilot study compared the pharmacologic treatment history and clinical outcomes observed in pediatric outpatients with psychiatric disorders exposed to drugs of abuse in utero to those of an age-matched, sex-matched and psychiatric disorder-matched, non-drug-exposed group. In this matched cohort study, medical records of children treated at an academic, child and adolescent psychiatry outpatient clinic were reviewed. Children with caregiver-reported history of prenatal drug exposure were compared with a non-drug-exposed control group being cared for by the same providers. Patients were rated with the Clinical Global Impressions-Severity scale (CGI-S) throughout treatment. The changes in pre-treatment and post-treatment CGI-S scores and the total number of medication trials were determined between groups. The drug-exposed group (n = 30) had a higher total number of lifetime medication trials compared with the non-drug-exposed group (n = 28) and were taking significantly more total medications, at their final assessment. Unlike the non-drug-exposed group, the drug-exposed group demonstrated a lack of clinical improvement. These results suggest that in utero drug-exposed children may be more treatment-refractory to or experience greater side effects from the pharmacologic treatment of psychiatric disorders than controls, although we cannot determine if early environment or drugs exposure drives these findings. Copyright © 2015 John Wiley & Sons, Ltd.

  19. Long-lasting neurobehavioral effects of prenatal exposure to xylene in rats

    DEFF Research Database (Denmark)

    Hass, Ulla; Lund, S. P.; Simonsen, L.

    1997-01-01

    The persistence of neurobehavioral effects in female rats (Mol:WIST) exposed to 500 ppm technical xylene (dimethylbenzene, GAS-no 1330-20-7) for 6 hours per day on days 7-20 of prenatal development was studied. The dose level was selected so as not to induce maternal toxicity or decreased viabili...... are planned to investigate whether neurobehavioral effects resulting from prenatal xylene exposure can interact with neurophysiological aging processes. (C) 1997 Inter Press, Inc....

  20. Prenatal zinc prevents communication impairments and BDNF disturbance in a rat model of autism induced by prenatal lipopolysaccharide exposure.

    Science.gov (United States)

    Kirsten, Thiago B; Queiroz-Hazarbassanov, Nicolle; Bernardi, Maria M; Felicio, Luciano F

    2015-06-01

    Aims: Previous investigations by our group have shown that prenatal exposure to lipopolysaccharide (LPS),which mimics infections by Gram-negative bacteria, induced autistic-like behavior. No effective treatment yet exists for autism. Therefore, we used our rat model to test a possible treatment for autism.We selected zinc as the prenatal treatment to prevent or ease the impairments induced by LPS because LPS induces hypozincaemia.Materials and methods:We evaluated the effects of LPS and zinc on female reproductive performance. Communication,which is impaired in autism,was tested in pups by ultrasonic vocalizations. Plasma levels of brain-derived neurotrophic factor (BDNF) were determined because it has been considered an autism important biomarker.Key findings: Prenatal LPS exposure reduced offspring number and treatment with zinc prevented this reduction.Moreover, pups that were prenatally exposed to LPS spent longer periods without calling their mothers, and posttreatment with zinc prevented this impairment induced by LPS to the same levels as controls. Prenatal LPS also increased BDNF levels in adult offspring, and posttreatment with zinc reduced the elevation of BDNF to the same levels as controls.Significance: BDNF hyperactivity was also found in several studies of autistic patients. Together with our previous studies, our model of prenatal LPS induced autistic-like behavioral, brain, and immune disturbances. This suggests that it is a valid rat model of autism. Prenatal zinc prevented reproductive, communication, and BDNF impairments.The present study revealed a potential beneficial effect of prenatal zinc administration for the prevention of autism with regard to the BDNF pathway.

  1. Changes in peripheral nervous system activity produced in rats by prenatal exposure to carbon monoxide

    Energy Technology Data Exchange (ETDEWEB)

    Carratu, M.R. (Inst. of Pharmacology, Bari Univ. (Italy)); Renna, G. (Inst. of Pharmacology, Bari Univ. (Italy)); Giustino, A. (Inst. of Pharmacology, Bari Univ. (Italy)); De Salvia, M.A. (Inst. of Pharmacology, Bari Univ. (Italy)); Cuomo, V. (Inst. of Pharmacology, Bari Univ. (Italy))

    1993-06-01

    The present experiments were designed to investigate whether alterations of peripheral nervous system activity may be produced in male Wistar rats by prenatal exposure (from day 0 to day 20 of pregnancy) to relatively low levels of CO (75 and 150 ppm). The voltage clamp analysis of ionic currents recorded from sciatic nerve fibres showed that prenatal exposure to CO produced modifications of sodium current properties. In particular, in 40-day-old rats exposed to CO (75 and 150 ppm) during gestation, the inactivation kinetics of transient sodium current were significantly slowed. Analysis of the potential dependence of steady-state Na inactivation, h[sub [infinity

  2. Alteration in follistatin gene expression detected in prenatally androgenized rats.

    Science.gov (United States)

    Salehi Jahromi, Marziyeh; Ramezani Tehrani, Fahimeh; Hill, Jennifer W; Noroozzadeh, Mahsa; Zarkesh, Maryam; Ghasemi, Asghar; Zadeh-Vakili, Azita

    2017-06-01

    Impaired ovarian follicle development, the hallmark of polycystic ovarian syndrome (PCOS), is believed to be due to the changes in expression of related genes such as follistatin (FST). Expression of FST gene and methylation level of its promoter in theca cells from adult female rats, prenatally exposed to androgen excess, during different phases of the estrus cycle was determined and compared with controls. Eight pregnant Wistar rats (experimental group) were treated by subcutaneous injection of 5 mg free testosterone on day 20 of pregnancy, while controls (n = 8) received 500 ml solvent. Based on observed vaginal smear, adult female offspring of mothers were divided into three groups. Levels of serum steroidogenic sexual hormones and gonadotropins, expression and promoter methylation of the FST gene were measured using ELISA, cyber-green real-time PCR and bisulfite sequence PCR (BSP), respectively. Compared to controls, the relative expression of FST gene in the treated group decreased overall by 0.85 fold; despite significant changes in different phases, but no significant differences in methylation of FST promoter. Our results reveal that manifestation of PCOS-like phenotype following prenatal exposure to excess androgen is associated with irregularity in expression of the FST gene during the estrus cycle.

  3. Brain magnetic resonance imaging of infants exposed prenatally to buprenorphine

    International Nuclear Information System (INIS)

    Kahila, H.; Kivitie-Kallio, S.; Halmesmaki, E.; Valanne, L.; Autti, T.

    2007-01-01

    Purpose: To evaluate the brains of newborns exposed to buprenorphine prenatally. Material and Methods: Seven neonates followed up antenatally in connection with their mothers' buprenorphine replacement therapy underwent 1.5T magnetic resonance imaging (MRI) of the brain before the age of 2 months. The infants were born to heavy drug abusers. Four mothers were hepatitis C positive, and all were HIV negative. All mothers smoked tobacco and used benzodiazepines. All pregnancies were full term, and no perinatal asphyxia occurred. All but one neonate had abstinence syndrome and needed morphine replacement therapy. Results: Neither structural abnormalities nor abnormalities in signal intensity were recorded. Conclusion: Buprenorphine replacement therapy does not seem to cause any major structural abnormalities of the brain, and it may prevent known hypoxic-ischemic brain changes resulting from uncontrolled drug abuse. Longitudinal studies are needed to assess possible abnormalities in the brain maturation process

  4. Brain magnetic resonance imaging of infants exposed prenatally to buprenorphine

    Energy Technology Data Exchange (ETDEWEB)

    Kahila, H.; Kivitie-Kallio, S.; Halmesmaki, E.; Valanne, L.; Autti, T. [Dept. of Obstetrics and Gynecology, Dept. of Pediatrics, and Helsinki Medical Imaging Center, Helsinki Univ. Central Hospital (Finland)

    2007-02-15

    Purpose: To evaluate the brains of newborns exposed to buprenorphine prenatally. Material and Methods: Seven neonates followed up antenatally in connection with their mothers' buprenorphine replacement therapy underwent 1.5T magnetic resonance imaging (MRI) of the brain before the age of 2 months. The infants were born to heavy drug abusers. Four mothers were hepatitis C positive, and all were HIV negative. All mothers smoked tobacco and used benzodiazepines. All pregnancies were full term, and no perinatal asphyxia occurred. All but one neonate had abstinence syndrome and needed morphine replacement therapy. Results: Neither structural abnormalities nor abnormalities in signal intensity were recorded. Conclusion: Buprenorphine replacement therapy does not seem to cause any major structural abnormalities of the brain, and it may prevent known hypoxic-ischemic brain changes resulting from uncontrolled drug abuse. Longitudinal studies are needed to assess possible abnormalities in the brain maturation process.

  5. Impaired contextual fear extinction and hippocampal synaptic plasticity in adult rats induced by prenatal morphine exposure.

    Science.gov (United States)

    Tan, Ji-Wei; Duan, Ting-Ting; Zhou, Qi-Xin; Ding, Ze-Yang; Jing, Liang; Cao, Jun; Wang, Li-Ping; Mao, Rong-Rong; Xu, Lin

    2015-07-01

    Prenatal opiate exposure causes a series of neurobehavioral disturbances by affecting brain development. However, the question of whether prenatal opiate exposure increases vulnerability to memory-related neuropsychiatric disorders in adult offspring remains largely unknown. Here, we found that rats prenatally exposed to morphine (PM) showed impaired acquisition but enhanced maintenance of contextual fear memory compared with control animals that were prenatally exposed to saline (PS). The impairment of acquisition was rescued by increasing the intensity of footshocks (1.2 mA rather than 0.8 mA). Meanwhile, we also found that PM rats exhibited impaired extinction of contextual fear, which is associated with enhanced maintenance of fear memory. The impaired extinction lasted for 1 week following extinction training. Furthermore, PM rats exhibited reduced anxiety-like behavior in the elevated plus-maze and light/dark box test without differences in locomotor activity. These alterations in PM rats were mirrored by abnormalities in synaptic plasticity in the Schaffer collateral-CA1 synapses of the hippocampus in vivo. PS rats showed blocked long-term potentiation and enabled long-term depression in CA1 synapses following contextual fear conditioning, while prenatal morphine exposure restricted synaptic plasticity in CA1 synapses. The smaller long-term potentiation in PM rats was not further blocked by contextual fear conditioning, and the long-term depression enabled by contextual fear conditioning was abolished. Taken together, our results provide the first evidence suggesting that prenatal morphine exposure may increase vulnerability to fear memory-related neuropsychiatric disorders in adulthood. © 2014 Society for the Study of Addiction.

  6. Effects of prenatal stress on vulnerability to stress in prepubertal and adult rats.

    Science.gov (United States)

    Fride, E; Dan, Y; Feldon, J; Halevy, G; Weinstock, M

    1986-01-01

    This study investigated the hypotheses that unpredictable prenatal stress has effects on the offspring, similar to those induced by perinatal administration of glucocorticoids and increases the vulnerability to stressful situations at adulthood. Rats were exposed to random noise and light stress throughout pregnancy. Offspring were tested for the development of spontaneous alternation behavior (SA) and at adulthood, their response to novel or aversive situations, open field, extinction and punishment following acquisition of an appetitive response and two-way active avoidance, were assessed. In prenatally stressed rats, the development of SA was significantly delayed. On repeated exposure to an open field they were less active; control rats had elevated plasma corticosterone (CCS) on days 2 and 4 of open field exposure, while prenatally stressed rats had significantly raised plasma CCS after each exposure (days 1-8). Furthermore, punishment-induced suppression of an appetitive response was enhanced. Acquisition of active avoidance was faciliated in female but reduced in male prenatally stressed offspring. It is suggested that random prenatal noise and light stress may cause impairment of development of hippocampal function which lasts into adulthood. This impairment is manifested as an increase in vulnerability and a decrease in habituation to stressful stimuli.

  7. Some behavioral aspects of adult rats irradiated prenatally

    International Nuclear Information System (INIS)

    Vekovishcheva, O.Yu.; Blagova, O.E.; Borovitskaya, A.E.; Evtushenko, V.I.; Khanson, K.P.

    1992-01-01

    This is a study of the effects of prenatal irradiation on the behavior of rats. The experiments were performed on 42 eighteen month old rats of both sexes. Eight of the males and thirteen females had been irradiated prenatally. The results of this experiment indicated that in general, the activation of behavior, the appearance of aggression and the increase in chaos along with the presence of behavior poses were typical of the suppressed condition of the prenatal irradiated animal. Also, among prenatally irradiated animals, there was a greater degree of anxiety, a slow rate of adjustment to unfamiliar situations and unfriendly relationships between animals of the same sex. These results were compared with the results of behavioral experiments on irradiated adult rats

  8. The effect of prenatal exposure to diazepam on aspects of postnatal development and behavior in rats.

    Science.gov (United States)

    Gai, N; Grimm, V E

    1982-01-01

    In the present study the effects of chronic treatment of pregnant rats with diazepam on the physical and behavioral development of their offspring were investigated. Rats that were diazepam-exposed prenatally were compared to age-matched controls in terms of the following: number of littermates; birth weight and weight gain until weaning: motor development and coordination; simple motor learning; open field activity; performance on learning tasks of varying complexity; retention of these tasks. Nulliparous Wistar rats were injected s.c. for 16 days of their pregnancy was either 2.5, 5, of 10 mg/kg diazepam or an equal volume of vehicle. Prenatal diazepam treatment did not alter litter size, birth weight, or the righting reflex, but seemed to retard early motor development transiently. Diazepam pups showed longer latencies and less rearing in the open field. There were no differences between animals exposed to drug and vehicle in simple motor learning or in acquiring a simple successive discrimination task. However, there were significant dose-dependent differences on a complex six-choice simultaneous discrimination learning task, the diazepam-exposed rats making more errors and taking more time to reach the goal. A significant difference was seen again between diazepam- and vehicle-exposed rats on the retention test 10 days later. The results indicate that diazepam administered to pregnant rats has long-range effects on the behavior of the offspring, some becoming manifest even in maturity.

  9. Characterization of the cognitive impairments induced by prenatal exposure to stress in the rat

    Directory of Open Access Journals (Sweden)

    Julie A. Markham

    2010-11-01

    Full Text Available We have previously shown that male rats exposed to gestational stress exhibit phenotypes resembling what is observed in schizophrenia, including hypersensitivity to amphetamine, blunted sensory gating, disrupted social behavior, impaired stress axis regulation, and aberrant prefrontal expression of genes involved in synaptic plasticity. Maternal psychological stress during pregnancy has been associated with adverse cognitive outcomes among children, as well as an increased risk for developing schizophrenia, which is characterized by significant cognitive deficits. We sought to characterize the long-term cognitive outcome of prenatal stress using a preclinical paradigm, which is readily amenable to the development of novel therapeutic strategies. Rats exposed to repeated variable prenatal stress during the third week of gestation were evaluated using a battery of cognitive tests, including the novel object recognition task, cued and contextual fear conditioning, the Morris water maze, and iterative versions of a paradigm in which working and reference memory for both objects and spatial locations can be assessed (the ‘Can Test’. Prenatally stressed males were impaired relative to controls on each of these tasks, confirming the face validity of this preclinical paradigm and extending the cognitive implications of prenatal stress exposure beyond the hippocampus. Interestingly, in experiments where both sexes were included, the performance of females was found to be less affected by prenatal stress compared to that of males. This could be related to the finding that women are less vulnerable than men to schizophrenia, and merits further investigation.

  10. Language Outcomes at 12 Years for Children Exposed Prenatally to Cocaine

    Science.gov (United States)

    Lewis, Barbara A.; Minnes, Sonia; Short, Elizabeth J.; Min, Meeyoung O.; Wu, Miaoping; Lang, Adelaide; Weishampel, Paul; Singer, Lynn T.

    2013-01-01

    Purpose: In this study, the authors aimed to examine the long-term effects of prenatal cocaine exposure (PCE) on the language development of 12-year-old children using a prospective design, controlling for confounding prenatal drug exposure and environmental factors. Method: Children who were exposed to cocaine in utero (PCE; "n" = 183)…

  11. Increased preference for ethanol in the infant rat after prenatal ethanol exposure, expressed on intake and taste reactivity tests.

    Science.gov (United States)

    Arias, Carlos; Chotro, M Gabriela

    2005-03-01

    Previous studies have shown that prenatal exposure during gestational days 17 to 20 to low or moderate doses of ethanol (1 or 2 g/kg) increases alcohol intake in infant rats. Taking into account that higher consumption does not necessarily suggest a preference for alcohol, in the present study, the hedonic nature of the prenatal experience was analyzed further with the use of a taste reactivity test. General activity, wall climbing, passive drips, paw licking, and mouthing in response to intraoral infusions of alcohol, water, and a sucrose-quinine solution (which resembles alcohol taste in rats) were tested in 161 preweanling 14-day-old rat pups that were prenatally exposed to 0, 1, or 2 g/kg of alcohol during gestational days 17 to 20. Consumption of those substances was measured during the taste reactivity test and on postnatal day 15. Pups that were prenatally exposed to both doses of ethanol displayed lower levels of general activity and wall climbing than controls in response to ethanol. Infant rats that were treated prenatally with both doses of ethanol showed higher intake of the drug and also more mouthing and paw licking in response to ethanol taste. Only pups that were exposed to the higher ethanol dose in utero generalized those responses to the sucrose-quinine compound. These results seem to indicate that for the infant rat, the palatability of ethanol is enhanced after exposure to the drug during the last days of gestation.

  12. Visual evoked potentials in children prenatally exposed to methylmercury

    DEFF Research Database (Denmark)

    Yorifuji, Takashi; Murata, Katsuyuki; Bjerve, Kristian S

    2013-01-01

    Prenatal exposure to methylmercury can cause both neurobehavioral deficits and neurophysiological changes. However, evidence of neurotoxic effects within the visual nervous system is inconsistent, possibly due to incomplete statistical adjustment for beneficial nutritional factors. We evaluated t...

  13. Postnatal development of rat pups is altered by prenatal methamphetamine exposure.

    Science.gov (United States)

    Slamberová, Romana; Pometlová, Marie; Charousová, Petra

    2006-01-01

    There are studies showing that drug abuse during pregnancy may have impairing effect on progeny of drug-abusing mothers. Methamphetamine (MA) is one of the most common illicit drugs throughout the world. The purpose of the present study was to assess the effect of prenatal MA exposure on postnatal development of rat pups before the time of separation from their mothers. Female rats were injected with MA (5 mg/kg daily) for the duration of their pregnancy. Pups were then tested throughout the lactation period. They were weighed daily and the ano-genital distance was measured on postnatal day (PD) 1. Development of postural motor reaction was tested by righting reflex on surface between PD 1 and 12, and righting reflex in mid-air after PD 12 until successfully accomplished. On PD 15 homing test was examined as a test of pup acute learning. On PD 23 sensory-motor coordination was examined using the rotarod and bar-holding tests. Additionally, the markers of physical maturation, such as eye opening, testes descent in males and vaginal opening in females were also recorded. The birth weight in prenatally MA-exposed pups was lower than in controls or saline-exposed pups regardless of sex. There were no changes induced by prenatal MA exposure in weight gain or in sexual maturation. In righting reflexes, we demonstrated that pups exposed prenatally to MA were slower in righting reflex on surface and that they accomplished the test of righting reflex in mid-air later than controls or saline-exposed pups. The performance of homing test was not affected by prenatal drug exposure. The sensory-motor coordination was impaired in prenatally MA-exposed pups when testing in the rotarod test. Also, the number of falls in the bar-holding test was higher in MA-exposed pups than in controls. There were no sex differences in any measures. Thus, the present study demonstrated that prenatal MA exposure impairs development of postural motor movements of rat pups during the first 3 weeks

  14. Effects of prenatal exposure to chronic mild stress and toluene in rats

    DEFF Research Database (Denmark)

    Hougaard, Karin; Andersen, Maibritt B; Hansen, Ase M

    2005-01-01

    The aim of the present study was to elucidate whether prenatal chronic stress, in combination with exposure to a developmental neurotoxicant, would increase effects in the offspring compared with the effects of either exposure alone. Development and neurobehavioral effects were investigated...... in female offspring of pregnant rats (Mol:WIST) exposed to chronic mild stress (CMS) during gestational days (GD) 9-20, or 1500 ppm toluene, 6 h/day during gestational days 7-20, or a combination of the two. Prenatal CMS was associated with decreased thymic weight and increased auditory startle response....... The corticosterone response to restraint seemed modified by prenatal exposure to toluene. Lactational body weight was decreased in offsprings subjected to CMS, primarily due to effects in the combined exposure group. Cognitive function was investigated in the Morris water maze, and some indications of improved...

  15. Prenatal uterine environment and sexual differentiation of rats

    NARCIS (Netherlands)

    E.J. Houtsmuller (Elisabeth Judith)

    1993-01-01

    textabstractprenatal factors relevant to hormonal environment on the sexual differentiation of behavior, morphology and central nervous system in rats. The effects of such factors as prenatal sex composition of the litter and position in utero on the sexual differentiation of normally developed

  16. Prenatal androgen excess programs metabolic derangements in pubertal female rats.

    Science.gov (United States)

    Yan, Xiaonan; Dai, Xiaonan; Wang, Jing; Zhao, Nannan; Cui, Yugui; Liu, Jiayin

    2013-04-01

    Owing to the heterogeneity in the clinical symptoms of polycystic ovary syndrome (PCOS), the early pathophysiological mechanisms of PCOS remain unclear. Clinical, experimental, and genetic evidence supports an interaction between genetic susceptibility and the influence of maternal environment in the pathogenesis of PCOS. To determine whether prenatal androgen exposure induced PCOS-related metabolic derangements during pubertal development, we administrated 5α-dihydrotestosterone (DHT) in pregnant rats and observed their female offspring from postnatal 4 to 8 weeks. The prenatally androgenized (PNA) rats exhibited more numerous total follicles, cystic follicles, and atretic follicles than the controls. Fasting glucose, insulin, leptin levels, and homeostatic model assessment for insulin resistance were elevated in the PNA rats at the age of 5-8 weeks. Following intraperitoneal glucose tolerance tests, glucose and insulin levels did not differ between two groups; however, the PNA rats showed significantly higher 30- and 60-min glucose levels than the controls after insulin stimulation during 5-8 weeks. In addition, prenatal DHT treatment significantly decreased insulin-stimulated phosphorylation of AKT in the skeletal muscles of 6-week-old PNA rats. The abundance of IR substrate 1 (IRS1) and IRS2 was decreased in the skeletal muscles and liver after stimulation with insulin in the PNA group, whereas phosphorylation of insulin-signaling proteins was unaltered in the adipose tissue. These findings validate the contribution of prenatal androgen excess to metabolic derangements in pubertal female rats, and the impaired insulin signaling through IRS and AKT may result in the peripheral insulin resistance during pubertal development.

  17. Behavioural effects of prenatal exposure to carbon disulphide and to aromatol in rats.

    Science.gov (United States)

    Lehotzky, K; Szeberényi, J M; Ungváry, G; Kiss, A

    1985-01-01

    The neurotoxic effects of prenatal organosolvent inhalation were studied in rats, because of the expectation that a developing organism may be more sensitive than the adult to the induction of functional deficits. The aim was to determine whether prenatal exposure to the new organosolvent mixture, Aromatol, and the well known neurotoxic carbon disulphide, would impair reflex ontogeny or produce neurobehavioural dysfunctions in the offspring. Development of gait, motor coordination, and activity, avoidance learning and swimming were tested in the offspring of CFY rat mothers, exposed to CS2 inhalation (0, less than 10, 700 and 2000 mg/m3) and to Aromatol (0, 600, 1000 and 2000 mg/m3) on days 7-15 gestation. Prenatal CS2 inhalation induced dose related perinatal mortality of pups. Eye opening and the auditory startle were retarded. There were immature gait, motor incoordination, diminished open field activity and altered behavioural patterns on day 21 and 36 but they were nearly age-appropriate on day 90. As signs of disturbed learning ability, there were diminished performance and lengthened latency of the conditioned avoidance response, related to the concentrations administered. Contrary to expectations, prenatal Aromatol inhalation had no effect on maturation of gait, behaviour patterns, or learning ability.

  18. Effect of prenatal ethanol exposure on sexual motivation in adult rats.

    Science.gov (United States)

    Ávila, Mara Aparecida P; Marthos, Gabriela Cristina P; Oliveira, Liliane Gibram M; Figueiredo, Eduardo Costa; Giusti-Paiva, Alexandre; Vilela, Fabiana Cardoso

    2016-08-01

    Maternal alcohol use during pregnancy adversely affects prenatal and postnatal growth and increases the risk of behavioral deficits. The aim of the present study was to evaluate the effect of prenatal exposure to a moderate dose of alcohol on sexual motivation during adulthood. Rats were prenatally exposed to ethanol by feeding pregnant dams a liquid diet containing 25% ethanol-derived calories on days 6 through 19 of gestation. The controls consisted of pair-fed dams (receiving an isocaloric liquid diet containing 0% ethanol-derived calories) and dams with ad libitum access to a liquid control diet. The sexual motivation of offspring was evaluated during adulthood. The results revealed that the male and female pups of dams treated with alcohol exhibited reduced weight gain, which persisted until adulthood. Both male and female adult animals from dams that were exposed to alcohol showed a reduction in the preference score in the sexual motivation test. Taken together, these results provide evidence of the damaging effects of prenatal alcohol exposure on sexual motivation responses in adulthood. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Visual selective attention is impaired in children prenatally exposed to opioid agonist medication.

    Science.gov (United States)

    Konijnenberg, Carolien; Melinder, Annika

    2015-01-01

    To examine whether prenatal exposure to opioid agonist medication is associated with visual selective attention and general attention problems in early childhood. Twenty-two children (mean age = 52.17 months, SD = 1.81) prenatally exposed to methadone, 9 children (mean age = 52.41 months, SD = 1.42) prenatally exposed to buprenorphine and 25 nonexposed comparison children (mean age = 51.44 months, SD = 1.31) were tested. Visual selective attention was measured with a Tobii 1750 Eye Tracker using a spatial negative priming paradigm. Attention problems were measured using the Child Behavior Checklist. The comparison group demonstrated a larger spatial negative priming effect (mean = 23.50, SD = 45.50) than the exposed group [mean = -6.84, SD = 86.39, F(1,50) = 5.91, p = 0.019, η(2) = 0.11]. No difference in reported attention problems was found [F(1,51) = 1.63, p = 0.21, η(2) = 0.03]. Neonatal abstinence syndrome and prenatal exposure to marijuana were found to predict slower saccade latencies in the exposed group (b = 54.55, SE = 23.56, p = 0.03 and b = 88.86, SE = 32.07, p = 0.01, respectively). Although exposed children did not appear to have attention deficits in daily life, lower performance on the SNP task indicates subtle alteration in the attention system. © 2014 S. Karger AG, Basel.

  20. Prenatal PCBs disrupt early neuroendocrine development of the rat hypothalamus

    International Nuclear Information System (INIS)

    Dickerson, Sarah M.; Cunningham, Stephanie L.; Gore, Andrea C.

    2011-01-01

    Neonatal exposure to endocrine disrupting chemicals (EDCs) such as polychlorinated biphenyls (PCBs) can interfere with hormone-sensitive developmental processes, including brain sexual differentiation. We hypothesized that disruption of these processes by gestational PCB exposure would be detectable as early as the day after birth (postnatal day (P) 1) through alterations in hypothalamic gene and protein expression. Pregnant Sprague-Dawley rats were injected twice, once each on gestational days 16 and 18, with one of the following: DMSO vehicle; the industrial PCB mixture Aroclor 1221 (A1221); a reconstituted mixture of the three most prevalent congeners found in humans, PCB138, PCB153, and PCB180; or estradiol benzoate (EB). On P1, litter composition, anogenital distance (AGD), and body weight were assessed. Pups were euthanized for immunohistochemistry of estrogen receptor α (ERα) or TUNEL labeling of apoptotic cells or quantitative PCR of 48 selected genes in the preoptic area (POA). We found that treatment with EB or A1221 had a sex-specific effect on developmental apoptosis in the neonatal anteroventral periventricular nucleus (AVPV), a sexually dimorphic hypothalamic region involved in the regulation of reproductive neuroendocrine function. In this region, exposed females had increased numbers of apoptotic nuclei, whereas there was no effect of treatment in males. For ERα, EB treatment increased immunoreactive cell numbers and density in the medial preoptic nucleus (MPN) of both males and females, while A1221 and the PCB mixture had no effect. PCR analysis of gene expression in the POA identified nine genes that were significantly altered by prenatal EDC exposure, in a manner that varied by sex and treatment. These genes included brain-derived neurotrophic factor, GABA B receptors-1 and -2, IGF-1, kisspeptin receptor, NMDA receptor subunits NR2b and NR2c, prodynorphin, and TGFα. Collectively, these results suggest that the disrupted sexual differentiation

  1. Prenatal exposure to escitalopram and/or stress in rats: a prenatal stress model of maternal depression and its treatment

    Science.gov (United States)

    Bourke, Chase H.; Capello, Catherine F.; Rogers, Swati M.; Yu, Megan L.; Boss-Williams, Katherine A.; Weiss, Jay M.; Stowe, Zachary N.; Owens, Michael J.

    2014-01-01

    Rationale A rigorously investigated model of stress and antidepressant administration during pregnancy is needed to evaluate possible effects on the mother. Objective The objective of this study was to develop a model of clinically relevant prenatal exposure to an antidepressant and stress during pregnancy to evaluate the effects on maternal care behavior. Results Female rats implanted with 28 day osmotic minipumps delivering the SSRI escitalopram throughout pregnancy had serum escitalopram concentrations in a clinically observed range (17-65 ng/mL). A separate cohort of pregnant females exposed to a chronic unpredictable mild stress paradigm on gestational days 10-20 showed elevated baseline (305 ng/mL), and acute stress-induced (463 ng/mL), plasma corticosterone concentrations compared to unstressed controls (109 ng/mL). A final cohort of pregnant dams were exposed to saline (control), escitalopram, stress, or stress and escitalopram to determine the effects on maternal care. Maternal behavior was continuously monitored over the first 10 days post parturition. A reduction of 35% in maternal contact and 11% in nursing behavior was observed due to stress during the light cycle. Licking and grooming behavior was unaffected by stress or drug exposure in either the light or dark cycle. Conclusions These data indicate that: 1) clinically relevant antidepressant treatment during human pregnancy can be modeled in rats using escitalopram; 2) chronic mild stress can be delivered in a manner that does not compromise fetal viability; and 3) neither of these prenatal treatments substantially altered maternal care post parturition. PMID:23436130

  2. The effect of colostrum on pigs pre-natally or post-natally exposed to Schistosoma japonicum

    DEFF Research Database (Denmark)

    Techau, M.E.; Johansen, M.V.; Lind, Peter

    2004-01-01

    Pre-natal infection of Schistosoma japonicum in pigs may prove to be a useful model in shedding light on human pre-natal schistosomiasis. This study describes the effects of immune colostrum on worm burdens, tissue egg counts, liver pathology and crude worm or egg antigen-specific IgG and Ig......A responses, in groups of pigs pre-natally, pre-natally + post-natally or post-natally exposed to S. japonicum. Results suggest that pre-natal exposure and immune colostrum did not affect the establishment of a post-natal challenge infection. However, immune colostrum seemed to increase the levels of septal...

  3. Effect of low level prenatal X-irradiation on postnatal growth in the Wistar rat

    International Nuclear Information System (INIS)

    Jensh, R.P.; Brent, R.L.

    1988-01-01

    Forty-five pregnant Wistar strain rats were exposed to 0.0, 0.4, 0.6, or 0.8 Gy X-radiation on the 9th or 17th day of gestation to determined if prenatal X-irradiation would result in alterations in postnatal growth or growth rate. The mothers delivered their offspring, and the litters were reduced to a maximum of eight per litter on the second postnatal day. The 336 offspring were weighed weekly from day 3 until day 86, at which time they were killed, an autopsy was performed, and selected organs were removed and weighed. Postnatal growth rates did not differ significantly in irradiated offspring compared to sham irradiated animals. Irradiation on the 9th day, at any of the 3 dosage levels, did not result in significant differences in weekly weight. Weekly weight remained significantly lower due to irradiation on the 17th day of gestation. The gonadal weight ratio was significantly reduced in males irradiated on the 9th day. There were not other statistically significant changes in organ weight or organ/body weight ratios due to these levels of prenatal X-irradiation on the 9th or 17th day of pregnancy. These results indicate that low level prenatal X-irradiation, on the 17th day of rat gestation, causes prenatal growth retardation, evident at birth, which is not recuperable postnatally. Exposure to x-radiation at this time, however, does not affect the rate at which offspring grow during postnatal life. Offspring are smaller because they never fully recover from the original radiation-induced prenatal growth retardation

  4. Mother-child interaction and cognitive development in children prenatally exposed to methadone or buprenorphine.

    Science.gov (United States)

    Konijnenberg, Carolien; Sarfi, Monica; Melinder, Annika

    2016-10-01

    To assess the influence of mother-child interaction on children's cognitive development in a group of children prenatally exposed to methadone or buprenorphine. The study is part of a prospective longitudinal project investigating the development of children born to women in opioid maintenance therapy (OMT). The sample includes 67 children born between 2005 and 2007, 35 of which prenatally exposed to either methadone or buprenorphine and 32 non-exposed comparison children. Both groups scored within the normal range of development. However, the OMT group scored significantly lower on measures of cognitive development and mother-child interaction compared to the comparison group. Cognitive development was found to be affected by both group status, F(1,54)=5.65, p=0.02, η(2)=0.10 and mother-child interaction F(1,54)=5.26, p=0.03, η(2)=0.09. Behavioral inhibition (statue), sensorimotor function (imitating hand positions), and short-term memory (sentences) was influenced by group status while narrative memory and vocabulary were found to be more influenced by mother-child interaction. Different risk factors may influence different cognitive functions in children of women in OMT. Specifically, language-related cognitive skills may be more related to mother-child interaction while performance in higher cognitive functions requiring precise control over sensorimotor responses may be more sensitive to other factors such as prenatal OMT exposure, genetics, and/or prenatal exposure to other substances. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Prenatal exposure to nanosized zinc oxide in rats: neurotoxicity and postnatal impaired learning and memory ability.

    Science.gov (United States)

    Xiaoli, Feng; Junrong, Wu; Xuan, Lai; Yanli, Zhang; Limin, Wei; Jia, Liu; Longquan, Shao

    2017-04-01

    To examine the neurotoxicity of prenatal exposure to ZnO nanoparticles on rat offspring. Pregnant Sprague-Dawley rats were exposed to ZnO nanoparticles (NPs) by gavage. Toxicity was assessed including zinc biodistribution, cerebral histopathology, antioxidant status and learning and memory capability. A significantly elevated concentration of zinc was detected in offspring brains. Transmission electron microscope observations showed abnormal neuron ultrastructures. Histopathologic changes such as decreased proliferation and higher apoptotic death were observed. An obvious imbalanced antioxidant status occurred in brains. Adult experimental offspring exhibited impaired learning and memory behavior in the Morris water maze test compared with control groups. These adverse effects on offspring brain may cause impaired learning and memory capabilities in adulthood, particularly in female rats.

  6. Development Enamel Defects in Children Prenatally Exposed to Anti-Epileptic Drugs

    DEFF Research Database (Denmark)

    Jacobsen, Pernille Endrup; Henriksen, Tine Brink; Haubek, Dorte

    2013-01-01

    Objective Some anti-epileptic drugs (AED) have well-known teratogenic effects. The aim of the present study was to elucidate the effect of prenatal exposure to AED and the risk of enamel defects in the primary and permanent dentition. Methods A total of 38 exposed and 129 non-exposed children, 6......–10 years of age, were recruited from the Aarhus Birth Cohort and the Department of Neurology, Viborg Regional Hospital, Denmark. Medication during pregnancy was confirmed by the Danish Prescription Database. All children had their teeth examined and outcomes in terms of enamel opacities and enamel...... hypoplasia were recorded. Results Children prenatally exposed to AED have an increased prevalence of enamel hypoplasia (11% vs. 4%, odds ratio (OR) = 3.6 [95% confidence interval (CI): 0.9 to 15.4]), diffuse opacities (18% vs. 7%, OR = 3.0; [95% CI: 1.0 to 8.7, p3) white opacities (18...

  7. Impact of low dose prenatal ethanol exposure on glucose homeostasis in Sprague-Dawley rats aged up to eight months.

    Directory of Open Access Journals (Sweden)

    Megan E Probyn

    Full Text Available Excessive exposure to alcohol prenatally has a myriad of detrimental effects on the health and well-being of the offspring. It is unknown whether chronic low-moderate exposure of alcohol prenatally has similar and lasting effects on the adult offspring's health. Using our recently developed Sprague-Dawley rat model of 6% chronic prenatal ethanol exposure, this study aimed to determine if this modest level of exposure adversely affects glucose homeostasis in male and female offspring aged up to eight months. Plasma glucose concentrations were measured in late fetal and postnatal life. The pancreas of 30 day old offspring was analysed for β-cell mass. Glucose handling and insulin action was measured at four months using an intraperitoneal glucose tolerance test and insulin challenge, respectively. Body composition and metabolic gene expression were measured at eight months. Despite normoglycaemia in ethanol consuming dams, ethanol-exposed fetuses were hypoglycaemic at embryonic day 20. Ethanol-exposed offspring were normoglycaemic and normoinsulinaemic under basal fasting conditions and had normal pancreatic β-cell mass at postnatal day 30. However, during a glucose tolerance test, male ethanol-exposed offspring were hyperinsulinaemic with increased first phase insulin secretion. Female ethanol-exposed offspring displayed enhanced glucose clearance during an insulin challenge. Body composition and hepatic, muscle and adipose tissue metabolic gene expression levels at eight months were not altered by prenatal ethanol exposure. Low-moderate chronic prenatal ethanol exposure has subtle, sex specific effects on glucose homeostasis in the young adult rat. As aging is associated with glucose dysregulation, further studies will clarify the long lasting effects of prenatal ethanol exposure.

  8. Prenatal Caffeine Exposure Impairs Pregnancy in Rats

    Directory of Open Access Journals (Sweden)

    Maryam Yadegari

    2016-12-01

    Full Text Available Background: In recent years, concerns have been raised about human reproductive disorders. Caffeine consumption is increasing by the world’s population and there is a relationship between caffeine intake and adverse reproductive outcomes. The aim of this study was to evaluate the effects of caffeine on implantation sites, number of live births, birth weight, crown-rump length (CRL and abnormality in pregnant rats. Materials and Methods: In this experimental study, 40 female albino rats (170-190 g were randomly divided into two experimental and two control groups (n=10/each group. In both experimental groups, animals received caffeine intraperitoneally (IP: 150 mg/kg/day on days 1-5 of pregnancy. In experimental group 1, treated animals were euthanized on day 7of pregnancy and the number of implantation sites was counted. In experimental group 2, treated animals maintained pregnant and after delivery, the number of live births, birth weight, CRL and abnormality of neonates were investigated. In control group, animals received IP injections of distilled water. Data were analyzed by independent t test. Results: Results showed that administration of caffeine significantly decreased the number of implantation sites, number of live births and CRL as compared with control group (P<0.05. There were no significant differences regarding birth weight and abnormality of neonate rats between experimental and control groups. Conclusion: These results suggest that caffeine caused anti-fertility effect and significantly decreased CRL in neonate rats.

  9. Prenatal Mercuric Chloride Exposure Causes Developmental Deficits in Rat Cortex

    Directory of Open Access Journals (Sweden)

    Tayebeh Rastegar

    2011-09-01

    Full Text Available Introduction: Environmental pollution with heavy metals such as mercury is a major health problem. Growing studies on the field have shown the deleterious effects of mercury on human and nonhuman nervous system, especially in infants, however the effects of prenatal exposure to mercuricchloride on cortical development are not yet well understood. The aim of this study was to investigate the effect of prenatal exposure to mercuric chloride on morphological characteristics of brain cortex. Methods: Mercuric chloride (2 mg/kg or normal saline were injected (I.P. to 36 Sprague – dawley rats in the 8th, 9th or 10th day of gestation. The embryos were surgically removed in the 15th day of gestation, and brain cortices were studied by histological techniques. Results: Histological studies showed that embryos of mercuric chloride treated rats hadcortical neuronal disarrangement withdifferent orientations of nuclei, increased diameter of cortex, increased mitosis of cells, increased cell death, decreased cellular density and increased intracellular space. Conclusion: These findings suggest some micro structural abnormalities in cortical regions after prenatal exposure to mercuric chloride. These structural abnormalities may underliesome neurologic disturbances following mercury intoxication.

  10. Effects of prenatal low dose beta radiation from tritiated water on rat hippocampus neurons. Electrophysiological and neuro behavioural changes

    International Nuclear Information System (INIS)

    Gao Weimin; Zhou Xiangyan

    1997-01-01

    Pregnent Wistar rats were exposed to tritiated water (HTO) on day 13 of gestation so that for their offsprings, the absorbed doses were estimated to be 0.000, 0.044, 0.088 and 0.264 Gy. The influence of HTO to the morphology and number of hippocampus pyramidal neurons and the maximum electric current of Ca 2+ in neurons was observed for the in-vitro-cultured hippocampus of new-born rats and the learning and memory behaviours were assessed by the electric avoidance reflex test in a Y-maze and the condition reflex test for young rats. The results show that prenatal exposure to HTO in a cumulative dose of 0.088 Gy can cause a reduction in number of neurons in hippocampus cultured in vitro, and that the electric current of Ca 2+ tends to decline with cumulative dose increasing, with the significant decrease in offsprings prenatally exposed to HTO in dose of 0.264 Gy. The results of electric avoidance reflex test in a Y-maze and condition reflex test indicate that for young rats prenatally exposed to HTO, a cumulative dose of 0.088 Gy could induce damage in their learning and memory behaviours

  11. Beneficial effects of co-treatment with dextromethorphan on prenatally methadone-exposed offspring.

    Science.gov (United States)

    Chiang, Yao-Chang; Ye, Li-Ci; Hsu, Kuei-Ying; Liao, Chien-Wei; Hung, Tsai-Wei; Lo, Wan-Jou; Ho, Ing-Kang; Tao, Pao-Luh

    2015-03-20

    Heroin use among young women of reproductive age has drawn much attention around the world. Although methadone is widely used in maintenance therapy for heroin/morphine addiction, the long-term effects of prenatal exposure to methadone and preventative therapy remain unclear. For revealing this question, female pregnant Sprague-Dawley rats were sub-grouped to receive (1) vehicle, (2) methadone 5 mg/kg at embryonic day 3 (E3) and then 7 mg/kg from E4 to E20, (3) dextromethorphan (DM) 3 mg/kg, and (4) methadone + DM (the rats received methadone followed by DM treatment), subcutaneously, twice a day from E3 to E20. The body weight, natural withdrawal, pain sensitivity, ED50, conditioned place preference and water maze were conducted at different postnatal stages (P1 to P79) of offspring. The quantitative real-time RT-PCR and electrophysiology were also used to measure the gene expression of opioid receptors in the spinal cord and changes of LTP/LTD in the hippocampus, separately. Prenatal exposure to methadone or DM did not affect survival rate, body weight, water maze and LTP or LTD of offspring. However, prenatal methadone significantly increased the withdrawal symptoms, pain sensitivity, addiction liability and decreased the mRNA expression of pain related opioid receptors. Co-administration of DM with methadone in the maternal rats effectively prevented these abnormalities of offspring induced by methadone. Our study clearly showed that co-administration of dextromethorphan with methadone in the maternal rats prevented the adverse effects induced by prenatal methadone exposure. It implies that dextromethorphan may have a potential to be used in combination with methadone for maintenance treatment in pregnant heroin-addicted women to prevent the adverse effects induced by methadone on offspring.

  12. The effects of prenatal cocaine, post-weaning housing and sex on conditioned place preference in adolescent rats.

    Science.gov (United States)

    Dow-Edwards, Diana; Iijima, Maiko; Stephenson, Stacy; Jackson, April; Weedon, Jeremy

    2014-04-01

    Gestational exposure to cocaine now affects several million people including adolescents and young adults. Whether prenatal drug exposures alter an individual's tendency to take and/or abuse drugs is still a matter of debate. This study sought to answer the question "Does prenatal exposure to cocaine, in a dose-response fashion, alter the rewarding effects of cocaine using a conditioned place preference (CPP) procedure during adolescence in the rat?" Further, we wanted to assess the possible sex differences and the role of being raised in an enriched versus impoverished environment. Virgin female Sprague-Dawley rats were dosed daily with cocaine at 30 mg/kg (C30), 60 mg/kg (C60), or vehicle intragastrically prior to mating and throughout gestation. Pups were culled, fostered and, on postnatal day (PND) 23, placed into isolation cages or enriched cages with three same-sex littermates and stimulus objects. On PND43-47, CPP was determined across a range of cocaine doses. C30 exposure increased sensitivity to the rewarding effects of cocaine in adolescent males, and being raised in an enriched environment further enhanced this effect. Rats exposed to C60 resembled the controls in cocaine CPP. Overall, females were modestly affected by prenatal cocaine and enrichment. These data support the unique sensitivity of males to the effects of gestational cocaine, that moderate prenatal cocaine doses produce greater effects on developing reward circuits than high doses and that housing condition interacts with prenatal treatment and sex such that enrichment increases cocaine CPP mostly in adolescent males prenatally exposed to moderate cocaine doses.

  13. Prenatal ethanol exposure alters steroidogenic enzyme activity in newborn rat testes.

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    Kelce, W R; Rudeen, P K; Ganjam, V K

    1989-10-01

    We have examined the in utero effects of ethanol exposure on testicular steroidogenesis in newborn male pups. Pregnant Sprague-Dawley rats were fed a liquid ethanol diet (35% ethanol-derived calories), a pair-fed isocaloric liquid diet, or a standard laboratory rat chow and water diet beginning on Day 12 of gestation and continuing through parturition. Although there were no significant differences in the enzymatic activity of 5-ene-3 beta-hydroxysteroid dehydrogenase/isomerase or C17,20-lyase, the enzymatic activity of 17 alpha-hydroxylase was significantly (p less than 0.01) reduced (i.e., approximately 36%) in the ethanol-exposed pups compared to those from the pair-fed and chow treatment groups. This lesion in testicular steroidogenic enzyme activity in newborn male pups exposed to alcohol in utero was transient as 17 alpha-hydroxylase activity from the ethanol-exposed animals returned to control levels by postnatal Day 20 and remained at control levels through adulthood (postnatal Day 60). These data suggest that the suppression of the perinatal testosterone surge in male rats exposed to alcohol in utero and the associated long term demasculinizing effects of prenatal ethanol exposure might be the result of reduced testicular steroidogenic enzyme activity in the perinatal animal.

  14. Active coping of prenatally stressed rats in the forced swimming test: involvement of the Nurr1 gene.

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    Montes, Pedro; Ruiz-Sánchez, Elizabeth; Calvillo, Minerva; Rojas, Patricia

    2016-09-01

    Depending on genetic predisposition, prenatal stress may result in vulnerability or resilience to develop psychiatric disorders in adulthood. Nurr1 is an immediate early gene, important in the brain for the stress response. We tested the hypothesis that prenatal stress and the decrease of hippocampal Nurr1 alter offspring behavioral responses in the forced swimming test (FST). Pregnant Wistar rats were exposed to restraint stress (45 min, thrice daily) from gestation day 14. Prenatally stressed (PS) and non-prenatally stressed (NPS) male offspring were treated bilaterally with a Nurr1 antisense oligodeoxynucleotide (ODN; or control) into the hippocampus at 97 d of age. After 1 h, the rats were exposed to the FST (acute stressor) to analyze their behavioral responses. Thirty minutes after the FST, we analyzed the gene expression of Nurr1, Bdnf and Nr3c1 (genes for Nurr1, brain-derived neurotrophic factor (BDNF) and glucocorticoid receptor (GR), respectively) in the hippocampus, prefrontal cortex (PFC) and hypothalamus. Results showed that the decrease of hippocampal Nurr1 after the antisense ODN in adult NPS rats induces immobility (indicating depressive-like behavior). The PS adult rats, including the group with decreased hippocampal Nurr1, presented low immobility in the FST. This low immobility was concordant with maintenance of Nurr1 and Bdnf expression levels in the three analyzed brain regions; Nr3c1 gene expression was also maintained in the PFC and hypothalamus. These findings suggest that Nurr1 and associated genes could participate in the brain modifications induced by prenatal stress, allowing active coping (resilience) with acute stress in adulthood.

  15. Disturbances of perinatal carbohydrate metabolism in rats exposed to methylmercury in utero

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    Snell, K; Ashby, S L; Barton, S J

    1977-12-01

    Pregnant rats were given a single subcutaneous injection of methylmercuric chloride (at 4 or 8 mg/kg) on the ninth day of gestation. Fetal (2 days prenatal), newborn and postnatal (6 days post partum) animals from the methylmercury-treated mothers were investigated with respect to parameters of carbohydrate metabolism. In the absence of any physical abnormalities, fetal rats exposed to methylmercury in utero showed diminished concentrations of plasma glucose and liver glycogen concentrations and a lower hepatic glucose-6-phosphatase activity compared to control animals. Newborn rats from the methylmercury-treated mothers showed an impairment in glycogen mobilization in the first hours of extra-uterine life which was accompanied by a severe and protracted hypoglycemic response. Postnatal rats exposed to methylmercury in utero exhibited higher liver glycogen concentration and decreased body weights compared to control rats. The results point to a derangement of perinatal carbohydrate metabolism in the offspring of pregnant rats exposed briefly to low doses of methylmercury during gestation (''metabolic teratogenesis''). The postnatal hypoglycemic episode in exposed rats may contribute to the pathogenesis of the neurological disturbances revealed by these animals in later life.

  16. Go/no-go discriminated avoidance learning in prenatally x-irradiated rats

    International Nuclear Information System (INIS)

    Tamaki, Y.; Inouye, M.

    1988-01-01

    Male Fischer344 rats were exposed to x-irradiation at a dose of 200 rad on Day 17 of gestation. Irradiated and control rats were tested at 10-13 weeks of age with the paradigm of go/no-go (active-passive) discriminated avoidance conditioning for three consecutive daily sessions. During the first conditioning session, they learned only active avoidance responses to two different warning signals. During the second and third sessions, they learned active and passive avoidance responses: in response to one warning signal, rats were required to make an active response to avoid a shock, but not to run in response to the other signal in order to avoid a shock. Prenatally irradiated rats made more active avoidance responses to both warning signals than controls (first session). In the early training phase of the go/no-go task, irradiated rats performed significantly higher active and lower passive avoidance responses than controls. Irradiated rats established a strong tendency to respond actively to the no-go signal, but eventually learned to respond to it

  17. The effect of exposure of rats during prenatal period to radiation spreading from mobile phones on renal development.

    Science.gov (United States)

    Bedir, Recep; Tumkaya, Levent; Şehitoğlu, İbrahim; Kalkan, Yıldıray; Yilmaz, Adnan; Şahin, Osman Zikrullah

    2015-03-01

    The aim of this study was to investigate the effects of exposure to a 900-MHz electromagnetic field (EMF) produced by mobile phones on the renal development of prenatal rats. Histopathological changes and apoptosis in the kidneys, together with levels of urea, creatinine and electrolyte in serum were determined. A total of 14 Sprague-Dawley rats were studied. Pregnant rats were divided into two equal groups: a control group and an EMF-exposed group. The study group was exposed to 900-MHz of EMF during the first 20 days of pregnancy, while the control group was unexposed to EMF. Sections obtained from paraffin blocks were stained for caspase-3 by immunohistochemistry, hematoxylin-eosin and Masson's trichrome. Mild congestion and tubular defects, and dilatation of Bowman's capsule were observed in the kidney tissues of rats in the exposed group. Apoptosis was evaluated using anti-caspase-3; stronger positive staining was observed in the renal tubular cells in the study group than those of the control group. Although there was a significant difference between the study and control groups in terms of K+ level (p0.05). Our study shows that the electromagnetic waves propagated from mobile phones have harmful effects on the renal development of prenatal rats.

  18. Neurodevelopment of children prenatally exposed to selective reuptake inhibitor antidepressants: Toronto sibling study.

    Science.gov (United States)

    Nulman, Irena; Koren, Gideon; Rovet, Joanne; Barrera, Maru; Streiner, David L; Feldman, Brian M

    2015-07-01

    The reproductive safety of selective reuptake inhibitor (SRI) antidepressants needs to be established to provide optimal control of maternal depression while protecting the fetus. To define a child's neurodevelopment following prenatal exposure to SRIs and to account for genetic and environmental confounders in a sibling design using the Toronto Motherisk prospective database. Intelligence and behavior of siblings prenatally exposed and unexposed to SRIs were assessed by using the Wechsler Preschool and Primary Scale of Intelligence-Third Edition, Child Behavior Checklist, and Conners Parent Rating Scale-Revised and subsequently compared. Mothers, diagnosed with depression using DSM-IV, were assessed for intelligence quotient (IQ) and for severity of depressive symptoms with the Center for Epidemiologic Studies Depression scale. Prenatal drug doses and durations of exposure, child's age, child's sex, birth order, severity of maternal depression symptoms, and Full Scale IQ, the primary outcome measure, of both the mother and the child were considered in the analyses. Forty-five sibling pairs (ages 3 years to 6 years 11 months, prenatally exposed and unexposed to SRIs) did not differ in their mean ± SD Full Scale IQs (103 ± 13 vs 106 ± 12; P = .30; 95% CI, -7.06 to 2.21) or rates of problematic behaviors. Significant predictor of children's intelligence was maternal IQ (P = .043, β = 0.306). Severity of maternal depression was a significant predictor of Child Behavior Checklist Internalizing (P = .019, β = 0.366), Externalizing (P = .003, β = 0.457), and Total scores (P = .001, β = 0.494). Drug doses and durations of exposure during pregnancy did not predict any outcomes of interest in the exposed siblings. SRI antidepressants were not found to be neurotoxic. Maternal depression may risk the child's future psychopathology. The sibling design in behavioral teratology aids in separating the effects of maternal depression from those of SRIs, providing stronger

  19. Depression-like effect of prenatal buprenorphine exposure in rats.

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    Chih-Jen Hung

    Full Text Available Studies indicate that perinatal opioid exposure produces a variety of short- and long-term neurobehavioral consequences. However, the precise modes of action are incompletely understood. Buprenorphine, a mixed agonist/antagonist at the opioid receptors, is currently being used in clinical trials for managing pregnant opioid addicts. This study provides evidence of depression-like consequence following prenatal exposure to supra-therapeutic dose of buprenorphine and sheds light on potential mechanisms of action in a rat model involving administration of intraperitoneal injection to pregnant Sprague-Dawley rats starting from gestation day 7 and lasting for 14 days. Results showed that pups at postnatal day 21 but not the dams had worse parameters of depression-like neurobehaviors using a forced swimming test and tail suspension test, independent of gender. Neurobehavioral changes were accompanied by elevation of oxidative stress, reduction of plasma levels of brain-derived neurotrophic factor (BDNF and serotonin, and attenuation of tropomyosin-related kinase receptor type B (TrkB phosphorylation, extracellular signal-regulated kinase (ERK phosphorylation, protein kinase A activity, cAMP response element-binding protein (CREB phosphorylation, and CREB DNA-binding activity. Since BDNF/serotonin and CREB signaling could orchestrate a positive feedback loop, our findings suggest that the induction of oxidative stress, reduction of BDNF and serotonin expression, and attenuation of CREB signaling induced by prenatal exposure to supra-therapeutic dose of buprenorphine provide evidence of potential mechanism for the development of depression-like neurobehavior.

  20. Prenatal stress, regardless of concurrent escitalopram treatment, alters behavior and amygdala gene expression of adolescent female rats

    Science.gov (United States)

    Ehrlich, David E.; Neigh, Gretchen N.; Bourke, Chase H.; Nemeth, Christina L.; Hazra, Rimi; Ryan, Steven J.; Rowson, Sydney; Jairam, Nesha; Sholar, Courtney; Rainnie, Donald G.; Stowe, Zachary N.; Owens, Michael J.

    2015-01-01

    Depression during pregnancy has been linked to in utero stress and is associated with long-lasting symptoms in offspring, including anxiety, helplessness, attentional deficits, and social withdrawal. Depression is diagnosed in 10-20% of expectant mothers, but the impact of antidepressant treatment on offspring development is not well documented, particularly for females. Here, we used a prenatal stress model of maternal depression to test the hypothesis that in utero antidepressant treatment could mitigate the effects of prenatal stress. We also investigated the effects of prenatal stress and antidepressant treatment on gene expression related to GABAergic and serotonergic neurotransmission in the amygdala, which may underlie behavioral effects of prenatal stress. Nulliparous female rats were implanted with osmotic minipumps delivering clinically-relevant concentrations of escitalopram and mated. Pregnant dams were exposed to 12 days of mixed-modality stressors, and offspring were behaviorally assessed in adolescence (postnatal day 28) and adulthood (beyond day 90) to determine the extent of behavioral change. We found that in utero stress exposure, regardless of escitalopram treatment, increased anxiety-like behavior in adolescent females and profoundly influenced amygdala expression of the chloride transporters KCC2 and NKCC1, which regulate GABAergic function. In contrast, prenatal escitalopram exposure alone elevated amygdala expression of 5-HT1A receptors. In adulthood, anxiety-like behavior returned to baseline and gene expression effects in the amygdala abated, whereas deficits emerged in novel object recognition for rats exposed to stress during gestation. These findings suggest prenatal stress causes age-dependent deficits in anxiety-like behavior and amygdala function in female offspring, regardless of antidepressant exposure. PMID:26032436

  1. Prenatal exposure to aflatoxin B1: developmental, behavioral, and reproductive alterations in male rats

    Science.gov (United States)

    Supriya, Ch.; Reddy, P. Sreenivasula

    2015-06-01

    studies revealed a significant decrease in the mating index in experimental rats with an increase in the pre- and post-implantation losses in rats mated with prenatal AfB1-exposed males, indicating poor male reproductive performance. These results indicate that in utero exposure to AfB1 severely compromised postnatal development of neonatal rats, and caused a delay in testes descent and reduction in steroidogenesis and spermatogenesis that were accomplished by suppressed reproduction at adulthood.

  2. Neurobehavioral Deficits and Increased Blood Pressure in School-Age Children Prenatally Exposed to Pesticides

    Science.gov (United States)

    Harari, Raul; Julvez, Jordi; Murata, Katsuyuki; Barr, Dana; Bellinger, David C.; Debes, Frodi; Grandjean, Philippe

    2010-01-01

    Background The long-term neurotoxicity risks caused by prenatal exposures to pesticides are unclear, but a previous pilot study of Ecuadorian school children suggested that blood pressure and visuospatial processing may be vulnerable. Objectives In northern Ecuador, where floriculture is intensive and relies on female employment, we carried out an intensive cross-sectional study to assess children’s neurobehavioral functions at 6–8 years of age. Methods We examined all 87 children attending two grades in the local public school with an expanded battery of neurobehavioral tests. Information on pesticide exposure during the index pregnancy was obtained from maternal interview. The children’s current pesticide exposure was assessed from the urinary excretion of organophosphate metabolites and erythrocyte acetylcholine esterase activity. Results Of 84 eligible participants, 35 were exposed to pesticides during pregnancy via maternal occupational exposure, and 23 had indirect exposure from paternal work. Twenty-two children had detectable current exposure irrespective of their prenatal exposure status. Only children with prenatal exposure from maternal greenhouse work showed consistent deficits after covariate adjustment, which included stunting and socioeconomic variables. Exposure-related deficits were the strongest for motor speed (Finger Tapping Task), motor coordination (Santa Ana Form Board), visuospatial performance (Stanford-Binet Copying Test), and visual memory (Stanford-Binet Copying Recall Test). These associations corresponded to a developmental delay of 1.5–2 years. Prenatal pesticide exposure was also significantly associated with an average increase of 3.6 mmHg in systolic blood pressure and a slight decrease in body mass index of 1.1 kg/m2. Inclusion of the pilot data strengthened these results. Conclusions These findings support the notion that prenatal exposure to pesticides—at levels not producing adverse health outcomes in the mother

  3. Dietary choline levels modify the effects of prenatal alcohol exposure in rats.

    Science.gov (United States)

    Idrus, Nirelia M; Breit, Kristen R; Thomas, Jennifer D

    Prenatal alcohol exposure can cause a range of physical and behavioral alterations; however, the outcome among children exposed to alcohol during pregnancy varies widely. Some of this variation may be due to nutritional factors. Indeed, higher rates of fetal alcohol spectrum disorders (FASD) are observed in countries where malnutrition is prevalent. Epidemiological studies have shown that many pregnant women throughout the world may not be consuming adequate levels of choline, an essential nutrient critical for brain development, and a methyl donor. In this study, we examined the influence of dietary choline deficiency on the severity of fetal alcohol effects. Pregnant Sprague-Dawley rats were randomly assigned to receive diets containing 40, 70, or 100% recommended choline levels. A group from each diet condition was exposed to ethanol (6.0g/kg/day) from gestational day 5 to 20 via intubation. Pair-fed and ad lib lab chow control groups were also included. Physical and behavioral development was measured in the offspring. Prenatal alcohol exposure delayed motor development, and 40% choline altered performance on the cliff avoidance task, independent of one another. However, the combination of low choline and prenatal alcohol produced the most severe impairments in development. Subjects exposed to ethanol and fed the 40% choline diet exhibited delayed eye openings, significantly fewer successes in hindlimb coordination, and were significantly overactive compared to all other groups. These data suggest that suboptimal intake of a single nutrient can exacerbate some of ethanol's teratogenic effects, a finding with important implications for the prevention of FASD. Copyright © 2016. Published by Elsevier Inc.

  4. Brain abnormalities among the mentally retarded prenatally exposed atomic bomb survivors

    International Nuclear Information System (INIS)

    Schull, W.J.; Otake, Masanori; Nishitani, Hiromu; Hasuo, Kanehiro; Kobayashi, Takuro; Goto, Ikuo.

    1992-07-01

    An increased occurrence of severe mental retardation, with or without accompanying small head size, at specific gestational ages has been the most conspicuous effect on brain development of prenatal exposure to the bombings of Hiroshima and Nagasaki. A variety of biological mechanisms could be responsible for this finding, including cell killing and mismanaged neuronal migration. We describe here the findings on magnetic resonance imaging of the brains of five of these mentally retarded individuals, all of whom were exposed in the 8th through the 15th weeks following fertilization, the gestational period shown to be the most vulnerable to radiation-related damage. In the two cases exposed at the 8th or 9th week following fertilization, large areas of ectopic gray matter are seen, strong evidence of a failure of the neurons to migrate to their proper functional sites. The two individuals exposed in the 12th or 13th week show no readily recognized ectopic gray areas but do show mild macrogyria, which implies some impairment in the development of the cortical zone. Moreover, both have mega cisterna magna. Finally, the one individual seen who was exposed still later in development, in the 15th week, shows none of the changes seen in the other four individuals. This person's brain, though small, appears to have normal architecture. These findings are discussed in terms of the embryological events transpiring at the time of the prenatal exposure of these individuals to ionizing radiation. (author)

  5. The developmental neurobehavioral effects of fenugreek seeds on prenatally exposed mice.

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    Khalki, Loubna; Bennis, Mohamed; Sokar, Zahra; Ba-M'hamed, Saâdia

    2012-01-31

    Fenugreek (Trigonella foenum graecum (L.)), is a medicinal plant whose seeds and leaves are widely used in Moroccan traditional medicine. Consumption of fenugreek seeds during pregnancy has been associated with a range of congenital malformations, including hydrocephalus, anencephaly and spina bifida. In previous work we have shown that exposure of pregnant mice to aqueous extract of fenugreek seeds (AEFS) leads to reduced litter size, intrauterine growth retardation, and malformations. However, there have been no studies to date of its longer-term neurobehavioral effects. We investigated these effects in prenatally exposed mice. Pregnant females were exposed to 0, 500 or 1000 mg/kg/day AEFS, by gavage, for the whole period of gestation. Pups body weight was measured at 1, 7, 14, 21 and 28 day of age. Behavior of progeny was evaluated three weeks after birth using the open field, the rotarod test and the continuous alternation task by the T-maze. At 28 postnatal day age, brain of progeny was removed and cut for histological evaluation. The progeny of exposed mice displayed reduced body weight at birth (1000 mg/kg group: 27%; 500 mg/kg group: 32%) and reduced brain weight (10% in both treated groups). Both males and females mice prenatally exposed to AEFS displayed a significant decrease in the locomotor activity, in the boli deposits during the open field test and in motor coordination. These results seem to show that exposure to AEFS induces a depressive effect in the offspring. Assessment on a continuous alternation T-maze test showed a significant reduction in successful spontaneous alternations in males and females but only in the 1000 mg/kg group. These results suggest that prenatal exposure of mice to high dose of fenugreek seeds causes growth retardation and altered neurobehavioral performance in the post-weaning period in both male and female. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  6. Effect of prenatal exposure to different salt concentration on the third month's weight and blood pressure in wistar rat

    International Nuclear Information System (INIS)

    Fereidoun, H.

    2009-01-01

    In utero alterations in fluid and electrolyte endocrine systems may result in permanent effects on offspring. A low sodium intake during prenatal life jeopardizes growth in young rats, prenatal high-salt diet in Sprague-Dawley rats caused an increase in MAP at postnatal day 30. The objective of this study was to determine the effect of prenatal exposure to different salt concentrations on the third month's weight and blood pressure in Wistar rat. This study was performed at the Department of Physiology, Isfahan University of Medical Science, Isfahan, Iran, over a period from 1998 to 2003. Six groups of rat, 1 male and 5 female in each group were exposed to 0.5, 1, 1.4, 1.6, 1.8 and 2 percent of salt concentrations during pre-pregnancy, pregnancy and lactation period, another test group consumed distilled water and control group used Isfahan tap water, other living conditions for all groups were similar. Exposure to different salt concentrations on the third month's weight and blood pressure was evaluated. Prenatal exposure to 0.5 and 1% salt concentrations gives birth to more alive and healthy infants, and third month's weight increased significantly, but blood pressure was not influenced significantly. Salt concentrations higher than 1% increased the maternal and infant mortality rate and blood pressure significantly, but some concentrations decreased third month's weight significantly. Level of dietary salt during intrauterine development can influence on the number of alive and healthy infants, birth weight, third month' weight and blood pressure significantly. There is no need to introduce a salt restricted diet in prenatal care, a balanced diet in sodium during pregnancy is recommended, high salt diet creates harmful effect. (author)

  7. Prenatal programming of rat cortical collecting tubule sodium transport.

    Science.gov (United States)

    Cheng, Chih-Jen; Lozano, German; Baum, Michel

    2012-03-15

    Prenatal insults have been shown to lead to elevated blood pressure in offspring when they are studied as adults. Prenatal administration of dexamethasone and dietary protein deprivation have demonstrated that there is an increase in transporter abundance for a number of nephron segments but not the subunits of the epithelial sodium channel (ENaC) in the cortical collecting duct. Recent studies have shown that aldosterone is elevated in offspring of protein-deprived mothers when studied as adults, but the physiological importance of the increase in serum aldosterone is unknown. As an indirect measure of ENaC activity, we compared the natriuretic response to benzamil in offspring of mothers who ate a low-protein diet (6%) with those who ate a normal diet (20%) for the last half of pregnancy. The natriuretic response to benzamil was greater in the 6% group (821.1 ± 161.0 μmol/24 h) compared with the 20% group (279.1 ± 137.0 μmol/24 h), consistent with greater ENaC activity in vivo (P sodium transport (-1.9 ± 3.1 pmol·mm(-1)·min(-1)), the offspring of rats that ate a 6% protein diet during the last half of pregnancy had a net sodium flux of 10.7 ± 2.6 pmol·mm(-1)·min(-1) (P = 0.01) in tubules perfused in vitro. Sodium transport was measured using ion-selective electrodes, a novel technique allowing measurement of sodium in nanoliter quantities of fluid. Thus we directly demonstrate that there is prenatal programming of cortical collecting duct sodium transport.

  8. Methylomic changes in individuals with psychosis, prenatally exposed to endocrine disrupting compounds: Lessons from diethylstilbestrol.

    Directory of Open Access Journals (Sweden)

    Fabrice Rivollier

    Full Text Available In the Western world, between 1940 and 1970, more than 2 million people were exposed in utero to diethylstilbestrol (DES. In exposed individuals, and in their descendants, adverse outcomes have been linked to such exposure, including cancers, genital malformations, and less consistently, psychiatric disorders. We aimed to explore whether prenatal DES exposure would be associated with DNA methylation changes, and whether these epigenetic modifications would be associated with increased risk of psychosis.From 247 individuals born from mothers exposed to DES, we selected 69 siblings from 30 families. In each family, at least one sibling was exposed in utero to DES. We performed a methylome-wide association study using HumanMethylation450 DNA Analysis BeadChip® in peripheral blood. We analyzed methylation changes at individual CpGs or regions in exposed (n = 37 versus unexposed individuals (n = 32. We also compared exposed individuals with (n = 7 and without psychosis (n = 30.There were more individuals with schizophrenia in the DES-exposed group. We found no significant differences between exposed and unexposed individuals with respect to differentially methylated CpGs or regions. The largest difference was in a region near the promoter of an ADAMTS proteoglycanase gene (ADAMTS9. Compared to exposed individuals without psychosis, exposed individuals with psychosis had differential methylation in the region encompassing the gene encoding the zinc finger protein 57 (ZFP57.In utero exposure to DES was not associated with methylation changes at specific CpG or regions. In exposed individuals, however, psychosis was associated with specific methylomic modifications that could impact neurodevelopment and neuroplasticity.

  9. Anxiety-like behaviour and associated neurochemical and endocrinological alterations in male pups exposed to prenatal stress.

    Science.gov (United States)

    Laloux, Charlotte; Mairesse, Jérôme; Van Camp, Gilles; Giovine, Angela; Branchi, Igor; Bouret, Sebastien; Morley-Fletcher, Sara; Bergonzelli, Gabriela; Malagodi, Marithé; Gradini, Roberto; Nicoletti, Ferdinando; Darnaudéry, Muriel; Maccari, Stefania

    2012-10-01

    Epidemiological studies suggest that emotional liability in infancy could be a predictor of anxiety-related disorders in the adulthood. Rats exposed to prenatal restraint stress ("PRS rats") represent a valuable model for the study of the interplay between environmental triggers and neurodevelopment in the pathogenesis of anxious/depressive like behaviours. Repeated episodes of restraint stress were delivered to female Sprague-Dawley rats during pregnancy and male offspring were studied. Ultrasonic vocalization (USV) was assessed in pups under different behavioural paradigms. After weaning, anxiety was measured by conventional tests. Expression of GABA(A) receptor subunits and metabotropic glutamate (mGlu) receptors was assessed by immunoblotting. Plasma leptin levels were measured using a LINCOplex bead assay kit. The offspring of stressed dams emitted more USVs in response to isolation from their mothers and showed a later suppression of USV production when exposed to an unfamiliar male odour, indicating a pronounced anxiety-like profile. Anxiety like behaviour in PRS pups persisted one day after weaning. PRS pups did not show the plasma peak in leptin levels that is otherwise seen at PND14. In addition, PRS pups showed a reduced expression of the γ2 subunit of GABA(A) receptors in the amygdala at PND14 and PND22, an increased expression of mGlu5 receptors in the amygdala at PND22, a reduced expression of mGlu5 receptors in the hippocampus at PND14 and PND22, and a reduced expression of mGlu2/3 receptors in the hippocampus at PND22. These data offer a clear-cut demonstration that the early programming triggered by PRS could be already translated into anxiety-like behaviour during early postnatal life. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Cytofluorometric analysis of proliferation kinetics of cerebral cells of prenatally irradiated rats

    International Nuclear Information System (INIS)

    Borovitskaya, A.E.; Evtushenko, V.I.; Tokalov, S.V.; Yagunov, A.S.; Khanson, K.P.

    1994-01-01

    Prenatal irradiation of humans or animals causes serious and life-long functional and structural damage to the central nervous system. Irradiation of a fetus decreases its brain mass, an effect accompanied by a broad spectrum of disorders in higher nervous activity and behavior. The extent of cerebral damage depends on the kind of radiation, dosage, and on the stage of embryonic development. In rodents, the most serious damage resulted from the irradiation of 15-18 day embryos. Prenatally irradiated animals had pronounced morphological and biochemical changes within the brain, as well as serious deviations from normal behavior. The cerebral structural-functional disorders are known to result from the destruction of irradiated cells, primarily of neuroblasts. The authors used flow cytofluorometry to study the proliferation of cerebral cells at various ontogenetic stages in rats antenatally exposed to γ-neutron radiation. For one-week old animals, the postradiation changes of cell distributions over the cell cycle were found only within the cerebellum. This likely reflects the compensatory cell proliferation, because delayed postnatal development is typical of this part of the brain. There were no detectable differences in brain cytokinetics between two week-old control and irradiated animals. Most of the brain cells (except a limited population of glia, endothelial cells, and cells of the secondary germinal layer) are in the resting state during this period, and radiation does not change their cell cycle distributions. Thus, the increasing occurrence of the S + G 2 + M phases in the cell cycle observed in newborn irradiated rats may reflect the enhanced proliferation of nervous cells surviving the irradiation. However, this compensatory proliferation does not prevent the brain mass from being deficient in the postnatal development of prenatally irradiated animals

  11. Prenatal stress down-regulates Reelin expression by methylation of its promoter and induces adult behavioral impairments in rats.

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    Ismael Palacios-García

    Full Text Available Prenatal stress causes predisposition to cognitive and emotional disturbances and is a risk factor towards the development of neuropsychiatric conditions like depression, bipolar disorders and schizophrenia. The extracellular protein Reelin, expressed by Cajal-Retzius cells during cortical development, plays critical roles on cortical lamination and synaptic maturation, and its deregulation has been associated with maladaptive conditions. In the present study, we address the effect of prenatal restraint stress (PNS upon Reelin expression and signaling in pregnant rats during the last 10 days of pregnancy. Animals from one group, including control and PNS exposed fetuses, were sacrificed and analyzed using immunohistochemical, biochemical, cell biology and molecular biology approaches. We scored changes in the expression of Reelin, its signaling pathway and in the methylation of its promoter. A second group included control and PNS exposed animals maintained until young adulthood for behavioral studies. Using the optical dissector, we show decreased numbers of Reelin-positive neurons in cortical layer I of PNS exposed animals. In addition, neurons from PNS exposed animals display decreased Reelin expression that is paralleled by changes in components of the Reelin-signaling cascade, both in vivo and in vitro. Furthermore, PNS induced changes in the DNA methylation levels of the Reelin promoter in culture and in histological samples. PNS adult rats display excessive spontaneous locomotor activity, high anxiety levels and problems of learning and memory consolidation. No significant visuo-spatial memory impairment was detected on the Morris water maze. These results highlight the effects of prenatal stress on the Cajal-Retzius neuronal population, and the persistence of behavioral consequences using this treatment in adults, thereby supporting a relevant role of PNS in the genesis of neuropsychiatric diseases. We also propose an in vitro model that

  12. Low dose prenatal alcohol exposure does not impair spatial learning and memory in two tests in adult and aged rats.

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    Carlie L Cullen

    Full Text Available Consumption of alcohol during pregnancy can have detrimental impacts on the developing hippocampus, which can lead to deficits in learning and memory function. Although high levels of alcohol exposure can lead to severe deficits, there is a lack of research examining the effects of low levels of exposure. This study used a rat model to determine if prenatal exposure to chronic low dose ethanol would result in deficits in learning and memory performance and if this was associated with morphological changes within the hippocampus. Sprague Dawley rats were fed a liquid diet containing 6% (vol/vol ethanol (EtOH or an isocaloric control diet throughout gestation. Male and Female offspring underwent behavioural testing at 8 (Adult or 15 months (Aged of age. Brains from these animals were collected for stereological analysis of pyramidal neuron number and dendritic morphology within the CA1 and CA3 regions of the dorsal hippocampus. Prenatal ethanol exposed animals did not differ in spatial learning or memory performance in the Morris water maze or Y maze tasks compared to Control offspring. There was no effect of prenatal ethanol exposure on pyramidal cell number or density within the dorsal hippocampus. Overall, this study indicates that chronic low dose prenatal ethanol exposure in this model does not have long term detrimental effects on pyramidal cells within the dorsal hippocampus or impair spatial learning and memory performance.

  13. Dental health of young children prenatally exposed to buprenorphine. A concern of child neglect?

    Science.gov (United States)

    Kivistö, K; Alapulli, H; Tupola, S; Alaluusua, S; Kivitie-Kallio, S

    2014-06-01

    To study the oral health and dental neglect of prenatally buprenorphine-exposed 3-year-old children. The study consisted of 51 children who as newborns tested positive for buprenorphine in a urine screen. The control group comprised 68 children previously unexposed to narcotics. The dentist examined the children and interviewed their guardians. Buprenorphine-exposed children exhibited significantly more early childhood caries than did the control group. Caries indices, the number of decayed, missing and filled teeth or tooth surfaces and decayed teeth were greater in the buprenorphine-exposed children than the control children (p = 0.004, p = 0.004, p = 0.001, respectively). In the buprenorphine group, more children showed visible plaque (p = 0.003) and fewer children were caries-free (p = 0.009) than in the control group. The control children's teeth were also brushed more often than the buprenorphine-exposed children's teeth (p = 0.001) and the parents were more involved in their children's tooth brushing than were those in the buprenorphine-exposed group (p = 0.035). More caries and dental neglect were found in buprenorphine-exposed children than in controls. These findings highlight the importance of routine dental appointments, caries screening and preventive care for children in substance-abusing families.

  14. [Cognitive impairments in persons exposed to radiation during the period of prenatal development].

    Science.gov (United States)

    Burtovaya, E Yu; Kantina, T E; Belova, M V; Akleyev, A V

    2015-01-01

    To assess the cognitive status in persons exposed to ionizing radiation in prenatal period. The study included in-utero exposed people (n = 77), and the comparison group (n = 73), which consisted of people who lived in the territories of the Chelyabinsk Oblast that were not radioactive. The following methods were used: clinical, clinical-psychological (Mini-Mental State Examination (MMSE), the WAIS test, the proverb interpretation task, neurophysiological (EEG) methods, laboratory-based methods (cholesterol, high and low-density lipoproteins, triglycerides, cortisol, melatonin), and methods of statistical data processing. The number of people with non-psychotic mental disorders with the prevalence of organic mental disorders (cognitive and asthenic) was significantly higher among in-utero exposed subjects. A neurophysiological study revealed more severe changes in the bioelectric brain activity with the presence of pathological and theta-rhythms in exposed persons. The clinical-psychological study revealed a significant decrease in the analytic/synthetic ability in exposed people and significantly lower level of the general and verbal IQ. These changes were accompanied by higher levels of cortisol and melatonin which led to the activation and tension of the adaptation mechanisms in in-utero exposed subjects.

  15. Premorbid Anomalies and Risk of Schizophrenia and Depressive Disorders in a Birth Cohort Exposed to Prenatal Rubella

    Science.gov (United States)

    Penner, Justin D.; Brown, Alan S.

    2007-01-01

    In a birth cohort prenatally exposed to rubella, we assessed whether prospectively documented premorbid neuromotor dysfunction, mannerisms, deviant behaviors, and temperament during childhood and adolescence were impaired in cases who developed depressive disorder (DD) relative to rubella-exposed controls and cases who developed schizophrenia…

  16. Neurobehavioral deficits associated with PCB in 7-year-old children prenatally exposed to seafood neurotoxicants

    DEFF Research Database (Denmark)

    Grandjean, Philippe; Weihe, Pál; Burse, Virlyn W.

    2001-01-01

    Methylmercury compounds, Neuropsychological tests, Polychlorinated biphenyls, Prenatal exposure delayed effects, Preschool child......Methylmercury compounds, Neuropsychological tests, Polychlorinated biphenyls, Prenatal exposure delayed effects, Preschool child...

  17. Maternal DHA supplementation protects rat offspring against impairment of learning and memory following prenatal exposure to valproic acid.

    Science.gov (United States)

    Gao, Jingquan; Wu, Hongmei; Cao, Yonggang; Liang, Shuang; Sun, Caihong; Wang, Peng; Wang, Ji; Sun, Hongli; Wu, Lijie

    2016-09-01

    Docosahexaenoic acid (22:6n-3; DHA) is known to play a critical role in postnatal brain development. However, there have been no studies investigating the preventive effect of DHA on prenatal valproic acid (VPA)-induced behavioral and molecular alterations in offspring. The present study was to evaluate the neuroprotective effects in offspring using maternal feeding of DHA to rats exposed to VPA in pregnancy. In the present study, rats were exposed to VPA on day 12.5 of pregnancy; DHA was administered at the dosages of 100, 300 and 500 mg/kg/day for 3 weeks from day 1 to 21 of pregnancy. The results showed that maternal feeding of DHA to the prenatal exposed to VPA (1) prevented VPA-induced learning and memory impairment but did not change social-related behavior, (2) increased total DHA content in offspring plasma and hippocampus, (3) rescued VPA-induced neuronal loss and apoptosis of pyramidal cells in hippocampal CA1, (4) influenced the content of malondialdehyde and glutathione and the activities of superoxide dismutase and glutathione in the hippocampus, (5) altered levels of apoptosis-related proteins (Bcl-2, Bax and caspase-3) and inhibited the activity of caspase-3 in offspring hippocampus and (6) enhanced relative levels of p-CaMKII and p-CREB proteins in the hippocampus. These findings suggest that maternal feeding with DHA may prevent prenatal VPA-induced impairment of learning and memory, normalize several different molecules associated with oxidative stress and apoptosis in the hippocampus of offspring, and exert preventive effects on prenatal VPA-induced brain dysfunction. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Prenatal testosterone exposure worsen the reproductive performance of male rat at adulthood.

    Science.gov (United States)

    Ramezani Tehrani, Fahimeh; Noroozzadeh, Mahsa; Zahediasl, Saleh; Ghasemi, Asghar; Piryaei, Abbas; Azizi, Fereidoun

    2013-01-01

    The reproductive system is extremely susceptible to environmental insults, for example exogenous steroids during gestational development and differentiation. Experimental induction of androgen excess during prenatal life in female animal models reprograms their reproductive physiology, however the fetal programming of the male reproductive system by androgen excess has not been well studied. We aimed to determine the effect of prenatal exposure of two different doses of testosterone on different gestational days, on the male reproductive system using a rat model. Sixteen pregnant rats were randomly divided into two experimental groups and two control groups. Experimental group І were subcutaneously injected with 3 mg free testosterone on gestational days 16-19 and its controls received solvent for that time; experimental group П were subcutaneously injected with 20 mg free testosterone on day 20 of gestational period and its controls received solvent at the same time. The reproductive system morphology and function of 32 male offspring of these study groups were compared at days 6-30-60 of age and after puberty. The anogenital distance of the male offspring of both experimental groups had no significant differences on the different days of measurement, compared with controls. In the offspring of experimental group І, the testes weight, number of Sertoli, Spermatocyte and Spermatid cells, sperm count and motility and the serum concentration of testosterone after puberty were significantly decreased; except for reduction of sperm motility (pmale rat fetuses to excess testosterone disrupted reproductive function, an effect highly dependent on the time, duration and level of exposure. It seems that the reproductive system in individuals exposed to high levels of androgens during fetal life should be evaluated at puberty and likely to be treated.

  19. Lower birth weight and increased body fat at school age in children prenatally exposed to modern pesticides: A prospective study

    DEFF Research Database (Denmark)

    Wohlfahrt-Veje, Christine; Main, Katharina Maria; Schmidt, Ida Maria

    2011-01-01

    of prenatal exposure to currently used pesticides on children's growth, endocrine and reproductive function. METHOD: In a prospective study of 247 children born by women working in greenhouses in early pregnancy, 168 were categorized as prenatally exposed to pesticides. At three months (n=203) and at 6 to11......: Occupational exposure to currently used pesticides may have adverse effects in spite of the added protection offered to pregnant women. Maternal exposure to combinations of modern, non-persistent pesticides during early pregnancy was associated with affected growth, both prenatally and postnatally. We found...... a biphasic association with lower weight at birth followed by increased body fat accumulation from birth to school age. We cannot rule out some residual confounding due to differences in social class, although this was adjusted for. Associations were stronger in highly exposed than in medium exposed children...

  20. Cerebellar level of neurotransmitters in rats exposed to paracetamol during development.

    Science.gov (United States)

    Blecharz-Klin, Kamilla; Joniec-Maciejak, Ilona; Jawna-Zboińska, Katarzyna; Pyrzanowska, Justyna; Piechal, Agnieszka; Wawer, Adriana; Widy-Tyszkiewicz, Ewa

    2016-12-01

    The present study was designed to clarify the effect of prenatal and postnatal paracetamol administration on the neurotransmitter level and balance of amino acids in the cerebellum. Biochemical analysis to determine the concentration of neurotransmitters in this brain structure was performed on two-month-old Wistar male rats previously exposed to paracetamol in doses of 5 (P5, n=10) or 15mg/kg (P15, n=10) throughout the entire prenatal period, lactation and until the completion of the second month of life, when the experiment was terminated. Control animals were given tapped water (Con, n=10). The cerebellar concentration of monoamines, their metabolites and amino acids were assayed using High Performance Liquid Chromatography (HPLC). The present experiment demonstrates that prenatal and postnatal paracetamol exposure results in modulation of cerebellar neurotransmission with changes concerning mainly 5-HIAA and MHPG levels. The effect of paracetamol on monoaminergic neurotransmission in the cerebellum is reflected by changes in the level of catabolic end-products of serotonin (5-HIAA) and noradrenaline (MHPG) degradation. Further work is required to define the mechanism of action and impact of prenatal and postnatal exposure to paracetamol in the cerebellum and other structures of the central nervous system (CNS). Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  1. Does prenatal valproate interact with a genetic reduction in the serotonin transporter?A rat study on anxiety and cognition

    Directory of Open Access Journals (Sweden)

    Bart A Ellenbroek

    2016-09-01

    Full Text Available There is ample evidence that prenatal exposure to valproate (or valproic acid, VPA enhances the risk of developing Autism Spectrum Disorders (ASD. In line with this, a single injection of VPA induces a multitude of ASD-like symptoms in animals such as rats and mice. However, there is equally strong evidence that genetic factors contribute significantly to the risk of ASD and indeed, like most other psychiatric disorders, ASD is now generally thought to results from an interaction between genetic and environmental factors. Given that VPA significantly impacts on the serotonergic system, and serotonin has strong biochemical and genetic links to ASD, we aimed to investigate the interaction between genetic reduction in the serotonin transporter and prenatal valproate administration. More specifically, we exposed both wildtype (SERT+/+ rats and rats heterozygous for the serotonin transporter deletion (SERT+/- to a single injection of 400 mg/kg VPA at gestational day (GD 12. The offspring, in adulthood, was assessed in four different tests: Elevated Plus Maze and Novelty Suppressed Feeding as measures for anxiety and prepulse inhibition (PPI and latent inhibition as measures for cognition and information processing. The results show that prenatal VPA significantly increased anxiety in both paradigm, reduced PPI and reduced conditioning in the latent inhibition paradigm. However, we failed to find a significant gene – environment interaction. We propose that this may be related to the timing of the VPA injection and suggest that whereas GD12 might be optimal for affecting normal rat, rats with a genetically compromised serotonergic system may be more sensitive to VPA at earlier time points during gestation. Overall our data are the first to investigate gene * environmental interactions in a genetic rat model for ASD suggest that timing may be of crucial importance to the long-term outcome.

  2. Spatial learning impairment in prepubertal guinea pigs prenatally exposed to the organophosphorus pesticide chlorpyrifos: Toxicological implications

    Science.gov (United States)

    Mamczarz, Jacek; Pescrille, Joseph D.; Gavrushenko, Lisa; Burke, Richard D.; Fawcett, William P.; DeTolla, Louis J.; Chen, Hegang; Pereira, Edna F.R.; Albuquerque, Edson X.

    2017-01-01

    Exposure of the developing brain to chlorpyrifos (CPF), an organophosphorus (OP) pesticide used extensively in agriculture worldwide, has been associated with increased prevalence of cognitive deficits in children, particularly boys. The present study was designed to test the hypothesis that cognitive deficits induced by prenatal exposure to sub-acute doses of CPF can be reproduced in precocial small species. To address this hypothesis, pregnant guinea pigs were injected daily with CPF (25 mg/kg, s.c.) or vehicle (peanut oil) for 10 days starting on presumed gestation day (GD) 53–55. Offspring were born around GD 65, weaned on postnatal day (PND) 20, and subjected to behavioral tests starting around PND 30. On the day of birth, butyrylcholinesterase (BuChE), an OP bioscavenger used as a biomarker of OP exposures, and acetylcholinesterase (AChE), a major molecular target of OP compounds, were significantly inhibited in the blood of CPF-exposed offspring. In their brains, BuChE, but not AChE, was significantly inhibited. Prenatal CPF exposure had no significant effect on locomotor activity or on locomotor habituation, a form of non-associative memory assessed in open fields. Spatial navigation in the Morris water maze (MWM) was found to be sexually dimorphic among guinea pigs, with males outperforming females. Prenatal CPF exposure impaired spatial learning more significantly among male than female guinea pigs and, consequently, reduced the sexual dimorphism of the task. The results presented here, which strongly support the test hypothesis, reveal that the guinea pig is a valuable animal model for preclinical assessment of the developmental neurotoxicity of OP pesticides. These findings are far reaching as they lay the groundwork for future studies aimed at identifying therapeutic interventions to treat and/or prevent the neurotoxic effects of CPF in the developing brain. PMID:27296654

  3. PFOS prenatal exposure induce mitochondrial injury and gene expression change in hearts of weaned SD rats

    International Nuclear Information System (INIS)

    Xia, Wei; Wan, Yanjian; Li, Yuan-yuan; Zeng, Huaicai; Lv, Ziquan; Li, Gengqi; Wei, Zhengzheng; Xu, Shun-qing

    2011-01-01

    Xenobiotics exposure in early life may have adverse effects on animals' development through mitochondrial injury or dysfunction. The current study demonstrated the possibility of cardiac mitochondrial injury in prenatal PFOS-exposed weaned rat heart. Pregnant Sprague-Dawley (SD) rats were exposed to perfluorooctane sulfonate (PFOS) at doses of 0.1, 0.6 and 2.0 mg/kg/d and 0.05% Tween 80 as control by gavage from gestation days 2-21. The dams were allowed to give nature delivery and then heart tissues from weaned (postnatal day 21) offspring rats were analyzed for mitochondrial injury through ultrastructure observation by electron microscope, global gene expression profile by microarray, as well as related mRNA and proteins expression levels by quantitative PCR and western blot. Ultrastructural analysis revealed significant vacuolization and inner membrane injury occurred at the mitochondria of heart tissues from 2.0 mg/kg/d dosage group. Meanwhile, the global gene expression profile showed significant difference in level of some mRNA expression associated with mitochondrial function at 2.0 mg/kg/d dosage group, compared to the control. Furthermore, dose-response trends for the expression of selected genes were analyzed by quantitative PCR and western blot analysis. The selected genes were mainly focused on those encoding for proteins involved in energy production, control of ion levels, and maintenance of heart function. The down-regulation of mitochondrial ATP synthetase (ATP5E, ATP5I and ATP5O) implicated a decrease in energy supply. This was accompanied by down-regulation of gene transcripts involved in energy consumption such as ion transporting ATPase (ATP1A3 and ATP2B2) and inner membrane protein synthesis (SLC25A3, SLC25A4, SLC25A10, SLC25A29). The up-regulation of gene transcripts encoding for uncoupling proteins (UCP1 and UCP3), epidermal growth factor receptor (EGFR) and connective tissue growth factor (CTGF), was probably a protective process to maintain

  4. Elevated expression of steroidogenesis pathway genes; CYP17, GATA6 and StAR in prenatally androgenized rats.

    Science.gov (United States)

    Jahromi, Marziyeh Salehi; Tehrani, Fahimeh Ramezani; Noroozzadeh, Mahsa; Zarkesh, Maryam; Ghasemi, Asghar; Zadeh-Vakili, Azita

    2016-11-15

    It is believed that excess androgen exposure of the fetus, via altered gene expression, causes hyperandrogenism a key feature of polycystic ovary syndrome (PCOS). The aim of this study was to evaluate expression of Cytochrome P450-17 (CYP17), GATA-binding protein (GAGT6) and Steroidogenic acute regulatory protein (StAR), genes of adult female rats prenatally exposed to androgen excess, closely reflect endocrine and ovarian disturbances of PCOS in women, by comparing them during different phases of estrus cycle with those of non-treated rats. Both the adult prenatally testosterone exposed and control rats (n=23, each) were divided into four groups based on their observed vaginal smear (proestrus, estrus, metestrus and diestrus) and the relative expression of CYP17, GATA6 and StAR genes was measured in ovarian theca cells using Cyber-green Real-Time PCR. Serum sex steroid hormones and gonadotropins levels were measured using the ELISA method; a comparison of these two groups showed that there was an overall increase in the studied genes (CYP17; 2.39 fold change, 95% CI: 1.23-3.55; PPCOS. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Failure to upregulate Agrp and Orexin in response to activity based anorexia in weight loss vulnerable rats characterized by passive stress coping and prenatal stress experience.

    Science.gov (United States)

    Boersma, Gretha J; Liang, Nu-Chu; Lee, Richard S; Albertz, Jennifer D; Kastelein, Anneke; Moody, Laura A; Aryal, Shivani; Moran, Timothy H; Tamashiro, Kellie L

    2016-05-01

    We hypothesize that anorexia nervosa (AN) poses a physiological stress. Therefore, the way an individual copes with stress may affect AN vulnerability. Since prenatal stress (PNS) exposure alters stress responsivity in offspring this may increase their risk of developing AN. We tested this hypothesis using the activity based anorexia (ABA) rat model in control and PNS rats that were characterized by either proactive or passive stress-coping behavior. We found that PNS passively coping rats ate less and lost more weight during the ABA paradigm. Exposure to ABA resulted in higher baseline corticosterone and lower insulin levels in all groups. However, leptin levels were only decreased in rats with a proactive stress-coping style. Similarly, ghrelin levels were increased only in proactively coping ABA rats. Neuropeptide Y (Npy) expression was increased and proopiomelanocortin (Pomc) expression was decreased in all rats exposed to ABA. In contrast, agouti-related peptide (Agrp) and orexin (Hctr) expression were increased in all but the PNS passively coping ABA rats. Furthermore, DNA methylation of the orexin gene was increased after ABA in proactive coping rats and not in passive coping rats. Overall our study suggests that passive PNS rats have innate impairments in leptin and ghrelin in responses to starvation combined with prenatal stress associated impairments in Agrp and orexin expression in response to starvation. These impairments may underlie decreased food intake and associated heightened body weight loss during ABA in the passively coping PNS rats. Published by Elsevier Ltd.

  6. Dextromethorphan attenuated the higher vulnerability to inflammatory thermal hyperalgesia caused by prenatal morphine exposure in rat offspring

    Directory of Open Access Journals (Sweden)

    Chen Chien-Fang

    2011-08-01

    Full Text Available Abstract Background Co-administration of dextromethorphan (DM with morphine during pregnancy and throughout lactation has been found to reduce morphine physical dependence and tolerance in rat offspring. No evidence was presented, however, for the effect of DM co-administered with morphine during pregnancy on inflammatory hyperalgesia in morphine-exposed offspring. Therefore, we attempt to investigate the possible effect of prenatal morphine exposure on the vulnerability to hyperalgesia and the possible therapeutic effect of DM in the present study. Methods Fifty μl of carrageenan (20 mg/ml was injected subcutaneously into the plantar surface of the right hind paw in p18 rats to induce hyperalgesia. Mean paw withdrawal latency was measured in the plantar test to index the severity of hyperalgesia. Using Western blotting and RT-PCR, the quantitative analyses of NMDA receptor NR1 and NR2B subunits were performed in spinal cords from different groups of animals. Results In the carrageenan-induced hyperalgesia model, rat offspring passively exposed to morphine developed a severe hyperalgesia on postnatal day 18 (p18, which also had a more rapid time course than those in the controls. Co-administration of DM with morphine in the dams prevented this adverse effect of morphine in the offspring rats. Western blot and RT-PCR analysis showed that the levels of protein and mRNA of NMDA receptor NR1 and NR2B subunits were significantly higher in the lumbar spinal cords of rats (p14 exposed to prenatal morphine; the co-administration of DM could reverse the effect of morphine on NR1 and attenuate the effect on NR2B. Conclusions Thus, DM may have a great potential in the prevention of higher vulnerability to inflammatory thermal hyperalgesia in the offspring of morphine-addicted mothers.

  7. Prenatal Stress Produces Sex Specific Changes in Depression-like Behavior in Rats: Implications for Increased Vulnerability in Females

    DEFF Research Database (Denmark)

    Sickmann, Helle Mark; Arentzen, Tine S; Dyrby, Tim

    2015-01-01

    Stress during rat gestation can elicit depression-like physiological and behavioral responses in the offspring. However, human clinical depression is more prevalent among females than males. Accordingly, we examined how repeated variable prenatal stress (PS) alters rat anxiety- and depression...... and measured anxiety- (elevated plus maze, EPM) and depression-like (forced swim test, FST) behaviors in the offspring at a young adult age. As a stressful event later in life (in addition to PS) may be needed to actually trigger an episode of clinical depression, half of the animals were exposed to an acute...... affected in control animals after acute stressor exposure, however, this response was blunted in PS offspring. Moreover, FST immobility, as an indicator of depressive-like behavior, was increased in female but not male PS rats. Altogether, our results identify both sex- and circadian phase-specific effects...

  8. Children prenatally exposed to maternal anxiety devote more attentional resources to neutral pictures.

    Science.gov (United States)

    van den Heuvel, Marion I; Henrichs, Jens; Donkers, Franc C L; Van den Bergh, Bea R H

    2017-10-22

    Maternal anxiety during pregnancy can negatively affect fetal neurodevelopment, predisposing the offspring to a higher risk of behavioral and emotional problems later in life. The current study investigates the association between maternal anxiety during pregnancy and child affective picture processing using event-related brain potentials (ERPs). Mothers reported anxiety during the second trimester using the anxiety subscale of the Symptom Checklist (SCL-90). At age 4 years, child affective picture processing (N = 86) was measured by recording ERPs during viewing of neutral, pleasant, and unpleasant pictures selected from the International Affective Pictures System. The late positive potential (LPP)-an ERP component reflecting individual differences in affective processing-was used as child outcome. The expected positive association between maternal anxiety and LPP amplitude for unpleasant pictures was not found. Nevertheless, we found a positive association between maternal anxiety during pregnancy and LPP amplitudes for neutral pictures in the middle and late time window at anterior locations (all p anxiety and gestational age at birth and after FDR correction for multiple comparisons. Our study provides neurophysiological evidence that children prenatally exposed to higher maternal anxiety devote more attentional resources to neutral pictures, but not to unpleasant pictures. Possibly, these children show enhanced vigilance for threat when viewing neutral pictures. Although useful in dangerous environments, this enhanced vigilance may predispose children prenatally exposed to higher maternal anxiety to developing behavioral and/or emotional problems later in life. A video abstract of this article can be viewed at: https://www.youtube.com/watch?v=kEzYi6IS2HA. © 2017 John Wiley & Sons Ltd.

  9. Prenatal developmental toxicity study with 7-hydroxymatairesinol potassium acetate (HMRlignan) in rats

    NARCIS (Netherlands)

    Wolterbeek, A.P.M.; Roberts, A.; Korte, H.; Unkila, M.; Waalkens-Berendsen, D.H.

    2004-01-01

    Plant lignan 7-hydromatairesinol, a novel precursor of the mammalian lignan enterolactone was evaluated in a prenatal developmental toxicity study conducted in the Wistar rat. Mated female rats were fed diets containing 0, 0.25, 1, and 4% (w/w) of 7-hydroxymatairesinol in the form of potassium

  10. Serum-thyroxine levels in microwave-exposed rats

    International Nuclear Information System (INIS)

    Lu, S.T.; Lebda, N.; Michaelson, S.M.; Pettit, S.

    1985-01-01

    The nature of the response of the thyroid gland in animals exposed to microwave irradiation is controversial. Animal experimentation has contributed to the controversy because both increased and decreased thyroid functions have been reported. The thyroxine concentration in rats as representative of thyroid function in animals exposed to 2.45-GHz, 120-Hz amplitude-modulated microwaves has been studied. These studies covered a long time span; rats from two commercial sources (BS and CR) were used and subjected to different numbers of exposures, and therefore these data were evaluated for their stability. Two factors could influence in the result significantly, i.e., source of animal and number of sham exposures. Rats used in the 2-hr exposures were from two different commercial sources; rats from CR had a higher (but normal) thyroxine concentration than did rats from BS. Therefore the data of these animals were separated by commercial source for reevaluation. Instead of increased thyroxine concentration in rats exposed at 25, 30, and 40 mW/cm 2 , changes were not noted in any microwave-exposed rats. The influence of sham exposure revealed that appropriate concurrent control and specification of animal source are needed in longitudinal studies. Furthermore, statistical procedures used can greatly influence the conclusions. Thus the specificity of changes in thyroxine concentration in rats exposed to microwaves because of its sporadic occurrence and because of inconsistencies among experiments was doubted

  11. Association of testicular undescent induced by prenatal flutamide treatment with thickening of the cremaster muscle in rats

    Science.gov (United States)

    Matsuno, Yoshiharu; Komiyama, Masatoshi; Tobe, Toyofusa; Toyota, Naoji; Adachi, Tetsuya

    2003-01-01

    Background and Aims:  Previously, in cryptorchid rats, which were induced by prenatal exposure to flutamide, we found a thickening of the cremaster muscle. This study was undertaken to quantify the increase of the cremaster muscle thickness in the cryptorchid rats, and to examine its possible relationship with the proliferation of muscle cells. Methods:  To obtain cryptorchid rats, pregnant Wistar rats were subcutaneously injected with flutamide (100 mg/kg per day) during gestational days 16–17. Serial sections of the scrotum, containing the testis and cremaster muscle, were prepared from the control and cryptorchid rats that were 2–6 weeks of age, and stained with hematoxylin–eosin for morphometry, or stained with antibody against the proliferating cell nuclear antigen (PCNA) to analyze the cell proliferation ability. Results:  The thickened cremaster muscle was always associated with cryptorchid testis and, in the case of unilateral cryptorchidism, the cremaster muscle of the contralateral (descended testis) side exhibited normal thickness. The average thickness of the affected cremaster muscle was 0.80 and 1.89 mm at 4 and 6 weeks of age, respectively, although that of the normal muscle was 0.28 and 0.33 mm at the same time period, respectively. Conclusion:  Our results showed that the cremaster muscle of the cryptorchid rats was significantly thicker than that of the control rats. The immunohistochemical analysis revealed that a thickened cremaster muscle contained many PCNA‐positive nuclei even at 4 weeks of age, in contrast to the control, which had only a few positive nuclei. Our present study indicates that continuous proliferation of the muscle cells associated with cryptorchid testis increases the thickness of cremaster cells in rats exposed to flutamide prenatally. (Reprod Med Biol 2003; 2: 109–113) PMID:29699173

  12. Susceptibility or resilience? Prenatal stress predisposes male rats to social subordination, but facilitates adaptation to subordinate status.

    Science.gov (United States)

    Scott, Karen A; de Kloet, Annette D; Smeltzer, Michael D; Krause, Eric G; Flak, Jonathan N; Melhorn, Susan J; Foster, Michelle T; Tamashiro, Kellie L K; Sakai, Randall R

    2017-09-01

    Mood disorders such as major depressive disorder (MDD) affect a significant proportion of the population. Although progress has been made in the development of therapeutics, a large number of individuals do not attain full remission of symptoms and adverse side effects affect treatment compliance for some. In order to develop new therapies, there is a push for new models that better reflect the multiple risk factors that likely contribute to the development of depressive illness. We hypothesized that early life stress would exacerbate the depressive-like phenotype that we have previously observed in socially subordinate (SUB) adult male rats in the visible burrow system (VBS), a semi-natural, ethologically relevant environment in which males in a colony form a dominance hierarchy. Dams were exposed to chronic variable stress (CVS) during the last week of gestation, resulting in a robust and non-habituating glucocorticoid response that did not alter maternal food intake, body weight or litter size and weight. As adults, one prenatal CVS (PCVS) and one non-stressed (NS) male were housed in the VBS with adult females. Although there were no overt differences between PCVS and NS male offspring prior to VBS housing, a greater percentage of PCVS males became SUB. However, the depressive-like phenotype of SUB males was not exacerbated in PCVS males; rather, they appeared to better cope with SUB status than NS SUB males. They had lower basal plasma corticosterone than NS SUB males at the end of VBS housing. In situ hybridization for CRH in the PVN and CeA did not reveal any prenatal treatment or status effects, while NPY expression was higher within the MeA of dominant and subordinate males exposed to the VBS in comparison with controls, but with no effect of prenatal treatment. These data suggest that prenatal chronic variable stress may confer resilience to offspring when exposed to social stress in adulthood. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Altered functional connectivity to stressful stimuli in prenatally cocaine-exposed adolescents.

    Science.gov (United States)

    Zakiniaeiz, Yasmin; Yip, Sarah W; Balodis, Iris M; Lacadie, Cheryl M; Scheinost, Dustin; Constable, R Todd; Mayes, Linda C; Sinha, Rajita; Potenza, Marc N

    2017-11-01

    Prenatal cocaine exposure (PCE) is linked to addiction and obesity vulnerability. Neural responses to stressful and appetitive cues in adolescents with PCE versus those without have been differentially linked to substance-use initiation. However, no prior studies have assessed cue-reactivity responses among PCE adolescents using a connectivity-based approach. Twenty-two PCE and 22 non-prenatally drug-exposed (NDE) age-, sex-, IQ- and BMI-matched adolescents participated in individualized guided imagery with appetitive (favorite-food), stressful and neutral-relaxing cue scripts during functional magnetic resonance imaging. Subjective favorite-food craving scores were collected before and after script exposure. A data-driven voxel-wise intrinsic connectivity distribution analysis was used to identify between-group differences and examine relationships with craving scores. A group-by-cue interaction effect identified a parietal lobe cluster where PCE versus NDE adolescents showed less connectivity during stressful and more connectivity during neutral-relaxing conditions. Follow-up seed-based connectivity analyses revealed that, among PCE adolescents, the parietal seed was positively connected to inferior parietal and sensory areas and negatively connected to corticolimbic during both stress and neutral-relaxing conditions. For NDE, greater parietal connectivity to parietal, cingulate and sensory areas and lesser parietal connectivity to medial prefrontal areas were found during stress compared to neutral-relaxing cueing. Craving scores inversely correlated with corticolimbic connectivity in PCE, but not NDE adolescents, during the favorite-food condition. Findings from this first data-driven intrinsic connectivity analysis of PCE influences on adolescent brain function indicate differences relating to PCE status and craving. These findings provide insight into the developmental impact of in utero drug exposure. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Development of auditory event-related potentials in infants prenatally exposed to methadone.

    Science.gov (United States)

    Paul, Jonathan A; Logan, Beth A; Krishnan, Ramesh; Heller, Nicole A; Morrison, Deborah G; Pritham, Ursula A; Tisher, Paul W; Troese, Marcia; Brown, Mark S; Hayes, Marie J

    2014-07-01

    Developmental features of the P2 auditory ERP in a change detection paradigm were examined in infants prenatally exposed to methadone. Opiate dependent pregnant women maintained on methadone replacement therapy were recruited during pregnancy (N = 60). Current and historical alcohol and substance use, SES, and psychiatric status were assessed with a maternal interview during the third trimester. Medical records were used to collect information regarding maternal medications, monthly urinalysis, and breathalyzer to confirm comorbid drug and alcohol exposures. Between birth and 4 months infant ERP change detection performance was evaluated on one occasion with the oddball paradigm (.2 probability oddball) using pure-tone stimuli (standard = 1 kHz and oddball = 2 kHz frequency) at midline electrode sites, Fz, Cz, Pz. Infant groups were examined in the following developmental windows: 4-15, 16-32, or 33-120 days PNA. Older groups showed increased P2 amplitude at Fz and effective change detection performance at P2 not seen in the newborn group. Developmental maturation of amplitude and stimulus discrimination for P2 has been reported in developing infants at all of the ages tested and data reported here in the older infants are consistent with typical development. However, it has been previously reported that the P2 amplitude difference is detectable in neonates; therefore, absence of a difference in P2 amplitude between stimuli in the 4-15 days group may represent impaired ERP performance by neonatal abstinence syndrome or prenatal methadone exposure. © 2013 Wiley Periodicals, Inc.

  15. Low level prenatal exposure to methylmercury disrupts neuronal migration in the developing rat cerebral cortex

    International Nuclear Information System (INIS)

    Guo, Bao-Qiang; Yan, Chong-Huai; Cai, Shi-Zhong; Yuan, Xiao-Bing; Shen, Xiao-Ming

    2013-01-01

    Highlights: ► Low level MeHg exposure causes migratory defect of rat cerebrocortical neurons. ► The migration defect is due to the impact of MeHg on the neuronal migration itself. ► Rho GTPases seem to be involved in MeHg-induced disruption of neuronal migration. -- Abstract: We determined the effects of low-level prenatal MeHg exposure on neuronal migration in the developing rat cerebral cortex using in utero electroporation. We used offspring rats born to dams that had been exposed to saline or various doses of MeHg (0.01 mg/kg/day, 0.1 mg/kg/day, and 1 mg/kg/day) from gestational day (GD) 11–21. Immunohistochemical examination of the brains of the offspring was conducted on postnatal day (PND) 0, PND3, and PND7. Our results showed that prenatal exposure to low levels of MeHg (0.1 mg/kg/day or 1 mg/kg/day) during the critical stage in neuronal migration resulted in migration defects of the cerebrocortical neurons in offspring rats. Importantly, our data revealed that the abnormal neuronal distribution induced by MeHg was not caused by altered proliferation of neural progenitor cells (NPCs), induction of apoptosis of NPCs and/or newborn neurons, abnormal differentiation of NPCs, and the morphological changes of radial glial scaffold, indicating that the defective neuronal positioning triggered by exposure to low-dose of MeHg is due to the impacts of MeHg on the process of neuronal migration itself. Moreover, we demonstrated that in utero exposure to low-level MeHg suppresses the expression of Rac1, Cdc42, and RhoA, which play key roles in the migration of cerebrocortical neurons during the early stage of brain development, suggesting that the MeHg-induced migratory disturbance of cerebrocortical neurons is likely associated with the Rho GTPases signal pathway. In conclusion, our results provide a novel perspective on clarifying the mechanisms underlying the impairment of neuronal migration induced by MeHg

  16. Delayed neurochemical effects of prenatal exposure to MeHg in the cerebellum of developing rats.

    Science.gov (United States)

    Heimfarth, Luana; Delgado, Jeferson; Mingori, Moara Rodrigues; Moresco, Karla Suzana; Pureur, Regina Pessoa; Gelain, Daniel Pens; Moreira, José Cláudio Fonseca

    2018-03-01

    Human fetuses and neonates are particularly vulnerable to methylmercury (MeHg)-induced brain damage and are sensitive even to low exposure levels. Previous work of our group evidence that prenatal exposure to MeHg causes cognitive and behavioral alterations and disrupt hippocampus signaling. The current study aimed to investigate the effect of gestational exposure of rats to MeHg at low doses (1 or 2 mg/kg) on parameters of redox imbalance and key signaling pathways in the cerebellum of their offspring. Pregnant females received MeHg (treated group) or 0.9% saline water (control group) by gavage in alternated days from gestational day 5 (GD5) until parturition and analyzes were proceed in the cerebellum of 30-day-old pups. We found increased lipid peroxidation and protein carbonylation levels as well as decreased SH content in pups prenatally exposed to 2 mg/kg MeHg. In addition, misregulated SOD/catalase activities supported imbalanced redox equilibrium. We found decreased GSK3β(Ser9) phosphorylation, suggesting activation of this enzyme and dephosphorylation/inhibition of ERK1/2 and JNK pathways. Increased PKAα catalytic subunit could be upstream of hyperphosphorylated c-Raf(Ser259) and downregulated MAPK pathway. In addition, we found raised levels of the Ca 2+ -dependent protein phosphatase 2 B (PP2B). We also found preserved immunohistochemical staining for both glial fibrillary acidic protein (GFAP) and NeuN in MeHg-exposed pups. Western blot analysis showed unaltered levels of BAX/BCL-XL, BAD/BCL-2 and active caspase 3. Together, these findings support absence of reactive astrocytes, neuronal damage and apoptotic cell death in the cerebellum of MeHg treated pups. The present study provides evidence that prenatal exposure to MeHg leads to later redox imbalance and disrupted signaling mechanisms in the cerebellum of 30-day-old pups potentially predisposing them to long-lasting neurological impairments in CNS. Copyright © 2017 Elsevier B.V. All rights

  17. Prenatal alcohol exposure alters gene expression in the rat brain: Experimental design and bioinformatic analysis of microarray data

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    Alexandre A. Lussier

    2015-09-01

    Full Text Available We previously identified gene expression changes in the prefrontal cortex and hippocampus of rats prenatally exposed to alcohol under both steady-state and challenge conditions (Lussier et al., 2015, Alcohol.: Clin. Exp. Res., 39, 251–261. In this study, adult female rats from three prenatal treatment groups (ad libitum-fed control, pair-fed, and ethanol-fed were injected with physiological saline solution or complete Freund׳s adjuvant (CFA to induce arthritis (adjuvant-induced arthritis, AA. The prefrontal cortex and hippocampus were collected 16 days (peak of arthritis or 39 days (during recovery following injection, and whole genome gene expression was assayed using Illumina׳s RatRef-12 expression microarray. Here, we provide additional metadata, detailed explanations of data pre-processing steps and quality control, as well as a basic framework for the bioinformatic analyses performed. The datasets from this study are publicly available on the GEO repository (accession number GSE63561.

  18. Training on motor and visual spatial learning tasks in early adulthood produces large changes in dendritic organization of prefrontal cortex and nucleus accumbens in rats given nicotine prenatally.

    Science.gov (United States)

    Muhammad, A; Mychasiuk, R; Hosain, S; Nakahashi, A; Carroll, C; Gibb, R; Kolb, B

    2013-11-12

    Experience-dependent plasticity is an ongoing process that can be observed and measured at multiple levels. The first goal of this study was to examine the effects of prenatal nicotine on the performance of rats in three behavioral tasks (elevated plus maze (EPM), Morris water task (MWT), and Whishaw tray reaching). The second goal of this experiment sought to examine changes in dendritic organization following exposure to the behavioral training paradigm and/or low doses of prenatal nicotine. Female Long-Evans rats were administered daily injections of nicotine for the duration of pregnancy and their pups underwent a regimen of behavioral training in early adulthood (EPM, MWT, and Whishaw tray reaching). All offspring exposed to nicotine prenatally exhibited substantial increases in anxiety. Male offspring also showed increased efficiency in the Whishaw tray-reaching task and performed differently than the other groups in the probe trial of the MWT. Using Golgi-Cox staining we examined the dendritic organization of the medial and orbital prefrontal cortex as well as the nucleus accumbens. Participation in the behavioral training paradigm was associated with dramatic reorganization of dendritic morphology and spine density in all brain regions examined. Although both treatments (behavior training and prenatal nicotine exposure) markedly altered dendritic organization, the effects of the behavioral experience were much larger than those of the prenatal drug exposure, and in some cases interacted with the drug effects. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  19. The effect of the timing of prenatal exposure to x-irradiation on Purkinje cell numbers in rat cerebellum

    International Nuclear Information System (INIS)

    Miki, T.; Satriotomo, I.; Matsumoto, Y.; Kuma, H.; Takeuchi, Y.; Gu

    2003-01-01

    Full text: Prenatal exposure of the developing brain to X-irradiation is known to cause various deleterious consequences. We have examined the effects of prenatal X-irradiation on the development of the cerebellum. Wistar rats were exposed to 1.5 Gy X-irradiation either on the 14, 15 or 16th day of gestation (E14, E15, E16). Sham-irradiated animals were used as controls. At seven postnatal weeks of age, male rats were deeply anesthetized and killed by intracardiac perfusion with 2.5 % glutaraldehyde in 0.1 M phosphate buffer. The unbiased stereological procedure known as the fractionator method was used to estimate the total number of Purkinje cells in the cerebellum. Body and cerebellar weights from E14 and E15, but not E16 irradiated rats showed significant deficits compared to control animals. Rats irradiated on E16 and control rats had about 285,100 - 304,800 Purkinje cells in the cerebellum. There was no significant difference between these values. However, E14 and E15 irradiated animals had about 117,500 and 196,300 Purkinje cells, respectively. These estimates were significantly different from those observed in both control and E16 irradiated rats. Given that the phase of division of Purkinje cell progenitors is mainly between E14-E15 and the phase of differentiation and migration is between E16-E20, it is concluded that the vulnerable period of the Purkinje cells to X-irradiation closely overlaps the phase of division of progenitors

  20. Increased gluconeogenesis in rats exposed to hyper-G stress

    International Nuclear Information System (INIS)

    Daligcon, B.C.; Oyama, J.; Hannak, K.

    1985-01-01

    The role of gluconeogenesis on the increase in plasma glucose and liver glycogen of rats exposed to hyper-G (radial acceleration) stress was determined. Overnight-fasted, male Sprague-Dawley rats (250-300 g) were injected i.p. with uniformly labeled 14 C lactate, alanine, or glycerol (5 μCi/rat) and immediately exposed to 3.1 G for 0.25, 0.50, and 1.0 hr. 14 C incorporation of the labeled substrates into plasma glucose and liver glycogen was measured and compared to noncentrifuged control rats injected in a similar manner. Significant increases in 14 C incorporation of all three labeled substrates into plasma glucose were observed in centrifuged rats at all exposure periods; 14 C incorporation into liver glycogen was significantly increased only at 0.50 and 1.0 hr. The i.p. administration (5 mg/100-g body wt) of 5-methoxyindole-2-carboxylic acid, a potent gluconeogenesis inhibitor, prior to centrifugation blocked the increase in plasma glucose and liver glycogen during the first hour of centrifugation. The increase in plasma glucose and liver glycogen was also abolished in adrenodemedullated rats exposed to centrifugation for 1.0 hr. Propranolol, a beta-adrenergic blocker, suppressed the increase in plasma glucose of rats exposed to centrifugation for 0.25 hr. From the results of this study, it is concluded that the initial, rapid rise in plasma glucose as well as the increase in liver glycogen of rats exposed to hyper-G stress can be attributed to an increased rate of gluconeogenesis, and that epinephrine plays a dominant role during the early stages of exposure to centrifugation. 11 references, 3 tables

  1. Effects of Prenatal Irradiation with an Accelerated Heavy-Ion Beam on Postnatal Development in Rats

    Science.gov (United States)

    Wang, B.; Murakami, M.; Eguchi-Kasai, K.; Nojima, K.; Shang, Y.; Tanaka, K.; Fujita, K.; Coffigny, H.; Hayata, I.

    Effects on postnatal neurophysiological development in offspring were studied following exposure of pregnant Wistar rats to accelerated neon-ion beams with a LET value of about 30 keV mu m at a dose range from 0 1 Gy to 2 0Gy on the 15th day of gestation The age at which four physiologic markers appeared and five reflexes were acquired was examined prior to weaning Gain in body weight was monitored until the offspring were 3 months old Male offspring were evaluated as young adults using two behavioral tests The effects of X-rays at 200 kVp measured for the same biological end points were studied for comparison Our previous study on carbon-ion beams with a LET value of about 13 keV mu m was also cited to elucidate a possible LET-related effect For most of the endpoints at early age significant alteration was even observed in offspring prenatally received 0 1 Gy of accelerated neon ions while neither X rays nor carbon-ions under the same dose resulted in such a significant alteration compared to that from the sham-irradiated dams All offspring whose mothers received 2 0 Gy died prior to weaning Offspring from dams irradiated with accelerated neon ions generally showed higher incidences of prenatal death and preweaning mortality markedly delayed accomplishment in their physiological markers and reflexes and gain in body weight compared to those exposed to X-rays or carbon ions at doses of 0 1 to 1 5 Gy Significantly reduced ratios of main organ weight to body weight at postnatal ages of 30 60 and 90 days were also observed

  2. Studies concerning the effects of low level prenatal X-irradiation on postnatal growth and adult behaviour in the Wistar rat

    International Nuclear Information System (INIS)

    Jensh, R.P.; Brent, R.L.; Vogel, W.H.

    1986-01-01

    Fifty-nine pregnant Wistar strain rats were sham irradiated or given a 0.1 or 0.2 Gy exposure of X-radiation on the 9th or 17th day of gestation. Twenty-seven were killed at term for teratologic analysis. The remaining mothers raised their young. At 60 days of age the 252 offspring were randomly assigned three of six tests: open field, swimming, hanging, activity wheel, water T-maze, or conditioned avoidance response. Male offspring exposed at the 0.2 Gy level exhibited retarded growth only during the first few weeks of postnatal life. Female offspring exposed on the 17th day to 0.2 Gy X-radiation were growth retarded throughout the test period. Postnatal growth rates were not significantly different between the irradiated and control groups. There were no significant alterations in adult behaviour due to prenatal X-irradiation. There were sex differences in activity wheel and forelimb hanging performance, unrelated to radiation exposure. These results indicate that prenatal low level X-irradiation on the 9th or 17th day of gestation dose not result in significant alterations in rat adult behavioural performance but prenatal growth retardation persists postnatally. Growth may be a more sensitive indicator of the effects of prenatal exposure than postnatal behaviour. (author)

  3. Prenatal programming of renal salt wasting resets postnatal salt appetite, which drives food intake in the rat.

    Science.gov (United States)

    Alwasel, Saleh H; Barker, David J P; Ashton, Nick

    2012-03-01

    Sodium retention has been proposed as the cause of hypertension in the LP rat (offspring exposed to a maternal low-protein diet in utero) model of developmental programming because of increased renal NKCC2 (Na+/K+/2Cl- co-transporter 2) expression. However, we have shown that LP rats excrete more rather than less sodium than controls, leading us to hypothesize that LP rats ingest more salt in order to maintain sodium balance. Rats were fed on either a 9% (low) or 18% (control) protein diet during pregnancy; male and female offspring were studied at 4 weeks of age. LP rats of both sexes held in metabolism cages excreted more sodium and urine than controls. When given water to drink, LP rats drank more and ate more food than controls, hence sodium intake matched excretion. However, when given a choice between saline and water to drink, the total volume of fluid ingested by LP rats fell to control levels, but the volume of saline taken was significantly larger [3.8±0.1 compared with 8.8±1.3 ml/24 h per 100 g of body weight in control and LP rats respectively; Psodium content and ECF (extracellular fluid) volumes were greater in LP rats. These results show that prenatal programming of renal sodium wasting leads to a compensatory increase in salt appetite in LP rats. We speculate that the need to maintain salt homoeostasis following malnutrition in utero stimulates greater food intake, leading to accelerated growth and raised BP (blood pressure).

  4. Prenatal exposure to ethanol during late gestation facilitates operant self-administration of the drug in 5-day-old rats.

    Science.gov (United States)

    Miranda-Morales, Roberto Sebastián; Nizhnikov, Michael E; Spear, Norman E

    2014-02-01

    Prenatal ethanol exposure modifies postnatal affinity to the drug, increasing the probability of ethanol use and abuse. The present study tested developing rats (5-day-old) in a novel operant technique to assess the degree of ethanol self-administration as a result of prenatal exposure to low ethanol doses during late gestation. On a single occasion during each of gestational days 17-20, pregnant rats were intragastrically administered ethanol 1 g/kg, or water (vehicle). On postnatal day 5, pups were tested on a novel operant conditioning procedure in which they learned to touch a sensor to obtain 0.1% saccharin, 3% ethanol, or 5% ethanol. Immediately after a 15-min training session, a 6-min extinction session was given in which operant behavior had no consequence. Pups were positioned on a smooth surface and had access to a touch-sensitive sensor. Physical contact with the sensor activated an infusion pump, which served to deliver an intraoral solution as reinforcement (Paired group). A Yoked control animal evaluated at the same time received the reinforcer when its corresponding Paired pup touched the sensor. Operant behavior to gain access to 3% ethanol was facilitated by prenatal exposure to ethanol during late gestation. In contrast, operant learning reflecting ethanol reinforcement did not occur in control animals prenatally exposed to water only. Similarly, saccharin reinforcement was not affected by prenatal ethanol exposure. These results suggest that in 5-day-old rats, prenatal exposure to a low ethanol dose facilitates operant learning reinforced by intraoral administration of a low-concentration ethanol solution. This emphasizes the importance of intrauterine experiences with ethanol in later susceptibility to drug reinforcement. The present operant conditioning technique represents an alternative tool to assess self-administration and seeking behavior during early stages of development. Published by Elsevier Inc.

  5. Differential cardiac effects in rats exposed to atmospheric ...

    Science.gov (United States)

    The results of this study demonstrate that atmospheric smog generated from both isoprene and toluene cause cardiac effects in rats. In addition, it appears that smog from toluene is more toxic in terms of cardiac arrhythmogenicity. Smog, which is a complex mixture of particulate matter and gaseous irritants (ozone, sulfur dioxide, reactive aldehydes), as well as components which react with sunlight to form secondary pollutants, has recently been linked to increased risk of adverse cardiac responses. The components, and therefore health effects, of atmospheric smog are determined by the fuel used to generate them. In this study we examined the difference between isoprene- and toluene-generated smog in causing cardiac effects in rats and hypothesized that both atmospheres would cause cardiac electrical and functional changes in rats. Male Wistar-Kyoto rats were exposed to either atmospheric smog generated by the USEPA’s mobile reaction chamber using either isoprene or toluene, or filtered air for four hours. One day later, rats were anesthetized and left ventricular functional responses to dobutamine were measured using a Millar probe and arrhythmia sensitivity to aconitine. Baseline left ventricular pressure (LVP) was lower in toluene-exposed animals but not isoprene when compared to air. Increases in LVP with increasing doses of dobutamine were impaired only in toluene-exposed rats. Both isoprene and toluene impaired the rate of ventri

  6. Growth and development of children prenatally exposed to telbivudine administered for the treatment of chronic hepatitis B in their mothers.

    Science.gov (United States)

    Zeng, Huihui; Cai, Haodong; Wang, Ying; Shen, Ying

    2015-04-01

    We studied the growth and development of children prenatally exposed to telbivudine used to treat chronic hepatitis B virus (HBV) infection in their mothers. Maternal abnormalities during pregnancy and delivery and infant congenital anomalies, physical development status, developmental quotient (DQ), HBV vertical transmission status, and HBV vaccination outcomes of 54 infants were evaluated (2010-2013). No fetal abnormalities were observed during pregnancy or delivery. Postpartum, three infants (5.56%) had abnormalities: ankyloglossia, cutaneous hemangioma, and vaginal canal leak. Height and weight were within the normal range at birth and at 6 weeks, but were higher than the reference at 12 months (pchildren (68.52%), abnormal or suspicious for a developmental delay (15.19%, 41/270) in 17 children (31.48%), and indicated a developmental delay (4.07%, 11/270) in seven children (12.96%). There were no significant differences in developmental delay between children prenatally exposed to telbivudine and controls (p>0.05). HBV vertical transmission was successfully blocked in all infants. The effective HBV vaccination rate was 98.15% (53/54). The growth and development of children prenatally exposed to telbivudine was normal, indicating that telbivudine treatment during pregnancy is safe and effective. Copyright © 2015. Published by Elsevier Ltd.

  7. Brain biochemistry of infant mice and rats exposed to lead

    Energy Technology Data Exchange (ETDEWEB)

    Berber, G.B.; Maes, J.; Gilliavod, N.; Casale, G.

    1978-05-01

    Brains of rats and mice exposed to lead from birth receive biochemical examinations. Mice are given drinking water with lead and are studied until they are 17 days old. Rats ae given lead in the diet and followed for more than a year. In mice a retardation in body growth and development in brain DNA is found. In rats, cathepsin is enhanced at almost all times. An important role of proteolytic processes and biogenic animes is suggested in lead encephalopathy. (33 references, 7 tables)

  8. Differential Recruitment of Brain Regions During Response Inhibition in Children Prenatally Exposed to Alcohol.

    Science.gov (United States)

    Kodali, Vikas N; Jacobson, Joseph L; Lindinger, Nadine M; Dodge, Neil C; Molteno, Christopher D; Meintjes, Ernesta M; Jacobson, Sandra W

    2017-02-01

    Response inhibition is a distinct aspect of executive function that is frequently impaired in children with fetal alcohol spectrum disorders (FASD). We used a Go/NoGo (GNG) task in a functional MRI protocol to investigate differential activation of brain regions in the response inhibition network in children diagnosed with full or partial fetal alcohol syndrome (FAS/PFAS), compared with healthy controls. A rapid, event-related task with 120 Go and 60 NoGo trials was used to study children aged 8 to 12 years-8 with FAS/PFAS, 17 controls. Letters were projected sequentially, with Go and NoGo trials randomly interspersed across the task. BOLD signal in the whole brain was contrasted for the correct NoGo minus correct Go trials between the FAS/PFAS and control groups. Compared to the FAS/PFAS group, controls showed greater activation of the inferior frontal and anterior cingulate network linked to response inhibition in typically developing children. By contrast, the FAS/PFAS group showed greater BOLD response in dorsolateral prefrontal cortex and other middle prefrontal regions, suggesting compensation for inefficient function of pathways that normally mediate inhibitory processing. All group differences were significant after control for potential confounding variables. None of the effects of prenatal alcohol exposure on activation of the regions associated with response inhibition were attributable to the effects of this exposure on IQ. This is the first FASD GNG study in which all participants in the exposed group met criteria for a diagnosis of full FAS or PFAS. Although FASD is frequently comorbid with attention deficit hyperactivity disorder, the pattern of brain activation seen in these disorders differs, suggesting that different neural pathways mediate response inhibition in FASD and that different interventions for FASD are, therefore, warranted. Copyright © 2017 by the Research Society on Alcoholism.

  9. Corticosterone mediates some but not other behavioural changes induced by prenatal stress in rats.

    Science.gov (United States)

    Salomon, S; Bejar, C; Schorer-Apelbaum, D; Weinstock, M

    2011-02-01

    The effect of daily varied stress from days 13-21 of gestation in Wistar rats was investigated by tests of learning and memory and anxiogenic behaviour in the 60-day-old offspring of both sexes. Prenatal stress decreased the anogenital distance in males at 1 day of age. Anxiogenic behaviour in the elevated plus maze was seen in prenatally-stressed rats of both genders. There was no significant gender difference in the rate of spatial learning in the Morris water maze but prenatal stress only slowed that of males. In the object recognition test with an inter-trial interval of 40 min, females but not males, discriminated between a familiar and novel object. Prenatal stress did not affect object discrimination in females but feminised that in males. Maternal adrenalectomy with replacement of basal corticosterone levels in the drinking fluid prevented all of the above effects of prenatal stress in the offspring. To mimic the peak corticosterone levels and time course of elevation in response to stress, corticosterone (3 mg/kg) was injected twice (0 and 30 min) on days 13-16 and once on days 17-20 of gestation to adrenalectomised mothers. This treatment re-instated anxiogenic behaviour similar to that induced by prenatal stress, indicating that it is mediated by exposure of the foetal brain to raised levels of corticosterone. However, steroid administration to adrenalectomised dams did not decrease anogenital distance, feminise object recognition memory or slow spatial learning in their male offspring. The findings indicate that other adrenal hormones are necessary to induce these effects of prenatal stress. © 2011 The Authors. Journal of Neuroendocrinology © 2011 Blackwell Publishing Ltd.

  10. [Free radical modification of proteins in brain structure of Sprague-Dawley rats and some behaviour indicators after prenatal stress].

    Science.gov (United States)

    V'iushina, A V; Pritvorova, A V; Flerov, M A

    2012-08-01

    We studied the influence of late prenatal stress on free radical oxidation processes in Sprague-Dawley rats cortex, striatum, hippocampus, hypothalamus proteins. It was shown that after prenatal stress most changes were observed in hypothalamus and hippocampus. It was shown that in hypothalamus spontaneous oxidation level increased, but level of induced oxidation decreased, the opposite changes were found in hippocampus. Simultaneously minor changes of protein modification were observed in cortex and striatum. It was shown that prenatal stress changed both correlation of proteins free radical oxidation in studied structures and values of these data regarding to control. In test of "open field" motor activity in rats after prenatal stress decreased and time of freezing and grooming increased; opposite, in T-labyrinth motor activity and time of grooming in rats after prenatal stress increased, but time of freezing decreased.

  11. 'Unicorn' among rats exposed to mycotoxins from Fusarium.

    Science.gov (United States)

    Schoental, R

    1983-05-01

    A horn-like nodule developed in the middle of the forehead of a white rat, exposed perinatally to T-2 toxin and to zearalenone, the secondary metabolites of Fusarium. The hard nodule consisted mainly of keratine, derived from a squamous carcinoma spreading through the nasal turbinals and invading the brain.

  12. Activation of presynaptic oxytocin receptors enhances glutamate release in the ventral hippocampus of prenatally restraint stressed rats.

    Science.gov (United States)

    Mairesse, Jérôme; Gatta, Eleonora; Reynaert, Marie-Line; Marrocco, Jordan; Morley-Fletcher, Sara; Soichot, Marion; Deruyter, Lucie; Camp, Gilles Van; Bouwalerh, Hammou; Fagioli, Francesca; Pittaluga, Anna; Allorge, Delphine; Nicoletti, Ferdinando; Maccari, Stefania

    2015-12-01

    Oxytocin receptors are known to modulate synaptic transmission and network activity in the hippocampus, but their precise function has been only partially elucidated. Here, we have found that activation of presynaptic oxytocin receptor with the potent agonist, carbetocin, enhanced depolarization-evoked glutamate release in the ventral hippocampus with no effect on GABA release. This evidence paved the way for examining the effect of carbetocin treatment in "prenatally restraint stressed" (PRS) rats, i.e., the offspring of dams exposed to repeated episodes of restraint stress during pregnancy. Adult PRS rats exhibit an anxious/depressive-like phenotype associated with an abnormal glucocorticoid feedback regulation of the hypothalamus-pituitary-adrenal (HPA) axis, and, remarkably, with a reduced depolarization-evoked glutamate release in the ventral hippocampus. Chronic systemic treatment with carbetocin (1mg/kg, i.p., once a day for 2-3 weeks) in PRS rats corrected the defect in glutamate release, anxiety- and depressive-like behavior, and abnormalities in social behavior, in the HPA response to stress, and in the expression of stress-related genes in the hippocampus and amygdala. Of note, carbetocin treatment had no effect on these behavioral and neuroendocrine parameters in prenatally unstressed (control) rats, with the exception of a reduced expression of the oxytocin receptor gene in the amygdala. These findings disclose a novel function of oxytocin receptors in the hippocampus, and encourage the use of oxytocin receptor agonists in the treatment of stress-related psychiatric disorders in adult life. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Genetic effects in children exposed in prenatal period to ionizing radiation after the Chornobyl nuclear power plant accident.

    Science.gov (United States)

    Stepanova, Ye I; Vdovenko, V Yu; Misharina, Zh A; Kolos, V I; Mischenko, L P

    2016-12-01

    To study the genetic effects in children exposed to radiation in utero as a result of the Chornobyl nuclear power plant accident accounting the total radiation doses and equivalent radiation doses to the red bone marrow. Incidence of minor developmental anomalies was studied in children exposed to radiation in utero (study group) and in the control group (1144 subjects surveyed in total). Cytogenetic tests using the method of differential G-banding of chromosomes were conducted in 60 children of both study and control groups (10-12-year-olds) and repeatedly in 39 adolescents (15-17-year-olds). A direct correlation was found between the number of minor developmental anomalies and fetal dose of radiation, and a reverse one with fetal gestational age at the time of radiation exposure. Incidence of chromosomal damage in somatic cells of 10-12-year-old children exposed prenatally was associated with radiation dose to the red bone marrow. The repeated testing has revealed that an increased level of chromosomal aberrations was preserved in a third of adolescents. The persons exposed to ionizing radiation at prenatal period should be attributed to the group of carcinogenic risk due to persisting increased levels of chromosome damage. This article is a part of a Special Issue entitled "The Chornobyl Nuclear Accident: Thirty Years After".

  14. Impaired brain development in the rat following prenatal exposure to methylazoxymethanol acetate at gestational day 17 and neurotrophin distribution

    NARCIS (Netherlands)

    Fiore, M; Grace, AA; Korf, J; Stampachiacchiere, B; Aloe, L

    2004-01-01

    Several neuropsychiatric disorders, including schizophrenia, are the consequence of a disrupted development of the CNS. Accordingly, intrauterine exposure to toxins may increase the risk for psychopathology. We investigated whether prenatal exposure of rats to the neurotoxin methylaxoxymethanol

  15. Emotional Contagion is not Altered in Mice Prenatally Exposed to Poly (I:C) on Gestational Day 9.

    Science.gov (United States)

    Gonzalez-Liencres, Cristina; Juckel, Georg; Esslinger, Manuela; Wachholz, Simone; Manitz, Marie-Pierre; Brüne, Martin; Friebe, Astrid

    2016-01-01

    Prenatal immune activation has been associated with increased risk of developing schizophrenia. The polyinosinic-polycytidylic acid (Poly(I:C)) mouse model replicates some of the endophenotype characteristic of this disorder but the social deficits observed in schizophrenia patients have not been well studied in this model. Therefore we aimed to investigate social behavior, in particular emotional contagion for pain, in this mouse model. We injected pregnant mouse dams with Poly(I:C) or saline (control) on gestation day 9 (GD9) and we evaluated their offspring in the pre-pulse inhibition (PPI) test at age 50-55 days old to confirm the reliability of our model. Mice were then evaluated in an emotional contagion test immediately followed by the light/dark test to explore post-test anxiety-like behavior at 10 weeks of age. In the emotional contagion test, an observer (prenatally exposed to Poly(I:C) or to saline) witnessed a familiar wild-type (WT) mouse (demonstrator) receiving electric foot shocks. Our results replicate the sensory gating impairments in the Poly(I:C) offspring but we only observed minor group differences in the social tasks. One of the differences we found was that demonstrators deposited fewer feces in the presence of control observers than of observers prenatally exposed to Poly(I:C), which we suggest could be due to the observers' behavior. We discuss the findings in the context of age, sex and day of prenatal injection, suggesting that Poly(I:C) on GD9 may be a valuable tool to assess other symptoms or symptom clusters of schizophrenia but perhaps not comprising the social domain.

  16. Radiation-related small head sizes among prenatally exposed atomic bomb survivors

    International Nuclear Information System (INIS)

    Otaki, Masanori; Schull, William J.

    2004-01-01

    The population prenatally exposed to the atomic bombings of Hiroshima and Nagasaki, referred to as the In Utero Clinical Sample, on whom Dosimetry System 1986 doses are available consists of 1566 individuals (1242 in Hiroshima and 324 in Nagasaki). Of these study subjects, 1473 had the circumference of their heads measured at least once between ages 9 to 19. Among these 1473 individuals, 62 had small heads - the circumference of the head was two standard deviations or more below the observed specific age-at-measurement mean. Twenty-six of the 30 cases with severe mental retardation described elsewhere are included among these subjects. Of these 26 severely mentally retarded cases, 15 (58%) had small heads. Most (86%) of the individuals with small heads were exposed in the first or second trimester of pregnancy - 55% in the former period and 31% in the latter. Various dose-response relationships, with and without a threshold, have been fitted to the data grouped by the trimester or postovulatory age (weeks after ovulation) at which exposure occurred. A significant effect of radiation on the frequency of individuals with atypically small heads is observed only in the first and second trimesters and for the intervals postovulation of 0-7 weeks and 8-15 weeks. Although the risk of a small head at 0-7 weeks postovulation increases significantly with increasing dose, no increase in risk for severe mental retardation is noted in this period. No excess risk of a small head was seen in the third trimester or among individuals exposed at ≥ 16 weeks postovulation. The estimated threshold, based either on a linear or a linear-quadratic dose-response relationship, is zero or thereabouts. This apparent absence of a threshold and the somewhat different periods of vulnerability suggest an embryological difference in the development of both a small head and mental retardation. Mean IQ (using the Koga test) and its standard deviation are 63.8 and 8.5, respectively, for the

  17. Toxicity of lunar dust assessed in inhalation-exposed rats.

    Science.gov (United States)

    Lam, Chiu-wing; Scully, Robert R; Zhang, Ye; Renne, Roger A; Hunter, Robert L; McCluskey, Richard A; Chen, Bean T; Castranova, Vincent; Driscoll, Kevin E; Gardner, Donald E; McClellan, Roger O; Cooper, Bonnie L; McKay, David S; Marshall, Linda; James, John T

    2013-10-01

    Humans will again set foot on the moon. The moon is covered by a layer of fine dust, which can pose a respiratory hazard. We investigated the pulmonary toxicity of lunar dust in rats exposed to 0, 2.1, 6.8, 20.8 and 60.6 mg/m(3) of respirable-size lunar dust for 4 weeks (6 h/day, 5 days/week); the aerosols in the nose-only exposure chambers were generated from a jet-mill ground preparation of a lunar soil collected during the Apollo 14 mission. After 4 weeks of exposure to air or lunar dust, groups of five rats were euthanized 1 day, 1 week, 4 weeks or 13 weeks after the last exposure for assessment of pulmonary toxicity. Biomarkers of toxicity assessed in bronchoalveolar fluids showed concentration-dependent changes; biomarkers that showed treatment effects were total cell and neutrophil counts, total protein concentrations and cellular enzymes (lactate dehydrogenase, glutamyl transferase and aspartate transaminase). No statistically significant differences in these biomarkers were detected between rats exposed to air and those exposed to the two low concentrations of lunar dust. Dose-dependent histopathology, including inflammation, septal thickening, fibrosis and granulomas, in the lung was observed at the two higher exposure concentrations. No lesions were detected in rats exposed to ≤6.8 mg/m(3). This 4-week exposure study in rats showed that 6.8 mg/m(3) was the highest no-observable-adverse-effect level (NOAEL). These results will be useful for assessing the health risk to humans of exposure to lunar dust, establishing human exposure limits and guiding the design of dust mitigation systems in lunar landers or habitats.

  18. Low dose prenatal ethanol exposure induces anxiety-like behaviour and alters dendritic morphology in the basolateral amygdala of rat offspring.

    Directory of Open Access Journals (Sweden)

    Carlie L Cullen

    Full Text Available Prenatal exposure to high levels of alcohol is strongly associated with poor cognitive outcomes particularly in relation to learning and memory. It is also becoming more evident that anxiety disorders and anxiety-like behaviour can be associated with prenatal alcohol exposure. This study used a rat model to determine if prenatal exposure to a relatively small amount of alcohol would result in anxiety-like behaviour and to determine if this was associated with morphological changes in the basolateral amygdala. Pregnant Sprague Dawley rats were fed a liquid diet containing either no alcohol (Control or 6% (vol/vol ethanol (EtOH throughout gestation. Male and Female offspring underwent behavioural testing at 8 months (Adult or 15 months (Aged of age. Rats were perfusion fixed and brains were collected at the end of behavioural testing for morphological analysis of pyramidal neuron number and dendritic morphology within the basolateral amygdala. EtOH exposed offspring displayed anxiety-like behaviour in the elevated plus maze, holeboard and emergence tests. Although sexually dimorphic behaviour was apparent, sex did not impact anxiety-like behaviour induced by prenatal alcohol exposure. This increase in anxiety - like behaviour could not be attributed to a change in pyramidal cell number within the BLA but rather was associated with an increase in dendritic spines along the apical dendrite which is indicative of an increase in synaptic connectivity and activity within these neurons. This study is the first to link increases in anxiety like behaviour to structural changes within the basolateral amygdala in a model of prenatal ethanol exposure. In addition, this study has shown that exposure to even a relatively small amount of alcohol during development leads to long term alterations in anxiety-like behaviour.

  19. Effects of environmental enrichment on behavioral deficits and alterations in hippocampal BDNF induced by prenatal exposure to morphine in juvenile rats.

    Science.gov (United States)

    Ahmadalipour, A; Sadeghzadeh, J; Vafaei, A A; Bandegi, A R; Mohammadkhani, R; Rashidy-Pour, A

    2015-10-01

    Prenatal morphine exposure throughout pregnancy can induce a series of neurobehavioral and neurochemical disturbances by affecting central nervous system development. This study was designed to investigate the effects of an enriched environment on behavioral deficits and changes in hippocampal brain-derived neurotrophic factor (BDNF) levels induced by prenatal morphine in rats. On pregnancy days 11-18, female Wistar rats were randomly injected twice daily with saline or morphine. Offspring were weaned on postnatal day (PND) 21. They were subjected to a standard rearing environment or an enriched environment on PNDs 22-50. On PNDs 51-57, the behavioral responses including anxiety and depression-like behaviors, and passive avoidance memory as well as hippocampal BDNF levels were investigated. The light/dark (L/D) box and elevated plus maze (EPM) were used for the study of anxiety, forced swimming test (FST) was used to assess depression-like behavior and passive avoidance task was used to evaluate learning and memory. Prenatal morphine exposure caused a reduction in time spent in the EPM open arms and a reduction in time spent in the lit side of the L/D box. It also decreased step-through latency and increased time spent in the dark side of passive avoidance task. Prenatal morphine exposure also reduced immobility time and increased swimming time in FST. Postnatal rearing in an enriched environment counteracted with behavioral deficits in the EPM and passive avoidance task, but not in the L/D box. This suggests that exposure to an enriched environment during adolescence period alters anxiety profile in a task-specific manner. Prenatal morphine exposure reduced hippocampal BDNF levels, but enriched environment significantly increased BDNF levels in both saline- and morphine-exposed groups. Our results demonstrate that exposure to an enriched environment alleviates behavioral deficits induced by prenatal morphine exposure and up-regulates the decreased levels of BDNF

  20. A putative role for hypothalamic glucocorticoid receptors in hypertension induced by prenatal undernutrition in the rat.

    Science.gov (United States)

    Pérez, Hernán; Soto-Moyano, Rubén; Ruiz, Samuel; Hernández, Alejandro; Sierralta, Walter; Olivares, Ricardo; Núñez, Héctor; Flores, Osvaldo; Morgan, Carlos; Valladares, Luis; Gatica, Arnaldo; Flores, Francisco J

    2010-10-08

    Prenatal undernutrition induces hypertension later in life, possibly by disturbing the hypothalamo-pituitary-adrenal axis through programming decreased expression of hypothalamic glucocorticoid receptors. We examined the systolic blood pressure, heart rate and plasma corticosterone response to intra-paraventricular dexamethasone, mifepristone and corticosterone in eutrophic and prenatally undernourished young rats. Undernutrition was induced during fetal life by restricting the diet of pregnant mothers to 10 g daily (40% of diet consumed by well-nourished controls). At day 40 of postnatal life (i) intra-paraventricular administration of dexamethasone significantly reduced at least for 24h both the systolic pressure (-11.6%), the heart rate (-20.8%) and the plasma corticosterone (-40.0%) in normal animals, while producing lower effects (-5.5, -8.7, and -22.3%, respectively) on undernourished rats; (ii) intra-paraventricular administration of the antiglucocorticoid receptor ligand mifepristone to normal rats produced opposite effects (8.2, 20.3, and 48.0% increase, respectively) to those induced by dexamethasone, being these not significant in undernourished animals; (iii) intra-paraventricular corticosterone did not exert any significant effect. Results suggest that the low sensitivity of paraventricular neurons to glucocorticoid receptor ligands observed in prenatally undernourished rats could be due to the already reported glucocorticoid receptor expression, found in the hypothalamus of undernourished animals. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

  1. Micronuclei frequency in albino rats exposed to high natural radiation

    International Nuclear Information System (INIS)

    Aneesh, D.; Godwin Wesley, S.

    2013-01-01

    Genotoxicity and DNA damage endpoints are used to evaluate results in the context of cell survival. Genotoxicity in mammalian cells is monitored mostly by using cytokinesis-block micronucleus (CBMN) assay. The score of micronuclei (MN) in peripheral blood lymphocytes can be used as a biomarker and also as a bio-dosimeter of radiation exposure. In the present study the effect of natural radiation on albino rats has been investigated, to find out if there is any increase in MN frequency in peripheral blood lymphocytes. Animals at the age of 2-3 weeks were exposed to natural radiation, at the dose of 10.38 μGyh -1 for a period of 6 months. A parallel control set was also maintained (0.12 μGy h -1 '). Blood samples were collected from both test (exposed to natural radiation) and control rats. Lymphocyte culture was done following 'microculture techniques' for 72 h. Cytochalasin B, at a concentration of 6.0 μg/ml, was added to the lymphocyte cultures at 44 h to block cytokinesis. The frequency of MN was evaluated by scoring a total of 1000 binucleated (BN) cells from one slide. The frequency of MN among the rats exposed to natural radiation was found to be 1.83±0.05 per 1000 BN cells and in the control it was 1.82±0.07 per 1000 BN cells. No statistically significant difference in the MN frequencies of exposed and control groups (p>0.05) was seen. The lower MN frequency in natural radiation exposed rats could be an indication of adaptive response. (author)

  2. Development of rat telencephalic neurons after prenatal x-irradiation

    International Nuclear Information System (INIS)

    Norton, S.

    1979-01-01

    Telencephalic neurons of rats, irradiated at day 15 of gestation with 125 R, develop synaptic connections on dendrites during maturation which appear to be normal spines in Golgi-stained light microscope preparations. At six weeks of postnatal age both control and irradiated rats have spiny dendritic processes on cortical pyramidal cells and caudate Golgi type II neurons. However, when the rats are 6 months old the irradiated rats have more neurons with beaded dendritic processes that lack spines or neurons and are likely to be degenerating neurons. The apparently normal development of the neurons followed by degeneration in the irradiated rat has a parallel in previous reports of the delayed hyperactivity which develops in rats irradiated on the fifteenth gestational day

  3. Effect of prenatal restraint stress and morphine co-administration on plasma vasopressin concentration and anxiety behaviors in adult rat offspring.

    Science.gov (United States)

    Nakhjiri, Elnaz; Saboory, Ehsan; Roshan-Milani, Shiva; Rasmi, Yousef; Khalafkhani, Davod

    2017-03-01

    Stressful events and exposure to opiates during gestation have important effects on the later mental health of the offspring. Anxiety is among the most common mental disorders. The present study aimed to identify effects of prenatal restraint stress and morphine co-administration on plasma vasopressin concentration (PVC) and anxiety behaviors in rats. Pregnant rats were divided into four groups (n = 6, each): saline, morphine, stress + saline and stress + morphine treatment. The stress procedure consisted of restraint twice per day, two hours per session, for three consecutive days starting on day 15 of pregnancy. Rats in the saline and morphine groups received either 0.9% saline or morphine intraperitoneally on the same days. In the morphine/saline + stress groups, rats were exposed to restraint stress and received either morphine or saline intraperitoneally. All offspring were tested in an elevated plus maze (EPM) on postnatal day 90 (n = 6, each sex), and anxiety behaviors of each rat were recorded. Finally, blood samples were collected to determine PVC. Prenatal morphine exposure reduced anxiety-like behaviors. Co-administration of prenatal stress and morphine increased locomotor activity (LA) and PVC. PVC was significantly lower in female offspring of the morphine and morphine + stress groups compared with males in the same group, but the opposite was seen in the saline + stress group. These data emphasize the impact of prenatal stress and morphine on fetal neuroendocrine development, with long-term changes in anxiety-like behaviors and vasopressin secretion. These changes are sex specific, indicating differential impact of prenatal stress and morphine on fetal neuroendocrine system development. Lay Summary Pregnant women are sometimes exposed to stressful and painful conditions which may lead to poor outcomes for offspring. Opiates may provide pain and stress relief to these mothers. In this study, we used an experimental model of

  4. Effects of prenatal exposure to a low dose atrazine metabolite mixture on pubertal timing and prostate development of male Long-Evans rats

    Energy Technology Data Exchange (ETDEWEB)

    Stanko, Jason [National Institute of Environmental Health Sciences (NIEHS); Enoch, Rolondo [North Carolina Central University, Durham; Rayner, Jennifer L [ORNL; Davis, Christine [U.S. Environmental Protection Agency; Wolf, Douglas [U.S. Environmental Protection Agency; Malarkey, David [University of North Carolina, Chapel Hill; Fenton, Suzanne [National Institute of Environmental Health Sciences (NIEHS)

    2010-12-01

    The present study examines the postnatal reproductive development of male rats following prenatal exposure to an atrazine metabolite mixture (AMM) consisting of the herbicide atrazine and its environmental metabolites diaminochlorotriazine, hydroxyatrazine, deethylatrazine, and deisopropylatrazine. Pregnant Long-Evans rats were treated by gavage with 0.09, 0.87, or 8.73 mg AMM/kg body weight (BW), vehicle, or 100 mg ATR/kg BW positive control, on gestation days 15 19. Preputial separation was significantly delayed in 0.87 mg and 8.73 mg AMM-exposed males. AMM-exposed males demonstrated a significant treatment-related increase in incidence and severity of inflammation in the prostate on postnatal day (PND) 120. A dose-dependent increase in epididymal fat masses and prostate foci were grossly visible in AMM-exposed offspring. These results indicate that a short, late prenatal exposure to mixture of chlorotriazine metabolites can cause chronic prostatitis in male LE rats. The mode of action for these effects is presently unclear.

  5. Melatonin attenuates prenatal dexamethasone-induced blood pressure increase in a rat model.

    Science.gov (United States)

    Tain, You-Lin; Chen, Chih-Cheng; Sheen, Jiunn-Ming; Yu, Hong-Ren; Tiao, Mao-Meng; Kuo, Ho-Chang; Huang, Li-Tung

    2014-04-01

    Although antenatal corticosteroid is recommended to accelerate fetal lung maturation, prenatal dexamethasone exposure results in hypertension in the adult offspring. Since melatonin is a potent antioxidant and has been known to regulate blood pressure, we examined the beneficial effects of melatonin therapy in preventing prenatal dexamethasone-induced programmed hypertension. Male offspring of Sprague-Dawley rats were assigned to four groups (n = 12/group): control, dexamethasone (DEX), control + melatonin, and DEX + melatonin. Pregnant rats received intraperitoneal dexamethasone (0.1 mg/kg) from gestational day 16 to 22. In the melatonin-treatment groups, rats received 0.01% melatonin in drinking water during their entire pregnancy and lactation. Blood pressure was measured by an indirect tail-cuff method. Gene expression and protein levels were analyzed by real-time quantitative polymerase chain reaction and Western blotting, respectively. At 16 weeks of age, the DEX group developed hypertension, which was partly reversed by maternal melatonin therapy. Reduced nephron numbers due to prenatal dexamethasone exposure were prevented by melatonin therapy. Renal superoxide and NO levels were similar in all groups. Prenatal dexamethasone exposure led to increased mRNA expression of renin and prorenin receptor and up-regulated histone deacetylase (HDAC)-1 expression in the kidneys of 4-month-old offspring. Maternal melatonin therapy augmented renal Mas protein levels in DEX + melatonin group, and increased renal mRNA expression of HDAC-1, HDAC-2, and HDAC-8 in control and DEX offspring. Melatonin attenuated prenatal DEX-induced hypertension by restoring nephron numbers, altering RAS components, and modulating HDACs. Copyright © 2014 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

  6. Lower birth weight and increased body fat at school age in children prenatally exposed to modern pesticides: a prospective study

    Directory of Open Access Journals (Sweden)

    Grandjean Philippe

    2011-09-01

    Full Text Available Abstract Background Endocrine disrupting chemicals have been hypothesized to play a role in the obesity epidemic. Long-term effects of prenatal exposure to non-persistent pesticides on body composition have so far not been investigated. The purpose of this study was to assess possible effects of prenatal exposure to currently used pesticides on children's growth, endocrine and reproductive function. Methods In a prospective study of 247 children born by women working in greenhouses in early pregnancy, 168 were categorized as prenatally exposed to pesticides. At three months (n = 203 and at 6 to11 years of age (n = 177 the children underwent a clinical examination and blood sampling for analysis of IGF-I, IGFBP3 and thyroid hormones. Body fat percentage at age 6 to11 years was calculated from skin fold measurements. Pesticide related associations were tested by linear multiple regression analysis, adjusting for relevant confounders. Results Compared to unexposed children birth weight and weight for gestational age were lower in the highly exposed children: -173 g (-322; -23, -4.8% (-9.0; -0.7 and medium exposed children: -139 g (-272; -6, -3.6% (-7.2; -0.0. Exposed (medium and highly together children had significantly larger increase in BMI Z-score (0.55 SD (95% CI: 0.1; 1.0 from birth to school age and highly exposed children had 15.8% (0.2; 34.6 larger skin folds and higher body fat percentage compared to unexposed. If prenatally exposed to both pesticides and maternal smoking (any amount, the sum of four skin folds was 46.9% (95% CI: 8.1; 99.5 and body fat percentage 29.1% (95% CI: 3.0; 61.4 higher. There were subtle associations between exposure and TSH Z-score -0.66(-1.287; -0.022 and IGF-I Z-score (girls: -0.62(-1.0; -0.22, boys: 0.38(-0.03; 0.79, but not IGFBP3. Conclusions Occupational exposure to currently used pesticides may have adverse effects in spite of the added protection offered to pregnant women. Maternal exposure to

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

    OpenAIRE

    Smith, Dani; Aherrera, Angela; Lopez, Armando; Neptune, Enid; Winickoff, Jonathan P.; Klein, Jonathan D.; Chen, Gang; Lazarus, Philip; Collaco, Joseph M.; McGrath-Morrow, Sharon A.

    2015-01-01

    Nicotine exposure has been associated with an increased likelihood of developing attention deficit hyperactivity disorder (ADHD) in offspring of mothers who smoked during pregnancy. The goal of this study was to determine if exposure to E-cigarette nicotine vapors during late prenatal and early postnatal life altered behavior in adult mice. Methods: Timed-pregnant C57BL/6J mice were exposed to 2.4% nicotine in propylene glycol (PG) or 0% nicotine /PG once a day from gestational day 15 until d...

  8. Neurobehavioral deficits and increased blood pressure in school-age children prenatally exposed to pesticides

    DEFF Research Database (Denmark)

    Harari, Raul; Julvez, Jordi; Murata, Katsuyuki

    2010-01-01

    -Binet Copying Recall Test). These associations corresponded to a developmental delay of 1.5-2 years. Prenatal pesticide exposure was also significantly associated with an average increase of 3.6 mmHg in systolic blood pressure and a slight decrease in body mass index of 1.1 kg/m2. Inclusion of the pilot data...

  9. Automated cerebellar segmentation: Validation and application to detect smaller volumes in children prenatally exposed to alcohol

    Directory of Open Access Journals (Sweden)

    Valerie A. Cardenas

    2014-01-01

    Discussion: These results demonstrate excellent reliability and validity of automated cerebellar volume and mid-sagittal area measurements, compared to manual measurements. These data also illustrate that this new technology for automatically delineating the cerebellum leads to conclusions regarding the effects of prenatal alcohol exposure on the cerebellum consistent with prior studies that used labor intensive manual delineation, even with a very small sample.

  10. Prenatal exposure to lipopolysaccharide combined with pre- and postnatal high-fat diet result in lowered blood pressure and insulin resistance in offspring rats.

    Science.gov (United States)

    Hao, Xue-Qin; Du, Jing-Xia; Li, Yan; Li, Meng; Zhang, Shou-Yan

    2014-01-01

    Adult metabolic syndrome may in part have origins in fetal or early life. This study was designed to explore the effect of prenatal exposure to lipopolysaccharide and high-fat diet on metabolic syndrome in offspring rats. 32 pregnant rats were randomly divided into four groups, including Control group; LPS group (pregnant rats were injected with LPS 0.4 mg/kg intraperitoneally on the 8(th), 10(th) and 12(th) day of pregnancy); High-fat group (maternal rats had high-fat diet during pregnancy and lactation period, and their pups also had high-fat diet up to the third month of life); LPS + High-fat group (rats were exposed to the identical experimental scheme with LPS group and High-fat group). Blood pressure elevated in LPS group and High-fat group, reduced in LPS+High-fat group, accompanied by the increase of serum leptin level in LPS and High-fat group and increase of serum IL-6, TNF-a in High-fat group; both serum insulin and cholesterol increased in High-fat and LPS+High-fat group, as well as insulin in LPS group. HOMA-IR value increased in LPS, High-fat and LPS+High-fat group, and QUICKI decreased in these groups; H-E staining showed morphologically pathological changes in thoracic aorta and liver tissue in the three groups. Increased serum alanine and aspartate aminotransferase suggest impaired liver function in LPS+High-fat group. Prenatal exposure to lipopolysaccharide combined with pre- and postnatal high-fat diet result in lowered blood pressure, insulin resistance and impaired liver function in three-month old offspring rats. The lowered blood pressure might benefit from the predictive adaptive response to prenatal inflammation.

  11. Metabolic trajectories based on 1H NMR spectra of urines from sheep exposed to nutritional challenges during prenatal and early postnatal life

    DEFF Research Database (Denmark)

    Nyberg, Nils; Nielsen, Mette Benedicte Olaf; Jaroszewski, Jerzy W.

    2010-01-01

    1H NMR metabolic profiles of urine from sheep exposed to prenatal nutritional restriction (n = 19) and a control group with normal prenatal nutritional requirements (n = 19), followed by either conventional (n = 10 + 10) or high carbohydrate high fat postnatal diet (n = 9 + 9), were studied. Urine...... undernutrition followed by normal postnatal diet showed metabolic patters that are ahead in time on the metabolic trajectory relative to the prenatal control group. No long-term effects of fetal undernutrition, alone or in combination with postnatal hypernutrition were observed....... amount of glucose, indicative of monogastric-like metabolism, and exhibiting concomitant increase of metabolites related to rumen microflora (mainly glycine conjugates of benzoic and phenylacetic acid) as the ruminal metabolism developed. Urines from young (2-month-old) animals exposed to prenatal...

  12. The neurotoxic effects of prenatal gabapentin and oxcarbazepine exposure on newborn rats.

    Science.gov (United States)

    Erisgin, Zuleyha; Ayas, Bulent; Nyengaard, Jens R; Ercument Beyhun, N; Terzi, Yuksel

    2017-10-05

    Teratogenicity is a problematic issue for pregnant women because of X-ray radiation, drugs, and genetic and unknown variables. First-generation antiepileptic drugs (AED) like valproic acid are well-known teratogens for developing fetuses. However, their usage is necessary in order to prevent maternal seizures. The underlying mechanism of birth defects associated with AED exposure remains unclear and information about the neurotoxic effects of prenatal exposure to AED is still limited. Oxcarbazepine (OXC) and gabapentin (GBP) are second-generation AED. It still remains unclear how much these drugs are safe during pregnancy. This study aimed to investigate whether any neurotoxic effect of OXC and GBP in utero exposure on the developing brain. Eighteen pregnant Wistar albino rats were divided into six groups. The first group was exposed to OXC at 100 mg/kg/day, the second to GBP at 50 mg/kg/day, and third to saline (0.9% NaCl) at 1.5 ml/day between the first and the fifth days of gestation. The same procedure was applied at the same dosages between the 6th and the 15th days of gestation for the 2nd three groups. Five female offspring (total n = 30, 45 days old) were taken from each group and stereological methods were applied in order to analyze the total and dopaminergic neuron number of the substantia nigra pars compacta (SNc). The result is that the OXC and GBP exposure at different gestational periods may not give rise to congenital malformation and it appears that the GBP exposure during the organogenesis period proliferatively affects the total number of neurons.

  13. Altered attentional processing in male and female rats in a prenatal valproic acid exposure model of autism spectrum disorder.

    Science.gov (United States)

    Anshu, Kumari; Nair, Ajay Kumar; Kumaresan, U D; Kutty, Bindu M; Srinath, Shoba; Laxmi, T Rao

    2017-12-01

    Attention is foundational to efficient perception and optimal goal driven behavior. Intact attentional processing is crucial for the development of social and communication skills. Deficits in attention are therefore likely contributors to the core pathophysiology of autism spectrum disorder (ASD). Clinical evidence in ASD is suggestive of impairments in attention and its control, but the underlying mechanisms remain elusive. We examined sustained, spatially divided attention in a prenatal valproic acid (VPA) model of ASD using the 5-choice serial reaction time task (5-CSRTT). As compared to controls, male and female VPA rats had progressively lower accuracy and higher omissions with increasing attentional demands during 5-CSRTT training, and showed further performance decrements when subjected to parametric task manipulations. It is noteworthy that although VPA exposure induced attentional deficits in both sexes, there were task parameter specific sex differences. Importantly, we did not find evidence of impulsivity or motivational deficits in VPA rats but we did find reduced social preference, as well as sensorimotor deficits that suggest pre-attentional information processing impairments. Importantly, with fixed rules, graded difficulty levels, and more time, VPA rats could be successfully trained on the attentional task. To the best of our knowledge, this is the first study examining attentional functions in a VPA model. Our work underscores the need for studying both sexes in ASD animal models and validates the use of the VPA model in the quest for mechanistic understanding of aberrant attentional functions and for evaluating suitable therapeutic targets. Autism Res 2017, 10: 1929-1944. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. We studied rats prenatally exposed to valproic acid (VPA), an established rodent model of autism. Both male and female VPA rats had a range of attentional impairments with sex-specific characteristics

  14. Brain dysfunctions in Wistar rats exposed to municipal landfill leachates

    Directory of Open Access Journals (Sweden)

    Chibuisi G. Alimba

    2015-12-01

    Full Text Available Brain damage induced by Olusosun and Aba-Eku municipal landfill leachates was investigated in Wistar rats. Male rats were orally exposed to 1–25% concentrations of the leachates for 30 days. Catalase (CAT and superoxide dismutase (SOD activities, and malondialdehyde (MDA concentrations in the brain and serum of rats were evaluated; body and brain weight gain and histopathology were examined. There was significant (p < 0.05 decrease in body weight gain and SOD activity but increase in absolute and relative brain weight gain, MDA concentration and CAT activity in both brain and serum of treated rats. The biochemical parameters, which were more altered in the brain than serum, corroborated the neurologic lesions; neurodegeneration of purkinje cells with loss of dendrites, perineural vacuolations of the neuronal cytoplasm (spongiosis and neuronal necrosis in the brain. The concentrations of Cr, Cu, Pb, As, Cd, Mn, Ni, sulphates, ammonia, chloride and phosphate in the leachate samples were above standard permissible limits. The interactions of the neurotoxic constituents of the leachates induced the observed brain damage in the rats via oxidative damage. This suggests health risk in wildlife and human populations.

  15. Responses of vibrissa-sensitive cortical neurons in normal and prenatally x-irradiated rat

    International Nuclear Information System (INIS)

    Ito, M.; Kawabata, M.; Shoji, R.

    1979-01-01

    Rats were irradiated by 200 R of x ray on day 17 of gestation through the body wall of the mother. When they underwent the following electrophysiological tests at the age of 3 to 4 month, the somatosensory cortex showed a lack of layers II, III, IV, and Va. Spike responses to quick whisker deflections were recorded from single cells in the somatosenory cortex of normal and prenatally x-irradiated rats. For the irradiated rats the response latency was prolonged when compared to the normal controls. Cortical laminar analysis of field potentials revealed that there was no difference in the latency of these potentials between the two groups, suggesting that vibrissal sensory signals reach the cortical level normally even in the irradiated rats. The prolonged latency of the irradiated cortical neuronal response could thus be ascribed to an abnormal intracortical delay, which was most likely associated with the failure of development of layer IV stellate cells in these preparations

  16. Early developmental and temporal characteristics of stress-induced secretion of pituitary-adrenal hormones in prenatally stressed rat pups.

    Science.gov (United States)

    Takahashi, L K; Kalin, N H

    1991-08-30

    Previous experiments revealed that 14-day-old prenatally stressed rats have significantly elevated concentrations of plasma adrenocorticotrophic hormone (ACTH) and corticosterone suggesting these animals have an overactive hypothalamic-pituitary-adrenal (HPA) system. In these studies, however, stress-induced hormone levels were determined only immediately after exposure to an acute stressor. Therefore, in the current study, we examined in postnatal days 7, 14 and 21 prenatally stressed rats the stress-induced time course of this pituitary-adrenal hormone elevation. Plasma ACTH and corticosterone were measured in the basal state and at 0.0, 0.5, 1.0, 2.0 and 4.0 h after a 10-min exposure period to foot shocks administered in the context of social isolation. Results indicated that at all 3 ages, plasma ACTH in prenatally stressed rats was significantly elevated. Corticosterone concentrations were also significantly higher in prenatally stressed than in control rats, especially in day 14 rats. Analysis of stress-induced hormone fluctuations over time indicated that by 14 days of age, both prenatally stressed than in control and control rats had significant increases in plasma ACTH and corticosterone after exposure to stress. Furthermore, although prenatally stressed rats had significantly higher pituitary-adrenal hormone concentrations than control animals, the post-stress temporal patterns of decline in ACTH and corticosterone levels were similar between groups. Results suggest that throughout the preweaning period, prenatal stress produces an HPA system that functions in a manner similar to that of controls but at an increased level.

  17. Brain anomalies in children exposed prenatally to a common organophosphate pesticide

    OpenAIRE

    Rauh, Virginia A.; Perera, Frederica P.; Horton, Megan K.; Whyatt, Robin M.; Bansal, Ravi; Hao, Xuejun; Liu, Jun; Barr, Dana Boyd; Slotkin, Theodore A.; Peterson, Bradley S.

    2012-01-01

    Prenatal exposure to chlorpyrifos (CPF), an organophosphate insecticide, is associated with neurobehavioral deficits in humans and animal models. We investigated associations between CPF exposure and brain morphology using magnetic resonance imaging in 40 children, 5.9–11.2 y, selected from a nonclinical, representative community-based cohort. Twenty high-exposure children (upper tertile of CPF concentrations in umbilical cord blood) were compared with 20 low-exposure children on cortical sur...

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

    Directory of Open Access Journals (Sweden)

    Dani Smith

    Full Text Available Timed-pregnant C57BL/6J mice were exposed to 2.4% nicotine in propylene glycol (PG or 0% nicotine /PG once a day from gestational day 15 until delivery. After delivery, offspring and mothers were exposed to E-cigarette vapors for an additional 14 days from postnatal day 2 through 16. Following their last exposure serum cotinine levels were measured in female juvenile mice. Male mice underwent behavioral testing at 14 weeks of age to assess sensorimotor, affective, and cognitive functional domains.Adult male mice exposed to 2.4% nicotine/PG E-cigarette vapors had significantly more head dips in the zero maze test and higher levels of rearing activity in the open field test compared to 0% nicotine/PG exposed mice and untreated controls. In the water maze test after reversal training, the 2.4% nicotine/PG mice spent more than 25% of time in the new location whereas the other groups did not.Adult male mice exhibited increased levels of activity in the zero maze and open field tests when exposed to E-cigarette vapor containing nicotine during late prenatal and early postnatal life. These findings indicate that nicotine exposure from E-cigarettes may cause persistent behavioral changes when exposure occurs during a period of rapid brain growth.

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

    Science.gov (United States)

    Smith, Dani; Aherrera, Angela; Lopez, Armando; Neptune, Enid; Winickoff, Jonathan P; Klein, Jonathan D; Chen, Gang; Lazarus, Philip; Collaco, Joseph M; McGrath-Morrow, Sharon A

    2015-01-01

    Timed-pregnant C57BL/6J mice were exposed to 2.4% nicotine in propylene glycol (PG) or 0% nicotine /PG once a day from gestational day 15 until delivery. After delivery, offspring and mothers were exposed to E-cigarette vapors for an additional 14 days from postnatal day 2 through 16. Following their last exposure serum cotinine levels were measured in female juvenile mice. Male mice underwent behavioral testing at 14 weeks of age to assess sensorimotor, affective, and cognitive functional domains. Adult male mice exposed to 2.4% nicotine/PG E-cigarette vapors had significantly more head dips in the zero maze test and higher levels of rearing activity in the open field test compared to 0% nicotine/PG exposed mice and untreated controls. In the water maze test after reversal training, the 2.4% nicotine/PG mice spent more than 25% of time in the new location whereas the other groups did not. Adult male mice exhibited increased levels of activity in the zero maze and open field tests when exposed to E-cigarette vapor containing nicotine during late prenatal and early postnatal life. These findings indicate that nicotine exposure from E-cigarettes may cause persistent behavioral changes when exposure occurs during a period of rapid brain growth.

  20. Regulation of glutamate dehydrogenase expression in the developing rat liver: control at different levels in the prenatal period

    NARCIS (Netherlands)

    Das, A. T.; Salvadó, J.; Boon, L.; Biharie, G.; Moorman, A. F.; Lamers, W. H.

    1996-01-01

    To study the regulation of the expression of glutamate dehydrogenase (Glu-DH) in rat liver during development, the Glu-DH mRNA concentration in the liver of rats ranging in age from 14 days prenatal development to 3 months after birth was determined. This concentration increased up to two days

  1. Chronic prenatal caffeine exposure impairs novel object recognition and radial arm maze behaviors in adult rats.

    Science.gov (United States)

    Soellner, Deborah E; Grandys, Theresa; Nuñez, Joseph L

    2009-12-14

    In this report, we demonstrate that chronic prenatal exposure to a moderate dose of caffeine disrupts novel object recognition and radial arm maze behaviors in adult male and female rats. Pregnant dams were administered either tap water or 75 mg/L caffeinated tap water throughout gestation. Oral self-administration in the drinking water led to an approximate maternal intake of 10mg/kg/day, equivalent to 2-3 cups of coffee/day in humans based on a metabolic body weight conversion. In adulthood, the offspring underwent testing on novel object recognition, radial arm maze, and Morris water maze tasks. Prenatal caffeine exposure was found to impair 24-h memory retention in the novel object recognition task and impair both working and reference memory in the radial arm maze. However, prenatal caffeine exposure did not alter Morris water maze performance in either a simple water maze procedure or in an advanced water maze procedure that included reversal and working memory paradigms. These findings demonstrate that chronic oral intake of caffeine throughout gestation can alter adult cognitive behaviors in rats.

  2. Physical and behavioral development in rats after late prenatal exposure to diazepam.

    Science.gov (United States)

    Lall, S B; Sahoo, R N

    1990-01-01

    The effect of late prenatal exposure to diazepam (DZP) on physical and behavioral development of rat pups was investigated. Prenatal exposure to DZP (20 mg/kg, sc, in last week of pregnancy) did not alter litter size and no gross malformations were noted at birth. Body weight at birth and subsequent weight gain was significantly less in these animals. The development of reflexes and neuromuscular maturation was normal. Open field locomotor activity and rearing scores were significantly decreased. Test of social play in juvenile rats revealed normal pattern of sexual dimorphism with increased masculinized behavior. Acquisition and retention of passive avoidance task was not affected by DZP exposure, however, retention of brightness discrimination task was significantly decreased. The hypnotic effect of a challenge dose of DZP and convulsive effect of pentylene tetrazole remained unaltered. Open field activity test in adult animals revealed increased ambulation. Probe dose of amphetamine in these animals caused paradoxical decrease in activity. It is concluded that exposure to high dose of DZP during late prenatal period may not manifest in physical or neuromuscular impairment during early development period, except for weight loss, however, it may have long term effects on behavior becoming manifest in adolescence and at maturity.

  3. Frequency of marriage and live birth among survivors prenatally exposed to the atomic bomb

    International Nuclear Information System (INIS)

    Blot, W.J.; Shimizu, Y.; Kato, H.; Miller, R.W.

    1975-01-01

    Frequency of marriage and birth as of January 1973 was determined for persons exposed in utero to the atomic bombs in 1945 and for controls. The marriage rate was lower in persons heavily exposed in utero than in the non-exposed or lightly exposed. This difference is attributed partly to the lesser marriageability of persons with mental retardation who are significantly more numerous among the heavily exposed, and partly to unmeasured variables, possibly including social discrimination against survivors of the atomic bomb. No consistent relation was observed between radiation exposure and three reproductive indices: childless marriages, number of births, and interval between marriage and first birth

  4. Evaluation of passive avoidance learning and spatial memory in rats exposed to low levels of lead during specific periods of early brain development.

    Science.gov (United States)

    Rao Barkur, Rajashekar; Bairy, Laxminarayana K

    2015-01-01

    Widespread use of heavy metal lead (Pb) for various commercial purposes has resulted in the environmental contamination caused by this metal. The studies have shown a definite relationship between low level lead exposure during early brain development and deficit in children's cognitive functions. This study investigated the passive avoidance learning and spatial learning in male rat pups exposed to lead through their mothers during specific periods of early brain development. Experimental male rats were divided into 5 groups: i) the normal control group (NC) (N = 12) consisted of rat offspring born to mothers who were given normal drinking water throughout gestation and lactation, ii) the pre-gestation lead exposed group (PG) (N = 12) consisted of rat offspring, mothers of these rats had been exposed to 0.2% lead acetate in the drinking water for 1 month before conception, iii) the gestation lead exposed group (G) (N = 12) contained rat offspring born to mothers who had been exposed to 0.2% lead acetate in the drinking water throughout gestation, iv) the lactation lead exposed group (L) (N = 12) had rat offspring, mothers of these rats exposed to 0.2% lead acetate in the drinking water throughout lactation and v) the gestation and lactation lead exposed group (GL) (N = 12) contained rat offspring, mothers of these rats were exposed to 0.2% lead acetate throughout gestation and lactation. The study found deficit in passive avoidance learning in the G, L and GL groups of rats. Impairment in spatial learning was found in the PG, G, L and GL groups of rats. Interestingly, the study found that gestation period only and lactation period only lead exposure was sufficient to cause deficit in learning and memory in rats. The extent of memory impairment in the L group of rats was comparable with the GL group of rats. So it can be said that postnatal period of brain development is more sensitive to neurotoxicity compared to prenatal exposure. This work is available in Open

  5. Abnormal regulation for progesterone production in placenta with prenatal cocaine exposure in rats.

    Science.gov (United States)

    Wu, L; Yan, J; Qu, S C; Feng, Y Q; Jiang, X L

    2012-12-01

    Cocaine abuse in pregnant women is currently a significant public hygiene problem and is tightly associated with elevated risk for preterm delivery. Placental steroidogenesis especially progesterone production was essential for success and maintenance of pregnancy in humans and rodents. In the present study, we determined the impact of prenatal cocaine exposure on pathways of placental progesterone synthesis in rats. Pregnant rats were treated cocaine twice daily (15 mg/kg/day) during the third trimester, and the maternal and fetal plasma progesterone and pregnenolone concentrations were detected. We also examined both the protein and mRNA expression of some key enzymes and regulators for progesterone production in placenta. Results showed that, after maternal cocaine use during pregnancy, progesterone and pregnenolone concentrations in both maternal and fetal rats were significantly decreased. Although prenatal cocaine exposure had no effects on placental 3β-hydroxysteroid dehydrogenase type 1 (3βHSD1) expression, protein and mRNA expression of the cholesterol side-chain cleavage enzyme (P450scc/CYP11a) in placenta was significantly inhibited. Moreover, protein and mRNA expressions of MLN64 that regulating cholesterol transport and activating protein 2γ (AP2γ/Tfap2c) that controlling P450scc/CYP11a gene expression in placenta were both decreased following maternal cocaine use in pregnancy. Collectively, this study suggested that prenatal cocaine exposure could insult the placental progesterone production in rats possibly associated with the high risk for preterm delivery. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Mild prenatal protein malnutrition increases alpha 2C-adrenoceptor expression in the rat cerebral cortex during postnatal life.

    Science.gov (United States)

    Sierralta, Walter; Hernández, Alejandro; Valladares, Luis; Pérez, Hernán; Mondaca, Mauricio; Soto-Moyano, Rubén

    2006-05-15

    Mild reduction in the protein content in the diet of pregnant rats from 25 to 8% casein, calorically compensated by carbohydrates, does not alter body and brain weights of rat pups at birth, but results in significant changes of the concentration and release of cortical noradrenaline during postnatal life, together with impaired long-term potentiation and memory formation. Since some central noradrenergic receptors are critically involved in neuroplasticity, the present study evaluated, by utilizing immunohistochemical methods, the effect of mild prenatal protein malnutrition on the alpha 2C-adrenoceptor expression in the frontal and occipital cortices of 8- and 60-day-old rats. At day 8 of postnatal age, prenatally malnourished rats exhibited a three-fold increase of alpha 2C-adrenoceptor expression in both the frontal and the occipital cortices, as compared to well-nourished controls. At 60 days of age, prenatally malnourished rats showed normal expression levels scores of alpha 2C-adrenoceptor in the neocortex. Results suggest that overexpression of neocortical alpha 2C-adrenoceptors during early postnatal life, subsequent to mild prenatal protein malnutrition, could in part be responsible for neural and behavioral disturbances showing prenatally malnourished animals during the postnatal life.

  7. Brain anomalies in children exposed prenatally to a common organophosphate pesticide.

    Science.gov (United States)

    Rauh, Virginia A; Perera, Frederica P; Horton, Megan K; Whyatt, Robin M; Bansal, Ravi; Hao, Xuejun; Liu, Jun; Barr, Dana Boyd; Slotkin, Theodore A; Peterson, Bradley S

    2012-05-15

    Prenatal exposure to chlorpyrifos (CPF), an organophosphate insecticide, is associated with neurobehavioral deficits in humans and animal models. We investigated associations between CPF exposure and brain morphology using magnetic resonance imaging in 40 children, 5.9-11.2 y, selected from a nonclinical, representative community-based cohort. Twenty high-exposure children (upper tertile of CPF concentrations in umbilical cord blood) were compared with 20 low-exposure children on cortical surface features; all participants had minimal prenatal exposure to environmental tobacco smoke and polycyclic aromatic hydrocarbons. High CPF exposure was associated with enlargement of superior temporal, posterior middle temporal, and inferior postcentral gyri bilaterally, and enlarged superior frontal gyrus, gyrus rectus, cuneus, and precuneus along the mesial wall of the right hemisphere. Group differences were derived from exposure effects on underlying white matter. A significant exposure × IQ interaction was derived from CPF disruption of normal IQ associations with surface measures in low-exposure children. In preliminary analyses, high-exposure children did not show expected sex differences in the right inferior parietal lobule and superior marginal gyrus, and displayed reversal of sex differences in the right mesial superior frontal gyrus, consistent with disruption by CPF of normal behavioral sexual dimorphisms reported in animal models. High-exposure children also showed frontal and parietal cortical thinning, and an inverse dose-response relationship between CPF and cortical thickness. This study reports significant associations of prenatal exposure to a widely used environmental neurotoxicant, at standard use levels, with structural changes in the developing human brain.

  8. Multiple endocrine disrupting effects in rats perinatally exposed to butylparaben

    DEFF Research Database (Denmark)

    Boberg, Julie; Petersen, Marta Axelstad; Svingen, Terje

    2016-01-01

    ) expression was reduced in prepubertal, but not adult animals exposed to butylparaben. In adult testes, Nr5a1 expression was reduced at all doses, indicating persistent disruption of steroidogenesis. Prostate histology was altered at prepuberty and adult prostate weights were reduced in the high dose group......Parabens comprise a group of preservatives commonly added to cosmetics, lotions and other consumer products. Butylparaben has estrogenic and anti-androgenic properties and is known to reduce sperm counts in rats following perinatal exposure. Whether butylparaben exposure can affect other endocrine...

  9. Methylmercury chloride induces learning deficits in prenatally treated rats

    Energy Technology Data Exchange (ETDEWEB)

    Muesch, H.R.; Bornhausen, M.; Kriegel, H.; Greim, H.

    1978-01-01

    Methylmercury chloride (MMC) was given to pregnant rats on the 6th, 7th, 8th, and 9th day after conception in doses of 0.05 and 2.0 mg/kg/day. The female offspring of these animals were tested 90 days after birth for learning ability using operant conditioning procedures. The rats were kept at 90% of their normal body weight and trained in a lever-box to press a bar in order to obtain a food pellet. Significant differences in the acquisition speed became apparent when the ratio of bar presses to reward was increased in a classical contingency of differential reinforcement of high rates even at MMC-doses of 4 x 0.05 mg/kg. These differences were not found in the general motility level nor in motor coordination.

  10. Selective elimination of intracortically projecting neurons of the rat neocortex by prenatal x-irradiation

    International Nuclear Information System (INIS)

    Jensen, K.F.

    1981-01-01

    The development of new racing methods has suggested that there are species differences in the extent of the contribution of the different layers of the neocortex to the callosal projection. The present investigation has utilized prenatal x-irradiation to selectively eliminate the late forming neurons of the supragranular layers of the rat neocortex. The reduction in the neuronal population of the supragranular layers closely parallels the reduction in the corpus callosum. These results indicate that the primary source of neurons of the callosal projection, are the late forming neurons of the supragranular layers. Thus, the current results suggest that low dose prenatal x-irradiation may be used to evaluate important developmental events in the formation of neocortical circuitry

  11. Prenatal noise and restraint stress interact to alter exploratory behavior and balance in juvenile rats, and mixed stress reverses these effects.

    Science.gov (United States)

    Badache, Soumeya; Bouslama, Slim; Brahmia, Oualid; Baïri, Abdel Madjid; Tahraoui, Abdel Krim; Ladjama, Ali

    2017-05-01

    We aimed to investigate in adolescent rats the individual and combined effects of prenatal noise and restraint stress on balance control, exploration, locomotion and anxiety behavior. Three groups of pregnant rats were exposed to daily repeated stress from day 11 to day 19 of pregnancy: 3 min noise (Noise Stress, NS); 10 min restraint (restraint stress, RS); or 3 min noise followed by 10 min restraint (mixed stress, MS). On postnatal days (PND) 44, 45 and 46, four groups of male rats (Control, NS, RS:, MS; 16 rats each), were tested as follows: (1) beam walking (BW), (2) open field (OF) and (3) elevated plus maze (EPM). Our results show that the NS group had significantly impaired balance control, locomotion and both horizontal and vertical exploration (p time in EPM open arms: p time to complete BW: p < .05). Hence, combined prenatal stressors exert non-additive effects on locomotion, exploration and balance control, but induce greater anxiety through additive effects. Terminal plasma ACTH concentration was increased by prenatal stress, especially noise, which group had the largest adrenal glands. Overall, contrary to expectation, combined prenatal stressors can interact to increase anxiety level, but diminish alteration of exploration, locomotion and impaired balance control, which were strongly induced by noise stress. Lay summary: Experience of stress in pregnancy can have negative effects on the offspring that are long-lasting. Here, we used laboratory rats to see whether repeated episodes of exposure to loud noise or preventing free movement, alone or together, during pregnancy had different effects on behaviors of the adolescent offspring. Using standard tests, we found the prenatal stresses caused the offspring to be anxious, and not to balance when moving around as well as normal offspring; the degree of impairment depended on the type of stress - loud noise exposure had the greatest effects, but if the stresses were combined the effects

  12. Maternal Melatonin Therapy Rescues Prenatal Dexamethasone and Postnatal High-Fat Diet Induced Programmed Hypertension in Male Rat Offspring

    OpenAIRE

    Tain, You-Lin; Sheen, Jiunn-Ming; Yu, Hong-Ren; Chen, Chih-Cheng; Tiao, Mao-Meng; Hsu, Chien-Ning; Lin, Yu-Ju; Kuo, Kuang-Che; Huang, Li-Tung

    2015-01-01

    Prenatal dexamethasone (DEX) exposure and high-fat (HF) intake are linked to hypertension. We examined whether maternal melatonin therapy prevents programmed hypertension synergistically induced by prenatal DEX plus postnatal HF in adult offspring. We also examined whether DEX and melatonin causes renal programming using next-generation RNA sequencing (NGS) technology. Pregnant Sprague-Dawley rats received intraperitoneal dexamethasone (0.1 mg/kg) or vehicle from gestational day 16 to 22. In ...

  13. Influence of prenatal noise and music on the spatial memory and neurogenesis in the hippocampus of developing rats.

    Science.gov (United States)

    Kim, Hong; Lee, Myoung-Hwa; Chang, Hyun-Kyung; Lee, Taeck-Hyun; Lee, Hee-Hyuk; Shin, Min-Chul; Shin, Mal-Soon; Won, Ran; Shin, Hye-Sook; Kim, Chang-Ju

    2006-03-01

    During the prenatal period, the development of individual is influenced by the environmental factors. In the present study, the influence of prenatal noise and music on the spatial memory and neurogenesis in the hippocampus of developing rats was investigated. The exposure to the noise during pregnancy caused growth retardation, decreased neurogenesis in the hippocampus, and impaired spatial learning ability in pups. The exposure to music during pregnancy, on the other hand, caused increased neurogenesis in the hippocampus and enhanced spatial learning ability in pups. The present study has shown the importance of the prenatal environmental conditions for the cognition and brain development.

  14. Effects of prenatal exposure to N-methylpyrrolidone on postnatal development and behavior in rats

    DEFF Research Database (Denmark)

    Hass, Ulla; Lund, S. P.; Elsner, J.

    1994-01-01

    Pregnant rats (Mol: WIST) were exposed to 150 ppm N-methylpyrrolidone for 6 hours per day on gestation days 7-20. The dose level was selected so as not to induce maternal toxicity or decrease viability of offspring. In the preweaning period, the exposed offspring had a lower body weight and their...

  15. Effects of environmentally differential rearing upon maze performance in prenatally irradiated microcephalic rats

    International Nuclear Information System (INIS)

    Seo, M.L.; Inouye, M.; Kiyono, S.; Shibagaki, M.

    1982-01-01

    Pregnant rats received 100 rads of X-irradiation on day 17 of gestation. Control pregnant rats were sham-irradiated on the same gestation day. The male offspring were reared under environmentally enriched, standard colony, and impoverished conditions for 30 days after weaning. Then the Hebb-Williams maze test was carried out. All the prenatally X-irradiated rats were microcephalic: their mean cerebral wet weight was 15.5% less than controls. The effect of X-irradiation was not significant in error scores and running times, whereas the effect of environment was significant in these items; initial and total error scores and running times were decreased in enriched groups compared to impoverished groups in controls as well as in X-irradiated animals

  16. Prenatal androgen excess enhances stimulation of the GNRH pulse in pubertal female rats.

    Science.gov (United States)

    Yan, Xiaonan; Yuan, Chun; Zhao, Nannan; Cui, Yugui; Liu, Jiayin

    2014-07-01

    In adolescent girls with polycystic ovary syndrome (PCOS), neuroendocrine derangements manifest after the onset of puberty, characterized by rapid LH pulse frequency. The early mechanism underlying the pubertal regulation of the GNRH/LH pulsatile release in adolescents with PCOS remains uncertain. To determine the effects of prenatal androgen exposure on the activation of GNRH neurons and generation of LH pulse at puberty, we administrated 5α-dihydrotestosterone to pregnant rats and observed serum LH levels and expression of hypothalamic genes in female offspring from postnatal 4 to 8 weeks. The 6-week-old prenatally androgenized (PNA) female rats exhibited an increase in LH pulse frequency. The hypothalamic expression of neurokinin B (Nkb (Tac2)) and Lepr mRNA levels in PNA rats increased remarkably before puberty and remained high during puberty, whereas elevated Kiss1 mRNA levels were detected only after the onset of puberty. Exogenous kisspeptin, NK3R agonist, and leptin triggered tonic stimulation of GNRH neurons and increased LH secretion in 6-week-old PNA rats. Leptin upregulated Kiss1 mRNA levels in the hypothalamus of pubertal PNA rats; however, pretreatment with a kisspeptin antagonist failed to suppress the elevated serum LH stimulated by leptin, indicating that the stimulatory effects of leptin may be conveyed indirectly to GNRH neurons via other neural components within the GNRH neuronal network, rather than through the kisspeptin-GPR54 pathway. These findings validate the hypotheses that NKB and leptin play an essential role in the activation of GNRH neurons and initiation of increased LH pulse frequency in PNA female rats at puberty and that kisspeptin may coordinate their stimulatory effects on LH release. © 2014 Society for Endocrinology.

  17. SRXRF study of trace elements in hippocampus of pup rats after prenatal and postnatal exposure to low-level mercury

    International Nuclear Information System (INIS)

    Zhang Fang; Feng Weiyue; Chai Zhifang; Wang Meng; Shi Junwen; Huang Yuying; He Wei

    2005-01-01

    copper and zinc content and remarkable decrease of iron content. Compared with the control group, the activities of antioxidant enzymes such as GSH and SOD and the content of MDA in hippocampus of mercury-exposed group fell down obviously. Thus, it was demonstrated that prenatal exposure to low-level mercury could lead to the variations of trace elements and oxidative damage in hippocampus of pup rats.

  18. Ontogenetic changes in the ultrastructure of rat hepatocyte organelles after prenatal x irradiation

    International Nuclear Information System (INIS)

    Chedid, A.; Nair, V.

    1975-01-01

    The effects of prenatal x irradiation on the development of hepatocyte organelles have been studied in Sprague-Dawley rats. Pregnant rats received 50 R to the pelvic region on the 13th gestation day (g.d.). Animals were sacrificed on g.d.'s 15 and 20, day of birth, and 5th postnatal day. The fetal and neonatal livers were obtained and processed for electron-microscopic examination. The most striking discernible change after irradiation involves the appearance of cytoplasmic ''polyribosomal aggregates'' in the hepatocyte specimens of 15th and 20th g.d.'s. In the control rat, smooth endoplasmic reticulum (SER) appears for the first time on 20th g.d., while no SER could be detected in the hepatocytes from the irradiated animals at this period nor on day of birth. In the irradiated animals, SER was observed on the 5th postnatal day. Our results are consistent with the hypothesis that lipid peroxidation membrane alteration, delayed appearance of SER, and ''polyribosomal aggregation'' may be sequentially linked events after prenatal x irradiation. (U.S.)

  19. The influence of aripiprazole and olanzapine on neurotransmitters level in frontal cortex of prenatally stressed rats.

    Science.gov (United States)

    Ratajczak, P; Kus, K; Gołembiowska, K; Noworyta-Sokołowska, K; Woźniak, A; Zaprutko, T; Nowakowska, E

    2016-09-01

    The study aims to verify whether alterations in the level of neurotransmitters have occurred in prenatally stressed rats (animal model of schizophrenia), and whether aripiprazole (ARI) and olanzapine (OLA) modify this level. The effects of ARI (1.5mg/kg) and OLA (0.5mg/kg) were studied by means of microdialysis in freely moving rats (observation time 120min). The level of neurotransmitters (DA, 5-HT, NA) and their metabolites (DOPAC, HVA, 5-HIAA) was analyzed by HPLC with coulochemical detection. Obtained results indicate that after a single administration of ARI and OLA in the prenatally stressed rats the increase of DA, DOPAC, and 5-HT was observed. In turn ARI administration increase the level of HVA and 5-HIAA and also decrease the level of NA. After OLA administration the level of NA and HVA increased and no significant change in 5-HIAA was observed. Alterations observed as a result of ARI and OLA administration may be pivotal in identifying animal models of mental disorders and in the analysis of neuroleptics effectiveness. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Prenatal undernutrition disrupted the sexual maturation, but not the sexual behavior, in male rats.

    Science.gov (United States)

    Matsuzaki, Toshiya; Munkhzaya, Munkhsaikhan; Tungalagsuvd, Altankhuu; Mayila, Yiliyasi; Iwasa, Takeshi; Yano, Kiyohito; Yanagihara, Rie; Tokui, Takako; Kato, Takeshi; Kuwahara, Akira; Matsui, Sumika; Irahara, Minoru

    2017-10-01

    Exposure to various stressors, including psychological, metabolic, and immune, in the perinatal period induces long-lasting effects in physiological function and increase the risk of metabolic disorders in later life. In the present study, sexual maturation and sexual behavior were assessed in prenatally undernourished mature male rats. All the pregnant rats were divided into the maternal normal nutrition (mNN) group and the maternal undernutrition (mUN) group. The mUN mothers received 50% of the amount of the daily food intake of the mNN mothers. Preputial separation and sexual behavior were observed in randomly selected pups of the mNN and mUN groups. The body weight of the mothers was significantly lighter in the mUN group than in the mNN group. Similarly, the pups in the mUN group showed a significantly lower body weight than those in the mNN group from postnatal day (PND) 1 to PND 15. The preputial separation day was significantly delayed in the mUN group, compared to the mNN group. Sexual behavior did not show any significant difference between the two groups. These findings indicated that prenatal undernutrition delayed sexual maturation, but did not suppress sexual behavior, in mature male rats.

  1. Postnatal Treadmill Exercise Alleviates Prenatal Stress-Induced Anxiety in Offspring Rats by Enhancing Cell Proliferation Through 5-Hydroxytryptamine 1A Receptor Activation

    Directory of Open Access Journals (Sweden)

    Sam Jun Lee

    2016-05-01

    Full Text Available Purpose: Stress during pregnancy is a risk factor for the development of anxiety-related disorders in offspring later in life. The effects of treadmill exercise on anxiety-like behaviors and hippocampal cell proliferation were investigated using rats exposed to prenatal stress. Methods: Exposure of pregnant rats to a hunting dog in an enclosed room was used to induce stress. Anxiety-like behaviors of offspring were evaluated using the elevated plus maze test. Immunohistochemistry for the detection of 5-bromo-2ʹ- deoxyuridine and doublecortin (DCX in the hippocampal dentate gyrus and 5-hydroxytryptamine 1A receptors (5-HT1A in the dorsal raphe was conducted. Brain-derived neurotrophic factor (BDNF and tyrosine kinase B (TrkB levels in the hippocampus were evaluated by western blot analysis. Results: Offspring of maternal rats exposed to stress during pregnancy showed anxiety-like behaviors. Offspring also showed reduced expression of BDNF, TrkB, and DCX in the dentate gyrus, decreased cell proliferation in the hippocampus, and reduced 5-HT1A expression in the dorsal raphe. Postnatal treadmill exercise by offspring, but not maternal exercise during pregnancy, enhanced cell proliferation and expression of these proteins. Conclusions: Postnatal treadmill exercise ameliorated anxiety-like behaviors in offspring of stressed pregnant rats, and the alleviating effect of exercise on these behaviors is hypothesized to result from enhancement of cell proliferation through 5-HT1A activation in offspring rats.

  2. Prenatal exposure to a novel antipsychotic quetiapine: impact on neuro-architecture, apoptotic neurodegeneration in fetal hippocampus and cognitive impairment in young rats.

    Science.gov (United States)

    Singh, K P; Tripathi, Nidhi

    2015-05-01

    Reports on prenatal exposure to some of the first generation antipsychotic drugs like, haloperidol, their effects on fetal neurotoxicity and functional impairments in the offspring, are well documented. But studies on in utero exposure to second generation antipsychotics, especially quetiapine, and its effects on fetal neurotoxicity, apoptotic neurodegeneration, postnatal developmental delay and neurobehavioral consequences are lacking. Therefore, the present study was undertaken to evaluate the effect of prenatal administration to equivalent therapeutic doses of quetiapine on neuro-architectural abnormalities, neurohistopathological changes, apoptotic neurodegeneration in fetal hippocampus, and postnatal development and growth as well as its long-lasting imprint on cognitive impairment in young-adult offspring. Pregnant Wistar rats (n=24) were exposed to selected doses (55 mg, 80 mg and 100mg/kg) of quetiapine, equivalent to human therapeutic doses, from gestation day 6 to 21 orally with control subjects. Half of the pregnant subjects of each group were sacrificed at gestation day 21 for histopathological, confocal and electron microscopic studies and rest of the dams were allowed to deliver naturally. Their pups were reared postnatally up to 10 weeks of age for neurobehavioral observations. In quetiapine treated groups, there was significant alterations in total and differential thickness of three typical layers of hippocampus associated with neuronal cells deficit and enhanced apoptotic neurodegeneration in the CA1 area of fetal hippocampus. Prenatally drug treated rat offspring displayed post-natal developmental delay till postnatal day 70, and these young-adult rats displayed cognitive impairment in Morris water maze and passive avoidance regimes as long-lasting impact of the drug. Therefore, quetiapine should be used with cautions considering its developmental neurotoxicological and neurobehavioral potential in animal model, rat. Copyright © 2015 Elsevier

  3. Influence of chronic prenatal hypoxia on the specialized contact apparatus of rat heart ventricles during ontogeny

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    N. S. Petruk

    2014-08-01

    Full Text Available Background. During prenatal development embryonic mammalian heart undergoes deep dynamic changes due to size, structure and functions. Pathological intrauterine hypoxia influences fetal development generally and cardiogeny particularly, it affects the structure and function of the heart muscle and can lead to a variety of cardiovascular abnormalities and congenital heart defects. It is known that as a result of chronic intrauterine hypoxia during the stages of prenatal ontogeny specialized intercellular apparatus of cardiomyocytes is damaged, which plays a role not only in the mechanical connections of the cardiomyocytes, but also in the electric cooperatives, metabolic conversions, the homeostasis of the ionic balance and transport morphogenetic signaling molecules which are involved into the mechanisms of cardiogeny. It contributes to the development of diseases that may be associated with impaired local distribution of specialized intercellular junctions, and manifests as arrhythmias and cardiac conduction. Objective. To determine the effects of chronic prenatal hypoxia on the structure and distribution of specialized intercellular junctions of typical cardiomyocytes in the rat ventricular myocardium at the stages of prenatal ontogeny and to evaluate morphometric parameters of intercalated disks in the postnatal period. Materials and methods. White rats were used as a material. Intrauterine hypoxia was modelled by intraperitoneal injection of sodium nitrite from 10th to 21st day of pregnancy. Hearts were investigated by the transmission electron microscopy during the stages of prenatal and postnatal ontogeny and in adult animals. Morphometric and statistical methods were applied. Pairwise comparisons between means of different groups were performed using Student’s t-test where, for each couple of normally distributed populations, the null hypothesis that the means are equal was verified. Results. The average length of desmosomes on the 20th

  4. Effect of tritium (tritium water) on prenatal and postnatal development of rats

    International Nuclear Information System (INIS)

    Bajrakova, A.; Baev, I.; Yagova, A.

    1983-01-01

    Female rats were injected intraperitoneally on the first day after their fecundation with 3,7 kBq/g b.w. tritium water - activity which under these conditions does not increase prenatal death rate. The postnatal development of the born alive was traced in respect to the lethality rate and growth rate (mean bodily weight in dynamics up to the 60-th day p.p.) and compared with that of the offsprings from the control group. It was shown that the used activity tritium water during the initial stages of embryonic development does not result in deviations from the norm. (authors)

  5. Aversive conditioning in prenatally gamma-irradiated rats

    International Nuclear Information System (INIS)

    Tamaki, Yoshitaka; Hoshino, Kiyoshi; Kameyama, Yoshiro

    1987-01-01

    To examine how intrauterine exposure to gamma rays would exert on four kinds of aversive conditioning, rat fetuses were irradiated with 0.27, 0.48, or 1.46 Gy at Day 15 post conception. When ordinary avoidance conditioning was given to the groups with 0.27 and 0.48 Gy, there was no significant difference between the irradiated groups and the control group in the rate of positive avoidance response. Nor was this different in the irradiated groups and the control group, when the rate of baseline response was examined in avoidance conditioning. In positive avoidance conditioning to two kinds of anticipatory electric stimuli, the acquisition of avoidance was significantly inferior in all irradiated groups to that in the control group. When giving succesive discrimination learning, the group with 1.46 Gy tended to have higher rate of positive avoidance response and remarkably lower rate of passive avoidance response than the control group. (Namekawa, K.)

  6. NanoTIO2 (UV-Titan does not induce ESTR mutations in the germline of prenatally exposed female mice

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    Boisen Anne Mette

    2012-06-01

    Full Text Available Abstract Background Particulate air pollution has been linked to an increased risk of cardiovascular disease and cancer. Animal studies have shown that inhalation of air particulates induces mutations in the male germline. Expanded simple tandem repeat (ESTR loci in mice are sensitive markers of mutagenic effects on male germ cells resulting from environmental exposures; however, female germ cells have received little attention. Oocytes may be vulnerable during stages of active cell division (e.g., during fetal development. Accordingly, an increase in germline ESTR mutations in female mice prenatally exposed to radiation has previously been reported. Here we investigate the effects of nanoparticles on the female germline. Since pulmonary exposure to nanosized titanium dioxide (nanoTiO2 produces a long-lasting inflammatory response in mice, it was chosen for the present study. Findings Pregnant C57BL/6 mice were exposed by whole-body inhalation to the nanoTiO2 UV-Titan L181 (~42.4 mg UV-Titan/m3 or filtered clean air on gestation days (GD 8–18. Female C57BL/6 F1 offspring were raised to maturity and mated with unexposed CBA males. The F2 descendents were collected and ESTR germline mutation rates in this generation were estimated from full pedigrees (mother, father, offspring of F1 female mice (192 UV-Titan-exposed F2 offspring and 164 F2 controls. ESTR mutation rates of 0.029 (maternal allele and 0.047 (paternal allele in UV-Titan-exposed F2 offspring were not statistically different from those of F2 controls: 0.037 (maternal allele and 0.061 (paternal allele. Conclusions We found no evidence for increased ESTR mutation rates in F1 females exposed in utero to UV-Titan nanoparticles from GD8-18 relative to control females.

  7. Acute prenatal exposure to ethanol on gestational day 12 elicits opposing deficits in social behaviors and anxiety-like behaviors in Sprague Dawley rats.

    Science.gov (United States)

    Diaz, Marvin R; Mooney, Sandra M; Varlinskaya, Elena I

    2016-09-01

    Our previous research has shown that in Long Evans rats acute prenatal exposure to a high dose of ethanol on gestational day (G) 12 produces social deficits in male offspring and elicits substantial decreases in social preference relative to controls, in late adolescents and adults regardless of sex. In order to generalize the observed detrimental effects of ethanol exposure on G12, pregnant female Sprague Dawley rats were exposed to ethanol or saline and their offspring were assessed in a modified social interaction (SI) test as early adolescents, late adolescents, or young adults. Anxiety-like behavior was also assessed in adults using the elevated plus maze (EPM) or the light/dark box (LDB) test. Age- and sex-dependent social alterations were evident in ethanol-exposed animals. Ethanol-exposed males showed deficits in social investigation at all ages and age-dependent alterations in social preference. Play fighting was not affected in males. In contrast, ethanol-exposed early adolescent females showed no changes in social interactions, whereas older females demonstrated social deficits and social indifference. In adulthood, anxiety-like behavior was decreased in males and females prenatally exposed to ethanol in the EPM, but not the LDB. These findings suggest that social alterations associated with acute exposure to ethanol on G12 are not strain-specific, although they are more pronounced in Long Evans males and Sprague Dawley females. Furthermore, given that anxiety-like behaviors were attenuated in a test-specific manner, this study indicates that early ethanol exposure can have differential effects on different forms of anxiety. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Respiratory tract toxicity in rats exposed to Mexico City air.

    Science.gov (United States)

    Moss, O R; Gross, E A; James, R A; Janszen, D B; Ross, P W; Roberts, K C; Howard, A M; Harkema, J R; Calderón-Garcidueñas, L; Morgan, K T

    2001-03-01

    The rat has been used extensively as a health sentinel, indicator, or monitor of environmental health hazards, but this model has not been directly validated against human exposures. Humans in Mexico City show upper respiratory tract lesions and evidence of pulmonary damage related to their environmental inhalation exposure. In this study, male and female F344 rats were exposed (23 hr/day) in Mexico City to local Mexico City air (MCA)* for up to seven weeks. Controls were maintained at the same location under filtered air. Prior to these exposures, several steps were taken. First, the nasal passages of normal male rats shipped from the United States and housed in Mexico City were examined for mycoplasma infection; no evidence of infection was found. In addition, a mobile exposure and monitoring system was assembled and, with an ozone (O3) exposure atmosphere, was tested along with supporting histopathology techniques and analysis of rat nasal and lung tissues. Last, the entire exposure model (equipment and animals) was transported to Mexico City and validated for a three-week period. During the seven-week study there were 18 one-hour intervals during which the average O3 concentration of MCA in the exposure chamber exceeded the US National Ambient Air Quality Standard (NAAQS) of 0.120 ppm 03 (hourly average, not to be exceeded more than once per year). This prolonged exposure of healthy F344 rats to MCA containing episodically low to moderate concentrations of 03 (as well as other urban air pollutants) did not induce inflammatory or epithelial lesions in the nasal airways or lung as measured by qualitative histologic techniques or quantitative morphometric techniques. These findings agree with those of previous controlled O3 inhalation studies, but they are in contrast to reports indicating that O3-polluted MCA causes significant nasal mucosal injury in adults and children living in southwestern Mexico City. Taken together, these findings may suggest that human

  9. Prenatal choline supplementation attenuates MK-801-induced deficits in memory, motor function, and hippocampal plasticity in adult male rats.

    Science.gov (United States)

    Nickerson, Chelsea A; Brown, Alexandra L; Yu, Waylin; Chun, Yoona; Glenn, Melissa J

    2017-10-11

    Choline is essential to the development and function of the central nervous system and supplemental choline during development is neuroprotective against a variety of insults, including neurotoxins like dizocilpine (MK-801). MK-801 is an NMDA receptor antagonist that is frequently used in rodent models of psychological disorders, particularly schizophrenia. At low doses, it causes cognitive impairments, and at higher doses it induces motor deficits, anhedonia, and neuronal degeneration. The primary goals of the present study were to investigate whether prenatal choline supplementation protects against the cognitive impairments, motor deficits, and neuropathologies that are precipitated by MK-801 administration in adulthood. Adult male Sprague-Dawley rats were fed a standard or supplemented choline diet prenatally. Using the novelty preference test of object recognition, we found that only prenatal standard-fed rats displayed memory consolidation deficits induced by low-dose MK-801 administered immediately following study of sample objects; all other groups, including prenatal choline supplemented rats given MK-801, showed intact memory. Following high-dose MK-801, prenatal choline supplementation significantly alleviated rats' motor response to MK-801, particularly ataxia. Using doublecortin and Ki67 to mark neurogenesis and cell division, respectively, in the hippocampus, we found that prenatal choline supplementation, in the face of MK-801 toxicity, protected against reduced hippocampal plasticity. Taken together, the current findings suggest that prenatal choline supplementation protects against a variety of behavioral and neural pathologies induced by the neurotoxin, MK-801. This research contributes to the growing body of evidence supporting the robust neuroprotective capacity of choline. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. Alterations of proliferation and differentiation of hippocampal cells in prenatally stressed rats.

    Science.gov (United States)

    Sun, Hongli; Su, Qian; Zhang, Huifang; Liu, Weimin; Zhang, Huiping; Ding, Ding; Zhu, Zhongliang; Li, Hui

    2015-06-01

    To clarify the alterations of proliferation and differentiation of hippocampal cells in prenatally stressed rats. We investigated the impact of prenatal restraint stress on the hipocampal cell proliferation in the progeny with 5-bromo-2'-deoxyuridine (BrdU), which is a marker of proliferating cells and their progeny. In addition, we observed the differentiation of neural stem cells (NSCs) with double labeling of BrdU/neurofilament (NF), BrdU/glial fibrillary acidic protein (GFAP) in the hipocampus. Prenatal stress (PS) increased cell proliferation in the dentate gyrus (DG) only in female and neuron differentiation of newly divided cells in the DG and CA4 in both male and female. Moreover, the NF and GFAP-positive cells, but not the BrdU-positive cells, BrdU/NF and BrdU/GFAP-positive cells, were found frequently in the CA3 and CA1 in the offspring of each group. These results possibly suggest a compensatory adaptive response to neuronal damage or loss in hippocampus induced by PS. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  11. Reduced Bone and Body Mass in Young Male Rats Exposed to Lead

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    Fellipe Augusto Tocchini de Figueiredo

    2014-01-01

    Full Text Available The aim of this study was to see whether there would be differences in whole blood versus tibia lead concentrations over time in growing rats prenatally. Lead was given in the drinking water at 30 mg/L from the time the dams were pregnant until offspring was 28- or 60-day-old. Concentrations of lead were measured in whole blood and in tibia after 28 (28D and 60 days (60D in control (C and in lead-exposed animals (Pb. Lead measurements were made by GF-AAS. There was no significant difference (P>0.05 in the concentration of whole blood lead between Pb-28D (8.0±1.1 μg/dL and Pb-60D (7.2±0.89 μg/dL, while both significantly varied (P<0.01 from controls (0.2 μg/dL. Bone lead concentrations significantly varied between the Pb-28D (8.02±1.12 μg/g and the Pb-60D (43.3±13.26 μg/g lead-exposed groups (P<0.01, while those exposed groups were also significantly higher (P<0.0001 than the 28D and 60D control groups (Pb < 1 μg/g. The Pb-60D group showed a 25% decrease in tibia mass as compared to the respective control. The five times higher amount of lead found in the bone of older animals (Pb-60D versus Pb-28D, which reinforces the importance of using bone lead as an exposure biomarker.

  12. Prenatal development toxicity study of zinc oxide nanoparticles in rats

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    Hong JS

    2014-12-01

    Full Text Available Jeong-Sup Hong,1,2 Myeong-Kyu Park,1 Min-Seok Kim,1 Jeong-Hyeon Lim,1 Gil-Jong Park,1 Eun-Ho Maeng,1 Jae-Ho Shin,3 Meyoung-Kon Kim,4 Jayoung Jeong,5 Jin-A Park,2 Jong-Choon Kim,6 Ho-Chul Shin2 1Health Care Research Laboratory, Korea Testing and Research Institute, Gimpo, South Korea; 2College of Veterinary Medicine, Konkuk University, Seoul, South Korea; 3Department of Biomedical Laboratory Science, Eulji University, Seongnam-si, South Korea; 4Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, South Korea; 5Toxicological Research Division, National Institute of Food and Drug Safety Evaluation, Chungcheongbuk-do, South Korea; 6College of Veterinary Medicine, Chonnam National University, Gwangju, South Korea Abstract: This study investigated the potential adverse effects of zinc oxide nanoparticles ([ZnOSM20(+ NPs] zinc oxide nanoparticles, positively charged, 20 nm on pregnant dams and embryo–fetal development after maternal exposure over the period of gestational days 5–19 with Sprague-Dawley rats. ZnOSM20(+ NPs were administered to pregnant rats by gavage at 0, 100, 200, and 400 mg/kg/day. All dams were subjected to a cesarean section on gestational day 20, and all of the fetuses were examined for external, visceral, and skeletal alterations. Toxicity in the dams manifested as significantly decreased body weight after administration of 400 mg/kg/day NPs; reduced food consumption after administration of 200 and 400 mg/kg/day NPs; and decreased liver weight and increased adrenal glands weight after administration of 400 mg/kg/day NPs. However, no treatment-related difference in: number of corpora lutea; number of implantation sites; implantation rate (%; resorption; dead fetuses; litter size; fetal deaths and placental weights; and sex ratio were observed between the groups. On the other hand, significant decreases between treatment groups and controls were seen for fetal weights after

  13. Mitigating the Effects of Poverty and Crime: The Long-Term Effects of an Early Intervention Programme for Children Who Were Developmentally Delayed and Prenatally Exposed to Cocaine

    Science.gov (United States)

    Ullery, Mary Anne; Gonzalez, Antonio; Katz, Lynne

    2016-01-01

    This study explores the long-term impact on participation in the Linda Ray Intervention Program (LRIP) for children (n = 54) who were developmentally delayed and prenatally exposed to cocaine. By identifying a group of programme graduates from a high crime/high poverty neighbourhood in Miami-Dade County using ArcGIS 10.2 software, a…

  14. Development of rat visual system after prenatal X-irradiation

    International Nuclear Information System (INIS)

    Brueckner, G.; Biesold, D.; Mares, V.

    1980-01-01

    Rats pregnant for 16 or 19 days (ED 16 or 19) were irradiated with 1 Gy and killed after 24 hrs or at age 24 or 180 days. The primary influence of X-rays consists in a lethal lesion of cells located in the periventricular zone as well as some of the more differentiated cells in the brain parenchyma. After irradiation on ED 16, the acute damage was greater in the cerebral cortex and the superior colliculus (SC) than in the lateral geniculate nucleus (LGN). Irradiation on ED 19 damaged mainly the cortical part of the visual system. In adult animals the acute radiation damage results in a deficit in packing density and the total number of neurons. Animals irradiated on ED 16 revealed more pronounced changes in deep layers of the cortex (L VI) than in the superficial layers. The deficit was smaller in the SC, and in the LGN an increase in the packing density of nerve cells was found. In animals irradiated on ED 19, the deficit in neurons density occurred mainly in more superficial layers of the cortex, with a maximum deficit in layer IV. From comparison of acute and final changes it may be concluded that the damage of preneuroblastic cell populations is compensated during later embryonic development, while the damage induced in populations already at early neuroblast stage is irreversible and leads to a permanent deficit. Glia cell population is altered in a similar way as the number of neurons in regions poor in myelin, while in regions rich in myelin the number of glia cells seems to depend on changes in the number of efferent and afferent nerve fibres. (author)

  15. Environmental Enrichment during Gestation Improves Behavior Consequences and Synaptic Plasticity in Hippocampus of Prenatal-Stressed Offspring Rats

    International Nuclear Information System (INIS)

    Li, Mingbo; Wang, Miao; Ding, Siqing; Li, Changqi; Luo, Xuegang

    2012-01-01

    Prenatal stress can result in various behavior deficits in offspring. Here we tested the effects of environmental enrichment during gestation used as a preventive strategy on the behavior deficits of prenatal-stressed offspring rats as well as the underlying structure basis. We compared the effect size of environmental enrichment during gestation on prenatal-stressed offspring to that of environmental enrichment after weaning. Our results showed that environmental enrichment during gestation partially prevented anxiety and the damage in learning and memory in prenatal-stressed offspring as evaluated by elevated plus-maze test and Morris water maze test. At the same time, environmental enrichment during gestation inhibited the decrease in spine density of CA1 and dentate gyrus neurons and preserved the expression of synaptophysin and glucocorticoid receptors (GRs) in the hippocampus of prenatal-stressed offspring. There was no significant difference in offspring behavior between 7-day environmental enrichment during gestation and 14-day offspring environmental enrichment after weaning. These data suggest that environmental enrichment during gestation effectively prevented the behavior deficits and the abnormal synapse structures in prenatal-stressed offspring, and that it can be used as an efficient preventive strategy against prenatal stresses

  16. Prenatal Protein Malnutrition Decreases KCNJ3 and 2DG Activity in Rat Prefrontal Cortex

    Science.gov (United States)

    Amaral, A.C.; Jakovcevski, M.; McGaughy, J.A.; Calderwood, S.K.; Mokler, D.J.; Rushmore, R.J.; Galler, J.R.; Akbarian, S.A.; Rosene, D.L.

    2014-01-01

    Prenatal protein malnutrition (PPM) in rats causes enduring changes in brain and behavior including increased cognitive rigidity and decreased inhibitory control. A preliminary gene microarray screen of PPM rat prefrontal cortex (PFC) identified alterations in KCNJ3 (GIRK1/Kir3.1), a gene important for regulating neuronal excitability. Follow-up with polymerase chain reaction and Western blot showed decreased KCNJ3 expression in PFC, but not hippocampus or brainstem. To verify localization of the effect to the PFC, baseline regional brain activity was assessed with 14C-2-deoxyglucose. Results showed decreased activation in PFC but not hippocampus. Together these findings point to the unique vulnerability of the PFC to the nutritional insult during early brain development, with enduring effects in adulthood on KCNJ3 expression and baseline metabolic activity. PMID:25446346

  17. A self-medication hypothesis for increased vulnerability to drug abuse in prenatally restraint stressed rats.

    Science.gov (United States)

    Reynaert, Marie-Line; Marrocco, Jordan; Gatta, Eleonora; Mairesse, Jérôme; Van Camp, Gilles; Fagioli, Francesca; Maccari, Stefania; Nicoletti, Ferdinando; Morley-Fletcher, Sara

    Stress-related events that occur in the perinatal period can permanently change brain and behavior of the developing individual and there is increasing evidence that early-life adversity is a contributing factor in the etiology of drug abuse and mood disorders. Neural adaptations resulting from early-life stress may mediate individual differences in novelty responsiveness and in turn contribute to drug abuse vulnerability. Prenatal restraint stress (PRS) in rats is a well-documented model of early stress known to induce long-lasting neurobiological and behavioral alterations including impaired feedback mechanisms of the HPA axis, enhanced novelty seeking, and increased sensitiveness to psychostimulants as well as anxiety/depression-like behavior. Together with the HPA axis, functional alterations of the mesolimbic dopamine system and of the metabotropic glutamate receptors system appear to be involved in the addiction-like profile of PRS rats.

  18. Prenatal caffeine ingestion induces transgenerational neuroendocrine metabolic programming alteration in second generation rats

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    Luo, Hanwen [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Deng, Zixin; Liu, Lian; Shen, Lang; Kou, Hao; He, Zheng [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Ping, Jie; Xu, Dan [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China); Ma, Lu [Department of Epidemiology and Health Statistics, Public Health School of Wuhan University, Wuhan 430071 (China); Chen, Liaobin, E-mail: lbchen@whu.edu.cn [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)

    2014-02-01

    Our previous studies have demonstrated that prenatal caffeine ingestion induces an increased susceptibility to metabolic syndrome with alterations of glucose and lipid metabolic phenotypes in adult first generation (F1) of intrauterine growth retardation (IUGR) rats, and the underlying mechanism is originated from a hypothalamic–pituitary–adrenal (HPA) axis-associated neuroendocrine metabolic programming alteration in utero. This study aims to investigate the transgenerational effects of this programming alteration in adult second generation (F2). Pregnant Wistar rats were administered with caffeine (120 mg/kg·d) from gestational day 11 until delivery. Four groups in F2 were set according to the cross-mating between control and caffeine-induced IUGR rats. F2 were subjected to a fortnight ice water swimming stimulus on postnatal month 4, and blood samples were collected before and after stress. Results showed that the majority of the activities of HPA axis and phenotypes of glucose and lipid metabolism were altered in F2. Particularly, comparing with the control group, caffeine groups had an enhanced corticosterone levels after chronic stress. Compared with before stress, the serum glucose levels were increased in some groups whereas the triglyceride levels were decreased. Furthermore, total cholesterol gain rates were enhanced but the high-density lipoprotein-cholesterol gain rates were decreased in most caffeine groups after stress. These transgenerational effects were characterized partially with gender and parental differences. Taken together, these results indicate that the reproductive and developmental toxicities and the neuroendocrine metabolic programming mechanism by prenatal caffeine ingestion have transgenerational effects in rats, which may help to explain the susceptibility to metabolic syndrome and associated diseases in F2. - Highlights: • Caffeine-induced neuroendocrine metabolic programming of HPA has hereditary effect. • Caffeine

  19. Prenatal caffeine ingestion induces transgenerational neuroendocrine metabolic programming alteration in second generation rats

    International Nuclear Information System (INIS)

    Luo, Hanwen; Deng, Zixin; Liu, Lian; Shen, Lang; Kou, Hao; He, Zheng; Ping, Jie; Xu, Dan; Ma, Lu; Chen, Liaobin; Wang, Hui

    2014-01-01

    Our previous studies have demonstrated that prenatal caffeine ingestion induces an increased susceptibility to metabolic syndrome with alterations of glucose and lipid metabolic phenotypes in adult first generation (F1) of intrauterine growth retardation (IUGR) rats, and the underlying mechanism is originated from a hypothalamic–pituitary–adrenal (HPA) axis-associated neuroendocrine metabolic programming alteration in utero. This study aims to investigate the transgenerational effects of this programming alteration in adult second generation (F2). Pregnant Wistar rats were administered with caffeine (120 mg/kg·d) from gestational day 11 until delivery. Four groups in F2 were set according to the cross-mating between control and caffeine-induced IUGR rats. F2 were subjected to a fortnight ice water swimming stimulus on postnatal month 4, and blood samples were collected before and after stress. Results showed that the majority of the activities of HPA axis and phenotypes of glucose and lipid metabolism were altered in F2. Particularly, comparing with the control group, caffeine groups had an enhanced corticosterone levels after chronic stress. Compared with before stress, the serum glucose levels were increased in some groups whereas the triglyceride levels were decreased. Furthermore, total cholesterol gain rates were enhanced but the high-density lipoprotein-cholesterol gain rates were decreased in most caffeine groups after stress. These transgenerational effects were characterized partially with gender and parental differences. Taken together, these results indicate that the reproductive and developmental toxicities and the neuroendocrine metabolic programming mechanism by prenatal caffeine ingestion have transgenerational effects in rats, which may help to explain the susceptibility to metabolic syndrome and associated diseases in F2. - Highlights: • Caffeine-induced neuroendocrine metabolic programming of HPA has hereditary effect. • Caffeine

  20. Fetal development and renal function in adult rats prenatally subjected to sodium overload.

    Science.gov (United States)

    Cardoso, Henriqueta D; Cabral, Edjair V; Vieira-Filho, Leucio D; Vieyra, Adalberto; Paixão, Ana D O

    2009-10-01

    The aims of this study were (1) to evaluate two factors that affect fetal development--placental oxidative stress (Ox) and plasma volume (PV)--in dams with sodium overload and (2) to correlate possible alterations in these factors with subsequent modifications in the renal function of adult offspring. Wistar dams were maintained on 0.17 M NaCl instead of water from 20 days before mating until either the twentieth pregnancy day/parturition or weaning. Colorimetric methods were used to measure Ox in maternal and offspring tissues, PV, 24-h urinary protein (U(Prot24 h)) and serum triacylglycerols (TG) and cholesterol (Chol). Renal hemodynamics was evaluated in the offspring at 90 days of age using a blood pressure transducer, a flow probe and inulin clearance to measure mean arterial pressure (MAP), renal blood flow and glomerular filtration rate (GFR), respectively. The number of nephrons (NN) was counted in kidney suspensions. Dams showed unchanged PV, placental Ox and fetal weight but increased U(Prot24 h) (150%, P sodium-overloaded pups showed increased U(Prot24 h) (45%, P sodium-overloaded rats showed increased U(Prot24 h) (27%, P sodium-overloaded group. We conclude that salt overload from the prenatal stage until weaning leads to alterations in lipid metabolism and in the renal function of the pups, which are additional to those alterations seen in rats only overloaded prenatally.

  1. Hypersynchrony in MEG spectral amplitude in prospectively-identified 6-month-old infants prenatally exposed to alcohol

    Directory of Open Access Journals (Sweden)

    Julia M. Stephen

    2018-01-01

    amplitude at 6 months of age. These results provide new evidence that hypersynchrony, previously observed in neonates prenatally exposed to high levels of alcohol, persists until 6 months of age and this measure is detectable with low to moderate exposure of alcohol with a dose-response effect. These results indicate that hypersynchrony may provide a sensitive early marker of prenatal alcohol exposure in infants up to 6 months of age.

  2. Cancer Mortality Among Techa Riverside Residents (Southern Urals). Chronically Exposed to Radiation During the Prenatal Period and in Childhood

    International Nuclear Information System (INIS)

    Ostroumova, E. V.; Akleyev, A. V.

    2004-01-01

    Imperfect technology and lack of management and utilization facilities for reprocessing liquid waste released by the Mayak PA resulted in a protracted combined (external and internal) environmental radiation exposure of the population resident on the banks of the Techa River. The followup of 8.640 subjects exposed during the prenatal period and in childhood covered the period of 49 years (1.1.1950-31.12.1998), the total person-years under observation amounted to 222,686. From 1950 through 1998 1,231 death cases were registered in the catchment area (5 raions in Chelyabinsk OBlast through which the Techa flows). In 70 cases death was caused by solid cancers, and in 12 cases by leukemia. Analyses of solid cancer mortality yielded higher rates for men as compared to women (p<0.001). No significant differences in death rates were observed between different ethnic groups (Slavs vs Tartars and Bashkirs). A statistically significant increase in solid cancer mortality with attained age was shown (p<0.001). The age at first exposure was demonstrated to be a factor modifying the solid cancer mortality rate (p=0.049). The highest risk of death from solid cancers was manifested by persons whose exposure started in the prenatal period or at the age under 5 years. There were 4.6 excess cases in this group of 30 observed solid cancer cases, whereas in the group including subjects aged 5 years or older at first exposure only 1 excess case was registered among the 40 observed cancer cases. The obtained leukemia mortality ERR value (CLL excluded) was 7.76, p=0.09. The excess leukemia death was found to be 7.6 out of of 10 observed cases. The analysis performed should be regarded as a preliminary one, taking into account the need to further extend the followup of the cohort and a potential verification of dose estimates in the future. (Author) 11 refs

  3. Study of the effects of a prenatal or postnatal irradiation of 150 rads in adult rats

    International Nuclear Information System (INIS)

    Coffigny, H.; Pasquier, C.

    Pregnant females and newborn rats were exposed to a gamma irradiation of 150 rads. The stage of gestation at the time of irradiation varied from 14 to 21 days. The newborn rats were irradiated at 0, 1 and 2 days of age. The effect of irradiation of foetus and newborn rats depends on the age of the animal at the time of irradiation. This effect was specially important at the beginning of the foetal life. Neonatal mortality, growth of body weight and adult brain development were investigated. A modification of germ cell radiosensitivity during the period studied, was emphasized [fr

  4. Effects of prenatal caffeine exposure on glucose homeostasis of adult offspring rats

    Science.gov (United States)

    Kou, Hao; Wang, Gui-hua; Pei, Lin-guo; Zhang, Li; Shi, Chai; Guo, Yu; Wu, Dong-fang; Wang, Hui

    2017-12-01

    Epidemiological evidences show that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR). The IUGR offspring also present glucose intolerance and type 2 diabetes mellitus after maturity. We have previously demonstrated that PCE induced IUGR and increased susceptibility to adult metabolic syndrome in rats. This study aimed to further investigate the effects of PCE on glucose homeostasis in adult offspring rats. Pregnant rats were administered caffeine (120 mg/kg/day, intragastrically) from gestational days 11 to 20. PCE offspring presented partial catch-up growth pattern after birth, characterizing by the increased body weight gain rates. Meanwhile, PCE had no significant influences on the basal blood glucose and insulin phenotypes of adult offspring but increased the glucose tolerance, glucose-stimulated insulin section and β cell sensitivity to glucose in female progeny. The insulin sensitivity of both male and female PCE offspring were enhanced accompanied with reduced β cell fraction and mass. Western blotting results revealed that significant augmentation in protein expression of hepatic insulin signaling elements of PCE females, including insulin receptor (INSR), insulin receptor substrate 1 (IRS-1) and the phosphorylation of serine-threonine protein kinase (Akt), was also potentiated. In conclusion, we demonstrated that PCE reduced the pancreatic β mass but increased the glucose tolerance in adult offspring rats, especially for females. The adaptive compensatory enhancement of β cell responsiveness to glucose and elevated insulin sensitivity mainly mediated by upregulated hepatic insulin signaling might coordinately contribute to the increased glucose tolerance.

  5. Behavioral changes in rats prenatally irradiated with low dose of gamma-rays

    International Nuclear Information System (INIS)

    Kiskova, J.; Smajda, B.; Capicikova, M.; Lievajova, K.

    2006-01-01

    In this work, the effects of prenatal gamma-irradiation on behavior in adult Sprague-Dawley rats were studied. Four months old female rats were irradiated with a dose of 1 Gy of gamma-rays on day 15 of gestation. The offspring of irradiated mothers (n=26) and that of control, non-irradiated mothers (n=36) of both sexes at the age of 3 month were tested in Morris's water maze and in open field test. All experimental groups showed a tendency to shortening the time needed to reach the platform in each trial in Morris water maze. Statistically significant difference between irradiated and control rats was detected only in males on 3 rd experimental day. The ability to remember the position of the platform was not altered in irradiated animals after a 4 day pause. In open field test, statistically significant differences in comparison with controls were detected in number of squares entered and in crossings of the central square (P ≤ 0.05) in males. These findings suggest, when comparing with results of other authors, that irradiation effects on postnatal behavior in rats are extremely dependent on the time point of irradiation and that a correlation exist between the developmental stage of the individual brain structures at time of irradiation and the late behavioral effects. (authors)

  6. Sleep in prenatally restraint stressed rats, a model of mixed anxiety-depressive disorder.

    Science.gov (United States)

    Mairesse, Jérôme; Van Camp, Gilles; Gatta, Eleonora; Marrocco, Jordan; Reynaert, Marie-Line; Consolazione, Michol; Morley-Fletcher, Sara; Nicoletti, Ferdinando; Maccari, Stefania

    2015-01-01

    Prenatal restraint stress (PRS) can induce persisting changes in individual's development. PRS increases anxiety and depression-like behaviors and induces changes in the hypothalamo-pituitary-adrenal (HPA) axis in adult PRS rats after exposure to stress. Since adaptive capabilities also depend on temporal organization and synchronization with the external environment, we studied the effects of PRS on circadian rhythms, including the sleep-wake cycle, that are parameters altered in depression. Using a restraint stress during gestation, we showed that PRS induced phase advances in hormonal/behavioral circadian rhythms in adult rats, and an increase in the amount of paradoxical sleep, positively correlated to plasma corticosterone levels. Plasma corticosterone levels were also correlated with immobility in the forced swimming test, indicating a depressive-like profile in the PRS rats. We observed comorbidity with anxiety-like profile on PRS rats that was correlated with a reduced release of glutamate in the ventral hippocampus. Pharmacological approaches aimed at modulating glutamate release may represent a novel therapeutic strategy to treat stress-related disorders. Finally, since depressed patients exhibit changes in HPA axis activity and in circadian rhythmicity as well as in the paradoxical sleep regulation, we suggest that PRS could represent an original animal model of depression.

  7. Tiagabine improves hippocampal long-term depression in rat pups subjected to prenatal inflammation.

    Directory of Open Access Journals (Sweden)

    Aline Rideau Batista Novais

    Full Text Available Maternal inflammation during pregnancy is associated with the later development of cognitive and behavioral impairment in the offspring, reminiscent of the traits of schizophrenia or autism spectrum disorders. Hippocampal long-term potentiation and long-term depression of glutamatergic synapses are respectively involved in memory formation and consolidation. In male rats, maternal inflammation with lipopolysaccharide (LPS led to a premature loss of long-term depression, occurring between 12 and 25 postnatal days instead of after the first postnatal month, and aberrant occurrence of long-term potentiation. We hypothesized this would be related to GABAergic system impairment. Sprague Dawley rats received either LPS or isotonic saline ip on gestational day 19. Male offspring's hippocampus was studied between 12 and 25 postnatal days. Morphological and functional analyses demonstrated that prenatal LPS triggered a deficit of hippocampal GABAergic interneurons, associated with presynaptic GABAergic transmission deficiency in male offspring. Increasing ambient GABA by impairing GABA reuptake with tiagabine did not interact with the low frequency-induced long-term depression in control animals but fully prevented its impairment in male offspring of LPS-challenged dams. Tiagabine furthermore prevented the aberrant occurrence of paired-pulse triggered long-term potentiation in these rats. Deficiency in GABA seems to be central to the dysregulation of synaptic plasticity observed in juvenile in utero LPS-challenged rats. Modulating GABAergic tone may be a possible therapeutic strategy at this developmental stage.

  8. Effects of Vitamin C on Kidney and Bone of Rats Exposed to Low ...

    African Journals Online (AJOL)

    ABSTRACT: In this study, the effect of vitamin C on cadmium-induced toxicity was investigated. Wister rats were exposed to ... and muscles of cadmium exposed rats (1.0- ..... Fauci, A.S., Braunwald, K., Isselbacher, K.J., Wilson,. J.D., Martin ...

  9. Prenatal exposure to vapors of gasoline-ethanol blends causes few cognitive deficits in adult rats

    Science.gov (United States)

    Developmental exposure to inhaled ethanol-gasoline fuel blends is a potential public health concern. Here we assessed cognitive functions in adult offspring of pregnant rats that were exposed to vapors of gasoline blended with a range of ethanol concentrations, including gasoli...

  10. Biochemical Changes in the Serum and Liver of albino rats exposed ...

    African Journals Online (AJOL)

    Biochemical changes in the serum and liver of albino rats chronically exposed to rats administered 5gk-1 , 7.5gk-1 and 15gk-1 of gasoline , kerosine and crude petroleum(bonny light) respectively were studied. The petroleum samples were administered intraperitoneally and the biochemical changes in the rat serum and the ...

  11. Incidence of brain tumours in rats exposed to an aerosol of 239PuO2

    International Nuclear Information System (INIS)

    Sanders, C.L.; Dagle, G.E.; Mahaffey, J.A.

    1992-01-01

    Incidence of brain tumours was investigated in 3390 female and male Wistar rats exposed to an aerosol of 239 PuO 2 , or as sham-exposed controls. Lung doses ranged from 0.05 to 22 Gy. In females, six brain tumours were found in 1058 control rats (incidence, 0.6%) and 24 brain tumours in 2134 rats exposed to Pu (incidence, 1.1%); the survival-adjusted level of significance was p = 0.29 for comparing control with exposed females. In males, two brain tumours were found in 60 control rats (incidence, 3.3%) and seven brain tumours in 138 rats exposed to Pu (incidence, 5.1%); the survival-adjusted level of significance was p = 0.33. Brain tumour incidence was about five times greater in male than in female rats (p = 0.0001), a highly significant sex difference in brain tumour incidence. Tumour types were distributed similarly among control and Pu-exposed groups of both sexes; most were astrocytomas. Mean lifespans for rats with brain tumours were not significantly different between control and Pu-exposed rats. (author)

  12. Reproductive hormone profile and pubertal development in 14-year-old boys prenatally exposed to polychlorinated biphenyls

    DEFF Research Database (Denmark)

    Grandjean, Philippe; Grønlund, Ciea; Kjær, Ina M

    2012-01-01

    to covariate adjustment. In a structural equation model, a doubling in prenatal PCB exposure was associated with a decrease in LH of 6% (p=0.03). Prenatal exposure to PCB and DDE showed weak, non-significant inverse associations with testicular size and Tanner stage. DDE was highly correlated with PCB...

  13. Spermaturia and serum hormone concentrations at the age of puberty in boys prenatally exposed to polychlorinated biphenyls

    DEFF Research Database (Denmark)

    Mol, Nanette M; Sørensen, Nicolina; Weihe, Pal

    2002-01-01

    To determine whether prenatal exposure to polychlorinated biphenyls (PCBs) with possible hormone-disrupting effects is capable of affecting sexual differentiation in boys at the age of puberty.......To determine whether prenatal exposure to polychlorinated biphenyls (PCBs) with possible hormone-disrupting effects is capable of affecting sexual differentiation in boys at the age of puberty....

  14. Early and late effects of prenatal corticosteroid treatment on the microRNA profiles of lung tissue in rats

    Science.gov (United States)

    YU, HONG-REN; LI, SUNG-CHOU; TSENG, WAN-NING; TAIN, YOU-LIN; CHEN, CHIH-CHENG; SHEEN, JIUNN-MING; TIAO, MAO-MENG; KUO, HO-CHANG; HUANG, CHAO-CHENG; HSIEH, KAI-SHENG; HUANG, LI-TUNG

    2016-01-01

    Glucocorticoids have been administered to mothers at risk of premature delivery to induce maturation of preterm fetal lungs and prevent the development of respiratory distress syndrome. Micro (mi)RNAs serve various crucial functions in cell proliferation, differentiation and organ development; however, few studies have demonstrated an association between miRNAs and lung development. The aim of the present study was to investigate alterations in the miRNA profiles of rat lung tissue following prenatal glucocorticoid therapy for fetal lung development. The differences in miRNA expression profiles were compared between postnatal days 7 (D7) and 120 (D120) rat lung tissues, followed by validation using reverse transcription-quantitative polymerase chain reaction. The miRNA profiles of rat lung tissues following prenatal dexamethasone (DEX) therapy were also investigated. miRNAs with 2-fold changes were selected for further analysis. At D120, 6 upregulated and 6 downregulated miRNAs were detected, compared with D7. Among these differentially expressed miRNAs, miR-101-3p and miR-99b-5p were associated with the lowest and highest expressions of miRNA at D7, respectively. A limited impact on the miRNA profiles of rat lung tissues was observed following prenatal DEX treatment, which may help to further clarify the mechanisms underlying normal lung development. However, the results of the present study cannot entirely elucidate the effects of prenatal DEX treatment on the lung development of premature infants, and further studies investigating the impact of prenatal corticosteroids on fetal lung miRNA profiles are required. PMID:26997989

  15. Population kinetics studies in mouse jejunum exposed prenatally to gamma rays at different dose rates

    International Nuclear Information System (INIS)

    Godha, Meena; Nand Chahal, K.

    2001-01-01

    Pregnant Swiss albino mice of 18 days post conception were exposed to 0.80 Gy, 0.40 Gy and 0.20 Gy of gamma rays from a Cobalt-60 source at different dose rates (.0584 Gy/min and .00091 Gy/min). Post irradiation variations in the cell population of crypts and villus of jejunum were studied in the F 1 -generation at 1 day, 3 day and 1,2,4,6 and 12 weeks of post-partum age. In all the exposure groups at 1 day post-partum age, crypts show a decrease in total cells, mitotic figures and goblet cells on one hand and an increase in PNNC on the other hand in comparison to coeval controls. At this interval a decrease in the number of total cells as well as goblet cells/villus column was also noticeable. Dead cells which were prominently seen in crypts were totally absent in villi. The first signs of recovery can be observed on day 3 p.p. when total cell population, mitotic activity and goblet cells of crypt registered an increase while percentage of PNNC showed a fall. Percentage of total cell population and goblet cells/villus column also increased. The recovery continued up to 2 week of p.p. age. At p.p. age of 4 weeks a relapse of damage was observed when values for all the parameters of crypt and villi registered a fall except PNNC. This is followed by a second phase of recovery and by 6 and 12 weeks of post-partum age, normal value were obtained for all the parameters. (author)

  16. Hippocampal phosphoproteomics of F344 rats exposed to 1-bromopropane

    International Nuclear Information System (INIS)

    Huang, Zhenlie; Ichihara, Sahoko; Oikawa, Shinji; Chang, Jie; Zhang, Lingyi; Hu, Shijie; Huang, Hanlin; Ichihara, Gaku

    2015-01-01

    1-Bromopropane (1-BP) is neurotoxic in both experimental animals and human. To identify phosphorylated modification on the unrecognized post-translational modifications of proteins and investigate their role in 1-BP-induced neurotoxicity, changes in hippocampal phosphoprotein expression levels were analyzed quantitatively in male F344 rats exposed to 1-BP inhalation at 0, 400, or 1000 ppm for 8 h/day for 1 or 4 weeks. Hippocampal protein extracts were analyzed qualitatively and quantitatively by Pro-Q Diamond gel staining and SYPRO Ruby staining coupled with two-dimensional difference in gel electrophoresis (2D-DIGE), respectively, as well as by matrix-assisted laser-desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) to identify phosphoproteins. Changes in selected proteins were further confirmed by Manganese II (Mn 2+ )-Phos-tag SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Bax and cytochrome c protein levels were determined by western blotting. Pro-Q Diamond gel staining combined with 2D-DIGE identified 26 phosphoprotein spots (p < 0.05), and MALDI-TOF/MS identified 18 up-regulated proteins and 8 down-regulated proteins. These proteins are involved in the biological process of response to stimuli, metabolic processes, and apoptosis signaling. Changes in the expression of phosphorylated 14-3-3 θ were further confirmed by Mn 2+ -Phos-tag SDS-PAGE. Western blotting showed overexpression of Bax protein in the mitochondria with down-regulation in the cytoplasm, whereas cytochrome c expression was high in the cytoplasm but low in the mitochondria after 1-BP exposure. Our results suggest that the pathogenesis of 1-BP-induced hippocampal damage involves inhibition of antiapoptosis process. Phosphoproteins identified in this study can potentially serve as biomarkers for 1-BP-induced neurotoxicity. - Highlights: • 1-BP modified hippocampal phosphoproteome in rat and 23 altered proteins were identified. • 1-BP changed phosphorylation of GRP78

  17. Hippocampal phosphoproteomics of F344 rats exposed to 1-bromopropane

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Zhenlie [Guangdong Provincial Key Laboratory of Occupational Disease Prevention and Treatment, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510-300 (China); Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Ichihara, Sahoko [Graduate School of Regional Innovation Studies, Mie University, Tsu 514-8507 (Japan); Oikawa, Shinji [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie 514-8507 (Japan); Chang, Jie [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Graduate School of Regional Innovation Studies, Mie University, Tsu 514-8507 (Japan); Zhang, Lingyi [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Department of Occupational and Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda 278-8510 (Japan); Hu, Shijie [Guangdong Provincial Key Laboratory of Occupational Disease Prevention and Treatment, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510-300 (China); Huang, Hanlin, E-mail: huanghl@gdoh.org [Guangdong Provincial Key Laboratory of Occupational Disease Prevention and Treatment, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510-300 (China); Ichihara, Gaku, E-mail: gak@rs.tus.ac.jp [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Department of Occupational and Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda 278-8510 (Japan)

    2015-01-15

    1-Bromopropane (1-BP) is neurotoxic in both experimental animals and human. To identify phosphorylated modification on the unrecognized post-translational modifications of proteins and investigate their role in 1-BP-induced neurotoxicity, changes in hippocampal phosphoprotein expression levels were analyzed quantitatively in male F344 rats exposed to 1-BP inhalation at 0, 400, or 1000 ppm for 8 h/day for 1 or 4 weeks. Hippocampal protein extracts were analyzed qualitatively and quantitatively by Pro-Q Diamond gel staining and SYPRO Ruby staining coupled with two-dimensional difference in gel electrophoresis (2D-DIGE), respectively, as well as by matrix-assisted laser-desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) to identify phosphoproteins. Changes in selected proteins were further confirmed by Manganese II (Mn{sup 2+})-Phos-tag SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Bax and cytochrome c protein levels were determined by western blotting. Pro-Q Diamond gel staining combined with 2D-DIGE identified 26 phosphoprotein spots (p < 0.05), and MALDI-TOF/MS identified 18 up-regulated proteins and 8 down-regulated proteins. These proteins are involved in the biological process of response to stimuli, metabolic processes, and apoptosis signaling. Changes in the expression of phosphorylated 14-3-3 θ were further confirmed by Mn{sup 2+}-Phos-tag SDS-PAGE. Western blotting showed overexpression of Bax protein in the mitochondria with down-regulation in the cytoplasm, whereas cytochrome c expression was high in the cytoplasm but low in the mitochondria after 1-BP exposure. Our results suggest that the pathogenesis of 1-BP-induced hippocampal damage involves inhibition of antiapoptosis process. Phosphoproteins identified in this study can potentially serve as biomarkers for 1-BP-induced neurotoxicity. - Highlights: • 1-BP modified hippocampal phosphoproteome in rat and 23 altered proteins were identified. • 1-BP changed phosphorylation

  18. Prenatal Metformin Therapy Attenuates Hypertension of Developmental Origin in Male Adult Offspring Exposed to Maternal High-Fructose and Post-Weaning High-Fat Diets

    Directory of Open Access Journals (Sweden)

    You-Lin Tain

    2018-04-01

    Full Text Available Widespread consumption of a Western diet, comprised of highly refined carbohydrates and fat, may play a role in the epidemic of hypertension. Hypertension can take origin from early life. Metformin is the preferred treatment for type 2 diabetes. We examined whether prenatal metformin therapy can prevent maternal high-fructose plus post-weaning high-fat diets-induced hypertension of developmental origins via regulation of nutrient sensing signals, uric acid, oxidative stress, and the nitric oxide (NO pathway. Gestating Sprague–Dawley rats received regular chow (ND or chow supplemented with 60% fructose diet (HFR throughout pregnancy and lactation. Male offspring were onto either the ND or high-fat diet (HFA from weaning to 12 weeks of age. A total of 40 male offspring were assigned to five groups (n = 8/group: ND/ND, HFR/ND, ND/HFA, HFR/HFA, and HFR/HFA+metformin. Metformin (500 mg/kg/day was administered via gastric gavage for three weeks during the pregnancy period. Combined maternal HFR plus post-weaning HFA induced hypertension in male adult offspring, which prenatal metformin therapy prevented. The protective effects of prenatal metformin therapy on HFR/HFA-induced hypertension, including downregulation of the renin-angiotensin system, decrease in uric acid level, and reduction of oxidative stress. Our results highlighted that the programming effects of metformin administered prenatally might be different from those reported in adults, and that deserves further elucidation.

  19. The Threshold of Toxicological Concern for prenatal developmental toxicity in rats and rabbits

    Science.gov (United States)

    van Ravenzwaay, B.; Jiang, X.; Luechtefeld, T.; Hartung, T.

    2018-01-01

    The Threshold Toxicological Concern (TTC) is based on the concept that in absence of experimental data reasonable assurance of safety can be given if exposure is sufficiently low. Using the REACH database the low 5th percentile of the NO(A)EL distribution, for prenatal developmental toxicity (OECD guideline 414) was determined. For rats, (434 NO(A)ELs values) for maternal toxicity, this value was 10 mg/kg-bw/day. For developmental toxicity (469 NO(A)ELs): 13 mg/kg-bw/day. For rabbits, (100 NO(A)ELs), the value for maternal toxicity was 4 mg/kg-bw/day, for developmental toxicity, (112 NO(A)EL values): 10 mg/kg-bw/day. The maternal organism may thus be slightly more sensitive than the fetus. Combining REACH- (industrial chemicals) and published BASF-data (mostly agrochemicals), 537 unique compounds with NO(A)EL values for developmental toxicity in rats and 150 in rabbits were evaluated. The low 5th percentile NO(A)EL for developmental toxicity in rats was 10 mg/kg-bw/day and 9.5 mg/kg-bw/day for rabbits. Using an assessment factor of 100, a TTC value for developmental toxicity of 100 µg/kg-bw/day for rats and 95 µg/kg-bw/day for rabbits is calculated. These values could serve as guidance whether or not to perform an animal experiment, if exposure is sufficiently low. In emergency situations this value may be useful for a first tier risk assessment. PMID:28645885

  20. Prenatal restraint stress generates two distinct behavioral and neurochemical profiles in male and female rats.

    Directory of Open Access Journals (Sweden)

    Anna Rita Zuena

    Full Text Available Prenatal Restraint Stress (PRS in rats is a validated model of early stress resulting in permanent behavioral and neurobiological outcomes. Although sexual dimorphism in the effects of PRS has been hypothesized for more than 30 years, few studies in this long period have directly addressed the issue. Our group has uncovered a pronounced gender difference in the effects of PRS (stress delivered to the mothers 3 times per day during the last 10 days of pregnancy on anxiety, spatial learning, and a series of neurobiological parameters classically associated with hippocampus-dependent behaviors. Adult male rats subjected to PRS ("PRS rats" showed increased anxiety-like behavior in the elevated plus maze (EPM, a reduction in the survival of newborn cells in the dentate gyrus, a reduction in the activity of mGlu1/5 metabotropic glutamate receptors in the ventral hippocampus, and an increase in the levels of brain-derived neurotrophic factor (BDNF and pro-BDNF in the hippocampus. In contrast, female PRS rats displayed reduced anxiety in the EPM, improved learning in the Morris water maze, an increase in the activity of mGlu1/5 receptors in the ventral and dorsal hippocampus, and no changes in hippocampal neurogenesis or BDNF levels. The direction of the changes in neurogenesis, BDNF levels and mGlu receptor function in PRS animals was not consistent with the behavioral changes, suggesting that PRS perturbs the interdependency of these particular parameters and their relation to hippocampus-dependent behavior. Our data suggest that the epigenetic changes in hippocampal neuroplasticity induced by early environmental challenges are critically sex-dependent and that the behavioral outcome may diverge in males and females.

  1. Prenatal ethanol exposure reduces the effects of excitatory amino acids in the rat hippocampus

    International Nuclear Information System (INIS)

    Noble, E.P.; Ritchie, T.

    1989-01-01

    Chronic alcohol ingestion during pregnancy can lead to the Fetal Alcohol Syndrome (FAS), a disorder marked by learning disabilities. A rat model of FAS was used by introducing pregnant Sprague-Dawley rats to a liquid diet containing 35% ethanol-derived calories (E), while a second group was pair-fed an isocaloric liquid diet without ethanol (P). A third group of pregnant dams received ad libitum lab chow (C). At parturition, pups from the E and P groups were cross fostered by C mothers and all groups received lab chow. During adulthood, male offspring were sacrificed and hippocampal and prefrontal cortical slices were prelabeled with [3H]inositol. Phosphoinositide (PI) hydrolysis was determined by measuring the accumulation of [3H]inositol phosphates in the presence of LiCl in response to activation of various excitatory amino acid (EAA) receptors. In hippocampal slices, ibotenate- and quisqualate-induced PI hydrolysis was reduced in E compared to P and C animals. Moreover, the inhibitory effect of N-methyl-D-aspartate (NMDA) on carbachol-induced PI hydrolysis, evident in P and C animals, was completely abolished in the hippocampus of E animals. In contrast, in the prefrontal cerebral cortex, this inhibitory effect of NMDA prevailed even in the E animals. The evidence suggests that prenatal ethanol exposure alters the activity of EAA receptors in the hippocampal generation of 2nd messengers

  2. Preference for safflower oil in rats exposed to a cold environment under free-feeding conditions.

    Science.gov (United States)

    Saitoh, Masaji; Ishii, Toshiaki; Takewaki, Tadashi; Nishimura, Masakazu

    2005-07-01

    There are several benefits to a high-fat diet for animals exposed to cold, including improved tolerance to severe cold conditions and increased survival rates in cold environments. It is therefore of interest to examine whether animals exposed to cold will selectively consume lipids. We examined the intake of safflower oil (SO) by rats exposed to cold (4 +/- 2 degrees C) under a feeding condition in which the rats were given free access to SO. Rats exposed to cold consumed more SO than those housed at 25 +/- 2 degrees C. This finding suggests that rats prefer SO in a cold environment. There was no significant difference in the ratio of calories of SO ingested to that of matter (standard laboratory chow plus SO) ingested between rats exposed to cold and those at 25 +/- 2 degrees C. The high SO intake also affected cold tolerance and metabolite kinetics in the rats. Factors that affected the SO intake of rats exposed to cold are also discussed.

  3. Postnatal development and behaviour of Wistar rats after prenatal toluene exposure

    Energy Technology Data Exchange (ETDEWEB)

    Thiel, R. [Fachbereich Humanmedizin, Universitaetsklinikum Benjamin Franklin, Inst. fuer Toxikologie und Embryopharmakologie, Freie Univ. Berlin (Germany); Chahoud, I. [Fachbereich Humanmedizin, Universitaetsklinikum Benjamin Franklin, Inst. fuer Toxikologie und Embryopharmakologie, Freie Univ. Berlin (Germany)

    1997-02-01

    Pregnant Wistar rats were treated with different concentrations of toluene by inhalation (300, 600, 1000 and 1200 ppm) from day 9 to day 21 of pregnancy for 6 h a day in a whole-body inhalation chamber (controls inhaled fresh air only). From day 22, rats were kept single-caged and were allowed to deliver. Besides a detailed evaluation of the physical development of the offspring we performed the following tests: forelimb-grasp reflex, righting reflex, cliff-drop aversion reflex, maintainance of balance on a rotating rod, measurement of locomotor activity and learning ability in a discrimination learning test. A toluene exposure of 1200 ppm resulted in a reduced body weight of rat dams and offspring and a higher mortality until weaning. The physical development (incisor eruption, eye opening and vaginal opening) was retarded in this group. There were no clear-cut and concentration-dependent differences in the development of reflexes, rota rod performance and locomotor activity between the offspring of animals exposed to toluene and the controls. Likewise, no effects were found on learning ability in the operant conditioning task. Compared to the controls there were no differences in mating, fertility and pregnancy indexes in the F{sub 1}-generation. The tests performed have provided no evidence that toluene exposures {<=} 1200 ppm induce adverse effects on the behaviour of rat offspring exposed during late embryonic and fetal development. (orig.). With 8 figs., 7 tabs.

  4. Analysis of emotionality and locomotion in radio-frequency electromagnetic radiation exposed rats.

    Science.gov (United States)

    Narayanan, Sareesh Naduvil; Kumar, Raju Suresh; Paval, Jaijesh; Kedage, Vivekananda; Bhat, M Shankaranarayana; Nayak, Satheesha; Bhat, P Gopalakrishna

    2013-07-01

    In the current study the modulatory role of mobile phone radio-frequency electromagnetic radiation (RF-EMR) on emotionality and locomotion was evaluated in adolescent rats. Male albino Wistar rats (6-8 weeks old) were randomly assigned into the following groups having 12 animals in each group. Group I (Control): they remained in the home cage throughout the experimental period. Group II (Sham exposed): they were exposed to mobile phone in switch-off mode for 28 days, and Group III (RF-EMR exposed): they were exposed to RF-EMR (900 MHz) from an active GSM (Global system for mobile communications) mobile phone with a peak power density of 146.60 μW/cm(2) for 28 days. On 29th day, the animals were tested for emotionality and locomotion. Elevated plus maze (EPM) test revealed that, percentage of entries into the open arm, percentage of time spent on the open arm and distance travelled on the open arm were significantly reduced in the RF-EMR exposed rats. Rearing frequency and grooming frequency were also decreased in the RF-EMR exposed rats. Defecation boli count during the EPM test was more with the RF-EMR group. No statistically significant difference was found in total distance travelled, total arm entries, percentage of closed arm entries and parallelism index in the RF-EMR exposed rats compared to controls. Results indicate that mobile phone radiation could affect the emotionality of rats without affecting the general locomotion.

  5. Prenatal inhibition of the kynurenine pathway leads to structural changes in the hippocampus of adult rat offspring

    OpenAIRE

    Khalil, Omari S; Pisar, Mazura; Forrest, Caroline M; Vincenten, Maria C J; Darlington, L Gail; Stone, Trevor W

    2014-01-01

    Glutamate receptors for N-methyl-d-aspartate (NMDA) are involved in early brain development. The kynurenine pathway of tryptophan metabolism includes the NMDA receptor agonist quinolinic acid and the antagonist kynurenic acid. We now report that prenatal inhibition of the pathway in rats with 3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulphonamide (Ro61-8048) produces marked changes in hippocampal neuron morphology, spine density and the immunocytochemical localisation of developme...

  6. 90 days bioassay in sprague-dawley rats exposed to 20KHz magnetic field

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sung-Ho [College of Veterinary Medicine, Chonnam National Univ. Kwangju (Korea, Republic of); Song, Ji-Eun; Lee, Yun-Sil [Korea Cancer Center Hospital, Seoul (Korea, Republic of); Pack, Jeong-Ki [ETRI, Daejon (Korea, Republic of); Yoo, Done-SIk [College of Engineering, Daejon (Korea, Republic of)

    2002-07-01

    Sprague Dawley rats (20 rats/group [10 males, 10 females] in sham and magnetic field exposed groups) were exposed in carrousel irradiator to an 20 KHz magnetic field for 8 hrs/day, 5 days/week, for 90 days. Urine analysis (pH, SG, protein, ketone body, RBC, WBC, glucose, bilirubin, and urobilinogen), blood analysis (WBC, RBC, HGB; henoglubin concentration, HCT; hematocrit, MCV; mean corpuscular volume, MCH; mean corpuscular hemoglobin, MCHC; mean corpuscular hemoglobin concentration, and PLT; platelet or thrombocyte count), blood biochemistry (total protein, blood urea nitrogen, creatinine, glucose, total bilirubin, total cholesterol, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase), histopathological analysis for organs such as liver, kidney, testis, ovary, spleen, brain, heart, and lung were performed. When compared to the sham control rats, there were no significant differences in above analysis of magnetic field exposed rats. From the results, there were no significant differences between control and exposed fetus.

  7. Cerebellar malformations in prenatally x-irradiated rats: quantitative analysis and detailed description

    International Nuclear Information System (INIS)

    Inouye, M.

    1979-01-01

    Pregnant WKA/HoK rats were exposed to 100 R or 200 R x-irradiation on one of gestation days 16 through 21. Offspring were killed at 60 days of age and the cerebellum was examined. The cerebellum of animals exposed to 200 R was slightly reduced in weight but not in width. The observed reduction in the dorsoventral length of the cerebellum was more evident when the x-irradiation was early in gestation. The anterior portions of hemispheres were situated anterior to the culmen in every 200 R group. Histologically, ectopic Purkinje cells in the granule cell layer and white matter appeared following x-irradiation on day 20 or 21, but they were not found following earlier treatment. In the cerebellum of animals exposed to 100 R the reduction in size was mild and the folial abnormalities were rare, but the number of sublobules decreased

  8. Clinical Signs and Organ Pathology in Rats Exposed To Graded ...

    African Journals Online (AJOL)

    Olaleye

    pyrethroids-containing insecticides on farm and market produce and in human ... Key words: Pyrethroids, insecticides, rats, tissue pathology, public health hazard ... ingredients, differing in chemical structure or in ... meat shops, in poultry pens and on dogs and cats ... A total of 54 (27 male and 27 female) albino rats.

  9. Prenatal ethanol enhances rotational behavior to apomorphine in the 24-month-old rat offspring with small striatal lesion.

    Science.gov (United States)

    Gomide, Vânia C; Chadi, Gerson

    2004-01-01

    Pregnant Wistar rats received a hyperproteic liquid diet containing 37.5% ethanol-derived calories during gestation. Isocaloric amount of liquid diet, with maltose-dextrin substituted for ethanol, was given to control pair-fed dams. Offsprings were allowed to survive until 24 months of age. A set of aged female offsprings of both control diet and ethanol diet groups was registered for spontaneous motor activity, by means of an infrared motion sensor activity monitor, or for apomorphine-induced rotational behavior, while another lot of male offsprings was submitted to an unilateral striatal small mechanical lesion by a needle, 6 days before rotational recordings. Prenatal ethanol did not alter spontaneous motor parameters like resting time as well as the events of small and large movements in the aged offsprings. Bilateral circling behavior was already increased 5 min after apomorphine in the unlesioned offsprings of both the control and ethanol diet groups. However, it lasted more elevated for 45- to 75-min time intervals in the gestational ethanol-exposed offsprings, while decreasing faster in the control offsprings. Apomorphine triggered a strong and sustained elevation of contraversive turns in the striatal-lesioned 24-month-old offsprings of the ethanol group, but only a small and transient elevation was seen in the offsprings of the control diet group. Astroglial and microglial reactions were seen surrounding the striatal needle track lesion. Microdensitometric image analysis demonstrated no differences in the levels of tyrosine hydroxylase immunoreactivity in the striatum of 24-month-old unlesioned and lesioned offsprings of control and alcohol diet groups. The results suggest that ethanol exposure during gestation may alter the sensitivity of dopamine receptor in aged offsprings, which is augmented by even a small striatal lesion.

  10. Technical Nuances of Exposing Rat Common Carotid Arteries for Practicing Microsurgical Anastomosis.

    Science.gov (United States)

    Tayebi Meybodi, Ali; Aklinski, Joseph; Gandhi, Sirin; Lawton, Michael T; Preul, Mark C

    2018-04-17

    Animal models are commonly used in training protocols for microsurgical vascular anastomosis. Rat common carotid arteries (CCAs) are frequently used for this purpose. Much attention has been paid to the technical details of various anastomosis configurations using these arteries. However, technical nuances of exposing rat CCAs have been understudied. The purpose of this study is to describe nuances of technique for safely and efficiently exposing rat CCAs in preparation for a vascular anastomosis. Bilateral CCAs were exposed and prepared for anastomosis in 10 anesthetized Sprague-Dawley rats through a midline cervical incision. The exposed length of the CCA was measured. Additionally, technical nuances of exposure and surgically relevant anatomic details were recorded. The CCAs were exposed from the sternoclavicular joint to their bifurcation (average length, 19.1 ± 2.8 mm). Tenets important for a safe and efficient exposure of the CCAs included 1) generous subcutaneous dissection to expose the external jugular veins (EJVs), 2) avoiding injury to or compression of the EJVs, 3) superior mobilization of the salivary glands, 4) division of internal jugular veins, 5) opening the carotid sheath at its midlevel and from medial to lateral, and 6) avoiding injury to the vagus nerve or sympathetic trunk. Using the principles introduced in this study, trainees may safely and efficiently expose rat CCAs in preparation for a bypass. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Prenatal Dexamethasone and Postnatal High-Fat Diet Decrease Interferon Gamma Production through an Age-Dependent Histone Modification in Male Sprague-Dawley Rats

    Science.gov (United States)

    Yu, Hong-Ren; Tain, You-Lin; Sheen, Jiunn-Ming; Tiao, Mao-Meng; Chen, Chih-Cheng; Kuo, Ho-Chang; Hung, Pi-Lien; Hsieh, Kai-Sheng; Huang, Li-Tung

    2016-01-01

    Overexposure to prenatal glucocorticoid (GC) disturbs hypothalamic-pituitary-adrenocortical axis-associated neuroendocrine metabolism and susceptibility to metabolic syndrome. A high-fat (HF) diet is a major environmental factor that can cause metabolic syndrome. We aimed to investigate whether prenatal GC plus a postnatal HF diet could alter immune programming in rat offspring. Pregnant Sprague-Dawley rats were given intraperitoneal injections of dexamethasone or saline at 14–21 days of gestation. Male offspring were then divided into four groups: vehicle, prenatal dexamethasone exposure, postnatal HF diet (VHF), and prenatal dexamethasone exposure plus a postnatal HF diet (DHF). The rats were sacrificed and adaptive immune function was evaluated. Compared to the vehicle, the DHF group had lower interferon gamma (IFN-γ) production by splenocytes at postnatal day 120. Decreases in H3K9 acetylation and H3K36me3 levels at the IFN-γ promoter correlated with decreased IFN-γ production. The impaired IFN-γ production and aberrant site-specific histone modification at the IFN-γ promoter by prenatal dexamethasone treatment plus a postnatal HF diet resulted in resilience at postnatal day 180. Prenatal dexamethasone and a postnatal HF diet decreased IFN-γ production through a site-specific and an age-dependent histone modification. These findings suggest a mechanism by which prenatal exposure to GC and a postnatal environment exert effects on fetal immunity programming. PMID:27669212

  12. Prenatal Dexamethasone and Postnatal High-Fat Diet Decrease Interferon Gamma Production through an Age-Dependent Histone Modification in Male Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Hong-Ren Yu

    2016-09-01

    Full Text Available Overexposure to prenatal glucocorticoid (GC disturbs hypothalamic-pituitary-adrenocortical axis-associated neuroendocrine metabolism and susceptibility to metabolic syndrome. A high-fat (HF diet is a major environmental factor that can cause metabolic syndrome. We aimed to investigate whether prenatal GC plus a postnatal HF diet could alter immune programming in rat offspring. Pregnant Sprague-Dawley rats were given intraperitoneal injections of dexamethasone or saline at 14–21 days of gestation. Male offspring were then divided into four groups: vehicle, prenatal dexamethasone exposure, postnatal HF diet (VHF, and prenatal dexamethasone exposure plus a postnatal HF diet (DHF. The rats were sacrificed and adaptive immune function was evaluated. Compared to the vehicle, the DHF group had lower interferon gamma (IFN-γ production by splenocytes at postnatal day 120. Decreases in H3K9 acetylation and H3K36me3 levels at the IFN-γ promoter correlated with decreased IFN-γ production. The impaired IFN-γ production and aberrant site-specific histone modification at the IFN-γ promoter by prenatal dexamethasone treatment plus a postnatal HF diet resulted in resilience at postnatal day 180. Prenatal dexamethasone and a postnatal HF diet decreased IFN-γ production through a site-specific and an age-dependent histone modification. These findings suggest a mechanism by which prenatal exposure to GC and a postnatal environment exert effects on fetal immunity programming.

  13. Lung development and postnatal survival for rats exposed in utero to a high-boiling coal liquid

    Energy Technology Data Exchange (ETDEWEB)

    Springer, D.L.; Hackett, P.L.; Miller, R.A.; Buschbom, R.L.

    1986-01-01

    The study reported determines postnatal viability and development of survivors following in utero exposure to Harmarville process solvent (HPS), a wide-boiling-range (150 to > 455/sup 0/C) coal liquid. For this study, 0.74 g kg/sup -1/ of the coal liquid was administered (by intragastric intubation) to rats from 12 to 14 dg. Offspring were evaluated for postnatal survival, growth and lung and thymus weights. Fifty-four percent of the exposed pups and 9% of the control pups died between birth and 3 days postpartum. Of the treated pups that died, 10% (6/5; pups/litters) had cleft palate, 27% (17/9) had small lungs and 33% (21/8) had both cleft palate and small lungs. No gross malformations were observed in the remaining 30% of the dead pups. Microscopic examination of lungs from HPS-treated pups revealed no evident histological abnormalities. Body, lung and thymus weights for treated animals that died were significantly less than those of controls. Surviving exposed pups weighed significantly less than control pups from 0.25 to 21 days postpartum and their thymus weights were also depressed through 21 days postpartum. These data suggest that retarded lung growth during prenatal life as a result of in utero exposure to the coal liquid contributes to a significant portion of the observed neonatal mortality. Furthermore, lung weights of survivors, although significantly lower than control values through 7 days postpartum, appeared to have recovered by 21 days postpartum.

  14. Prenatal iron deficiency causes sex-dependent mitochondrial dysfunction and oxidative stress in fetal rat kidneys and liver.

    Science.gov (United States)

    Woodman, Andrew G; Mah, Richard; Keddie, Danae; Noble, Ronan M N; Panahi, Sareh; Gragasin, Ferrante S; Lemieux, Hélène; Bourque, Stephane L

    2018-06-01

    Prenatal iron deficiency alters fetal developmental trajectories, which results in persistent changes in organ function. Here, we studied the effects of prenatal iron deficiency on fetal kidney and liver mitochondrial function. Pregnant Sprague-Dawley rats were fed partially or fully iron-restricted diets to induce a state of moderate or severe iron deficiency alongside iron-replete control rats. We assessed mitochondrial function via high-resolution respirometry and reactive oxygen species generation via fluorescence microscopy on gestational d 21. Hemoglobin levels were reduced in dams in the moderate (-31%) and severe groups (-54%) compared with controls, which was accompanied by 55% reductions in fetal hemoglobin levels in both moderate and severe groups versus controls. Male iron-deficient kidneys exhibited globally reduced mitochondrial content and respiration, as well as increased cytosolic superoxide and decreased NO. Female iron-deficient kidneys exhibited complex II down-regulation and increased mitochondrial oxidative stress. Male iron-deficient livers exhibited reduced complex IV respiration and increased cytosolic superoxide, whereas female liver tissues exhibited no alteration in oxidant levels or mitochondrial function. These findings indicate that prenatal iron deficiency causes changes in mitochondrial content and function as well as oxidant status in a sex- and organ-dependent manner, which may be an important mechanism that underlies the programming of cardiovascular disease.-Woodman, A. G., Mah, R., Keddie, D., Noble, R. M. N., Panahi, S., Gragasin, F. S., Lemieux, H., Bourque, S. L. Prenatal iron deficiency causes sex-dependent mitochondrial dysfunction and oxidative stress in fetal rat kidneys and liver.

  15. Effects of prenatal stress on anxiety- and depressive-like behaviors are sex-specific in prepubertal rats.

    Science.gov (United States)

    Iturra-Mena, Ann Mary; Arriagada-Solimano, Marcia; Luttecke-Anders, Ariane; Dagnino-Subiabre, Alexies

    2018-05-17

    The fetal brain is highly susceptible to stress in late pregnancy, with lifelong effects of stress on physiology and behavior. The aim of this study was to determine the physiological and behavioral effects of prenatal stress during the prepubertal period of female and male rats. We subjected pregnant Sprague-Dawley rats to a restraint stress protocol from gestational day 14 until 21, a critical period for fetal brain susceptibility to stress effects. Male and female offspring were subsequently assessed at postnatal day 24 for anxiety- and depressive-like behaviors, and spontaneous social interaction. We also assessed maternal behaviors and two stress markers: basal vs. acute-evoked stress levels of serum corticosterone and body weight gain. Prenatal stress did not affect the maternal behavior, while both female and male offspring had higher body weight gain. On the other hand, lower levels of corticosterone after acute stress stimulation as well as anxiety- and depressive-like behaviors were only evident in stressed males compared to control males. These results suggest that prenatal stress induced sex-specific effects on the hypothalamus-pituitary-adrenal (HPA) axis activity and on behavior during prepuberty. The HPA axis of prenatally stressed male rats was less active compared to control males, as well as they were more anxious and experienced depressive-like behaviors. Our results can be useful to study the neurobiological basis of childhood depression at a pre-clinical level. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  16. Effect of fish oil and coconut fat supplementation on depressive-type behavior and corticosterone levels of prenatally stressed male rats.

    Science.gov (United States)

    Borsonelo, Elizabethe Cristina; Suchecki, Deborah; Galduróz, José Carlos Fernandes

    2011-04-18

    Prenatal stress (PNS) during critical periods of brain development has been associated with numerous behavioral and/or mood disorders in later life. These outcomes may result from changes in the hypothalamic-pituitary-adrenal (HPA) axis activity, which, in turn, can be modulated by environmental factors, such as nutritional status. In this study, the adult male offspring of dams exposed to restraint stress during the last semester of pregnancy and fed different diets were evaluated for depressive-like behavior in the forced swimming test and for the corticosterone response to the test. Female Wistar rats were allocated to one of three groups: regular diet, diet supplemented with coconut fat or with fish oil, offered during pregnancy and lactation. When pregnancy was confirmed, they were distributed into control or stress groups. Stress consisted of restraint and bright light for 45 min, three times per day, in the last week of pregnancy. The body weight of the adult offspring submitted to PNS was lower than that of controls. In the forced swimming test, time of immobility was reduced and swimming was increased in PNS rats fed fish oil and plasma corticosterone levels immediately after the forced swimming test were lower in PNS rats fed regular diet than their control counterparts; this response was reduced in control rats whose mothers were fed fish oil and coconut fat. The present results indicate that coconut fat and fish oil influenced behavioral and hormonal responses to the forced swimming test in both control and PNS adult male rats. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. Prenatal stress increases the obesogenic effects of a high-fat-sucrose diet in adult rats in a sex-specific manner.

    Science.gov (United States)

    Paternain, L; de la Garza, A L; Batlle, M A; Milagro, F I; Martínez, J A; Campión, J

    2013-03-01

    Stress during pregnancy can induce metabolic disorders in adult offspring. To analyze the possible differential response to a high-fat-sucrose (HFS) diet in offspring affected by prenatal stress (PNS) or not, pregnant Wistar rats (n = 11) were exposed to a chronic mild stress during the third week of gestation. The aim of this study was to model a chronic depressive-like state that develops over time in response to exposure of rats to a series of mild and unpredictable stressors. Control dams (n = 11) remained undisturbed. Adult offspring were fed chow or HFS diet (20% protein, 35% carbohydrate, 45% fat) for 10 weeks. Changes in adiposity, biochemical profile, and retroperitoneal adipose tissue gene expression by real-time polymerase chain reaction were analyzed. An interaction was observed between HFS and PNS concerning visceral adiposity, with higher fat mass in HFS-fed stressed rats, statistically significant only in females. HFS modified lipid profile and increased insulin resistance biomarkers, while PNS reduced insulin concentrations and the homeostasis model assessment index. HFS diet increased gene (mRNA) expression for leptin and apelin and decreased cyclin-dependent kinase inhibitor 1A and fatty acid synthase (Fasn), whereas PNS increased Fasn and stearoyl-CoA desaturase1. An interaction between diet and PNS was observed for adiponutrin (Adpn) and peroxisome proliferator-activated receptor-γ coactivator1-α (Ppargc1a) gene expression: Adpn was increased by the PNS only in HFS-fed rats, whereas Ppargc1a was increased by the PNS only in chow-fed rats. From these results, it can be concluded that experience of maternal stress during intrauterine development can enhance predisposition to obesity induced by a HFS diet intake.

  18. Effect of Prenatal Protein Malnutrition on Long-Term Potentiation and BDNF Protein Expression in the Rat Entorhinal Cortex after Neocortical and Hippocampal Tetanization

    Directory of Open Access Journals (Sweden)

    Alejandro Hernández

    2008-01-01

    Full Text Available Reduction of the protein content from 25 to 8% casein in the diet of pregnant rats results in impaired neocortical long-term potentiation (LTP of the offspring together with lower visuospatial memory performance. The present study was aimed to investigate whether this type of maternal malnutrition could result in modification of plastic capabilities of the entorhinal cortex (EC in the adult progeny. Unlike normal eutrophic controls, 55–60-day-old prenatally malnourished rats were unable to develop LTP in the medial EC to tetanizing stimulation delivered to either the ipsilateral occipital cortex or the CA1 hippocampal region. Tetanizing stimulation of CA1 also failed to increase the concentration of brain-derived neurotrophic factor (BDNF in the EC of malnourished rats. Impaired capacity of the EC of prenatally malnourished rats to develop LTP and to increase BDNF levels during adulthood may be an important factor contributing to deficits in learning performance having adult prenatally malnourished animals.

  19. Effect of prenatal protein malnutrition on long-term potentiation and BDNF protein expression in the rat entorhinal cortex after neocortical and hippocampal tetanization.

    Science.gov (United States)

    Hernández, Alejandro; Burgos, Héctor; Mondaca, Mauricio; Barra, Rafael; Núñez, Héctor; Pérez, Hernán; Soto-Moyano, Rubén; Sierralta, Walter; Fernández, Victor; Olivares, Ricardo; Valladares, Luis

    2008-01-01

    Reduction of the protein content from 25 to 8% casein in the diet of pregnant rats results in impaired neocortical long-term potentiation (LTP) of the offspring together with lower visuospatial memory performance. The present study was aimed to investigate whether this type of maternal malnutrition could result in modification of plastic capabilities of the entorhinal cortex (EC) in the adult progeny. Unlike normal eutrophic controls, 55-60-day-old prenatally malnourished rats were unable to develop LTP in the medial EC to tetanizing stimulation delivered to either the ipsilateral occipital cortex or the CA1 hippocampal region. Tetanizing stimulation of CA1 also failed to increase the concentration of brain-derived neurotrophic factor (BDNF) in the EC of malnourished rats. Impaired capacity of the EC of prenatally malnourished rats to develop LTP and to increase BDNF levels during adulthood may be an important factor contributing to deficits in learning performance having adult prenatally malnourished animals.

  20. Effect of prenatal exposure to low dose beta radiation from tritiated water on postnatal growth and neurobehavior of rats

    International Nuclear Information System (INIS)

    Gao Weimin; Zhou Xiangyan

    1998-01-01

    Objective: Effects of prenatal exposure to HTO (tritiated water) on postnatal growth and neurobehavior of rats were studied by determination of multiple parameters. Methods: Pregnant adult Wistar rats were randomly assigned to 4 groups, of which 3 groups were irradiated with beta-rays from tritiated water (HTO) by one single intraperitoneal injection on the 13th day of gestation. Offspring of these rats received cumulative doses of 0.000, 0.044, 0.088 and 0.264 Gy utero, respectively, and were observed for the appearance of three physiologic markers (eye opening, pinna detachment, incisor eruption), the age of acquisition of two reflexes (surface righting, negative geotaxis) and sensuous function (auditory startle), movement and coordination functions and activity (forelimb hanging, continuous corridor activity), and learning and memory (electric avoidance reflex in Y-maze, conditional reflex). Results: Results for most parameters in the 0.044 and 0.088 Gy groups were different significantly from those in the controls and for most parameters a dose-dependent effect was found. Conclusion: Offspring of rats having received prenatal low dose irradiation from HTO showed delayed growth and abnormal neurobehavior

  1. Behavioural Outcomes of Four-Year-Old Children Prenatally Exposed to Methadone or Buprenorphine: A Test of Three Risk Models

    Science.gov (United States)

    Konijnenberg, Carolien; Lund, Ingunn Olea; Melinder, Annika

    2015-01-01

    It is still under debate whether the reported effects of opioid maintenance therapy (OMT) on child behaviour are a direct effect of prenatal exposure, or whether other factors are involved. This prospective cohort study investigated three models: the teratogenic risk model, the maternal risk model, and a combined risk model in a group of 35…

  2. Effects of Unpredictable Variable Prenatal Stress (UVPS) on Bdnf DNA Methylation and Telomere Length in the Adult Rat Brain

    Science.gov (United States)

    Blaze, Jennifer; Asok, A.; Moyer, E. L.; Roth, T. L.; Ronca, A. E.

    2015-01-01

    In utero exposure to stress can shape neurobiological and behavioral outcomes in offspring, producing vulnerability to psychopathology later in life. Animal models of prenatal stress likewise have demonstrated long-­-term alterations in brain function and behavioral deficits in offspring. For example, using a rodent model of unpredictable variable prenatal stress (UVPS), in which dams are exposed to unpredictable, variable stress across pregnancy, we have found increased body weight and anxiety-­-like behavior in adult male, but not female, offspring. DNA methylation (addition of methyl groups to cytosines which normally represses gene transcription) and changes in telomere length (TTAGGG repeats on the ends of chromosomes) are two molecular modifications that result from stress and could be responsible for the long-­-term effects of UVPS. Here, we measured methylation of brain-­-derived neurotrophic factor (bdnf), a gene important in development and plasticity, and telomere length in the brains of adult offspring from the UVPS model. Results indicate that prenatally stressed adult males have greater methylation in the medial prefrontal cortex (mPFC) compared to non-­-stressed controls, while females have greater methylation in the ventral hippocampus compared to controls. Further, prenatally stressed males had shorter telomeres than controls in the mPFC. These findings demonstrate the ability of UVPS to produce epigenetic alterations and changes in telomere length across behaviorally-­-relevant brain regions, which may have linkages to the phenotypic outcomes.

  3. Taurine Ameliorates Renal Oxidative Damage and Thyroid Dysfunction in Rats Chronically Exposed to Fluoride.

    Science.gov (United States)

    Adedara, Isaac A; Ojuade, Temini Jesu D; Olabiyi, Bolanle F; Idris, Umar F; Onibiyo, Esther M; Ajeigbe, Olufunke F; Farombi, Ebenezer O

    2017-02-01

    Excessive exposure to fluoride poses several detrimental effects to human health particularly the kidney which is a major organ involved in its elimination from the body. The influence of taurine on fluoride-induced renal toxicity was investigated in a co-exposure paradigm for 45 days using five groups of eight rats each. Group I rats received normal drinking water alone, group II rats were exposed to sodium fluoride (NaF) in drinking water at 15 mg/L alone, group III received taurine alone at a dose of 200 mg/kg group IV rats were co-administered with NaF and taurine (100 mg/kg), while group V rats were co-administered with NaF and taurine (200 mg/kg). Administration of taurine significantly reversed the fluoride-mediated decrease in absolute weight and organo-somatic index of the kidney in the exposed rats. Taurine significantly prevented fluoride-induced elevation in plasma urea and creatinine levels in the exposed rats. Moreover, taurine restored fluoride-mediated decrease in the circulatory concentrations of triiodothyronine, thyroxine, and the ratio of triiodothyronine to thyroxine. Taurine ameliorated fluoride-mediated decrease in renal antioxidant status by significantly enhancing the antioxidant enzyme activities as well as glutathione level in the exposed rats. Additionally, taurine inhibited fluoride-induced renal oxidative damage by markedly decreasing the hydrogen peroxide and malondialdehyde levels as well as improved the kidney architecture in the treated rats. Collectively, taurine protected against fluoride-induced renal toxicity via enhancement of thyroid gland function, renal antioxidant status, and histology in rats.

  4. LHRH and LH in peripubertal female rats following prenatal and/or postnatal ethanol exposure

    International Nuclear Information System (INIS)

    Morris, D.L.; Harms, P.G.; Petersen, H.D.; McArthur, N.H.

    1989-01-01

    The effects of pre- and postnatal exposure to ethanol (ETHO) on LHRH and LH were investigated. Pregnant and/or lactating dams were fed ETHOD during: (1) gestation, (2) lactation, or (3) gestation-lactation. Female offspring were decapitated at 30 or 40 days-of-age; trunk blood was collected for plasma LH RIA; and hypothalamic tissues were collected for LHRH RIA. Hypothalamic LHRH content of all ETOH-exposed groups was less than that of non-ETOH-fed controls at 30 and 40 days-of-age. Plasma LH concentrations of all ETOH-exposed groups were less than those of non-ETOD-fed controls at 30 and 40 days-of-age. Also, at 30 and 40 days-of-age, the plasma LH concentrations of the animals exposed to ETOH during lactation and gestation-lactation were less than those of the animals exposed to ETOH during gestation. These data suggest that ETOH exposure during gestation and/or lactation negatively affects hypothalamic LHRH content of femal rat offspring. Decreased hypothalamic LHRH content with corresponding lowered plasma LH concentration suggests that ETOH influences development or maturation of hypothalamic LHRH neurons by possibly decreasing their number or synthesizing capability

  5. Bone metabolism of male rats chronically exposed to cadmium

    International Nuclear Information System (INIS)

    Brzoska, Malgorzata M.; Moniuszko-Jakoniuk, Janina

    2005-01-01

    Recently, based on a female rat model of human exposure, we have reported that low-level chronic exposure to cadmium (Cd) has an injurious effect on the skeleton. The purpose of the current study was to investigate whether the exposure may also affect bone metabolism in a male rat model and to estimate the gender-related differences in the bone effect of Cd. Young male Wistar rats received drinking water containing 0, 1, 5, or 50 mg Cd/l for 12 months. The bone effect of Cd was evaluated using bone densitometry and biochemical markers of bone turnover. Renal handling of calcium (Ca) and phosphate, and serum concentrations of vitamin D metabolites, calcitonin, and parathormone were estimated as well. At treatment with 1 mg Cd/l, corresponding to the low environmental exposure in non-Cd-polluted areas, the bone mineral content (BMC) and density (BMD) at the femur and lumbar spine (L1-L5) and the total skeleton BMD did not differ compared to control. However, from the 6th month of the exposure, the Z score BMD indicated osteopenia in some animals and after 12 months the bone resorption very clearly tended to an increase. The rats' exposure corresponding to human moderate (5 mg Cd/l) and especially relatively high (50 mg Cd/l) exposure dose- and duration-dependently disturbed the processes of bone turnover and bone mass accumulation leading to formation of less dense than normal bone tissue. The effects were accompanied by changes in the serum concentration of calciotropic hormones and disorders in Ca and phosphate metabolism. It can be concluded that low environmental exposure to Cd may be only a subtle risk factor for skeletal demineralization in men. The results together with our previous findings based on an analogous model using female rats give clear evidence that males are less vulnerable to the bone effects of Cd compared to females

  6. Maternal Melatonin Therapy Rescues Prenatal Dexamethasone and Postnatal High-Fat Diet Induced Programmed Hypertension in Male Rat Offspring

    Directory of Open Access Journals (Sweden)

    You-Lin eTain

    2015-12-01

    Full Text Available Prenatal dexamethasone (DEX exposure and high-fat (HF intake are linked to hypertension. We examined whether maternal melatonin therapy prevents programmed hypertension synergistically induced by prenatal DEX plus postnatal HF in adult offspring. We also examined whether DEX and melatonin causes renal programming using next-generation RNA sequencing (NGS technology. Pregnant Sprague-Dawley rats received intraperitoneal dexamethasone (0.1 mg/kg or vehicle from gestational day 16 to 22. In the melatonin-treatment groups (M, rats received 0.01% melatonin in drinking water during their entire pregnancy and lactation. Male offspring were assigned to five groups: control, DEX, HF, DEX+HF, and DEX+HF+M. Male offspring in the HF group were fed a HF diet from weaning to 4 months of age. Prenatal DEX and postnatal HF diet synergistically induced programmed hypertension in adult offspring, which melatonin prevented. Maternal melatonin treatment modified over 3000 renal transcripts in the developing offspring kidney. Our NGS data indicate that PPAR signaling and fatty acid metabolism are two significantly regulated pathways. In addition, maternal melatonin therapy elicits longstanding alterations on renal programming, including regulation of the melatonin signaling pathway and upregulation of Agtr1b and Mas1 expression in the renin-angiotensin system (RAS, to protect male offspring against programmed hypertension. Postnatal HF aggravates prenatal DEX induced programmed hypertension in adult offspring, which melatonin prevented. The protective effects of melatonin on programmed hypertension is associated with regulation of the RAS and melatonin receptors. The long-term effects of maternal melatonin therapy on renal transcriptome require further clarification.

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

    International Nuclear Information System (INIS)

    Shen, Lang; Liu, Zhongfen; Gong, Jun; Zhang, Li; Wang, Linlong; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2014-01-01

    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

  8. 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 [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

  9. Effect of histochrome on the severity of delayed effects of prenatal exposure to lead nitrate in the rat brain.

    Science.gov (United States)

    Ryzhavsky, B Ya; Lebedko, O A; Belolubskaya, D S

    2008-08-01

    The effects of histochrome on the severity of delayed effects of prenatal exposure to lead nitrate were studied in the rat brain. Exposure of pregnant rats to lead nitrate during activation of free radical oxidation reduced activity of NADH- and NADPH-dehydrogenases in cortical neurons of their 40-day-old progeny, reduced the number of neurons in a visual field, increased the number of pathologically modified neurons, and stimulated rat motor activity in an elevated plus-maze. Two intraperitoneal injections of histochrome in a dose of 0.1 mg/kg before and after lead citrate challenge attenuated the manifestations of oxidative stress and prevented the changes in some morphological and histochemical parameters of the brain, developing under the effect of lead exposure.

  10. Prenatal alcohol exposure increases postnatal acceptability of nicotine odor and taste in adolescent rats.

    Directory of Open Access Journals (Sweden)

    Nicole M Mantella

    Full Text Available Human studies indicate that alcohol exposure during gestation not only increases the chance for later alcohol abuse, but also nicotine dependence. The flavor attributes of both alcohol and nicotine can be important determinants of their initial acceptance and they both share the component chemosensory qualities of an aversive odor, bitter taste and oral irritation. There is a growing body of evidence demonstrating epigenetic chemosensory mechanisms through which fetal alcohol exposure increases adolescent alcohol acceptance, in part, by decreasing the aversion to alcohol's bitter and oral irritation qualities, as well as its odor. Given that alcohol and nicotine have noteworthy chemosensory qualities in common, we investigated whether fetal exposure to alcohol increased the acceptability of nicotine's odor and taste in adolescent rats. Study rats were alcohol-exposed during fetal development via the dams' liquid diet. Control animals received ad lib access to an iso-caloric, iso-nutritive diet throughout gestation. Odorant-induced innate behavioral responses to nicotine odor (Experiment 1 or orosensory-mediated responses to nicotine solutions (Experiment 2 were obtained, using whole-body plethysmography and brief access lick tests, respectively. Compared to controls, rats exposed to fetal alcohol showed an enhanced nicotine odor response that was paralleled by increased oral acceptability of nicotine. Given the common aversive component qualities imbued in the flavor profiles of both drugs, our findings demonstrate that like postnatal alcohol avidity, fetal alcohol exposure also influences nicotine acceptance, at a minimum, by decreasing the aversion of both its smell and taste. Moreover, they highlight potential chemosensory-based mechanism(s by which fetal alcohol exposure increases the later initial risk for nicotine use, thereby contributing to the co-morbid expression with enhanced alcohol avidity. Where common chemosensory mechanisms are

  11. Prenatal alcohol exposure increases postnatal acceptability of nicotine odor and taste in adolescent rats.

    Science.gov (United States)

    Mantella, Nicole M; Youngentob, Steven L

    2014-01-01

    Human studies indicate that alcohol exposure during gestation not only increases the chance for later alcohol abuse, but also nicotine dependence. The flavor attributes of both alcohol and nicotine can be important determinants of their initial acceptance and they both share the component chemosensory qualities of an aversive odor, bitter taste and oral irritation. There is a growing body of evidence demonstrating epigenetic chemosensory mechanisms through which fetal alcohol exposure increases adolescent alcohol acceptance, in part, by decreasing the aversion to alcohol's bitter and oral irritation qualities, as well as its odor. Given that alcohol and nicotine have noteworthy chemosensory qualities in common, we investigated whether fetal exposure to alcohol increased the acceptability of nicotine's odor and taste in adolescent rats. Study rats were alcohol-exposed during fetal development via the dams' liquid diet. Control animals received ad lib access to an iso-caloric, iso-nutritive diet throughout gestation. Odorant-induced innate behavioral responses to nicotine odor (Experiment 1) or orosensory-mediated responses to nicotine solutions (Experiment 2) were obtained, using whole-body plethysmography and brief access lick tests, respectively. Compared to controls, rats exposed to fetal alcohol showed an enhanced nicotine odor response that was paralleled by increased oral acceptability of nicotine. Given the common aversive component qualities imbued in the flavor profiles of both drugs, our findings demonstrate that like postnatal alcohol avidity, fetal alcohol exposure also influences nicotine acceptance, at a minimum, by decreasing the aversion of both its smell and taste. Moreover, they highlight potential chemosensory-based mechanism(s) by which fetal alcohol exposure increases the later initial risk for nicotine use, thereby contributing to the co-morbid expression with enhanced alcohol avidity. Where common chemosensory mechanisms are at play, our

  12. Impact of Combined Prenatal Ethanol and Prenatal Stress Exposures on Markers of Activity-Dependent Synaptic Plasticity in Rat Dentate Gyrus

    OpenAIRE

    Staples, Miranda C.; Porch, Morgan W.; Savage, Daniel D.

    2014-01-01

    Prenatal ethanol exposure and prenatal stress can each cause long-lasting deficits in hippocampal synaptic plasticity and disrupt learning and memory processes. However, the mechanisms underlying these perturbations following a learning event are still poorly understood. We examined the effects of prenatal ethanol exposure and prenatal stress exposure, either alone or in combination, on the cytosolic expression of activity-regulated cytoskeletal (ARC) protein and the synaptosomal expression o...

  13. Prenatal chronic mild stress induces depression-like behavior and sex-specific changes in regional glutamate receptor expression patterns in adult rats.

    Science.gov (United States)

    Wang, Y; Ma, Y; Hu, J; Cheng, W; Jiang, H; Zhang, X; Li, M; Ren, J; Li, X

    2015-08-20

    Chronic stress during critical periods of human fetal brain development is associated with cognitive, behavioral, and mood disorders in later life. Altered glutamate receptor (GluR) expression has been implicated in the pathogenesis of stress-dependent disorders. To test whether prenatal chronic mild stress (PCMS) enhances offspring's vulnerability to stress-induced behavioral and neurobiological abnormalities and if this enhanced vulnerability is sex-dependent, we measured depression-like behavior in the forced swimming test (FST) and regional changes in GluR subunit expression in PCMS-exposed adult male and female rats. Both male and female PCMS-exposed rats exhibited stronger depression-like behavior than controls. Males and females exhibited unique regional changes in GluR expression in response to PCMS alone, FST alone (CON-FST), and PCMS with FST (PCMS-FST). In females, PCMS alone did not alter N-methyl-d-aspartate receptor (NMDAR) or metabotropic glutamate receptor (mGluR) expression, while in PCMS males, higher mGluR2/3, mGluR5, and NR1 expression levels were observed in the prefrontal cortex. In addition, PCMS altered the change in GluR expression induced by acute stress (the FST test), and this too was sex-specific. Male PCMS-FST rats expressed significantly lower mGluR5 levels in the hippocampus, lower mGluR5, NR1, postsynaptic density protein (PSD)95, and higher mGluR2/3 in the prefrontal cortex, and higher mGluR5 and PSD95 in the amygdala than male CON-FST rats. Female PCMS-FST rats expressed lower NR1 in the hippocampus, lower NR2B and PSD95 in the prefrontal cortex, lower mGluR2/3 in the amygdala, and higher PSD95 in the amygdala than female CON-FST rats. PCMS may increase the offspring's vulnerability to depression by altering sex-specific stress-induced changes in glutamatergic signaling. Copyright © 2015. Published by Elsevier Ltd.

  14. Sensitivity difference between anterior and posterior lobes of rat cerebellum to prenatal exposure to 2.5 Gy X-irradiation. A histological study

    International Nuclear Information System (INIS)

    Darmanto, W.; Hayasaka, Shizu; Takagishi, Yoshiko; Aolad, H.M.; Inouye, Minoru

    1997-01-01

    We investigated the histological differences in abnormality between anterior lobes (vermian lobules II, III and culmen IV, V) and posterior lobes (lobules IX, X) of the rat cerebellum following prenatal exposure to X-irradiation. Pregnant rats were exposed to 2.5 Gy X-irradiation at gestation day-21 (GD-21), and pups were sacrificed from birth through 15 days of age. Their cerebella were examined histologically and immunohistochemically for glial fibrillary acidic protein in Bergmann fibers. Extensive cell death was found in the external granular layer (EGL) of the cerebellum on the day of birth. In the anterior lobes, the number of cell deaths was higher than in the posterior lobes. During 5 days after birth, the recovery of EGL was earlier in the posterior lobes than in the anterior lobes. Seven days after birth, Bergmann fibers were more irregular in the anterior lobes than in the posterior lobes. The number of Purkinje cells in ectopic locations was higher in the anterior lobes than in the posterior lobes. The EGL and migrating Purkinje cells showed different responses to X-irradiation in the anterior than in the posterior lobes of the cerebellum. (author)

  15. Effects of prenatal X-irradiation on the 14th-18th days of gestation on postnatal growth and development in the rat

    International Nuclear Information System (INIS)

    Jensh, R.P.; Brent, R.L.

    1988-01-01

    Thirty-nine pregnant adult Wistar strain rats were randomly assigned to one of three exposure groups: 0, 0.75, or 1.50 Gy X-radiation total exposure. Animals were exposed from the 14th to the 18th days of gestation at 0, 0.15, or 0.30 Gy per day. At term, 15 rats were killed and morphologic analyses were completed. Twenty-four rats were allowed to deliver their offspring. On the first day of postnatal life, litters were reduced to a maximum of eight pups per litter, with equal numbers of male and female offspring wherever possible. A total of 187 pups were observed for the age of acquisition of five reflexes (air righting, surface righting, visual placing, negative geotaxis, auditory startle) and the appearance of four physiologic markers (pinna detachment, eye opening, vaginal opening, testes descent). There was significant dose-related weight reduction in term fetuses and offspring throughout the 86-day postnatal period. Postnatal growth rate (g gained/day) was unaffected. Adult offspring brain and gonadal weight and organ weight:body weight ratios were reduced. Using the PAC50 methodology, dose-related alterations occurred in the acquisition of several reflexes. All physiologic markers exhibited a dose-related delay in appearance. These results indicate that fractionated exposure to X-radiation during the fetal period in the rat results in dose-dependent alterations in postnatal growth and physiologic development. These studies are important for our understanding of the long-range effects of prenatal exposure to ionizing radiation late in gestation

  16. Prenatal Exposure to Phthalates and Anogenital Distance in Male Infants from a Low-Exposed Danish Cohort (2010-2012)

    DEFF Research Database (Denmark)

    Jensen, Tina Kold; Frederiksen, Hanne; Kyhl, Henriette Boye

    2016-01-01

    BACKGROUND: Phthalates comprise a large class of chemicals used in a variety of consumer products. Several have anti-androgenic properties, and in rodents prenatal exposure has been associated with reduced anogenital distance (AGD)-the distance from the anus to the genitals in male offspring. Few...... (2010-2012). Environ Health Perspect 124:1107-1113; http://dx.doi.org/10.1289/ehp.1509870....

  17. Effects of prenatal irradiation with an accelerated heavy-ion beam on postnatal development in rats: II. Further study on neurophysiologic alterations

    Science.gov (United States)

    Wang, B.; Murakami, M.; Eguchi-Kasai, K.; Nojima, K.; Shang, Y.; Tanaka, K.; Watanabe, K.; Fujita, K.; Moreno, S. G.; Coffigny, H.; Hayata, I.

    Organogenesis is a highly radiosensitive period, study of prenatal exposure to high LET heavy ion beams on postnatal development is important for clarifying the radiation risk in space and promoting the evidence-based mechanism research. The effects from heavy ion irradiations are not well studied as those for low LET radiations such as X-rays in this field, even the ground-based investigations remain to be addressed. Using the Heavy Ion Medical Accelerator in Chiba (HIMAC) and Wistar rats, postnatal neurophysiological development in offspring was investigated following exposure of pregnant rats to accelerated neon-ion beams with a LET value of about 30 keV/μm at a dose range from 0.1 to 2.0 Gy on the 15th day of gestation. The age for appearance of four physiologic markers and attainment of five neonatal reflexes, and gain in body weight were monitored. Male offspring were evaluated as young adults using two behavioral tests including open field and hole-board dipping tests. The effects of X-rays at 200 kVp measured for the same biological end points were studied for comparison. For most of the endpoints at early age, significant neurophysiological alteration was observed even in offspring receiving 0.1 Gy of accelerated neon ions but not X-rays. All offspring receiving 2.0 Gy of accelerated neon ions died prior to weaning. Offspring prenatally irradiated with neon ions generally showed higher incidences of prenatal death, increased preweaning mortality, markedly delayed accomplishment in physiological markers and reflexes, significantly lower body weight and reduced ratios of main organ weight to body weight, and altered behavior compared to those exposed to X-rays at doses of 0.1 1.5 Gy. These findings indicate that irradiations with neon ions at 0.1 1.5 Gy on day 15 of gestation caused varied developmental alterations in offspring, and efficient dose leading to the detrimental effects seemed to be lower than that of X-rays.

  18. BENEFICIAL EFFECT OF CHRONIC NIMODIPINE TREATMENT ON BEHAVIORAL DYSFUNCTIONS OF AGED RATS EXPOSED TO PERINATAL ETHANOL TREATMENT

    NARCIS (Netherlands)

    MARKEL, E; FELSZEGHY, K; LUITEN, PGM; NYAKAS, C

    1995-01-01

    The long-term effects of prenatal and early postnatal ethanol exposure were assessed in adult (5-month), aged (24-month), and senescent (30-month) rats on non-aggressive intermale social behavior, and on black-white discrimination and spatial learning behaviors. Furthermore, the effects of chronic

  19. Neurodevelopmental outcomes at 5 years in children exposed prenatally to maternal dental amalgam: the Seychelles Child Development Nutrition Study.

    Science.gov (United States)

    Watson, Gene E; van Wijngaarden, Edwin; Love, Tanzy M T; McSorley, Emeir M; Bonham, Maxine P; Mulhern, Maria S; Yeates, Alison J; Davidson, Philip W; Shamlaye, Conrad F; Strain, J J; Thurston, Sally W; Harrington, Donald; Zareba, Grazyna; Wallace, Julie M W; Myers, Gary J

    2013-01-01

    Limited human data are available to assess the association between prenatal mercury vapor (Hg⁰)) exposure from maternal dental amalgam restorations and neurodevelopment of children. We evaluated the association between maternal dental amalgam status during gestation and children's neurodevelopmental outcomes at 5 years in the Seychelles Child Development Nutrition Study (SCDNS). Maternal amalgam status was determined prospectively in a longitudinal cohort study examining the associations of prenatal exposure to nutrients and methylmercury (MeHg) with neurodevelopment. A total of 236 mother-child pairs initially enrolled in the SCDNS in 2001 were eligible to participate. Maternal amalgam status was measured as number of amalgam surfaces (the primary metric) and number of occlusal points. The neurodevelopmental assessment battery was comprised of age-appropriate tests of cognitive, language, and perceptual functions, and scholastic achievement. Linear regression analysis controlled for MeHg exposure, maternal fatty acid status, and other covariates relevant to child development. Maternal amalgam status evaluation yielded an average of 7.0 surfaces (range 0-28) and 11.0 occlusal points (range 0-40) during pregnancy. Neither the number of maternal amalgam surfaces nor occlusal points were associated with any outcome. Our findings do not provide evidence to support a relationship between prenatal exposure to Hg⁰ from maternal dental amalgam and neurodevelopmental outcomes in children at 5 years of age. © 2013.

  20. Threshold dose to developing central nerve system of rats and mice from prenatal exposure to tritiated water

    International Nuclear Information System (INIS)

    Zhou Xiangyan; Wang Bing; Gao Weimin; Lu Huimin

    1999-01-01

    Objective: To study the threshold dose to the developing central nerve system of rats and mice from prenatal exposure to tritiated water. methods: Pregnant adult C 57 BL/6J strain mice and Wistar strain rats were irradiated with beta-rays from HTO by a single intraperitoneal injection on the 12.5 th and 13 th days of gestation. The activities of HTO were 24.09, 48.18 and 144.54 ( x 10 4 Bq/g bw), respectively. Fifty-six parameters including postnatal growth, neutro-behavior, pathology of brain, neuropeptide contents, changes of hippocampal neurons, Ca 2+ conductance of hippocampal neurons etc were used to test the teratogenic threshold dose the lowest dose was different from that of the control). Results: Of the observed 56 parameters of rats and mice 80.4% indicated that the threshold doses for prenatal HTO exposure ranged from 0.030 Gy to 0.092 Gy, and the other 19.6% showed the threshold doses from 0.093 to 0.300 Gy. Conclusions: There exists threshold dose from the low level tritiated water irradiation of the developing central nerve system

  1. Prenatal Stress Impairs Spatial Learning and Memory Associated with Lower mRNA Level of the CAMKII and CREB in the Adult Female Rat Hippocampus.

    Science.gov (United States)

    Sun, Hongli; Wu, Haibin; Liu, Jianping; Wen, Jun; Zhu, Zhongliang; Li, Hui

    2017-05-01

    Prenatal stress (PS) results in various behavioral and emotional alterations observed in later life. In particular, PS impairs spatial learning and memory processes but the underlying mechanism involved in this pathogenesis still remains unknown. Here, we reported that PS lowered the body weight in offspring rats, particularly in female rats, and impaired spatial learning and memory of female offspring rats in the Morris water maze. Correspondingly, the decreased CaMKII and CREB mRNA in the hippocampus were detected in prenatally stressed female offspring, which partially explained the effect of PS on the spatial learning and memory. Our findings suggested that CaMKII and CREB may be involved in spatial learning and memory processes in the prenatally stressed adult female offspring.

  2. Impairment of male reproduction in adult rats exposed to hydroxyprogesterone caproate in utero

    Science.gov (United States)

    Pushpalatha, T.; Ramachandra Reddy, P.; Sreenivasula Reddy, P.

    Hydroxyprogesterone caproate is one of the most effective and widely used drugs for the treatment of uterine bleeding and threatened miscarriage in women. Hydroxyprogesterone caproate was administered to pregnant rats in order to assess the effect of intraperitoneal exposure to supranormal levels of hydroxyprogesterone caproate on the male reproductive potential in the first generation. The cauda epididymal sperm count and motility decreased significantly in rats exposed to hydroxyprogesterone caproate during embryonic development, when compared with control rats. The levels of serum testosterone decreased with an increase in follicle stimulating hormone and luteinizing hormone in adult rats exposed to hydroxyprogesterone caproate during the embryonic stage. It was suggested that the impairment of male reproductive performance could be mediated through the inhibition of testosterone production.

  3. Gene Expression Profiling in Lung Tissues from Rat Exposed to Lunar Dust Particles

    Science.gov (United States)

    Zhang, Ye; Lam, Chiu-Wing; Zalesak, Selina M.; Kidane, Yared H.; Feiveson, Alan H.; Ploutz-Snyder, Robert; Scully, Robert R.; Williams, Kyle; Wu, Honglu; James, John T.

    2014-01-01

    The Moon's surface is covered by a layer of fine, reactive dust. Lunar dust contain about 1-2% of very fine dust (gene expression changes in lung tissues from rats exposed to lunar dust particles. F344 rats were exposed for 4 weeks (6h/d; 5d/wk) in nose-only inhalation chambers to concentrations of 0 (control air), 2.1, 6.8, 21, and 61 mg/m(exp 3) of lunar dust. Five rats per group were euthanized 1 day, and 3 months after the last inhalation exposure. The total RNAs were isolated from lung tissues after being lavaged. The Agilent Rat GE v3 microarray was used to profile global gene expression (44K). The genes with significant expression changes are identified and the gene expression data were further analyzed using various statistical tools.

  4. Hydrogen sulfide protects neonatal rat medulla oblongata against prenatal cigarette smoke exposure via anti-oxidative and anti-inflammatory effects.

    Science.gov (United States)

    Yan, Xiang; Lei, Fang; Hu, Yajie; Nie, Lihong; Jia, Qingyi; Zhou, Hua; Zhao, Fusheng; Zheng, Yu

    2018-01-01

    We previously demonstrated that hydrogen sulfide (H 2 S) protected neonatal rat medulla oblongata from prenatal cigarette smoke exposure (CSE) via anti-apoptotic effect. The present work further investigated the involvement of anti-oxidative and anti-inflammatory effects of H 2 S in the protection. Pregnant Sprague-Dawley rats were randomly divided into NaCl, CSE, CSE + NaHS (a donor of H 2 S) and NaHS groups. All the tests were performed with corresponding neonatal rats. Nissl staining revealed that NaHS treatment ameliorated neuronal chromatolysis in the hypoglossal nucleus and nucleus ambiguus resulted from prenatal CSE. Moreover, NaHS eliminated decrease of glutathione level, increase of malondialdehyde content and inhibition of superoxide dismutase activity within neonatal rat medulla oblongata caused by prenatal CSE. NaHS also relieved the up-regulation of tumor necrosis factor-α, interleukin-1β and interleukin-6 in the medulla oblongata of the neonatal CSE rats. These results suggest that H 2 S can alleviate prenatal CSE-induced injuries of neonatal rat medulla oblongata through anti-oxidative and anti-inflammatory effects. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Early metabolic defects in dexamethasone-exposed and undernourished intrauterine growth restricted rats.

    Directory of Open Access Journals (Sweden)

    Emmanuel Somm

    Full Text Available Poor fetal growth, also known as intrauterine growth restriction (IUGR, is a worldwide health concern. IUGR is commonly associated with both an increased risk in perinatal mortality and a higher prevalence of developing chronic metabolic diseases later in life. Obesity, type 2 diabetes or metabolic syndrome could result from noxious "metabolic programming." In order to better understand early alterations involved in metabolic programming, we modeled IUGR rat pups through either prenatal exposure to synthetic glucocorticoid (dams infused with dexamethasone 100 µg/kg/day, DEX or prenatal undernutrition (dams feeding restricted to 30% of ad libitum intake, UN. Physiological (glucose and insulin tolerance, morphometric (automated tissue image analysis and transcriptomic (quantitative PCR approaches were combined during early life of these IUGR pups with a special focus on their endocrine pancreas and adipose tissue development. In the absence of catch-up growth before weaning, DEX and UN IUGR pups both presented basal hyperglycaemia, decreased glucose tolerance, and pancreatic islet atrophy. Other early metabolic defects were model-specific: DEX pups presented decreased insulin sensitivity whereas UN pups exhibited lowered glucose-induced insulin secretion and more marked alterations in gene expression of pancreatic islet and adipose tissue development regulators. In conclusion, these results show that before any catch-up growth, IUGR rats present early physiologic, morphologic and transcriptomic defects, which can be considered as initial mechanistic basis of metabolic programming.

  6. Effects of continuous prenatal γ radiation on the pig and rat

    International Nuclear Information System (INIS)

    Erickson, B.H.; Martin, P.G.

    1976-01-01

    Little is known of the effects of continuous low-level irradiation applied prenatally to the long-lived mammal. As compared with the rodent, developmental events are protracted in long-lived species and consequently are at risk longer. Estimation of radiation risk to man therefore requires data from animals in which developmental events are similarly protracted. Pigs were irradiated continuously for the first 108 days of their 112-day gestation period at rates of 20, 9, 3 and 1.5 R per 22-hour day. Six pregnant gilts and six controls were employed at each dose rate. Foetal doses were 7, 3, 1 and 0.5 rad/d. Neither the health of the gilt nor the number of live births was affected by any exposure. Postnatal viability was also unaffected. Radiation effects on growth and organic development were assayed at birth, 70 and 150 days of age. Body weight and growth were unaffected by dose rates of 3 rad/d or less; and other than the gonad, only the weight of the brain was affected by 3 rad/d. At 1 rad/d or less only gonadal weight was reduced. The most spectacular finding at doses of 7 and 3 rad/d was sterility in both sexes. Following 1 rad/d, germ-cell number was reduced to 5% and 2% of control in the female and male, respectively. At 0.5 rad/d/, germ cells were reduced to 43% of control in the female and 11% of control in the male. In contrast to the pig, 7 rad/d reduced the germ-cell population of male and female rats to only 49% and 35% of control, respectively, and 1 rad/d produced no apparent effect in either sex. It appears, therefore, that interspecific differences in the response to continuous γ radiation are large and that the germ cell is the most labile cell type. (author)

  7. Prenatal ethanol exposure-induced adrenal developmental abnormality of male offspring rats and its possible intrauterine programming mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Hegui; He, Zheng; Zhu, Chunyan; Liu, Lian; Kou, Hao; Shen, Lang [Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071 (China); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071 (China); Hubei Provincial Key Laboratory of Developmentally Originated Disorder, Wuhan 430071 (China)

    2015-10-01

    Fetal adrenal developmental status is the major determinant of fetal tissue maturation and offspring growth. We have previously proposed that prenatal ethanol exposure (PEE) suppresses fetal adrenal corticosterone (CORT) synthesis. Here, we focused on PEE-induced adrenal developmental abnormalities of male offspring rats before and after birth, and aimed to explore its intrauterine programming mechanisms. A rat model of intrauterine growth retardation (IUGR) was established by PEE (4 g/kg·d). In PEE fetus, increased serum CORT concentration and decreased insulin-like growth factor 1 (IGF1) concentration, with lower bodyweight and structural abnormalities as well as a decreased Ki67 expression (proliferative marker), were observed in the male fetal adrenal cortex. Adrenal glucocorticoid (GC)-metabolic activation system was enhanced while gene expression of IGF1 signaling pathway with steroidogenic acute regulatory protein (StAR), 3β-hydroxysteroid dehydrogenase (3β-HSD) was decreased. Furthermore, in the male adult offspring of PEE, serum CORT level was decreased but IGF1 was increased with partial catch-up growth, and Ki67 expression demonstrated no obvious change. Adrenal GC-metabolic activation system was inhibited, while IGF1 signaling pathway and 3β-HSD was enhanced with the steroidogenic factor 1 (SF1), and StAR was down-regulated in the adult adrenal. Based on these findings, we propose a “two-programming” mechanism for PEE-induced adrenal developmental toxicity: “the first programming” is a lower functional programming of adrenal steroidogenesis, and “the second programming” is GC-metabolic activation system-related GC-IGF1 axis programming. - Highlights: • Prenatal ethanol exposure induces adrenal developmental abnormality in offspring rats. • Prenatal ethanol exposure induces intrauterine programming of adrenal steroidogenesis. • Intrauterine GC-IGF1 axis programming might mediate adrenal developmental abnormality.

  8. Prenatal ethanol exposure-induced adrenal developmental abnormality of male offspring rats and its possible intrauterine programming mechanisms

    International Nuclear Information System (INIS)

    Huang, Hegui; He, Zheng; Zhu, Chunyan; Liu, Lian; Kou, Hao; Shen, Lang; Wang, Hui

    2015-01-01

    Fetal adrenal developmental status is the major determinant of fetal tissue maturation and offspring growth. We have previously proposed that prenatal ethanol exposure (PEE) suppresses fetal adrenal corticosterone (CORT) synthesis. Here, we focused on PEE-induced adrenal developmental abnormalities of male offspring rats before and after birth, and aimed to explore its intrauterine programming mechanisms. A rat model of intrauterine growth retardation (IUGR) was established by PEE (4 g/kg·d). In PEE fetus, increased serum CORT concentration and decreased insulin-like growth factor 1 (IGF1) concentration, with lower bodyweight and structural abnormalities as well as a decreased Ki67 expression (proliferative marker), were observed in the male fetal adrenal cortex. Adrenal glucocorticoid (GC)-metabolic activation system was enhanced while gene expression of IGF1 signaling pathway with steroidogenic acute regulatory protein (StAR), 3β-hydroxysteroid dehydrogenase (3β-HSD) was decreased. Furthermore, in the male adult offspring of PEE, serum CORT level was decreased but IGF1 was increased with partial catch-up growth, and Ki67 expression demonstrated no obvious change. Adrenal GC-metabolic activation system was inhibited, while IGF1 signaling pathway and 3β-HSD was enhanced with the steroidogenic factor 1 (SF1), and StAR was down-regulated in the adult adrenal. Based on these findings, we propose a “two-programming” mechanism for PEE-induced adrenal developmental toxicity: “the first programming” is a lower functional programming of adrenal steroidogenesis, and “the second programming” is GC-metabolic activation system-related GC-IGF1 axis programming. - Highlights: • Prenatal ethanol exposure induces adrenal developmental abnormality in offspring rats. • Prenatal ethanol exposure induces intrauterine programming of adrenal steroidogenesis. • Intrauterine GC-IGF1 axis programming might mediate adrenal developmental abnormality.

  9. Metabolic profile and genotoxicity in obese rats exposed to cigarette smoke.

    Science.gov (United States)

    Damasceno, Debora C; Sinzato, Yuri K; Bueno, Aline; Dallaqua, Bruna; Lima, Paula H; Calderon, Iracema M P; Rudge, Marilza V C; Campos, Kleber E

    2013-08-01

    Experimental studies have shown that exposure to cigarette smoke has negative effects on lipid metabolism and oxidative stress status. Cigarette smoke exposure in nonpregnant and pregnant rats causes significant genotoxicity (DNA damage). However, no previous studies have directly evaluated the effects of obesity or the association between obesity and cigarette smoke exposure on genotoxicity. Therefore, the aim of the present investigation was to evaluate DNA damage levels, oxidative stress status and lipid profiles in obese Wistar rats exposed to cigarette smoke. Female rats subcutaneously (s.c.) received a monosodium glutamate solution or vehicle (control) during the neonatal period to induce obesity. The rats were randomly distributed into three experimental groups: control, obese exposed to filtered air, and obese exposed to tobacco cigarette smoke. After a 2-month exposure period, the rats were anesthetized and killed to obtain blood samples for genotoxicity, lipid profile, and oxidative stress status analyses. The obese rats exposed to tobacco cigarette smoke presented higher DNA damage, triglycerides, total cholesterol, free fatty acids, VLDL-c, HDL-c, and LDL-c levels compared to control and obese rats exposed to filtered air. Both obese groups showed reduced SOD activity. These results showed that cigarette smoke enhanced the effects of obesity. In conclusion, the association between obesity and cigarette smoke exposure exacerbated the genotoxicity, negatively impacted the biochemical profile and antioxidant defenses and caused early glucose intolerance. Thus, the changes caused by cigarette smoke exposure can trigger the earlier onset of metabolic disorders associated with obesity, such as diabetes and metabolic syndrome. Copyright © 2012 The Obesity Society.

  10. Possible cause for altered spatial cognition of prepubescent rats exposed to chronic radiofrequency electromagnetic radiation.

    Science.gov (United States)

    Narayanan, Sareesh Naduvil; Kumar, Raju Suresh; Karun, Kalesh M; Nayak, Satheesha B; Bhat, P Gopalakrishna

    2015-10-01

    The effects of chronic and repeated radiofrequency electromagnetic radiation (RFEMR) exposure on spatial cognition and hippocampal architecture were investigated in prepubescent rats. Four weeks old male Wistar rats were exposed to RF-EMR (900 MHz; SAR-1.15 W/kg with peak power density of 146.60 μW/cm(2)) for 1 h/day, for 28 days. Followed by this, spatial cognition was evaluated by Morris water maze test. To evaluate the hippocampal morphology; H&E staining, cresyl violet staining, and Golgi-Cox staining were performed on hippocampal sections. CA3 pyramidal neuron morphology and surviving neuron count (in CA3 region) were studied using H&E and cresyl violet stained sections. Dendritic arborization pattern of CA3 pyramidal neuron was investigated by concentric circle method. Progressive learning abilities were found to be decreased in RF-EMR exposed rats. Memory retention test performed 24 h after the last training revealed minor spatial memory deficit in RF-EMR exposed group. However, RF-EMR exposed rats exhibited poor spatial memory retention when tested 48 h after the final trial. Hirano bodies and Granulovacuolar bodies were absent in the CA3 pyramidal neurons of different groups studied. Nevertheless, RF-EMR exposure affected the viable cell count in dorsal hippocampal CA3 region. RF-EMR exposure influenced dendritic arborization pattern of both apical and basal dendritic trees in RF-EMR exposed rats. Structural changes found in the hippocampus of RF-EMR exposed rats could be one of the possible reasons for altered cognition.

  11. Effects of Circadian Disruption on Methamphetamine Consumption in Methamphetamine-Exposed Rats

    Science.gov (United States)

    Doyle, Susan E.; Feng, Hanting; Garber, Garrett; Menaker, Michael; Lynch, Wendy J.

    2015-01-01

    Rationale A substantial number of clinical studies indicate associations between sleep abnormalities and drug abuse; however, the role played by the circadian system in the development of addiction is largely unknown. Objective The aim of this study was to examine the effects of experimentally induced chronic jet lag on methamphetamine consumption in a rat model of methamphetamine drinking. Methods Male Sprague-Dawley rats (n=32) were housed in running wheel cages in a 12:12 light:dark cycle. One group of rats (n=16) was given two weeks of forced methamphetamine consumption (0.01% in drinking water; meth pre-exposed) while a second group (n=16, not pre-exposed) received water only. This was followed by a two week abstinence period during which half of the animals from each group were exposed to 4 consecutive 6-hr advancing phase shifts of the light:dark cycle, while the other half remained on the original light:dark cycle. Methamphetamine consumption was assessed in all rats following the deprivation period using a two-bottle choice paradigm. Results Methamphetamine consumption was initially lower in methamphetamine pre-exposed vs. not pre-exposed rats. However, during the second week following abstinence, consumption was significantly higher in phase shifted rats of the methamphetamine pre-exposed group compared to all other groups. Conclusions These data reveal an effect of circadian rhythm disturbance on methamphetamine consumption, and suggest that dysregulation of the circadian system be considered in the etiology of relapse and addiction. PMID:25543849

  12. Inhibition of HMGB1 Translocation by Green Tea Extract in Rats Exposed to Environmental Tobacco Smoke

    OpenAIRE

    Sirintip Chaichalotornkul; Wisuda Suvitayavat; Vanida Sangalangkarn; Yuko Nawa; Kiyoshi Kikuchi; Koichi Kawahara; Tawee Saiwichai; Somphong Narkpinit; Pratap Singhasivanon; Ikuro Maruyama; Salunya Tancharoen

    2012-01-01

    Environmental tobacco smoke (ETS) exposure is linked to carcinogenic, oxidative and inflammatory cellular reactions. Green tea polyphenol reportedly plays a role in the prevention of inflammation-related diseases. To evaluate the effects of green tea extract (GTE) on cellular location of High Mobility Group Box-1 (HMGB1) protein, we studied the lung tissue in rats exposed to cigarette smoke (CS). Rats were divided into three groups; CS, CSG, and C, which were groups of CS-treated only, CS-tre...

  13. Lipid spectrum of the newborn rats' blood at the radioactive and chemical effects in the prenatal period

    International Nuclear Information System (INIS)

    Buzan, Kh.

    1998-01-01

    The radioactive and chemical factors used in complex or separately during the prenatal period in the experiment induce ambiguous effects on the lipid metabolism in blood plasma and erythrocytes of newborn rats. The chemicals cause more significant changes in the blood plasma lipid metabolism than the radioactive irradiation does. Being used combined the radioactive and chemical factors do not increase each other's effect- their effects have opposite directions. The radiochemical exposure induce more significant shifts in the lipid spectrum in erythrocytic membranes than the separate factors

  14. Neuroprotection with metformin and thymoquinone against ethanol-induced apoptotic neurodegeneration in prenatal rat cortical neurons

    Directory of Open Access Journals (Sweden)

    Ullah Ikram

    2012-01-01

    Full Text Available Abstract Background Exposure to ethanol during early development triggers severe neuronal death by activating multiple stress pathways and causes neurological disorders, such as fetal alcohol effects or fetal alcohol syndrome. This study investigated the effect of ethanol on intracellular events that predispose developing neurons for apoptosis via calcium-mediated signaling. Although the underlying molecular mechanisms of ethanol neurotoxicity are not completely determined, mitochondrial dysfunction, altered calcium homeostasis and apoptosis-related proteins have been implicated in ethanol neurotoxicity. The present study was designed to evaluate the neuroprotective mechanisms of metformin (Met and thymoquinone (TQ during ethanol toxicity in rat prenatal cortical neurons at gestational day (GD 17.5. Results We found that Met and TQ, separately and synergistically, increased cell viability after ethanol (100 mM exposure for 12 hours and attenuated the elevation of cytosolic free calcium [Ca2+]c. Furthermore, Met and TQ maintained normal physiological mitochondrial transmembrane potential (ΔψM, which is typically lowered by ethanol exposure. Increased cytosolic free [Ca2+]c and lowered mitochondrial transmembrane potential after ethanol exposure significantly decreased the expression of a key anti-apoptotic protein (Bcl-2, increased expression of Bax, and stimulated the release of cytochrome-c from mitochondria. Met and TQ treatment inhibited the apoptotic cascade by increasing Bcl-2 expression. These compounds also repressed the activation of caspase-9 and caspase-3 and reduced the cleavage of PARP-1. Morphological conformation of cell death was assessed by TUNEL, Fluoro-Jade-B, and PI staining. These staining methods demonstrated more cell death after ethanol treatment, while Met, TQ or Met plus TQ prevented ethanol-induced apoptotic cell death. Conclusion These findings suggested that Met and TQ are strong protective agents against ethanol

  15. Endocrine disrupting effects in rats perinatally exposed to a dietary relevant mixture of phytoestrogens

    DEFF Research Database (Denmark)

    Boberg, Julie; Mandrup, Karen; Jacobsen, Pernille Rosenskjold

    2013-01-01

    Dietary phytoestrogens may prevent certain human diseases, but endocrine activity has been reported in animal studies. Sprague-Dawley rats were exposed perinatally to a 1-, 10- or 100-fold “high human dietary intake” mixture of 12 phytoestrogens consisting of mainly the lignan secoisolarici resinol...... genes in testis and prostate were unaffected. Decreased serum estradiol was seen in genistein-exposed dams. This study indicated adverse effects at high intake levels in rats, but does not provide evidence for risk of phytoestrogen-mediated endocrine disruption at normal human dietary consumption levels...

  16. [The activity of blood cholinesterase in rats exposed to dimehypo].

    Science.gov (United States)

    Wan, Weiguo; Xu, Mailing; Zou, Hejian; Lu, Ailing; Shen, Xinyu; Chen, Yuming

    2002-12-01

    To determine whether and to what degree the activity of cholinesterase(ChE) is inhibited by dimehypo at different doses of dimehypo [scientific name: 2-dimethylamine-1,3-bi(sodium hyposulfit)]. Rats were dosed with dimehypo or methamidophos orally, and were randomly divided into four subgroups according to the pesticide doses, which were 1/16, 1/8, 1/4 and 1/2 of LD50 respectively(the LD50 of dimethypo and methamidophos is 342 mg/kg and 20 mg/kg respectively). The activity of ChE in blood was determined before and 30 min, 1, 2, 4 and 24 h after exposure. The modified Ellman Method was employed to measure the activity of ChE. 1/16 LD50 dose of dimehypo did not affect the activity of ChE. When the dose increased, the activity of ChE decreased accordingly. 1/2 LD50 dose of dimehypo inhibited the activity of ChE by 35.9% compared with that of control group(P dimehypo at various doses was significantly lower than that in the rats dosed with corresponding doses of methamidophos(P dimehypo may inhibit the activity of ChE. However, as compared with methamidophos, dimehypo is a weaker inhibitor of ChE.

  17. Prenatal exposure to an NMDA receptor antagonist, MK-801 reduces density of parvalbumin-immunoreactive GABAergic neurons in the medial prefrontal cortex and enhances phencyclidine-induced hyperlocomotion but not behavioral sensitization to methamphetamine in postpubertal rats.

    Science.gov (United States)

    Abekawa, Tomohiro; Ito, Koki; Nakagawa, Shin; Koyama, Tsukasa

    2007-06-01

    Neurodevelopmental deficits of parvalbumin-immunoreactive gamma-aminobutyric acid (GABA)ergic interneurons in prefrontal cortex have been reported in schizophrenia. Glutamate influences the proliferation of this type of interneuron by an N-methyl-D-aspartate (NMDA)-receptor-mediated mechanism. The present study hypothesized that prenatal blockade of NMDA receptors would disrupt GABAergic neurodevelopment, resulting in differences in effects on behavioral responses to a noncompetitive NMDA antagonist, phencyclidine (PCP), and a dopamine releaser, methamphetamine (METH). GABAergic neurons were immunohistochemically stained with parvalbumin antibody. Psychostimulant-induced hyperlocomotion was measured using an infrared sensor. Prenatal exposure (E15-E18) to the NMDA receptor antagonist MK-801 reduced the density of parvalbumin-immunoreactive neurons in rat medial prefrontal cortex on postnatal day 63 (P63) and enhanced PCP-induced hyperlocomotion but not the acute effects of METH on P63 or the development of behavioral sensitization. Prenatal exposure to MK-801 reduced the number of parvalbumin-immunoreactive neurons even on postnatal day 35 (P35) and did not enhance PCP-induced hyperlocomotion, the acute effects of METH on P35, or the development of behavioral sensitization to METH. These findings suggest that prenatal blockade of NMDA receptors disrupts GABAergic neurodevelopment in medial prefrontal cortex, and that this disruption of GABAergic development may be related to the enhancement of the locomotion-inducing effect of PCP in postpubertal but not juvenile offspring. GABAergic deficit is unrelated to the effects of METH. This GABAergic neurodevelopmental disruption and the enhanced PCP-induced hyperlocomotion in adult offspring prenatally exposed to MK-801 may prove useful as a new model of the neurodevelopmental process of pathogenesis of treatment-resistant schizophrenia via an NMDA-receptor-mediated hypoglutamatergic mechanism.

  18. Toxicological Assessments of Rats Exposed Prenatally to Inhaled Vapors of Gasoline and Gasoline-Ethanol Blends

    Science.gov (United States)

    The primary alternative to petroleum-based fuels is ethanol, which is blended with gasoline in the United States at concentrations up to 15% for most automobiles. Efforts to increase the amount of ethanol in gasoline have prompted concerns about the potential toxicity of inhaled ...

  19. Age-Related Differences in NMDA Receptor Subunits of Prenatally Methamphetamine-Exposed Male Rats

    Czech Academy of Sciences Publication Activity Database

    Vrajová, M.; Schutová, B.; Klaschka, Jan; Štěpánková, H.; Řípová, D.; Šlamberová, R.

    2014-01-01

    Roč. 39, č. 11 (2014), s. 2040-2046 ISSN 0364-3190 Grant - others:GA ČR(CZ) GAP303/10/0580; Ministerstvo školství(CZ) CSM 7/CRP/2014; Univerzita Karlova(CZ) Prvouk P34; Univerzita Karlova(CZ) 260045/SVV/2014; Prague Psychiatric Center(CZ) MH CZ–DRO: 00023752 Institutional support: RVO:67985807 Keywords : methamphetamine * in-utero * NMDA receptor subunits * hippocampus Subject RIV: FH - Neurology Impact factor: 2.593, year: 2014

  20. Histomorphometric Evaluation of the Small Coronary Arteries in Rats Exposed to Industrial Noise

    Directory of Open Access Journals (Sweden)

    Ana Lousinha

    2015-05-01

    Full Text Available Morphological changes induced by industrial noise (IN have been experimentally observed in several organs. Histological observations of the coronary arteries showed prominent perivascular tissue and fibrosis among IN-exposed rats. The effects on the small arteries are unknown. Objective: To evaluate the histomorphometric changes induced by IN on rat heart small arteries. Methods: Twenty Wistar rats exposed to IN during a maximum period of seven months and 20 age-matched controls were studied. Hearts were transversely sectioned from ventricular apex to atria and a mid-ventricular fragment was selected for analysis. The histological images were obtained with an optical microscope using 400× magnifications. A total of 634 arterial vessels (298 IN-exposed and 336 controls were selected. The mean lumen-to-vessel wall (L/W and mean vessel wall-to-perivascular tissue (W/P ratios were calculated using image J software. Results: There were no differences between exposed and control animals in their L/W ratios (p = 0.687 and time variations in this ratio were non-significant (p = 0.110. In contrast, exposed animals showed lower W/P ratios than control animals (p < 0.001, with significant time variations (p = 0.004. Conclusions: Industrial noise induced an increase in the perivascular tissue of rat small coronary arteries, with significant development of periarterial fibrosis.

  1. Influence of prenatal application of angiotensin II and postnatal salt diet on GABAergic and oxytocin system in rat brain steam and cerebellum

    International Nuclear Information System (INIS)

    Jackova, L.; Olexova, L.; Svitok, P.; Senko, T.; Stefanik, P.

    2015-01-01

    Our goal was to determinate how gene expression of GABA transporter 1 (GAT1), glutamate decarboxylase 67 (GAD67) and oxytocin receptor (OTR) is influenced with prenatal exposition to angiotensin II (Ang II) and postnatal salt diet in nucleus tractus solitarii (NTS) and cerebellum in rats. In NTS we observed strong tendency in different reaction of OTR gene expression between Ang II prenatal treatment and control rats after high salt diet. We observed significant influence of sex on GAD67 gene expression in cerebellum. Also, sex in combination with salt diet is significant factor in expression of GAT1 gene in cerebellum. (authors)

  2. Haematological evaluation of Wistar rats exposed to chronic doses ...

    African Journals Online (AJOL)

    Two groups (A and B) were respectively exposed to CdCl2 (0.25 and 2.5 mg/kg), two other groups (C and D) respectively received HgCl2 (0.12 and 1.2 mg/kg) and the last two groups (E and F) were respectively treated with the combination of these two metals: (0.25 mg/kg Cd + 0.12 mg/kg Hg) and (2.5 mg/kg Cd + 1.2 ...

  3. Prenatal immune challenge in rats: Altered responses to dopaminergic and glutamatergic agents, prepulse inhibition of acoustic startle, and reduced route-based learning as a function of maternal body weight gain after prenatal exposure to Poly IC

    OpenAIRE

    Vorhees, Charles V.; Graham, Devon L.; Braun, Amanda A.; Schaefer, Tori L.; Skelton, Matthew R.; Richtand, Neil M.; Williams, Michael T.

    2012-01-01

    Prenatal maternal immune activation has been used to test the neurodevelopmental hypothesis of schizophrenia. Most of the data are in mouse models; far less is available for rats. We previously showed that maternal weight change in response to the immune activator polyinosinic-polycytidylic (Poly IC) in rats differentially affects offspring. Therefore, we treated gravid Harlan Sprague-Dawley rats i.p. on embryonic day 14 with 8 mg/kg of Poly IC or Saline. The Poly IC group was divided into th...

  4. Proteinase activity in cell nuclei of rats exposed to γ-radiation and methyl nitrosourea

    International Nuclear Information System (INIS)

    Malakhova, L.V.; Surkenova, G.N.; Gaziev, A.I.

    1990-01-01

    Activity of nuclear proteinases in blood and liver cells of rats exposed to whole-body γ-irradiation (10 Gy) has been comparatively studied by the capacity of splitting the caseic substrate. Proteinase activity in nuclei of irradiated rat leukocytes was shown to increase by 2.5 times and to gradually decrease after 48 h reaching 150-160% as compared to the control. Two hours following a single injection of methyl nitrosourea the alteration in the activity of proteinases in nuclei of rat hepatocytes and leukocytes was different from the alteration of this index after γ-irradiation

  5. Increased bone calcium dissociation in lead-exposed rats

    Directory of Open Access Journals (Sweden)

    Eko Suhartono

    2012-12-01

    Full Text Available Background Lead is still a major environmental and occupational health hazard, since it is extensively used in the production of paints, gasoline and cosmetics. This causes the metal to be ubiquitous in the environment, being found in the air, soil, and water, from which it can enter the human body by inhalation or ingestion. Absorbed lead is capable of altering the calcium levels in bone. The aim of this study was to demonstrate the effect of lead on bone calcium levels by measuring the reaction constant, Gibbs free energy, and enthalpy. Methods This study was of pure experimental design using 100 male albino rats (Rattus norvegicus. The experimental animals were assigned by simple randomization to two groups, one group receiving lead acetate orally at a dosage of 100 mg/kgBW, while the other group did not receive lead acetate. The intervention was given for 4 weeks and the rats were observed weekly for measurement of bone calcium levels by the permanganometric method. Results This study found that k1 (hydroxyapatite dissociation rate constant was 0.90 x 10-3 dt-1, and that k2 (hydroxyapatite association rate constant was 6.16 x 10-3 dt-1 for the control group, whereas for the intervention group k1 = 26.20 x 10-3 dt-1 and k2 = 16.75 x 10-3 dt-1. Thermodynamically, the overall reaction was endergonic and endothermic (DG > 0 and DH > 0. ConclusionS Lead exposure results in increased dissociation rate of bone in comparison with its association rate. Overall, the reaction was endergonic and endothermic (DG > 0 and DH > 0.

  6. Increased bone calcium dissociation in lead-exposed rats

    Directory of Open Access Journals (Sweden)

    Eko Suhartono

    2015-12-01

    Full Text Available BACKGROUND Lead is still a major environmental and occupational health hazard, since it is extensively used in the production of paints, gasoline and cosmetics. This causes the metal to be ubiquitous in the environment, being found in the air, soil, and water, from which it can enter the human body by inhalation or ingestion. Absorbed lead is capable of altering the calcium levels in bone. The aim of this study was to demonstrate the effect of lead on bone calcium levels by measuring the reaction constant, Gibbs free energy, and enthalpy. METHODS This study was of pure experimental design using 100 male albino rats (Rattus norvegicus. The experimental animals were assigned by simple randomization to two groups, one group receiving lead acetate orally at a dosage of 100 mg/ kgBW, while the other group did not receive lead acetate. The intervention was given for 4 weeks and the rats were observed weekly for measurement of bone calcium levels by the permanganometric method. RESULTS This study found that k1 (hydroxyapatite dissociation rate constant was 0.90 x 10-3 dt-1, and that k2 (hydroxyapatite association rate constant was 6.16 x 10-3 dt-1 for the control group, whereas for the intervention group k1 = 26.20 x 10-3 dt-1 and k2 = 16.75 x 10-3 dt-1. Thermodynamically, the overall reaction was endergonic and endothermic (ΔG > 0 and ΔH > 0. CONCLUSIONS Lead exposure results in increased dissociation rate of bone in comparison with its association rate. Overall, the reaction was endergonic and endothermic (ΔG > 0 and ΔH > 0.

  7. Liver polyribosome distribution in intact and adrenalectomized rats exposed to. gamma. radiation

    Energy Technology Data Exchange (ETDEWEB)

    Yatvin, M B; Abdel-Halim, M N [Wisconsin Univ., Madison (USA). Dept. of Radiology; Wisconsin Univ., Madison (USA). Dept. of Human Oncology)

    1978-06-01

    The mechanism(s) by which gamma radiation influences liver polyribosome distribution was studied in groups of intact and adrenalectomized male rats. A shift from light to heavy aggregates occurred in the polyribosomes of both intact and adrenalectomized rats after they were exposed to gamma rays. In irradiated adrenalectomized rats, however, the shift to heavier aggregates was not as great as that which occurred in irradiated adrenal-intact animals. Subcutaneous injection of cortisone acetate (10 mg/100 g body weight) also altered the liver polyribosome patterns of both intact and adrenalectomized rats within 8 hours of its administration. The shift which occurred following cortisone administration, however, was less striking than that seen after irradiation only. Thus, although adrenal glucocorticoids contribute to the radiation-indu ied shift in liver polyribosomes in adrenal-intact rats, other factors appear to be involved, since the shift is also obtained in adrenalectomized animals.

  8. Substitution effects of a carbonated hydroxyapatite biomaterial against intoxication chloride nickel-exposed rats.

    Science.gov (United States)

    Boulila, Salha; Elfeki, Abdelfattah; Oudadesse, Hassane; Elfeki, Hafed

    2015-03-01

    This study aimed to investigate the potential effects of a synthetic apatite (carbonated hydroxyapatite) on the detoxification of a group of male "Wistar" rats exposed to nickel chloride. Toxicity was evaluated by rats' bioassay of nickel chloride. Wistar rats received this metal daily by gavage for seven days (4 mg/ml nickel chloride/200 g body weight, BW). To detoxify this organism, a subcutaneous implantation of the apatite is made. The results revealed that exposure to nickel induced oxidative stress, disorders in the balances of ferric phosphocalcic, renal failures, liver toxicity and significant increase in nickel rates in the bones of intoxicated rats. The application of the carbonated hydroxyapatite presented in this study restored those disorders back to normal. The synthetic apatite protected the rats against the toxic effects of nickel by lowering the levels of lipid peroxidation markers and improving the activities of defense enzymes. It also amended ferric and phosphocalcic equilibriums, protected liver and kidney functions and reduced the nickel rate in the bones of the rats. Overall, the results provided strong support for the protective role of carbonated hydroxyapatite in the detoxification of rats exposed to nickel. Those beneficial effects were further confirmed by physico-chemical characterization (X-ray diffraction and infrared spectroscopy), which revealed its property of anionic and cationic substitution, thus supporting its promising candidacy for future biomedical application. The hydroxyapatite is an effective biomaterial to solve health problems, particularly detoxification against metals (nickel).

  9. Effects of hyperbaric oxygen on crystalline lens and retina in nicotine-exposed rats.

    Science.gov (United States)

    Ari, Seyhmus; Nergiz, Yusuf; Cingü, Abdullah Kürşat; Atay, Ahmet Engin; Sahin, Alparslan; Cinar, Yasin; Caca, Ihsan

    2013-03-01

    To determine histopathological changes on crystalline lens and retina of rats after subcutaneous injection of nicotine and to examine the effects of hyperbaric oxygen (HBO) on these changes related to nicotine exposure. Twenty-eight female Sprague-Dawley rats were enrolled in the study and the rats were divided into four equal sized groups randomly (Group N: the rats exposed only to nicotine, group HB: the rats received only HBO, group N+HB: the rats that underwent to nicotine injection and subsequently received HBO, group C: the control group that neither exposed to nicotine nor received HBO). The rats were sacrificed by decapitation method and all were enucleated immediately after scarification. Tissue samples from crystalline lens, lens capsule, and the retina from the right eyes of the rats were examined by light microscopy. While the histological appearances of the retina and the lens was similar in group HB, group N+HB, and the control group; group N showed some pathological changes like decrement in the retinal ganglion cell density, atrophy of the retinal nerve fiber layer, congestion of the vessels in the optic nerve head, thinning of the internal plexiform layer, thinning of the lens capsule, and transformation of the anterior subcapsular epithelium into squamous epithelia. Subcutaneous injection of nicotine was found to be related with some pathological changes in the retina and lens of the Sprague-Dawley rats. However HBO caused no significant negative effect. Furthermore, the histopathological changes related to nicotine exposure in the lens and retina of the rats recovered by the application of HBO.

  10. Effects of glutamine pretreatment on learning and memory in heat-exposed rats

    Institute of Scientific and Technical Information of China (English)

    Shenghao Zhao; Lei Wang; Qin Wang; Siyi Wang; Chundi Deng; Xianfei Xie; Youe Yan; Hui Wang

    2008-01-01

    BACKGROUND: Glutamine (Gln) pretreatment can protect neural cells from injuries due to heat, ischemia, hypoxia, endotoxemia, and inflammatory factors.OBJECTIVE: To observe the effects of Gln pretreatment on learning and memory, survival time, and rectal temperature in heat-exposed rats.DESIGN, TIME AND SETTING: The present randomized grouping, neurobehavioral experiment was performed at the Laboratory of Department of Pharmacology, Basic School of Medicine, Wuhan University between March and September 2007.MATERIALS: Twenty-four healthy, Wistar rats were included in this study. SPX-160B biochemistry incubator (Shanghai Experimental Equipment Co., Ltd., China), probe electronic thermometer (11000 type, Maikepai Science and Technology Co., Ltd., China), Y-type maze box used in conjunction with MG-2 maze stimulator (Zhangjiagang Biomedical Instrument Factory, China), L-Gin (Batch No. 061218, 5 g/bottle, prepared into 10% aqueous solution, Amresco Company, USA) were used.METHODS: Twenty-four rats were randomly and evenly divided into 3 groups: heat-exposed, Gln low-lose, and Gln high-dose. Following learning and memory testing with the Y-maze, rats in the heat-exposed group were subjected to heat injury (40.5-41.5℃) in a biochemistry incubator. Rectal temperature was measured every 5 minutes. Thirty-five minutes after heat exposure, rats were removed and placed in the Y-type maze to test learning and memory again. Subsequently, the rats were returned to the same environment of thermal stimulation until they died. Rat survival time was recorded. Subsequent to learning and memory testing, rats in the Gln low-dose and high-dose groups received an i.p. injection of Gln (0.4 g/kg and 0.8 g/kg, respectively), and were exposed to heat injury. The remaining experimental procedures remained the same as for the heat-exposed group.MAIN OUTCOME MEASURES: Rat learning and memory, rectal temperature, and survival time in heat exposure environment.RESULTS: (1) In the Y

  11. Proteomic analysis of liver in rats chronically exposed to fluoride.

    Directory of Open Access Journals (Sweden)

    Heloísa Aparecida Barbosa da Silva Pereira

    Full Text Available Fluoride (F is a potent anti-cariogenic element, but when ingestion is excessive, systemic toxicity may be observed. This can occur as acute or chronic responses, depending on both the amount of F and the time of exposure. The present study identified the profile of protein expression possibly associated with F-induced chronic hepatotoxicity. Weanling male Wistar rats (three-weeks old were divided into three groups and treated with drinking water containing 0, 5 or 50 mg/L F for 60 days (n=6/group. At this time point, serum and livers were collected for F analysis, which was done using the ion-sensitive electrode, after hexamethyldisiloxane-facilitated diffusion. Livers were also submitted to histological and proteomic analyses (2D-PAGE followed by LC-MS/MS. Western blotting was done for confirmation of the proteomic data A dose-response was observed in serum F levels. In the livers, F levels were significantly increased in the 50 mg/L F group compared to groups treated with 0 and 5 mg/L F. Liver morphometric analysis did not reveal alterations in the cellular structures and lipid droplets were present in all groups. Proteomic quantitative intensity analysis detected 33, 44, and 29 spots differentially expressed in the comparisons between control vs. 5 mg/L F, control vs. 50 mg/L F, and 5 mg/L vs. 50 mg/L F, respectively. From these, 92 proteins were successfully identified. In addition, 18, 1, and 5 protein spots were shown to be exclusive in control, 5, and 50 mg/L F, respectively. Most of proteins were related to metabolic process and pronounced alterations were seen for the high-F level group. In F-treated rats, changes in the apolipoprotein E (ApoE and GRP-78 expression may account for the F-induced toxicity in the liver. This can contribute to understanding the molecular mechanisms underlying hepatoxicity induced by F, by indicating key-proteins that should be better addressed in future studies.

  12. Prenatal nicotine and maternal deprivation stress de-regulate the development of CA1, CA3, and dentate gyrus neurons in hippocampus of infant rats.

    Directory of Open Access Journals (Sweden)

    Hong Wang

    Full Text Available Adverse experiences by the developing fetus and in early childhood are associated with profound effects on learning, emotional behavior, and cognition as a whole. In this study we investigated the effects of prenatal nicotine exposure (NIC, postnatal maternal deprivation (MD or the combination of the two (NIC+MD to determine if hippocampal neuron development is modulated by exposure to drugs of abuse and/or stress. Growth of rat offspring exposed to MD alone or NIC+MD was repressed until after weaning. In CA1 but not CA3 of postnatal day 14 (P14 pups, MD increased pyramidal neurons, however, in dentate gyrus (DG, decreased granule neurons. NIC had no effect on neuron number in CA1, CA3 or DG. Unexpectedly, NIC plus MD combined caused a synergistic increase in the number of CA1 or CA3 neurons. Neuron density in CA regions was unaffected by treatment, but in the DG, granule neurons had a looser packing density after NIC, MD or NIC+MD exposure. When septotemporal axes were analyzed, the synergism of stress and drug exposure in CA1 and CA3 was associated with rostral, whereas MD effects were predominantly associated with caudal neurons. TUNEL labeling suggests no active apoptosis at P14, and doublecortin positive neurons and mossy fibers were diminished in NIC+MD relative to controls. The laterality of the effect of nicotine and/or maternal deprivation in right versus left hippocampus was also analyzed and found to be insiginificant. We report for the first time that early life stressors such as postnatal MD and prenatal NIC exposure, when combined, may exhibit synergistic consequences for CA1 and CA3 pyramidal neuron development, and a potential antagonistic influence on developing DG neurons. These results suggest that early stressors may modulate neurogenesis, apoptosis, or maturation of glutamatergic neurons in the hippocampus in a region-specific manner during critical periods of neurodevelopment.

  13. Taurine promotes cognitive function in prenatally stressed juvenile rats via activating the Akt-CREB-PGC1α pathway.

    Science.gov (United States)

    Jia, Ning; Sun, Qinru; Su, Qian; Dang, Shaokang; Chen, Guomin

    2016-12-01

    Substantial evidence has shown that the oxidative damage to hippocampal neurons is associated with the cognitive impairment induced by adverse stimuli during gestation named prenatal stress (PS). Taurine, a conditionally essential amino acid, possesses multiple roles in the brain as a neuromodulator or antioxidant. In this study, to explore the roles of taurine in PS-induced learning and memory impairment, prenatal restraint stress was set up and Morris water maze (MWM) was employed for testing the cognitive function in the one-month-old rat offspring. The mitochondrial reactive oxygen species (ROS) level,mitochondrial membrane potential (MMP), ATP and cytochrome c oxidase (CcO) activity and apoptosis-related proteins in the hippocampus were detected. The activity of the Akt-cyclic AMP response element-binding protein (CREB)-peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) pathway in the hippocampus was measured. The results showed that high dosage of taurine administration in the early postnatal period attenuated impairment of spatial learning and memory induced by PS. Meanwhile, taurine administration diminished the increase in mitochondrial ROS, and recovered the reduction of MMP, ATP level and the activities of CcO, superoxide dismutase 2 (SOD2) and catalase induced by PS in the hippocampus. In addition, taurine administration recovered PS-suppressed SOD2 expression level. Taurine administration blocked PS-induced decrease in the ratio of Bcl-2/Bax and increase in the ratio of cleaved caspase-3/full-length caspase-3. Notably, taurine inhibited PS-decreased phosphorylation of Akt (pAkt) and phosphorylation of CREB (pCREB), which consequently enhanced the mRNA and protein levels of PGC1α. Taken together, these results suggest that high dosage of taurine administration during the early postnatal period can significantly improve the cognitive function in prenatally stressed juvenile rats via activating the Akt-CREB-PGC1α pathway. Therefore

  14. Taurine promotes cognitive function in prenatally stressed juvenile rats via activating the Akt-CREB-PGC1α pathway

    Directory of Open Access Journals (Sweden)

    Ning Jia

    2016-12-01

    Full Text Available Substantial evidence has shown that the oxidative damage to hippocampal neurons is associated with the cognitive impairment induced by adverse stimuli during gestation named prenatal stress (PS. Taurine, a conditionally essential amino acid, possesses multiple roles in the brain as a neuromodulator or antioxidant. In this study, to explore the roles of taurine in PS-induced learning and memory impairment, prenatal restraint stress was set up and Morris water maze (MWM was employed for testing the cognitive function in the one-month-old rat offspring. The mitochondrial reactive oxygen species (ROS level,mitochondrial membrane potential (MMP, ATP and cytochrome c oxidase (CcO activity and apoptosis-related proteins in the hippocampus were detected. The activity of the Akt-cyclic AMP response element-binding protein (CREB-peroxisome proliferator-activated receptor–γ coactivator-1α (PGC1α pathway in the hippocampus was measured. The results showed that high dosage of taurine administration in the early postnatal period attenuated impairment of spatial learning and memory induced by PS. Meanwhile, taurine administration diminished the increase in mitochondrial ROS, and recovered the reduction of MMP, ATP level and the activities of CcO, superoxide dismutase 2 (SOD2 and catalase induced by PS in the hippocampus. In addition, taurine administration recovered PS-suppressed SOD2 expression level. Taurine administration blocked PS-induced decrease in the ratio of Bcl-2/Bax and increase in the ratio of cleaved caspase-3/full-length caspase-3. Notably, taurine inhibited PS-decreased phosphorylation of Akt (pAkt and phosphorylation of CREB (pCREB, which consequently enhanced the mRNA and protein levels of PGC1α. Taken together, these results suggest that high dosage of taurine administration during the early postnatal period can significantly improve the cognitive function in prenatally stressed juvenile rats via activating the Akt-CREB-PGC1

  15. Comparison of three methods of exposing rats to cigarette smoke

    Energy Technology Data Exchange (ETDEWEB)

    Mauderly, J L; Bechtold, W E; Bond, J A; Brooks, A L; Chen, B T; Cuddihy, R G; Harkema, J R; Henderson, R F; Johnson, N F; Ritchideh, K; Thomassen, D G

    1988-12-01

    We compared smoke composition and biological effects resulting from exposures of rats for 5 wk to cigarette smoke by nose-only intermittent (NOI), nose-only continuous (NOC) and whole-body continuous (WBC) exposure methods. Exposure concentrations and times were adjusted to achieve the same daily concentration x time product for particulate matter. There were few differences in smoke composition or biological effects among exposure modes. WBC smoke was lower in particle-borne nicotine and higher in some organic vapors and carbon monoxide than smoke in nose-only modes. Body weight was depressed less by WBC than by NOI or NOC exposures. Plasma and urine nicotine levels were higher for WBC than for NOI or NOC, suggesting greater absorption from body surfaces or by grooming. Smoke exposures increased nasal epithelial proliferation, tracheal epithelial cell transformation, chromosomal aberrations in alveolar macrophages, and lung DNA adduct levels, and caused inflammatory changes in airway fluid and slight alterations of respiratory function, but there were no significant differences among exposure modes. The results indicate that WBC exposures should produce long-term effects similar to those of nose-only exposures, but might allow increased delivery of smoke to lungs while reducing stress, acute toxicity and the manpower requirements associated with performing these experiments. (author)

  16. Proteomic analysis of urine in rats chronically exposed to fluoride.

    Science.gov (United States)

    Kobayashi, Claudia Ayumi Nakai; Leite, Aline de Lima; da Silva, Thelma Lopes; dos Santos, Lucilene Delazari; Nogueira, Fábio César Sousa; Santos, Keity Souza; de Oliveira, Rodrigo Cardoso; Palma, Mario Sérgio; Domont, Gilberto Barbosa; Buzalaf, Marília Afonso Rabelo

    2011-01-01

    Urine is an ideal source of materials to search for potential disease-related biomarkers as it is produced by the affected tissues and can be easily obtained by noninvasive methods. 2-DE-based proteomic approach was used to better understand the molecular mechanisms of injury induced by fluoride (F(-)) and define potential biomarkers of dental fluorosis. Three groups of weanling male Wistar rats were treated with drinking water containing 0 (control), 5, or 50 ppm F(-) for 60 days (n = 15/group). During the experimental period, the animals were kept individually in metabolic cages, to analyze the water and food consumption, as well as fecal and urinary F(-) excretion. Urinary proteome profiles were examined using 2-DE and Colloidal Coomassie Brilliant Blue staining. A dose-response regarding F(-) intake and excretion was detected. Quantitative intensity analysis revealed 8, 11, and 8 significantly altered proteins between control vs. 5 ppm F(-), control vs. 50 ppm F(-) and 5 ppm F(-) vs. 50 ppm F(-) groups, respectively. Two proteins regulated by androgens (androgen-regulated 20-KDa protein and α-2μ-globulin) and one related to detoxification (aflatoxin-B1-aldehyde-reductase) were identified by MALDI-TOF-TOF MS/MS. Thus, proteomic analysis can help to better understand the mechanisms underlying F(-) toxicity, even in low doses. Copyright © 2010 Wiley Periodicals, Inc.

  17. Comparison of three methods of exposing rats to cigarette smoke

    International Nuclear Information System (INIS)

    Mauderly, J.L.; Bechtold, W.E.; Bond, J.A.; Brooks, A.L.; Chen, B.T.; Cuddihy, R.G.; Harkema, J.R.; Henderson, R.F.; Johnson, N.F.; Ritchideh, K.; Thomassen, D.G.

    1988-01-01

    We compared smoke composition and biological effects resulting from exposures of rats for 5 wk to cigarette smoke by nose-only intermittent (NOI), nose-only continuous (NOC) and whole-body continuous (WBC) exposure methods. Exposure concentrations and times were adjusted to achieve the same daily concentration x time product for particulate matter. There were few differences in smoke composition or biological effects among exposure modes. WBC smoke was lower in particle-borne nicotine and higher in some organic vapors and carbon monoxide than smoke in nose-only modes. Body weight was depressed less by WBC than by NOI or NOC exposures. Plasma and urine nicotine levels were higher for WBC than for NOI or NOC, suggesting greater absorption from body surfaces or by grooming. Smoke exposures increased nasal epithelial proliferation, tracheal epithelial cell transformation, chromosomal aberrations in alveolar macrophages, and lung DNA adduct levels, and caused inflammatory changes in airway fluid and slight alterations of respiratory function, but there were no significant differences among exposure modes. The results indicate that WBC exposures should produce long-term effects similar to those of nose-only exposures, but might allow increased delivery of smoke to lungs while reducing stress, acute toxicity and the manpower requirements associated with performing these experiments. (author)

  18. Are there any remarkable effects of prenatal exposure to food colourings on neurobehaviour and learning process in rat offspring?

    Science.gov (United States)

    Doguc, Duygu Kumbul; Aylak, Firdevs; Ilhan, Ilter; Kulac, Esin; Gultekin, Fatih

    2015-01-01

    Artificial food colourings and additives (AFCAs) have long been discussed to have adverse effects on cognition and behaviour in children. In this study, our aim was to assess the probable side effects of prenatal exposure to colouring food additives on neurobehaviour and spatial learning process. We administered 'no observable adverse effect levels' (NOAELs) of common used AFCAs as a mixture (erythrosine, Ponceau 4R, Allura Red AC, Sunset yellow FCF, tartrazine, Amaranth, Brilliant Blue, Azorubine and Indigotine) to female rats before and during gestation and tested their effects on spatial working memory and behaviour in their offspring. Effects of AFCAs on spatial working memory were evaluated by Morris water maze, behavioural and locomotor effects by open-field and forced-swim tests. Prenatal exposure to commonly used AFCAs had no adverse effects on spatial working memory; however, assessment of interaction of sex and AFCAs on 'latency to locate the visible platform', which was used as a measure of motivation, showed a significant interaction (P < 0.05) on female rats. In addition, AFCAs caused an increase in anxiolytic like effect in the open-field test (P < 0.05) and an increase in mobility time (P < 0.05) in the forced-swim test. We also detected a significant interaction of sex and AFCAs on forced-swim test parameters (P < 0.05). These findings indicated that prenatal exposure to NOAELs of AFCAs resulted in implicit adverse effects that caused an increase in motility and a decrease in motivation and anxiety in offspring in sex-related manner.

  19. Prenatal ethanol exposure modifies locomotor activity and induces selective changes in Met-enk expression in adolescent rats.

    Science.gov (United States)

    Abate, P; Reyes-Guzmán, A C; Hernández-Fonseca, K; Méndez, M

    2017-04-01

    Several studies suggest that prenatal ethanol exposure (PEE) facilitates ethanol intake. Opioid peptides play a main role in ethanol reinforcement during infancy and adulthood. However, PEE effects upon motor responsiveness elicited by an ethanol challenge and the participation of opioids in these actions remain to be understood. This work assessed the susceptibility of adolescent rats to prenatal and/or postnatal ethanol exposure in terms of behavioral responses, as well as alcohol effects on Met-enk expression in brain areas related to drug reinforcement. Motor parameters (horizontal locomotion, rearings and stereotyped behaviors) in pre- and postnatally ethanol-challenged adolescents were evaluated. Pregnant rats received ethanol (2g/kg) or water during gestational days 17-20. Adolescents at postnatal day 30 (PD30) were tested in a three-trial activity paradigm (habituation, vehicle and drug sessions). Met-enk content was quantitated by radioimmunoassay in several regions: ventral tegmental area [VTA], nucleus accumbens [NAcc], prefrontal cortex [PFC], substantia nigra [SN], caudate-putamen [CP], amygdala, hypothalamus and hippocampus. PEE significantly reduced rearing responses. Ethanol challenge at PD30 decreased horizontal locomotion and showed a tendency to reduce rearings and stereotyped behaviors. PEE increased Met-enk content in the PFC, CP, hypothalamus and hippocampus, but did not alter peptide levels in the amygdala, VTA and NAcc. These findings suggest that PEE selectively modifies behavioral parameters at PD30 and induces specific changes in Met-enk content in regions of the mesocortical and nigrostriatal pathways, the hypothalamus and hippocampus. Prenatal and postnatal ethanol actions on motor activity in adolescents could involve activation of specific neural enkephalinergic pathways. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Effects of Vitamin C on Kidney and Bone of Rats Exposed to Low ...

    African Journals Online (AJOL)

    . Wister rats were exposed to cadmium (as CdSO4.8H2O), by sub-cutaneous injection, at doses of 1.0, 2.0 and 3.0 ìg/kg body weight, with or without vitamin C supplementation, for four weeks. Serum alkaline phosphatase activity of the group of ...

  1. GENE ARRAY ANALYSIS OF THE VENTRAL PROSTATE IN RATS EXPOSED TO EITHER VINCLOZOLIN OR PROCYMIDONE

    Science.gov (United States)

    GENE ARRAY ANALYSIS OF THE VENTRAL PROSTATE IN RATS EXPOSED TO EITHER VINCLOZOLIN OR PROCYMIDONE. MB Rosen, VS Wilson, JE Schmid, and LE Gray Jr. US EPA, ORD, NHEERL, RTP, NC.Vinclozolin (Vi) and procymidone (Pr) are antiandrogenic fungicides. While changes in gene expr...

  2. Housing under the pyramid reduces susceptibility of hippocampal CA3 pyramidal neurons to prenatal stress in the developing rat offspring.

    Science.gov (United States)

    Murthy, Krishna Dilip; George, Mitchel Constance; Ramasamy, Perumal; Mustapha, Zainal Arifin

    2013-12-01

    Mother-offspring interaction begins before birth. The foetus is particularly vulnerable to environmental insults and stress. The body responds by releasing excess of the stress hormone cortisol, which acts on glucocorticoid receptors. Hippocampus in the brain is rich in glucocorticoid receptors and therefore susceptible to stress. The stress effects are reduced when the animals are placed under a model wooden pyramid. The present study was to first explore the effects of prenatal restraint-stress on the plasma corticosterone levels and the dendritic arborisation of CA3 pyramidal neurons in the hippocampus of the offspring. Further, to test whether the pyramid environment would alter these effects, as housing under a pyramid is known to reduce the stress effects, pregnant Sprague Dawley rats were restrained for 9 h per day from gestation day 7 until parturition in a wire-mesh restrainer. Plasma corticosterone levels were found to be significantly increased. In addition, there was a significant reduction in the apical and the basal total dendritic branching points and intersections of the CA3 hippocampal pyramidal neurons. The results thus suggest that, housing in the pyramid dramatically reduces prenatal stress effects in rats.

  3. The Beneficial Impact of Antidepressant Drugs on Prenatal Stress-Evoked Malfunction of the Insulin-Like Growth Factor-1 (IGF-1) Protein Family in the Olfactory Bulbs of Adult Rats.

    Science.gov (United States)

    Trojan, Ewa; Głombik, Katarzyna; Ślusarczyk, Joanna; Budziszewska, Bogusława; Kubera, Marta; Roman, Adam; Lasoń, Władysław; Basta-Kaim, Agnieszka

    2016-02-01

    Insulin-like growth factor-1 (IGF-1) promotes the growth, differentiation, and survival of both neurons and glial cells, and it is believed to exert antidepressant-like activity. Thus, disturbances in the IGF-1 system could be responsible for the course of depression. To date, there have been no papers showing the impact of chronic antidepressant treatment on the IGF-1 network in the olfactory bulb (OB) in an animal model of depression. Prenatal stress was used as model of depression. Twenty-four 3-month-old male offspring of control and stressed mothers were subjected to behavioral testing (forced swim test). The mRNA expression of IGF-1 and IGF-1 receptor (IGF-1R) and the protein level of IGF-1 and its phosphorylation, as well as the concentrations of IGF-binding proteins (IGFBP-2, -4, -3, and -6), were measured in OBs before and after chronic imipramine, fluoxetine, or tianeptine administration. Adult rats exposed prenatally to stressful stimuli displayed not only depression-like behavior but also decreased IGF-1 expression, dysregulation in the IGFBP network, and diminished mRNA expression, as well as IGF-1R phosphorylation, in the OB. The administration of antidepressants normalized most of the changes in the IGF-1 system of the OB evoked by prenatal stress. These results suggested a beneficial effect of chronic antidepressant drug treatment in the alleviation of IGF-1 family malfunction in OBs in an animal model of depression.

  4. PRENATAL HYPOXIA IN DIFFERENT PERIODS OF EMBRYOGENESIS DIFFERENTIALLY AFFECTS CELL MIGRATION, NEURONAL PLASTICITY AND RAT BEHAVIOR IN POSTNATAL ONTOGENESIS

    Directory of Open Access Journals (Sweden)

    Dmitrii S Vasilev

    2016-03-01

    Full Text Available Long-term effects of prenatal hypoxia on embryonic days E14 or E18 on the number, type and localization of cortical neurons, density of labile synaptopodin-positive dendritic spines and parietal cortex-dependent behavioral tasks were examined in the postnatal ontogenesis of rats. An injection of 5’ethynyl-2’deoxyuridine to pregnant rats was used to label neurons generated on E14 or E18 in the fetuses. In control rat pups a majority of cells labeled on E14 were localized in the lower cortical layers V-VI while the cells labeled on E18 were mainly found in the superficial cortical layers II-III. It was shown that hypoxia both on E14 and E18 results in disruption of neuroblast generation and migration but affects different cell populations. In rat pups subjected to hypoxia on E14, the total number of labeled cells in the parietal cortex was decreased while the number of labeled neurons scattered within the superficial cortical layers was increased. In rat pups subjected to hypoxia on E18, the total number of labeled cells in the parietal cortex was also decreased but the number of scattered labeled neurons was higher in the lower cortical layers. It can be suggested that prenatal hypoxia both on E14 and E18 causes a disruption in neuroblast migration but with a different outcome. Only in rats subjected to hypoxia on E14 did we observe a reduction in the total number of pyramidal cortical neurons and the density of labile synaptopodin-positive dendritic spines in the molecular cortical layer during the first month after birth which affected development of the cortical functions. As a result, rats subjected to hypoxia on E14, but not on E18, had impaired development of the whisker-placing reaction and reduced ability to learn reaching by a forepaw. The data obtained suggest that hypoxia on E14 in the period of generation of the cells, which later differentiate into the pyramidal cortical neurons of the V-VI layers and form cortical minicolumns

  5. A hypothalamic–pituitary–adrenal axis-associated neuroendocrine metabolic programmed alteration in offspring rats of IUGR induced by prenatal caffeine ingestion

    Energy Technology Data Exchange (ETDEWEB)

    Xu, D. [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China); Wu, Y.; Liu, F.; Liu, Y.S.; Shen, L.; Lei, Y.Y.; Liu, J. [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Ping, J. [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China); Qin, J. [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Zhang, C. [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Chen, L.B. [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Magdalou, J. [UMR 7561 CNRS-Nancy Université, Faculté de Médicine, Vandoeuvre-lès-Nancy (France); Wang, H., 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)

    2012-11-01

    Caffeine is a definite factor of intrauterine growth retardation (IUGR). Previously, we have confirmed that prenatal caffeine ingestion inhibits the development of hypothalamic–pituitary–adrenal (HPA) axis, and alters the glucose and lipid metabolism in IUGR fetal rats. In this study, we aimed to verify a programmed alteration of neuroendocrine metabolism in prenatal caffeine ingested-offspring rats. The results showed that prenatal caffeine (120 mg/kg.day) ingestion caused low body weight and high IUGR rate of pups; the concentrations of blood adrenocorticotropic hormone (ACTH) and corticosterone in caffeine group were significantly increased in the early postnatal period followed by falling in late stage; the level of blood glucose was unchanged, while blood total cholesterol (TCH) and triglyceride (TG) were markedly enhanced in adult. After chronic stress, the concentrations and the gain rates of blood ACTH and corticosterone were obviously increased, meanwhile, the blood glucose increased while the TCH and TG decreased in caffeine group. Further, the hippocampal mineralocorticoid receptor (MR) expression in caffeine group was initially decreased and subsequently increased after birth. After chronic stress, the 11β-hydroxysteroid dehydrogenase-1, glucocorticoid receptor (GR), MR as well as the MR/GR ratio were all significantly decreased. These results suggested that prenatal caffeine ingestion induced the dysfunction of HPA axis and associated neuroendocrine metabolic programmed alteration in IUGR offspring rats, which might be related with the functional injury of hippocampus. These observations provide a valuable experimental basis for explaining the susceptibility of IUGR offspring to metabolic syndrome and associated diseases. -- Highlights: ► Prenatal caffeine ingestion induced HPA axis dysfunction in IUGR offspring rats. ► Caffeine induced a neuroendocrine metabolic programmed alteration in offspring rats. ► Caffeine induced a functional injury

  6. A hypothalamic–pituitary–adrenal axis-associated neuroendocrine metabolic programmed alteration in offspring rats of IUGR induced by prenatal caffeine ingestion

    International Nuclear Information System (INIS)

    Xu, D.; Wu, Y.; Liu, F.; Liu, Y.S.; Shen, L.; Lei, Y.Y.; Liu, J.; Ping, J.; Qin, J.; Zhang, C.; Chen, L.B.; Magdalou, J.; Wang, H.

    2012-01-01

    Caffeine is a definite factor of intrauterine growth retardation (IUGR). Previously, we have confirmed that prenatal caffeine ingestion inhibits the development of hypothalamic–pituitary–adrenal (HPA) axis, and alters the glucose and lipid metabolism in IUGR fetal rats. In this study, we aimed to verify a programmed alteration of neuroendocrine metabolism in prenatal caffeine ingested-offspring rats. The results showed that prenatal caffeine (120 mg/kg.day) ingestion caused low body weight and high IUGR rate of pups; the concentrations of blood adrenocorticotropic hormone (ACTH) and corticosterone in caffeine group were significantly increased in the early postnatal period followed by falling in late stage; the level of blood glucose was unchanged, while blood total cholesterol (TCH) and triglyceride (TG) were markedly enhanced in adult. After chronic stress, the concentrations and the gain rates of blood ACTH and corticosterone were obviously increased, meanwhile, the blood glucose increased while the TCH and TG decreased in caffeine group. Further, the hippocampal mineralocorticoid receptor (MR) expression in caffeine group was initially decreased and subsequently increased after birth. After chronic stress, the 11β-hydroxysteroid dehydrogenase-1, glucocorticoid receptor (GR), MR as well as the MR/GR ratio were all significantly decreased. These results suggested that prenatal caffeine ingestion induced the dysfunction of HPA axis and associated neuroendocrine metabolic programmed alteration in IUGR offspring rats, which might be related with the functional injury of hippocampus. These observations provide a valuable experimental basis for explaining the susceptibility of IUGR offspring to metabolic syndrome and associated diseases. -- Highlights: ► Prenatal caffeine ingestion induced HPA axis dysfunction in IUGR offspring rats. ► Caffeine induced a neuroendocrine metabolic programmed alteration in offspring rats. ► Caffeine induced a functional injury

  7. Effect of acetaminophen administration to rats chronically exposed to depleted uranium

    International Nuclear Information System (INIS)

    Gueguen, Y.; Grandcolas, L.; Baudelin, C.; Grison, S.; Tissandie, E.; Jourdain, J.R.; Paquet, F.; Voisin, P.; Aigueperse, J.; Gourmelon, P.; Souidi, M.

    2007-01-01

    The extensive use of depleted uranium (DU) in both civilian and military applications results in the increase of the number of human beings exposed to this compound. We previously found that DU chronic exposure induces the expression of CYP enzymes involved in the metabolism of xenobiotics (drugs). In order to evaluate the consequences of these changes on the metabolism of a drug, rats chronically exposed to DU (40 mg/l) were treated by acetaminophen (APAP, 400 mg/kg) at the end of the 9-month contamination. Acetaminophen is considered as a safe drug within the therapeutic range but in the case of overdose or in sensitive animals, hepatotoxicity and nephrotoxicity could occur. In the present work, plasma concentration of APAP was higher in the DU group compared to the non-contaminated group. In addition, administration of APAP to the DU-exposed rats increased plasma ALT (p < 0.01) and AST (p < 0.05) more rapidly than in the control group. Nevertheless, no histological alteration of the liver was observed but renal injury characterized by incomplete proximal tubular cell necrosis was higher for the DU-exposed rats. Moreover, in the kidney, CYP2E1 gene expression, an important CYP responsible for APAP bioactivation and toxicity, is increased (p < 0.01) in the DU-exposed group compared to the control group. In the liver, CYP's activities were decreased between control and DU-exposed rats. These results could explain the worse elimination of APAP in the plasma and confirm our hypothesis of a modification of the drug metabolism following a DU chronic contamination

  8. Prenatal dietary load of Maillard reaction products combined with postnatal Coca-Cola drinking affects metabolic status of female Wistar rats

    OpenAIRE

    Gurecká, Radana; Koborová, Ivana; Janšáková, Katarína; Tábi, Tamás; Szökő, Éva; Somoza, Veronika; Šebeková, Katarína; Celec, Peter

    2015-01-01

    Aim To assess the impact of prenatal exposure to Maillard reaction products (MRPs) -rich diet and postnatal Coca- Cola consumption on metabolic status of female rats. Diet rich in MRPs and consumption of saccharose/fructose sweetened soft drinks is presumed to impose increased risk of development of cardiometabolic afflictions, such as obesity or insulin resistance. Methods At the first day of pregnancy, 9 female Wistar rats were randomized into two groups, pair-fed ei...

  9. Bromodeoxyuridine and methylazoxymethanol exposure during brain development affects behavior in rats : consideration for a role of nerve growth factor and brain derived neurotrophic factor

    NARCIS (Netherlands)

    Fiore, M; Aloe, L; Westenbroek, C; Amendola, T; Antonelli, A; Korf, J

    2001-01-01

    Rats prenatally exposed to the neurotoxins methylazoxymethanol (MAM) or 5-Bromo-2'-deoxyuridine (BrdU) are used as animal models of brain maldevelopment. We administered in rats MAM (20 mg/kg), or BrdU (100 mg/kg) or both at gestational day 11. Locomotion was not affected by any prenatal treatment

  10. Turmeric extract inhibits apoptosis of hippocampal neurons of trimethyltin-exposed rats.

    Science.gov (United States)

    Yuliani, S; Widyarini, S; Mustofa; Partadiredja, G

    2017-01-01

    The aim of the present study was to reveal the possible antiapoptotic effect of turmeric (Curcuma longa Linn.) on the hippocampal neurons of rats exposed to trimethyltin (TMT). Oxidative damage in the hippocampus can induce the apoptosis of neurons associated with the pathogenesis of dementiaMETHODS. The ethanolic turmeric extract and a citicoline (as positive control) solution were administered to the TMT-exposed rats for 28 days. The body weights of rats were recorded once a week. The hippocampal weights and imumunohistochemical expression of caspase 3 proteins in the CA1 and CA2-CA3 regions of the hippocampi were examined at the end of the experiment. Immunohistochemical analysis showed that the injection of TMT increased the expression of caspase 3 in the CA1 and CA2-CA3 regions of hippocampus. TMT also decreased the body and hippocampal weights. Furthermore, the administration of 200 mg/kg bw dose of turmeric extract decreased the caspase 3 expression in the CA2-CA3 pyramidal neurons but not in the CA1 neurons. It also prevented the decrease of the body and hippocampal weights. We suggest that the 200 mg/kg bw dose of turmeric extract may exert antiapoptotic effect on the hippocampal neurons of the TMT-exposed rats (Tab. 1, Fig. 3, Ref. 49).

  11. Does melatonin influence the apoptosis in rat uterus of animals exposed to continuous light?

    Science.gov (United States)

    Ferreira, Cecília S; Carvalho, Kátia C; Maganhin, Carla C; Paiotti, Ana P R; Oshima, Celina T F; Simões, Manuel J; Baracat, Edmund C; Soares, José M

    2016-02-01

    Melatonin has been described as a protective agent against cell death and oxidative stress in different tissues, including in the reproductive system. However, the information on the action of this hormone in rat uterine apoptosis is low. Our objective was to evaluate the effects of melatonin on mechanisms of cell death in uterus of rats exposed to continuous light stress. Twenty adult Wistar rats were divided into two groups: GContr (vehicle control) and GExp which were treated with melatonin (0.4 mg/mL), both were exposed to continuous light for 90 days. The uterus was removed and processed for quantitative real time PCR (qRT-PCR), using PCR-array plates of the apoptosis pathway; for immunohistochemistry and TUNEL. The results of qRT-PCR of GEXP group showed up-regulation of 13 and 7, pro-apoptotic and anti-apoptotic genes, respectively, compared to GContr group. No difference in pro-apoptotic proteins (Bax, Fas and Faslg) expression was observed by immunohistochemistry, although the number of TUNEL-positive cells was lower in the group treated with melatonin compared to the group not treated with this hormone. Our data suggest that melatonin influences the mechanism and decreases the apoptosis in uterus of rats exposed to continuous light.

  12. In vivo genotoxicity assessment in rats exposed to Prestige-like oil by inhalation.

    Science.gov (United States)

    Valdiglesias, Vanessa; Kiliç, Gözde; Costa, Carla; Amor-Carro, Óscar; Mariñas-Pardo, Luis; Ramos-Barbón, David; Méndez, Josefina; Pásaro, Eduardo; Laffon, Blanca

    2012-01-01

    One of the largest oil spill disasters in recent times was the accident of the oil tanker Prestige in front of the Galician coast in 2002. Thousands of people participated in the cleanup of the contaminated areas, being exposed to a complex mixture of toxic substances. Acute and prolonged respiratory symptoms and genotoxic effects were reported, although environmental exposure measurements were restricted to current determinations, such that attribution of effects observed to oil exposure is difficult to establish. The aim of this study was to analyze peripheral blood leukocytes (PBL) harvested from a rat model of subchronic exposure to a fuel oil with similar characteristics to that spilled by the Prestige tanker, in order to determine potential genotoxic effects under strictly controlled, in vivo exposure. Wistar Han and Brown Norway rats were exposed to the oil for 3 wk, and micronucleus test (MN) and comet assay, standard and modified with 8-oxoguanine DNA glycosylase (OGG1) enzyme, were employed to assess genotoxicity 72 h and 15 d after the last exposure. In addition, the potential effects of oil exposure on DNA repair capacity were determined by means of mutagen sensitivity assay. Results obtained from this study showed that inhalation oil exposure induced DNA damage in both Brown Norway and Wistar Han rats, especially in those animals evaluated 15 d after exposure. Although alterations in the DNA repair responses were noted, the sensitivity to oil substances varied depending on rat strain. Data support previous positive genotoxicity results reported in humans exposed to Prestige oil during cleanup tasks.

  13. Catecholamine levels in the brain of rats exposed by inhalation to benzalkonium chloride.

    Science.gov (United States)

    Swiercz, Radosław; Grzelińska, Zofia; Gralewicz, Sławomir; Wasowicz, Wojciech

    2009-01-01

    The aim of the study was to obtain quantitative data on the effect of inhalation exposure to benzalkonium chloride (BAC) on the concentration of catecholamines and their metabolites in selected brain structures. Additionally, concentration of corticosterone (CORT) in plasma was estimated. Wistar rats were subjected to a single (6-hour) or repeated (3 days, 6 h/day) exposure to BAC aerosol at ca. 30 mg/m3. The Waters integrated analytical system of HPLC was used to determine the plasma corticosterone. Qualitative and quantitative determinations of catecholamines and their metabolites: 3,4-dihydroxyphenylacetic (DOPAC) and homovanillic (HVA) acids were performed with the use of the Waters integrity HPLC. The determinations have shown that in the BAC-exposed rats the plasma CORT concentration was several times higher than in the control rats. A significant increase of the concentration of dopamine (DA) (striatum and diencephalon) and noradrenaline (NA) (hippocampus and cerebellum) and a significant reduction of adrenaline (A) level (cortex, hippocampus, striatum and mesencephaloon) was found to occur in the brain of rats exposed to BAC compared to control. In the animals exposed to BAC, the concentration of DOPAC, a DA metabolite, was significantly reduced, but the change occurred mainly in the striatum. This resulted in a significant decrease of the DOPAC/DA and HVA/DA metabolic ratio in this structure. It is assumed that the alterations in the concentration of catecholamines and their metabolites in the BAC-exposed rats were related to the unexpectedly strong and persistent activation of the hypothalamo-pituitary-adrenocortical (HPA) axis evidenced by the high plasma CORT concentration.

  14. Expression of phosphorylated extracellular signal-regulated kinase in rat kidneys exposed to high +Gz

    Directory of Open Access Journals (Sweden)

    Hyun-Soo Kim

    2012-11-01

    Full Text Available Exposure to high gravitational acceleration forces acting along the body axis from the head to the feet (+Gz severely reduces blood flow to the visceral organs, including the kidneys. Extracellular signal-regulated kinase (ERK figures predominantly in mediating kidney cell responses to a wide variety of stress-related stimuli. Though previous studies have shown the activation of ERK in some experimental models, the regulation of ERK associated with +Gz exposure has not yet been investigated. The aim of this study was to examine the effect of high +Gz exposure on ERK activation in the kidneys. Using a small animal centrifuge, eight male Sprague-Dawley rats were exposed to +10Gz or +13Gz three times for 3 minutes each. The bilateral kidneys were obtained from each rat, and the expression levels of phosphorylated ERK (p-ERK were evaluated using immunohistochemistry. In the control group, the collecting duct epithelium displayed faint cytoplasmic staining with no nuclear staining of p-ERK. By contrast, rats exposed to +10Gz showed strong nuclear staining intensity for p-ERK. In the renal papilla, the epithelial cells of collecting ducts and thin segments of the loop of Henle exhibited strong nuclear immunoreactivity for p-ERK. Rats exposed to +13Gz also showed the same staining intensity and distribution of p-ERK expression as that of rats exposed to +10Gz. This study is the first to describe +Gz exposure-induced alteration in the expression of p-ERK in the kidneys. Our finding suggests that high +Gz exposure leads to the activation of ERK in the renal papilla.

  15. Physiological and Histopathological Investigations on the Effects of -Lipoic Acid in Rats Exposed to Malathion

    Directory of Open Access Journals (Sweden)

    Atef M. Al-Attar

    2010-01-01

    Full Text Available The present study was designed to evaluate the influence of -lipoic acid treatment in rats exposed to malathion. Forty adult male rats were used in this study and distributed into four groups. Animals of group 1 were untreated and served as control. Rats of group 2 were orally given malathion at a dose level of 100 mg/kg body weight (BW for a period of one month. Experimental animals of group 3 were orally given -lipoic acid at a dose level of 20 mg/kg BW and after 3 hours exposed to malathion at the same dose given to group 2. Rats of group 4 were supplemented with -lipoic acid at the same dose given to group 3. The activities of serum glutamic oxaloacetic acid transaminase (GOT, glutamic pyruvic acid transaminase (GPT, alkaline phosphatase (ALP, and acid phosphatase (ACP, and the values of creatinine, urea, and uric acid were statistically increased, while the values of total protein and total albumin were significantly decreased in rats exposed to malathion. Moreover, administration of malathion for one month resulted in damage of liver and kidney structures. Administration of -lipoic acid before malathion exposure to rat can prevent severe alterations of hematobiochemical parameters and disruptions of liver and kidney structures. In conclusion, this study obviously demonstrated that pretreatment with -lipoic acid significantly attenuated the physiological and histopathological alterations induced by malathion. Also, the present study identifies new areas of research for development of better therapeutic agents for liver, kidney, and other organs' dysfunctions and diseases.

  16. NICOTINE EFFECTS ON THE MOTOR ACTIVITY OF MICE EXPOSED PRENATALLY TO THE NICOTINIC AGONIST ANATOXIN-A.

    Science.gov (United States)

    Several studies in the literature have shown that exposure of mice and rats to nicotine early in development alters its effects when the rodents are subsequently challenged with nicotine. Anatoxin-a is a nicotinic agonist produced by several genera of cyanobacteria, and has caus...

  17. The effects of prenatal sound stress on the spatial learning and memory of rat's male offspring

    Directory of Open Access Journals (Sweden)

    Barzegar M

    2011-01-01

    Full Text Available "n 800x600 Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman","serif";} Background: Numerous evidences indicate that various environmental stresses during pregnancy affect physiological behavior of the offspring. This experimental study was designed to investigate the effect of noise stress during prenatal period of rats on spatial learning and memory and plasma corticostrone level in postnatal life."n"nMethods: Three groups of pregnant rats were given daily noise stress with durations of two and/ or four hours in last week of pregnancy period. The fourth group was left unstressed. The male offspring from the unstressed and different stressed groups were assigned as controls and stressed groups. The animals were introduced to a spatial task in Morris water maze 4 trials/day for five consecutive days. The probe test was performed on the 5th day of the experiment. The delay in findings and the distance passed to locate the target platform were assessed as the spatial learning. "n"nResults: Our results showed that prenatal exposure to noise stress for two and/ or four hours a day, leads to impaired acquisition of spatial learning in the postnatal animals. The plasma level of corticostrone in the two stressed groups of rats markedly matched with their behavioral function. Prenatal exposure to 1- hour noise stress revealed no effects on the offsprings' behavior and plasma corticostrone level."n"nConclusion: Based on our study results, it seems that applied range of stress which is executed through the noise stress could increase the plasma corticostrone level and

  18. Brightness discrimination learning in a Skinner box in prenatally X-irradiated rats

    International Nuclear Information System (INIS)

    Tamaki, Y.; Inouye, M.

    1976-01-01

    Male MP 1 albino rats were exposed to x-irradiation in utero at a single dose of 200 R on day 17 of gestation. The light-dark discrimination training in a Skinner box was continued until the animals attained a learning criterion of 0.80 correct response ratio for 3 consecutive days. Although during the unreinforced baseline sessions the total number of bar pressings in the irradiated animals was superior to that in the controls, performance between the control and the irradiated animals did not differ significantly in (a) the number of training days required to attain the learning criterion, (b) the total number of days on which the animals produced a correct response ratio more than 0.80, and (c) the number of consecutive days during which the correct response ratio was more than 0.75. The results obtained suggest that the irradiated animals were able to discriminate in brightness cues as well, or nearly as well, as the controls. The cortical-subcortical system mediating brightness discrimination in the irradiated animals is discussed. (author)

  19. Effect of prenatal methadone and ethanol on opioid receptor development in rats

    Energy Technology Data Exchange (ETDEWEB)

    Peters, M.A.; Braun, R.L. (Loma Linda Univ., CA (United States))

    1991-03-11

    The current literature shows that the offspring of female rats exposed to methadone or ethanol display similar neurochemical and neurobehavioral alterations, and suggests that these drugs may be operating through a common mechanism. If this hypothesis is true, their effect on the endogenous opioid systems should be qualitatively similar. In this study virgin females were treated with methadone or 10% ethanol oral solution starting prior to conception and continued throughout gestation. When the offspring had reached 15 or 30 days of age they were sacrificed, the brain was removed and prepared for opioid receptor binding studies. ({sup 3}H)DAGO and ({sup 3}H)DADLE were used as ligands for the mu and delta receptors, respectively. These studies show significant treatment-related differences in both the number of mu and delta binding sites as well as in apparent receptor affinity. Significant sex- and age-related differences between treatments were also observed. These data show that methadone and ethanol, while manifesting some similar neurochemical and behavioral effects, have unique effects on opioid receptor binding, suggesting that they may be acting by different mechanisms.

  20. Dynamic Metabolic Disruption in Rats Perinatally Exposed to Low Doses of Bisphenol-A.

    Directory of Open Access Journals (Sweden)

    Marie Tremblay-Franco

    Full Text Available Along with the well-established effects on fertility and fecundity, perinatal exposure to endocrine disrupting chemicals, and notably to xeno-estrogens, is strongly suspected of modulating general metabolism. The metabolism of a perinatally exposed individual may be durably altered leading to a higher susceptibility of developing metabolic disorders such as obesity and diabetes; however, experimental designs involving the long term study of these dynamic changes in the metabolome raise novel challenges. 1H-NMR-based metabolomics was applied to study the effects of bisphenol-A (BPA, 0; 0.25; 2.5, 25 and 250 μg/kg BW/day in rats exposed perinatally. Serum and liver samples of exposed animals were analyzed on days 21, 50, 90, 140 and 200 in order to explore whether maternal exposure to BPA alters metabolism. Partial Least Squares-Discriminant Analysis (PLS-DA was independently applied to each time point, demonstrating a significant pair-wise discrimination for liver as well as serum samples at all time-points, and highlighting unequivocal metabolic shifts in rats perinatally exposed to BPA, including those exposed to lower doses. In BPA exposed animals, metabolism of glucose, lactate and fatty acids was modified over time. To further explore dynamic variation, ANOVA-Simultaneous Component Analysis (A-SCA was used to separate data into blocks corresponding to the different sources of variation (Time, Dose and Time*Dose interaction. A-SCA enabled the demonstration of a dynamic, time/age dependent shift of serum metabolome throughout the rats' lifetimes. Variables responsible for the discrimination between groups clearly indicate that BPA modulates energy metabolism, and suggest alterations of neurotransmitter signaling, the latter finding being compatible with the neurodevelopmental effect of this xenoestrogen. In conclusion, long lasting metabolic effects of BPA could be characterized over 200 days, despite physiological (and thus metabolic changes

  1. Effects of prenatal exposure to chronic mild stress and toluene in rats

    DEFF Research Database (Denmark)

    Hougaard, K. S.; Andersen, Maud Bering; Hansen, A. M.

    2005-01-01

    The aim of the present study was to elucidate whether prenatal chronic stress, in combination with exposure to a developmental neurotoxicant, would increase effects in the offspring compared with the effects of either exposure alone. Development and neurobehavioral effects were investigated in fe...

  2. Morphologic and Immunologic effects in the rat after prenatal exposure to Cyclophosphamide

    NARCIS (Netherlands)

    Hessel EM; Verhoef A; van Loveren H; Piersma AH

    1993-01-01

    Several teratogens have been shown to alter postnatal immune function after prenatal exposure. Until now, relatively little is known about the perinatal maturation of the immune system and about the effects of teratogens on this process. Therefore, further research is necessary into the field of

  3. Biogenic amines, amino acids and regional blood flow in rat brain after prenatal irradiation

    International Nuclear Information System (INIS)

    Deroo, J.; Gerber, G.B.; Maes, J.

    1986-01-01

    Damage to nerve cells after prenatal irradiation could affect their later ability to function normally. The concentration of several biogenic amines and amino acids was therefore determined at different times after prenatal irradiation with 0.95 Gy on day 10, 12 or 15 of pregnancy. The offspring was sacrified 0.5, 1, 3 and 6 months after birth and the following structures were dissected: Cortex, hippocampus, striatum, thalamus, hypothalamus, cerebellum and medulla. Biogenic amines isolated by HPLC and detected electrochemically were: Dopamine, DOPA, DOPAC, epinephrine, norepinephrine, serotonin and hydroxyindolacetate. Amino acids converted to their dansyl derivatives and separated by HPLC were: Aspartate, glutamate, glutamine, gamma aminobutyrate and taurine. Many neurotransmitters were found increased in brain after prenatal irradiation, particularly on day 12 and 15 p.c. Marked changes were found for serotonin in several brain structures and for dopamin in striatum. An increase was also found in glutamate, glutamine and GABA. Studies on regional blood flow using injection of labelled 15 μ microspheres did not reveal significant alterations after prenatal irradiation. (orig.)

  4. Fibrogenic response of hepatic stellate cells in ovariectomised rats exposed to ketogenic diet.

    Science.gov (United States)

    Bobowiec, R; Wojcik, M; Jaworska-Adamu, J; Tusinska, E

    2013-02-01

    The discrepancy about the role of estrogens in hepatic fibrogenesis and lack of studies addressed of ketogenic diet (KD) on hepatic stellate cells (HSC), prompted us to investigate the activity of HSC in control, KD- and thioacetamide (TAA)-administrated rats with different plasma concentration of estradiol (E2). HSC were isolated by the collagenase perfusion methods and separated by the Percoll gradient centrifugation. After the 4(th) and 8(th) day of incubation, lysates of HSC and the media were collected for further analysis. The HSC derived from KD-rats released remarkably more transforming growth factor (TGF)-β1 than cells obtained from animals fed with a standard diet. The ovariectomy of KD-rats markedly intensified the secretion of this fibrogenic cytokine on the 8(th) day of incubation (201.33 ±1 7.15 pg/ml). In HSC of rats exposed to E2, the TGF-β1 concentration did not exceed 157 ± 34.39 pg/ml. In respect to the collagen type I, the HSC obtained from ovariectomised KD-rats released an augmented amount of this ECM protein after the 8(th) day of culture (1.83 ± 0.14 U/ml). In the same time, higher quantities of ASMA appeared in the KD rats (1.41 ± 0.3 pg/mg protein). Exposition of rats to E2 did not markedly decrease the amount of ASMA. In summary, KD was able to induce morphological and functional changes in HSC, especially derived from rats deprived of ovarian estrogens. However, the preservation of E2 in ovariectomised rats didn't substantially alter the activation of HSC.

  5. Changes in some Hematological Parameters and Thyroid Hormones in Rats Exposed to Pulsed Electromagnetic Field

    International Nuclear Information System (INIS)

    EL-Abiad, N.M.; Marzook, E.A.; EI-Aragi, G.M.

    2007-01-01

    In the present study pulsed electromagnetic spectrum was used to evaluate the effect of exposure on some biochemical and hematological parameters in male albino rats. Three groups of rats (10 each) were exposed to 10, 15, 20 pulses of electromagnetic spectrum 3 times per week for 3 weeks, the unexposed group was considered as the control group. At the end of experiment, serum levels of thyroid hormones triiodothryronine and thyroxine (T 3 ,T 4 ) and some hematological parameters were estimated. The hematological studies revealed that exposure to electromagnetic spectrum induced significant reduction in red blood cell count(RBC),and also in hemoglobin concentration(Hb), while reticulocytic count(Ret.) was elevated in the three exposed groups, platelets count was increased only on the second exposed group, while leukocytic count (WBC's), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MGH), mean corpuscular hemoglobin concentration (MCHC) were not affected, lymphocytic count was decreased only on the second exposed group, the impairment of thyroid functions was noticed by elevation of T 3 and T 4 in the three exposed groups

  6. Prenatal exposure to dietary fat induces changes in the transcriptional factors, TEF and YAP, which may stimulate differentiation of peptide neurons in rat hypothalamus.

    Directory of Open Access Journals (Sweden)

    Kinning Poon

    Full Text Available Gestational exposure to a high-fat diet (HFD stimulates the differentiation of orexigenic peptide-expressing neurons in the hypothalamus of offspring. To examine possible mechanisms that mediate this phenomenon, this study investigated the transcriptional factor, transcription enhancer factor-1 (TEF, and co-activator, Yes-associated protein (YAP, which when inactivated stimulate neuronal differentiation. In rat embryos and postnatal offspring prenatally exposed to a HFD compared to chow, changes in hypothalamic TEF and YAP and their relationship to the orexigenic peptide, enkephalin (ENK, were measured. The HFD offspring at postnatal day 15 (P15 exhibited in the hypothalamic paraventricular nucleus a significant reduction in YAP mRNA and protein, and increased levels of inactive and total TEF protein, with no change in mRNA. Similarly, HFD-exposed embryos at embryonic day 19 (E19 showed in whole hypothalamus significantly decreased levels of YAP mRNA and protein and TEF mRNA, and increased levels of inactive TEF protein, suggesting that HFD inactivates TEF and YAP. This was accompanied by increased density and fluorescence intensity of ENK neurons. A close relationship between TEF and ENK was suggested by the finding that TEF co-localizes with this peptide in hypothalamic neurons and HFD reduced the density of TEF/ENK co-labeled neurons, even while the number and fluorescence intensity of single-labeled TEF neurons were increased. Increased YAP inactivity by HFD was further evidenced by a decrease in number and fluorescence intensity of YAP-containing neurons, although the density of YAP/ENK co-labeled neurons was unaltered. Genetic knockdown of TEF or YAP stimulated ENK expression in hypothalamic neurons, supporting a close relationship between these transcription factors and neuropeptide. These findings suggest that prenatal HFD exposure inactivates both hypothalamic TEF and YAP, by either decreasing their levels or increasing their inactive

  7. Sexually dimorphic effects of a prenatal immune challenge on social play and vasopressin expression in juvenile rats

    Directory of Open Access Journals (Sweden)

    Taylor Patrick V

    2012-06-01

    Full Text Available Abstract Background Infectious diseases and inflammation during pregnancy increase the offspring’s risk for behavioral disorders. However, how immune stress affects neural circuitry during development is not well known. We tested whether a prenatal immune challenge interferes with the development of social play and with neural circuits implicated in social behavior. Methods Pregnant rats were given intraperitoneal injections of the bacterial endotoxin lipopolysaccharide (LPS – 100 μg /kg or saline on the 15th day of pregnancy. Offspring were tested for social play behaviors between postnatal days 26–40. Brains were harvested on postnatal day 45 and processed for arginine vasopressin (AVP mRNA in situ hybridization. Results In males, LPS treatment reduced the frequency of juvenile play behavior and reduced AVP mRNA expression in the medial amygdala and bed nucleus of the stria terminalis. These effects were not found in females. LPS treatment did not change AVP mRNA expression in the suprachiasmatic nucleus, paraventricular nucleus, or supraoptic nucleus of either sex, nor did it affect the sex difference in the size of the sexually dimorphic nucleus of the preoptic area. Conclusions Given AVP’s central role in regulating social behavior, the sexually dimorphic effects of prenatal LPS treatment on male AVP mRNA expression may contribute to the sexually dimorphic effect of LPS on male social play and may, therefore, increase understanding of factors that contribute to sex differences in social psychopathology.

  8. PHYTOTHERAPEUTIC EFFECT OF AVOCADOS AND SOYA AS DRUG ON HEART OF RATS EXPOSED TO GAMMA RADIATION

    International Nuclear Information System (INIS)

    OMRAN, M.F.; IBRAHIM, N.K.; ABU-ZIED, N.M.

    2008-01-01

    This study was planed to determine the role of single oral dose of avocados and soya in irradiated rats exposed to gamma radiation. the experimental animals were randomly divided into four groups; 12 rats for each. Group 1: kept as control. Group 2: rats received piascledine for 14 consecutive days. Group 3: rats submitted to whole body gamma rays (4 Gy). Group 4: rats received the same piascledine 14 days post-exposure to 4 Gy gamma radiation. The animals were weighed then dissected after one and fourteen days post-administration and the cardiac tissue and plasma were stored at 12 oC till used for biochemical analysis and kept in ice. The following parameters were determined: plasma total cholesterol, triacylglycerol, high density lipoprotein-cholesterol, low density lipoprotein-cholesterol, LDH, phospholipids, ALT, CPK and TBARS. In cardiac tissue, determinations of total cholesterol, triacylglycerol, phospholipids and TBARS were conducted.It can be concluded that administration of avocados and soy as natural drug (piascledine) post-irradiation in rats is a favorable modificator against the impaired physiological processes in animal body due to gamma irradiation

  9. Deep-body temperature changes in rats exposed to chronic centrifugation.

    Science.gov (United States)

    Oyama, J.; Platt, W. T.; Holland, V. B.

    1971-01-01

    Deep-body temperature was monitored continuously by implant biotelemetry in unrestrained rats before, during, and after exposure to prolonged and almost continuous centrifugation. Rats subjected to centrifugation for the first time at various G loads ranging up to 2.5 G show a rapid and significant fall in temperature which is sustained below normal levels for periods as long as 3 days. The magnitude of the temperature fall and the recovery time were generally proportional to the G load imposed. The initial fall and recovery of body temperature closely parallels the decrease in food consumption and to a lesser degree the decrease in body mass experienced by centrifuged rats. After exposure to 2 weeks of centrifugation, rats show either no change or only a small transient increase in temperature when decelerated to a lower G level or when returned to normal gravity. Rats repeatedly exposed to centrifugation consistently showed a smaller temperature response compared to the initial exposure. Implant temperature biotelemetry has been found to be a sensitive, reliable, and extremely useful technique for assessing the initial stress of centrifugation and in monitoring the time course of recovery and acclimation of rats to increase as well as*decrease G.

  10. The effect of melatonin on eye lens of rats exposed to ultraviolet radiation.

    Science.gov (United States)

    Anwar, M M; Moustafa, M A

    2001-05-01

    We investigated the influence of exogenously administered melatonin on adult rats eye lenses exposed to ultraviolet radiation (UV) A and B ranging from 356-254 nm irradiation at 8 microW/cm(2). Rats exposed to this range of UV for 15 min for one week showed a significant (PUV-radiation significantly (PUV irradiation, may be the main cause of lens opacification. Melatonin injection with radiation significantly reduced (Pradiation, SOD and GSH-Px enzyme activities increased significantly (PUV radiation was as effective as melatonin treatment concurrent with UV irradiation. We conclude that melatonin may protect the eye lens from the damaging effects of UV exposure, and its actions protect lens from oxidative stress, elevating Ca(2+) levels, which are considered as an important causes of cataractogenesis.

  11. In-vitro secretion of inhibin-like activity by Sertoli cells from normal and prenatally irradiated immature rats

    International Nuclear Information System (INIS)

    Ultee-van Gessel, A.M.; Leemborg, F.G.; Jong, F.H. de; Molen, H.J. van der

    1986-01-01

    The influence of in-vitro conditions on the production of inhibin by Sertoli cells from 21-day-old normal and prenatally irradiated rat testes was studied by measuring inhibin activity in culture media, using the suppression of the release of FSH from cultured rat pituitary cells. Sertoli cells secreted inhibin-like activity during at least 21 days of culture, and cells cultured at 37 0 C produced significantly more inhibin than those cultured at 32 0 C. The presence of fetal calf serum had no significant effect on inhibin production at 32 0 C, while at 37 0 C the production was decreased. The presence of ovine FSH stimulated inhibin secretion, while inhibin concentrations in Sertoli cell culture media were decreased after the addition of testosterone. Testosterone, added together with ovine FSH, suppressed inhibin secretion when compared with the levels found in the presence of FSH alone. The presence of spermatogenic cells decreased the release of inhibin. From these results it was concluded that both Sertoli cells isolated from normal immature rat testes and those from testes without spermatogenic cells can secrete inhibin-like activity in culture. A number of discrepancies with in-vivo observations was observed. (author)

  12. Prenatal ethanol exposure increases osteoarthritis susceptibility in female rat offspring by programming a low-functioning IGF-1 signaling pathway

    Science.gov (United States)

    Ni, Qubo; Tan, Yang; Zhang, Xianrong; Luo, Hanwen; Deng, Yu; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2015-10-01

    Epidemiological evidence indicates that osteoarthritis (OA) and prenatal ethanol exposure (PEE) are both associated with low birth weight but possible causal interrelationships have not been investigated. To investigate the effects of PEE on the susceptibility to OA in adult rats that experienced intrauterine growth retardation (IUGR), and to explore potential intrauterine mechanisms, we established the rat model of IUGR by PEE and dexamethasone, and the female fetus and 24-week-old adult offspring subjected to strenuous running for 6 weeks were sacrificed. Knee joints were collected from fetuses and adult offspring for histochemistry, immunohistochemistry and qPCR assays. Histological analyses and the Mankin score revealed increased cartilage destruction and accelerated OA progression in adult offspring from the PEE group compared to the control group. Immunohistochemistry showed reduced expression of insulin-like growth factor-1 (IGF-1) signaling pathway components. Furthermore, fetuses in the PEE group experienced IUGR but exhibited a higher postnatal growth rate. The expression of many IGF-1 signaling components was downregulated, which coincided with reduced amounts of type II collagen in the epiphyseal cartilage of fetuses in the PEE group. These results suggest that PEE enhances the susceptibility to OA in female adult rat offspring by down-regulating IGF-1 signaling and retarding articular cartilage development.

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

    Science.gov (United States)

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

    2015-07-01

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

  14. Cyclooxygenase-2-dependent bronchoconstriction in perfused rat lungs exposed to endotoxin.

    OpenAIRE

    Uhlig, S.; Nüsing, R.; von Bethmann, A.; Featherstone, R. L.; Klein, T.; Brasch, F.; Müller, K. M.; Ullrich, V.; Wendel, A.

    1996-01-01

    BACKGROUND: Lipopolysaccharides (LPS), widely used to study the mechanisms of gram-negative sepsis, increase airway resistance by constriction of terminal bronchioles. The role of the cyclooxygenase (COX) isoenzymes and their prostanoid metabolites in this process was studied. MATERIALS AND METHODS: Pulmonary resistance, the release of thromboxane (TX) and the expression of COX-2 mRNA were measured in isolated blood-free perfused rat lungs exposed to LPS. RESULTS: LPS induced the release of T...

  15. Associations between prenatal cigarette smoke exposure and externalized behaviors at school age among Inuit children exposed to environmental contaminants.

    Science.gov (United States)

    Desrosiers, Caroline; Boucher, Olivier; Forget-Dubois, Nadine; Dewailly, Eric; Ayotte, Pierre; Jacobson, Sandra W; Jacobson, Joseph L; Muckle, Gina

    2013-01-01

    Smoking during pregnancy is common among Inuit women from the Canadian Arctic. Yet prenatal cigarette smoke exposure (PCSE) is seen as a major risk factor for childhood behavior problems. Recent data also suggest that co-exposure to neurotoxic environmental contaminants can exacerbate the effects of PCSE on behavior. This study examined the association between PCSE and behavior at school age in a sample of Inuit children from Nunavik, Québec, where co-exposure to environmental contaminants is also an important issue. Interactions with lead (Pb) and mercury (Hg), two contaminants associated with behavioral problems, were also explored. Participants were 271 children (mean age=11.3years) involved in a prospective birth-cohort study. PCSE was assessed through maternal recall. Assessment of child behavior was obtained from the child's classroom teacher on the Teacher Report Form (TRF) and the Disruptive Behavior Disorders Rating Scale (DBD). Exposure to contaminants was assessed from umbilical cord and child blood samples. Other confounders were documented by maternal interview. After control for contaminants and confounders, PCSE was associated with increased externalizing behaviors and attention problems on the TRF and higher prevalence of attention deficit hyperactivity disorder (ADHD) assessed on the DBD. No interactions were found with contaminants. This study extends the existing empirical evidence linking PCSE to behavioral problems in school-aged children by reporting these effects in a population where tobacco use is normative rather than marginal. Co-exposure to Pb and Hg do not appear to exacerbate tobacco effects, suggesting that these substances act independently. © 2013. Published by Elsevier Inc. All rights reserved.

  16. Psychomotor Ability in Children Prenatally Exposed to Methylmercury: The 18-Month Follow-Up of Tohoku Study of Child Development.

    Science.gov (United States)

    Tatsuta, Nozomi; Murata, Katsuyuki; Iwai-Shimada, Miyuki; Yaginuma-Sakurai, Kozue; Satoh, Hiroshi; Nakai, Kunihiko

    2017-05-01

    Fish contain nutrients essential to the developing fetal brain, but they are contaminated with methylmercury. The Tohoku Study of Child Development, now underway in the Sanriku coastal area of Miyagi prefecture, Japan, follows mother-child pairs to examine the risks and benefits of fish consumption during pregnancy, especially the effects of prenatal exposures to methylmercury, selenium, and docosahexaenoic acid (DHA) on child neurodevelopment. Children aged 18 months were administered the Bayley Scales of Infant Development second edition (BSID-II) and Kyoto Scale of Psychological Development (KSPD) in 2004-2008. Complete data of cord-blood total mercury (THg), cord-plasma selenium, maternal-plasma DHA, the above test scores, and confounders for 566 mother-child pairs were available. The median cord-blood THg level was 15.7 (range, 2.7-96.1) ng/g. Since the BSID-II and KSPD scores were significantly lower in the 285 boys than in the 281 girls, analyses were conducted separately. The Psychomotor Development Index (PDI) of BSID-II was significantly correlated with cord-blood THg only in the boys, and significance of the association remained unchanged after adjusting for possible confounders; i.e., a 10-fold increase in cord-blood THg was associated with a 8.3-point decrease in the score of the PDI. Other significant correlations of THg were not seen in the boys or girls. Selenium and DHA showed no significant correlations with the BSID-II or KSPD scores in either sex. In conclusion, intrauterine methylmercury exposure may affect psychomotor development, and boys appear to be more vulnerable to the exposure than girls.

  17. Prenatal dietary load of Maillard reaction products combined with postnatal Coca-Cola drinking affects metabolic status of female Wistar rats.

    Science.gov (United States)

    Gurecká, Radana; Koborová, Ivana; Janšáková, Katarína; Tábi, Tamás; Szökő, Éva; Somoza, Veronika; Šebeková, Katarína; Celec, Peter

    2015-04-01

    To assess the impact of prenatal exposure to Maillard reaction products (MRPs) -rich diet and postnatal Coca-Cola consumption on metabolic status of female rats. Diet rich in MRPs and consumption of saccharose/fructose sweetened soft drinks is presumed to impose increased risk of development of cardiometabolic afflictions, such as obesity or insulin resistance. At the first day of pregnancy, 9 female Wistar rats were randomized into two groups, pair-fed either with standard rat chow (MRP-) or MRPs-rich diet (MRP+). Offspring from each group of mothers was divided into two groups and given either water (Cola-) or Coca-Cola (Cola+) for drinking ad libitum for 18 days. Oral glucose tolerance test was performed, and circulating markers of inflammation, oxidative stress, glucose and lipid metabolism were assessed. MRP+ groups had higher weight gain, significantly so in the MRP+/Cola- vs MRP-/Cola-. Both prenatal and postnatal intervention increased carboxymethyllysine levels and semicarbazide-sensitive amine oxidase activity, both significantly higher in MRP+/Cola + than in MRP-/Cola-. Total antioxidant capacity was lower in MRP+ groups, with significant decrease in MRP+/Cola + vs MRP-/Cola+. Rats drinking Coca-Cola had higher insulin, homeostatic model assessment of insulin resistance, heart rate, advanced oxidation of protein products, triacylglycerols, and oxidative stress markers measured as thiobarbituric acid reactive substances compared to rats drinking water, with no visible effect of MRPs-rich diet. Metabolic status of rats was affected both by prenatal and postnatal dietary intervention. Our results suggest that combined effect of prenatal MRPs load and postnatal Coca-Cola drinking may play a role in development of metabolic disorders in later life.

  18. Prenatal cigarette smoke exposure: Pregnancy outcome and gestational changes in plasma nicotine concentration, hematocrit, and carboxyhemoglobin in a newly standardized rat model

    International Nuclear Information System (INIS)

    Farkas, Svetlana; Hussein, Jabeen; Ariano, Robert E.; Sitar, Daniel S.; Hasan, Shabih U.

    2006-01-01

    Epidemiological studies support an association between perinatal cigarette smoke (CS) exposure and a number of severe pre- and postnatal complications. However, the mechanisms through which CS enhances such risks largely remain unknown. One of the reasons for our inability to discover such mechanisms has been the unavailability of a clinically relevant and physiologically concordant animal model. A number of studies have previously used nicotine (Nic) as surrogate for CS. We sought to (1) establish the amount of CS exposure to achieve plasma Nic concentrations observed among moderate to heavy smokers (20-60 ng/ml) (2) investigate the temporal changes in plasma Nic concentrations, carboxyhemoglobin, and hematocrit with advancing pregnancy, and (3) elucidate the effects of CS exposure on pregnancy outcome. Pregnant Sprague-Dawley rats were exposed to various doses of CS or room air (Sham) from days 6 to 21 of gestation. Exposure to 6000 ml/day of CS led to very high plasma Nic concentrations and increased maternal and fetal mortality (P < 0.001). The plasma Nic concentrations remained higher than those observed in moderate smokers until the CS dose was reduced to 1000 ml/day and showed dose-dependent temporal changes with advancing gestational age. Significant increases in carboxyhemoglobin and hematocrit were observed in the CS group as compared with the Sham group (P < 0.001). In addition, prenatally CS exposed fetuses had lower birth weight as compared with the Sham group (P = 0.04). Our current study establishes a newly standardized and physiologically relevant model to investigate the mechanisms of CS-mediated adverse effects during the critical period of fetal development

  19. Placental and Fetal Disposition of Mercuric Ions in Rats Exposed to Methylmercury: Role of Mrp2

    Science.gov (United States)

    Bridges, Christy C.; Joshee, Lucy; Zalups, Rudolfs K.

    2012-01-01

    Methylmercury is a prevalent environmental toxicant that can have deleterious effects on a developing fetus. Previous studies indicate that the multidrug resistance-associated protein 2 (Mrp2) is involved in renal and hepatic export of mercuric ions. Therefore, we hypothesize that Mrp2 is also involved in export of mercuric ions from placental trophoblasts and fetal tissues. To test this hypothesis, we assessed the disposition of mercuric ions in pregnant Wistar and TR– (Mrp2-deficient) rats exposed to a single dose of methylmercury. The amount of mercury in renal tissues (cortex and outer stripe of outer medulla), liver, blood, amniotic fluid, uterus, placentas and fetuses was significantly greater in TR– rats than in Wistar rats. Urinary and fecal elimination of mercury was greater in Wistar dams than in TR– dams. Thus, our findings suggest that Mrp2 may be involved in the export of mercuric ions from maternal and fetal organs following exposure to methylmercury. PMID:23059061

  20. Changes in operant behavior of rats exposed to lead at the accepted no-effect level.

    Science.gov (United States)

    Gross-Selbeck, E; Gross-Selbeck, M

    1981-11-01

    After weaning, male and female Wistar rats were fed a daily diet containing 1 g lead acetate/kg food until a level of about 20 micrograms/100 mL blood was obtained. The male rats were subjected to the different behavioral tests, whereas the females were mated to untreated males and further exposed until weaning of the offspring. Behavioral testing of the male offspring was performed between 3 and 4 months of age. General behavior of both groups was tested in the open-field task including locomotion, local movements, and emotionality. The conditioned instrumental behavior was tested in the Skinner box from simple to more complex programs. The blood-lead level was measured by flameless atomic absorption spectrometry. No behavioral changes became apparent in the open-field task and in the preliminary operant training. In the more complex programs (DRH = Differential Reinforcement of High Rates), the rats exposed to lead after weaning showed slight changes of DRH performance. By contrast, in pre- and neonatally exposed animals, DRH performance was significantly increased, although blood-lead levels had returned to normal at the time of testing. A comparison of lead effects in animals to possible effects in man is discussed in this paper, and it is concluded that lead exposure to man at doses which presently are suggested to be innocuous may result in subclinical functional changes of the central nervous system.

  1. Adiponectin alleviates genioglossal mitochondrial dysfunction in rats exposed to intermittent hypoxia.

    Directory of Open Access Journals (Sweden)

    Hanpeng Huang

    Full Text Available Genioglossal dysfunction is involved in the pathophysiology of obstructive sleep apnea hypoxia syndrome (OSAHS characterized by nocturnal chronic intermittent hypoxia (CIH. The pathophysiology of genioglossal dysfunction and possible targeted pharmacotherapy for alleviation of genioglossal injury in CIH require further investigation.Rats in the control group were exposed to normal air, while rats in the CIH group and CIH+adiponectin (AD group were exposed to the same CIH condition (CIH 8 hr/day for 5 successive weeks. Furthermore, rats in CIH+AD group were administrated intravenous AD supplementation at the dosage of 10 µg, twice a week for 5 consecutive weeks. We found that CIH-induced genioglossus (GG injury was correlated with mitochondrial dysfunction, reduction in the numbers of mitochondrias, impaired mitochondrial ultrastructure, and a reduction in type I fibers. Compared with the CIH group, impaired mitochondrial structure and function was significantly improved and a percentage of type I fiber was elevated in the CIH+AD group. Moreover, compared with the control group, the rats' GG in the CIH group showed a significant decrease in phosphorylation of LKB1, AMPK, and PGC1-α, whereas there was significant rescue of such reduction in phosphorylation within the CIH+AD group.CIH exposure reduces mitochondrial biogenesis and impairs mitochondrial function in GG, while AD supplementation increases mitochondrial contents and alleviates CIH-induced mitochondrial dysfunction possibly through the AMPK pathway.

  2. Modulating efficacy of foeniculum vulgare mill. essential oil in rats exposed to oxidative stress

    International Nuclear Information System (INIS)

    Nada, A.S.; Amin, N.E.; Ahmed, O.M.; Abdel-Reheim, E.S.; Ali, M.M.

    2011-01-01

    This study was conducted to evaluate the modulating efficacy of prolonged oral administration of Foeniculum vulgare Mill. essential oil (FEO) against gamma irradiation-induced oxidative stress in male rats. To achieve the ultimate goal of this study, 32 male Swiss Albino rats were divided into 4 groups, each consists of 8 rats: Group 1 was normal control group, group 2 irradiated with a single dose (6.5 Gy), and sacrificed 7 days irradiation, group 3 received FEO (250 mg/kg body wt) for 28 successive days by intra-gastric gavages and group 4 received treatment of FEO for 21 days, then was exposed to gamma-radiation (6.5 Gy), followed by treatment with FEO 7 days later to be 28 days as group 3. Sacrifice of all animals was performed after 28 days from the beginning of the experiment. Liver and kidney glutathione (GSH) contents; lipid peroxidation (TBARS) and metallothioneins (MTs) levels were determined. In addition, levels of some trace elements (Fe, Cu, Zn and Se) in liver and kidney tissues were also estimated. Rats exposed to gamma radiation exhibited a profound elevation in TBARS and MTs level of liver and kidney tissues. Noticeable drop in liver and kidney glutathione contents were also observed. Tissue organs displayed some changes in trace element concentrations. Rats treated with fennel oil before and after whole body gamma irradiation showed significant modulation in the activity of antioxidants (GSH, MTs). FEO was also effective in minimizing the radiation-induced increase in TBARS as well as trace elements alteration in some tissue organs comparing with irradiated control rats. It could be concluded that FEO exerts a beneficial protective potential against radiation-induced biochemical perturbations and oxidative stress

  3. Prenatal alcohol exposure results in long-term serotonin neuron deficits in female rats: modulatory role of ovarian steroids.

    Science.gov (United States)

    Sliwowska, Joanna H; Song, Hyun Jung; Bodnar, Tamara; Weinberg, Joanne

    2014-01-01

    Previous studies on male rodents found that prenatal alcohol exposure (PAE) decreases the number of serotonin immunoreactive (5-HT-ir) neurons in the brainstem. However, data on the effects of PAE in females are lacking. In light of known sex differences in responsiveness of the 5-HT system and known effects of estrogen (E2 ) and progesterone (P4 ) in the brain, we hypothesized that sex steroids will modulate the adverse effects of PAE on 5-HT neurons in adult females. Adult females from 3 prenatal groups (Prenatal alcohol-exposed [PAE], Pair-fed [PF], and ad libitum-fed Controls [C]) were ovariectomized (OVX), with or without hormone replacement, or underwent Sham OVX. 5-HT-ir cells were examined in key brainstem areas. Our data support the hypothesis that PAE has long-term effects on the 5-HT system of females and that ovarian steroids have a modulatory role in these effects. Intact (Sham OVX) PAE females had marginally lower numbers of 5-HT-ir neurons in the dorsal raphe nucleus of the brainstem compared with PF and C females. This marginal difference became significant following removal of hormones by OVX. Replacement with E2 restored the number of 5-HT-ir neurons in PAE females to control levels, while P4 reversed the effects of E2 . Importantly, despite these differential responses of the 5-HT system to ovarian steroids, there were no differences in E2 and P4 levels among prenatal treatment groups. These data demonstrate long-term, adverse effects of PAE on the 5-HT system of females, as well as differential sensitivity of PAE compared with control females to the modulatory effects of ovarian steroids on 5-HT neurons. Our findings have important implications for understanding sex differences in 5-HT dysfunction in depression/anxiety disorders and the higher rates of these mental health problems in individuals with fetal alcohol spectrum disorder. Copyright © 2013 by the Research Society on Alcoholism.

  4. Inhibition of Mammary Cancer Progression in Fetal Alcohol Exposed Rats by β-Endorphin Neurons.

    Science.gov (United States)

    Zhang, Changqing; Franklin, Tina; Sarkar, Dipak K

    2016-01-01

    Fetal alcohol exposure (FAE) increases the susceptibility to carcinogen-induced mammary cancer progression in rodent models. FAE also decreases β-endorphin (β-EP) level and causes hyperstress response, which leads to inhibition of immune function against cancer. Previous studies have shown that injection of nanosphere-attached dibutyryl cyclic adenosine monophosphate (dbcAMP) into the third ventricle increases the number of β-EP neurons in the hypothalamus. In this study, we assessed the therapeutic potential of stress regulation using methods to increase hypothalamic levels of β-EP, a neuropeptide that inhibits stress axis activity, in treatment of carcinogen-induced mammary cancer in fetal alcohol exposed rats. Fetal alcohol exposed and control Sprague Dawley rats were given a dose of N-Nitroso-N-methylurea (MNU) at postnatal day 50 to induce mammary cancer growth. Upon detection of mammary tumors, the animals were either transplanted with β-EP neurons or injected with dbcAMP-delivering nanospheres into the hypothalamus to increase β-EP peptide production. Spleen cytokines were detected using reverse transcription polymerase chain reaction assays. Metastasis study was done by injecting mammary cancer cells MADB106 into jugular vein of β-EP-activated or control fetal alcohol exposed animals. Both transplantation of β-EP neurons and injection of dbcAMP-delivering nanospheres inhibited MNU-induced mammary cancer growth in control rats, and reversed the effect of FAE on the susceptibility to mammary cancer. Similar to the previously reported immune-enhancing and stress-suppressive effects of β-EP transplantation, injection of dbcAMP-delivering nanospheres increased the levels of interferon-γ and granzyme B and decreased the levels of epinephrine and norepinephrine in fetal alcohol exposed rats. Mammary cancer cell metastasis study also showed that FAE increased incidence of lung tumor retention, while β-EP transplantation inhibited lung tumor growth in

  5. Thioredoxin and impaired spatial learning and memory in the rats exposed to intermittent hypoxia

    Institute of Scientific and Technical Information of China (English)

    YANG Xiu-hong; LIU Hui-guo; LIU Xue; CHEN Jun-nan

    2012-01-01

    Background Obstructive sleep apnea (OSA) can cause cognitive dysfunction and may be a reversible cause of cognitive loss in patients with Alzheimer's disease (AD).Chronic exposure to intermittent hypoxia (IH),such as encountered in OSA,is marked by neurodegenerative changes in rat brain.We investigated the change of thioredoxin (Trx),spatial learning and memory in rats exposed to chronic intermittent hypoxia (CIH).Methods Forty healthy male Sprague-Dawley (SD) rats were randomly divided into four groups of ten each:a CIH+normal saline (CIH+NS group),a N-acetylcystein-treated CIH (CIH+NAC) group,a sham CIH group (sham CIH+NS),and a sham NAC-treated sham CIH (CIH+NAC) group.Spatial learning and memory in each group was assessed with the Morris water maze.Real-time PCR and Western blotting were used to examine mRNA and protein expression of Trx in the hippocampus tissue.The terminal deoxynucleotidyl transferase-mediated dUTP-nick end-labeling (TUNEL) method was used to detect the apoptotic cells of the hippocampus CA1 region.Results ClH-rats showed impaired spatial learning and memory in the Morris water maze,including longer mean latencies for the target platform,reduced numbers of passes over the previous target platform and a smaller percentage of time spent in the target quadrant.Trx mRNA and protein levels were significantly decreased in the CIH-hippocampus,meanwhile,an elevated apoptotic index revealed apoptosis of hippocampal neurons of rats exposed to CIH.The rats,which acted better in the Morris water maze,showed higher levels of the Trx mRNA and protein in the hippocampus;apoptotic index of the neurons in the hippocampus of each group was negatively correlated with the Trx mRNA and protein levels.Conclusion The Trx deficit likely plays an important role in the impaired spatial learning and memory in the rats exposed to CIH and may work through the apoptosis of neurons in the hippocampus.

  6. Buspirone before prenatal stress protects against adverse effects of stress on emotional and inflammatory pain-related behaviors in infant rats: age and sex differences.

    Science.gov (United States)

    Butkevich, Irina P; Mikhailenko, Viktor A; Vershinina, Elena A; Otellin, Vladimir A; Aloisi, Anna Maria

    2011-10-24

    Prenatal stress strengthens tonic pain and provokes depression. The serotoninergic system is involved in these processes. We recently showed that maternal buspirone, a 5-HT1A receptor agonist, protects against the adverse effects of in utero stress on depression and pain in adult rat offspring. Using a similar maternal treatment with buspirone, we focus here on the infant stage, which is important for the correction of prenatal abnormalities. Maternal buspirone before restraint stress during the last week of pregnancy decreased the time of immobility in the forced swim test in the infant offspring. Prenatal stress increased formalin-induced pain in the second part of the time-course of the response to formalin in males of middle infancy but in the first part of the response in males of late infancy. The effect was reversed by maternal buspirone. Pain dominated in males of both middle and late infancy but the time-course of formalin pain in infant females revealed a slower development of the processes. The results show that the time-course of formalin-induced pain in infant rats reacts to prenatal stress in an age-dependent and sexually dimorphic manner. Our finding of opposite influences of prenatal stress and buspirone before prenatal stress on formalin-induced pain during the interphase indicates that functional maturity of the descending serotonergic inhibitory system occurs in late infancy males (11-day-olds), and 5-HT1A receptors participate in this process. The data provide evidence that maternal treatment with buspirone prior to stress during pregnancy alleviates depression-like and tonic pain-related behaviors in the infant offspring. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. Effects of chronic prenatal MK-801 treatment on object recognition, cognitive flexibility, and drug-induced locomotor activity in juvenile and adult rat offspring.

    Science.gov (United States)

    Gallant, S; Welch, L; Martone, P; Shalev, U

    2017-06-15

    Patients with schizophrenia display impaired cognitive functioning and increased sensitivity to psychomimetic drugs. The neurodevelopmental hypothesis of schizophrenia posits that disruption of the developing brain predisposes neural networks to lasting structural and functional abnormalities resulting in the emergence of such symptoms in adulthood. Given the critical role of the glutamatergic system in early brain development, we investigated whether chronic prenatal exposure to the glutamate NMDA receptor antagonist, MK-801, induces schizophrenia-like behavioural and neurochemical changes in juvenile and adult rats. Pregnant Long-Evans rats were administered saline or MK-801 (0.1mg/kg; s.c.) at gestation day 7-19. Object recognition memory and cognitive flexibility were assessed in the male offspring using a novel object preference task and a maze-based set-shifting procedure, respectively. Locomotor-activating effects of acute amphetamine and MK-801 were also assessed. Adult, but not juvenile, prenatally MK-801-treated rats failed to show novel object preference after a 90min delay, suggesting that object recognition memory may have been impaired. In addition, the set-shifting task revealed impaired acquisition of a new rule in adult prenatally MK-801-treated rats compared to controls. This deficit appeared to be driven by regression to the previously learned behaviour. There were no significant differences in drug-induced locomotor activity in juvenile offspring or in adult offspring following acute amphetamine challenges. Unexpectedly, MK-801-induced locomotor activity in adult prenatally MK-801-treated rats was lower compared to controls. Glutamate transmission dysfunction during early development may modify behavioural parameters in adulthood, though these parameters do not appear to model deficits observed in schizophrenia. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Fetal rat metabonome alteration by prenatal caffeine ingestion probably due to the increased circulatory glucocorticoid level and altered peripheral glucose and lipid metabolic pathways

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yansong [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan University, Wuhan, 430071 (China); Xu, Dan [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan University, Wuhan, 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan, 430071 (China); Feng, Jianghua, E-mail: jianghua.feng@xmu.edu.cn [Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, 430071 (China); Department of Electronic Science, Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance, Xiamen University, Xiamen, 361005 (China); Kou, Hao; Liang, Gai [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan University, Wuhan, 430071 (China); Yu, Hong; He, Xiaohua; Zhang, Baifang; Chen, Liaobin [Research Center of Food and Drug Evaluation, Wuhan University, Wuhan, 430071 (China); Magdalou, Jacques [UMR 7561 CNRS-Nancy Université, Faculté de Médicine, Vandoeuvre-lès-Nancy (France); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan University, Wuhan, 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan, 430071 (China)

    2012-07-15

    The aims of this study were to clarify the metabonome alteration in fetal rats after prenatal caffeine ingestion and to explore the underlying mechanism pertaining to the increased fetal circulatory glucocorticoid (GC). Pregnant Wistar rats were daily intragastrically administered with different doses of caffeine (0, 20, 60 and 180 mg/kg) from gestational days (GD) 11 to 20. Metabonome of fetal plasma and amniotic fluid on GD20 were analyzed by {sup 1}H nuclear magnetic resonance-based metabonomics. Gene and protein expressions involved in the GC metabolism, glucose and lipid metabolic pathways in fetal liver and gastrocnemius were measured by real-time RT-PCR and immunohistochemistry. Fetal plasma metabonome were significantly altered by caffeine, which presents as the elevated α- and β‐glucose, reduced multiple lipid contents, varied apolipoprotein contents and increased levels of a number of amino acids. The metabonome of amniotic fluids showed a similar change as that in fetal plasma. Furthermore, the expressions of 11β-hydroxysteroid dehydrogenase 2 (11β-HSD-2) were decreased, while the level of blood GC and the expressions of 11β-HSD-1 and glucocorticoid receptor (GR) were increased in fetal liver and gastrocnemius. Meanwhile, the expressions of insulin-like growth factor 1 (IGF-1), IGF-1 receptor and insulin receptor were decreased, while the expressions of adiponectin receptor 2, leptin receptors and AMP-activated protein kinase α2 were increased after caffeine treatment. Prenatal caffeine ingestion characteristically change the fetal metabonome, which is probably attributed to the alterations of glucose and lipid metabolic pathways induced by increased circulatory GC, activated GC metabolism and enhanced GR expression in peripheral metabolic tissues. -- Highlights: ► Prenatal caffeine ingestion altered the metabonome of IUGR fetal rats. ► Caffeine altered the glucose and lipid metabolic pathways of IUGR fetal rats. ► Prenatal caffeine

  9. Fetal rat metabonome alteration by prenatal caffeine ingestion probably due to the increased circulatory glucocorticoid level and altered peripheral glucose and lipid metabolic pathways

    International Nuclear Information System (INIS)

    Liu, Yansong; Xu, Dan; Feng, Jianghua; Kou, Hao; Liang, Gai; Yu, Hong; He, Xiaohua; Zhang, Baifang; Chen, Liaobin; Magdalou, Jacques; Wang, Hui

    2012-01-01

    The aims of this study were to clarify the metabonome alteration in fetal rats after prenatal caffeine ingestion and to explore the underlying mechanism pertaining to the increased fetal circulatory glucocorticoid (GC). Pregnant Wistar rats were daily intragastrically administered with different doses of caffeine (0, 20, 60 and 180 mg/kg) from gestational days (GD) 11 to 20. Metabonome of fetal plasma and amniotic fluid on GD20 were analyzed by 1 H nuclear magnetic resonance-based metabonomics. Gene and protein expressions involved in the GC metabolism, glucose and lipid metabolic pathways in fetal liver and gastrocnemius were measured by real-time RT-PCR and immunohistochemistry. Fetal plasma metabonome were significantly altered by caffeine, which presents as the elevated α- and β‐glucose, reduced multiple lipid contents, varied apolipoprotein contents and increased levels of a number of amino acids. The metabonome of amniotic fluids showed a similar change as that in fetal plasma. Furthermore, the expressions of 11β-hydroxysteroid dehydrogenase 2 (11β-HSD-2) were decreased, while the level of blood GC and the expressions of 11β-HSD-1 and glucocorticoid receptor (GR) were increased in fetal liver and gastrocnemius. Meanwhile, the expressions of insulin-like growth factor 1 (IGF-1), IGF-1 receptor and insulin receptor were decreased, while the expressions of adiponectin receptor 2, leptin receptors and AMP-activated protein kinase α2 were increased after caffeine treatment. Prenatal caffeine ingestion characteristically change the fetal metabonome, which is probably attributed to the alterations of glucose and lipid metabolic pathways induced by increased circulatory GC, activated GC metabolism and enhanced GR expression in peripheral metabolic tissues. -- Highlights: ► Prenatal caffeine ingestion altered the metabonome of IUGR fetal rats. ► Caffeine altered the glucose and lipid metabolic pathways of IUGR fetal rats. ► Prenatal caffeine ingestion

  10. Protective Effects of Hydroalcoholic Extract of Nasturtium officinale on Rat Blood Cells Exposed to Arsenic

    Directory of Open Access Journals (Sweden)

    Felor Zargari

    2015-06-01

    Full Text Available Background: Arsenic is one of the most toxic metalloids. Anemia and leukopenia are common results of poisoning with arsenic, which may happen due to a direct hemolytic or cytotoxic effect on blood cells. The aim of this study was to examine the effects of hydroalcoholic extract of Nasturtium officinale on blood cells and antioxidant enzymes in rats exposed to sodium (metaarsenite. Methods: 32 Male Sprague Dawley rats were randomly divided into four groups; Group I (normal healthy rats, Group II (treated with 5.5mg/kg of body weight of NaAsO2, Group III (treated with 500mg/kg of body weight of hydro-alcoholic extract of N. officinale, and Group IV (treated with group II and III supplementations. Blood samples were collected and red blood cell, white blood cell, hematocrit, hemoglobin, platelet, total protein and albumin levels and total antioxidant capacity were measured. Data was analyzed with Mann-Whitney U test. Results: WBC, RBC and Hct were decreased in the rats exposed to NaAsO2 (p<0.05. A significant increase was seen in RBC and Hct after treatment with the plant extract (p<0.05. There was no significant decrease in serum albumin and total protein in the groups exposed to NaAsO2 compared to the group I, but NaAsO2 decreased the total antioxidant capacity, significantly. Conclusion: The Nasturtium officinale extract have protective effect on arsenic-induced damage of blood cells.

  11. Ototoxicity in rats exposed to ethylbenzene and to two technical xylene vapours for 13 weeks

    Energy Technology Data Exchange (ETDEWEB)

    Gagnaire, Francois; Langlais, Cristina; Grossmann, Stephane; Wild, Pascal [Institut National de Recherche et de Securite, Departement Polluants et Sante, Vandoeuvre Cedex (France)

    2007-02-15

    Male Sprague-Dawley rats were exposed to ethylbenzene (200, 400, 600 and 800 ppm) and to two mixed xylenes (250, 500, 1,000 and 2,000 ppm total compounds) by inhalation, 6 h/day, 6 days/week for 13 weeks and sacrificed for morphological investigation 8 weeks after the end of exposure. Brainstem auditory-evoked responses were used to determine auditory thresholds at different frequencies. Ethylbenzene produced moderate to severe ototoxicity in rats exposed to the four concentrations studied. Increased thresholds were observed at 2, 4, 8 and 16 kHz in rats exposed to 400, 600 and 800 ppm ethylbenzene. Moderate to severe losses of outer hair cells of the organ of Corti occurred in animals exposed to the four concentrations studied. Exposure to both mixed xylenes produced ototoxicity characterized by increased auditory thresholds and losses of outer hair cells. Ototoxicity potentiation caused by ethylbenzene was observed. Depending on the mixed xylene studied and the area of the concentration-response curves taken into account, the concentrations of ethylbenzene in mixed xylenes necessary to cause a given ototoxicity were 1.7-2.8 times less than those of pure ethylbenzene. Given the high ototoxicity of ethylbenzene, the safety margin of less or equal to two (LOAEL/TWA) might be too small to protect workers from the potential risk of ototoxicity. Moreover, the enhanced ototoxicity of ethylbenzene and para-xylene observed in mixed xylenes should encourage the production of mixed xylenes with the lowest possible concentrations of ethylbenzene and para-xylene. (orig.)

  12. Ototoxicity in rats exposed to ethylbenzene and to two technical xylene vapours for 13 weeks.

    Science.gov (United States)

    Gagnaire, François; Langlais, Cristina; Grossmann, Stéphane; Wild, Pascal

    2007-02-01

    Male Sprague-Dawley rats were exposed to ethylbenzene (200, 400, 600 and 800 ppm) and to two mixed xylenes (250, 500, 1,000 and 2,000 ppm total compounds) by inhalation, 6 h/day, 6 days/week for 13 weeks and sacrificed for morphological investigation 8 weeks after the end of exposure. Brainstem auditory-evoked responses were used to determine auditory thresholds at different frequencies. Ethylbenzene produced moderate to severe ototoxicity in rats exposed to the four concentrations studied. Increased thresholds were observed at 2, 4, 8 and 16 kHz in rats exposed to 400, 600 and 800 ppm ethylbenzene. Moderate to severe losses of outer hair cells of the organ of Corti occurred in animals exposed to the four concentrations studied. Exposure to both mixed xylenes produced ototoxicity characterized by increased auditory thresholds and losses of outer hair cells. Ototoxicity potentiation caused by ethylbenzene was observed. Depending on the mixed xylene studied and the area of the concentration-response curves taken into account, the concentrations of ethylbenzene in mixed xylenes necessary to cause a given ototoxicity were 1.7-2.8 times less than those of pure ethylbenzene. Given the high ototoxicity of ethylbenzene, the safety margin of less or equal to two (LOAEL/TWA) might be too small to protect workers from the potential risk of ototoxicity. Moreover, the enhanced ototoxicity of ethylbenzene and para-xylene observed in mixed xylenes should encourage the production of mixed xylenes with the lowest possible concentrations of ethylbenzene and para-xylene.

  13. Memantine prevents cardiomyocytes nuclear size reduction in the left ventricle of rats exposed to cold stress

    Directory of Open Access Journals (Sweden)

    Adriano Meneghini

    2009-01-01

    Full Text Available OBJECTIVES: Memantine is an N-methyl-d-aspartate (NMDA glutamate receptor antagonist used to treat Alzheimer's disease. Previous studies have suggested that receptor blockers act as neuroprotective agents; however, no study has specifically investigated the impact that these drugs have on the heart. We sought to evaluate the effects of memantine on nuclear size reduction in cardiac cells exposed to cold stress. METHOD: We used male EPM-Wistar rats (n=40 divided into 4 groups: 1 Matched control (CON; 2 Memantine-treated rats (MEM; 3 Rats undergoing induced hypothermia (IH and 4 Rats undergoing induced hypothermia that were also treated with memantine (IHM. Animals in the MEM and IHM groups were treated by oral gavage administration of 20 mg/kg/day memantine over an eight-day period. Animals in the IH and IHM groups were submitted to 4 hours of hypothermia in a controlled environment with a temperature of - 8ºC on the last day of the study. RESULTS: The MEM group had the largest cardiomyocyte nuclear size (151 ± 3.5 μm³ vs. CON: 142 ± 2.3 μm³; p<0.05, while the IH group had the smallest mean value of nuclear size. The nuclear size of the IHM group was preserved (125 ± 2.9 μm³ compared to the IH group (108 ± 1.7 μm³; p<0.05. CONCLUSION: Memantine prevented the nuclear size reduction of cardiomyocytes in rats exposed to cold stress.

  14. Prenatal low-dose methylmercury exposure impairs neurite outgrowth and synaptic protein expression and suppresses TrkA pathway activity and eEF1A1 expression in the rat cerebellum

    Energy Technology Data Exchange (ETDEWEB)

    Fujimura, Masatake, E-mail: fujimura@nimd.go.jp [Department of Basic Medical Sciences, National Institute for Minamata Disease, Kumamoto (Japan); Usuki, Fusako [Department of Clinical Medicine, National Institute for Minamata Disease, Kumamoto (Japan); Cheng, Jinping; Zhao, Wenchang [School of Environmental Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240 (China)

    2016-05-01

    Methylmercury (MeHg) is a highly neurotoxic environmental chemical that can cause developmental impairments. Human fetuses and neonates are particularly susceptible to MeHg toxicity; however, the mechanisms governing its effects in the developing brain are unclear. In the present study, we investigated the effects of prenatal and lactational MeHg exposure on the developing cerebellum in rats. We demonstrated that exposure to 5 ppm MeHg decreased postnatal expression of pre- and postsynaptic proteins, suggesting an impairment in synaptic development. MeHg exposure also reduced neurite outgrowth, as shown by a decrease in the expression of the neurite marker neurofilament H. These changes were not observed in rats exposed to 1 ppm MeHg. In order to define the underlying mechanism, we investigated the effects of MeHg exposure on the tropomyosin receptor kinase (Trk) A pathway, which plays important roles in neuronal differentiation and synapse formation. We demonstrated suppression of the TrkA pathway on gestation day 20 in rats exposed to 5 ppm MeHg. In addition, down-regulation of eukaryotic elongation factor 1A1 (eEF1A1) was observed on postnatal day 1. eEF1A1 knockdown in differentiating PC12 cells impaired neurite outgrowth and synaptic protein expression, similar to the results of MeHg exposure in the cerebellum. These results suggest that suppression of the TrkA pathway and subsequent decreases in eEF1A1 expression induced by prenatal exposure to MeHg may lead to reduced neurite outgrowth and synaptic protein expression in the developing cerebellum. - Highlights: • Prenatal exposure to MeHg decreased postnatal expression of synaptic proteins. • MeHg exposure also reduced neurite outgrowth postnatally. • Suppression of the TrkA pathway and eEF1A1 expression was induced by MeHg exposure. • eEF1A1 knockdown impaired neurite outgrowth and synaptic protein expression.

  15. Prenatal low-dose methylmercury exposure impairs neurite outgrowth and synaptic protein expression and suppresses TrkA pathway activity and eEF1A1 expression in the rat cerebellum

    International Nuclear Information System (INIS)

    Fujimura, Masatake; Usuki, Fusako; Cheng, Jinping; Zhao, Wenchang

    2016-01-01

    Methylmercury (MeHg) is a highly neurotoxic environmental chemical that can cause developmental impairments. Human fetuses and neonates are particularly susceptible to MeHg toxicity; however, the mechanisms governing its effects in the developing brain are unclear. In the present study, we investigated the effects of prenatal and lactational MeHg exposure on the developing cerebellum in rats. We demonstrated that exposure to 5 ppm MeHg decreased postnatal expression of pre- and postsynaptic proteins, suggesting an impairment in synaptic development. MeHg exposure also reduced neurite outgrowth, as shown by a decrease in the expression of the neurite marker neurofilament H. These changes were not observed in rats exposed to 1 ppm MeHg. In order to define the underlying mechanism, we investigated the effects of MeHg exposure on the tropomyosin receptor kinase (Trk) A pathway, which plays important roles in neuronal differentiation and synapse formation. We demonstrated suppression of the TrkA pathway on gestation day 20 in rats exposed to 5 ppm MeHg. In addition, down-regulation of eukaryotic elongation factor 1A1 (eEF1A1) was observed on postnatal day 1. eEF1A1 knockdown in differentiating PC12 cells impaired neurite outgrowth and synaptic protein expression, similar to the results of MeHg exposure in the cerebellum. These results suggest that suppression of the TrkA pathway and subsequent decreases in eEF1A1 expression induced by prenatal exposure to MeHg may lead to reduced neurite outgrowth and synaptic protein expression in the developing cerebellum. - Highlights: • Prenatal exposure to MeHg decreased postnatal expression of synaptic proteins. • MeHg exposure also reduced neurite outgrowth postnatally. • Suppression of the TrkA pathway and eEF1A1 expression was induced by MeHg exposure. • eEF1A1 knockdown impaired neurite outgrowth and synaptic protein expression.

  16. A milk-based wolfberry preparation prevents prenatal stress-induced cognitive impairment of offspring rats, and inhibits oxidative damage and mitochondrial dysfunction in vitro.

    Science.gov (United States)

    Feng, Zhihui; Jia, Haiqun; Li, Xuesen; Bai, Zhuanli; Liu, Zhongbo; Sun, Lijuan; Zhu, Zhongliang; Bucheli, Peter; Ballèvre, Olivier; Wang, Junkuan; Liu, Jiankang

    2010-05-01

    Lycium barbarum (Fructus Lycii, Wolfberry, or Gouqi) belongs to the Solanaceae. The red-colored fruits of L. barbarum have been used for a long time as an ingredient in Chinese cuisine and brewing, and also in traditional Chinese herbal medicine for improving health. However, its effects on cognitive function have not been well studied. In the present study, prevention of a milk-based wolfberry preparation (WP) on cognitive dysfunction was tested in a prenatal stress model with rats and the antioxidant mechanism was tested by in vitro experiments. We found that prenatal stress caused a significant decrease in cognitive function (Morris water maze test) in female offspring. Pretreatment of the mother rats with WP significantly prevented the prenatal stress-induced cognitive dysfunction. In vitro studies showed that WP dose-dependently scavenged hydroxyl and superoxide radicals (determined by an electron spin resonance spectrometric assay), and inhibited FeCl(2)/ascorbic acid-induced dysfunction in brain tissue and tissue mitochondria, including increases in reactive oxygen species and lipid peroxidation and decreases in the activities of complex I, complex II, and glutamate cysteine ligase. These results suggest that dietary supplementation with WP may be an effective strategy for preventing the brain oxidative mitochondrial damage and cognitive dysfunction associated with prenatal stress.

  17. Cocaine enhances resistance to extinction of responding for brain-stimulation reward in adult prenatally stressed rats.

    Science.gov (United States)

    Gao, Shuibo; Suenaga, Toshiko; Oki, Yutaka; Yukie, Masao; Nakahara, Daiichiro

    2011-10-01

    The present experiment assessed whether prenatal stress (PS) can alter the ability of acute and chronic cocaine administration to increase and decrease the rewarding effectiveness of the medial forebrain bundle (MFB) using intracranial self-stimulation (ICSS), and also whether PS can affect the extinction of the MFB stimulation response. Adult male offspring of female rats that received PS or no PS (nPS) were implanted with MFB stimulating electrodes, and were then tested in ICSS paradigms. In both nPS and PS offspring, acute cocaine injection decreased ICSS thresholds dose-dependently. However, the threshold-lowering effects at any dose were not significantly different between groups. There was also no group-difference in the threshold-elevating effects of chronic cocaine administration. Nevertheless, chronically drug-administered PS rats exhibited a resistance to the extinguishing of the response for brain-stimulation reward when acutely treated with cocaine, as compared to extinction without cocaine treatment. The results suggest that PS may weaken the ability for response inhibition under cocaine loading in male adult offspring. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. Spirulina platensis attenuates the associated neurobehavioral and inflammatory response impairments in rats exposed to lead acetate.

    Science.gov (United States)

    Khalil, Samah R; Khalifa, Hesham A; Abdel-Motal, Sabry M; Mohammed, Hesham H; Elewa, Yaser H A; Mahmoud, Hend Atta

    2018-08-15

    Heavy metals are well known as environmental pollutants with hazardous impacts on human and animal health because of their wide industrial usage. In the present study, the role of Spirulina platensis in reversing the oxidative stress-mediated brain injury elicited by lead acetate exposure was evaluated. In order to accomplish this aim, rats were orally administered with 300 mg/kg bw Spirulina for 15 d, before and simultaneously with an intraperitoneal injection of 50 mg/kg bw lead acetate [6 injections through the two weeks]. As a result, the co-administration of Spirulina with lead acetate reversed the most impaired open field behavioral indices; however, this did not happen for swimming performance, inclined plane, and grip strength tests. In addition, it was observed that Spirulina diminished the lead content that accumulated in both the blood and the brain tissue of the exposed rats, and reduced the elevated levels of oxidative damage indices, and brain proinflammatory markers. Also, because of the Spirulina administration, the levels of the depleted biomarkers of antioxidant status and interleukin-10 in the lead-exposed rats were improved. Moreover, Spirulina protected the brain tissue (cerebrum and cerebellum) against the changes elicited by lead exposure, and also decreased the reactivity of HSP70 and Caspase-3 in both cerebrum and cerebellum tissues. Collectively, our findings demonstrate that Spirulina has a potential use as a food supplement in the regions highly polluted with heavy metals. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Inhibition of HMGB1 Translocation by Green Tea Extract in Rats Exposed to Environmental Tobacco Smoke

    Directory of Open Access Journals (Sweden)

    Sirintip Chaichalotornkul

    2012-01-01

    Full Text Available Environmental tobacco smoke (ETS exposure is linked to carcinogenic, oxidative and inflammatory cellular reactions. Green tea polyphenol reportedly plays a role in the prevention of inflammation-related diseases. To evaluate the effects of green tea extract (GTE on cellular location of High Mobility Group Box-1 (HMGB1 protein, we studied the lung tissue in rats exposed to cigarette smoke (CS. Rats were divided into three groups; CS, CSG, and C, which were groups of CS-treated only, CS-treated with GTE dietary supplement, and the control, respectively. Our findings by immunocytochemistry showed that abundant HMGB1 translocated from the nucleus to the cytoplasm in the lung tissues of rats that were exposed to CS, whereas HMGB1 was localized to the nuclei of CSG and C group. For in vitro studies, cotinine stimulated the secretion of HMGB1 in a dose and time dependent manner and the HMGB1 level was suppressed by GTE in murine macrophage cell lines. Our results could suggest that GTE supplementation which could suppress HMGB1 may offer a beneficial effect against diseases.

  20. Antioxidant activity of eggplant (Solanum melongena) in male albino rats exposed to gamma irradiation

    International Nuclear Information System (INIS)

    Abdel-Magied, N.; Ahmed, A.G.; Abo zid, N.M.

    2012-01-01

    The aim of the study was to evaluate the potential benefits of dietary supplementation of eggplant (Solanum melongena) as antioxidant against γ- rays-induced biochemical changes in male albino rats by estimating some of the components of antioxidant defense in the; liver glutathione content (GSH), superoxide dismutase activity (SOD) and malondialdehyde (MDA), serum aspartate amino transferase,(AST), alanine amino transferase (ALT), alkaline phosphatase (ALP), gamma glutamyl transaminase (GGT), cholesterol, triglycerides, low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol(HDL-C). Male albino rats (120-150 g) were divided into four groups as Control group, group 2 received diet supplemented with 10% of eggplant (Solanum melongnea) fruit for 21 successive days , group 3: irradiated with a single dose (6.5 Gy), group 4 received eggplant for 21 successive days then exposed to 6.5 Gy. All animals were sacrificed after 1, 3 and 8 days post irradiation. Rats exposed to γ-rays exhibited a profound elevation of AST, ALT, ALP and GGT activities, and lipid abnormalities .Noticeable drop in liver GSH content and SOD activity associated with increase of MDA was recorded. Treatment with dietary eggplant for 21 days before irradiation significantly abolished radiation induced elevations in MDA and significantly elevates hepatic GSH content and SOD activity. The levels of cholesterol, TG, HDL-C, LDL-C as well as the activities of AST, ALT, and GGT in serum were significantly ameliorated and noticeable improvement in the lipid profile levels

  1. Concentration and distribution of 210Po in rats exposed to radon

    International Nuclear Information System (INIS)

    Pan Peng; Yang Zhanshan; Wang Tianchang; Tong Jian; Zhou Jianwei

    2007-01-01

    Objective: To study the concentration and distribution of 210 Po in rats exposed to radon and its daughters. Methods: Fifteen male wistar rats were randomly divided into three groups, including one control group and two radon exposed groups with the cumulative doses of 100 WLM (low dose) and 200 WLM (high dose), respectively. Tissue samples containing 210 Po were spontaneously deposited onto silvery discs with the diameter of 20 mm by means of wet ashing and electrodeposition. The concentration of 210 Po in tissues were measured by α spectroscopy, and tissue burden were calculated. Results: The concentrations of 210 Po were significantly different among the three dose groups in femur, liver, sex gland and hair (P 210 Po were different between the exposed groups and the control group in lung and soleus muscle (P 210 Po in lung, spleen and hair were higher than that in liver, bone and sex gland, the lowest was in intestine. The tissue burdens of liver, bone and sex gland were significantly different from those in other organs or tissues. Conclusions: 210 Po was mainly distributed in lung, liver, spleen, femur and sex gland. The concentrations of 210 Po in organs or tissues and the tissue burdens were correspondingly increased with the exposure dose of radon and its daughters. The results of this experiment provide a dosimetric basis for further studies on the carcinogenic effect of radon and its daughters. (authors)

  2. Life-span radiation effects studies in prenatally and postnatally exposed beagle dogs at Colorado State University

    International Nuclear Information System (INIS)

    Benjamin, S.A.; Lee, A.C.; Angleton, G.M.; Jaenke, R.S.; Saunders, W.J.; Miller, G.K.; Brewster, R.D.

    1986-01-01

    The lifetime hazards associated with exposure to ionizing radiation during development are studied in 1680 beagle dogs given whole-body exposures to 60 Co gamma radiation. Eight groups of 120 dogs each received 20-R or 100-R exposures at 8, 28, or 55 days postcoitus (dpc) or at 2 days postpartum (dpp). In addition, exposures of 100 R were given to 120 dogs at 70 dpp and to 240 dogs at 365 dpp. An additional 360 dogs were sham exposed. Smaller groups of dogs were used to identify organs and tissues of particular sensitivity to radiation injury during development and to evaluate mechanisms of radiation injury. The research is concerned primarily with evaluating the role of age at exposure as a factor influencing response to radiation injury. As of December 31, 1982, of the 1680 dogs, 1058 were dead. Survivors ranged from 9.9 to 15 years of age. Through 10 years of age, no differences in survival were evident in any exposure groups. A variety of clinical, pathophysiologic, and pathologic responses have been studied. Irradiation during development has been found to be associated with abnormalities of skeletal, dental, and central nervous system development. Irradiation during ocular development has induced dysplastic and atrophic retinal lesions. Perinatal irradiation of the kidney has resulted in dysplasia, and, in animals receiving higher doses, significant chronic renal disease. The thymus gland, particularly thymic epithelium, has been found to be highly radiosensitive during fetal development

  3. Prenatal Exposure to a Maternal High-Fat Diet Affects Histone Modification of Cardiometabolic Genes in Newborn Rats

    Directory of Open Access Journals (Sweden)

    Bijaya Upadhyaya

    2017-04-01

    Full Text Available Infants born to women with diabetes or obesity are exposed to excess circulating fuels during fetal heart development and are at higher risk of cardiac diseases. We have previously shown that late-gestation diabetes, especially in conjunction with a maternal high-fat (HF diet, impairs cardiac functions in rat-offspring. This study investigated changes in genome-wide histone modifications in newborn hearts from rat-pups exposed to maternal diabetes and HF-diet. Chromatin-immunoprecipitation-sequencing revealed a differential peak distribution on gene promoters in exposed pups with respect to acetylation of lysines 9 and 14 and to trimethylation of lysines 4 and 27 in histone H3 (all, false discovery rate, FDR < 0.1. In the HF-diet exposed offspring, 54% of the annotated genes showed the gene-activating mark trimethylated lysine 4. Many of these genes (1 are associated with the “metabolic process” in general and particularly with “positive regulation of cholesterol biosynthesis” (FDR = 0.03; (2 overlap with 455 quantitative trait loci for blood pressure, body weight, serum cholesterol (all, FDR < 0.1; and (3 are linked to cardiac disease susceptibility/progression, based on disease ontology analyses and scientific literature. These results indicate that maternal HF-diet changes the cardiac histone signature in offspring suggesting a fuel-mediated epigenetic reprogramming of cardiac tissue in utero.

  4. Improved Social Interaction, Recognition and Working Memory with Cannabidiol Treatment in a Prenatal Infection (poly I:C) Rat Model.

    Science.gov (United States)

    Osborne, Ashleigh L; Solowij, Nadia; Babic, Ilijana; Huang, Xu-Feng; Weston-Green, Katrina

    2017-06-01

    Neuropsychiatric disorders such as schizophrenia are associated with cognitive impairment, including learning, memory and attention deficits. Antipsychotic drugs are limited in their efficacy to improve cognition; therefore, new therapeutic agents are required. Cannabidiol (CBD), the non-intoxicating component of cannabis, has anti-inflammatory, neuroprotective and antipsychotic-like properties; however, its ability to improve the cognitive deficits of schizophrenia remains unclear. Using a prenatal infection model, we examined the effect of chronic CBD treatment on cognition and social interaction. Time-mated pregnant Sprague-Dawley rats (n=16) were administered polyinosinic-polycytidilic acid (poly I:C) (POLY; 4 mg/kg) or saline (CONT) at gestation day 15. Male offspring (PN56) were injected twice daily with 10 mg/kg CBD (CONT+CBD, POLY+CBD; n=12 per group) or vehicle (VEH; CONT+VEH, POLY+VEH; n=12 per group) for 3 weeks. Body weight, food and water intake was measured weekly. The Novel Object Recognition and rewarded T-maze alternation tests assessed recognition and working memory, respectively, and the social interaction test assessed sociability. POLY+VEH offspring exhibited impaired recognition and working memory, and reduced social interaction compared to CONT+VEH offspring (psocial interaction deficits in the poly I:C model (p0.05). In conclusion, chronic CBD administration can attenuate the social interaction and cognitive deficits induced by prenatal poly I:C infection. These novel findings present interesting implications for potential use of CBD in treating the cognitive deficits and social withdrawal of schizophrenia.

  5. Increased precipitation of spasms in an animal model of infantile spasms by prenatal stress exposure.

    Science.gov (United States)

    Shi, Xiu-Yu; Ju, Jun; Zou, Li-Ping; Wang, Juan; Shang, Ning-Xiu; Zhao, Jian-Bo; Wang, Jing; Zhang, Jun-Yan

    2016-05-01

    Infantile spasms (IS) represent a serious epileptic syndrome, called West syndrome (WS) that occurs in the early infantile age. Although several hypotheses and animal models have been proposed to explain the pathogenesis of IS, the pathophysiology of IS has not been elucidated. Recently, we proposed a hypothesis for IS under prenatal stress exposure (also called Zou's hypothesis) by correlating diverse etiologies and prenatal stresses with IS development. This research aims to determine the mechanism through which prenatal stress affects the offspring and establish the potential underlying mechanisms. Pregnant rats were subjected to forced swimming in cold water. Rat pups exposed to prenatal stress were administered with N-methyl-D-aspartate (NMDA). Exposure to prenatal stress sensitized the rats against development of NMDA-induced spasms. However, this phenomenon was altered by administering adrenocorticotropin. Prenatal stress exposure also altered the hormonal levels and neurotransmitter receptor expression of the developing rats as well as influenced the tissue structure of the brain. These findings suggest that maternal stress could alter the level of endogenous glucocorticoid, which is the basis of IS, and cerebral dysplasia, hypoxic-ischemic encephalopathy (HIE), inherited metabolic diseases, and other factors activated this disease in developmental brain. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Gross hepatic changes in developing albino rats exposed to valproic acid

    International Nuclear Information System (INIS)

    Khan, M.; Khattak, S.T.; Elahi, M.

    2011-01-01

    Background: Valproid Acid (VPA) is a broad spectrum antiepileptic drug. Its use during pregnancy has been associated with congenital anomalies and hepatotoxicity. This study was designed to assess the effects of VPA on the gross structure of liver in developing albino rats exposed to the drug during various trimesters of pregnancy. Methods: In this experimental study 40 pregnant rats were divided into 4 equal groups A, B, C and D. Group A received VPA in a dose of 500 mg/Kg/day intraperitonealy (I/P) on days 3, 4 and 5 of gestation. Group B received the drug in a dose of 500 mg/Kg/day I/P on days 8, 9 and 10 of gestation. Group C received VPA in a dose of 500 mg/Kg/day I/P on days 16, 17 and 18 of gestation. Group D received no treatment and was kept as a control group. On day 21, the rats were euthanised by cervical dislocation. The liver of the foetuses were dissected out for the assessment of their gross structure. Results: Foetal liver of the experimental groups showed significant decrease in weight as well as relative tissue weight index (RTWI) as compared to the control group, although the gross appearance of the foetal liver was normal in all the groups. Conclusion: The use of VPA during various trimesters of pregnancy produces hepatotoxicity in the developing rats. So, the use of this drug during pregnancy should be carefully decided. (author)

  7. Neonatal erythropoietin mitigates impaired gait, social interaction and diffusion tensor imaging abnormalities in a rat model of prenatal brain injury.

    Science.gov (United States)

    Robinson, Shenandoah; Corbett, Christopher J; Winer, Jesse L; Chan, Lindsay A S; Maxwell, Jessie R; Anstine, Christopher V; Yellowhair, Tracylyn R; Andrews, Nicholas A; Yang, Yirong; Sillerud, Laurel O; Jantzie, Lauren L

    2018-04-01

    Children who are born preterm are at risk for encephalopathy of prematurity, a leading cause of cerebral palsy, cognitive delay and behavioral disorders. Current interventions are limited and none have been shown to reverse cognitive and behavioral impairments, a primary determinant of poor quality of life for these children. Moreover, the mechanisms of perinatal brain injury that result in functional deficits and imaging abnormalities in the mature brain are poorly defined, limiting the potential to target interventions to those who may benefit most. To determine whether impairments are reversible after a prenatal insult, we investigated a spectrum of functional deficits and diffusion tensor imaging (DTI) abnormalities in young adult animals. We hypothesized that prenatal transient systemic hypoxia-ischemia (TSHI) would induce multiple functional deficits concomitant with reduced microstructural white and gray matter integrity, and tested whether these abnormalities could be ameliorated using postnatal erythropoietin (EPO), an emerging neurorestorative intervention. On embryonic day 18 uterine arteries were transiently occluded for 60min via laparotomy. Shams underwent anesthesia and laparotomy for 60min. Pups were born and TSHI pups were randomized to receive EPO or vehicle via intraperitoneal injection on postnatal days 1 to 5. Gait, social interaction, olfaction and open field testing was performed from postnatal day 25-35 before brains underwent ex vivo DTI to measure fractional anisotropy, axial diffusivity and radial diffusivity. Prenatal TSHI injury causes hyperactivity, impaired gait and poor social interaction in young adult rats that mimic the spectrum of deficits observed in children born preterm. Collectively, these data show for the first time in a model of encephalopathy of prematurity that postnatal EPO treatment mitigates impairments in social interaction, in addition to gait deficits. EPO also normalizes TSHI-induced microstructural abnormalities

  8. Effects of prenatal irradiation with accelerated heavy-ion beams on postnatal development in rats: III. Testicular development and breeding activity

    Science.gov (United States)

    Wang, B.; Murakami, M.; Eguchi-Kasai, K.; Nojima, K.; Shang, Y.; Tanaka, K.; Watanabe, K.; Fujita, K.; Moreno, S. G.; Coffigny, H.; Hayata, I.

    With a significant increase in human activities dealing with space missions, potential teratogenic effects on the mammalian reproductive system from prenatal exposure to space radiation have become a hot topic that needs to be addressed. However, even for the ground experiments, such effects from exposure to high LET ionizing radiation are not as well studied as those for low LET ionizing radiations such as X-rays. Using the Heavy-Ion Medical Accelerator in Chiba (HIMAC) and Wistar rats, effects on gonads in prenatal male fetuses, on postnatal testicular development and on breeding activity of male offspring were studied following exposure of the pregnant animals to either accelerated carbon-ion beams with a LET value of about 13 keV/μm or neon-ion beams with a LET value of about 30 keV/μm at a dose range from 0.1 to 2.0 Gy on gestation day 15. The effects of X-rays at 200 kVp estimated for the same biological end points were studied for comparison. A significantly dose-dependent increase of apoptosis in gonocytes appeared 6 h after irradiations with a dose of 0.5 Gy or more. Measured delayed testis descent and malformed testicular seminiferous tubules were observed to be significantly different from the control animals at a dose of 0.5 Gy. These effects are observed to be dose- and LET-dependent. Markedly reduced testicular weight and testicular weight to body weight ratio were scored at postnatal day 30 even in the offspring that were prenatally irradiated with neon-ions at a dose of 0.1 Gy. A dose of 0.5 Gy from neon-ion beams induced a marked decrease in breeding activity in the prenatally irradiated male rats, while for the carbon-ion beams or X-rays, the significantly reduced breeding activity was observed only when the prenatal dose was at 1.0 Gy or more. These findings indicated that prenatal irradiations with heavy-ion beams on gestation day 15 generally induced markedly detrimental effects on prenatal gonads, postnatal testicular development and male

  9. Enriched but not depleted uranium affects central nervous system in long-term exposed rat.

    Science.gov (United States)

    Houpert, Pascale; Lestaevel, Philippe; Bussy, Cyrill; Paquet, François; Gourmelon, Patrick

    2005-12-01

    Uranium is well known to induce chemical toxicity in kidneys, but several other target organs, such as central nervous system, could be also affected. Thus in the present study, the effects on sleep-wake cycle and behavior were studied after chronic oral exposure to enriched or depleted uranium. Rats exposed to 4% enriched uranium for 1.5 months through drinking water, accumulated twice as much uranium in some key areas such as the hippocampus, hypothalamus and adrenals than did control rats. This accumulation was correlated with an increase of about 38% of the amount of paradoxical sleep, a reduction of their spatial working memory capacities and an increase in their anxiety. Exposure to depleted uranium for 1.5 months did not induce these effects, suggesting that the radiological activity induces the primary events of these effects of uranium.

  10. Comparison of rats and dogs exposed to 239PuO2

    International Nuclear Information System (INIS)

    Mahaffey, J.A.; Sanders, C.L.; Park, J.F.; Dagle, G.E.

    1979-01-01

    Rats and dogs inhaled aerosols of 239 PuO 2 at comparable ages relative to their lifespan. Both received a single exposure. The estimated lung doses at death in dogs were between 1100 and 11,000 rad. From two inhalation experiments, rats receiving doses in this range were chosen from the high-level exposed animals for comparison. Based on this data base, several comparisons were investigated. Metabolism of the material was compared for all animals and for animals which developed lung tumors. The differences in histopathology and tumor incidence in the lung were also reviewed. Although there were several differences between species, there were also many similarities. On-going research in dogs should produce data which will allow clarification of these relationships

  11. Global Gene Expression Profiling in Lung Tissues of Rat Exposed to Lunar Dust Particles

    Science.gov (United States)

    Yeshitla, Samrawit A.; Lam, Chiu-Wing; Kidane, Yared H.; Feiveson, Alan H.; Ploutz-Snyder, Robert; Wu, Honglu; James, John T.; Meyers, Valerie E.; Zhang, Ye

    2014-01-01

    The Moon's surface is covered by a layer of fine, potential reactive dust. Lunar dust contain about 1-2% respirable very fine dust (less than 3 micrometers). The habitable area of any lunar landing vehicle and outpost would inevitably be contaminated with lunar dust that could pose a health risk. The purpose of the study is to analyze the dynamics of global gene expression changes in lung tissues of rats exposed to lunar dust particles. F344 rats were exposed for 4 weeks (6h/d; 5d/wk) in nose-only inhalation chambers to concentrations of 0 (control air), 2.1, 6.8, 21, and 61 mg/m3 of lunar dust. Animals were euthanized at 1 day and 13 weeks after the last inhalation exposure. After being lavaged, lung tissue from each animal was collected and total RNA was isolated. Four samples of each dose group were analyzed using Agilent Rat GE v3 microarray to profile global gene expression of 44K transcripts. After background subtraction, normalization, and log transformation, t tests were used to compare the mean expression levels of each exposed group to the control group. Correction for multiple testing was made using the method of Benjamini, Krieger, and Yekuteli (1) to control the false discovery rate. Genes with significant changes of at least 1.75 fold were identified as genes of interest. Both low and high doses of lunar dust caused dramatic, dose-dependent global gene expression changes in the lung tissues. However, the responses of lung tissue to low dose lunar dust are distinguished from those of high doses, especially those associated with 61mg/m3 dust exposure. The data were further integrated into the Ingenuity system to analyze the gene ontology (GO), pathway distribution and putative upstream regulators and gene targets. Multiple pathways, functions, and upstream regulators have been identified in response to lunar dust induced damage in the lung tissue.

  12. Short- and long-term reproductive effects of prenatal and lactational growth restriction caused by maternal diabetes in male rats

    Directory of Open Access Journals (Sweden)

    Amorim Elaine MP

    2011-12-01

    Full Text Available Abstract Background A suboptimal intrauterine environment may have a detrimental effect on gonadal development and thereby increases the risk for reproductive disorders and infertility in adult life. Here, we used uncontrolled maternal diabetes as a model to provoke pre- and perinatal growth restriction and evaluate the sexual development of rat male offspring. Methods Maternal diabetes was induced in the dams through administration of a single i.v. dose of 40 mg/kg streptozotocin, 7 days before mating. Female rats presenting glycemic levels above 200 mg/dL after the induction were selected for the experiment. The male offspring was analyzed at different phases of sexual development, i.e., peripuberty, postpuberty and adulthood. Results Body weight and blood glucose levels of pups, on the third postnatal day, were lower in the offspring of diabetic dams compared to controls. Maternal diabetes also provoked delayed testicular descent and preputial separation. In the offspring of diabetic dams the weight of reproductive organs at 40, 60 and 90 days-old was lower, as well as sperm reserves and sperm transit time through the epididymis. However the plasma testosterone levels were not different among experimental groups. Conclusions It is difficult to isolate the effects directly from diabetes and those from IUGR. Although the exposure to hyperglycemic environment during prenatal life and lactation delayed the onset of puberty in male rats, the IUGR, in the studied model, did not influenced the structural organization of the male gonads of the offspring at any point during sexual development. However the decrease in sperm reserves in epididymal cauda and the acceleration in sperm transit time in this portion of epididymis may lead to an impairment of sperm quality and fertility potential in these animals. Additional studies are needed in attempt to investigate the fertility of animals with intrauterine growth restriction by maternal diabetes and

  13. Dose and temporal effects on gene expression profiles of urothelial cells from rats exposed to diuron

    International Nuclear Information System (INIS)

    Ihlaseh-Catalano, Shadia M.; Bailey, Kathryn A.; Cardoso, Ana Paula F.; Ren, Hongzu; Fry, Rebecca C.; Camargo, João Lauro V.de; Wolf, Douglas C.

    2014-01-01

    Diuron (3-(3,4-dichlorophenyl)-1,1-dimethylurea) is a substituted urea herbicide that at high dietary levels (2500 ppm) induces rat urinary bladder hyperplasia after 20 weeks of exposure and neoplasia after 2 years. The effects on the urothelium after short-term exposure have not been described. The present 7-day study evaluated the dose-dependency of urothelial alterations in the urinary bladder using light microscopy, scanning electron microscopy, and genome-wide transcriptional profiling. Male Wistar rats were fed 0, 125, 500, 2500 ppm diuron for 7 days. The urinary bladder and isolated urothelial cells of these animals were processed for microscopic examination and gene expression profiling, respectively. No significant treatment-related morphologic effects were observed. The number of differentially expressed genes (DEGs) in the exposed groups increased with diuron levels. Diuron-altered genes involved in cell-to-cell interactions and tissue organization were identified in all treatment groups. After 7 days of diuron exposure, transcriptional responses were observed in the urothelium in the absence of clear morphologic changes. These morphological findings are different from those observed in a previous study in which 20 weeks of diuron exposure was associated with simple hyperplasia secondary to the persistent cytotoxicity and necrosis associated with continuous cellular regeneration. Comparison of the gene expression profiles of rats exposed to the 2500 ppm carcinogenic diuron dose for 7 days versus 20 weeks revealed few similarities between these two time points at the gene or pathway level. Taken together, these data provide insight into the dose- and temporal-dependent morphological and transcriptional changes associated with diuron exposure that may lead to the development of tumors in the rat urinary bladder

  14. Dose and temporal effects on gene expression profiles of urothelial cells from rats exposed to diuron.

    Science.gov (United States)

    Ihlaseh-Catalano, Shadia M; Bailey, Kathryn A; Cardoso, Ana Paula F; Ren, Hongzu; Fry, Rebecca C; de Camargo, João Lauro V; Wolf, Douglas C

    2014-11-05

    Diuron (3-(3,4-dichlorophenyl)-1,1-dimethylurea) is a substituted urea herbicide that at high dietary levels (2500 ppm) induces rat urinary bladder hyperplasia after 20 weeks of exposure and neoplasia after 2 years. The effects on the urothelium after short-term exposure have not been described. The present 7-day study evaluated the dose-dependency of urothelial alterations in the urinary bladder using light microscopy, scanning electron microscopy, and genome-wide transcriptional profiling. Male Wistar rats were fed 0, 125, 500, 2500 ppm diuron for 7 days. The urinary bladder and isolated urothelial cells of these animals were processed for microscopic examination and gene expression profiling, respectively. No significant treatment-related morphologic effects were observed. The number of differentially expressed genes (DEGs) in the exposed groups increased with diuron levels. Diuron-altered genes involved in cell-to-cell interactions and tissue organization were identified in all treatment groups. After 7 days of diuron exposure, transcriptional responses were observed in the urothelium in the absence of clear morphologic changes. These morphological findings are different from those observed in a previous study in which 20 weeks of diuron exposure was associated with simple hyperplasia secondary to the persistent cytotoxicity and necrosis associated with continuous cellular regeneration. Comparison of the gene expression profiles of rats exposed to the 2500 ppm carcinogenic diuron dose for 7 days versus 20 weeks revealed few similarities between these two time points at the gene or pathway level. Taken together, these data provide insight into the dose- and temporal-dependent morphological and transcriptional changes associated with diuron exposure that may lead to the development of tumors in the rat urinary bladder. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  15. Ameliorative Effect of Honey and Propolis Mixture on Rats Exposed to Gamma Irradiation

    International Nuclear Information System (INIS)

    Hemieda, S.F.; Abd-El Nour, K.N.; Hassan, A.I.; Abdou, M.I.; Khalil, W.A.

    2016-01-01

    This study aims to evaluate the ameliorative effect of honey and propolis mixture treatment on some biochemical and biophysical parameters in rats exposed to oxidative stress of gamma irradiation. Male rats were exposed to a fractionated dose gamma irradiation of total 5 Gy in five successive days. A mixture of dose 250 mg/kg/day honey and 90 mg/kg/day propolis was administrated to rats, ten days before irradiation, five days during irradiation and 14 days post irradiation. Blood samples were collected at 1 st , 7 th and 14 th day post the 5 th day of irradiation. Biochemical parameters such as serum liver enzymes (ALT and AST), serum renal function as (BUN and Creatinine) and serum total antioxidants were estimated. Also biophysical studies including hemoglobin investigations (Hb absorption spectra and dielectric measurements) were investigated.The results demonstrated that the levels of AST, ALT, BUN and creatinine were significantly elevated, while levels of total antioxidants were significantly reduced post irradiation. Moreover the absolute values of permittivity ε', dielectric loss ε'' and ac - conductivity σ ac increased in addition to a pronounced decrease in the absorbance at Sort band after irradiation compared to control group.Treatment of the irradiated group with honey and propolis mixture showed significant amelioration in the levels of the biochemical parameters. Also, the values of ε', ε'' and σ ac were nearly close to those of control group. Finally, the average value of peak height of Sort band was significantly increased compared to irradiated rat.

  16. Isolation and identification of previtamin D3 from the skin of rats exposed to ultraviolet irradiation

    International Nuclear Information System (INIS)

    Holick, M.F.; Richtand, N.M.; McNeill, S.C.; Holick, S.A.; Frommer, J.E.; Henley, J.W.; Potts, J.T. Jr.

    1979-01-01

    The process of the photolytic activation of vitamin D precursor(s) in the skin has been elucidated by a detailed analysis of the products formed after ultraviolet light exposure. The photolytic product isolated from the skin of rats exposed to ultraviolet irradiation was identified as previtamin D 3 by several criteria including its characteristic ultraviolet absorption spectrum, mass spectrum, and thermal isomerization to vitamin D 3 , which itself was identified also by mass spectroscopy. Vitamin D 3 per se was not formed by ultraviolet irradiation-vitamin D 3 arises exclusively from the thermal conversion of previtamin D 3 . Detectable amounts of lumisterol 3 or tachysterol 3 were not seen

  17. Gene Expression Profiling of Lung Tissue of Rats Exposed to Lunar Dust Particles

    Science.gov (United States)

    Zhang, Ye; Feiveson, Alan H.; Lam, Chiu-Wing; Kidane, Yared H.; Ploutz-Snyder Robert; Yeshitla, Samrawit; Zalesak, Selina M.; Scully, Robert R.; Wu, Honglu; James, John T.

    2014-01-01

    The purpose of the study is to analyze the dynamics of global gene expression changes in the lung tissue of rats exposed to lunar dust particles. Multiple pathways and transcription factors were identified using the Ingenuity Pathway Analysis tool, showing the potential networks of these signaling regulations involved in lunar dust-induced prolonged proflammatory response and toxicity. The data presented in this study, for the first time, explores the molecular mechanisms of lunar dust induced toxicity. This work contributes not only to the risk assessment for future space exploration, but also to the understanding of the dust-induced toxicity to humans on earth.

  18. Mucous flow and ciliary activity in the trachea of rats exposed to pulmonary irritant gas

    Energy Technology Data Exchange (ETDEWEB)

    Dalhamm, T; Rhodin, J

    1956-01-01

    Tracheal mucous secretion was increased in rats exposed to 10 ppM SO/sub 2/, 6 hr/day for 10 weeks. Mucous transport was decreased from 13.5 to 5 mm/min although ciliary beat remained a constant 1320 beats/min. The mucous layer was 5 times as thick as the normal ..mu..m. Histologically, cilia were generally unaffected whereas tracheal epithelium was irregular with deep crypts, and the lamina propria showed severe edema, fragmentation of collagen fibrils, and profuse vascularization with blood escaping perivascularly.

  19. Paroxetine ameliorates changes in hippocampal energy metabolism in chronic mild stress-exposed rats

    Directory of Open Access Journals (Sweden)

    Khedr LH

    2015-11-01

    Full Text Available Lobna H Khedr, Noha N Nassar, Ezzeldin S El-Denshary, Ahmed M Abdel-tawab 1Department of Pharmacology, Faculty of Pharmacy, Misr International University, 2Department of Pharmacology, Faculty of Pharmacy, Cairo University, 3Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt Abstract: The molecular mechanisms underlying stress-induced depression have not been fully outlined. Hence, the current study aimed at testing the link between behavioral changes in chronic mild stress (CMS model and changes in hippocampal energy metabolism and the role of paroxetine (PAROX in ameliorating these changes. Male Wistar rats were divided into three groups: vehicle control, CMS-exposed rats, and CMS-exposed rats receiving PAROX (10 mg/kg/day intraperitoneally. Sucrose preference, open-field, and forced swimming tests were carried out. Corticosterone (CORT was measured in serum, while adenosine triphosphate and its metabolites, cytosolic cytochrome-c (Cyt-c, caspase-3 (Casp-3, as well as nitric oxide metabolites (NOx were measured in hippocampal tissue homogenates. CMS-exposed rats showed a decrease in sucrose preference as well as body weight compared to control, which was reversed by PAROX. The latter further ameliorated the CMS-induced elevation of CORT in serum (91.71±1.77 ng/mL vs 124.5±4.44 ng/mL, P<0.001 as well as the changes in adenosine triphosphate/adenosine diphosphate (3.76±0.02 nmol/mg protein vs 1.07±0.01 nmol/mg protein, P<0.001. Furthermore, PAROX reduced the expression of Cyt-c and Casp-3, as well as restoring NOx levels. This study highlights the role of PAROX in reversing depressive behavior associated with stress-induced apoptosis and changes in hippocampal energy metabolism in the CMS model of depression. Keywords: rats, CMS, hippocampus, paroxetine, apoptosis, adenine nucleotides, cytochrome-c, caspase-3

  20. Long-term effects of 239Pu injection in adult, weanling, newborn and fetal rats

    International Nuclear Information System (INIS)

    Sikov, M.R.; Mahlum, D.D.; Hess, J.O.; Carr, D.B.

    1979-01-01

    We have completed biological evaluations comparing long-term effects in rats exposed to 239 Pu citrate as adults, weanlings, newborns, or late fetuses, and statistical analyses have been initiated. In rats exposed postnatally, statistically significant alterations in terminal body weight and in weights of several organs were found at higher doses. Survivorship decreased with increasing dose in the postnatal groups, but not in rats exposed prenatally

  1. Behavior and memory evaluation of Wistar rats exposed to 1·8 GHz radiofrequency electromagnetic radiation.

    Science.gov (United States)

    Júnior, Luiz Carlos de Caires; Guimarães, Ernesto da Silveira Goulart; Musso, Camila Manso; Stabler, Collin Turner; Garcia, Raúl Marcel González; Mourão-Júnior, Carlos Alberto; Andreazzi, Ana Eliza

    2014-09-01

    The development of communication systems has brought great social and economic benefits to society. As mobile phone use has become widespread, concerns have emerged regarding the potential adverse effects of radiofrequency electromagnetic radiation (RF-EMR) used by these devices. To verify potential effects of mobile phone radiation on the central nervous system (CNS) in an animal model. Male Wistar rats (60 days old) were exposed to RF-EMR from a Global System for Mobile (GSM) cell phone (1·8 GHz) for 3 days. At the end of the exposure, the following behavioral tests were performed: open field and object recognition. Our results showed that exposed animals did not present anxiety patterns or working memory impairment, but stress behavior actions were observed. Given the results of the present study, we speculate that RF-EMR does not promote CNS impairment, but suggest that it may lead to stressful behavioral patterns.

  2. Quantitative and qualitative changes in the lymphocytes of rats chronically exposed to radiation and chemical factors

    International Nuclear Information System (INIS)

    Ivanov, V.V.

    1986-01-01

    Quantitative and qualitative characteristics of lymphocytes in peripheral blood, thymus and spleen of rats chronically exposed to combined external γ-radiation trichlorfon pesticide effect have been studied. It is shown that chronical combined trichlorfon and γ irradiation effect is accompanied by suppression of lymphopoiesis already at the early stages of the experience. The observed effects are formed depending on both daily and cumulative doses of the effect. The development of the combined effect is based on the summation of effects of chronical effect of ionizing radiation and pesticide. The revealed changes in lymphocytes population exposed to radiation and chemical factors can lead to substantial decrease of natural immunity thereby decreasing to various diseases

  3. [Quantitative analysis of urinary ethylene glycol in rats exposed to ethylene oxide].

    Science.gov (United States)

    Koga, M; Hori, H; Tanaka, I; Akiyama, T; Inoue, N

    1985-03-01

    A gas chromatographic method was used for determining ethylene glycol in urine. The analytical procedure is based on an azeotropic distillation and on esterification with n-butyl boronic acid. The linear calibration curve was obtained up to 500 micrograms/ml of ethylene glycol. The detection limit was estimated to be 10 micrograms/ml and relative standard deviation was 3.5% for 100 micrograms/ml of ethylene glycol. This method was applied to determine the urinary excretion of ethylene glycol in rats exposed to ethylene oxide at various concentrations (from 50 to 500 ppm). The excretion amounts of ethylene glycol were observed to be dependent on the concentration of ethylene oxide exposed.

  4. Intrauterine low-functional programming of IGF1 by prenatal nicotine exposure mediates the susceptibility to osteoarthritis in female adult rat offspring.

    Science.gov (United States)

    Tie, Kai; Zhang, Xianrong; Tan, Yang; Deng, Yu; Li, Jing; Ni, Qubo; Wang, Hui; Chen, Liaobin

    2016-02-01

    This study aimed to evaluate whether female adult offspring born with intrauterine growth retardation induced by prenatal nicotine exposure (PNE) are susceptible to osteoarthritis (OA) and to explore the underlying programming mechanisms. Pregnant rats were treated with nicotine or saline at 2.0 mg/kg/d from gestational d 11 to 20. The female adult offspring with or without PNE were forced with a strenuous treadmill running for 6 wk to induce OA. Nicotine's effects on fetal articular chondrocytes were studied by exposing chondrocytes to nicotine for 10 d, and dihydro-β-erythroidine, a selective α4β2-nicotinic acetylcholine receptor (nAChR) inhibitor, was used to identify the change of nicotine's effect. For adult offspring, increased cartilage destruction and accelerated OA progression were observed in the PNE group with running; the expression of α1 chain of type II collagen (Col2A1), aggrecan, SRY-type high mobility group box 9 (Sox9), and IGF1 signaling molecules in the cartilage of PNE offspring were decreased. For fetuses, elevated serum corticosteroid and nicotine levels and suppressed IGF1 levels were observed; expression of Col2A1, aggrecan, Sox9, and IGF1 were reduced. The result of chondrocytes revealed that nicotine impeded the expression of Col2A1, aggrecan, and IGF1; blocking α4β2-nAChR rescued nicotine's suppression. In conclusion, PNE increases the susceptibility of adult offspring to OA; the potential mechanism involves IGF1 low-functional programming in articular cartilage caused directly by the action of nicotine on α4β2-nAChR. © FASEB.

  5. Neuroinflammation and Behavior in HIV-1 Transgenic Rats Exposed to Chronic Adolescent Stress.

    Science.gov (United States)

    Rowson, Sydney A; Harrell, Constance S; Bekhbat, Mandakh; Gangavelli, Apoorva; Wu, Matthew J; Kelly, Sean D; Reddy, Renuka; Neigh, Gretchen N

    2016-01-01

    Highly active antiretroviral therapy (HAART) has improved prognosis for people living with HIV (PLWH) and dramatically reduced the incidence of AIDS. However, even when viral load is controlled, PLWH develop psychiatric and neurological disorders more frequently than those living without HIV. Adolescents with HIV are particularly susceptible to the development of psychiatric illnesses and neurocognitive impairments. While both psychiatric and neurocognitive disorders have been found to be exacerbated by stress, the extent to which chronic stress and HIV-1 viral proteins interact to impact behavior and relevant neuroinflammatory processes is unknown. Determination of the individual contributions of stress and HIV to neuropsychiatric disorders is heavily confounded in humans. In order to isolate the influence of HIV-1 proteins and chronic stress on behavior and neuroinflammation, we employed the HIV-1 transgenic (Tg) rat model, which expresses HIV-1 proteins with a gag and pol deletion, allowing for viral protein expression without viral replication. This Tg line has been characterized as a model of HAART-controlled HIV-1 infection due to the lack of viral replication but continued presence of HIV-1 proteins. We exposed male and female adolescent HIV-1 Tg rats to a mixed-modality chronic stress paradigm consisting of isolation, social defeat and restraint, and assessed behavior, cerebral vascularization, and neuroinflammatory endpoints. Stress, sex, and presence of the HIV-1 transgene impacted weight gain in adolescent rats. Female HIV-1 Tg rats showed decreases in central tendency during the light cycle in the open field regardless of stress exposure. Both male and female HIV-1 Tg rats exhibited decreased investigative behavior in the novel object recognition task, but no memory impairments. Adolescent stress had no effect on the tested behaviors. Microglia in female HIV-1 Tg rats exhibited a hyper-ramified structure, and gene expression of complement factor B was

  6. Prenatal Alcohol Exposure Increases Histamine H3 Receptor-Mediated Inhibition of Glutamatergic Neurotransmission in Rat Dentate Gyrus.

    Science.gov (United States)

    Varaschin, Rafael K; Allen, Nyika A; Rosenberg, Martina J; Valenzuela, C Fernando; Savage, Daniel D

    2018-02-01

    We have reported that prenatal alcohol exposure (PAE)-induced deficits in dentate gyrus, long-term potentiation (LTP), and memory are ameliorated by the histamine H 3 receptor inverse agonist ABT-239. Curiously, ABT-239 did not enhance LTP or memory in control offspring. Here, we initiated an investigation of how PAE alters histaminergic neurotransmission in the dentate gyrus and other brain regions employing combined radiohistochemical and electrophysiological approaches in vitro to examine histamine H 3 receptor number and function. Long-Evans rat dams voluntarily consumed either a 0% or 5% ethanol solution 4 hours each day throughout gestation. This pattern of drinking, which produces a mean peak maternal serum ethanol concentration of 60.8 ± 5.8 mg/dl, did not affect maternal weight gain, litter size, or offspring birthweight. Radiohistochemical studies in adult offspring revealed that specific [ 3 H]-A349821 binding to histamine H 3 receptors was not different in PAE rats compared to controls. However, H 3 receptor-mediated G i /G o protein-effector coupling, as measured by methimepip-stimulated [ 35 S]-GTPγS binding, was significantly increased in cerebral cortex, cerebellum, and dentate gyrus of PAE rats compared to control. A LIGAND analysis of detailed methimepip concentration-response curves in dentate gyrus indicated that PAE significantly elevates receptor-effector coupling by a lower affinity H 3 receptor population without significantly altering the affinities of H 3 receptor subpopulations. In agreement with the [ 35 S]-GTPγS studies, a similar range of methimepip concentrations also inhibited electrically evoked field excitatory postsynaptic potential responses and increased paired-pulse ratio, a measure of decreased glutamate release, to a significantly greater extent in dentate gyrus slices from PAE rats than in controls. These results suggest that a PAE-induced elevation in H 3 receptor-mediated inhibition of glutamate release from

  7. Unpredictable Variable Prenatal Stress Programs Expression of Genes Involved in Appetite Control and Energy Expenditure

    Science.gov (United States)

    Moyer, E. L.; Al-Shayeb, B.; Baer, L. A.; Ronca, A. E.

    2016-01-01

    Exposure to stress in the womb shapes neurobiological and physiological outcomes of offspring in later life, including body weight regulation and metabolic profiles. Our previous work utilizing a centrifugation-induced hyper-gravity demonstrated significantly increased (8-15%) body mass in male, but not female, rats exposed throughout gestation to chronic 2-g from conception to birth. We reported a similar outcome in adult offspring exposed throughout gestation to Unpredictable Variable Prenatal Stress (UVPS). Here we examine gene expression changes and the plasma of animals treated with our UVPS model to identify a potential role for prenatal stress in this hypergravity programming effect. Specifically we focused on appetite control and energy expenditure pathways in prenatally stressed adult (90-day-old) male Sprague-Dawley rats.

  8. Postnatal development of rats exposed to fluoxetine or venlafaxine during the third week of pregnancy

    Directory of Open Access Journals (Sweden)

    V.A. da-Silva

    1999-01-01

    Full Text Available The aim of the present study was to compare the toxic effects of fluoxetine (F (8 and 16 mg/kg and venlafaxine (V (40 and 80 mg/kg administered during the third week of pregnancy on early development of rats. Both antidepressants were administered by gavage on pregnancy days 15 to 20 to groups of 10 to 12 animals each. Duration of gestation, food and water consumption, number of live pups and birth weight were recorded. Litters were culled to six pups at birth (day 1 and followed for growth until weaning (day 25. On day 60, a male and a female from each litter were injected with the 5-HT1 agonist, 5-methoxy-N,N-dimethyltryptamine (6 mg/kg, ip and the serotonergic syndrome was graded. Fluoxetine but not venlafaxine reduced the duration of pregnancy when compared to the control (C group (F = 21.1 days and C = 21.6 days, mean, P<0.02; maximum = 22 days and minimum = 21 days in both groups. The highest doses of both fluoxetine, 16 mg/kg (F16, and venlafaxine, 80 mg/kg (V80, reduced the food intake of pregnant rats, resulting in different rates of body weight gain during treatment (from pregnancy day 15 to day 20: F16 = 29.0 g, V80 = 28.7 g vs C = 39.5 g (median. Birth weight was influenced by treatment and sex (P<0.05; two-way ANOVA. Both doses of fluoxetine or venlafaxine reduced the body weight of litters; however, the body weight of litters from treated dams was equal to the weight of control litters by the time of weaning. At weaning there was no significant difference in weight between sexes. There was no difference among groups in number of live pups at birth, stillbirths, mortality during the lactation period or in the manifestation of serotonergic syndrome in adult rats. The occurrence of low birth weight among pups born to dams which did not show reduced food ingestion or reduction of body weight gain during treatment with lower doses of fluoxetine or venlafaxine suggests that these drugs may have a deleterious effect on prenatal

  9. Behavioural effects in rats after prenatal exposure to dearomatized white spirit

    DEFF Research Database (Denmark)

    Hass, Ulla; Ladefoged, Ole; Lam, H.R.

    2001-01-01

    in the offspring were investigated using a test battery including assessment of physical development, reflex ontogeny, motor function, motor activity and, learning and memory. No significant effects were recorded on motor function and the activity in Open Field. In the initial learning period (age 1 month......), the performance in a Morris water maze was similar in exposed and control animals. When testing for memory at the age of 2 months, the exposed male offspring used more time to locate the hidden platform. After platform relocation, impaired cognitive function was revealed in the exposed females. At the age of 5...

  10. Developmental disturbance of rat cerebral cortex following prenatal low-dose gamma-irradiation: a quantitative study

    International Nuclear Information System (INIS)

    Fukui, Y.; Hoshino, K.; Hayasaka, I.; Inouye, M.; Kameyama, Y.

    1991-01-01

    Pregnant rats were exposed to a single whole-body gamma-irradiation on Day 15 of gestation at a dose of 0.27, 0.48, 1.00, or 1.46 Gy. They were allowed to give birth and the offspring were killed at 6 or 12 weeks of age for microscopic and electron microscopic examinations of the cerebrum. Their body weight, brain weight, cortical thickness, and numerical densities of whole cells and synapses in somatosensory cortex were examined. Growth of the dendritic arborization of layer V pyramidal cells was also examined quantitatively with Golgi-Cox specimens. A significant dose-related reduction in brain weight was found in all irradiated groups. Neither gross malformation nor abnormality of cortical architecture was observed in the groups exposed to 0.27 Gy. A significant change was found in thickness of cortex in the groups exposed to 0.48 Gy or more. Cell packing density increased significantly in the group exposed to 1.00 Gy. Significant reduction in the number of intersections of dendrites with the zonal boundaries were found in the groups exposed to 0.27 Gy or more. There was no difference in the numerical density of synapses in layer I between the control and irradiated groups. These results suggested that doses as low as 0.27 Gy could cause a morphologically discernible change in the mammalian cerebrum

  11. Evaluation of reproductive function of female rats exposed to radiofrequency fields (27. 12 MHz) near a shortwave diathermy device

    Energy Technology Data Exchange (ETDEWEB)

    Brown-Woodman, P.D.; Hadley, J.A.; Richardson, L.; Bright, D.; Porter, D.

    1989-04-01

    In recent years, there has been increased concern regarding effects of operator exposure to the electromagnetic (EM) field associated with shortwave diathermy devices. The present study was designed to investigate the effects, on rats, of repeated exposure to such an EM field. Following repeated exposure for 5 wk, a reduction in fertility occurred as indicated by a reduced number of matings in exposed rats compared to sham-irradiated rats and a reduction in the number of rats that conceived after mating. The data suggest that female operators could experience reduced fertility, if they remained close to the console for prolonged periods. This has particular significant for the physiotherapy profession.

  12. Uranium XAFS analysis of kidney from rats exposed to uranium.

    Science.gov (United States)

    Kitahara, Keisuke; Numako, Chiya; Terada, Yasuko; Nitta, Kiyohumi; Shimada, Yoshiya; Homma-Takeda, Shino

    2017-03-01

    The kidney is the critical target of uranium exposure because uranium accumulates in the proximal tubules and causes tubular damage, but the chemical nature of uranium in kidney, such as its chemical status in the toxic target site, is poorly understood. Micro-X-ray absorption fine-structure (µXAFS) analysis was used to examine renal thin sections of rats exposed to uranyl acetate. The U L III -edge X-ray absorption near-edge structure spectra of bulk renal specimens obtained at various toxicological phases were similar to that of uranyl acetate: their edge position did not shift compared with that of uranyl acetate (17.175 keV) although the peak widths for some kidney specimens were slightly narrowed. µXAFS measurements of spots of concentrated uranium in the micro-regions of the proximal tubules showed that the edge jump slightly shifted to lower energy. The results suggest that most uranium accumulated in kidney was uranium (VI) but a portion might have been biotransformed in rats exposed to uranyl acetate.

  13. Effect of nephrotoxic treatment with gentamicin on rats chronically exposed to uranium.

    Science.gov (United States)

    Rouas, Caroline; Stefani, Johanna; Grison, Stéphane; Grandcolas, Line; Baudelin, Cédric; Dublineau, Isabelle; Pallardy, Marc; Gueguen, Yann

    2011-01-11

    Uranium is a radioactive heavy metal with a predominantly chemical toxicity, affecting especially the kidneys and more particularly the proximal tubular structure. Until now, few experimental studies have examined the effect of chronic low-dose exposure to uranium on kidney integrity: these mainly analyse standard markers such as creatinine and urea, and none has studied the effect of additional co-exposure to a nephrotoxic agent on rats chronically exposed to uranium. The aim of the present study is to examine the potential cumulative effect of treating uranium-exposed rats with a nephrotoxic drug. Neither physiological indicators (diuresis and creatinine clearance) nor standard plasma and urine markers (creatinine, urea and total protein) levels were deteriorated when uranium exposure was combined with gentamicin-induced nephrotoxicity. A histological study confirmed the preferential impact of gentamicin on the tubular structure and showed that uranium did not aggravate the histopathological renal lesions. Finally, the use of novel markers of kidney toxicity, such as KIM-1, osteopontin and kallikrein, provides new knowledge about the nephrotoxicity threshold of gentamicin, and allows us to conclude that under our experimental conditions, low dose uranium exposure did not induce signs of nephrotoxicity or enhance renal sensitivity to another nephrotoxicant. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  14. Effect of nephrotoxic treatment with gentamicin on rats chronically exposed to uranium

    International Nuclear Information System (INIS)

    Rouas, Caroline; Stefani, Johanna; Grison, Stephane; Grandcolas, Line; Baudelin, Cedric; Dublineau, Isabelle; Pallardy, Marc; Gueguen, Yann

    2011-01-01

    Uranium is a radioactive heavy metal with a predominantly chemical toxicity, affecting especially the kidneys and more particularly the proximal tubular structure. Until now, few experimental studies have examined the effect of chronic low-dose exposure to uranium on kidney integrity: these mainly analyse standard markers such as creatinine and urea, and none has studied the effect of additional co-exposure to a nephrotoxic agent on rats chronically exposed to uranium. The aim of the present study is to examine the potential cumulative effect of treating uranium-exposed rats with a nephrotoxic drug. Neither physiological indicators (diuresis and creatinine clearance) nor standard plasma and urine markers (creatinine, urea and total protein) levels were deteriorated when uranium exposure was combined with gentamicin-induced nephrotoxicity. A histological study confirmed the preferential impact of gentamicin on the tubular structure and showed that uranium did not aggravate the histopathological renal lesions. Finally, the use of novel markers of kidney toxicity, such as KIM-1, osteopontin and kallikrein, provides new knowledge about the nephrotoxicity threshold of gentamicin, and allows us to conclude that under our experimental conditions, low dose uranium exposure did not induce signs of nephrotoxicity or enhance renal sensitivity to another nephrotoxicant.

  15. Cytomorphometric changes in hippocampal CA1 neurons exposed to simulated microgravity using rats as model

    Directory of Open Access Journals (Sweden)

    Amit eRanjan

    2014-05-01

    Full Text Available Microgravity and sleep loss lead to cognitive and learning deficits. These behavioral alterations are likely to be associated with cytomorphological changes and loss of neurons. To understand the phenomenon, we exposed rats (225-275g to 14 days simulated microgravity (SMg and compared its effects on CA1 hippocampal neuronal plasticity, with that of normal cage control rats. We observed that the mean area, perimeter, synaptic cleft and length of active zone of CA1 hippocampal neurons significantly decreased while dendritic arborization and number of spines significantly increased in SMg group as compared with controls. The mean thickness of the post synaptic density and total dendritic length remained unaltered. The changes may be a compensatory effect induced by exposure to microgravity; however, the effects may be transient or permanent, which need further study. These findings may be useful for designing effective prevention for those, including the astronauts, exposed to microgravity. Further, subject to confirmation we propose that SMg exposure might be useful for recovery of stroke patients.

  16. A hypothalamic-pituitary-adrenal axis-associated neuroendocrine metabolic programmed alteration in offspring rats of IUGR induced by prenatal caffeine ingestion.

    Science.gov (United States)

    Xu, D; Wu, Y; Liu, F; Liu, Y S; Shen, L; Lei, Y Y; Liu, J; Ping, J; Qin, J; Zhang, C; Chen, L B; Magdalou, J; Wang, H

    2012-11-01

    Caffeine is a definite factor of intrauterine growth retardation (IUGR). Previously, we have confirmed that prenatal caffeine ingestion inhibits the development of hypothalamic-pituitary-adrenal (HPA) axis, and alters the glucose and lipid metabolism in IUGR fetal rats. In this study, we aimed to verify a programmed alteration of neuroendocrine metabolism in prenatal caffeine ingested-offspring rats. The results showed that prenatal caffeine (120 mg/kg.day) ingestion caused low body weight and high IUGR rate of pups; the concentrations of blood adrenocorticotropic hormone (ACTH) and corticosterone in caffeine group were significantly increased in the early postnatal period followed by falling in late stage; the level of blood glucose was unchanged, while blood total cholesterol (TCH) and triglyceride (TG) were markedly enhanced in adult. After chronic stress, the concentrations and the gain rates of blood ACTH and corticosterone were obviously increased, meanwhile, the blood glucose increased while the TCH and TG decreased in caffeine group. Further, the hippocampal mineralocorticoid receptor (MR) expression in caffeine group was initially decreased and subsequently increased after birth. After chronic stress, the 11β-hydroxysteroid dehydrogenase-1, glucocorticoid receptor (GR), MR as well as the MR/GR ratio were all significantly decreased. These results suggested that prenatal caffeine ingestion induced the dysfunction of HPA axis and associated neuroendocrine metabolic programmed alteration in IUGR offspring rats, which might be related with the functional injury of hippocampus. These observations provide a valuable experimental basis for explaining the susceptibility of IUGR offspring to metabolic syndrome and associated diseases. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Participation of catalase in voluntary ethanol consumption in perinatally low-level lead-exposed rats.

    Science.gov (United States)

    Mattalloni, Mara S; De Giovanni, Laura N; Molina, Juan C; Cancela, Liliana M; Virgolini, Miriam B

    2013-10-01

    Environmental lead (Pb) exposure and alcohol abuse pose significant public health problems for our society. One of the proposed mechanisms of action of the developmental neurotoxicant Pb is related to its ability to affect antioxidant enzymes, including catalase (CAT). Ethanol's (EtOH) motivational effects are postulated to be mediated by the CAT-dependent acetaldehyde generated in the brain. The current study sought to investigate the role of this enzyme in the elevated EtOH intake previously reported in perinatally Pb-exposed rats. Thirty-five-day-old male Wistar rats exposed to 220 ppm Pb during gestation and lactation were offered escalating EtOH solutions (2 to 10%) or water, 2 h/d for 28 days. Once baseline 10% EtOH intake was achieved, they were injected with (i) saline (SAL), (ii) 3-amino 1,2,4 triazole (aminotriazole [AT], a CAT inhibitor, 250 mg/kg intraperitoneally [i.p.], 5 hours before the last 8 EtOH intake sessions), or (iii) 3-nitropropionic acid (3NPA; a CAT activator, 20 mg/kg subcutaneously [s.c.], 45 minutes before the last 4 EtOH intake sessions). Rats were then sacrificed, blood collected, and brain regions harvested for CAT activity determination. Additional studies evaluated EtOH intake and CAT activity in response to 10 and 30 mg/kg 3NPA. Both 3NPA and AT were evaluated for striatal cytotoxicity. We observed that AT pretreatment blunted the increased EtOH intake, as well as the elevated CAT activity in blood, cerebellum, and hippocampus evidenced in the developmentally Pb-exposed rats that have consumed EtOH. Conversely, 20 mg/kg 3NPA further increased voluntary EtOH intake in these animals as compared with controls, concomitantly with a slight elevation in CAT activity both in blood and in the striatum, associated with no changes in striatal cytotoxicity. These results suggest a participation of CAT, and possibly acetaldehyde, in Pb-induced high EtOH intake, and open up new avenues to elucidate the mechanism that underlies the Pb and Et

  18. Steroidogenesis-related gene expression in the rat ovary exposed to melatonin supplementation

    Directory of Open Access Journals (Sweden)

    Gisele Negro Lima

    2015-02-01

    Full Text Available OBJECTIVE: To analyze steroidogenesis-related gene expression in the rat ovary exposed to melatonin supplementation. METHODS: Thirty-two virgin adult female rats were randomized to two groups as follows: the control group GI received vehicle and the experimental group GII received melatonin supplementation (10 µg/night per animal for 60 consecutive days. After the treatment, animals were anesthetized and the collected ovaries were immediately placed in liquid nitrogen for complementary deoxyribonucleic acid microarray analyses. A GeneChip¯ Kit Rat Genome 230 2.0 Affymetrix Array was used for gene analysis and the experiment was repeated three times for each group. The results were normalized with the GeneChip¯ Operating Software program and confirmed through analysis with the secondary deoxyribonucleic acid-Chip Analyzer (dChip software. The data were confirmed by real-time reverse transcription polymerase chain reaction analysis. Genes related to ovarian function were further confirmed by immunohistochemistry. RESULTS: We found the upregulation of the type 9 adenylate cyclase and inhibin beta B genes and the downregulation of the cyclic adenosine monophosphate response element modulator and cytochrome P450 family 17a1 genes in the ovarian tissue of GII compared to those of the control group. CONCLUSION: Our data suggest that melatonin supplementation decreases gene expression of cyclic adenosine monophosphate, which changes ovarian steroidogenesis.

  19. Protein expression in the nucleus accumbens of rats exposed to developmental vitamin D deficiency.

    Directory of Open Access Journals (Sweden)

    John McGrath

    Full Text Available INTRODUCTION: Developmental vitamin D (DVD deficiency is a candidate risk factor for schizophrenia. Animal models have confirmed that DVD deficiency is associated with a range of altered genomic, proteomic, structural and behavioural outcomes in the rat. Because the nucleus accumbens has been implicated in neuropsychiatric disorders, in the current study we examined protein expression in this region in adult rats exposed to DVD deficiency METHODS: Female Sprague Dawley rats were maintained on a vitamin D deficient diet for 6 weeks, mated and allowed to give birth, after which a diet containing vitamin D was reintroduced. Male adult offspring (n = 8 were compared to control male (n = 8. 2-D gel electrophoresis-based proteomics and mass spectroscopy were used to investigate differential protein expression. RESULTS: There were 35 spots, mapped to 33 unique proteins, which were significantly different between the two groups. Of these, 22 were down-regulated and 13 up-regulated. The fold changes were uniformly small, with the largest FC being -1.67. Within the significantly different spots, three calcium binding proteins (calbindin1, calbindin2 and hippocalcin were altered. Other proteins associated with DVD deficiency related to mitochondrial function, and the dynamin-like proteins. CONCLUSIONS: Developmental vitamin D deficiency was associated with subtle changes in protein expression in the nucleus accumbens. Disruptions in pathways related to calcium-binding proteins and mitochondrial function may underlie some of the behavioural features associated with animal models of developmental vitamin D deficiency.

  20. Morphometric study on age-dependent pulmonary lesions in rats exposed to nitrogen dioxide

    Energy Technology Data Exchange (ETDEWEB)

    Kyono, H.; Kawai, K.

    1982-01-01

    Electronmicroscopic morphometry was performed on lung of 1, 3, 12 and 21 months-old rats exposed to 0.1, 0.5, 3 and 10 ppm nitrogen dioxide (NO/sub 2/) continuously for one month. The rats used in this experiment were all supplied at one time from one colony and kept under a barrier system until exposure. Effects of aging on the responses of lungs to NO/sub 2/ were studied by comparing the dose-effect reaction patterns among the age groups. A trend of dose-dependent increase of arithmetic mean thickness of air-blood barrier was found in all age groups examined. The response of lung to NO/sub 2/ exposure showed age-related differences. Based on the morphometric index, the response declines from 1 to 12 months, but increases again in 21-months-old rats. The compartmental components of alveolar wall tissue such as type I epithelial cells, type II epithelial cells, interstitial cells, interstitial matrix and capillary endothelium appeared to have various degrees of response due to both age at onset of exposure and NO/sub 2/ concentration, resulting in the appearance of varying stages in impairment or repair. Accordingly, the response of each compartmental component of lung to the concentrations of NO/sub 2/ did not always exhibit a simple dose-dependent increase or decrease but sometimes indicated a multiphasic reaction pattern.

  1. Excretion of 14C-labeled cyanide in rats exposed to chronic intake of potassium cyanide

    International Nuclear Information System (INIS)

    Okoh, P.N.

    1983-01-01

    The excretion of an acute dose of 14C-labeled cyanide in urine, feces, and expired air was studied in rats exposed to daily intake of unlabeled KCN in the diet for 6 weeks. Urinary excretion was the main route of elimination of cyanide carbon in these rats, accounting for 83% of the total excreted radioactivity in 12 hr and 89% of the total excreted radioactivity in 24 hr. The major excretion metabolite of cyanide in urine was thiocyanate, and this metabolite accounted for 71 and 79% of the total urinary activity in 12 hr and 24 hr, respectively. The mean total activity excreted in expired air after 12 hr was only 4%, and this value did not change after 24 hr. Of the total activity in expired air in 24 hr, 90% was present as carbon dioxide and 9% as cyanide. When these results were compared with those observed for control rats, it was clear that the mode of elimination of cyanide carbon in both urine and breath was not altered by the chronic intake of cyanide

  2. Neurobehavioral, reflexological and physical development of Wistar rat offspring exposed to ayahuasca during pregnancy and lactation

    Directory of Open Access Journals (Sweden)

    Carolina Dizioli Rodrigues de Oliveira

    2011-09-01

    Full Text Available Ayahuasca is a hallucinogenic beverage prepared by the decoction of plants native to the Amazon Basin region. The beverage has been used throughout the world by members of some syncretic religious movements. Despite the recent legalization of ayahuasca in Brazil for religious purposes, there is little pre-clinical and clinical information attesting to its safety, particularly in relation to the use during pregnancy. The aim of the current work was to determine the effects of perinatal exposure to ayahuasca (from the 6th day of pregnancy to the 10th day of lactation on physical, reflexology and neurobehavioral parameters of the Wistar rat offspring. The offspring showed no statistically significant changes in the physical and reflexology parameters evaluated. However, in adult rats, perinatally exposed to ayahuasca, an increase in frequency of entries in open arms in elevated plus-maze test, a decrease in total time of interaction in social interaction test, a decrease in time of latency for the animal to start swimming and a decrease of the minimum convulsant dose induced by pentylenetetrazol were observed. In conclusion, our results showed that the use of ayahuasca by mothers during pregnancy and lactation reduced the general anxiety and social motivation of the rat offspring. Besides, it promoted a higher sensitivity for initiation and spread of seizure activity.

  3. Neurobehavioral, reflexological and physical development of Wistar rat offspring exposed to ayahuasca during pregnancy and lactation

    Directory of Open Access Journals (Sweden)

    Carolina Dizioli Rodrigues de Oliveira

    2011-12-01

    Full Text Available Ayahuasca is a hallucinogenic beverage prepared by the decoction of plants native to the Amazon Basin region. The beverage has been used throughout the world by members of some syncretic religious movements. Despite the recent legalization of ayahuasca in Brazil for religious purposes, there is little pre-clinical and clinical information attesting to its safety, particularly in relation to the use during pregnancy. The aim of the current work was to determine the effects of perinatal exposure to ayahuasca (from the 6th day of pregnancy to the 10th day of lactation on physical, reflexology and neurobehavioral parameters of the Wistar rat offspring. The offspring showed no statistically significant changes in the physical and reflexology parameters evaluated. However, in adult rats, perinatally exposed to ayahuasca, an increase in frequency of entries in open arms in elevated plus-maze test, a decrease in total time of interaction in social interaction test, a decrease in time of latency for the animal to start swimming and a decrease of the minimum convulsant dose induced by pentylenetetrazol were observed. In conclusion, our results showed that the use of ayahuasca by mothers during pregnancy and lactation reduced the general anxiety and social motivation of the rat offspring. Besides, it promoted a higher sensitivity for initiation and spread of seizure activity.

  4. Polycystic ovary syndrome resembling histopathological alterations in ovaries from prenatal androgenized female rats

    Directory of Open Access Journals (Sweden)

    Wang Fang

    2012-05-01

    Full Text Available Abstract Background The polycystic ovary syndrome (PCOS affects approximately 6-10% of women of reproductive age and is characterized by chronic anovulation and hyperandrogenism. However, a comprehensive understanding of the mechanisms that dictate androgen overproduction is lacking, which may account for inconsistencies between measures of androgen excess and clinical presentation in individual cases. Methods A rat model of PCOS was established by injecting dehydroepiandrosterone sulfoconjugate (DHEAS into pregnant females. Rats were administered with DHEAS (60 mg/kg/d subcutaneously (s.c. for all 20 days of pregnancy (Group A, or for the first 10 days (Group B, or from day 11 to day 20 (Group C. Controls were administered with injection oil (0.2 ml/day s.c. throughout pregnancy (Group D. The litter rate, abortion rate, and offspring survival rate in each group were recorded. Serum androgen and estrogen were measured and the morphological features of the ovaries were examined by light and electron microscopy in the offspring of each group. Results We found that rats injected with DHEAS throughout pregnancy (group A lost fertility. Rats injected with DHEAS during early pregnancy (group B exhibited more serious aberrations in fertility than both Group C, in which rats were injected with DHEAS during late pregnancy (P  Conclusions Our results indicate that androgen excess during pregnancy can decrease rat fertility. Excess androgen at the early stage of pregnancy causes high reproductive toxicity, leading to abnormality of ovarian morphology and functions in female offspring.

  5. Effects of thyroxine on the migration of hippocampal neurons in newborn rat exposed to HTO

    International Nuclear Information System (INIS)

    Cai Erpeng; Qiu Jun; Wang Yongsheng; Wu Cuiping; Yao Xiaobo; Wang Mingming

    2012-01-01

    Objective: To explore the effect of thyroxine (TH) on the migration of hippocampal neurons in newborn rat exposed to tritiated water (HTO). Methods: The hippocampal neurons from neonatal rats were primarily cultured, 7 days later, randomly divided into control group, HTO group, TH group and HTO + TH group (3.7 × 10 5 Bq/ml HTO and 0.3 μg/ml TH were simultaneously added). After 24 h, the distance of neuronal migration was measured with Leica AF 6000, the expressions of BDNF and Reelin mRNA in neurons were analyzed with reverse transcription polymerase chain reaction (RT-PCR), the expression of β-tubulin protein in neurons was assayed with Western blot and immunocytochemical staining. Results: Compared with control group, the expression of Reelin mRNA, BDNF mRNA and β-tubulin in HTO group were significantly reduced (t=5.80, 5.48, 5.47, P<0.01), but those in HTO + TH group and TH group were obviously increased (t=7.75, 12.06, 13.65, P<0.01; t=4.34, 5.47, 5.65, P<0.01) and higher than that in HTO group (t=2.92, 10.32, 8.76, P<0.01; t=18.07, 20.55, 40.13, P<0.01). Accordingly, the neuronal migration distance in HTO group was much shorter than that in control (t=8.62, P<0.01), and in HTO + TH group and TH group was far longer than that in control (t=7.64, 4.93, P<0.01). Moreover, the neuronal migration distance in HTO + TH group was notably elongated in comparison with that in HTO group (t=11.32, 12.31, P<0.01). Conclusions: Thyroxine may promote the migration of hippocampal neurons in newborn rat exposed to HTO. (authors)

  6. Chronic impairments in spatial learning and memory in rats previously exposed to chlorpyrfos or diisopropylfluorophosphate.

    Science.gov (United States)

    Terry, A V; Beck, W D; Warner, S; Vandenhuerk, L; Callahan, P M

    2012-01-01

    The acute toxicity of organophosphates (OPs) has been studied extensively; however, much less attention has been given to the subject of repeated exposures that are not associated with overt signs of toxicity (i.e., subthreshold exposures). The objective of this study was to determine if the protracted spatial learning impairments we have observed previously after repeated subthreshold exposures to the insecticide chlorpyrifos (CPF) or the alkylphosphate OP, diisopropylfluorophosphate (DFP) persisted for longer periods after exposure. Male Wistar rats (beginning at two months of age) were initially injected subcutaneously with CPF (10.0 or 18.0mg/kg) or DFP (0.25 or 0.75 mg/kg) every other day for 30 days. After an extended OP-free washout period (behavioral testing begun 50 days after the last OP exposure), rats previously exposed to CPF, but not DFP, were impaired in a radial arm maze (RAM) win-shift task as well as a delayed non-match to position procedure. Later experiments (i.e., beginning 140 days after the last OP exposure) revealed impairments in the acquisition of a water maze hidden platform task associated with both OPs. However, only rats previously exposed to DFP were impaired in a second phase of testing when the platform location was changed (indicative of deficits of cognitive flexibility). These results indicate, therefore, that repeated, subthreshold exposures to CPF and DFP may lead to chronic deficits in spatial learning and memory (i.e., long after cholinesterase inhibition has abated) and that insecticide and alkylphosphate-based OPs may have differential effects depending on the cognitive domain evaluated. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Prenatal Stress Induces Long-Term Effects in Cell Turnover in the Hippocampus-Hypothalamus-Pituitary Axis in Adult Male Rats

    Science.gov (United States)

    Baquedano, Eva; García-Cáceres, Cristina; Diz-Chaves, Yolanda; Lagunas, Natalia; Calmarza-Font, Isabel; Azcoitia, Iñigo; Garcia-Segura, Luis M.; Argente, Jesús; Chowen, Julie A.; Frago, Laura M.

    2011-01-01

    Subchronic gestational stress leads to permanent modifications in the hippocampus-hypothalamus-pituitary-adrenal axis of offspring probably due to the increase in circulating glucocorticoids known to affect prenatal programming. The aim of this study was to investigate whether cell turnover is affected in the hippocampus-hypothalamus-pituitary axis by subchronic prenatal stress and the intracellular mechanisms involved. Restraint stress was performed in pregnant rats during the last week of gestation (45 minutes; 3 times/day). Only male offspring were used for this study and were sacrificed at 6 months of age. In prenatally stressed adults a decrease in markers of cell death and proliferation was observed in the hippocampus, hypothalamus and pituitary. This was associated with an increase in insulin-like growth factor-I mRNA levels, phosphorylation of CREB and calpastatin levels and inhibition of calpain -2 and caspase -8 activation. Levels of the anti-apoptotic protein Bcl-2 were increased and levels of the pro-apoptotic factor p53 were reduced. In conclusion, prenatal restraint stress induces a long-term decrease in cell turnover in the hippocampus-hypothalamus-pituitary axis that might be at least partly mediated by an autocrine-paracrine IGF-I effect. These changes could condition the response of this axis to future physiological and pathophysiological situations. PMID:22096592

  8. Can prenatal low-dose irradiation affect behavior of adult rats?

    International Nuclear Information System (INIS)

    Smajda, B.; Tomasova, L.; Kokocova, N.

    2011-01-01

    The aim of our study was to determine whether exposure of very low dose gamma-rays during the critical phase of brain development affects some selected behavioral parameters in adult rats. Pregnant female Wistar rats were irradiated with 1 Gy gamma-rays from a cobalt source at 17 th day of pregnancy. The progeniture of irradiated as well as non-irradiated females have undergone behavioral tests at the age of 3 months. Irradiated animals exhibited lower locomotor and exploratory activity in the open field test. (authors)

  9. Prenatal ethanol exposure-induced adrenal developmental abnormality of male offspring rats and its possible intrauterine programming mechanisms.

    Science.gov (United States)

    Huang, Hegui; He, Zheng; Zhu, Chunyan; Liu, Lian; Kou, Hao; Shen, Lang; Wang, Hui

    2015-10-01

    Fetal adrenal developmental status is the major determinant of fetal tissue maturation and offspring growth. We have previously proposed that prenatal ethanol exposure (PEE) suppresses fetal adrenal corticosterone (CORT) synthesis. Here, we focused on PEE-induced adrenal developmental abnormalities of male offspring rats before and after birth, and aimed to explore its intrauterine programming mechanisms. A rat model of intrauterine growth retardation (IUGR) was established by PEE (4g/kg·d). In PEE fetus, increased serum CORT concentration and decreased insulin-like growth factor 1 (IGF1) concentration, with lower bodyweight and structural abnormalities as well as a decreased Ki67 expression (proliferative marker), were observed in the male fetal adrenal cortex. Adrenal glucocorticoid (GC)-metabolic activation system was enhanced while gene expression of IGF1 signaling pathway with steroidogenic acute regulatory protein (StAR), 3β-hydroxysteroid dehydrogenase (3β-HSD) was decreased. Furthermore, in the male adult offspring of PEE, serum CORT level was decreased but IGF1 was increased with partial catch-up growth, and Ki67 expression demonstrated no obvious change. Adrenal GC-metabolic activation system was inhibited, while IGF1 signaling pathway and 3β-HSD was enhanced with the steroidogenic factor 1 (SF1), and StAR was down-regulated in the adult adrenal. Based on these findings, we propose a "two-programming" mechanism for PEE-induced adrenal developmental toxicity: "the first programming" is a lower functional programming of adrenal steroidogenesis, and "the second programming" is GC-metabolic activation system-related GC-IGF1 axis programming. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Autoradiographic research on cell proliferation of prenatal rat lung cells and their influence using the mitogen Kallikrein

    International Nuclear Information System (INIS)

    Bock-Lamberlin, P.R.

    1980-01-01

    In this work autoradiographic experiments were carried out on the kinetics of proliferation of four cell populations of the prenatal rat lung with the help of the determination of the 3 H-thymidine marker indices, with the following results: 1. The four studied cell populations exhibited variable proliferation rates on the twentieth or twenty-first day of development. 2. The strongest affect of the exogenously applied mitogen Kallikrein was demonstrated on the vessel wall cells, the next strongest on the bronchial epithelial cells, then the cartilage cells and finally the alveolar wall cells. 3. The mitogenic effect is dependent on dose. Higher doses significantly increased the 3 H-thymidine marker indices of the four cell populations tested in this work. 4. When the exposure time of the Kallikrein was extended by one hour this lead partially to stronger mitogenic effects than by the shorter exposure times at the same and higher dose levels of mitogen. 5. The 3 H-thymidine marker indices are dependent on the exposure time. 6. With increasing litter size, the 3 H indices as a rule decrease. (orig./MG) [de

  11. Effects of prenatal exposure to hydoxylated PCB metabolites and some brominated flame retardants on the development of rats

    Energy Technology Data Exchange (ETDEWEB)

    Buitenhuis, C.; Cenijn, P.C.; Velzen, M. van; Gutleb, A.C.; Legler, J. [Institute for Environmental Studies (IVM), Amsterdam (Netherlands); Lilienthal, H. [Heinrich Univ., Duesseldorf (Germany). Dept. Neurobehavioural Toxicology, Medical Institute of Environmental Hygiene; Malmberg, T.; Bergman, Aa. [Stockholm Univ. (Sweden). Dept. of Environmental Chemistry; Brouwer, A.

    2004-09-15

    Possible human health effects from low-level exposure to environmental chemicals are an issue that has attracted much attention. Environmental compounds that may play a role are those that may disrupt endocrine function. Organohalogen compounds, and in particular their hydroxylated metabolites, show a striking resemblance to steroid hormones.The main objective of this research is to investigate comparative pathways of early life-stage exposure and long-term effects for several classes of organohalogens, including polychlorinated biphenyls (PCBs) and flame retardants, polybrominated bisphenols and -diphenylethers, and their hydroxylated metabolites. Due to their prevalence in human plasma, the hydroxylated PCB metabolites 4-OH-CB107 and 4-OH-CB187, as well as 6-OH-BDE47 and 2,4,6- tribromophenol, were selected as test compounds. BDE 47 has been included as a test compound due to its relatively high levels in the environment and biota, whereas tetrabromobisphenol A (TBBPA) was selected because of its high volume production. The in vivo studies involved prenatal exposure of rats to test compounds during critical stages of gonadal development and were focussed on low dose effects. Several endpoints were investigated, including endocrine (thyroid and sex steroid hormones) effects, developmental landmarks, sexual and neurobehavioural development. Blood plasma and tissue levels of test compounds were analysed to determine transplacental transfer of (hydroxylated) organohalogens.

  12. Proximal renal tubular injury in rats sub-chronically exposed to low fluoride concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Cárdenas-González, Mariana C.; Del Razo, Luz M. [Departmento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), México, D. F., México (Mexico); Barrera-Chimal, Jonatan [Unidad de Fisiología Molecular, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México and Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México, D. F., México (Mexico); Jacobo-Estrada, Tania [Departmento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), México, D. F., México (Mexico); López-Bayghen, Esther [Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), México, D. F., México (Mexico); and others

    2013-11-01

    Fluoride is usually found in groundwater at a very wide range of concentration between 0.5 and 25 ppm. At present, few studies have assessed the renal effects of fluoride at environmentally relevant concentrations. Furthermore, most of these studies have used insensitive and nonspecific biomarkers of kidney injury. The aim of this study was to use early and sensitive biomarkers to evaluate kidney injury after fluoride exposure to environmentally relevant concentrations. Recently weaned male Wistar rats were exposed to low (15 ppm) and high (50 ppm) fluoride concentrations in drinking water for a period of 40 days. At the end of the exposure period, kidney injury biomarkers were measured in urine and renal mRNA expression levels were assessed by real time RT-PCR. Our results showed that the urinary kidney injury molecule (Kim-1), clusterin (Clu), osteopontin (OPN) and heat shock protein 72 excretion rate significantly increased in the group exposed to the high fluoride concentration. Accordingly, fluoride exposure increased renal Kim-1, Clu and OPN mRNA expression levels. Moreover, there was a significant dose-dependent increase in urinary β-2-microglobulin and cystatin-C excretion rate. Additionally, a tendency towards a dose dependent increase of tubular damage in the histopathological light microscopy findings confirmed the preferential impact of fluoride on the tubular structure. All of these changes occurred at early stages in which, the renal function was not altered. In conclusion using early and sensitive biomarkers of kidney injury, we were able to found proximal tubular alterations in rats sub-chronically exposed to fluoride. - Highlights: • Exposure to low concentrations of fluoride induced proximal tubular injury • Increase in urinary Kim-1, Clu, OPN and Hsp72 in 50 ppm fluoride-exposed group • Increase in urinary B2M and CysC in 15 and 50 ppm fluoride-exposed groups • Fluoride exposure increased renal Kim, Clu and OPN mRNA expression levels.

  13. Exposure to perfluorooctane sulfonate during pregnancy in rat and mouse. I: maternal and prenatal evaluations

    Science.gov (United States)

    Abstract: The maternal and developmental toxicities of perfluorooctane sulfonate (PFOS, C8F17SO3-) were evaluated in the rat and mouse. PFOS is an environmentally persistent compound used as a surfactant and occurs as a degradation product of both perfluorooctane sulfonyl fluorid...

  14. PRENATAL EXPOSURE TO CHLORPYRIFOS ALTERS NEUROTROPHIN IMMUNOREACTIVITY AND APOPTOSIS IN RAT BRAIN.

    Science.gov (United States)

    In the present study, the effects of the organophosphate pesticide chlorpyrifos [CPF; O,O'diethyl O-3,5,6-trichloro-2-pyridyl) phosphorothionate] on the regional distribution of three neurotrophic factors and on levels of apoptosis in gestational rat brain were characterized. P...

  15. Concentration of hepatic vitamins A and E in rats exposed to chlorpyrifos and/or enrofloxacin.

    Science.gov (United States)

    Spodniewska, A; Barski, D

    2016-01-01

    The aim of the study was to determine the level of antioxidant vitamins A and E in the liver of rats exposed to chlorpyrifos and/or enrofloxacin. Chlorpyrifos (Group I) was administered at a dose of 0.04 LD50 (6 mg/kg b.w.) for 28 days, and enrofloxacin (Group II) at a dose of 5 mg/kg b.w. for 5 consecutive days. The animals of group III were given both of the mentioned above compounds at the same manner as groups I and II, but enrofloxacin was applied to rats for the last 5 days of chlorpyrifos exposure (i.e. on day 24, 25, 26, 27 and 28). Chlorpyrifos and enrofloxacin were administered to rats intragastrically via a gastric tube. The quantitative determination of vitamins was made by the HPLC method. The results of this study indicated a reduction in the hepatic concentrations of vitamins A and E, compared to the control, which sustained for the entire period of the experiment. The four-week administration of chlorpyrifos to rats resulted in a significant decrease of vitamins in the initial period of the experiment, i.e. up to 24 hours after exposure. For vitamin A the maximum drop was observed after 24 hours (19.24%) and for vitamin E after 6 hours (23.19%). Enrofloxacin caused a slight (3-9%) reduction in the level of the analysed vitamins. In the chlorpyrifos-enrofloxacin co-exposure group reduced vitamins A and E levels were also noted, but changes in this group were less pronounced in comparison to the animals intoxicated with chlorpyrifos only. The decrease in the antioxidant vitamin levels, particularly noticeable in the chlorpyrifos- and the chlorpyrifos combined with enrofloxacin-treated groups, may result not only from the increase in the concentration of free radicals, but also from the intensification of the secondary stages of lipid peroxidation.

  16. Alterations of metallothionein isomers in Hg{sup 0}-exposed rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Yasutake, A. [Biochemistry Section, National Institute for Minamata Disease, Minamata, Kumamoto 867-0008 (Japan); Nagano, M. [Morikawa Kenkodo Co., Ltd., 2170 Taguchi, Kosa, Kamimashiki, Kumamoto 861-4616 (Japan); Hirayama, K. [Kumamoto University College of Medical Science, Kuhonji, Kumamoto 862-0976 (Japan)

    2003-01-01

    Previously we found that exposure to mercury vapor effectively induced brain metallothionein (MT) in rats. Here, using FPLC-gel chromatography, we examined time-dependent alterations in the MT isomers, MT-I/II and MT-III, following 3 weeks of exposure. Rats were exposed to mercury vapor at 8.3 mg/m{sup 3} for 15 h in total over 5 consecutive days. Total MT levels in rat cerebrum and cerebellum increased by 65% and 155%, respectively, 24 h after the final exposure. The increased levels in both tissues remained unchanged for at least 2 weeks after termination of exposure. Interestingly, most MT in control rat cerebrum and cerebellum was accounted for by MT-III, with MT-I/II being less than 10%. Through mercury vapor exposure, MT-I/II was quickly induced to a significant extent in both tissues, reaching a level comparable to that of MT-III. The induction rate of MT-I/II in the cerebellum was somewhat higher than in the cerebrum. Chromatograms showed that the MT-I/II thus induced began to decline at an early stage in both tissues. In the cerebrum, the amount of MT-I/II on day 22 was about 30% of the maximum level on day 1. On the other hand, the induction of MT-III was not that dramatic, but it did become evident, at least in the latter stage, when MT-I/II had begun to decrease. Thus, though the induction rate of MT-III was not as high as MT-I/II, it was sustained throughout the experimental period. (orig.)

  17. Antioxidant Role of Pomegranates on Liver and Brain Tissues of Rats Exposed to an Organophosphorus Insecticide

    International Nuclear Information System (INIS)

    Abd Elmonem, H.A.

    2014-01-01

    Toxicities of organophosphorus insecticides cause oxidative damage on many organs such as the liver and brain due to generation of reactive oxygen species. Pomegranate is among the richest fruit in poly - phenols. The aim of this study was to compare between the antioxidant strength of pomegranate juice (PJ) and pomegranate molasses (PM) and their effects on alanine transferase (ALT), aspartate aminotransferase (AST), Alkaline phosphatase (ALP) and total protein (TP) in liver and levels of malondialdehyde (MAD), reduced glutathione (GSH) and nitric oxide (NO) in rat liver and brain tissues exposed to 1/10 LD 50 diazinon (DI). Six groups each of 6 male albino rats were used comprising control, DI, PJ, PM, PJ + DI and PM + DI for 15 days. The activities of ALT, AST, and TP concentration in liver have been increased due to treatment of rats with DI. These increases restored to normalcy when rats were supplemented with PJ or PM with DI. The results demonstrate that treatment with DI induced significant increase in MDA and NO concentrations and significant decrease in GSH levels of liver and brain tissues. The administration of PJ or PM along with DI significant decrease in MDA and NO levels and significant increase in GSH level compared to DI-group. The present study suggest that PJ or PM has a potential protective effect as it can elevate antioxidant defense system, lessens induced oxidative dam - ages and protect the brain and liver tissue against DI-induced toxicity. In addition, comaring PJ with PM it was noticed that PJ had higher antioxidant activity as evidenced by increased GSH content and decreased NO level in the liver by greater extend than PM.

  18. Developmental programming of vascular dysfunction by prenatal and postnatal zinc deficiency in male and female rats.

    Science.gov (United States)

    Mendes Garrido Abregú, Facundo; Gobetto, María Natalia; Juriol, Lorena Vanesa; Caniffi, Carolina; Elesgaray, Rosana; Tomat, Analía Lorena; Arranz, Cristina

    2018-06-01

    Micronutrient malnutrition during intrauterine and postnatal growth may program cardiovascular diseases in adulthood. We examined whether moderate zinc restriction in male and female rats throughout fetal life, lactation and/or postweaning growth induces alterations that can predispose to the onset of vascular dysfunction in adulthood. Female Wistar rats were fed low- or control zinc diets from pregnancy to offspring weaning. After weaning, offspring were fed either a low- or a control zinc diet until 81 days. We evaluated systolic blood pressure (SBP), thoracic aorta morphology, nitric oxide (NO) system and vascular reactivity in 6- and/or 81-day-old offspring. At day 6, zinc-deficient male and female offspring showed a decrease in aortic NO synthase (NOS) activity accompanied by an increase in oxidative stress. Zinc-deficient 81-day-old male rats exhibited an increase in collagen deposition in tunica media, as well as lower activity of endothelial NOS (eNOS) that could not be reversed with an adequate zinc diet during postweaning life. Zinc deficiency programmed a reduction in eNOS protein expression and higher SBP only in males. Adult zinc-deficient rats of both sexes showed reduced vasodilator response dependent on eNOS activity and impaired aortic vasoconstrictor response to angiotensin-II associated with alterations in intracellular calcium mobilization. Female rats were less sensitive to the effects of zinc deficiency and exhibited higher eNOS activity and/or expression than males, without alterations in SBP or aortic histology. This work strengthens the importance of a balanced intake of micronutrients during perinatal growth to ensure adequate vascular function in adult life. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Male-specific alteration in excitatory post-synaptic development and social interaction in pre-natal valproic acid exposure model of autism spectrum disorder.

    Science.gov (United States)

    Kim, Ki Chan; Kim, Pitna; Go, Hyo Sang; Choi, Chang Soon; Park, Jin Hee; Kim, Hee Jin; Jeon, Se Jin; Dela Pena, Ike Campomayor; Han, Seol-Heui; Cheong, Jae Hoon; Ryu, Jong Hoon; Shin, Chan Young

    2013-03-01

    Autism spectrum disorder (ASD) is a pervasive developmental disorder characterized by three main behavioral symptoms including social deficits, impaired communication, and stereotyped and repetitive behaviors. ASD prevalence shows gender bias to male. Prenatal exposure to valproic acid (VPA), a drug used in epilepsy and bipolar disorder, induces autistic symptoms in both human and rodents. As we reported previously, prenatally VPA-exposed animals at E12 showed impairment in social behavior without any overt reproductive toxicity. Social interactions were not significantly different between male and female rats in control condition. However, VPA-exposed male offspring showed significantly impaired social interaction while female offspring showed only marginal deficits in social interaction. Similar male inclination was observed in hyperactivity behavior induced by VPA. In addition to the ASD-like behavioral phenotype, prenatally VPA-exposed rat offspring shows crooked tail phenotype, which was not different between male and female groups. Both male and female rat showed reduced GABAergic neuronal marker GAD and increased glutamatergic neuronal marker vGluT1 expression. Interestingly, despite of the similar increased expression of vGluT1, post-synaptic marker proteins such as PSD-95 and α-CAMKII expression was significantly elevated only in male offspring. Electron microscopy showed increased number of post-synapse in male but not in female at 4 weeks of age. These results might suggest that the altered glutamatergic neuronal differentiation leads to deranged post-synaptic maturation only in male offspring prenatally exposed to VPA. Consistent with the increased post-synaptic compartment, VPA-exposed male rats showed higher sensitivity to electric shock than VPA-exposed female rats. These results suggest that prenatally VPA-exposed rats show the male preponderance of ASD-like behaviors including defective social interaction similar to human autistic patients, which

  20. Haloperidol normalized prenatal vitamin D depletion-induced reduction of hippocampal cell proliferation in adult rats.

    Science.gov (United States)

    Keilhoff, Gerburg; Grecksch, Gisela; Becker, Axel

    2010-05-31

    Considering the fact that schizophrenia is a highly complex disorder of the human brain, different models are needed to test specific causative or mechanistic hypotheses. The pathogenesis of schizophrenia is also characterized by abnormal neuronal development. It was found that schizophrenia as well as antipsychotic treatment are accompanied by alterations in neuronal proliferation. Recently we reported on increased neurogenesis and their controllability by neuroleptics in a pharmacological (ketamine) model of schizophrenia. To complete our understanding, here we studied neurogenesis and its sensitivity to the classical neuroleptic haloperidol in a developmental model of schizophrenia (maternal vitamin D deficiency). It was found that maternal vitamin D deficiency resulted in decreased neurogenesis. This effect was ameliorated by subchronic treatment with haloperidol. Thus, the results complete previous findings concerning the ability of haloperidol to ameliorate behavioral abnormalities induced by prenatal vitamin D deficiency and introduce the possibility to explain the curative effects of haloperidol, at least in part, due to re-establishment of disturbed cell proliferation. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  1. Biochemical parameters of pregnant rats and their offspring exposed to different doses of inorganic mercury in drinking water.

    Science.gov (United States)

    Oliveira, Cláudia S; Oliveira, Vitor A; Ineu, Rafael P; Moraes-Silva, Lucélia; Pereira, Maria E

    2012-07-01

    This work investigated the effects of low and high doses of inorganic mercury in drinking water on biochemical parameters of pregnant rats and their offspring. Female Wistar rats were treated during pregnancy with 0, 0.2, 0.5, 10 or 50 μg Hg(2+)/mL as HgCl(2). Rats were euthanized on day 20 of pregnancy. Pregnant rats presented a decrease in total water intake in all doses of mercury tested. At high doses, a decrease in the total food intake and in body weight gain was observed. Pregnant rats exposed to 50 μg Hg(2+)/mL presented an increase in kidney relative weight. Mercury exposure did not change serum urea and creatinine levels in any of the doses tested. Moreover, mercury exposure did not change porphobilinogen synthase activity of kidney, liver and placenta from pregnant rats in any of the doses tested, whereas fetuses of pregnant rats exposed to 50 μg Hg(2+)/mL presented an increase in the hepatic porphobilinogen synthase activity. In general, pregnant rats presented alterations due to HgCl(2) exposure in drinking water. However, only the dose 50 μg Hg(2+)/mL appeared to be enough to cross the blood-placenta barrier, since at this dose the fetuses presented change in the porphobilinogen synthase activity. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Administration of the Antioxidant N-Acetyl-Cysteine in Pregnant Mice Has Long-Term Positive Effects on Metabolic and Behavioral Endpoints of Male and Female Offspring Prenatally Exposed to a High-Fat Diet

    Directory of Open Access Journals (Sweden)

    Alessandra Berry

    2018-03-01

    Full Text Available A growing body of evidence suggests the consumption of high-fat diet (HFD during pregnancy to model maternal obesity and the associated increase in oxidative stress (OS, might act as powerful prenatal stressors, leading to adult stress-related metabolic or behavioral disorders. We hypothesized that administration of antioxidants throughout gestation might counteract the negative effects of prenatal exposure to metabolic challenges (maternal HFD feeding during pregnancy on the developing fetus. In this study, female C57BL/6J mice were fed HFD for 13 weeks (from 5-weeks of age until delivery and were exposed to the N-acetyl-cysteine (NAC antioxidant from 10-weeks of age until right before delivery. Body weight of the offspring was assessed following birth, up to weaning and at adulthood. The metabolic, neuroendocrine and emotional profile of the adult offspring was tested at 3-months of age. Prenatal HFD increased mother’s body weight and offspring’s weight at the time of weaning, when administered in conjunction with NAC. In females, NAC administration reduced high levels of leptin resulting from prenatal HFD. Prenatal NAC administration also resulted in greater glucose tolerance and insulin sensitivity while increasing adiponectin levels, as well as increasing exploratory behavior, an effect accompanied by reduced plasma corticosterone levels in response to restraint stress. Analysis of glutathione levels in the hypothalamus and in brown adipose tissue indicates that, while HFD administration to pregnant dams led to reduced levels of glutathione in the offspring, as in the male hypothalamus, NAC was able to revert this effect and to increase glutathione levels both in the periphery (Brown Adipose Tissue, both males and females and in the central nervous system (males. Overall, results from this study indicate that the body redox milieu should be tightly regulated during fetal life and that buffering OS during pregnancy can have important

  3. Administration of the Antioxidant N-Acetyl-Cysteine in Pregnant Mice Has Long-Term Positive Effects on Metabolic and Behavioral Endpoints of Male and Female Offspring Prenatally Exposed to a High-Fat Diet.

    Science.gov (United States)

    Berry, Alessandra; Bellisario, Veronica; Panetta, Pamela; Raggi, Carla; Magnifico, Maria C; Arese, Marzia; Cirulli, Francesca

    2018-01-01

    A growing body of evidence suggests the consumption of high-fat diet (HFD) during pregnancy to model maternal obesity and the associated increase in oxidative stress (OS), might act as powerful prenatal stressors, leading to adult stress-related metabolic or behavioral disorders. We hypothesized that administration of antioxidants throughout gestation might counteract the negative effects of prenatal exposure to metabolic challenges (maternal HFD feeding during pregnancy) on the developing fetus. In this study, female C57BL/6J mice were fed HFD for 13 weeks (from 5-weeks of age until delivery) and were exposed to the N-acetyl-cysteine (NAC) antioxidant from 10-weeks of age until right before delivery. Body weight of the offspring was assessed following birth, up to weaning and at adulthood. The metabolic, neuroendocrine and emotional profile of the adult offspring was tested at 3-months of age. Prenatal HFD increased mother's body weight and offspring's weight at the time of weaning, when administered in conjunction with NAC. In females, NAC administration reduced high levels of leptin resulting from prenatal HFD. Prenatal NAC administration also resulted in greater glucose tolerance and insulin sensitivity while increasing adiponectin levels, as well as increasing exploratory behavior, an effect accompanied by reduced plasma corticosterone levels in response to restraint stress. Analysis of glutathione levels in the hypothalamus and in brown adipose tissue indicates that, while HFD administration to pregnant dams led to reduced levels of glutathione in the offspring, as in the male hypothalamus, NAC was able to revert this effect and to increase glutathione levels both in the periphery (Brown Adipose Tissue, both males and females) and in the central nervous system (males). Overall, results from this study indicate that the body redox milieu should be tightly regulated during fetal life and that buffering OS during pregnancy can have important long

  4. Effects of oral, subchronic cadmium administration on fertility prenatal and postnatal progeny development in rats

    Energy Technology Data Exchange (ETDEWEB)

    Baranski, B.; Stetkiewicz, I.; Sitarek, K.; Szymczak, W.

    1983-12-01

    Cadmium chloride was administered by gavage to female rats 5 days a week for 5 weeks, then during mating and gestation periods at doses of 0.04, 0.4, and 4 mg Cd/kg/day. Treatment with cadmium neither affected the survival and fertility of females, nor produced overt fetotoxic effects. Fetal cadmium concentration was not related to the level of exposure. Litter size, body weight gain and viability of offspring during 2 months after parturition were similar in all groups. The exploratory locomotor activity of 2-month-old males and females born to rats given 0.4 and 4 mg Cd/kg/day was significantly reduced. The progeny of cadmium-treated females showed decreased performance in the rotarod test. In general, the degree of behavioral impairment was dose-related.

  5. Prenatal diagnosis by isoenzymic differentiation of Treacher Collins' syndrome induced by retinoids in rats

    DEFF Research Database (Denmark)

    Granström, G; Kirkeby, S

    1990-01-01

    A series of branchial arch malformations was induced in 618 embryos from 72 pregnant rats by a single intraperitoneal injection of 10 mg/kg etretinate at 8.5 days of gestation. The litters developed several malformations, including microtia, low set and dorsally placed outer ears, defective middle...... branchial arches is accompanied by a pathological differentiation pattern that can be traced by determinations of isoenzymes in the branchial arches as well as in amniotic fluid....

  6. Effect of administration of vitamins C and E on fertilization capacity of rats exposed to noise stress

    Directory of Open Access Journals (Sweden)

    Ghasem Saki

    2013-01-01

    Full Text Available The aims of this study were to evaluate the effects of administration of Vitamins C and E on fertilization capacity in rats exposed to noise stress. 40 adult male rats were randomly divided into 5 equal groups. Group 1 as controls who were not exposed to noise and groups 2-5 exposed to noise with 90-120 dB intensity and 300-350 Hz frequency from 7 pm to 7 am everyday for 50 days. Group 2 exposed to noise and did not receive Vitamins. Group 3 received vitamin C, Group 4 received Vitamin E. Group 5 received Vitamins C and E concomitantly. After 50 days, serum Follicle-stimulating hormone (FSH, Luteinizing hormone (LH and testosterone were calculated. Then each rat was left with three female rats for mating. Pregnant females were sacrificed on the 19 th day of pregnancy and evaluated for the presence and number of viable, dead and absorbed fetuses. The level of FSH, LH and testosterone significantly decreased in rats exposed to noise (P < 0.05. By administration of Vitamins in groups 3-5 we observed that the level of hormones significantly increased in compared to group 2 (P < 0.05. The fertilization capacity of male rats in groups 3-5 significantly increased in compared to group 2 (P < 0.05. There was significant difference between groups 1 and 2 in case of fertilization capacity (P = 0.001. The data in this study strongly suggests a negative role for noise stress on level of FSH, LH and testosterone level and also fertilization capacity of male rats. To complement the information it is suggested that this research be done on human samples.

  7. Relative importance of prenatal and postnatal androgen action in determining growth of the penis and anogenital distance in the rat before, during and after puberty.

    Science.gov (United States)

    van den Driesche, S; Scott, H M; MacLeod, D J; Fisken, M; Walker, M; Sharpe, R M

    2011-12-01

    Experimental animal studies show that measurement of anogenital distance (AGD) and/or penis length may provide lifelong 'read-outs' of foetal androgen exposure during the masculinization programming window (MPW). However, variation in postnatal androgen exposure may complicate interpretation of such measurements. This is important to clarify if such measurements are to be applied to humans. The present aim was to evaluate effects of prenatal and/or postnatal manipulation of androgen production/action on growth of AGD and the penis in rats. Pregnant rats were treated daily before (e13.5-e21.5) and after birth (postnatal days 1-15) with either vehicle, 500 mg/kg di(n-butyl) phthalate (DBP) or 100 mg/kg flutamide (postnatal only) in prenatal + postnatal treatment combinations (N = 6 treatment combinations); DBP impairs androgen production whereas flutamide impairs androgen action. Male offspring were killed on postnatal day 8 (prepuberty), 25 (early puberty) or 90 (adulthood) when AGD was measured, the penis dissected out and its weight and length measured; plasma testosterone and ventral prostate weight were measured at day 90 to assess endogenous androgen exposure. In controls, penis length, girth and AGD increased 2.2-, 5.3-and 5.9-fold respectively from day 8 to day 90. Significant inhibition of penis growth and final length and girth was induced by treatments that inhibited postnatal androgen action. Conversely, growth and ultimate (adult) AGD was inhibited by prenatal inhibition of androgen production whereas postnatal androgen inhibition had negligible effect. Nevertheless, AGD and penis length were highly correlated at every age (R(2) > 0.33; p penis size reflects both prenatal + postnatal androgen exposure. At the group treatment level, prepubertal measurement of either AGD or penis size accurately predicts their size in adulthood. © 2011 The Authors. International Journal of Andrology © 2011 European Academy of Andrology.

  8. Dose-response study in F344 rats exposed to (U,Pu)O2 or PuO2

    International Nuclear Information System (INIS)

    Mewhinney, J.A.; Eidson, A.F.; Hahn, F.F.; Scott, B.R.; Seiler, F.A.; Boecker, B.B.

    1987-01-01

    The relationship of radiation dose to lung and the biological effect observed was investigated following inhalation of two types of plutonium-containing particulate materials in rats. Bulk powder samples of the two materials were obtained from within gloveboxes used in the routine manufacture of mixed plutonium and uranium oxide nuclear fuel. The materials were a solid solution of uranium and plutonium treated at 1750 0 C and a PuO 2 feedstock. Groups of rats received a single inhalation exposure to a material to achieve one of three levels of initial pulmonary burden. Rats were maintained for their lifespan to observe the biological effects produced. These effects were observed in the lungs of rats exposed to either type of particle. The same types of lung cancer were produced by both particulate materials. The incidences of cancers were also similar at comparable levels of initial pulmonary burden for the two materials. The crude incidence of lung cancers for rats exposed to these materials was not different than those reported for similar studies that used laboratory-produced aerosols of PuO 2 . Using a linear dose-effect model, the relative risk of lung cancer for rats exposed to these industrial materials was 2.3 +- 1.0 (SE) at a lung dose of 100 rad. The doubling dose for lung cancers was 78 +- 63 rad to lung to median life span. 21 refs., 9 figs., 10 tabs

  9. Failure to produce taste-aversion learning in rats exposed to static electric fields and air ions

    Energy Technology Data Exchange (ETDEWEB)

    Creim, J.A.; Lovely, R.H.; Weigel, R.J.; Forsythe, W.C.; Anderson, L.E. [Pacific Northwest Labs., Richland, WA (United States)

    1995-12-01

    Taste-aversion (TA) learning was measured to determine whether exposure to high-voltage direct current (HVdc) static electric fields can produce TA learning in male Long Evans rats. Fifty-six rats were randomly distributed into four groups of 14 rats each. All rats were placed on a 20 min/day drinking schedule for 12 consecutive days prior to receiving five conditioning trials. During the conditioning trials, access to 0.1% sodium saccharin-flavored water was given for 20 min, followed 30 min later by one of four treatments. Two groups of 14 rats each were individually exposed to static electric fields and air ions, one group to +75 kV/m (+2 {times} 10{sup 5} air ions/cm{sup 3}) and the other group to {minus}75 kV/m ({minus}2 {times} 10{sup 5} air ions/cm{sup 3}). Two other groups of 14 rats each served as sham-exposed controls, with the following variation in one of the sham-exposed groups: this group was subdivided into two subsets of seven rats each, so that a positive control group could be included to validate the experimental design. The positive control group (n = 7) was injected with cyclophosphamide 25 mg/kg, i.p., 30 min after access to saccharin-flavored water on conditioning days, whereas the other subset of seven rats was similarly injected with an equivalent volume of saline. Access to saccharin-flavored water on conditioning days was followed by the treatments described above and was alternated daily with water recovery sessions in which the rats received access to water for 20 min in the home cage without further treatment. Following the last water-recovery session, a 20 min, two-bottle preference test (between water and saccharin-flavored water) was administered to each group. The positive control group did show TA learning, thus validating the experimental protocol.

  10. [Morphological structure of rat epiphysis exposed to electromagnetic radiation from communication devices].

    Science.gov (United States)

    Yashchenko, S G; Rybalko, S Yu

    Pineal gland is one of the most important components of homeostasis - the supporting system of the body. It participates in the launch of stress responses, restriction of their development, prevention of adverse effects on the body. There was proved an impact of electromagnetic radiation on the epiphysis. However, morphological changes in the epiphysis under exposure to electromagnetic radiation of modern communication devices are studied not sufficiently. For the time present the population is daily exposed to electromagnetic radiation, including local irradiation on the brain. These date determined the task of this research - the study of the structure of rat pineal gland under the exposure to electromagnetic radiation from personal computers and mobile phones. These date determined the task of this research - the study of the structure of rat pineal gland under the exposure to electromagnetic radiation from personal computers and mobile phones. Performed transmission electron microscopy revealed signs of degeneration of dark and light pinealocytes. These signs were manifested in the development of a complex of general and specific morphological changes. There was revealed the appearance of signs of aging and depletion transmission electron microscopy both in light and dark pinealocytes. These signs were manifested in the accumulation of lipofuscin granules and electron-dense "brain sand", the disappearance of nucleoli, cytoplasm vacuolization and mitochondrial cristae enlightenment.

  11. Chlorpyrifos induces anxiety-like behavior in offspring rats exposed during pregnancy.

    Science.gov (United States)

    Silva, Jonas G; Boareto, Ana C; Schreiber, Anne K; Redivo, Daiany D B; Gambeta, Eder; Vergara, Fernanda; Morais, Helen; Zanoveli, Janaína M; Dalsenter, Paulo R

    2017-02-22

    Chlorpyrifos is a pesticide, member of the organophosphate class, widely used in several countries to manage insect pests on many agricultural crops. Currently, chlorpyrifos health risks are being reevaluated due to possible adverse effects, especially on the central nervous system. The aim of this study was to investigate the possible action of this pesticide on the behaviors related to anxiety and depression of offspring rats exposed during pregnancy. Wistar rats were treated orally with chlorpyrifos (0.01, 0.1, 1 and 10mg/kg/day) on gestational days 14-20. Male offspring behavior was evaluated on post-natal days 21 and 70 by the elevated plus-maze test, open field test and forced swimming test. The results demonstrated that exposure to 0.1, 1 or 10mg/kg/day of chlorpyrifos could induce anxiogenic-like, but not depressive-like behavior at post-natal day 21, without causing fetal toxicity. This effect was reversed on post-natal day 70. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Cyclooxygenase-2-dependent bronchoconstriction in perfused rat lungs exposed to endotoxin.

    Science.gov (United States)

    Uhlig, S; Nüsing, R; von Bethmann, A; Featherstone, R L; Klein, T; Brasch, F; Müller, K M; Ullrich, V; Wendel, A

    1996-05-01

    Lipopolysaccharides (LPS), widely used to study the mechanisms of gram-negative sepsis, increase airway resistance by constriction of terminal bronchioles. The role of the cyclooxygenase (COX) isoenzymes and their prostanoid metabolites in this process was studied. Pulmonary resistance, the release of thromboxane (TX) and the expression of COX-2 mRNA were measured in isolated blood-free perfused rat lungs exposed to LPS. LPS induced the release of TX and caused increased airway resistance after about 30 min. Both TX formation and LPS-induced bronchoconstriction were prevented by treatment with the unspecific COX inhibitor acetyl salicylic acid, the specific COX-2 inhibitor CGP-28238, dexamethasone, actinomycin D, or cycloheximide. LPS-induced bronchoconstriction was also inhibited by the TX receptor antagonist BM-13177. The TX-mimetic compound, U-46619, increased airway resistance predominantly by constricting terminal bronchioles. COX-2-specific mRNA in lung tissue was elevated after LPS exposure, and this increase was attenuated by addition of dexamethasone or of actinomycin D. In contrast to LPS, platelet-activating factor (PAF) induced immediate TX release and bronchoconstriction that was prevented by acetyl salicylic acid, but not by CGP-28238. LPS elicits the following biochemical and functional changes in rat lungs: (i) induction of COX-2; (ii) formation of prostaglandins and TX; (iii) activation of the TX receptor on airway smooth muscle cells; (iv) constriction of terminal bronchioles; and (v) increased airway resistance. In contrast to LPS, the PAF-induced TX release is likely to depend on COX-1.

  13. Long Lasting Microvascular Tone Alteration in Rat Offspring Exposed In Utero to Maternal Hyperglycaemia.

    Directory of Open Access Journals (Sweden)

    Emilie Vessières

    Full Text Available Epidemiologic studies have demonstrated that cardiovascular risk is not only determined by conventional risk factors in adulthood, but also by early life events which may reprogram vascular function. To evaluate the effect of maternal diabetes on fetal programming of vascular tone in offspring and its evolution during adulthood, we investigated vascular reactivity of third order mesenteric arteries from diabetic mother offspring (DMO and control mother offspring (CMO aged 3 and 18 months. In arteries isolated from DMO the relaxation induced by prostacyclin analogues was reduced in both 3- and 18-month old animals although endothelium (acetylcholine-mediated relaxation was reduced in 18-month old DMO only. Endothelium-independent (sodium nitroprusside relaxation was not affected. Pressure-induced myogenic tone, which controls local blood flow, was reduced in 18-month old CMO compared to 3-month old CMO. Interestingly, myogenic tone was maintained at a high level in 18-month old DMO even though agonist-induced vasoconstriction was not altered. These perturbations, in 18-months old DMO rats, were associated with an increased pMLC/MLC, pPKA/PKA ratio and an activated RhoA protein. Thus, we highlighted perturbations in the reactivity of resistance mesenteric arteries in DMO, at as early as 3 months of age, followed by the maintenance of high myogenic tone in older rats. These modifications are in favour of excessive vasoconstrictor tone. These results evidenced a fetal programming of vascular functions of resistance arteries in adult rats exposed in utero to maternal diabetes, which could explain a re-setting of vascular functions and, at least in part, the occurrence of hypertension later in life.

  14. Neurobehavioral assessment of rats exposed to pristine polystyrene nanoplastics upon oral exposure.

    Science.gov (United States)

    Rafiee, Mohammad; Dargahi, Leila; Eslami, Akbar; Beirami, Elmira; Jahangiri-Rad, Mahsa; Sabour, Siamak; Amereh, Fatemeh

    2018-02-01

    The increasing use of plastics has raised concerns about pollution of freshwater by these polymeric materials. Knowledge about their potential effects on environmental and public health is limited. Recent publications have suggested that the degradation of plastics will result in the release of nano-sized plastic particles to the environment. Therefore, it is of utmost importance to gain knowledge about whether and how nanoplastics affect living organisms. The present study aimed to analyse potential neurobehavioral effects of polystyrene nanoparticles (PS-NPs) after long-term exposure on rat. Potential effects of PS-NPs were investigated using four test dosages (1, 3, 6, and 10 mg PS-NPs/kg of body weight/day) administrated orally with adult Wistar male rats for five weeks. Neurobehavioral tests were chosen to assess a variety of behavioral domains. Particle diameters in test suspensions were determined through dynamic light scattering and showed an average hydrodynamic diameter of approximately 38.92 nm. No statistically significant behavioral effects were observed in all tests performed (p > 0.05). In the elevated plus maze, PS-NPs-exposed rats showed greater number of entries into open arms compared to controls. Also, PS-NPs had no significant influence on body weight of animals. Taking into account the subtle and transient nature of neurobehavioral consequences, however, these results underline the possibility of even pristine plastic nanoparticles to induce behavioral alteration in the rest of the food web, including for marine biota and humans. Indeed even though studied neurobehavioral effects in our study was not statistically significant, the observed subtle effects may be clinically considerable. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Study on the influence of Sempervivum tectorum and Melatonin on Glutathion protective effects in rats blood exposed to Aluminum sulphate

    OpenAIRE

    Corina Gravila; Florin Muselin; Camelia Tulcan; Mirela Ahmadi – Khoie; Ariana- Bianca Velciov; Georgeta- Sofia Pintilie

    2014-01-01

    The present study was carried out to investigate the influence of Sempervivum tectorum aqueous extract and melatonin on reduced glutathione (GSH) protective effect in Wistar albino rat blood exposed to aluminium sulphate- Al2(SO4)3. The rats were divided in one control group (C) and 7 experimental groups (E). The control group received tap water. The experimental rats were feed the following way: E1 group – aluminum sulphate, daily, for 3 months; : E2 group – Sempervivum tectorum, daily, for ...

  16. Prenatal Tests

    Science.gov (United States)

    ... Careers Archives Health Topics Pregnancy Before or between pregnancies Nutrition, weight & fitness Prenatal care Is it safe? Labor & ... Report Cards Careers Archives Pregnancy Before or between pregnancies Nutrition, weight & fitness Prenatal care Is it safe? Labor & ...

  17. Neoplastic and life-span effects of chronic exposure to tritium. II. Rats exposed in utero

    International Nuclear Information System (INIS)

    Cahill, D.F.; Wright, J.F.; Godbold, J.H.; Ward, J.M.; Laskey, J.W.; Tompkins, E.A.

    1975-01-01

    A study was conducted to determine the effects on neoplasia incidence and life-span of exposure in utero to a major environmental radionuclide. Sprague-Dawley rats were continuously exposed to tritiated water (HTO) from conception through birth in doses of 0, 1, 10, 50, and 100 μCi HTO/ml body water. HTO administration was terminated at birth. Calculated cumulative doses during gestation were approximately 0, 6.6, 66, 330, and 660 rads of total body irradiation. Under these exposure conditions, the two highest doses resulted in sterile offspring. Animals surviving through 30 days postnatally were defined as the study population and observed until their deaths. Intrauterine exposures to doses up to 66 rads had no significant effects on either sex with respect to lifespan, overall neoplasia incidence, incidence rate, or onset of mammary fibroadenomas. Females exposed to 330 or 660 rads were sterile and had lower incidence rates of mammary fibroadenomas than did controls; at 660 rads females had a lower incidence of overall neoplasia and reduced mean lifespans. Sterile male offspring had reduced mean longevity after irradiation at 660 rads. Regardless of dose group, females had significantly higher incidences of neoplasia and longer life-spans than males

  18. Performance and exposure indices of rats exposed to low concentrations of lead.

    Science.gov (United States)

    Cory-Slechta, D A; Weiss, B; Cox, C

    1985-04-01

    To further characterize the lower end of the function relating lead exposure and biological exposure indices to behavior, male weanling rats were exposed chronically to drinking solutions containing 25 ppm sodium acetate (controls) or 25 ppm lead acetate. Behavioral training began when the animals reached 50 days of age, and performance on a fixed-interval 1-min schedule of food reinforcement was then assessed over 90 experimental sessions (136 days). This exposure produced overall response rate increases over the first 40 sessions that were similar to those observed previously with higher concentrations of lead. Response rates of the two groups tended to merge subsequently. The increased overall response rates in the treated group derived primarily from an increased frequency of shorter interresponse times (IRTs) and increased running rates (calculated without the postreinforcement interval). Blood lead (PbB) and zinc protoporphyrin (ZPP) values were determined following sessions 30, 60, and 90. PbB values of the lead-exposed group averaged 15 to 20 micrograms/dl throughout the study; ZPP did not differ. The mean brain lead value of the treated group was 0.07 micrograms Pb/g. Blood-brain ratios (1.38 to 4.06) were substantially greater than those previously observed at higher exposures. These data extend to even lower exposures, and lower blood lead concentrations, the effective concentration for behavioral effects, and further emphasize the importance of the sensitivity of the endpoint in assessing behavioral toxicity.

  19. Developmental and behavioral effects of prenatal primidone exposure in the rat.

    Science.gov (United States)

    Pizzi, W J; Alexander, T D; Loftus, J T

    1996-12-01

    Pregnant Sprague-Dawley rats were administered primidone (PRM) by oral gavage on gestation days 8-17 in doses of 0.40, and 80 mg/kg. Although these doses of PRM did not produce significant differences in litter size, birth weight, mortality, date of attainment of developmental landmarks or measures of preweaning reflex and motor development, there were a number of significant differences that developed as the animals approached and entered adulthood. When tested as adults, the 80 mg/kg male rats showed a deficit in the performance of an eight-arm radial maze task. These same animals showed a significant reduction in open field activity when tested as adults. In addition, both male and female PRM-treated animals showed reduced body weights at different periods corresponding to onset of sexual maturation during development. These findings are consistent with the larger body of literature reporting on the neurobehavioral teratology of phenobarbital, including its ability to produce lesions in the hippocampus and endocrine dysfunction resulting in reproductive deficits. These results suggest that PRM produces its adverse effects as a result of its metabolism to phenobarbital, which in turn affects the limbic system.

  20. Effects of environmental enrichment on the activity of the amygdala in micrencephalic rats exposed to a novel open field.

    Science.gov (United States)

    Matsuda, Wakoto; Ehara, Ayuka; Nakadate, Kazuhiko; Yoshimoto, Kanji; Ueda, Shuichi

    2018-01-01

    Environmental enrichment (EE) mediates recovery from sensory, motor, and cognitive deficits and emotional abnormalities. In the present study, we examined the effects of EE on locomotor activity and neuronal activity in the amygdala in control and methylazoxymethanol acetate (MAM)-induced micrencephalic rats after challenge in a novel open field. Control rats housed in EE (CR) showed reduced locomotor activity compared to rats housed in a conventional cage (CC), whereas hyperactivity was seen in MAM rats housed in a conventional cage (MC) and in MAM rats housed in EE (MR). Novel open field exposure in both CC and MC resulted in a marked increase in Fos expression in the anterior and posterior parts of the basolateral amygdaloid nucleus, basomedial nucleus, and medial nucleus, whereas these increases in expression were not observed in CR. The effect of EE on Fos expression in the amygdala was different in MR exposed to a novel open field compared to CR. Furthermore, we observed a quite different pattern of Fos expression in the central nucleus of the amygdala between control and MAM rats. The present results suggest that neuronal activity in the amygdala that responds to anxiety is altered in MAM rats, especially when the rats are reared in EE. These alterations may cause behavioral differences between control and MAM rats. © 2017 Japanese Teratology Society.

  1. Prenatal inhibition of the kynurenine pathway leads to structural changes in the hippocampus of adult rat offspring.

    Science.gov (United States)

    Khalil, Omari S; Pisar, Mazura; Forrest, Caroline M; Vincenten, Maria C J; Darlington, L Gail; Stone, Trevor W

    2014-05-01

    Glutamate receptors for N-methyl-d-aspartate (NMDA) are involved in early brain development. The kynurenine pathway of tryptophan metabolism includes the NMDA receptor agonist quinolinic acid and the antagonist kynurenic acid. We now report that prenatal inhibition of the pathway in rats with 3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulphonamide (Ro61-8048) produces marked changes in hippocampal neuron morphology, spine density and the immunocytochemical localisation of developmental proteins in the offspring at postnatal day 60. Golgi-Cox silver staining revealed decreased overall numbers and lengths of CA1 basal dendrites and secondary basal dendrites, together with fewer basal dendritic spines and less overall dendritic complexity in the basal arbour. Fewer dendrites and less complexity were also noted in the dentate gyrus granule cells. More neurons containing the nuclear marker NeuN and the developmental protein sonic hedgehog were detected in the CA1 region and dentate gyrus. Staining for doublecortin revealed fewer newly generated granule cells bearing extended dendritic processes. The number of neuron terminals staining for vesicular glutamate transporter (VGLUT)