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Sample records for maternal protein-restricted rats

  1. Maternal protein restriction impairs the transcriptional metabolic flexibility of skeletal muscle in adult rat offspring.

    PubMed

    da Silva Aragão, Raquel; Guzmán-Quevedo, Omar; Pérez-García, Georgina; Manhães-de-Castro, Raul; Bolaños-Jiménez, Francisco

    2014-08-14

    Skeletal muscle exhibits a remarkable flexibility in the usage of fuel in response to the nutrient intake and energy demands of the organism. In fact, increased physical activity and fasting trigger a transcriptional programme in skeletal muscle cells leading to a switch from carbohydrate to lipid oxidation. Impaired metabolic flexibility has been reported to be associated with obesity and type 2 diabetes, but it is not known whether the disability to adapt to metabolic demands is a cause or a consequence of these pathological conditions. Inasmuch as a poor nutritional environment during early life is a predisposing factor for the development of metabolic diseases in adulthood, in the present study, we aimed to determine the long-term effects of maternal malnutrition on the metabolic flexibility of offspring skeletal muscle. To this end, the transcriptional responses of the soleus and extensor digitorum longus muscles to fasting were evaluated in adult rats born to dams fed a control (17 % protein) or a low-protein (8 % protein, protein restricted (PR)) diet throughout pregnancy and lactation. With the exception of reduced body weight and reduced plasma concentrations of TAG, PR rats exhibited a metabolic profile that was the same as that of the control rats. In the fed state, PR rats exhibited an enhanced expression of key regulatory genes of fatty acid oxidation including CPT1a, PGC-1α, UCP3 and PPARα and an impaired expression of genes that increase the capacity for fat oxidation in response to fasting. These results suggest that impaired metabolic inflexibility precedes and may contribute to the development of metabolic disorders associated with early malnutrition. PMID:24823946

  2. Maternal protein restriction during gestation impairs female offspring pancreas development in the rat.

    PubMed

    Calzada, Lizbeth; Morales, Angélica; Sosa-Larios, Tonantzin C; Reyes-Castro, Luis A; Rodríguez-González, Guadalupe L; Rodríguez-Mata, Verónica; Zambrano, Elena; Morimoto, Sumiko

    2016-08-01

    A maternal low-protein (LP) diet programs fetal pancreatic islet β-cell development and function and predisposes offspring to metabolic dysfunction later in life. We hypothesized that maternal protein restriction during pregnancy differentially alters β- and α-cell populations in offspring by modifying islet ontogeny and function throughout life. We aimed to investigate the effect of an LP maternal diet on pancreatic islet morphology and cellular composition in female offspring on postnatal days (PNDs) 7, 14, 21, 36, and 110. Mothers were divided into 2 groups: during pregnancy, the control group (C) was fed a diet containing 20% casein, and the LP group was fed an isocaloric diet with 10% casein. Offspring pancreases were obtained at each PND and then processed. β and α cells were detected by immunohistochemistry, and cellular area and islet size were quantified. Islet cytoarchitecture and total area were similar in C and LP offspring at all ages studied. At the early ages (PNDs 7-21), the proportion of β cells was lower in LP than C offspring. The proportion of α cells was lower in LP than C offspring on PND 14 and higher on PND 21. The β/α-cell ratio was lower in LP compared with C offspring on PNDs 7 and 21 and higher on PND 36 (being similar on PNDs 14 and 110). We concluded that maternal protein restriction during pregnancy modifies offspring islet cell ontogeny by altering the proportions of islet sizes and by reducing the number of β cells postnatally, which may impact pancreatic function in adult life. PMID:27440540

  3. Maternal protein restriction reduces expression of angiotensin I-converting enzyme 2 in rat placental labyrinth zone in late pregnancy.

    PubMed

    Gao, Haijun; Yallampalli, Uma; Yallampalli, Chandra

    2012-02-01

    Both the systemic and the uteroplacental renin-angiotensin system (RAS) display dramatic changes during pregnancy. However, whether gestational protein insufficiency affects the expressions of RAS in the placenta remains unknown. In this study, we hypothesized that the expression of Ace2 in the placental labyrinth was reduced by maternal protein restriction. Pregnant Sprague-Dawley rats were fed a normal diet or a low-protein diet (LP) from Day 1 of pregnancy until they were killed at Day 14 or Day 18. The labyrinth zone (LZ) of the placenta was then dissected and snap frozen for expression analysis by quantitative real-time PCR of Ace, Ace2, Agtr1a, Agtr1b, and Agtr2. Formalin-fixed placentas were used for immunohistochemical analysis on ACE and ACE2 proteins. The findings include 1) the expression of Ace2 in rat LZ was reduced by maternal protein restriction in late pregnancy; 2) ACE protein was mainly present in syncytiotrophoblasts, whereas ACE2 protein was found predominantly in fetal mesenchymal tissue and fetal capillaries; 3) Agtr1a was predominant in the rat LZ, and its mRNA levels, but not protein levels, were reduced by LP; 4) expressions of Ace, Ace2, and Agtr1a in the rat LZ and their response to LP occurred in a gender-dependent manner. These results may indicate that a reduced expression of Ace2 and perhaps an associated reduction in angiotensin (1-7) production in the placenta by maternal protein restriction may be responsible for fetal growth restriction and associated programming of adulthood hypertension.

  4. Developmental Programming of Cardiovascular Disease Following Intrauterine Growth Restriction: Findings Utilising A Rat Model of Maternal Protein Restriction

    PubMed Central

    Zohdi, Vladislava; Lim, Kyungjoon; Pearson, James T.; Black, M. Jane

    2014-01-01

    Over recent years, studies have demonstrated links between risk of cardiovascular disease in adulthood and adverse events that occurred very early in life during fetal development. The concept that there are embryonic and fetal adaptive responses to a sub-optimal intrauterine environment often brought about by poor maternal diet that result in permanent adverse consequences to life-long health is consistent with the definition of “programming”. The purpose of this review is to provide an overview of the current knowledge of the effects of intrauterine growth restriction (IUGR) on long-term cardiac structure and function, with particular emphasis on the effects of maternal protein restriction. Much of our recent knowledge has been derived from animal models. We review the current literature of one of the most commonly used models of IUGR (maternal protein restriction in rats), in relation to birth weight and postnatal growth, blood pressure and cardiac structure and function. In doing so, we highlight the complexity of developmental programming, with regards to timing, degree of severity of the insult, genotype and the subsequent postnatal phenotype. PMID:25551250

  5. Developmental programming of cardiovascular disease following intrauterine growth restriction: findings utilising a rat model of maternal protein restriction.

    PubMed

    Zohdi, Vladislava; Lim, Kyungjoon; Pearson, James T; Black, M Jane

    2015-01-01

    Over recent years, studies have demonstrated links between risk of cardiovascular disease in adulthood and adverse events that occurred very early in life during fetal development. The concept that there are embryonic and fetal adaptive responses to a sub-optimal intrauterine environment often brought about by poor maternal diet that result in permanent adverse consequences to life-long health is consistent with the definition of "programming". The purpose of this review is to provide an overview of the current knowledge of the effects of intrauterine growth restriction (IUGR) on long-term cardiac structure and function, with particular emphasis on the effects of maternal protein restriction. Much of our recent knowledge has been derived from animal models. We review the current literature of one of the most commonly used models of IUGR (maternal protein restriction in rats), in relation to birth weight and postnatal growth, blood pressure and cardiac structure and function. In doing so, we highlight the complexity of developmental programming, with regards to timing, degree of severity of the insult, genotype and the subsequent postnatal phenotype.

  6. Maternal protein restriction compromises myocardial contractility in the young adult rat by changing proteins involved in calcium handling.

    PubMed

    de Belchior, Aucelia C S; Freire, David D; da Costa, Carlos P; Vassallo, Dalton V; Padilha, Alessandra S; Dos Santos, Leonardo

    2016-02-01

    Maternal protein restriction (MPR) during pregnancy is associated with increased cardiovascular risk in the offspring in adulthood. In this study we evaluated the cardiac function of young male rats born from mothers subjected to MPR during pregnancy, focusing on the myocardial mechanics and calcium-handling proteins. After weaning, rats received normal diet until 3 mo old, when the following parameters were assessed: arterial and left ventricular hemodynamics and in vitro cardiac contractility in isolated papillary muscles. The body weight was lower and arterial pressure higher in the MPR group compared with young adult offspring of female rats that received standard diet (controls); and left ventricle time derivatives increased in the MPR group. The force developed by the cardiac muscle was similar; but time to peak and relaxation time were longer, and the derivatives of force were depressed in the MPR. In addition, MPR group exhibited decreased post-pause potentiation of force, suggesting reduced reuptake function of the sarcoplasmic reticulum. Corroborating, the myocardial content of SERCA-2a and phosphorylated PLB-Ser16/total PLB ratio was decreased and sodium-calcium exchanger was increased in the MPR group. The contraction dependent on transsarcolemmal influx of calcium was higher in MPR if compared with the control group. In summary, young rats born from mothers subjected to protein restriction during pregnancy exhibit changes in the myocardial mechanics with altered expression of calcium-handling proteins, reinforcing the hypothesis that maternal malnutrition is related to increased cardiovascular risk in the offspring, not only for hypertension, but also cardiac dysfunction.

  7. Maternal protein restriction alters VEGF signaling and decreases pulmonary alveolar in fetal rats.

    PubMed

    Liu, Xiaomei; Lin, Yan; Tian, Baoling; Miao, Jianing; Xi, Chunyan; Liu, Caixia

    2014-01-01

    Epidemiological studies have demonstrated that intrauterine growth restriction (IUGR) increases the risk for respiratory morbidity from infancy, throughout childhood and into adulthood. Chronic restriction of nutrients causes abnormalities in the airways and lungs of offspring, but whether IUGR adversely impacts fetal pulmonary vascular development and underlying mechanisms remain under investigation. In this study, we investigated the effects of protein malnutrition in utero on pulmonary alveolarization and vascular growth of the fetal lung and placentae. Pregnant rats were feed with an isocaloric low-protein diet (8% protein) until delivery. Placenta and fetal lungs were harvested on 20th day of gestation (term 21 days of gestation). Lung index (lung weight as a percentage of body weight), total DNA and protein, radial alveolar count, arteriolar wall thickness, lung maturity and angiogenic factor VEGF were assessed. The lung was hypoplastic in IUGR fetus, evidenced by reduction in lung weight, DNA and protein content. Protein restriction in utero led to higher glycogen levels, but reduced number of alveoli as confirmed by the measurement of radial alveolar counts. IUGR fetus had significantly reduced VEGF, Flk-1 levels in lung but no changes in Flt-1 mRNA. Furthermore, IUGR was associated with increased lung miR-126-3p levels, which modulated the expression of angiogenic factor. In contrast, with regard to the placenta, IUGR fetus presented with decreased expression of VEGF, with no changes in VEGF receptors and expression-regulating miRNAs. This work suggested that VEGF signaling defect plays an important role in the defective lung development, which may explain the increased incidence of respiratory infections in IUGR patients. PMID:25031729

  8. Maternal protein restriction in the rat during pregnancy and/or lactation alters cognitive and anxiety behaviors of female offspring.

    PubMed

    Reyes-Castro, L A; Rodriguez, J S; Charco, R; Bautista, C J; Larrea, F; Nathanielsz, P W; Zambrano, E

    2012-02-01

    Maternal protein deficiencies can developmentally program offspring to lifelong dysfunction of many physiological systems. We hypothesized that maternal isocaloric low protein diet during fetal and early postnatal development would negatively affect female offspring anxiety, exploration, associative learning and motivation as measured by the elevated plus maze (EPM), open field test (OFT), operant conditioning and the progressive ratio task, respectively. Control mothers (C) received a 20% casein diet and restricted mothers (R) a 10% casein diet to provide four groups: CC, RR, CR, and RC (first letter pregnancy diet and second lactation diet) to enable evaluation of offspring effects influenced by maternal diet during pregnancy and lactation. Maternal protein restriction decreased open arm time and distance in RR and RC offspring, increased anxiety behavior, in the EPM. In the OFT, the RR and RC offspring displayed decreased exploration (increased stress) as indexed by decreased distance in the center zone. These behaviors in the EPM and OFT was associated with increased corticosterone levels during an immobilization test in the RR offspring with intermediary effects in the RC offspring. Learning impairment was observed in the RR, CR and RC offspring during fixed ratio 5 schedule of reinforcement. Motivational effects were measured in RR offspring responding less, decreased motivation, and CR offspring making more responses, increased motivation, than CC offspring. These findings reveal the negative effects of developmental protein restriction on female offspring behavior. The underlying basis for these negative outcomes remains to be elucidated.

  9. Maternal protein restriction regulates IGF2 system in placental labyrinth.

    PubMed

    Gao, Haijun; Sathishkumar, Kunju Reddiar; Yallampalli, Uma; Balakrishnan, Meena; Li, Xilong; Wu, Guoyao; Yallampalli, Chandra

    2012-01-01

    This study was to test the hypothesis that altered IGF2 system in the placental labyrinth zone (LZ) impairs feto-placental growth in response to maternal protein restriction. Rats were fed a 20% protein diet and an isocaloric 6 % protein diet (LP) from day 1 to days 14, 18, or 21 of pregnancy. The effects of diet, gender of placenta and fetus, and day of pregnancy on placental weight, fetal weight, and expression of the IGF2 axis in the placental LZ and amino acids in maternal plasma were analyzed. Growth restriction occurred in both female and male fetuses by LP, coincident with impaired LZ growth and efficiency. The expression of Igf2, Igf2P0, Igf1r, Igf2r, Insr, Igfbp1, and Igfbp2 in placental LZ were affected by diet, gender and/or day of pregnancy. Concentrations of total essential amino acids and total nonessential amino acids were reduced and increased, respectively, in maternal plasma of LP-fed rats. These results indicate that adaptation of the IGF2 system in rat LZ occurs in a sex- and time-dependent manner in response to maternal protein restriction; however, these adaptations cannot prevent the growth restriction of both male and female fetuses during late pregnancy.

  10. Long Non-Coding RNA Expression Profile in the Kidneys of Male, Low Birth Weight Rats Exposed to Maternal Protein Restriction at Postnatal Day 1 and Day 10

    PubMed Central

    Li, Yanhong; Wang, Xueqin; Li, Mengxia; Pan, Jian; Jin, Meifang; Wang, Jian; Li, Xiaozhong; Feng, Xing

    2015-01-01

    Background Long non-coding RNAs (lncRNAs), which are involved in a variety of biological functions and aberrantly expressed in many types of diseases, are required for postnatal development. In this study, we aimed to investigate the lncRNA profiles in low birth weight (LBW) rats with reduced nephron endowment induced by the restriction of maternal protein intake. LBW by reduced nephron endowment is a risk factor for hypertension and end-stage renal disease in adulthood. Methods Kidneys were obtained from LBW rats fed a low-protein diet throughout gestation and lactation as well as from normal control rats born from dams fed normal protein diets at postnatal day 1 (p1) and 10 (p10). The total number of glomeruli in the kidneys was counted at p10. LncRNA expression profiles were analyzed by sequencing and screening using the Agilent Rat lncRNA Array. Quantitative real-time PCR (qRT-PCR) analysis of these lncRNAs confirmed the identity of some genes. Results The total number of glomeruli per kidney at p10 was significantly lower in LBW rats than in controls. A total of 42 lncRNAs were identified to be significantly differentially expressed, with fold-changes ≥2.0, between the two groups. According to correlation analysis between the differentially expressed lncRNAs and mRNAs involved in kidney development, we randomly selected a number of lncRNAs for comparison analysis between LBW and control kidneys at the two time-points, p1 and p10, using qRT-PCR. Three lncRNAs (TCONS_00014139, TCONS_00014138, and TCONS_00017119), which were significantly correlated with the mRNA expression of mitogen-activated protein kinase 4, were aberrantly expressed in LBW rats, compared with controls, at both p1 and p10. Conclusions LncRNAs are aberrantly expressed in the kidneys of LBW rats, compared with controls, during nephron development, which indicates that lncRNAs might be involved in impaired nephron endowment. PMID:25826617

  11. Serum leptin and insulin levels in lactating protein-restricted rats: implications for energy balance.

    PubMed

    Ferreira, C L P; Macêdo, G M; Latorraca, M Q; Arantes, V C; Veloso, R V; Carneiro, E M; Boschero, A C; Nascimento, C M O; Gaíva, M H

    2007-01-01

    The present study analysed the effect of protein restriction on serum insulin and leptin levels and their relationship with energy balance during lactation. Four groups of rats received isocaloric diets containing 170 g protein/kg or 60 g protein/kg from pregnancy until the 14th day of lactation: control non-lactating, control lactating (both fed a control diet), low-protein non-lactating and low-protein lactating. Energy intake, body composition, energy balance, serum insulin and leptin concentrations and the relationship between these hormones and several factors related to obesity were analysed. Low-protein-intake lactating rats exhibited hypoinsulinaemia, hyperleptinaemia, hypophagia and decreased energy expenditure compared with control lactating rats. The protein level in the carcasses was lower in the low-protein lactating group than in the control lactating group, resulting in a higher fat content in the first group compared with the latter. Body fat correlated inversely with serum insulin and positively with serum leptin level. There was a significant negative correlation between serum leptin and energy intake, and a positive relationship between energy intake and serum insulin level in lactating rats and in the combined data from both groups. Energy expenditure was correlated positively with serum insulin and negatively with serum leptin in lactating rats and when data from control non-lactating and lactating rats were pooled. Lactating rats submitted to protein restriction, compared with lactating control rats, showed that maternal reserves were preserved owing to less severe negative energy balance. This metabolic adaptation was obtained, at least in part, by hypoinsulinaemia that resulted in increased insulin sensitivity favouring enhanced fat deposition, hyperleptinaemia and hypophagia. PMID:17217557

  12. Gestational protein restriction alters cell proliferation in rat placenta.

    PubMed

    Rebelato, Hércules Jonas; Esquisatto, Marcelo Augusto Marreto; de Sousa Righi, Eloá Fernanda; Catisti, Rosana

    2016-04-01

    We recently showed that gestational protein restriction (GPR) alters the structure of the rat placenta on day 19 of gestation (dG). The aim of the study was to investigate the spatial and temporal immunolocalization of proliferating cell antigen Ki67 in normal and GPR placental development. Pregnant Wistar rats were divided into two groups: normal (NP, 17 % casein) or low-protein diet (LP, 6 % casein). Placentas and fetus were collected and weighed at 15, 17, 19 and 21 dG. Morphological, morphometric and ultrastructural analyses were performed. Immunoperoxidase was used to identify nuclear antigen Ki67 in placental sections. We observed a significant reduction in the number of trophoblast giant cells and glycogen cells in the LP group. Placental weight was significantly reduced only at 17 dG in the LP group, in parallel to a decrease in glycogen cells. From 15 to 21 dG, the thickness of the junctional zone (JZ) decreased in NP and LP animals, while that of the labyrinth zone (LZ) increased in parallel to a reduction in the number of proliferating cells in this LZ zone. GPR significantly inhibits cell proliferation in the JZ, especially at 15 and 17 dG. The ultrastructural appearance of the cytoplasm of giant and cytotrophoblastic cells indicates degeneration from 15 to 21 dG and this effect is enhanced in LP animals suggesting early aging. Offspring of NP dams were significantly heavier than offspring of LP dams at 21 dG. GPR causes modifications in specific regions of the placenta, cell proliferation inhibition and fetal growth restriction. PMID:26779652

  13. Gestational protein restriction alters cell proliferation in rat placenta.

    PubMed

    Rebelato, Hércules Jonas; Esquisatto, Marcelo Augusto Marreto; de Sousa Righi, Eloá Fernanda; Catisti, Rosana

    2016-04-01

    We recently showed that gestational protein restriction (GPR) alters the structure of the rat placenta on day 19 of gestation (dG). The aim of the study was to investigate the spatial and temporal immunolocalization of proliferating cell antigen Ki67 in normal and GPR placental development. Pregnant Wistar rats were divided into two groups: normal (NP, 17 % casein) or low-protein diet (LP, 6 % casein). Placentas and fetus were collected and weighed at 15, 17, 19 and 21 dG. Morphological, morphometric and ultrastructural analyses were performed. Immunoperoxidase was used to identify nuclear antigen Ki67 in placental sections. We observed a significant reduction in the number of trophoblast giant cells and glycogen cells in the LP group. Placental weight was significantly reduced only at 17 dG in the LP group, in parallel to a decrease in glycogen cells. From 15 to 21 dG, the thickness of the junctional zone (JZ) decreased in NP and LP animals, while that of the labyrinth zone (LZ) increased in parallel to a reduction in the number of proliferating cells in this LZ zone. GPR significantly inhibits cell proliferation in the JZ, especially at 15 and 17 dG. The ultrastructural appearance of the cytoplasm of giant and cytotrophoblastic cells indicates degeneration from 15 to 21 dG and this effect is enhanced in LP animals suggesting early aging. Offspring of NP dams were significantly heavier than offspring of LP dams at 21 dG. GPR causes modifications in specific regions of the placenta, cell proliferation inhibition and fetal growth restriction.

  14. Gestational protein restriction induces alterations in placental morphology and mitochondrial function in rats during late pregnancy.

    PubMed

    Rebelato, Hércules Jonas; Esquisatto, Marcelo Augusto Marreto; Moraes, Camila; Amaral, Maria Esmeria Corezola; Catisti, Rosana

    2013-12-01

    The placenta acts a regulator of nutrient composition and supply from mother to fetus and is the source of hormonal signals that affect maternal and fetal metabolism. Thus, appropriate development of the placenta is crucial for normal fetal development. We investigated the effect of gestational protein restriction (GPR) on placental morphology and mitochondrial function on day 19 of gestation. Pregnant dams were divided into two groups: normal (NP 17 % casein) or low-protein diet (LP 6 % casein). The placentas were processed for biochemical, histomorphometric and ultrastructural analysis. The integrity of rat placental mitochondria (RPM) isolated by conventional differential centrifugation was measured by oxygen uptake (Clark-type electrode). LP animals presented an increase in adipose tissue and triacylglycerol and a decrease in serum insulin levels. No alterations were observed in body, liver, fetus, or placenta weight. There was also no change in serum glucose, total protein, or lipid content. Gestational protein restriction had tissue-specific respiratory effects, with the observation of a small change in liver respiration (~13 %) and considerable respiratory inhibition in placenta samples (~37 %). The higher oxygen uptake by RPM in the LP groups suggests uncoupling between respiration and oxidative phosphorylation. In addition, ultrastructural analysis of junctional zone giant cells from LP placenta showed a disorganized cytoplasm, with loss of integrity of most organelles and intense vacuolization. The present results led us to hypothesize that GPR alters placental structure and morphology, induces sensitivity to insulin, mitochondrial abnormalities and suggests premature aging of the placenta. Further studies are needed to test this hypothesis.

  15. Protein Restriction during Pregnancy Induces Hypertension in Adult Female Rat Offspring—Influence of Estradiol

    PubMed Central

    Sathishkumar, K; Elkins, Rebekah; Yallampalli, Uma; Yallampalli, Chandra

    2011-01-01

    We previously reported that gestational dietary protein restriction in rats causes gender-related differences in development of offspring's blood pressure (BP) that is more pronounced in the males than females. Since such effects may depend on sex hormones, we investigated the role of estradiol in the development of hypertension in female offspring of protein restricted dams. Female offspring of pregnant rats fed normal (20%) or protein restricted (6%) casein diets throughout pregnancy were kept either, intact, ovariectomized or ovariectomized with estradiol supplementation. BP, estradiol and testosterone levels and vascular estrogen receptor (ER) were examined. BP was significantly higher and plasma estradiol levels were significantly lower by 34% in intact protein restricted female offspring compared to corresponding controls. Further decrease in estradiol levels by ovariectomy exacerbated hypertension in the protein restricted females with an earlier onset and more prominent elevation in BP compared to controls. Estradiol supplementation in ovariectomized protein restricted females significantly reversed ovariectomy-induced hypertension but did not normalize BP to control levels. The hypertensive protein restricted females have reduced vascular ERα expression that was unaffected by ovariectomy or estradiol replacement. In addition, the testosterone levels were significantly higher by 2.4-, 3.4-, and 2.8-fold in intact, ovariectomized and estradiol replaced protein restricted females compared to corresponding controls. Our data show that: 1) hypertension in protein restricted adult female offspring is associated with reduced plasma estradiol levels, 2) estradiol protects and limits the severity of hypertension in protein restricted females and contribute for sexual dimorphism, and 3) Estradiol replacement fails to completely reverse hypertension, which may be related to limited availability of vascular ERα receptors and/or increased circulating testosterone

  16. Glucose homeostasis in pregnant rats submitted to dietary protein restriction.

    PubMed

    de Mello, Maria Alice Rostom; Luciano, Eliete; Carneiro, Everardo Magalhães; Latorraca, Márcia Queiroz; Machado de Oliveira, Camnila Aparecida; Boschero, Antonio Carlos

    2003-01-01

    In the present work, we examined the effects of feeding a low protein diet during pregnancy on glucose-induced insulin secretion and glucose homeostasis in rats. Young (60 days), pregnant (P) or non-pregnant (NP) rats were fed during pregnancy or for 21 days (the NP) a normal (17%) or a low (6%) protein diet. Serum glucose and insulin levels and pancreas insulin content in the fed state; total area under serum glucose curve (AG) after a glucose load and serum glucose disappearance rate (Kitt) after insulin administration; as well as 86Rb outflow, 45Ca uptake and insulin secretion by isolated pancreatic islets in response to glucose were evaluated. Serum glucose was lower in 17%-P (12%) and 6%-P (27%) than in corresponding NP-rats. Serum insulin was higher in 17%-P (153%) and 6%-P (77%) compared to the corresponding NP-rats. Pancreatic insulin was higher in 6%-rats (55%) than in 17%-rats. No differences were found in AG among the groups whereas Kitt was lower in 6%-NP and higher in 6%-P than in the equivalent 17% rats. Increasing glucose concentration from 2.8 to 16.7 mmol/l, reduced 86Rb outflow from isolated islets from all groups. Increasing glucose concentration from 2.8 to 16.7 mmol/l elevated 45Ca uptake by 17%-NP (47%), 17%-P (40%) and 6%-P (214%) islets but not by 6%-NP ones. The increase in 45Ca uptake was followed by an increase in insulin release by the 17%-NP (2767%), 17%-P (2850%) and 6%-P (1200%) islets. In conclusion, 6%-P rats show impaired glucose induced insulin secretion related to reduced calcium uptake by pancreatic islets. However, the poor insulin secretion did not fully compensate the high peripheral sensitivity to the hormone, resulting in hypoglycemia. PMID:15686122

  17. Metabolic and Genomic Response to Dietary Isocaloric Protein Restriction in the Rat*

    PubMed Central

    Kalhan, Satish C.; Uppal, Sonal O.; Moorman, Jillian L.; Bennett, Carole; Gruca, Lourdes L.; Parimi, Prabhu S.; Dasarathy, Srinivasan; Serre, David; Hanson, Richard W.

    2011-01-01

    We have examined hepatic, genomic, and metabolic responses to dietary protein restriction in the non-pregnant Sprague-Dawley rat. Animals were pair-fed either a 6 or 24% casein-based diet for 7–10 days. At the end of the dietary period, a microarray analysis of the liver was performed, followed by validation of the genes of interest. The rates of appearance of phenylalanine, methionine, serine, and glucose and the contribution of pyruvate to serine and glucose were quantified using tracer methods. Plasma and tissue amino acid levels, enzyme activities, and metabolic intermediates were measured. Protein restriction resulted in significant differential expression of a number of genes involved in cell cycle, cell differentiation, transport, transcription, and metabolic processes. RT-PCR showed that the expression of genes involved in serine biosynthesis and fatty acid oxidation was higher, and those involved in fatty acid synthesis and urea synthesis were lower in the liver of protein-restricted animals. Free serine and glycine levels were higher and taurine levels lower in all tissues examined. Tracer isotope studies showed an ∼50% increase in serine de novo synthesis. Pyruvate was the primary (∼90%) source of serine in both groups. Transmethylation of methionine was significantly higher in the protein-restricted group. This was associated with a higher S-adenosylmethionine/S-adenosylhomocysteine ratio and lower cystathione β-synthase and cystathionine γ-lyase activity. Dietary isocaloric protein restriction results in profound changes in hepatic one-carbon metabolism within a short period. These may be related to high methylation demands placed on the organism and caused by possible changes in cellular osmolarity as a result of the efflux of the intracellular taurine. PMID:21147771

  18. Perinatal protein restriction affects milk free amino acid and fatty acid profile in lactating rats: potential role on pup growth and metabolic status.

    PubMed

    Martin Agnoux, Aurore; Antignac, Jean-Philippe; Boquien, Clair-Yves; David, Agnes; Desnots, Emmanuelle; Ferchaud-Roucher, Veronique; Darmaun, Dominique; Parnet, Patricia; Alexandre-Gouabau, Marie-Cécile

    2015-07-01

    Perinatal undernutrition affects not only fetal and neonatal growth but also adult health outcome, as suggested by the metabolic imprinting concept. Although maternal milk is the only channel through which nutrients are transferred from mother to offspring during the postnatal period, the impact of maternal undernutrition on milk composition is poorly understood. The present study investigates, in a rat model of nutritional programming, the effects of feeding an isocaloric, low-protein diet throughout gestation and lactation on milk composition and its possible consequences on offspring's growth and metabolic status. We used an integrated methodological approach that combined targeted analyses of macronutrients, free amino acid and fatty acid content throughout lactation, with an untargeted mass-spectrometric-based metabolomic phenotyping. Whereas perinatal dietary protein restriction failed to alter milk protein content, it dramatically decreased the concentration of most free amino acids at the end of lactation. Interestingly, a decrease of several amino acids involved in insulin secretion or gluconeogenesis was observed, suggesting that maternal protein restriction during the perinatal period may impact the insulinotrophic effect of milk, which may, in turn, account for the slower growth of the suckled male offspring. Besides, the decrease in sulfur amino acids may alter redox status in the offspring. Maternal undernutrition was also associated with an increase in milk total fatty acid content, with modifications in their pattern. Altogether, our results show that milk composition is clearly influenced by maternal diet and suggest that alterations in milk composition may play a role in offspring growth and metabolic programming. PMID:25935308

  19. Time window-dependent effect of perinatal maternal protein restriction on insulin sensitivity and energy substrate oxidation in adult male offspring.

    PubMed

    Agnoux, Aurore Martin; Antignac, Jean-Philippe; Simard, Gilles; Poupeau, Guillaume; Darmaun, Dominique; Parnet, Patricia; Alexandre-Gouabau, Marie-Cécile

    2014-07-15

    Epidemiological and experimental evidence suggests that a suboptimal environment during perinatal life programs offspring susceptibility to the development of metabolic syndrome and Type 2 diabetes. We hypothesized that the lasting impact of perinatal protein deprivation on mitochondrial fuel oxidation and insulin sensitivity would depend on the time window of exposure. To improve our understanding of underlying mechanisms, an integrative approach was used, combining the assessment of insulin sensitivity and untargeted mass spectrometry-based metabolomics in the offspring. A hyperinsulinemic-euglycemic clamp was performed in adult male rats born from dams fed a low-protein diet during gestation and/or lactation, and subsequently exposed to a Western diet (WD) for 10 wk. Metabolomics was combined with targeted acylcarnitine profiling and analysis of liver gene expression to identify markers of adaptation to WD that influence the phenotype outcome evaluated by body composition analysis. At adulthood, offspring of protein-restricted dams had impaired insulin secretion when fed a standard diet. Moreover, rats who demonstrated catch-up growth at weaning displayed higher gluconeogenesis and branched-chain amino acid catabolism, and lower fatty acid β-oxidation compared with control rats. Postweaning exposure of intrauterine growth restriction-born rats to a WD exacerbated incomplete fatty acid β-oxidation and excess fat deposition. Control offspring nursed by protein-restricted mothers showed peculiar low-fat accretion through adulthood and preserved insulin sensitivity even after WD-exposure. Altogether, our findings suggest a testable hypothesis about how maternal diet might influence metabolic outcomes (insulin sensitivity) in the next generation such as mitochondrial overload and/or substrate oxidation inflexibility dependent on the time window of perinatal dietary manipulation. PMID:24808498

  20. Chronic Protein Restriction in Mice Impacts Placental Function and Maternal Body Weight before Fetal Growth.

    PubMed

    Gonzalez, Paula N; Gasperowicz, Malgorzata; Barbeito-Andrés, Jimena; Klenin, Natasha; Cross, James C; Hallgrímsson, Benedikt

    2016-01-01

    Mechanisms of resource allocation are essential for maternal and fetal survival, particularly when the availability of nutrients is limited. We investigated the responses of feto-placental development to maternal chronic protein malnutrition to test the hypothesis that maternal low protein diet produces differential growth restriction of placental and fetal tissues, and adaptive changes in the placenta that may mitigate impacts on fetal growth. C57BL/6J female mice were fed either a low-protein diet (6% protein) or control isocaloric diet (20% protein). On embryonic days E10.5, 17.5 and 18.5 tissue samples were prepared for morphometric, histological and quantitative RT-PCR analyses, which included markers of trophoblast cell subtypes. Potential endocrine adaptations were assessed by the expression of Prolactin-related hormone genes. In the low protein group, placenta weight was significantly lower at E10.5, followed by reduction of maternal weight at E17.5, while the fetuses became significantly lighter no earlier than at E18.5. Fetal head at E18.5 in the low protein group, though smaller than controls, was larger than expected for body size. The relative size and shape of the cranial vault and the flexion of the cranial base was affected by E17.5 and more severely by E18.5. The junctional zone, a placenta layer rich in endocrine and energy storing glycogen cells, was smaller in low protein placentas as well as the expression of Pcdh12, a marker of glycogen trophoblast cells. Placental hormone gene Prl3a1 was altered in response to low protein diet: expression was elevated at E17.5 when fetuses were still growing normally, but dropped sharply by E18.5 in parallel with the slowing of fetal growth. This model suggests that nutrients are preferentially allocated to sustain fetal and brain growth and suggests the placenta as a nutrient sensor in early gestation with a role in mitigating impacts of poor maternal nutrition on fetal growth. PMID:27018791

  1. Chronic Protein Restriction in Mice Impacts Placental Function and Maternal Body Weight before Fetal Growth.

    PubMed

    Gonzalez, Paula N; Gasperowicz, Malgorzata; Barbeito-Andrés, Jimena; Klenin, Natasha; Cross, James C; Hallgrímsson, Benedikt

    2016-01-01

    Mechanisms of resource allocation are essential for maternal and fetal survival, particularly when the availability of nutrients is limited. We investigated the responses of feto-placental development to maternal chronic protein malnutrition to test the hypothesis that maternal low protein diet produces differential growth restriction of placental and fetal tissues, and adaptive changes in the placenta that may mitigate impacts on fetal growth. C57BL/6J female mice were fed either a low-protein diet (6% protein) or control isocaloric diet (20% protein). On embryonic days E10.5, 17.5 and 18.5 tissue samples were prepared for morphometric, histological and quantitative RT-PCR analyses, which included markers of trophoblast cell subtypes. Potential endocrine adaptations were assessed by the expression of Prolactin-related hormone genes. In the low protein group, placenta weight was significantly lower at E10.5, followed by reduction of maternal weight at E17.5, while the fetuses became significantly lighter no earlier than at E18.5. Fetal head at E18.5 in the low protein group, though smaller than controls, was larger than expected for body size. The relative size and shape of the cranial vault and the flexion of the cranial base was affected by E17.5 and more severely by E18.5. The junctional zone, a placenta layer rich in endocrine and energy storing glycogen cells, was smaller in low protein placentas as well as the expression of Pcdh12, a marker of glycogen trophoblast cells. Placental hormone gene Prl3a1 was altered in response to low protein diet: expression was elevated at E17.5 when fetuses were still growing normally, but dropped sharply by E18.5 in parallel with the slowing of fetal growth. This model suggests that nutrients are preferentially allocated to sustain fetal and brain growth and suggests the placenta as a nutrient sensor in early gestation with a role in mitigating impacts of poor maternal nutrition on fetal growth.

  2. Effects of protein restriction, melatonin administration, and short daylength on brain benzodiazepine receptors in prepubertal male rats

    SciTech Connect

    Kennaway, D.J.; Royles, P.; Webb, H.; Carbone, F.

    1988-01-01

    The possibility that there are changes in brain benzodiazepine binding sites controlled by photoperiod was investigated in two strains of male rats. The hypothesis was tested by 3H-diazepam binding studies in various brain regions of prepubertal rats maintained in 14 or 10 h of light or treated with late-afternoon injections of melatonin (50 micrograms/day). Protein restriction was applied during the experiment to sensitize the animals to the treatments. Under the conditions employed, rats kept in short daylength throughout or kept on long photoperiod and given late-afternoon melatonin injections showed evidence of delayed puberty (seminal vesicle, ventral prostate, and testis weight decreased by 45%, 55%, and 60% respectively, compared to control rats). Binding measurements were made 1 h before and 2 and 5 h after the onset of darkness in the pubertal (42-day-old) or experimentally prepubertal rats. In the rats of the Porton strain (for which protein restriction was obligatory for the gonadal response) there was no consistent treatment or time effects on specific binding of 3H-diazepam to washed membranes of the hypothalamus, midbrain, or striatum. Similarly, there were no differences in the stimulation of 3H-diazepam binding by 100 microM GABA or the inhibition of binding by 50 microM N-acetyl 5 methoxy kynurenamine. By contrast, in Wistar rats, specific binding to midbrain membranes was reduced 5 h after dark compared to 2 h (37% saline; 20% melatonin) and the extent of stimulation by GABA in the hypothalamus was increased 5 h after darkness (35.6% to 46.7% saline; 37.4% to 50% melatonin). Melatonin treatment resulted in significantly higher specific binding in the hypothalamus 2 h after dark (10%, control fed; 20%, protein restricted) but reduced the GABA induced stimulation of binding in the midbrain (35.5% to 25%, control fed; 33.7% to 23.5%, protein restricted).

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

    PubMed

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

    2016-05-01

    Metabolic malprogramming has been associated with low birth weight; however, the interplay between insulin secretion disruption and adrenal function upon lipid metabolism is unclear in adult offspring from protein-malnourished mothers during the last third of gestation. Thus, we aimed to study the effects of a maternal low-protein diet during the last third of pregnancy on adult offspring metabolism, including pancreatic islet function and morphophysiological aspects of the liver, adrenal gland, white adipose tissue, and pancreas. Virgin female Wistar rats (age 70 d) were mated and fed a protein-restricted diet (4%, intrauterine protein restricted [IUPR]) from day 14 of pregnancy until delivery, whereas control dams were fed a 20.5% protein diet. At age 91 d, their body composition, glucose-insulin homeostasis, ACTH, corticosterone, leptin, adiponectin, lipid profile, pancreatic islet function and liver, adrenal gland, and pancreas morphology were assessed. The birth weights of the IUPR rats were 20% lower than the control rats (P < .001). Adult IUPR rats were heavier, hyperphagic, hyperglycemic, hyperinsulinemic, hyperleptinemic, and hypercorticosteronemic (P < .05) with higher low-density lipoprotein cholesterol and lower high-density lipoprotein cholesterol, adiponectin, ACTH, and insulin sensitivity index levels (P < .01). The insulinotropic action of glucose and acetylcholine as well as muscarinic and adrenergic receptor function were impaired in the IUPR rats (P < .05). Maternal undernutrition during the last third of gestation disrupts the pancreatic islet insulinotropic response and induces obesity-associated complications. Such alterations lead to a high risk of metabolic syndrome, characterized by insulin resistance, visceral obesity, and lower high-density lipoprotein cholesterol. PMID:27007071

  4. Taurine Supplementation Reduces Blood Pressure and Prevents Endothelial Dysfunction and Oxidative Stress in Post-Weaning Protein-Restricted Rats

    PubMed Central

    Maia, Aline R.; Batista, Thiago M.; Victorio, Jamaira A.; Clerici, Stefano P.; Delbin, Maria A.; Carneiro, Everardo M.; Davel, Ana P.

    2014-01-01

    Introduction Taurine is a sulfur-containing amino acid that exerts protective effects on vascular function and structure in several models of cardiovascular diseases through its antioxidant and anti-inflammatory properties. Early protein malnutrition reprograms the cardiovascular system and is linked to hypertension in adulthood. This study assessed the effects of taurine supplementation in vascular alterations induced by protein restriction in post-weaning rats. Methods and Results Weaned male Wistar rats were fed normal- (12%, NP) or low-protein (6%, LP) diets for 90 days. Half of the NP and LP rats concomitantly received 2.5% taurine supplementation in the drinking water (NPT and LPT, respectively). LP rats showed elevated systolic, diastolic and mean arterial blood pressure versus NP rats; taurine supplementation partially prevented this increase. There was a reduced relaxation response to acetylcholine in isolated thoracic aortic rings from the LP group that was reversed by superoxide dismutase (SOD) or apocynin incubation. Protein expression of p47phox NADPH oxidase subunit was enhanced, whereas extracellular (EC)-SOD and endothelial nitric oxide synthase phosphorylation at Ser 1177 (p-eNOS) were reduced in aortas from LP rats. Furthermore, ROS production was enhanced while acetylcholine-induced NO release was reduced in aortas from the LP group. Taurine supplementation improved the relaxation response to acetylcholine and eNOS-derived NO production, increased EC-SOD and p-eNOS protein expression, as well as reduced ROS generation and p47phox expression in the aortas from LPT rats. LP rats showed an increased aortic wall/lumen ratio and taurine prevented this remodeling through a reduction in wall media thickness. Conclusion Our data indicate a protective role of taurine supplementation on the high blood pressure, endothelial dysfunction and vascular remodeling induced by post-weaning protein restriction. The beneficial vascular effect of taurine was

  5. Pre- and/or postnatal protein restriction developmentally programs affect and risk assessment behaviors in adult male rats.

    PubMed

    Reyes-Castro, L A; Rodriguez, J S; Rodríguez-González, G L; Chavira, R; Bautista, C J; McDonald, T J; Nathanielsz, P W; Zambrano, E

    2012-02-14

    Developmental programming resulting from a suboptimal intrauterine environment can predispose offspring to a wide-range of lifelong health complications. Little is known about the effects maternal protein restriction during pregnancy and/or lactation has on offspring neurodevelopment. We hypothesized that maternal isocaloric low protein diet during pregnancy and/or lactation would negatively influence male offspring affect and risk assessment behaviors as measured by elevated plus maze and open field tests. Control mothers received 20% casein (C) and restricted mothers (R) 10% casein to provide four groups: CC, RR, CR, and RC (first letter pregnancy diet and second letter lactation diet) to evaluate effects of maternal diet on offspring risk assessment, anxiety and exploratory behaviors. Elevated plus maze results showed an effect of pre- and/or postnatal diet manipulation in open arm time (p<0.05) with increases seen in the RR (157±22.7s), CR (137±23.2s) and RC (146.8±10.8s) offspring relative to CC (52±8.6s) offspring. This behavior indicates decreased avoidance (less anxiety) and increased exploration by experimental groups. However, in the open field test the RR (17±4.2 entries) offspring entered the center zone less than the CC (35±6.6 entries) offspring thus exhibiting increased anxiety with no other groups showing effects. Elevated levels of corticosterone were measured before, during and after immobilization in the RR compared to CC offspring. These findings show protein restriction during critical periods of development negatively program offspring behavior. The underlying anatomical structures affected remain to be elucidated.

  6. Correlation of serum leptin and insulin levels of pregnant protein-restricted rats with predictive obesity variables.

    PubMed

    Macêdo, G S; Ferreira, C L P; Menegaz, A; Arantes, V C; Veloso, R V; Carneiro, E M; Boschero, A C; Oller do Nascimento, C M P; Latorraca, M Q; Gomes-da-Silva, M H G

    2008-06-01

    During pregnancy and protein restriction, changes in serum insulin and leptin levels, food intake and several metabolic parameters normally result in enhanced adiposity. We evaluated serum leptin and insulin levels and their correlations with some predictive obesity variables in Wistar rats (90 days), up to the 14th day of pregnancy: control non-pregnant (N = 5) and pregnant (N = 7) groups (control diet: 17% protein), and low-protein non-pregnant (N = 5) and pregnant (N = 6) groups (low-protein diet: 6%). Independent of the protein content of the diet, pregnancy increased total (F1,19 = 22.28, P < 0.001) and relative (F1,19 = 5.57, P < 0.03) food intake, the variation of weight (F1,19 = 49.79, P < 0.000) and final body weight (F1,19 = 19.52, P < 0.001), but glycemia (F1,19 = 9.02, P = 0.01) and the relative weight of gonadal adipose tissue (F1,19 = 17.11, P < 0.001) were decreased. Pregnancy (F1,19 = 18.13, P < 0.001) and low-protein diet (F1,19 = 20.35, P < 0.001) increased the absolute weight of brown adipose tissue. However, the relative weight of this tissue was increased only by protein restriction (F1,19 = 15.20, P < 0.001) and the relative lipid in carcass was decreased in low-protein groups (F1,19 = 4.34, P = 0.05). Serum insulin and leptin levels were similar among groups and did not correlate with food intake. However, there was a positive relationship between serum insulin levels and carcass fat depots in low-protein groups (r = 0.37, P < 0.05), while in pregnancy serum leptin correlated with weight of gonadal (r = 0.39, P < 0.02) and retroperitoneal (r = 0.41, P < 0.01) adipose tissues. Unexpectedly, protein restriction during 14 days of pregnancy did not alter the serum profile of adiposity signals and their effects on food intake and adiposity, probably due to the short term of exposure to low-protein diet. PMID:18622496

  7. Deoxyribonucleic acid-dependent ribonucleic acid polymerase activity in rat liver after protein restriction.

    PubMed Central

    Andersson, G M; von der Decken, A

    1975-01-01

    Rats were fed for 6 days on a diet containing either 3 or 20% high-quality protein. Nuclei were isolated from liver and DNA-dependent RNA polymerases (EC 2.7.7.6) extracted with 1 M-(NH4)2SO4. The proteins were then precipitated with 3.5 M-(NH4)2SO4 and after dialysis applied to a DEAE-Sephadex column. The column was developed with a gradient of (NH4)2SO4. Polymerase I separated well from alpha-amanitin-sensitive polymerase II. The enzyme activities were compared between the two dietary groups. Rats that had received 3% protein showed a lower polymerase I activity per g wet wt. of liver, per mg of DNA and per mg of protein. Polymerase II was lower in activity per g wet wt. of liver and per mg of DNA, but was higher per mg of protein. Polyacrylamide-gel electrophoretograms showed a higher proportion of contaminating proteins in polymerase II fractions isolated from 20%-protein-fed rats. The data explain the lower activity obtained per mg of protein in these rats. It is concluded that a decrease in dietary protein content from 20 to 3% induces a fall in content and specific activity of RNA polymerase I and II in liver. PMID:1156400

  8. Pre- and/or postnatal protein restriction in rats impairs learning and motivation in male offspring.

    PubMed

    Reyes-Castro, L A; Rodriguez, J S; Rodríguez-González, G L; Wimmer, R D; McDonald, T J; Larrea, F; Nathanielsz, P W; Zambrano, E

    2011-04-01

    Suboptimal developmental environments program offspring to lifelong health complications including affective and cognitive disorders. Little is known about the effects of suboptimal intra-uterine environments on associative learning and motivational behavior. We hypothesized that maternal isocaloric low protein diet during pregnancy and lactation would impair offspring associative learning and motivation as measured by operant conditioning and the progressive ratio task, respectively. Control mothers were fed 20% casein (C) and restricted mothers (R) 10% casein to provide four groups: CC, RR, CR, and RC (first letter pregnancy diet and second letter lactation diet), to evaluate effects of maternal diet on male offspring behavior. Impaired learning was observed during fixed ratio-1 operant conditioning in RC offspring that required more sessions to learn vs. the CC offspring (9.4±0.8 and 3.8±0.3 sessions, respectively, p<0.05). Performance in fixed ratio-5 conditioning showed the RR (5.4±1.1), CR (4.0±0.8), and RC (5.0±0.8) offspring required more sessions to reach performance criterion than CC offspring (2.5±0.5, p<0.05). Furthermore, motivational effects during the progressive ratio test revealed less responding in the RR (48.1±17), CR (74.7±8.4), and RC (65.9±11.2) for positive reinforcement vs. the CC offspring (131.5±7.5, p<0.05). These findings demonstrate negative developmental programming effects due to perinatal isocaloric low protein diet on learning and motivation behavior with the nutritional challenge in the prenatal period showing more vulnerability in offspring behavior.

  9. Pre- and/or postnatal protein restriction in rats impairs learning and motivation in male offspring.

    PubMed

    Reyes-Castro, L A; Rodriguez, J S; Rodríguez-González, G L; Wimmer, R D; McDonald, T J; Larrea, F; Nathanielsz, P W; Zambrano, E

    2011-04-01

    Suboptimal developmental environments program offspring to lifelong health complications including affective and cognitive disorders. Little is known about the effects of suboptimal intra-uterine environments on associative learning and motivational behavior. We hypothesized that maternal isocaloric low protein diet during pregnancy and lactation would impair offspring associative learning and motivation as measured by operant conditioning and the progressive ratio task, respectively. Control mothers were fed 20% casein (C) and restricted mothers (R) 10% casein to provide four groups: CC, RR, CR, and RC (first letter pregnancy diet and second letter lactation diet), to evaluate effects of maternal diet on male offspring behavior. Impaired learning was observed during fixed ratio-1 operant conditioning in RC offspring that required more sessions to learn vs. the CC offspring (9.4±0.8 and 3.8±0.3 sessions, respectively, p<0.05). Performance in fixed ratio-5 conditioning showed the RR (5.4±1.1), CR (4.0±0.8), and RC (5.0±0.8) offspring required more sessions to reach performance criterion than CC offspring (2.5±0.5, p<0.05). Furthermore, motivational effects during the progressive ratio test revealed less responding in the RR (48.1±17), CR (74.7±8.4), and RC (65.9±11.2) for positive reinforcement vs. the CC offspring (131.5±7.5, p<0.05). These findings demonstrate negative developmental programming effects due to perinatal isocaloric low protein diet on learning and motivation behavior with the nutritional challenge in the prenatal period showing more vulnerability in offspring behavior. PMID:21078378

  10. Folate supplementation during pregnancy improves offspring cardiovascular dysfunction induced by protein restriction.

    PubMed

    Torrens, Christopher; Brawley, Lee; Anthony, Frederick W; Dance, Caroline S; Dunn, Rebecca; Jackson, Alan A; Poston, Lucilla; Hanson, Mark A

    2006-05-01

    Dietary protein restriction in the rat compromises the maternal cardiovascular adaptations to pregnancy and leads to raised blood pressure and endothelial dysfunction in the offspring. In this study we have hypothesized that dietary folate supplementation of the low-protein diet will improve maternal vascular function and also restore offspring cardiovascular function. Pregnant Wistar rats were fed either a control (18% casein) or protein-restricted (9% casein) diet +/-5 mg/kg folate supplement. Function of isolated maternal uterine artery and small mesenteric arteries from adult male offspring was assessed, systolic blood pressure recorded, and offspring thoracic aorta levels of endothelial nitric oxide (NO) synthase mRNA measured. In the uterine artery of late pregnancy dams, vasodilatation to vascular endothelial growth factor was attenuated in the protein-restricted group but restored with folate supplementation, as was isoprenaline-induced vasodilatation (P<0.05). In male offspring, protein restriction during pregnancy led to raised systolic blood pressure (P<0.01), impaired acetylcholine-induced vasodilatation (P<0.01), and reduced levels of endothelial NO synthase mRNA (P<0.05). Maternal folate supplementation during pregnancy prevented this elevated systolic blood pressure associated with a protein restriction diet. With folate supplementation, endothelium-dependent vasodilatation and endothelial NO synthase mRNA levels were not significantly different from either the control or protein-restricted groups. Maternal folate supplementation of the control diet had no effect on blood pressure or vasodilatation. This study supports the hypothesis that folate status in pregnancy can influence fetal development and, thus, the risks of cardiovascular disease in the next generation. The concept of developmental origins of adult disease focuses predominately on fetal life but must also include a role for maternal cardiovascular function. PMID:16585422

  11. Nutritional recovery with a soybean diet after weaning reduces lipogenesis but induces inflammation in the liver in adult rats exposed to protein restriction during intrauterine life and lactation.

    PubMed

    Reis, Sílvia Regina de Lima; Feres, Naoel Hassan; Ignacio-Souza, Leticia Martins; Veloso, Roberto Vilela; Arantes, Vanessa Cristina; Kawashita, Nair Honda; Colodel, Edson Moleta; Botosso, Bárbara Laet; Reis, Marise Auxiliadora de Barros; Latorraca, Márcia Queiroz

    2015-01-01

    We evaluated the effects of postweaning nutritional recovery with a soybean flour diet on de novo hepatic lipogenesis and inflammation in adult rats exposed to protein restriction during intrauterine life and lactation. Rats from mothers fed with protein (casein) in a percentage of 17% (control, C) or 6% (low, L) during pregnancy and lactation were fed with diet that contained 17% casein (CC and LC groups, resp.) or soybean (CS and LS groups, resp.) after weaning until 90 days of age. LS and CS rats had low body weight, normal basal serum triglyceride levels, increased ALT concentrations, and high HOMA-IR indices compared with LC and CC rats. The soybean diet reduced PPARγ as well as malic enzyme and citrate lyase contents and activities. The lipogenesis rate and liver fat content were lower in LS and CS rats relative to LC and CC rats. TNFα mRNA and protein levels were higher in LS and CS rats than in LC and CC rats. NF-κB mRNA levels were lower in the LC and LS groups compared with the CC and LC groups. Thus, the soybean diet prevented hepatic steatosis at least in part through reduced lipogenesis but resulted in TNFα-mediated inflammation. PMID:25892856

  12. Nutritional Recovery with a Soybean Diet after Weaning Reduces Lipogenesis but Induces Inflammation in the Liver in Adult Rats Exposed to Protein Restriction during Intrauterine Life and Lactation

    PubMed Central

    Reis, Sílvia Regina de Lima; Feres, Naoel Hassan; Ignacio-Souza, Leticia Martins; Veloso, Roberto Vilela; Arantes, Vanessa Cristina; Kawashita, Nair Honda; Colodel, Edson Moleta; Botosso, Bárbara Laet; Reis, Marise Auxiliadora de Barros; Latorraca, Márcia Queiroz

    2015-01-01

    We evaluated the effects of postweaning nutritional recovery with a soybean flour diet on de novo hepatic lipogenesis and inflammation in adult rats exposed to protein restriction during intrauterine life and lactation. Rats from mothers fed with protein (casein) in a percentage of 17% (control, C) or 6% (low, L) during pregnancy and lactation were fed with diet that contained 17% casein (CC and LC groups, resp.) or soybean (CS and LS groups, resp.) after weaning until 90 days of age. LS and CS rats had low body weight, normal basal serum triglyceride levels, increased ALT concentrations, and high HOMA-IR indices compared with LC and CC rats. The soybean diet reduced PPARγ as well as malic enzyme and citrate lyase contents and activities. The lipogenesis rate and liver fat content were lower in LS and CS rats relative to LC and CC rats. TNFα mRNA and protein levels were higher in LS and CS rats than in LC and CC rats. NF-κB mRNA levels were lower in the LC and LS groups compared with the CC and LC groups. Thus, the soybean diet prevented hepatic steatosis at least in part through reduced lipogenesis but resulted in TNFα-mediated inflammation. PMID:25892856

  13. Nutritional recovery with a soybean diet after weaning reduces lipogenesis but induces inflammation in the liver in adult rats exposed to protein restriction during intrauterine life and lactation.

    PubMed

    Reis, Sílvia Regina de Lima; Feres, Naoel Hassan; Ignacio-Souza, Leticia Martins; Veloso, Roberto Vilela; Arantes, Vanessa Cristina; Kawashita, Nair Honda; Colodel, Edson Moleta; Botosso, Bárbara Laet; Reis, Marise Auxiliadora de Barros; Latorraca, Márcia Queiroz

    2015-01-01

    We evaluated the effects of postweaning nutritional recovery with a soybean flour diet on de novo hepatic lipogenesis and inflammation in adult rats exposed to protein restriction during intrauterine life and lactation. Rats from mothers fed with protein (casein) in a percentage of 17% (control, C) or 6% (low, L) during pregnancy and lactation were fed with diet that contained 17% casein (CC and LC groups, resp.) or soybean (CS and LS groups, resp.) after weaning until 90 days of age. LS and CS rats had low body weight, normal basal serum triglyceride levels, increased ALT concentrations, and high HOMA-IR indices compared with LC and CC rats. The soybean diet reduced PPARγ as well as malic enzyme and citrate lyase contents and activities. The lipogenesis rate and liver fat content were lower in LS and CS rats relative to LC and CC rats. TNFα mRNA and protein levels were higher in LS and CS rats than in LC and CC rats. NF-κB mRNA levels were lower in the LC and LS groups compared with the CC and LC groups. Thus, the soybean diet prevented hepatic steatosis at least in part through reduced lipogenesis but resulted in TNFα-mediated inflammation.

  14. Protein restriction during pregnancy affects postnatal growth in swine progeny.

    PubMed

    Schoknecht, P A; Pond, W G; Mersmann, H J; Maurer, R R

    1993-11-01

    Protein deficiency during pregnancy affects fetal development. The critical period, when the fetus is most susceptible to maternal protein deficiency and its effect on neonatal growth, is unknown. Therefore, we studied the effect of a protein-restricted diet during early and late pregnancy and throughout pregnancy on growth of pigs from birth to market weight. Sows were fed a control (13% protein) or protein-restricted (0.5% protein) diet throughout pregnancy or protein-restricted diet from d 1 to 44, then control diet to term or control diet from d 1 to 81, then the protein-restricted diet to term. In Experiment 1, birth weights were measured, and 12 pigs/diet group were weaned at 4 wk and raised to market weight. Feeding the protein-restricted diet throughout pregnancy reduced birth and slaughter weights, whereas the control followed by protein-restricted and protein-restricted followed by control diets reduced only birth weight relative to controls. Indices of carcass lean were reduced in the protein-restricted piglets, with carcass fat not affected. In Experiment 2, control and control-protein-restricted litters were reduced to six piglets and 3/litter cross-fostered to a sow of the other treatment group. After weaning at 4 wk, 4 piglets/group were individually fed to 8 wk. The control and control followed by protein-restricted diet fed piglets had similar weights at birth, but piglets raised by a control-protein-restricted sow tended to weight less at weaning than their littermates raised by a control sow. After weaning, these piglets had greater feed intakes relative to other groups and there were no weight differences by 8 wk.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Antipsychotic Drugs on Maternal Behavior in Rats

    PubMed Central

    Li, Ming

    2015-01-01

    Rat maternal behavior is a complex social behavior. Many clinically used antipsychotic drugs, including the typical drug haloperidol and atypical drugs clozapine, risperidone, olanzapine, quetiapine, aripiprazole and amisulpride, all disrupt active maternal responses (e.g. pup retrieval, pup licking and nest building) to various extents. In this review, I present a summary of recent studies on the behavioral effects and neurobiological mechanisms of antipsychotic action on maternal behavior in rats. I argue that antipsychotic drugs at the clinical relevant doses disrupt active maternal responses primarily by suppressing maternal motivation. Atypical drug-induced sedation also contributes to their disruptive effects, especially that on pup nursing. Among many potential receptor mechanisms, dopamine D2 receptors and serotonin 5-HT2A/2C receptors are shown to be critically involved in the mediation of the maternal disruptive effects of antipsychotic drugs, with D2 receptors contributing more to typical antipsychotic-induced disruptions, while 5-HT2A/2C receptors contributing more to atypical drug-induced disruption. The nucleus accumbens shell-related reward circuitry is an essential neural network in the mediation of the behavioral effects of antipsychotic drugs on maternal behavior. This research not only helps to understand the extent and mechanisms of impacts of antipsychotic medications on human maternal care, but also is important for enhancing our understanding of the neurochemical basis of maternal behavior. It is also valuable for understanding the complete spectrum of therapeutic and side-effects of antipsychotic treatment. This knowledge may facilitate the development of effective intervening strategies to help patients coping with such undesirable effects. PMID:26221833

  16. Maternal protein and folic acid intake during gestation does not program leptin transcription or serum concentration in rat progeny.

    PubMed

    Chmurzynska, Agata; Stachowiak, Monika; Pruszynska-Oszmalek, Ewa

    2012-04-01

    Maternal nutrition during gestation influences the development of the fetus, thereby determining its phenotype, including nutrient metabolism, appetite, and feeding behavior. The control of appetite is a very complex process and can be modulated by orexigenic and anorexigenic mediators such as leptin, which is involved in the regulation of energy homeostasis by controlling food intake and energy expenditure. Leptin transcription and secretion are regulated by numerous factors, nutrition being one of them. The present study was designed to test whether maternal nutrition can permanently affect leptin gene transcription and leptin serum concentration in rat progeny. Moreover, we analyzed whether leptin expression and secretion in response to high-fat postweaning feeding depends on the maternal diet during gestation. Pregnant rats were fed either a normal protein, normal folic acid diet (the AIN-93 diet); a protein-restricted, normal folic acid diet; a protein-restricted, folic acid-supplemented diet; or a normal protein, folic acid-supplemented diet. After weaning, the progeny was fed either the AIN-93 diet or a high-fat diet. Neither maternal nutrition nor the postweaning diet significantly affected Lep transcription. High-fat feeding after weaning was associated with higher serum leptin concentration, but the reaction of an organism to the fat content of the diet was not determined by maternal nutrition during gestation. There was no correlation between Lep mRNA level and serum leptin concentration. Global DNA methylation in adipose tissue was about 30% higher in rats fed postnatally the high-fat diet (P < 0.01). Our study showed that the protein and folic acid content in the maternal diet had no significant programming effect on Lep transcription and serum leptin concentration in the rats.

  17. Gestational protein restriction affects trophoblast differentiation.

    PubMed

    Gao, Haijun; Yallampalli, Uma; Yallampalli, Chandra

    2013-01-01

    Whether and how gestational protein restriction (PR) affects placental development and function remain unknown. To test the hypothesis that PR can affect trophoblast differentiation in mid-and late pregnancy, rats were fed a 20% or an isocaloric 6% protein diet from Day 1 to 14 or 18 of pregnancy and effects of PR on trophoblast differentiation were determined by changes in expressions of marker gene(s) for trophoblast lineages. At Day 18 of pregnancy, PR increased expressions of Esrrb, Id1 andId2 (trophoblast stem cell markers), decreased expressions of Ascl2 (spongiotrophblast cell marker) and Prl2c1 (trophoblast giant cell marker), but did not alter expressions of Gjb3 and Pcdh12(glycogen cell markers) in the junctional zone (JZ). In the labyrinth zone (LZ), PR did not change expressions of Prl2b1 (trophoblast giant cell marker), Gcm1 and Syna (syncytiotrophoblast cell markers), but decrease expression of Ctsq (sinusoidal trophoblast giant cell marker). These results indicate that PR impairs the differentiation of trophoblast stem cell into spongiotrophoblast and trophoblast giant cells in JZ, and formation of sinusoidal trophoblast giant cells in LZ.

  18. Mammary sensitivity to protein restriction and re-alimentation.

    PubMed

    Goodwill, M G; Jessop, N S; Oldham, J D

    1996-09-01

    The present study tested the influence of protein undernutrition and re-alimentation on mammary gland size and secretory cell activity in lactating rats. During gestation, female Sprague-Dawley rats were offered a high-protein diet (215 g crude protein (N x 6.25; CP)/kg DM; H); litters were standardized to twelve pups at parturition. During lactation, two diets were offered ad libitum, diet H and a low-protein diet (90 g CP/kg DM; L). Lactational dietary treatments were the supply ad libitum of either diet H (HHH) or diet L (LLL) for the first 12 d of lactation, or diet L transferring to diet H on either day 6 (LHH) or 9 (LLH) of lactation. On days 1, 6, 9 and 12 of lactation, rats from each group (n > or = 6) were used to estimate mammary dry mass, fat, protein, DNA and RNA; the activities of lactose synthetase (EC 2.4.1.22) enzyme and Na+,K(+)-ATPase (EC 3.6.1.37) were also measured. Rats offered a diet considered protein sufficient (H) from day 1 of lactation showed a decrease in mammary dry mass and fat but an increase in DNA, RNA and protein on day 6, after which there was no further change, except for mammary protein which continued to increase. However, rats offered diet L showed a steady loss in mammary mass and fat throughout the 12 d lactation period and no change in mammary DNA, RNA or protein. Rats previously protein restricted for either the first 6 or 9 d of lactation had their mammary dry mass and mammary fat loss halted and showed a rapid increase in mammary DNA, RNA and protein on re-alimentation. Lactose production in group HHH, as measured by lactose synthetase activity, was similar on days 1 and 6 of lactation, after which a significant increase was seen. Protein-restricted rats showed no change in lactose synthetase activity during the 12 d experimental period. Changing from diet L to diet H led to a significant increase in lactose synthetase activity to levels comparable with those offered diet H from day 1. These results show that rats

  19. MATERNAL AND DEVELOPMENTAL TOXICITY OF PERFLUOROOCTANE SULFONATE IN THE RAT

    EPA Science Inventory

    MATERNAL AND DEVELOPMENTAL TOXICITY OF PERFLUOROOCTANE SULFONATE IN THE RAT.
    C. Lau and J.M. Rogers, Reproductive Toxicology Division, NHEERL, ORD, USEPA, Research Triangle Park, NC, USA

    Perfluorooctane sulfonate (PFOS), an environmentally persistent compound used ...

  20. Long-term modification of the excretion of prostaglandin E(2) by fetal exposure to a maternal low protein diet in the rat.

    PubMed

    Sherman, R C; Jackson, A A; Langley-Evans, S C

    1999-01-01

    Prenatal exposure to maternal undernutrition in both humans and animals is associated with long-term changes in the structure, physiological functions and metabolism of key tissues and organs. This phenomenon, termed programming, is implicated in the aetiology of cardiovascular disease. Using an established rat model of hypertension programmed by prenatal protein restriction, assessment was made of the long-term influence of maternal diet upon prostaglandin metabolism. Pregnant rats were fed isoenergetic diets containing 18% casein (control) or 9% casein (low protein) from conception until littering. The offspring of these pregnancies were studied at day 20 of gestation, full-term gestation and at 4, 7 or 12 weeks postnatal age. Prostaglandin E(2) concentrations in plasma were similar in control and low-protein diet-exposed rats at 4 weeks of age. Urinary prostaglandin E(2) excretion was, however, significantly increased by prenatal undernutrition in rats at both 4 and 12 weeks postnatal age. The principal enzyme of prostaglandin E(2) degradation, 15-hydroxyprostaglandin dehydrogenase (PGDH) exhibited significantly lower activity in the kidneys of 4-week-old rats exposed to a maternal low-protein diet. This effect was transient and absent by 12 weeks postnatal age. There was also some evidence of an altered developmental profile of PGDH activity in the lungs of low-protein diet-exposed rats. These data are consistent with the long-term programming effects of the maternal diet upon renal prostaglandin metabolism. In the rat, increased local prostaglandin E(2) concentrations associated with impaired degradation may contribute to increased renovascular resistance and hypertension.

  1. Decline of maternal antibodies to plague in Norway rats.

    PubMed

    Williams, J E; Eisenberg, G H; Cavanaugh, D C

    1977-02-01

    The decline of maternal antibodies to the fraciton I antigen of Yersinia pestis was investigated in newly weaned Rattus norvegicus obtained from dams vaccinated with strain EV76(51F) of Y. pestis. IHA titre decreased by 50% each 7-3 days and CF titre declined 50% each 10-0 days in young rats. An analysis of available data indicated that maternal IHA and CF antibodies could persist to 3 months of age. Therefore, positive serologic reactions in young R. norvegicus, detected in the course of serological surveys, could be the result either of active immunization after exposure to the plague bacillus or of transient passive immunization (i.e. maternal antibody). PMID:264498

  2. Enzyme markers of maternal malnutrition in fetal rat brain.

    PubMed

    Shambaugh, G E; Mankad, B; Derecho, M L; Koehler, R R

    1987-01-01

    The impact of maternal starvation in late gestation on development of some enzymatic mechanisms concerned with neurotransmission and polyamine synthesis was studied in fetal rat brain. Between 17 and 20 d, acetylcholinesterase and choline acetyltransferase activity increased in fetal brains of fed dams, whereas maternal starvation from day 17 to day 20 resulted in heightened acetylcholinesterase but not choline acetyltransferase activity. Ornithine decarboxylase activity on a per-gram wet-weight basis fell between 17 and 20 d in fetal brain from fed dams. Increasing the duration of maternal starvation resulted in a progressive increase in fetal brain ornithine decarboxylase. Arginine and putrescine levels in the brain were lower in fetuses of starved mothers while spermidine and spermine concentrations were unchanged. Since the Km of ornithine decarboxylase for ornithine was found to vary directly with levels of putrescine in fetal brain, lower concentrations of putrescine and greater ornithine decarboxylase activity in fetal brains from starved mothers suggested that levels of this enzyme may be controlled in part by putrescine. Changes in the maternal nutritional state had no effect on the activity of glutamate decarboxylase in fetal brain, and tissue levels of the product, gamma-aminobutyric acid, were unchanged. Thus changes in ornithine decarboxylase and acetylcholinesterase activity in fetal brain may uniquely reflect biochemical alterations consequent to maternal starvation.

  3. Effects of protein restriction during gestation and lactation on cell proliferation in the hippocampus and subventricular zone: functional implications. Protein restriction alters hippocampal/SVZ cell proliferation.

    PubMed

    Godoy, Mariana Araya de; Souza, Amanda Santos de; Lobo, Mônica Alves; Sampaio, Omar Vidal Kress; Moraes, Louise; Baldanza, Marcelo Ribeiro; Magri, Tatiana Przybylski Ribeiro; Wernerck de Castro, João Pedro Saar; Tavares do Carmo, Maria das Graças; Soares-Mota, Márcia; Rocha, Monica Santos; Mendez-Otero, Rosalia; Santiago, Marcelo Felippe

    2013-02-16

    There is no consensus about the effects of protein restriction on neurogenesis and behavior. Here, for the first time, we evaluated the effects of protein restriction during gestation and lactation, on the two major neurogenic regions of the adult brain, the subgranular zone (SGZ) of the hippocampal dentate gyrus and the subventricular zone (SVZ), simultaneously. We also assessed different types of behavior relevant to each region. After mating, pregnant Wistar rats were divided into a control group (CG) that received a normal diet (20% protein); and a protein-restriction group (PRG) that received a low-protein diet (8% protein). After birth, the same diets were provided to the mother and pups until weaning, when some rats were analyzed and others received a normal-protein diet until adulthood. Different sets of rats were used for cellular and behavioral studies in juvenile or adult age. Brains were processed for immunohistochemistry anti-BrdU, anti-Ki67, or anti-pHisH3. Juvenile and adult rats from distinct litters also underwent several behavioral tests. Our data show that early protein restriction results in a reduction of hippocampal progenitors and deficits in object recognition during adult life. Moreover, longer periods of immobility in the tail suspension and in the forced swimming tests revealed that PRG rats show a depressive behavior at 21 days of age (P21) and in adulthood. Furthermore, we suggest that despite the reduced number/proliferation of neural stem cells (B and/or E cells) in SVZ there is a compensatory mechanism in which the progenitors (types C and A cells) proliferate in a higher rate, without affecting olfactory ability in adulthood.

  4. Metyrapone alleviates deleterious effects of maternal food restriction on lung development and growth of rat offspring.

    PubMed

    Paek, David S; Sakurai, Reiko; Saraswat, Aditi; Li, Yishi; Khorram, Omid; Torday, John S; Rehan, Virender K

    2015-02-01

    Maternal food restriction (MFR) causes intrauterine growth restriction, a known risk factor for developing chronic lung disease. However, it is unknown whether this negative outcome is gender specific or preventable by blocking the MFR-induced hyperglucocorticoidism. Using a well-established rat model, we used metyrapone (MTP), an inhibitor of glucocorticoid synthesis, to study the MFR-induced lung changes on postnatal day (p) 21 in a gender-specific manner. From embryonic day 10 until delivery, pregnant dams were fed either an ad libitum diet or a 50% caloric restricted diet with or without MTP supplementation. Postnatally, the offspring were fed ad libitum from healthy dams until p21. Morphometric, Western blot, and immunohistochemical analysis of the lungs demonstrated that MTP mitigated the MFR-mediated decrease in alveolar count, decrease in adipogenic protein peroxisome proliferator-activated receptor γ, increase in myogenic proteins (fibronectin, α-smooth muscle actin, and calponin), increase in Wnt signaling intermediates (lymphoid enhancer-binding factor 1 and β-catenin), and increase in glucocorticoid receptor (GR) levels. The MFR-induced lung phenotype and the effects of MTP were similar in both genders. To elucidate the mechanism of MFR-induced shift of the adipogenic-to-myogenic phenotype, lung fibroblasts were used to independently study the effects of (1) nutrient restriction and (2) excess steroid exposure. Nutrient deprivation increased myogenic proteins, Wnt signaling intermediates, and GR, all changes blocked by protein supplementation. MTP also blocked, likely by normalizing nicotinamide adenine dinucleotide phosphate levels, the corticosterone-induced increase in myogenic proteins, but had no effect on GR levels. In summary, protein restriction and increased glucocorticoid levels appear to be the key players in MFR-induced lung disease, affecting both genders.

  5. Metyrapone Alleviates Deleterious Effects of Maternal Food Restriction on Lung Development and Growth of Rat Offspring

    PubMed Central

    Paek, David S.; Sakurai, Reiko; Saraswat, Aditi; Li, Yishi; Khorram, Omid; Torday, John S.

    2015-01-01

    Maternal food restriction (MFR) causes intrauterine growth restriction, a known risk factor for developing chronic lung disease. However, it is unknown whether this negative outcome is gender specific or preventable by blocking the MFR-induced hyperglucocorticoidism. Using a well-established rat model, we used metyrapone (MTP), an inhibitor of glucocorticoid synthesis, to study the MFR-induced lung changes on postnatal day (p) 21 in a gender-specific manner. From embryonic day 10 until delivery, pregnant dams were fed either an ad libitum diet or a 50% caloric restricted diet with or without MTP supplementation. Postnatally, the offspring were fed ad libitum from healthy dams until p21. Morphometric, Western blot, and immunohistochemical analysis of the lungs demonstrated that MTP mitigated the MFR-mediated decrease in alveolar count, decrease in adipogenic protein peroxisome proliferator-activated receptor γ, increase in myogenic proteins (fibronectin, α-smooth muscle actin, and calponin), increase in Wnt signaling intermediates (lymphoid enhancer-binding factor 1 and β-catenin), and increase in glucocorticoid receptor (GR) levels. The MFR-induced lung phenotype and the effects of MTP were similar in both genders. To elucidate the mechanism of MFR-induced shift of the adipogenic-to-myogenic phenotype, lung fibroblasts were used to independently study the effects of (1) nutrient restriction and (2) excess steroid exposure. Nutrient deprivation increased myogenic proteins, Wnt signaling intermediates, and GR, all changes blocked by protein supplementation. MTP also blocked, likely by normalizing nicotinamide adenine dinucleotide phosphate levels, the corticosterone-induced increase in myogenic proteins, but had no effect on GR levels. In summary, protein restriction and increased glucocorticoid levels appear to be the key players in MFR-induced lung disease, affecting both genders. PMID:24916330

  6. Maternal age, reproduction and chromosomal aberrations in Wistar derived rats.

    PubMed

    Niggeschulze, A; Kast, A

    1994-01-01

    The fertility of rats ranges from one to 18 months. In standard teratogenicity testing young, mature females are used which may not reflect the situation in women above 35 years old. Reproduction among different age groups of Wistar ats (strain Chbb: THOM) was compared at 3, 6, 9, 12, 15 and 18 months. At least 20 virgin females were inseminated per age group. The copulation rate did not differ between the groups. From the maternal age of 12 months, the pregnancy rate was significantly decreased, from the age of 9 months, the litter values were significantly lowered and the resorption rates were increased. Maternal age did not influence the incidence of fetal variations and malformations. Additionally, the chromosomal aberration rate in the bone marrow was evaluated in male and female rats. Twelve animals of each sex were scheduled per group, and studied at the age of 1, 3, 6, 12, 15, 18, 21 or 24 months. In males, the aberration rate increased continuously from 0.18 through 3%, while in females the increase continued from 0.33 to 2.29% at 15 months old when a plateau was reached. When testing new compounds for embryotoxicity or genotoxicity in female rats, the animals should be of comparable age to man in order to avoid a misinterpretation of spontaneous abnormalities. From these studies, however, it was concluded that the use of higher age groups of female rats in teratogenicity studies would not improve the risk assessment.

  7. Hepatic autophagy contributes to the metabolic response to dietary protein restriction.

    PubMed

    Henagan, Tara M; Laeger, Thomas; Navard, Alexandra M; Albarado, Diana; Noland, Robert C; Stadler, Krisztian; Elks, Carrie M; Burk, David; Morrison, Christopher D

    2016-06-01

    Autophagy is an essential cellular response which acts to release stored cellular substrates during nutrient restriction, and particularly plays a key role in the cellular response to amino acid restriction. However, there has been limited work testing whether the induction of autophagy is required for adaptive metabolic responses to dietary protein restriction in the whole animal. Here, we found that moderate dietary protein restriction led to a series of metabolic changes in rats, including increases in food intake and energy expenditure, the downregulation of hepatic fatty acid synthesis gene expression and reduced markers of hepatic mitochondrial number. Importantly, these effects were also associated with an induction of hepatic autophagy. To determine if the induction of autophagy contributes to these metabolic effects, we tested the metabolic response to dietary protein restriction in BCL2-AAA mice, which bear a genetic mutation that impairs autophagy induction. Interestingly, BCL2-AAA mice exhibit exaggerated responses in terms of both food intake and energy expenditure, whereas the effects of protein restriction on hepatic metabolism were significantly blunted. These data demonstrate that restriction of dietary protein is sufficient to trigger hepatic autophagy, and that disruption of autophagy significantly alters both hepatic and whole animal metabolic response to dietary protein restriction. PMID:27173459

  8. Folic acid and protein content in maternal diet and postnatal high-fat feeding affect the tissue levels of iron, zinc, and copper in the rat.

    PubMed

    Król, Ewelina; Krejpcio, Zbigniew; Chmurzynska, Agata

    2011-12-01

    Although maternal, fetal, and placental mechanisms compensate for disturbances in the fetal environment, any nutritional inadequacies present during pregnancy may affect fetal metabolism, and their consequences may appear in later life. The aim of the present study is to investigate the influence of maternal diet during gestation on Fe, Zn, and Cu levels in the livers and kidneys of adult rats. The study was carried out on the offspring (n = 48) of mothers fed either a protein-balanced or a protein-restricted diet (18% vs. 9% casein) during pregnancy, with or without folic acid supplementation (0.005- vs. 0.002-g folic acid/kg diet). At 10 weeks of age, the offspring of each maternal group were randomly assigned to groups fed either the AIN-93G diet or a high-fat diet for 6 weeks, until the end of the experiment. The levels of Fe, Zn, and Cu in the livers and kidneys were determined by the F-AAS method. It was found that postnatal exposure to the high-fat diet was associated with increased hepatic Fe levels (p < 0.001), and with decreased liver Zn and Cu contents (p < 0.01 and p < 0.05, respectively), as well as with decreased renal Cu contents (p < 0.001). Moreover, the offspring's tissue mineral levels were also affected by protein and folic acid content in the maternal diet. Both prenatal protein restriction and folic acid supplementation increased the liver Zn content (p < 0.05) and the kidney Zn content (p < 0.001; p < 0.05, respectively), while folic acid supplementation resulted in a reduction in renal Cu level (p < 0.05). Summarizing, the results of this study show that maternal dietary folic acid and protein intake during pregnancy, as well as the type of postweaning diet, affect Fe, Zn, and Cu levels in the offspring of the rat. However, the mechanisms responsible for this phenomenon are unclear, and warrant further investigation.

  9. The effects of dietary protein restriction on chorda tympani nerve taste responses and terminal field organization.

    PubMed

    Thomas, J E; Hill, D L

    2008-11-19

    Prenatal dietary sodium restriction produces profound developmental effects on rat functional taste responses and formation of neural circuits in the brainstem. Converging evidence indicates that the underlying mechanisms for these effects are related to a compromised nutritional state and not to direct stimulus-receptor interactions. We explored whether early malnourishment produces similar functional and structural effects to those seen following dietary sodium restriction by using a protein deficient, sodium replete diet. To determine if early dietary protein-restriction affects the development of the peripheral gustatory system, multi-fiber neurophysiological recordings were made from the chorda tympani nerve and anterograde track tracing of the chorda tympani nerve into the nucleus of the solitary tract (NTS) was accomplished in rats fed a protein-restricted or a control diet (6% and 20%, respectively). The dietary regimens began on embryonic day 7 and continued until rats were used for neurophysiological recordings (postnatal days (P) 35-50) or for chorda tympani terminal field labeling (P40-50). Responses to a concentration series of NaCl, sodium acetate, KCl, and to 0.50 M sucrose, 0.03 M quinine-HCl, and 0.01 N HCl revealed attenuated responses (30-60%) to sodium-specific stimuli in rats fed the 6% protein diet compared with those fed the 20% protein diet. Responses to all other stimuli were similar between groups. Terminal field volumes were nearly twofold larger in protein-restricted rats compared with controls, with the differences located primarily in the dorsal-caudal zone of the terminal field. These results are similar to the results seen previously in rats fed a sodium-restricted diet throughout pre- and postnatal development, suggesting that dietary sodium- and protein-restriction share similar mechanisms in altering gustatory development.

  10. Lactating Rats Retain Nursing Behavior and Maternal Care in Space

    NASA Technical Reports Server (NTRS)

    Daly, Megan E.; Ronca, April E.; Dalton, Bonnie (Technical Monitor)

    2001-01-01

    In 1997, suckling mammals were flown in space for the first time as part of the NIH.R3 experiment sponsored jointly by NIH (National Institutes of Health) and NASA. Six rat dams and litters (Rattus norvegicus) were launched on an eight-day Space Shuttle mission at each of three postnatal ages (P5, P8, and P15). Dams and litters (N = 10 pups/litter) were housed within modified Animal Enclosure Modules (AEMs). Comparisons were made to ground controls. Dams and litters were videotaped daily in flight. The P8 and P15 flight litters showed excellent survival (99%) and weight gain relative to AEM ground controls, whereas P5 litters showed reduced survival (0% and 60%, respectively) and weight gain (less than 40% AEM). To examine the possibility that failures of maternal care contributed to P5 results, we analyzed the dams' in-flight nursing, licking and retrieving from four video segments ranging from twelve to fifteen minutes in length with control data derived from multiple ground segments. Video analyses revealed clear evidence of maternal care in flight. For P5 dams, frequency and duration of nursing and licking bouts fell within or above one standard deviation of control values. Retrieving was noted in the P5 and P8 groups only. The observed results suggest that factors other than maternal care contributed to the low survival rates and body weight gains of the P5 flight offspring.

  11. Maternal hyperthyroidism in rats impairs stress coping of adult offspring.

    PubMed

    Zhang, Limei; Hernández, Vito S; Medina-Pizarro, Mauricio; Valle-Leija, Pablo; Vega-González, Arturo; Morales, Teresa

    2008-05-01

    Given the evidence that maternal hyperthyroidism (MH) compromises expression of neuronal cytoskeletal proteins in the late fetal brain by accelerated neuronal differentiation, we investigated possible consequences of MH for the emotional and cognitive functions of adult offspring during acute and subchronic stress coping. Experimental groups consisted of male rat offspring from mothers implanted with osmotic minipumps infusing either thyroxine (MH) or vehicle (Ctrl) during pregnancy. Body weight and T4 level were monitored during the first 3 postnatal months, and no differences were found with the controls. We analyzed hippocampal CA3 pyramidal neurons and dentate granular cell morphology during several postnatal stages and found increased dendritic arborization. On postnatal day 90 a modified subchronic mild stress (SCMS) protocol was applied to experimental subjects for 10 days. The Morris water maze was used before, during, and after application of the SCMS protocol to measure spatial learning. The tail suspension test (TST) and forced-swimming test (FST) were used to evaluate behavioral despair. The MH rats displayed normal locomotor activity and spatial memory prior to SCMS, but impaired spatial learning after acute and chronic stress. In both the FST and TST we found that MH rats spent significantly more time immobile than did controls. Serum corticosterone level was found to increase after 30 min of restraint stress, and corticotropin-releasing factor immunoreactivity was found to be increased in the central nucleus of the amygdala. Our results suggest that MH in rats leads to the offspring being more vulnerable to stress in adulthood.

  12. Maternal zinc supplementation improves spatial memory in rat pups.

    PubMed

    Piechal, Agnieszka; Blecharz-Klin, Kamilla; Pyrzanowska, Justyna; Widy-Tyszkiewicz, Ewa

    2012-06-01

    A large body of evidence supports an opinion that adequate dietary zinc is essential for prenatal and postnatal brain development. Behavioural effects of maternal supplementation with ZnSO(4) were analysed in rat pups with the Morris water task performance, a hole board and a T-maze. Wistar females during pregnancy and lactation received a drinking water solution of ZnSO(4) at doses of 16 mg/kg (group Zn16) or 32 mg/kg (group Zn32). Behavioural tests were conducted on the 4-week-old male rat pups. Zinc concentration in the serum, hippocampus and prefrontal cortex of offsprings was determined by means of atomic absorption techniques. The Newman-Keuls multiple comparison test revealed an increase of climbing in the Zn16 group in comparison to the control group (Con) and the Zn32 group during the hole board test. ANOVA for repeated measures showed a significant memory improvement in both supplemented groups compared to the control in the probe trial on day 5 of the water maze test. ZnSO(4) treatment significantly elevated zinc levels in the rat serum. Follow-up data on brain content of zinc in the hippocampus revealed significant differences between the groups and in supplemented groups correlated with crossings above the original platform position. These findings suggest that pre- and postnatal zinc supplementation may improve cognitive development in rats.

  13. Protein Content and Methyl Donors in Maternal Diet Interact to Influence the Proliferation Rate and Cell Fate of Neural Stem Cells in Rat Hippocampus

    PubMed Central

    Amarger, Valérie; Lecouillard, Angèle; Ancellet, Laure; Grit, Isabelle; Castellano, Blandine; Hulin, Philippe; Parnet, Patricia

    2014-01-01

    Maternal diet during pregnancy and early postnatal life influences the setting up of normal physiological functions in the offspring. Epigenetic mechanisms regulate cell differentiation during embryonic development and may mediate gene/environment interactions. We showed here that high methyl donors associated with normal protein content in maternal diet increased the in vitro proliferation rate of neural stem/progenitor cells isolated from rat E19 fetuses. Gene expression on whole hippocampi at weaning confirmed this effect as evidenced by the higher expression of the Nestin and Igf2 genes, suggesting a higher amount of undifferentiated precursor cells. Additionally, protein restriction reduced the expression of the insulin receptor gene, which is essential to the action of IGFII. Inhibition of DNA methylation in neural stem/progenitor cells in vitro increased the expression of the astrocyte-specific Gfap gene and decreased the expression of the neuron-specific Dcx gene, suggesting an impact on cell differentiation. Our data suggest a complex interaction between methyl donors and protein content in maternal diet that influence the expression of major growth factors and their receptors and therefore impact the proliferation and differentiation capacities of neural stem cells, either through external hormone signals or internal genomic regulation. PMID:25317634

  14. Effect of dietary protein restriction on renal ammonia metabolism.

    PubMed

    Lee, Hyun-Wook; Osis, Gunars; Handlogten, Mary E; Guo, Hui; Verlander, Jill W; Weiner, I David

    2015-06-15

    Dietary protein restriction has multiple benefits in kidney disease. Because protein intake is a major determinant of endogenous acid production, it is important that net acid excretion change in parallel during protein restriction. Ammonia is the primary component of net acid excretion, and inappropriate ammonia excretion can lead to negative nitrogen balance. Accordingly, we examined ammonia excretion in response to protein restriction and then we determined the molecular mechanism of the changes observed. Wild-type C57Bl/6 mice fed a 20% protein diet and then changed to 6% protein developed an 85% reduction in ammonia excretion within 2 days, which persisted during a 10-day study. The expression of multiple proteins involved in renal ammonia metabolism was altered, including the ammonia-generating enzymes phosphate-dependent glutaminase (PDG) and phosphoenolpyruvate carboxykinase (PEPCK) and the ammonia-metabolizing enzyme glutamine synthetase. Rhbg, an ammonia transporter, increased in expression in the inner stripe of outer medullary collecting duct intercalated cell (OMCDis-IC). However, collecting duct-specific Rhbg deletion did not alter the response to protein restriction. Rhcg deletion did not alter ammonia excretion in response to dietary protein restriction. These results indicate 1) dietary protein restriction decreases renal ammonia excretion through coordinated regulation of multiple components of ammonia metabolism; 2) increased Rhbg expression in the OMCDis-IC may indicate a biological role in addition to ammonia transport; and 3) Rhcg expression is not necessary to decrease ammonia excretion during dietary protein restriction. PMID:25925252

  15. Effect of dietary protein restriction on renal ammonia metabolism.

    PubMed

    Lee, Hyun-Wook; Osis, Gunars; Handlogten, Mary E; Guo, Hui; Verlander, Jill W; Weiner, I David

    2015-06-15

    Dietary protein restriction has multiple benefits in kidney disease. Because protein intake is a major determinant of endogenous acid production, it is important that net acid excretion change in parallel during protein restriction. Ammonia is the primary component of net acid excretion, and inappropriate ammonia excretion can lead to negative nitrogen balance. Accordingly, we examined ammonia excretion in response to protein restriction and then we determined the molecular mechanism of the changes observed. Wild-type C57Bl/6 mice fed a 20% protein diet and then changed to 6% protein developed an 85% reduction in ammonia excretion within 2 days, which persisted during a 10-day study. The expression of multiple proteins involved in renal ammonia metabolism was altered, including the ammonia-generating enzymes phosphate-dependent glutaminase (PDG) and phosphoenolpyruvate carboxykinase (PEPCK) and the ammonia-metabolizing enzyme glutamine synthetase. Rhbg, an ammonia transporter, increased in expression in the inner stripe of outer medullary collecting duct intercalated cell (OMCDis-IC). However, collecting duct-specific Rhbg deletion did not alter the response to protein restriction. Rhcg deletion did not alter ammonia excretion in response to dietary protein restriction. These results indicate 1) dietary protein restriction decreases renal ammonia excretion through coordinated regulation of multiple components of ammonia metabolism; 2) increased Rhbg expression in the OMCDis-IC may indicate a biological role in addition to ammonia transport; and 3) Rhcg expression is not necessary to decrease ammonia excretion during dietary protein restriction.

  16. Effect of maternal diabetes on gliogensis in neonatal rat hippocampus

    PubMed Central

    Sadeghi, Akram; Esfandiary, Ebrahim; Hami, Javad; Khanahmad, Hossein; Hejazi, Zahra; Razavi, Shahnaz

    2016-01-01

    Background: Diabetes in pregnancy is a common metabolic disorder associated with various adverse outcomes in the offspring including impairments in attention and memory and alterations in social behavior. Glial cells are proven to have a critical role in normal function of neurons, and alteration in their activity could contribute to disturbance in the brain function. The aim of this study was to investigate the effect of maternal diabetes on hippocampal mRNA expression and distribution pattern of glial fibrillary acidic protein (GFAP) immunoreactive glial cells in the dentate gyrus (DG) of rat neonate at postnatal day 14 (P14). Materials and Methods: Wistar female rats were randomly allocated in control, diabetic, and insulin-treated diabetic groups. Diabetes was induced by injection of streptozotocin from 4 weeks before gestation until parturition. After delivery, the male offspring was euthanized at P14. Results: Our results showed a significant higher level of hippocampal GFAP expression and an increase in the mean number of GFAP positive cells in the DG of diabetic group offspring (P < 0.05). We also found an insignificant up-regulation in the expression of GFAP and the mean number of positive cells in the insulin-treated diabetic group neonates as compared to control group (P > 0.05). Conclusion: The present study revealed that diabetes during pregnancy strongly increased the glial cells production in the developing rat hippocampus. PMID:27656611

  17. Effect of maternal diabetes on gliogensis in neonatal rat hippocampus

    PubMed Central

    Sadeghi, Akram; Esfandiary, Ebrahim; Hami, Javad; Khanahmad, Hossein; Hejazi, Zahra; Razavi, Shahnaz

    2016-01-01

    Background: Diabetes in pregnancy is a common metabolic disorder associated with various adverse outcomes in the offspring including impairments in attention and memory and alterations in social behavior. Glial cells are proven to have a critical role in normal function of neurons, and alteration in their activity could contribute to disturbance in the brain function. The aim of this study was to investigate the effect of maternal diabetes on hippocampal mRNA expression and distribution pattern of glial fibrillary acidic protein (GFAP) immunoreactive glial cells in the dentate gyrus (DG) of rat neonate at postnatal day 14 (P14). Materials and Methods: Wistar female rats were randomly allocated in control, diabetic, and insulin-treated diabetic groups. Diabetes was induced by injection of streptozotocin from 4 weeks before gestation until parturition. After delivery, the male offspring was euthanized at P14. Results: Our results showed a significant higher level of hippocampal GFAP expression and an increase in the mean number of GFAP positive cells in the DG of diabetic group offspring (P < 0.05). We also found an insignificant up-regulation in the expression of GFAP and the mean number of positive cells in the insulin-treated diabetic group neonates as compared to control group (P > 0.05). Conclusion: The present study revealed that diabetes during pregnancy strongly increased the glial cells production in the developing rat hippocampus.

  18. Maternal-infant separation impedes changes in feeding behavior during estrous cycle of rats

    PubMed Central

    Iwasaki, Shinichi; Inoue, Koki

    2015-01-01

    Traumatic and stressful events during childhood are associated with the development of eating disorders. We conducted an animal study to test if association stress in childhood affects ingestive behavior later in life by using female rats that have an adjusted estrous cycle. First, electrical impedance of the vagina was conducted to test estrous cycle adjustment. Second, the effects of 6 h per day maternal separation from birth to weaning, which models a psychologically stressful experience in childhood, was used to test feeding behavior during an ovarian cycle in female adult rats with matched estrous cycles. Food and water intake in maternal separated and non-separated rats was measured in each estrous phase. Non-separated rats showed periodical changes, but maternal separated rats showed no significant changes in food and water intake during an estrous cycle. An opposing tendency for food and water intake was seen between maternal separated and non-separated rats. These observations suggest that electrical impedance of the vagina showed the highest value in the estrous phase of rats housed in a reversed light-dark cycle, and maternal separation was found to disturb changes in feeding behavior during the estrous cycle. PMID:26119792

  19. Effects of early maternal separation on subsequent reproductive and behavioral outcomes in male rats.

    PubMed

    Bodensteiner, Karin J; Christianson, Nina; Siltumens, Aldis; Krzykowski, Julie

    2014-01-01

    To investigate effects of maternal separation on reproductive and behavioral outcomes, male Wistar rats were separated from their mothers daily for 3 hr (maternal separation; MS) or 0 hr (control) from postnatal day (PND) 1 to 14. Timing of puberty, reproductive parameters, hormone levels, and aggressive behaviors in juvenile and adult rats were examined. Contrary to expectations, there was no effect of maternal separation on any measure of aggression. However, maternal separation altered peripubertal testosterone secretion and increased mean day of preputial separation. In addition, adult MS males demonstrated less total sexual behavior. There was no difference in sperm counts or testosterone levels at necropsy on PND 56 or in adulthood, but seminal vesicle weights were increased in adult MS rats. These results suggest that early life stress may influence hypothalamic-pituitary-gonadal axis development in males, at least during peripuberty.

  20. Pre-reproductive maternal enrichment influences rat maternal care and offspring developmental trajectories: behavioral performances and neuroplasticity correlates.

    PubMed

    Cutuli, Debora; Caporali, Paola; Gelfo, Francesca; Angelucci, Francesco; Laricchiuta, Daniela; Foti, Francesca; De Bartolo, Paola; Bisicchia, Elisa; Molinari, Marco; Farioli Vecchioli, Stefano; Petrosini, Laura

    2015-01-01

    Environmental enrichment (EE) is a widely used paradigm for investigating the influence of complex stimulations on brain and behavior. Here we examined whether pre-reproductive exposure to EE of female rats may influence their maternal care and offspring cognitive performances. To this aim, from weaning to breeding age enriched females (EF) were reared in enriched environments. Females reared in standard conditions were used as controls. At 2.5 months of age all females were mated and reared in standard conditions with their offspring. Maternal care behaviors and nesting activity were assessed in lactating dams. Their male pups were also behaviorally evaluated at different post-natal days (pnd). Brain BDNF, reelin and adult hippocampal neurogenesis levels were measured as biochemical correlates of neuroplasticity. EF showed more complex maternal care than controls due to their higher levels of licking, crouching and nest building activities. Moreover, their offspring showed higher discriminative (maternal odor preference T-maze, pnd 10) and spatial (Morris Water Maze, pnd 45; Open Field with objects, pnd 55) performances, with no differences in social abilities (Sociability test, pnd 35), in comparison to controls. BDNF levels were increased in EF frontal cortex at pups' weaning and in their offspring hippocampus at pnd 21 and 55. No differences in offspring reelin and adult hippocampal neurogenesis levels were found. In conclusion, our study indicates that pre-reproductive maternal enrichment positively influences female rats' maternal care and cognitive development of their offspring, demonstrating thus a transgenerational transmission of EE benefits linked to enhanced BDNF-induced neuroplasticity. PMID:25814946

  1. Pre-reproductive maternal enrichment influences rat maternal care and offspring developmental trajectories: behavioral performances and neuroplasticity correlates

    PubMed Central

    Cutuli, Debora; Caporali, Paola; Gelfo, Francesca; Angelucci, Francesco; Laricchiuta, Daniela; Foti, Francesca; De Bartolo, Paola; Bisicchia, Elisa; Molinari, Marco; Farioli Vecchioli, Stefano; Petrosini, Laura

    2015-01-01

    Environmental enrichment (EE) is a widely used paradigm for investigating the influence of complex stimulations on brain and behavior. Here we examined whether pre-reproductive exposure to EE of female rats may influence their maternal care and offspring cognitive performances. To this aim, from weaning to breeding age enriched females (EF) were reared in enriched environments. Females reared in standard conditions were used as controls. At 2.5 months of age all females were mated and reared in standard conditions with their offspring. Maternal care behaviors and nesting activity were assessed in lactating dams. Their male pups were also behaviorally evaluated at different post-natal days (pnd). Brain BDNF, reelin and adult hippocampal neurogenesis levels were measured as biochemical correlates of neuroplasticity. EF showed more complex maternal care than controls due to their higher levels of licking, crouching and nest building activities. Moreover, their offspring showed higher discriminative (maternal odor preference T-maze, pnd 10) and spatial (Morris Water Maze, pnd 45; Open Field with objects, pnd 55) performances, with no differences in social abilities (Sociability test, pnd 35), in comparison to controls. BDNF levels were increased in EF frontal cortex at pups' weaning and in their offspring hippocampus at pnd 21 and 55. No differences in offspring reelin and adult hippocampal neurogenesis levels were found. In conclusion, our study indicates that pre-reproductive maternal enrichment positively influences female rats' maternal care and cognitive development of their offspring, demonstrating thus a transgenerational transmission of EE benefits linked to enhanced BDNF-induced neuroplasticity. PMID:25814946

  2. Pre-reproductive maternal enrichment influences rat maternal care and offspring developmental trajectories: behavioral performances and neuroplasticity correlates.

    PubMed

    Cutuli, Debora; Caporali, Paola; Gelfo, Francesca; Angelucci, Francesco; Laricchiuta, Daniela; Foti, Francesca; De Bartolo, Paola; Bisicchia, Elisa; Molinari, Marco; Farioli Vecchioli, Stefano; Petrosini, Laura

    2015-01-01

    Environmental enrichment (EE) is a widely used paradigm for investigating the influence of complex stimulations on brain and behavior. Here we examined whether pre-reproductive exposure to EE of female rats may influence their maternal care and offspring cognitive performances. To this aim, from weaning to breeding age enriched females (EF) were reared in enriched environments. Females reared in standard conditions were used as controls. At 2.5 months of age all females were mated and reared in standard conditions with their offspring. Maternal care behaviors and nesting activity were assessed in lactating dams. Their male pups were also behaviorally evaluated at different post-natal days (pnd). Brain BDNF, reelin and adult hippocampal neurogenesis levels were measured as biochemical correlates of neuroplasticity. EF showed more complex maternal care than controls due to their higher levels of licking, crouching and nest building activities. Moreover, their offspring showed higher discriminative (maternal odor preference T-maze, pnd 10) and spatial (Morris Water Maze, pnd 45; Open Field with objects, pnd 55) performances, with no differences in social abilities (Sociability test, pnd 35), in comparison to controls. BDNF levels were increased in EF frontal cortex at pups' weaning and in their offspring hippocampus at pnd 21 and 55. No differences in offspring reelin and adult hippocampal neurogenesis levels were found. In conclusion, our study indicates that pre-reproductive maternal enrichment positively influences female rats' maternal care and cognitive development of their offspring, demonstrating thus a transgenerational transmission of EE benefits linked to enhanced BDNF-induced neuroplasticity.

  3. The effects of dopaminergic/serotonergic reuptake inhibition on maternal behavior, maternal aggression, and oxytocin in the rat.

    PubMed

    Johns, J M; Joyner, P W; McMurray, M S; Elliott, D L; Hofler, V E; Middleton, C L; Knupp, K; Greenhill, K W; Lomas, L M; Walker, C H

    2005-08-01

    Studies using dopaminergic and serotonergic agonists or antagonists implicate involvement of these systems in various aspects of early maternal behavior and postpartum aggression towards an intruder in rats, both of which are associated with the presence of oxytocin in specific brain regions. It is unclear however, if or how long-term uptake inhibition of either neurotransmitter system alone or in combination, affects oxytocin system dynamics or maternal behavior/aggression. Pregnant women frequently take drugs (antidepressants, cocaine) that induce long-term reuptake inhibition of dopamine and/or serotonin, thus it is important to understand these effects on behavior and biochemistry. Rat dams were treated throughout gestation with amfonelic acid, fluoxetine, or a combination of both, to investigate effects of reuptake inhibition of dopamine and serotonin systems respectively, on maternal behavior, aggression and oxytocin. The more appetitive aspects of maternal behavior (nesting, licking, touching) and activity were increased by the low dose of amfonelic acid, high dose of fluoxetine, or the high dose combination more than other treatments. Aggression was decreased by amfonelic acid and somewhat increased by fluoxetine. Dopamine uptake inhibition appears to have a strong effect on hippocampal oxytocin levels, while receptor dynamics may be more strongly affected by serotonin uptake inhibition. PMID:15996723

  4. Maternal Programming of Reproductive Function and Behavior in the Female Rat

    PubMed Central

    Cameron, Nicole M.

    2011-01-01

    Parental investment can be used as a forecast for the environmental conditions in which offspring will develop to adulthood. In the rat, maternal behavior is transmitted to the next generation through epigenetic modifications such as methylation and histone acetylation, resulting in variations in estrogen receptor alpha expression. Natural variations in maternal care also influence the sexual strategy adult females will adopt later in life. Lower levels of maternal care are associated with early onset of puberty as well as increased motivation to mate and greater receptivity toward males during mating. Lower levels of maternal care are also correlated with greater activity of the hypothalamus–pituitary–gonadal axis, responsible for the expression of these behaviors. Contrary to the transition of maternal care, sexual behavior cannot simply be explained by maternal attention, since adoption studies changed the sexual phenotypes of offspring born to low caring mothers but not those from high caring dams. Indeed, mothers showing higher levels of licking/grooming have embryos that are exposed to high testosterone levels during development, and adoption studies suggest that this androgen exposure may protect their offspring from lower levels of maternal care. We propose that in the rat, maternal care and the in utero environment interact to influence the reproductive strategy female offspring display in adulthood and that this favors the species by allowing it to thrive under different environmental conditions. PMID:22203802

  5. Behavioural deficits associated with maternal immune activation in the rat model of schizophrenia.

    PubMed

    Wolff, Amy R; Cheyne, Kirsten R; Bilkey, David K

    2011-11-20

    Schizophrenia is associated with changes in memory and contextual processing. As maternal infection is a risk factor in schizophrenia we tested for these impairments in a maternal immune activation (MIA) animal model. MIA rats displayed impaired object recognition memory, despite intact object discrimination, and a reduced reinstatement of rearing in response to a contextual manipulation. These results link MIA to contextual impairments in schizophrenia, possibly through changes in hippocampal function.

  6. Effects of maternally exposed food coloring additives on laryngeal histology in rats.

    PubMed

    Başak, Kayhan; Doguç, Duygu Kumbul; Aylak, Firdevs; Karadayi, Nimet; Gültekin, Fatih

    2014-01-01

    Experimental reports showed carcinogenic effects of artificial food colors and additives (AFCAs) on many organs, including the head and neck region. We aimed to investigate the effect of AFCAs on laryngeal histomorphology and immunohistochemical expression in maternally exposed rats. "No observable adverse effect levels" of commonly used AFCAs as a mixture were given to female rats before and during gestation. Histopathological and immunohistochemical findings were evaluated in their offspring. Significant decreasing in goblet cell count and cilia loss were observed with AFCAs in maternally exposed rats (p<0.05). Immunohistochemically, the Ki67 index was significantly increased and villin expression was significantly reduced in laryngeal epithelium in the study group (p<0.05), whereas expression of cyclooxygenase type 2, Muc-2, Muc-5AC, p53, and epidermal growth factor receptors did not differ between the groups. This study demonstrated that maternal exposure of AFCAs plays a role in the mucosal defense system and possibly in carcinogenesis. PMID:24941295

  7. Semax attenuates the influence of neonatal maternal deprivation on the behavior of adolescent white rats.

    PubMed

    Volodina, M A; Sebentsova, E A; Glazova, N Y; Levitskaya, N G; Andreeva, L A; Manchenko, D M; Kamensky, A A; Myasoedov, N F

    2012-03-01

    Maternal deprivation in the early postnatal period significantly affects the behavior and development of different animals. Here we studied delayed effects of daily maternal deprivation (5 h/day) on physical development and behavior of white rats during postnatal days 1 to 14. Here we studied the possibility of reducing the negative consequences of deprivation by daily intranasal treatment with Semax, an analog of ACTH(4-10), in a dose of 0.05 mg/kg from postnatal days 15 to 28. It was found that maternal deprivation decelerated the growth of young rats, boosted physical activity and emotional reactivity in novel environment, and increased anxiety in one-month-old animals. Semax weakened the impact of deprivation on animal body weight and normalized the levels of anxiety in rats.

  8. Hypothyroxinemia induced by maternal mild iodine deficiency impairs hippocampal myelinated growth in lactational rats.

    PubMed

    Wei, Wei; Wang, Yi; Dong, Jing; Wang, Yuan; Min, Hui; Song, Binbin; Shan, Zhongyan; Teng, Weiping; Xi, Qi; Chen, Jie

    2015-11-01

    Hypothyroxinemia induced by maternal mild iodine deficiency causes neurological deficits and impairments of brain function in offspring. Hypothyroxinemia is prevalent in developing and developed countries alike. However, the mechanism underlying these deficits remains less well known. Given that the myelin plays an important role in learning and memory function, we hypothesize that hippocampal myelinated growth may be impaired in rat offspring exposed to hypothyroxinemia induced by maternal mild iodine deficiency. To test this hypothesis, the female Wistar rats were used and four experimental groups were prepared: (1) control; (2) maternal mild iodine deficiency diet inducing hypothyroxinemia; (3) hypothyroidism induced by maternal severe iodine deficiency diet; (4) hypothyroidism induced by maternal methimazole water. The rats were fed the diet from 3 months before pregnancy to the end of lactation. Our results showed that the physiological changes occuring in the hippocampal myelin were altered in the mild iodine deficiency group as indicated by the results of immunofluorescence of myelin basic proteins on postnatal day 14 and postnatal day 21. Moreover, hypothyroxinemia reduced the expressions of oligodendrocyte lineage transcription factor 2 and myelin-related proteins in the treatments on postnatal day 14 and postnatal day 21. Our data suggested that hypothyroxinemia induced by maternal mild iodine deficiency may impair myelinated growth of the offspring.

  9. Diet-induced changes in maternal gut microbiota and metabolomic profiles influence programming of offspring obesity risk in rats.

    PubMed

    Paul, Heather A; Bomhof, Marc R; Vogel, Hans J; Reimer, Raylene A

    2016-01-01

    Maternal obesity and overnutrition during pregnancy and lactation can program an increased risk of obesity in offspring. In this context, improving maternal metabolism may help reduce the intergenerational transmission of obesity. Here we show that, in Sprague-Dawley rats, selectively altering obese maternal gut microbial composition with prebiotic treatment reduces maternal energy intake, decreases gestational weight gain, and prevents increased adiposity in dams and their offspring. Maternal serum metabolomics analysis, along with satiety hormone and gut microbiota analysis, identified maternal metabolic signatures that could be implicated in programming offspring obesity risk and highlighted the potential influence of maternal gut microbiota on maternal and offspring metabolism. In particular, the metabolomic signature of insulin resistance in obese rats normalized when dams consumed the prebiotic. In summary, prebiotic intake during pregnancy and lactation improves maternal metabolism in diet-induced obese rats in a manner that attenuates the detrimental nutritional programming of offspring associated with maternal obesity. Overall, these findings contribute to our understanding of the maternal mechanisms influencing the developmental programming of offspring obesity and provide compelling pre-clinical evidence for a potential strategy to improve maternal and offspring metabolic outcomes in human pregnancy.

  10. Diet-induced changes in maternal gut microbiota and metabolomic profiles influence programming of offspring obesity risk in rats

    PubMed Central

    Paul, Heather A.; Bomhof, Marc R.; Vogel, Hans J.; Reimer, Raylene A.

    2016-01-01

    Maternal obesity and overnutrition during pregnancy and lactation can program an increased risk of obesity in offspring. In this context, improving maternal metabolism may help reduce the intergenerational transmission of obesity. Here we show that, in Sprague-Dawley rats, selectively altering obese maternal gut microbial composition with prebiotic treatment reduces maternal energy intake, decreases gestational weight gain, and prevents increased adiposity in dams and their offspring. Maternal serum metabolomics analysis, along with satiety hormone and gut microbiota analysis, identified maternal metabolic signatures that could be implicated in programming offspring obesity risk and highlighted the potential influence of maternal gut microbiota on maternal and offspring metabolism. In particular, the metabolomic signature of insulin resistance in obese rats normalized when dams consumed the prebiotic. In summary, prebiotic intake during pregnancy and lactation improves maternal metabolism in diet-induced obese rats in a manner that attenuates the detrimental nutritional programming of offspring associated with maternal obesity. Overall, these findings contribute to our understanding of the maternal mechanisms influencing the developmental programming of offspring obesity and provide compelling pre-clinical evidence for a potential strategy to improve maternal and offspring metabolic outcomes in human pregnancy. PMID:26868870

  11. Developmental Triclosan Exposure Decreases Maternal and Offspring Thyroxine in Rats*

    EPA Science Inventory

    Epidemiological and laboratory data have demonstrated that disruption of maternal thyroid hormones during fetal developmental may result in irreversible neurological consequences in offspring. In a short-term exposure paradigm, triclosan decreased systemic thyroxine (T4) concentr...

  12. Intrauterine Growth Restricted Rats Exercised before and during Pregnancy: Maternal and Perinatal Repercussions

    PubMed Central

    Corvino, S. B.; Volpato, G. T.; Rudge, M. V. C.; Damasceno, D. C.

    2015-01-01

    This study aimed at evaluating the effect of swimming before and during pregnancy on rats born with intrauterine growth restriction (IUGR) and their offspring. For this, nondiabetic and streptozotocin-induced severely diabetic (SD) pregnant rats were mated and generated offspring with appropriate (control, C) and small (IUGR) for pregnancy age, respectively. Following that, C and IUGR groups were further distributed into nonexercised control (C), exercised control (Cex), nonexercised IUGR (IUGR), and exercised IUGR (IUGRex). IUGR rats presented lower mating rate than control rats. Regardless of physical exercise IUGR rats presented decreased body weight from birth to lactation. At 90 days of life, IUGR rats presented glucose intolerance. Maternal organ weights were increased and relative adiposity of IUGRex rats was lower than Cex. IUGR and IUGRex offspring presented reduced body weight than C and Cex, respectively. IUGRex dams presented an increased rate of appropriate for pregnancy age newborns. IUGEex male and female offspring relative brain weight was increased compared with Cex. Therefore, swimming before and during pregnancy prevented glucose intolerance, reduced general adiposity, and increased maternal and offspring organ weight in rats, showing the benefit of physical exercise for IUGR rats. PMID:26345406

  13. Effects of maternal separation on the dietary preference and behavioral satiety sequence in rats.

    PubMed

    da Silva, M C; de Souza, J A; Dos Santos, L O; Pinheiro, I L; Borba, T K F; da Silva, A A M; de Castro, R M; de Souza, S L

    2014-06-01

    This study investigated the effects of maternal separation on the feeding behavior of rats. A maternal separation model was used on postnatal day 1 (PND1), forming the following groups: in the maternal separation (MS) group, pups were separated from their mothers each day from PND1 to PND14, whereas in the control (C) group pups were kept with their mothers. Subgroups were formed to study the effects of light and darkness: control with dark and light exposure, female and male (CF and CM), and maternal separation with dark and light exposure, female and male (SDF, SDM, SLF and SLM). Female rats had higher caloric intake relative to body weight compared with male controls in the dark period only (CF=23.3±0.5 v. CM=18.2±0.7, P<0.001). Macronutrient feeding preferences were observed, with male rats exhibiting higher caloric intake from a protein diet as compared with female rats (CF=4.1±0.7, n=8 v. CM=7.0±0.5, n=8, P<0.05) and satiety development was not interrupted. Female rats had a higher adrenal weight as compared with male rats independently of experimental groups and exhibited a higher concentration of serum triglycerides (n=8, P<0.001). The study indicates possible phenotypic adjustments in the structure of feeding behavior promoted by maternal separation, especially in the dark cycle. The dissociation between the mother's presence and milk intake probably induces adjustments in feeding behavior during adulthood. PMID:24901662

  14. Maternal Copper Deficiency Perpetuates Altered Vascular Function in Sprague-Dawley Rat Offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Little is known about the consequences of maternal Cu (Cu) deficiency on the vascular function of offspring or on perpetuation of vascular effects to a second generation. We examined vascular functional responses in mesenteric arteries from Cu-deficient Sprague-Dawley rat dams and from offspring dir...

  15. EFFECTS OF PERFLUOROOCTANE SULFONATE (PFOS) ON MATERNAL AND DEVELOPMENTAL THYROID STATUS IN THE RAT

    EPA Science Inventory

    EFFECTS OF PERFLUOROOCTANE SULFONATE (PFOS) ON MATERNAL AND DEVELOPMENTAL THYROID STATUS IN THE RAT. JR Thibodeaux1, R Hanson1, B Grey1, JM Rogers1, ME Stanton2, and C Lau1. 1Reproductive Toxicology Division; 2Neurotoxicology Division, NHEERL, ORD, US EPA, Research Triangle P...

  16. Maternal obesity and post-natal high fat diet disrupt hepatic circadian rhythm in rat offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Offspring of obese (Ob) rat dams gain greater body wt and fat mass when fed high-fat diet (HFD) as compared to controls. Alterations of diurnal circadian rhythm are known to detrimentally impact metabolically active tissues such as liver. We sought to determine if maternal obesity (MOb) leads to p...

  17. MATERNAL AND DEVELOPMENTAL TOXICITY OF PERFLUOROOCATANE SULFONATE (PFOS) IN THE RAT

    EPA Science Inventory

    MATERNAL AND DEVELOPMENTAL TOXICITY OF PERFLUOROOCTANE SULFONATE (PFOS) IN THE RAT. C. Lau1, J.M. Rogers1, J.R. Thibodeaux1, R.G. Hanson1, B.E. Grey1, B.D. Barbee1, J.H. Richards2, J.L. Butenoff3. 1Reprod. Tox. Div., 2Exp. Tox. Div., NHEERL, USEPA, Research Triangle Park, NC, 3...

  18. LATE GESTATIONAL ATRAZINE EXPOSURE DECREASES MATERNAL BEHAVIOR IN LONG-EVANS RATS

    EPA Science Inventory

    Late Gestational Atrazine Exposure Alters Maternal Nursing Behavior in Rats

    Jennifer L. Rayner1 and Suzanne E. Fenton2

    1 University of North Carolina at Chapel Hill, DESE, Chapel Hill, NC, and 2 USEPA/ ORD/NHEERL/Reproductive Toxicology Division, RTP, NC.

    At...

  19. Exposure to perfluorooctane sulfonate during pregnancy in rat and mouse. I: maternal and prenatal evaluations

    EPA Science Inventory

    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...

  20. Immediate and Enduring Effects of Neonatal Isolation on Maternal Behavior in Rats

    PubMed Central

    Kosten, Therese A.; Kehoe, Priscilla

    2009-01-01

    Previously, we showed that neonatal isolation (1-hr isolation/day from dam, litter, and nest on PND 2-9) facilitates cocaine self-administration and increases extracellular dopamine responses in ventral striatum after stimulant administration in adulthood. Recent studies suggest that enduring alterations in neurobehavioral responses associated with early life manipulations reflect changes in maternal behavior. Thus, we sought to determine if neonatal isolation alters maternal care and if dams with neonatal isolation experience as pups showed differential maternal care towards their pups. In Experiment 1, litters were assigned to one of three conditions: neonatal isolation, handled (5-min separation of dam from litter), or non-handled (no separation). Maternal behaviors were rated on PND 2-9 for 60-min immediately following reunion of mother and litter. In Experiment 2, female rats with or without neonatal isolation experience were assigned to either the neonatal isolation or non-handled litter condition and maternal behaviors rated. Dams of isolated and handled litters spent more time licking pups and less time picking up pups to put outside the nest than dams of non-handled litters. Further, dams of isolated and handled vs non-handled litters showed less non-maternal behaviors of burrowing and grooming. Neonatal isolation-experienced dams with isolated litters failed to increase pup-licking and decrease non-maternal behaviors. Rather, these dams picked up pups to place outside the nest more than non-handled-experienced dams. Neonatal isolation alters maternal behavior that, in turn, may shape neurobehavioral responses of offspring including effects on maternal care. Such changes may reflect epigenetic effects resulting from changes in maternal behavior. PMID:19782745

  1. Effect of ethanol consumption during gestation on maternal-fetal amino acid metabolism in the rat

    SciTech Connect

    Lin, G.W.

    1981-01-01

    The distribution of /sup 14/C-alpha-aminoisobutyric acid (AIB), administered intravenously, in maternal, fetal and placental tissues was examined in the rat on gestation-day 21. Ethanol consumption during gestation (day 6 through 21) significantly reduced the uptake of AIB by the placenta and fetus while exerting no influence on maternal tissue AIB uptake. The concentration of fetal plasma free histidine was decreased 50% as a result of maternal ethanol ingestion, but the free histidine level of maternal plasma was not altered. Since no effect on protein content of fetal tissue could be detected, it is speculated that reduced histidine to the fetus might significantly alter the amounts of histamine and carnosine formed via their precursor. The significance of these findings in relation to the Fetal Alcohol Syndrome is discussed.

  2. Voluntary exercise reduces the neurotoxic effects of 6-hydroxydopamine in maternally separated rats

    PubMed Central

    Mabandla, Musa Vuyisile; Russell, Vivienne Ann

    2010-01-01

    Maternal separation has been associated with development of anxiety-like behaviour and learning impairments in adult rats. This has been linked to changes in brain morphology observed after exposure to high levels of circulating glucocorticoids during the stress-hyporesponsive period (P4 to P14). In the present study, adult rats that had been subjected to maternal separation (180 min/day for 14 days) during the stress-hyporesponsive period, received unilateral infusions of a small dose of 6-hydroxydopamine (6-OHDA, 5 μg/4 μl saline) into the medial forebrain bundle. The results showed that voluntary exercise had a neuroprotective effect in both non-stressed and maternally separated rats in that there was a decrease in forelimb akinesia (step test) and limb use asymmetry (cylinder test). Maternal separation increased forelimb akinesia and forelimb use asymmetry and reduced the beneficial effect of exercise on forelimb akinesia. It also reduced exploratory behaviour, consistent with anxiety-like behaviour normally associated with maternal separation. Exercise appeared to reduce dopamine neuron destruction in the lesioned substantia nigra when expressed as a percentage of the non-lesioned hemisphere. However, this appeared to be due to a compensatory decrease in completely stained tyrosine hydroxylase positive neurons in the contralateral, non-lesioned substantia nigra. In agreement with reports that maternal separation increases the 6-OHDA-induced loss of dopamine terminals in the striatum, there was a small increase in dopamine neuron destruction when expressed as a percentage of the non-lesioned hemisphere but there was no difference in dopamine cell number, suggesting that exposure to maternal separation did not exacerbate dopamine cell loss. PMID:20206210

  3. Maternal separation induced alterations of neurogenesis in the rat rostral migratory stream.

    PubMed

    Raceková, Eniko; Lievajová, Kamila; Danko, Ján; Martoncíková, Marcela; Flesárová, Slávka; Almasiová, Viera; Orendácová, Judita

    2009-09-01

    1. The aim of our study was to investigate the possibility that maternal separation, an experimental model for studies of early environmental influences, has an effect on postnatal neurogenesis in neurogenic pathway--the rostral migratory stream (RMS). 2. Rat pups were subjected to maternal separation daily for 3 h, starting from the first postnatal day (P1) till P14 or P21. In the first two groups, brains were analyzed at the age of P14 and P21, respectively. In the third group, after 3 weeks of maternal separation, 1 week of normal rearing was allowed, and the brains were analyzed at P28. The controls matched the age of maternally separated animals. Dividing cells were labeled by bromodeoxyuridine; dying cells were visualized by Fluoro-Jade C and nitric oxide (NO) producing cells by NADPH-diaphorase histochemistry. 3. Quantitative analysis of proliferating cells in the RMS showed that maternal separation decreased the number of dividing cells in all experimental groups. This decrease was most prominent in the caudal part of the RMS. The amount of dying cells was increased at the end of 3 weeks of maternal separation as well as 1 week later. The number of differentiated nitrergic cells in the RMS was increased at the end of 2 or 3 weeks of maternal separation, respectively. Besides quantitative changes, maternally separated animals showed an accelerated maturation of nitrergic cells. 4. Our results indicate that an exposure of rats to adverse environmental factors in early postnatal periods may induce acute site-specific changes in the RMS neurogenesis.

  4. Cognitive, emotional and neurochemical effects of repeated maternal separation in adolescent rats.

    PubMed

    Li, Man; Xue, Xiaofang; Shao, Shuang; Shao, Feng; Wang, Weiwen

    2013-06-26

    As an adverse early life experience, maternal separation (MS) induces profound neurochemical, cognitive and emotional dysfunction. Previous studies have reported that MS affected prepulse inhibition (PPI), anxiety-related behaviors, dopaminergic and serotonergic activity in adult rats, and in the present study, we investigated the effects of repeated (4h/day) maternal separation during postnatal days 1-21 on PPI and anxiety-related behaviors in an elevated plus maze, as well as dopamine D2 receptor (DRD2) and 5-HT1A receptor expression in the medial prefrontal cortex (mPFC), nucleus accumbens (NAc) and hippocampus in adolescent rats. Our findings show that repeated MS results in reduced PPI, increased anxiety-related behaviors, decreased DRD2 protein expression in the NAc and hippocampus, and decreased 5-HT1A protein expression in the mPFC and hippocampus in adolescent rats. These data further demonstrate that MS can be used as an animal model of neuropsychiatric disease.

  5. Pregnancy and maternal iron deficiency stimulate hepatic CRBPII expression in rats.

    PubMed

    Cottin, Sarah C; Gambling, Lorraine; Hayes, Helen E; Stevens, Valerie J; McArdle, Harry J

    2016-06-01

    Iron deficiency impairs vitamin A (VA) metabolism in the rat but the mechanisms involved are unknown and the effect during development has not been investigated. We investigated the effect of pregnancy and maternal iron deficiency on VA metabolism in the mother and fetus. 54 rats were fed either a control or iron deficient diet for 2weeks prior to mating and throughout pregnancy. Another 15 female rats followed the same diet and were used as non-pregnant controls. Maternal liver, placenta and fetal liver were collected at d21 for total VA, retinol and retinyl ester (RE) measurement and VA metabolic gene expression analysis. Iron deficiency increased maternal hepatic RE (P<.05) and total VA (P<.0001), fetal liver RE (P<.05), and decreased placenta total VA (P<.05). Pregnancy increased Cellular Retinol Binding Protein (CRBP)-II gene expression by 7 fold (P=.001), decreased VA levels (P=.0004) and VA metabolic gene expression (P<.0001) in the liver. Iron deficiency increased hepatic CRBPII expression by a further 2 fold (P=.044) and RBP4 by~20% (P=.005), increased RBPR2 and decreased CRBPII, LRAT, and TTR in fetal liver, while it had no effect on VA metabolic gene expression in the placenta. Hepatic CRBPII expression is increased by pregnancy and further increased by iron deficiency, which may play an important role in VA metabolism and homeostasis. Maternal iron deficiency also alters VA metabolism in the fetus, which is likely to have consequences for development. PMID:27142737

  6. Pregnancy and maternal iron deficiency stimulate hepatic CRBPII expression in rats.

    PubMed

    Cottin, Sarah C; Gambling, Lorraine; Hayes, Helen E; Stevens, Valerie J; McArdle, Harry J

    2016-06-01

    Iron deficiency impairs vitamin A (VA) metabolism in the rat but the mechanisms involved are unknown and the effect during development has not been investigated. We investigated the effect of pregnancy and maternal iron deficiency on VA metabolism in the mother and fetus. 54 rats were fed either a control or iron deficient diet for 2weeks prior to mating and throughout pregnancy. Another 15 female rats followed the same diet and were used as non-pregnant controls. Maternal liver, placenta and fetal liver were collected at d21 for total VA, retinol and retinyl ester (RE) measurement and VA metabolic gene expression analysis. Iron deficiency increased maternal hepatic RE (P<.05) and total VA (P<.0001), fetal liver RE (P<.05), and decreased placenta total VA (P<.05). Pregnancy increased Cellular Retinol Binding Protein (CRBP)-II gene expression by 7 fold (P=.001), decreased VA levels (P=.0004) and VA metabolic gene expression (P<.0001) in the liver. Iron deficiency increased hepatic CRBPII expression by a further 2 fold (P=.044) and RBP4 by~20% (P=.005), increased RBPR2 and decreased CRBPII, LRAT, and TTR in fetal liver, while it had no effect on VA metabolic gene expression in the placenta. Hepatic CRBPII expression is increased by pregnancy and further increased by iron deficiency, which may play an important role in VA metabolism and homeostasis. Maternal iron deficiency also alters VA metabolism in the fetus, which is likely to have consequences for development.

  7. Maternal Programming of Sexual Behavior and Hypothalamic-Pituitary-Gonadal Function in the Female Rat

    PubMed Central

    Cameron, Nicole; Del Corpo, Adina; Diorio, Josie; McAllister, Kelli; Sharma, Shakti; Meaney, Michael J.

    2008-01-01

    Variations in parental care predict the age of puberty, sexual activity in adolescence and the age at first pregnancy in humans. These findings parallel descriptions of maternal effects on phenotypic variation in reproductive function in other species. Despite the prevalence of such reports, little is known about potential biological mechanisms and this especially true for effects on female reproductive development. We examined the hypothesis that parental care might alter hypothalamic-pituitary-ovarian function and thus reproductive function in the female offspring of rat mothers that vary pup licking/grooming (LG) over the first week postpartum. As adults, the female offspring of Low LG mothers showed 1) increased sexual receptivity; 2) increased plasma levels of luteinizing hormone (LH) and progesterone at proestrus; 3) an increased positive-feedback effect of estradiol on both plasma LH levels and gonadotropin releasing-hormone (GnRH) expression in the medial preoptic region; and 4) increased estrogen receptor α (ERα) expression in the anterioventral paraventricular nucleus, a system that regulates GnRH. The results of a cross-fostering study provide evidence for a direct effect of postnatal maternal care as well as a possible prenatal influence. Indeed, we found evidence for increased fetal testosterone levels at embryonic day 20 in the female fetuses of High compared to Low LG mothers. Finally, the female offspring of Low LG mothers showed accelerated puberty compared to those of High LG mothers. These data suggest maternal effects in the rat on the development of neuroendocrine systems that regulate female sexual behaviour. Together with studies revealing a maternal effect on the maternal behavior of the female offspring, these findings suggest that maternal care can program alternative reproductive phenotypes in the rat through regionally-specific effects on ERα expression. PMID:18493313

  8. Developmental hypothyroxinaemia induced by maternal mild iodine deficiency delays hippocampal axonal growth in the rat offspring.

    PubMed

    Wei, W; Wang, Y; Wang, Y; Dong, J; Min, H; Song, B; Teng, W; Xi, Q; Chen, J

    2013-09-01

    Iodine is essential for the biosynthesis of thyroid hormones, including triiodothyronine and thyroxine. Thyroid hormones are important for central nervous system development. Mild maternal iodine deficiency (ID)-induced hypothyroxinaemia causes neurological deficits and mental retardation of the foetus. However, the detailed mechanism underlying these deficits is still largely unknown. Given that the growth-associated protein of 43 kDa (GAP-43), semaphorin 3A (Sema3A) and the glycogen synthase kinase 3β (GSK3β)/collapsin response mediator protein 2 (CRMP2) pathway are essential for axonal development, we hypothesise that hippocampal axonal growth-related proteins may be impaired, which may contribute to hippocampal axonal growth delay in rat offspring exposed to maternal hypothyroxinaemia. To test this hypothesis, maternal hypothyroxinaemia models were established in Wistar rats using a mild ID diet. Besides a negative control group, two maternal hypothyroidism models were created with either a severe ID diet or methimazole in the water. Our results showed that maternal hypothyroxinaemia exposure delayed offspring axonal growth on gestational day 19, postnatal day (PN) 7, PN14 and PN21. Consistent with this, the mean intensity of hippocampal CRMP2 and Tau1 immunofluorescence axonal protein was reduced in the mild ID group. Moreover, maternal hypothyroxinaemia disrupted expressions of GAP-43 and Sema3A. Furthermore, the phosphorylation of GSK3β and CRMP2 was also affected in the treated offspring, implying a potential mechanism by which hypothyroxinaemia-exposure affects neurodevelopment. Taken together, our data support the hypothesis that maternal hypothyroxinaemia may impair axonal growth of the offspring. PMID:23763342

  9. Developmental hypothyroxinaemia induced by maternal mild iodine deficiency delays hippocampal axonal growth in the rat offspring.

    PubMed

    Wei, W; Wang, Y; Wang, Y; Dong, J; Min, H; Song, B; Teng, W; Xi, Q; Chen, J

    2013-09-01

    Iodine is essential for the biosynthesis of thyroid hormones, including triiodothyronine and thyroxine. Thyroid hormones are important for central nervous system development. Mild maternal iodine deficiency (ID)-induced hypothyroxinaemia causes neurological deficits and mental retardation of the foetus. However, the detailed mechanism underlying these deficits is still largely unknown. Given that the growth-associated protein of 43 kDa (GAP-43), semaphorin 3A (Sema3A) and the glycogen synthase kinase 3β (GSK3β)/collapsin response mediator protein 2 (CRMP2) pathway are essential for axonal development, we hypothesise that hippocampal axonal growth-related proteins may be impaired, which may contribute to hippocampal axonal growth delay in rat offspring exposed to maternal hypothyroxinaemia. To test this hypothesis, maternal hypothyroxinaemia models were established in Wistar rats using a mild ID diet. Besides a negative control group, two maternal hypothyroidism models were created with either a severe ID diet or methimazole in the water. Our results showed that maternal hypothyroxinaemia exposure delayed offspring axonal growth on gestational day 19, postnatal day (PN) 7, PN14 and PN21. Consistent with this, the mean intensity of hippocampal CRMP2 and Tau1 immunofluorescence axonal protein was reduced in the mild ID group. Moreover, maternal hypothyroxinaemia disrupted expressions of GAP-43 and Sema3A. Furthermore, the phosphorylation of GSK3β and CRMP2 was also affected in the treated offspring, implying a potential mechanism by which hypothyroxinaemia-exposure affects neurodevelopment. Taken together, our data support the hypothesis that maternal hypothyroxinaemia may impair axonal growth of the offspring.

  10. Maternal separation stress leads to enhanced emotional responses to noxious stimuli in adult rats.

    PubMed

    Uhelski, Megan L; Fuchs, Perry N

    2010-10-15

    The purpose of the current study was to examine pain processing in adult rats following repeated maternal separation in infancy, a common model of early life stress. Sensory pain processing remained unaltered, as measured using threshold testing of nociception. However, affective pain processing was enhanced as revealed by increased responding during the tonic phase of the formalin test and during the place escape/avoidance test. The pattern of enhanced responses suggests that early life stress alters the emotional response to pain. Further research could determine if this pattern holds true for different pain models, or if post-weaning enrichment could reverse the effects of maternal separation on pain processing.

  11. Effect of fetal growth on maternal protein metabolism in postabsorptive rat

    SciTech Connect

    Ling, P.R.; Bistrian, B.R.; Blackburn, G.L.; Istfan, N.

    1987-03-01

    Rates of protein synthesis were measured in whole fetuses and maternal tissues at 17 and 20 days of gestation in postabsorptive rats using continuous infusion of L-(1-/sup 14/C)leucine. Fetal protein degradation rates were derived from the fractional rates of synthesis and growth. Whole-body (plasma) leucine kinetics in the mother showed a significant reduction of the fraction of plasma leucine oxidized in the mothers bearing older fetuses, a slight increase in the plasma flux, with total leucine oxidation and incorporation into protein remaining similar at the two gestational ages. Estimates of fractional protein synthesis in maternal tissues revealed an increase in placental and hepatic rates at 20 days of gestation, whereas the fractional synthetic rate in muscle remained unchanged. A model for estimation of the redistribution of leucine between plasma and tissues is described in detail. This model revealed a more efficient utilization of leucine in fetal protein synthesis in comparison with other maternal tissues, a greater dependency of the fetus on plasma supply of leucine, and a significant increase (2-fold) in the release of leucine from maternal muscle as the fetal requirements increased proportionately with its size. The latter conclusion, supported by nitrogen analysis and the ratio of bound-to-free leucine in maternal tissues, confirms the importance of maternal stores in maintaining the homeostasis of essential amino acids during late pregnancy.

  12. Maternal care interacts with prenatal stress in altering sexual dimorphism in male rats.

    PubMed

    Pérez-Laso, C; Ortega, E; Martín, J L R; Pérez-Izquierdo, M A; Gómez, F; Segovia, S; Del Cerro, M C R

    2013-09-01

    The present study analyzes the interaction between prenatal stress and mother's behavior on brain, hormonal, and behavioral development of male offspring in rats. It extends to males our previous findings, in females, that maternal care can alter behavioral dimorphism that becomes evident in the neonates when they mature. Experiment 1 compares the maternal behavior of foster mothers toward cross-fostered pups versus mothers rearing their own litters. Experiment 2 ascertains the induced "maternal" behavior of the male pups, derived from Experiment 1 when they reached maturity. The most striking effect was that the males non-exposed to the stress as fetuses and raised by stressed foster mothers showed the highest levels of "maternal" behavior of all the groups (i.e., induction of maternal behavior and retrieving behavior), not differing from the control, unstressed, female groups. Furthermore, those males showed significantly fewer olfactory bulb mitral cells than the control males that were non-stressed as fetuses and raised by their own non-stressed mothers. They also presented the lowest levels of plasma testosterone of all the male groups. The present findings provide evidence that prenatal environmental stress can "demasculinize" the behavior, brain anatomy and hormone secretion in the male fetuses expressed when they reach maturity. Moreover, the nature of the maternal care received by neonates can affect the behavior and physiology that they express at maturity.

  13. Maternal Low Quality Protein Diet Alters Plasma Amino Acid Concentrations of Weaning Rats.

    PubMed

    Kabasakal Cetin, Arzu; Dasgin, Halil; Gülec, Atila; Onbasilar, İlyas; Akyol, Asli

    2015-12-01

    Several studies have indicated the influence of a maternal low protein diet on the fetus. However, the effect of a maternal low quality protein diet on fetal growth and development is largely unknown. Wistar rats (11 weeks old) were mated and maintained on either a chow diet with 20% casein (n = 6) as the control group (C), or a low quality protein diet with 20% wheat gluten (n = 7) as the experimental group (WG) through gestation and lactation. Maternal body weights were similar in both groups throughout the study. Birth weights were not influenced by maternal diet and offspring body weights during lactation were similar between the groups. Offspring's plasma amino acid profiles showed that plasma methionine, glutamine and lysine were significantly lower and aspartic acid, ornithine and glycine-proline were significantly higher in the WG. Plant based protein comprises an important part of protein intake in developing countries. It is well-known that these diets can be inadequate in terms of essential amino acids. The current study shows differential effects of a maternal low quality protein diet on the offspring's plasma amino acids. Future studies will examine further aspects of the influence of maternal low quality protein diets on fetal growth and development.

  14. Maternal Low Quality Protein Diet Alters Plasma Amino Acid Concentrations of Weaning Rats

    PubMed Central

    Kabasakal Cetin, Arzu; Dasgin, Halil; Gülec, Atila; Onbasilar, İlyas; Akyol, Asli

    2015-01-01

    Several studies have indicated the influence of a maternal low protein diet on the fetus. However, the effect of a maternal low quality protein diet on fetal growth and development is largely unknown. Wistar rats (11 weeks old) were mated and maintained on either a chow diet with 20% casein (n = 6) as the control group (C), or a low quality protein diet with 20% wheat gluten (n = 7) as the experimental group (WG) through gestation and lactation. Maternal body weights were similar in both groups throughout the study. Birth weights were not influenced by maternal diet and offspring body weights during lactation were similar between the groups. Offspring’s plasma amino acid profiles showed that plasma methionine, glutamine and lysine were significantly lower and aspartic acid, ornithine and glycine-proline were significantly higher in the WG. Plant based protein comprises an important part of protein intake in developing countries. It is well-known that these diets can be inadequate in terms of essential amino acids. The current study shows differential effects of a maternal low quality protein diet on the offspring’s plasma amino acids. Future studies will examine further aspects of the influence of maternal low quality protein diets on fetal growth and development. PMID:26633475

  15. Neonatally Induced Mild Diabetes in Rats and Its Effect on Maternal, Placental, and Fetal Parameters

    PubMed Central

    Sinzato, Yuri Karen; Volpato, Gustavo Tadeu; Iessi, Isabela Lovizutto; Bueno, Aline; Calderon, Iracema de Mattos Paranhos; Rudge, Marilza Vieira Cunha; Damasceno, Débora Cristina

    2012-01-01

    The aim of this study was to assess placental changes and reproductive outcomes in neonatally induced mild diabetic dams and fetal development in their offspring. At birth, female rats were assigned either to control or diabetic group (100 mg of streptozotocin/Kg, subcutaneously). At adulthood, the female rats were mated. During pregnancy, the blood glucose levels and glucose and insulin tolerance tests were performed. At term, maternal reproductive outcomes, fetal and placental weight, and placental morphology were analyzed. Diabetic rats had smaller number of living fetuses, implantations and corpora lutea, and increased rate of embryonic loss. Placenta showed morphometric alterations in decidua area. Our results showed that mild diabetes was sufficient to trigger alterations in maternal organism leading to impaired decidua development contributing to failure in embryonic implantation and early embryonic losses. Regardless placental decidua alteration, the labyrinth, which is responsible for the maternal-fetal exchanges, showed no morphometric changes contributing to an appropriate fetal development, which was able to maintain normal fetal weight at term in mild diabetic rats. Thus, this experimental model of diabetes induction at the day of birth was more effective to reproduce the reproductive alterations of diabetic women. PMID:22778712

  16. Oxidized fish oil in rat pregnancy causes high newborn mortality and increases maternal insulin resistance.

    PubMed

    Albert, Benjamin B; Vickers, Mark H; Gray, Clint; Reynolds, Clare M; Segovia, Stephanie A; Derraik, José G B; Lewandowski, Paul A; Garg, Manohar L; Cameron-Smith, David; Hofman, Paul L; Cutfield, Wayne S

    2016-09-01

    Fish oil is commonly taken by pregnant women, and supplements sold at retail are often oxidized. Using a rat model, we aimed to assess the effects of supplementation with oxidized fish oil during pregnancy in mothers and offspring, focusing on newborn viability and maternal insulin sensitivity. Female rats were allocated to a control or high-fat diet and then mated. These rats were subsequently randomized to receive a daily gavage treatment of 1 ml of unoxidized fish oil, a highly oxidized fish oil, or control (water) throughout pregnancy. At birth, the gavage treatment was stopped, but the same maternal diets were fed ad libitum throughout lactation. Supplementation with oxidized fish oil during pregnancy had a marked adverse effect on newborn survival at day 2, leading to much greater odds of mortality than in the control (odds ratio 8.26) and unoxidized fish oil (odds ratio 13.70) groups. In addition, maternal intake of oxidized fish oil during pregnancy led to increased insulin resistance at the time of weaning (3 wks after exposure) compared with control dams (HOMA-IR 2.64 vs. 1.42; P = 0.044). These data show that the consumption of oxidized fish oil is harmful in rat pregnancy, with deleterious effects in both mothers and offspring. PMID:27385731

  17. Decreased maternal and fetal cholesterol following maternal bococizumab (anti-PCSK9 monoclonal antibody) administration does not affect rat embryo-fetal development.

    PubMed

    Campion, Sarah N; Han, Bora; Cappon, Gregg D; Lewis, Elise M; Kraynov, Eugenia; Liang, Hong; Bowman, Christopher J

    2015-11-01

    Bococizumab is a humanized monoclonal IgG2Δa antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9) for the treatment of hyperlipidemia. The evaluation of potential effects on embryo-fetal development was conducted in the rat. In a pharmacokinetic/pharmacodynamic study bococizumab was administered intravenously to pregnant Sprague-Dawley (SD) rats (n = 8/group) at 0, 10, 30, and 100 mg/kg during organogenesis. Maternal and fetal bococizumab, total cholesterol and HDL concentrations were determined. Bococizumab was well tolerated and there were no effects on ovarian or uterine parameters. Maternal and fetal bococizumab exposure increased with increasing dose, with a corresponding dose-dependent decrease in fetal cholesterol levels. Maternal cholesterol levels were decreased significantly, with reductions that were of a similar magnitude regardless of dose. In the definitive embryo-fetal development study bococizumab was administered to pregnant SD rats (n = 20/group) at 0, 10, 30, and 100 mg/kg and no adverse maternal or developmental effects were observed up to 100 mg/kg. These studies have provided an appropriate and relevant safety assessment of bococizumab in pregnant rats to inform human risk assessment, demonstrating no adverse effects on embryo-fetal development at magnitudes greater than anticipated clinical exposure and in the presence of maximal reductions in maternal cholesterol and dose-dependent reductions in fetal cholesterol.

  18. A study on fear memory retrieval and REM sleep in maternal separation and isolation stressed rats.

    PubMed

    Sampath, Dayalan; Sabitha, K R; Hegde, Preethi; Jayakrishnan, H R; Kutty, Bindu M; Chattarji, Sumantra; Rangarajan, Govindan; Laxmi, T R

    2014-10-15

    As rapid brain development occurs during the neonatal period, environmental manipulation during this period may have a significant impact on sleep and memory functions. Moreover, rapid eye movement (REM) sleep plays an important role in integrating new information with the previously stored emotional experience. Hence, the impact of early maternal separation and isolation stress (MS) during the stress hyporesponsive period (SHRP) on fear memory retention and sleep in rats were studied. The neonatal rats were subjected to maternal separation and isolation stress during postnatal days 5-7 (6h daily/3d). Polysomnographic recordings and differential fear conditioning was carried out in two different sets of rats aged 2 months. The neuronal replay during REM sleep was analyzed using different parameters. MS rats showed increased time in REM stage and total sleep period also increased. MS rats showed fear generalization with increased fear memory retention than normal control (NC). The detailed analysis of the local field potentials across different time periods of REM sleep showed increased theta oscillations in the hippocampus, amygdala and cortical circuits. Our findings suggest that stress during SHRP has sensitized the hippocampus-amygdala-cortical loops which could be due to increased release of corticosterone that generally occurs during REM sleep. These rats when subjected to fear conditioning exhibit increased fear memory and increased fear generalization. The development of helplessness, anxiety and sleep changes in human patients, thus, could be related to the reduced thermal, tactile and social stimulation during SHRP on brain plasticity and fear memory functions.

  19. Maternal PUFA ω-3 Supplementation Prevents Neonatal Lung Injuries Induced by Hyperoxia in Newborn Rats

    PubMed Central

    Sharma, Dyuti; Subayi Nkembi, Armande; Aubry, Estelle; Houeijeh, Ali; Butruille, Laura; Houfflin-Debarge, Véronique; Besson, Rémi; Deruelle, Philippe; Storme, Laurent

    2015-01-01

    Bronchopulmonary dysplasia (BPD) is one of the most common complications of prematurity, occurring in 30% of very low birth weight infants. The benefits of dietary intake of polyunsaturated fatty acids ω-3 (PUFA ω-3) during pregnancy or the perinatal period have been reported. The aim of this study was to assess the effects of maternal PUFA ω-3 supplementation on lung injuries in newborn rats exposed to prolonged hyperoxia. Pregnant female Wistar rats (n = 14) were fed a control diet (n = 2), a PUFA ω-6 diet (n = 6), or a PUFA ω-3 diet (n = 6), starting with the 14th gestation day. At Day 1, female and newborn rats (10 per female) were exposed to hyperoxia (O2, n = 70) or to the ambient air (Air, n = 70). Six groups of newborns rats were obtained: PUFA ω-6/O2 (n = 30), PUFA ω-6/air (n = 30), PUFA ω-3/O2 (n = 30), PUFA ω-3/air (n = 30), control/O2 (n = 10), and control/air (n = 10). After 10 days, lungs were removed for analysis of alveolarization and pulmonary vascular development. Survival rate was 100%. Hyperoxia reduced alveolarization and increased pulmonary vascular wall thickness in both control (n = 20) and PUFA ω-6 groups (n = 60). Maternal PUFA ω-3 supplementation prevented the decrease in alveolarization caused by hyperoxia (n = 30) compared to PUFA ω-6/O2 (n = 30) or to the control/O2 (n = 10), but did not significantly increase the thickness of the lung vascular wall. Therefore, maternal PUFA ω-3 supplementation may protect newborn rats from lung injuries induced by hyperoxia. In clinical settings, maternal PUFA ω-3 supplementation during pregnancy and during lactation may prevent BPD development after premature birth. PMID:26389878

  20. Maternal PUFA ω-3 Supplementation Prevents Neonatal Lung Injuries Induced by Hyperoxia in Newborn Rats.

    PubMed

    Sharma, Dyuti; Nkembi, Armande Subayi; Aubry, Estelle; Houeijeh, Ali; Butruille, Laura; Houfflin-Debarge, Véronique; Besson, Rémi; Deruelle, Philippe; Storme, Laurent

    2015-01-01

    Bronchopulmonary dysplasia (BPD) is one of the most common complications of prematurity, occurring in 30% of very low birth weight infants. The benefits of dietary intake of polyunsaturated fatty acids ω-3 (PUFA ω-3) during pregnancy or the perinatal period have been reported. The aim of this study was to assess the effects of maternal PUFA ω-3 supplementation on lung injuries in newborn rats exposed to prolonged hyperoxia. Pregnant female Wistar rats (n = 14) were fed a control diet (n = 2), a PUFA ω-6 diet (n = 6), or a PUFA ω-3 diet (n = 6), starting with the 14th gestation day. At Day 1, female and newborn rats (10 per female) were exposed to hyperoxia (O₂, n = 70) or to the ambient air (Air, n = 70). Six groups of newborns rats were obtained: PUFA ω-6/O₂ (n = 30), PUFA ω-6/air (n = 30), PUFA ω-3/O₂ (n = 30), PUFA ω-3/air (n = 30), control/O₂ (n = 10), and control/air (n = 10). After 10 days, lungs were removed for analysis of alveolarization and pulmonary vascular development. Survival rate was 100%. Hyperoxia reduced alveolarization and increased pulmonary vascular wall thickness in both control (n = 20) and PUFA ω-6 groups (n = 60). Maternal PUFA ω-3 supplementation prevented the decrease in alveolarization caused by hyperoxia (n = 30) compared to PUFA ω-6/O₂ (n = 30) or to the control/O₂ (n = 10), but did not significantly increase the thickness of the lung vascular wall. Therefore, maternal PUFA ω-3 supplementation may protect newborn rats from lung injuries induced by hyperoxia. In clinical settings, maternal PUFA ω-3 supplementation during pregnancy and during lactation may prevent BPD development after premature birth. PMID:26389878

  1. Maternal PUFA ω-3 Supplementation Prevents Neonatal Lung Injuries Induced by Hyperoxia in Newborn Rats.

    PubMed

    Sharma, Dyuti; Nkembi, Armande Subayi; Aubry, Estelle; Houeijeh, Ali; Butruille, Laura; Houfflin-Debarge, Véronique; Besson, Rémi; Deruelle, Philippe; Storme, Laurent

    2015-09-14

    Bronchopulmonary dysplasia (BPD) is one of the most common complications of prematurity, occurring in 30% of very low birth weight infants. The benefits of dietary intake of polyunsaturated fatty acids ω-3 (PUFA ω-3) during pregnancy or the perinatal period have been reported. The aim of this study was to assess the effects of maternal PUFA ω-3 supplementation on lung injuries in newborn rats exposed to prolonged hyperoxia. Pregnant female Wistar rats (n = 14) were fed a control diet (n = 2), a PUFA ω-6 diet (n = 6), or a PUFA ω-3 diet (n = 6), starting with the 14th gestation day. At Day 1, female and newborn rats (10 per female) were exposed to hyperoxia (O₂, n = 70) or to the ambient air (Air, n = 70). Six groups of newborns rats were obtained: PUFA ω-6/O₂ (n = 30), PUFA ω-6/air (n = 30), PUFA ω-3/O₂ (n = 30), PUFA ω-3/air (n = 30), control/O₂ (n = 10), and control/air (n = 10). After 10 days, lungs were removed for analysis of alveolarization and pulmonary vascular development. Survival rate was 100%. Hyperoxia reduced alveolarization and increased pulmonary vascular wall thickness in both control (n = 20) and PUFA ω-6 groups (n = 60). Maternal PUFA ω-3 supplementation prevented the decrease in alveolarization caused by hyperoxia (n = 30) compared to PUFA ω-6/O₂ (n = 30) or to the control/O₂ (n = 10), but did not significantly increase the thickness of the lung vascular wall. Therefore, maternal PUFA ω-3 supplementation may protect newborn rats from lung injuries induced by hyperoxia. In clinical settings, maternal PUFA ω-3 supplementation during pregnancy and during lactation may prevent BPD development after premature birth.

  2. Nitroglycerin prevents coagulopathies and foetal death associated with abnormal maternal inflammation in rats.

    PubMed

    Cotechini, Tiziana; Othman, Maha; Graham, Charles H

    2012-05-01

    Inflammation-associated foetal loss is often linked to maternal coagulopathies. Here, we characterised the role of maternal inflammation in the development of various systemic maternal coagulopathies and foetal death during mid-to-late gestation in rats. Since nitric oxide (NO) functions as an inhibitor of platelet aggregation and anti-oxidant, we also tested whether the NO mimetic nitroglycerin (glyceryl trinitrate, GTN) prevents inflammation-associated coagulopathies and foetal death. To induce chronic inflammation, pregnant Wistar rats were injected with low-doses of lipopolysaccharide (LPS; 10-40 μg/kg) on gestational days (GD) 13.5-16.5. To determine whether the effects of inflammation are mediated by tumour necrosis factor-α (TNF-α), the TNF-α inhibitor etanercept was injected on GD 13.5 and 15.5. Controls consisted of rats injected with saline. GTN was administered to LPS-treated rats via daily application of a transdermal patch on GD 12.5-16.5. Using thromboelastography (TEG), various coagulation parameters were assessed on GD 17.5; foetal viability was determined morphologically. Reference coagulation parameters were established based on TEG results obtained from control animals. LPS-treated rats exhibited distinct systemic coagulopathies: hypercoagulability, hypocoagulability, hyperfibrinolysis, and disseminated intravascular coagulation (DIC) stages I and III. A specific foetal death coagulation phenotype was observed, implicating TEG as a potential tool to identify inflammation-induced haemostatic alterations associated with pregnancy loss. Treatment with etanercept reduced the incidence of coagulopathy by 47%, while continuous delivery of GTN prevented foetal death and the inflammation-induced coagulopathies. These findings provide a rationale for investigating the use of GTN in the prevention of maternal coagulopathies and inflammation-mediated foetal death.

  3. Exercise in obese female rats has beneficial effects on maternal and male and female offspring metabolism

    PubMed Central

    Vega, Claudia C; Reyes-Castro, Luis A; Bautista, Claudia J; Larrea, Fernando; Nathanielsz, Peter W; Zambrano, Elena

    2013-01-01

    BACKGROUND Maternal obesity (MO) impairs maternal and offspring health. Mechanisms and interventions to prevent adverse maternal and offspring outcomes need to be determined. Human studies are confounded by socio-economic status providing the rationale for controlled animal data on effects of maternal exercise (MEx) intervention on maternal (F0) and offspring (F1) outcomes in MO. HYPOTHESIS MO produces metabolic and endocrine dysfunction, increases maternal and offspring glucocorticoid exposure, oxidative stress and adverse offspring outcomes by postnatal day (PND) 36. MEx prevents these outcomes. METHODS F0 female rats ate either control or obesogenic diet from weaning through lactation. Half of each group wheel ran (from day ninety of life through pregnancy beginning day 120) providing four groups (n=8/group) – i) controls, ii) obese, iii) exercised controls and iv) exercised obese. After weaning, PND 21, F1 offspring ate a control diet. Metabolic parameters of F0 prepregnancy and end of lactation and F1 offspring at PND 36 were analyzed. RESULTS Exercise did not change maternal weight. Before breeding, MO elevated F0 glucose, insulin, triglycerides, cholesterol, leptin, fat and oxidative stress. Exercise completely prevented the triglyceride rise and partially glucose, insulin, cholesterol and oxidative stress increases. MO decreased fertility, recovered by exercise. At the end of lactation, exercise returned all metabolic variables except leptin to control levels. Exercise partially prevented MO elevated corticosterone. F1 Offspring weights were similar at birth. At PND 36 MO increased F1 male but not female offspring leptin, triglycerides and fat mass. In controls exercise reduced male and female offspring glucose, prevented the offspring leptin increase and partially the triglyceride rise. CONCLUSIONS MEx before and during pregnancy has beneficial effects on maternal and offspring metabolism and endocrine function occurring with no weight change in mothers

  4. Late-onset exercise in female rat offspring ameliorates the detrimental metabolic impact of maternal obesity.

    PubMed

    Bahari, Hasnah; Caruso, Vanni; Morris, Margaret J

    2013-10-01

    Rising rates of maternal obesity/overweight bring the need for effective interventions in offspring. We observed beneficial effects of postweaning exercise, but the question of whether late-onset exercise might benefit offspring exposed to maternal obesity is unanswered. Thus we examined effects of voluntary exercise implemented in adulthood on adiposity, hormone profiles, and genes involved in regulating appetite and metabolism in female offspring. Female Sprague Dawley rats were fed either normal chow or high-fat diet (HFD) ad libitum for 5 weeks before mating and throughout gestation/lactation. At weaning, female littermates received either chow or HFD and, after 7 weeks, half were exercised (running wheels) for 5 weeks. Tissues were collected at 15 weeks. Maternal obesity was associated with increased hypothalamic inflammatory markers, including suppressor of cytokine signaling 3, TNF-α, IL-1β, and IL-6 expression in the arcuate nucleus. In the paraventricular nucleus (PVN), Y1 receptor, melanocortin 4 receptor, and TNF-α mRNA were elevated. In the hippocampus, maternal obesity was associated with up-regulated fat mass and obesity-associated gene and TNF-α mRNA. We observed significant hypophagia across all exercise groups. In female offspring of lean dams, the reduction in food intake by exercise could be related to altered signaling at the PVN melanocortin 4 receptor whereas in offspring of obese dams, this may be related to up-regulated TNF-α. Late-onset exercise ameliorated the effects of maternal obesity and postweaning HFD in reducing body weight, adiposity, plasma leptin, insulin, triglycerides, and glucose intolerance, with greater beneficial effects in offspring of obese dams. Overall, hypothalamic inflammation was increased by maternal obesity or current HFD, and the effect of exercise was dependent on maternal diet. In conclusion, even after a significant sedentary period, many of the negative impacts of maternal obesity could be improved by

  5. Homocysteine homeostasis in the rat is maintained by compensatory changes in cystathionine β-synthase, betaine-homocysteine methyltransferase, and phosphatidylethanolamine N-methyltransferase gene transcription occurring in response to maternal protein and folic acid intake during pregnancy and fat intake after weaning.

    PubMed

    Chmurzynska, Agata; Malinowska, Anna M

    2011-07-01

    The reactions of the methionine/homocysteine pathway are mediated by several enzymes, including phosphatidylethanolamine N-methyltransferase, cystathionine β-synthase, and betaine-homocysteine methyltransferase. Homocysteine homeostasis is regulated by these enzymes. We hypothesized here that the protein and folic acid content in the maternal diet affects methionine/homocysteine metabolism in the progeny. To test this hypothesis, pregnant rats were fed a diet with normal protein and normal folic acid levels (a modified casein-based AIN-93G diet), a protein-restricted and normal folic acid diet, a protein-restricted and folic acid-supplemented diet, or a normal protein and folic acid-supplemented diet. The progeny were fed either the modified AIN-93G diet or a high-fat lard-based diet. Progeny were analyzed for expression of the phosphatidylethanolamine N-methyltransferase, cystathionine β-synthase, and betaine-homocysteine methyltransferase genes in the liver and for serum homocysteine concentration. Interactions between prenatal and postnatal nutrition were also determined. The progeny of the dams fed the diets supplemented with folic acid showed decreased expression of all 3 genes (P < .001). An interaction effect between the protein and folic acid content in the maternal diet contributed to this down-regulation (P < .001), and the postweaning diet modified these effects. Serum homocysteine concentrations were approximately 15% higher in the male rats (P < .01), but neither prenatal nutrition nor the postweaning diet affected it significantly. We conclude that maternal diet during gestation has an important effect on the transcription level of these 3 genes, but changes in gene expression were not associated with significant changes in progeny homocysteine concentrations.

  6. Cocaine Treatment and Prenatal Environment Interact to Disrupt Intergenerational Maternal Behavior in Rats

    PubMed Central

    Johns, Josephine M.; Elliott, Deborah L.; Hofler, Vivian E.; Joyner, Paul W.; McMurray, Matthew S.; Jarrett, Thomas M.; Haslup, Amber M.; Middleton, Christopher L.; Elliott, Jay C.; Walker, Cheryl H.

    2011-01-01

    The link between impaired maternal behavior (MB) and cocaine treatment could result from drug-induced decreases in maternal reactivity to offspring, prenatal drug exposure (PDE) in offspring that could alter their ability to elicit MB, or the interaction of both, which could subsequently impair MB of the 1st-generation dams. Following chronic or intermittent cocaine or saline treatment during gestation, rat dams rearing natural or cross-fostered litters were compared along with untreated dams for MB. Untreated 1st-generation females with differentially treated rearing dams and PDE were tested for MB with their natural litters. The authors report disruptions in MB in dams and their 1st-generation offspring, attributable to main and interaction effects of maternal treatment, litter PDE, and rearing experience. PMID:16420163

  7. Effects of early life social stress on endocrinology, maternal behavior, and lactation in rats.

    PubMed

    Carini, Lindsay M; Nephew, Benjamin C

    2013-09-01

    Exposure to early life stress is a predictor of mental health disorders, and two common forms of early life stress are social conflict and impaired maternal care, which are predominant features of postpartum mood disorders. Exposure of lactating female rats to a novel male intruder involves robust social conflict and induces deficits in maternal care towards the F1 offspring. This exposure is an early life social stressor for female F1 pups that induces inefficient lactation associated with central changes in oxytocin (OXT), prolactin (PRL), and arginine vasopressin (AVP) gene expression in adult F1 females. The mothers of the rats in the current study were either allowed to raise their pups without exposure to a social stressor (control), or presented with a novel male intruder for 1h each day on lactation days 2-16 (chronic social stress). The effects of this early life chronic social stress (CSS) exposure on subsequent peripheral endocrinology, maternal behavior, and physiology were assessed. Exposure of female pups to early life CSS resulted in persistent alterations in maternal endocrinology at the end of lactation (attenuated prolactin and elevated corticosterone), depressed maternal care and aggression, increased restlessness and anxiety-related behavior, impaired lactation, and decreased saccharin preference. The endocrine and behavioral data indicate that early life CSS has long-term effects which are similar to changes seen in clinical populations of depressed mothers and provide support for the use of the chronic social stress paradigm as an ethologically relevant rodent model for maternal disorders such as postpartum depression and anxiety.

  8. Maternal environment alters social interactive traits but not open-field behavior in Fischer 344 rats.

    PubMed

    Yamamuro, Yutaka

    2008-10-01

    Although it is recognized that the genetic background governs behavioral phenotypes, environmental factors also play a critical role in the development of various behavioral processes. The maternal environment has a major impact on pups, and the cross-fostering procedure is used to determine the influence of early life experiences. The present study examined the influence of maternal environment on behavioral traits in inbred Fischer 344 (F344) rats. F344/DuCrlCrlj and Wistar (Crlj:WI) pups were fostered from postnatal day 1 as follows: Wistar pups raised by Wistar dams, F344 raised by Wistar, Wistar raised by F344, and F344 raised by F344. At 10 weeks of age, rats were randomly assigned to an open-field test and social interaction test. In the open-field test, irrespective of the rearing conditions, the activity during the first 1 min was significantly lower in F344 rats than in Wistar rats. Latency to the onset of movement showed no difference between groups. In the social interaction test, the recognition performance during the first 1 min in F344 raised by F344 was significantly shorter than that in the other groups. The onset of recognition to a novel social partner in F344 raised by F344 was significantly delayed, and the delay disappeared upon cross-fostering by Wistar dams. These results raise the possibility that the behavioral phenotype of F344 rats results from the interplay of genetic factors and maternal environment during early life, and that F344 rats are a strain with high susceptibility to rearing conditions for the formation of their emotionality.

  9. Maternal social separation of adolescent rats induces hyperactivity and anxiolytic behavior.

    PubMed

    Kwak, Hyong Ryol; Lee, Jae Won; Kwon, Kwang-Jun; Kang, Chang Don; Cheong, Il Young; Chun, Wanjoo; Kim, Sung-Soo; Lee, Hee Jae

    2009-04-01

    Exposure to early stressful adverse life events such as maternal and social separation plays an essential role in the development of the nervous system. Adolescent Sprague-Dawley rats that were separated on postnatal day 14 from their dam and litters (maternal social separation, MSS) showed hyperactivity and anxiolytic behavior in the open field test, elevated plus-maze test, and forced-swim test. Biologically, the number of astrocytes was significantly increased in the prefrontal cortex of MSS adolescent rats. The hyperactive and anxiolytic phenotype and biological alteration produced by this MSS protocol may provide a useful animal model for investigating the neurobiology of psychiatric disorders of childhood-onset diseases, such as attention deficient hyperactive disorder. PMID:19885001

  10. Effects of treadmill exercise-intensity on short-term memory in the rats born of the lipopolysaccharide-exposed maternal rats.

    PubMed

    Kim, Kijeong; Sung, Yun-Hee; Seo, Jin-Hee; Lee, Sang-Won; Lim, Baek-Vin; Lee, Choong-Yeol; Chung, Yong-Rak

    2015-12-01

    Maternal infection is an important factor causing neonatal brain injury and later developmental disability. In the present study, we investigated the effects of treadmill exercise intensity on short-term memory, hippocampal neurogenesis, and expression of brain-derived neurotrophic factor (BDNF), and tyrosine kinase receptor B (TrkB) in the rats born of lipopolysaccharide (LPS)-exposed maternal rats. The rats were divided into six groups: control group, mild-intensity exercise group, moderate-intensity exercise group, maternal LPS-exposed group, maternal LPS-exposed and mild-intensity exercise group, maternal LPS-exposed and moderate-intensity exercise group. The rats in the exercise groups were forced to run on a treadmill for 30 min 5 times a week for 4 weeks. The exercise load consisted of running at the speed of 8 m/min for the mild-intensity exercise groups and 14 m/min for moderate-intensity exercise groups. The latency in the step-down avoidance task was deter-mined for the short-term memory. Immunohistochemistry for 5-bro-mo-2'-deoxyuridine was performed to determine hippocampal cell proliferation and neurogenesis. Western blot analysis was performed for the detection of BDNF and TrkB expression. In the present study, tread-mill exercise improved short-term memory deteriorated by maternal LPS exposure. Treadmill exercise increased cell proliferation and neurogenesis in the hippocampal dentate gyrus of the rats born of the LPS-exposed maternal rats. Treadmill exercise increased BDNF and TrkB expression in the hippocampus of the rats born of the LPS-exposed maternal rats. These effects of treadmill exercise were similarly appeared at both mild-intensity and moderate-intensity.

  11. Effects of treadmill exercise-intensity on short-term memory in the rats born of the lipopolysaccharide-exposed maternal rats

    PubMed Central

    Kim, Kijeong; Sung, Yun-Hee; Seo, Jin-Hee; Lee, Sang-Won; Lim, Baek-Vin; Lee, Choong-Yeol; Chung, Yong-Rak

    2015-01-01

    Maternal infection is an important factor causing neonatal brain injury and later developmental disability. In the present study, we investigated the effects of treadmill exercise intensity on short-term memory, hippocampal neurogenesis, and expression of brain-derived neurotrophic factor (BDNF), and tyrosine kinase receptor B (TrkB) in the rats born of lipopolysaccharide (LPS)-exposed maternal rats. The rats were divided into six groups: control group, mild-intensity exercise group, moderate-intensity exercise group, maternal LPS-exposed group, maternal LPS-exposed and mild-intensity exercise group, maternal LPS-exposed and moderate-intensity exercise group. The rats in the exercise groups were forced to run on a treadmill for 30 min 5 times a week for 4 weeks. The exercise load consisted of running at the speed of 8 m/min for the mild-intensity exercise groups and 14 m/min for moderate-intensity exercise groups. The latency in the step-down avoidance task was deter-mined for the short-term memory. Immunohistochemistry for 5-bro-mo-2′-deoxyuridine was performed to determine hippocampal cell proliferation and neurogenesis. Western blot analysis was performed for the detection of BDNF and TrkB expression. In the present study, tread-mill exercise improved short-term memory deteriorated by maternal LPS exposure. Treadmill exercise increased cell proliferation and neurogenesis in the hippocampal dentate gyrus of the rats born of the LPS-exposed maternal rats. Treadmill exercise increased BDNF and TrkB expression in the hippocampus of the rats born of the LPS-exposed maternal rats. These effects of treadmill exercise were similarly appeared at both mild-intensity and moderate-intensity. PMID:26730379

  12. Histamine reverses a memory deficit induced in rats by early postnatal maternal deprivation.

    PubMed

    Benetti, Fernando; da Silveira, Clarice Kras Borges; da Silva, Weber Cláudio; Cammarota, Martín; Izquierdo, Iván

    2012-01-01

    Early partial maternal deprivation causes long-lasting neurochemical, behavioral and brain structural effects. In rats, it causes a deficit in memory consolidation visible in adult life. Some of these deficits can be reversed by donepezil and galantamine, which suggests that they may result from an impairment of brain cholinergic transmission. One such deficit, representative of all others, is an impairment of memory consolidation, clearly observable in a one-trial inhibitory avoidance task. Recent data suggest a role of brain histaminergic systems in the regulation of behavior, particularly inhibitory avoidance learning. Here we investigate whether histamine itself, its analog SKF-91844, or various receptor-selective histamine agonists and antagonists given into the CA1 region of the hippocampus immediately post-training can affect retention of one-trial inhibitory avoidance in rats submitted to early postnatal maternal deprivation. We found that histamine, SKF-91844 and the H2 receptor agonist, dimaprit enhance consolidation on their own and reverse the consolidation deficit induced by maternal deprivation. The enhancing effect of histamine was blocked by the H2 receptor antagonist, ranitidine, but not by the H1 receptor antagonist pyrilamine or by the H3 antagonist thioperamide given into CA1 at doses known to have other behavioral actions, without altering locomotor and exploratory activity or the anxiety state of the animals. The present results suggest that the memory deficit induced by early postnatal maternal deprivation in rats may in part be due to an impairment of histamine mediated mechanisms in the CA1 region of the rat hippocampus.

  13. Maternal caffeine exposure alters neuromotor development and hippocampus acetylcholinesterase activity in rat offspring.

    PubMed

    Souza, Ana Claudia; Souza, Andressa; Medeiros, Liciane Fernandes; De Oliveira, Carla; Scarabelot, Vanessa Leal; Da Silva, Rosane Souza; Bogo, Mauricio Reis; Capiotti, Katiucia Marques; Kist, Luiza Wilges; Bonan, Carla D; Caumo, Wolnei; Torres, Iraci L S

    2015-01-21

    The objective of this study was to evaluate the effects of maternal caffeine intake on the neuromotor development of rat offspring and on acetylcholine degradation and acetylcholinesterase (AChE) expression in the hippocampus of 14-day-old infant rats. Rat dams were treated with caffeine (0.3g/L) throughout gestation and lactation until the pups were 14 days old. The pups were divided into three groups: (1) control, (2) caffeine, and (3) washout caffeine. The washout group received a caffeine solution until the seventh postnatal day (P7). Righting reflex (RR) and negative geotaxis (NG) were assessed to evaluate postural parameters as an index of neuromotor reflexes. An open-field (OF) test was conducted to assess locomotor and exploratory activities as well as anxiety-like behaviors. Caffeine treatment increased both RR and NG latency times. In the OF test, the caffeine group had fewer outer crossings and reduced locomotion compared to control, while the washout group showed increased inner crossings in relation to the other groups and fewer rearings only in comparison to the control group. We found decreased AChE activity in the caffeine group compared to the other groups, with no alteration in AChE transcriptional regulation. Chronic maternal exposure to caffeine promotes important alterations in neuromotor development. These results highlight the ability of maternal caffeine intake to interfere with cholinergic neurotransmission during brain development.

  14. The effect of maternal ethanol ingestion on fetal vitamin A in the rat.

    PubMed

    Grummer, M A; Zachman, R D

    1990-09-01

    The effect of maternal ethanol ingestion on fetal tissue vitamin A was investigated. Pregnant rats were pair-fed control diets or diets containing 36% of energy as ethanol. After 17 or 21 d gestation, fetuses were removed and fetal and maternal tissues were analyzed by HPLC for retinol and retinyl palmitate. Ethanol consumption resulted in fewer fetuses per pregnancy, increased number of resorptions, and increased numbers of gross fetal abnormalities. In maternal tissues, ethanol consumption resulted in greater lung and kidney vitamin A concentrations. In the fetuses of ethanol-consuming pregnancies, free retinol in liver was higher at d 17. However, fetal liver palmitate levels and total retinyl palmitate in liver, lung, and kidney were lower in ethanol-fed rats at d 21 of gestation. Fetal lung retinyl palmitate concentrations were greater at both d 17 and d 21, and kidney levels were also greater at d 21. In conclusion, the ingestion of ethanol by pregnant rats is associated with a reduction in fetal liver vitamin A levels and an elevation in the levels of lung and kidney vitamin A, indicating possible altered vitamin A metabolism as a result of ethanol consumption. PMID:2235112

  15. Maternal caffeine exposure alters neuromotor development and hippocampus acetylcholinesterase activity in rat offspring.

    PubMed

    Souza, Ana Claudia; Souza, Andressa; Medeiros, Liciane Fernandes; De Oliveira, Carla; Scarabelot, Vanessa Leal; Da Silva, Rosane Souza; Bogo, Mauricio Reis; Capiotti, Katiucia Marques; Kist, Luiza Wilges; Bonan, Carla D; Caumo, Wolnei; Torres, Iraci L S

    2015-01-21

    The objective of this study was to evaluate the effects of maternal caffeine intake on the neuromotor development of rat offspring and on acetylcholine degradation and acetylcholinesterase (AChE) expression in the hippocampus of 14-day-old infant rats. Rat dams were treated with caffeine (0.3g/L) throughout gestation and lactation until the pups were 14 days old. The pups were divided into three groups: (1) control, (2) caffeine, and (3) washout caffeine. The washout group received a caffeine solution until the seventh postnatal day (P7). Righting reflex (RR) and negative geotaxis (NG) were assessed to evaluate postural parameters as an index of neuromotor reflexes. An open-field (OF) test was conducted to assess locomotor and exploratory activities as well as anxiety-like behaviors. Caffeine treatment increased both RR and NG latency times. In the OF test, the caffeine group had fewer outer crossings and reduced locomotion compared to control, while the washout group showed increased inner crossings in relation to the other groups and fewer rearings only in comparison to the control group. We found decreased AChE activity in the caffeine group compared to the other groups, with no alteration in AChE transcriptional regulation. Chronic maternal exposure to caffeine promotes important alterations in neuromotor development. These results highlight the ability of maternal caffeine intake to interfere with cholinergic neurotransmission during brain development. PMID:25451122

  16. Effect of water temperature on exercise-induced maternal hyperthermia on fetal development in rats.

    PubMed

    Mottola, M F; Fitzgerald, H M; Wilson, N C; Taylor, A W

    1993-07-01

    The objective of this study was to determine if water temperature influenced exercise-induced hyperthermia in swim-trained pregnant rats and the resulting fetal development. Pregnant Sprague-Dawley rats with 6 weeks pre-pregnancy training were exercised daily from day 1 to day 18 of gestation in water that was 34.6 +/- 0.4 degrees C (Cool Water Swimmers--CWS) or 37.6 +/- 0.1 degrees C (Warm Water Swimmers--WWS), for one hour/day. During this time period another group of pregnant rats was immersed to the neck in warm water (37.6 +/- 0.2 degrees C) (Warm Water Controls--WWC). On day 19 of gestation all animals were sacrificed and fetal development assessed. Maternal exercise in warm water elevated maternal body core temperature by 2.3 +/- 0.1 degrees C above resting values, with an increase in fetal abnormalities compared to the same exercise intensity in cool water. Fifty-eight percent of the abnormal fetuses and 60% of the resorption sites were found in the WWS group. Of the abnormalities determined, 65% were from the WWS group and 45% of these fetuses showed micrencephaly. Results suggest cool water may regulate maternal body temperature during swimming exercise and that swimming in warm water should be avoided during gestation because of potential teratogenic effects.

  17. Deconstructing the function of maternal stimulation in offspring development: Insights from the artificial rearing model in rats.

    PubMed

    Lomanowska, Anna M; Melo, Angel I

    2016-01-01

    This article is part of a Special Issue on "Parental Care". Maternal behavior has an important function in stimulating adequate growth and development of the young. Several approaches have been used in primates and rodents to deconstruct and examine the influence of specific components of maternal stimulation on offspring development. These approaches include observational studies of typical mother-infant interactions and studies of the effects of intermittent or complete deprivation of maternal contact. In this review, we focus on one unique approach using rats that enables the complete control of maternal variables by means of rearing rat pups artificially without contact with the mother or litter, while maintaining stable nutrition, temperature and exposure to stressful stimuli. This artificial rearing model permits the removal and controlled replacement of relevant maternal and litter stimuli and has contributed valuable insights regarding the influence of these stimuli on various developmental outcomes. It also enables the analysis of factors implicated in social isolation itself and their long-term influence. We provide an overview of the effects of artificial rearing on behavior, physiology, and neurobiology, including the influence of replacing maternal tactile stimulation and littermate contact on these outcomes. We then discuss the relevance of these effects in terms of the maternal role in regulating different aspects of offspring development and implications for human research. We emphasize that artificial rearing of rats does not lead to a global insult of nervous system development, making this paradigm useful in investigating specific developmental effects associated with maternal stimulation.

  18. Effects of Shiga toxin type 2 on maternal and fetal status in rats in the early stage of pregnancy.

    PubMed

    Sacerdoti, Flavia; Amaral, María M; Zotta, Elsa; Franchi, Ana M; Ibarra, Cristina

    2014-01-01

    Shiga toxin type 2 (Stx2), a toxin secreted by Shiga toxin-producing Escherichia coli (STEC), could be one of the causes of maternal and fetal morbimortality not yet investigated. In this study, we examined the effects of Stx2 in rats in the early stage of pregnancy. Sprague-Dawley pregnant rats were intraperitoneally (i.p.) injected with sublethal doses of Stx2, 0.25 and 0.5 ng Stx2/g of body weight (bwt), at day 8 of gestation (early postimplantation period of gestation). Maternal weight loss and food and water intake were analyzed after Stx2 injection. Another group of rats were euthanized and uteri were collected at different times to evaluate fetal status. Immunolocalization of Stx2 in uterus and maternal kidneys was analyzed by immunohistochemistry. The presence of Stx2 receptor (globotriaosylceramide, Gb3) in the uteroplacental unit was observed by thin layer chromatography (TLC). Sublethal doses of Stx2 in rats caused maternal weight loss and pregnancy loss. Stx2 and Gb3 receptor were localized in decidual tissues. Stx2 was also immunolocalized in renal tissues. Our results demonstrate that Stx2 leads to pregnancy loss and maternal morbidity in rats in the early stage of pregnancy. This study highlights the possibility of human pregnancy loss and maternal morbidity mediated by Stx2.

  19. The impact of emotional stress early in life on adult voluntary ethanol intake-results of maternal separation in rats.

    PubMed

    Roman, Erika; Nylander, Ingrid

    2005-09-01

    The combination of genetic and environmental factors determines the individual vulnerability for excessive ethanol intake, possibly leading to dependence. The environmental influences early in life represent examples of determinant factors for adult behaviour and can be protective as well as risk factors. Maternal separation is one model to examine the long-term consequences of early environmental experiences on neurochemistry and behaviour, including drug-taking behaviour in experimental animals. In the present review, findings from studies using repeated short and prolonged periods of maternal separation, with emphasis on effects on voluntary ethanol intake in rats with or without a genetic predisposition for high voluntary ethanol intake, are summarized. Despite some contradictory results, the general picture emerging shows that short periods of maternal separation during the postnatal period result in a lower adult voluntary ethanol intake in male rats. Prolonged periods of maternal separation were found to induce a high voluntary ethanol intake in male rats, including rats with a genetic predisposition for high ethanol intake. Results from the literature also show that changes were not just related to time of separation but were also related to the degree of handling. Interestingly, in terms of voluntary ethanol intake, female rats were generally not affected by postnatal maternal separation. The reasons for these sex differences need further investigation. In terms of neurobiological consequences of maternal separation, conclusive data are sparse and one of the future challenges will, therefore, be to identify and characterize underlying neurobiological mechanisms, especially in the individual animal.

  20. Maternal Style Selectively Shapes Amygdalar Development and Social Behavior in Rats Genetically Prone to High Anxiety

    PubMed Central

    Cohen, Joshua L.; Glover, Matthew E.; Pugh, Phyllis C.; Fant, Andrew D.; Simmons, Rebecca K.; Akil, Huda; Kerman, Ilan A.; Clinton, Sarah M.

    2015-01-01

    The early-life environment critically influences neurodevelopment and later psychological health. To elucidate neural and environmental elements that shape emotional behavior, we developed a rat model of individual differences in temperament and environmental reactivity. We selectively bred rats for high vs. low behavioral response to novelty and found that high reactive (bHR) rats display greater risk-taking, impulsivity, and aggression relative to low reactive (bLR) rats, which show high levels of anxiety/depression-like behavior and certain stress vulnerability. The bHR/bLR traits are heritable but prior work revealed bHR/bLR maternal style differences, with bLR dams showing more maternal attention than bHRs. The present study implemented a cross-fostering paradigm to examine the contribution of maternal behavior on bLR offspring’s brain development and emotional behavior. bLR offspring were reared by biological bLR mothers or fostered to a bLR or bHR mother and then evaluated to determine effects on: 1) developmental gene expression in the hippocampus and amygdala; and 2) adult anxiety/depression-like behavior. Genome-wide expression profiling showed that cross-fostering bLR rats to bHR mothers shifted developmental gene expression in the amygdala (but not hippocampus), reduced adult anxiety and enhanced social interaction. Our findings illustrate how an early-life manipulation such as cross-fostering changes the brain’s developmental trajectory and ultimately impacts adult behavior. Moreover, while earlier studies highlighted hippocampal differences contributing to the bHR/bLR phenotypes, our results point to a role of the amygdala as well. Future work will pursue genetic and cellular mechanisms within the amygdala that contribute to bHR/bLR behavior either at baseline or following environmental manipulations. PMID:25791846

  1. Coenzyme Q10 prevents hepatic fibrosis, inflammation, and oxidative stress in a male rat model of poor maternal nutrition and accelerated postnatal growth1

    PubMed Central

    Tarry-Adkins, Jane L; Fernandez-Twinn, Denise S; Hargreaves, Iain P; Neergheen, Viruna; Aiken, Catherine E; Martin-Gronert, Malgorzata S; McConnell, Josie M; Ozanne, Susan E

    2016-01-01

    Background: It is well established that low birth weight and accelerated postnatal growth increase the risk of liver dysfunction in later life. However, molecular mechanisms underlying such developmental programming are not well characterized, and potential intervention strategies are poorly defined. Objectives: We tested the hypotheses that poor maternal nutrition and accelerated postnatal growth would lead to increased hepatic fibrosis (a pathological marker of liver dysfunction) and that postnatal supplementation with the antioxidant coenzyme Q10 (CoQ10) would prevent this programmed phenotype. Design: A rat model of maternal protein restriction was used to generate low-birth-weight offspring that underwent accelerated postnatal growth (termed “recuperated”). These were compared with control rats. Offspring were weaned onto standard feed pellets with or without dietary CoQ10 (1 mg/kg body weight per day) supplementation. At 12 mo, hepatic fibrosis, indexes of inflammation, oxidative stress, and insulin signaling were measured by histology, Western blot, ELISA, and reverse transcriptase–polymerase chain reaction. Results: Hepatic collagen deposition (diameter of deposit) was greater in recuperated offspring (mean ± SEM: 12 ± 2 μm) than in controls (5 ± 0.5 μm) (P < 0.001). This was associated with greater inflammation (interleukin 6: 38% ± 24% increase; P < 0.05; tumor necrosis factor α: 64% ± 24% increase; P < 0.05), lipid peroxidation (4-hydroxynonenal, measured by ELISA: 0.30 ± 0.02 compared with 0.19 ± 0.05 μg/mL per μg protein; P < 0.05), and hyperinsulinemia (P < 0.05). CoQ10 supplementation increased (P < 0.01) hepatic CoQ10 concentrations and ameliorated liver fibrosis (P < 0.001), inflammation (P < 0.001), some measures of oxidative stress (P < 0.001), and hyperinsulinemia (P < 0.01). Conclusions: Suboptimal in utero nutrition combined with accelerated postnatal catch-up growth caused more hepatic fibrosis in adulthood, which was

  2. Serotonergic and noradrenergic lesions suppress the enhancing effect of maternal exercise during pregnancy on learning and memory in rat pups.

    PubMed

    Akhavan, M M; Emami-Abarghoie, M; Safari, M; Sadighi-Moghaddam, B; Vafaei, A A; Bandegi, A R; Rashidy-Pour, A

    2008-02-19

    The beneficial effects of exercise on learning and memory are well documented but the effects of prenatal exposure to maternal exercise on offspring are not clear yet. Using a two-trial-per-day Morris water maze for five consecutive days, succeeded by a probe trial 2 days later we showed that maternal voluntary exercise (wheel running) by pregnant rats increased the acquisition phase of the pups' learning. Maternal forced swimming by pregnant rats increased both acquisition and retention phases of the pups' learning. Also we found that the rat pups whose mother was submitted to forced-swimming during pregnancy had significantly higher brain, liver, heart and kidney weights compared with their sedentary counterparts. On the other hand we estimated the cell number of different regions of the hippocampus in the rat pups. We found that both exercise models during pregnancy increased the cell number in cornus ammonis subregion 1 (CA1) and dentate gyrus of the hippocampus in rat pups. To determine the role that noradrenergic and serotonergic neurotransmission and N-methyl-D-aspartate (NMDA) receptors hold in mediation of the maternal exercise in offspring, we used N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), p-chloroamphetamine (PCA) and MK-801 to eliminate or block the above systems, respectively. Blocking the NMDA receptors, significantly abolished learning and memory in rat pups from all three experimental groups. Elimination of noradrenergic or serotonergic input did not significantly attenuate the learning and memory in rat pups whose mothers were sedentary, while it significantly reversed the positive effects of maternal exercise during pregnancy on rat pups' learning and memory. The presented results suggest that noradrenergic and serotonergic systems in offspring brain seem to have a crucial specific role in mediating the effects of maternal physical activity during pregnancy on rat pups' cognitive function in both models of voluntary and forced exercise.

  3. Effects of maternal separation, early handling, and gonadal sex on regional metabolic capacity of the preweanling rat brain.

    PubMed

    Spivey, Jaclyn M; Padilla, Eimeira; Shumake, Jason D; Gonzalez-Lima, F

    2011-01-01

    This is the first study to assess the effects of mother-infant separation on regional metabolic capacity in the preweanling rat brain. Mother-infant separation is generally known to be stressful for rat pups. Holtzman adolescent rats show a depressive-like behavioral phenotype after maternal separation during the preweanling period. However, information is lacking on the effects of maternal separation on the brains of rat pups. We addressed this issue by mapping the brains of preweanling Holtzman rat pups using cytochrome oxidase histochemistry, which reflects long-term changes in brain metabolic capacity, following two weeks of repeated, prolonged maternal separation, and compared this to both early handled and non-handled pups. Quantitative image analysis revealed that maternal separation reduced cytochrome oxidase activity in the medial prefrontal cortex and nucleus accumbens shell. Maternal separation reduced prefrontal cytochrome oxidase to a greater degree in female pups than in males. Early handling reduced cytochrome oxidase activity in the posterior parietal cortex, ventral tegmental area, and subiculum, but increased cytochrome oxidase activity in the lateral frontal cortex. The sex-dependent effects of early handling on cytochrome oxidase activity were limited to the medial prefrontal cortex. Regardless of separation group, females had greater cytochrome oxidase activity in the habenula and ventral tegmental area compared to males. These findings suggest that early life mother-infant separation results in dysfunction of prefrontal and mesolimbic regions in the preweanling rat brain that may contribute to behavioral changes later in life.

  4. The effects of Love Canal soil extracts on maternal health and fetal development in rats.

    PubMed

    Silkworth, J B; Tumasonis, C; Briggs, R G; Narang, A S; Narang, R S; Rej, R; Stein, V; McMartin, D N; Kaminsky, L S

    1986-10-01

    The effects of a solvent extract of the surface soil of the Love Canal chemical dump site, Niagara Falls, New York, and of a natural extract, or leachate, which is drained from the canal for treatment, on the maternal health and fetal development were determined in rats. The solvent extract, which was contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (2, 3,7,8-TCDD) at 170 ppb and numerous other chlorinated organic compounds with the primary identified components being the isomers of benzenehexachloride (BHC), was dissolved in corn oil and administered by gavage to pregnant rats at 0,25,75, or 150 mg crude extract/kg/day on Days 6-15 of gestation. A 67% mortality was observed at the highest dose. The rats were sacrificed on Day 20. Dose-related increases in relative liver weight accompanied by hepatocyte hypertrophy were observed at all dose levels. Fetal birthweight was decreased at 75 and 150 mg extract/kg/day. No major treatment-related soft tissue or skeletal malformations, except for delayed ossification, were observed. Based on literature values for BHC, all of the observed toxicity could be accounted for by the BHC contaminants of the extract. The crude organic phase of the leachate was administered to pregnant rats at 0,10,100, or 250 mg/kg/day as described above. Maternal weight gain decreased at 100 and 250 mg/kg/day, accompanied by 5 and 14% maternal mortality, and 1 and 3 dead fetuses, respectively. Early resorptions and the percentage of dead implants increased whereas fetal birthweights were decreased at 250 mg/kg/day. No major treatment-related soft tissue or skeletal malformations, except for delayed ossification, were observed. The primary components of the complex leachate by mass were tetrachloroethanes; however, 2,3,7,8-TCDD, which was present at 3 ppm, probably accounted for all the observed toxicity. PMID:3781137

  5. Effects of Love Canal soil extracts on maternal health and fetal development in rats

    SciTech Connect

    Silkworth, J.B.; Tumasonis, C.; Briggs, R.G.; Narang, A.S.; Narang, R.S.; Rej, R.; Stein, V.; McMartin, D.N.; Kaminsky, L.S.

    1986-10-01

    The effects of a solvent extract of the surface soil of the Love Canal chemical dump site, Niagara Falls, New York, and of a natural extract, or leachate, which is drained from the canal for treatment, on the maternal health and fetal development were determined in rats. The solvent extract, which was contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (2, 3,7,8-TCDD) at 170 ppb and numerous other chlorinated organic compounds with the primary identified components being the isomers of benzenehexachloride (BHC), was dissolved in corn oil and administered by gavage to pregnant rats at 0,25,75, or 150 mg crude extract/kg/day on Days 6-15 of gestation. A 67% mortality was observed at the highest dose. The rats were sacrificed on Day 20. Dose-related increases in relative liver weight accompanied by hepatocyte hypertrophy were observed at all dose levels. Fetal birthweight was decreased at 75 and 150 mg extract/kg/day. No major treatment-related soft tissue or skeletal malformations, except for delayed ossification, were observed. Based on literature values for BHC, all of the observed toxicity could be accounted for by the BHC contaminants of the extract. The crude organic phase of the leachate was administered to pregnant rats at 0,10,100, or 250 mg/kg/day as described above. Maternal weight gain decreased at 100 and 250 mg/kg/day, accompanied by 5 and 14% maternal mortality, and 1 and 3 dead fetuses, respectively. Early resorptions and the percentage of dead implants increased whereas fetal birthweights were decreased at 250 mg/kg/day. No major treatment-related soft tissue or skeletal malformations, except for delayed ossification, were observed. The primary components of the complex leachate by mass were tetrachloroethanes; however, 2,3,7,8-TCDD, which was present at 3 ppm, probably accounted for all the observed toxicity.

  6. Effect of maternal exercise on biochemical parameters in rats submitted to neonatal hypoxia-ischemia.

    PubMed

    Marcelino, Thiago Beltram; de Lemos Rodrigues, Patrícia Idalina; Miguel, Patrícia Maidana; Netto, Carlos Alexandre; Pereira Silva, Lenir Orlandi; Matté, Cristiane

    2015-10-01

    Pregnancy is a critical period for brain metabolic programming, being affected by individual environment, such as nutrition, stress, and physical exercise. In this context, we previously reported a cerebral antioxidant upregulation and mitochondrial biogenesis in the offspring delivered from exercised mothers, which could provide neuroprotection against neonatal insults. Hypoxia-ischemia (HI) encephalopathy is one of the most studied models of neonatal brain injury; disrupting motor, cognitive, and learning abilities. Physiopathology includes oxidative stress, allied to mitochondria energy production failure, glutamatergic excitotoxicity, and cell death. In this study we evaluated the effect of maternal swimming during pregnancy on offspring׳s brain oxidative status evaluated fourteen days after HI stablishment. Swimming exercise was performed by female adult rats one week before and during pregnancy, in controlled environment. Their offspring was submitted to HI on postnatal day 7, and the brain samples for biochemical assays were obtained in the weaning. Contrary to our expectations, maternal exercise did not prevent the oxidative alterations observed in brain from HI-rats. In a general way, we found a positive modulation in the activities of antioxidant enzymes, measured two weeks after HI, in hippocampus, striatum, and cerebellum of pups delivered from exercised mothers. Reactive species levels were modulated differently in each structure evaluated. Considering the scenery presented, we concluded that HI elicited a neurometabolic adaptation in both brain hemispheres, particularly in hippocampus, parietal cortex, and cerebellum; while striatum appears to be most damaged. The protocol of aerobic maternal exercise was not enough to fully prevent HI-induced brain damages.

  7. A Transcriptomic Study of Maternal Thyroid Adaptation to Pregnancy in Rats

    PubMed Central

    Liu, Ji-Long; Wang, Tong-Song; Zhao, Miao; Peng, Ying; Fu, Yong-Sheng

    2015-01-01

    Thyroid disorders are relatively frequently observed in pregnant women. However, the impact of pregnancy on maternal thyroid has not been systematically evaluated. In the present study, using the rat as an animal model, we observed that the weight of maternal thyroid increased by about 18% in late pregnancy. To gain an insight into the molecular mechanisms, we took advantage of RNA-seq approaches to investigate global gene expression changes in the maternal thyroid. We identified a total of 615 differentially expressed genes, most of which (558 genes or 90.7%) were up-regulated in late pregnancy compared to the non-pregnant control. Gene ontology analysis showed that genes involved in cell cycle and metabolism were significantly enriched among up-regulated genes. Unexpectedly, pathway analysis revealed that expression levels for key components of the thyroid hormone synthesis pathway were not significantly altered. In addition, by examining of the promoter regions of up-regulated genes, we identified MAZ (MYC-associated zinc finger protein) and TFCP2 (transcription factor CP2) as two causal transcription factors. Our study contributes to an increase in the knowledge on the maternal thyroid adaptation to pregnancy. PMID:26580608

  8. Maternal reproductive experience enhances early postnatal outcome following gestation and birth of rats in hypergravity

    NASA Technical Reports Server (NTRS)

    Ronca, A. E.; Baer, L. A.; Daunton, N. G.; Wade, C. E.

    2001-01-01

    A major goal of space life sciences research is to broaden scientific knowledge of the influence of gravity on living systems. Recent spaceflight and centrifugation studies demonstrate that reproduction and ontogenesis in mammals are amenable to study under gravitational conditions that deviate considerably from those typically experienced on Earth (1 x g). In the present study, we tested the hypothesis that maternal reproductive experience determines neonatal outcome following gestation and birth under increased (hyper) gravity. Primigravid and bigravid female rats and their offspring were exposed to 1.5 x g centrifugation from Gestational Day 11 either through birth or through the first postnatal week. On the day of birth, litter sizes were identical across gravity and parity conditions, although significantly fewer live neonates were observed among hypergravity-reared litters born to primigravid dams than among those born to bigravid dams (82% and 94%, respectively; 1.0 x g controls, 99%). Within the hypergravity groups, neonatal mortality was comparable across parity conditions from Postnatal Day 1 through Day 7, at which time litter sizes stabilized. Maternal reproductive experience ameliorated neonatal losses during the first 24 h after birth but not on subsequent days, and neonatal mortality was associated with changes in maternal care patterns. These results indicate that repeated maternal reproductive experience affords protection against neonatal losses during exposure to increased gravity. Differential mortality of neonates born to primigravid versus bigravid dams denotes gravitational load as one environmental mechanism enabling the expression of parity-related variations in birth outcome.

  9. A Transcriptomic Study of Maternal Thyroid Adaptation to Pregnancy in Rats.

    PubMed

    Liu, Ji-Long; Wang, Tong-Song; Zhao, Miao; Peng, Ying; Fu, Yong-Sheng

    2015-01-01

    Thyroid disorders are relatively frequently observed in pregnant women. However, the impact of pregnancy on maternal thyroid has not been systematically evaluated. In the present study, using the rat as an animal model, we observed that the weight of maternal thyroid increased by about 18% in late pregnancy. To gain an insight into the molecular mechanisms, we took advantage of RNA-seq approaches to investigate global gene expression changes in the maternal thyroid. We identified a total of 615 differentially expressed genes, most of which (558 genes or 90.7%) were up-regulated in late pregnancy compared to the non-pregnant control. Gene ontology analysis showed that genes involved in cell cycle and metabolism were significantly enriched among up-regulated genes. Unexpectedly, pathway analysis revealed that expression levels for key components of the thyroid hormone synthesis pathway were not significantly altered. In addition, by examining of the promoter regions of up-regulated genes, we identified MAZ (MYC-associated zinc finger protein) and TFCP2 (transcription factor CP2) as two causal transcription factors. Our study contributes to an increase in the knowledge on the maternal thyroid adaptation to pregnancy. PMID:26580608

  10. Long-Term Effects of Maternal Deprivation on the Neuronal Soma Area in the Rat Neocortex

    PubMed Central

    Aksić, Milan; Radonjić, Nevena V.; Aleksić, Dubravka; Jevtić, Gordana; Marković, Branka; Petronijević, Nataša; Radonjić, Vidosava; Filipović, Branislav

    2014-01-01

    Early separation of rat pups from their mothers (separatio a matrem) is considered and accepted as an animal model of perinatal stress. Adult rats, separated early postnatally from their mothers, are developing long-lasting changes in the brain and neuroendocrine system, corresponding to the findings observed in schizophrenia and affective disorders. With the aim to investigate the morphological changes in this animal model we exposed 9-day-old (P9) Wistar rats to a 24 h maternal deprivation (MD). At young adult age rats were sacrificed for morphometric analysis and their brains were compared with the control group bred under the same conditions, but without MD. Rats exposed to MD had a 28% smaller cell soma area in the prefrontal cortex (PFCX), 30% in retrosplenial cortex (RSCX), and 15% in motor cortex (MCX) compared to the controls. No difference was observed in the expression of glial fibrillary acidic protein in the neocortex of MD rats compared to the control group. The results of this study demonstrate that stress in early life has a long-term effect on neuronal soma size in cingulate and retrosplenial cortex and is potentially interesting as these structures play an important role in cognition. PMID:24895554

  11. Vasopressin deficiency diminishes acute and long-term consequences of maternal deprivation in male rat pups.

    PubMed

    Zelena, Dóra; Stocker, Berhard; Barna, István; Tóth, Zsuzsanna E; Makara, Gábor B

    2015-01-01

    Early life events have special importance in the development as postnatal environmental alterations may permanently affect the lifetime vulnerability to diseases. For the interpretation of the long-term consequences it is important to understand the immediate effects. As the role of vasopressin in hypothalamic-pituitary-adrenal axis regulation as well as in affective disorders seem to be important we addressed the question whether the congenital lack of vasopressin will modify the stress reactivity of the pups and will influence the later consequences of single 24h maternal deprivation (MD) on both stress-reactivity and stress-related behavioral changes. Vasopressin-producing (di/+) and deficient (di/di) Brattleboro rat were used. In 10-day-old pups MD induced a remarkable corticosterone rise in both genotypes without adrenocorticotropin (ACTH) increase in di/di rats. Studying the later consequences at around weaning (25-35-day-old rats) we found somatic and hormonal alterations (body weight reduction, dysregulation of the stress axis) which were not that obvious in di/di rats. The more anxious state of MD rats was not detectable in di/di rats both at weaning and in adulthood (7-12-week-old). The lack of vasopressin abolished all chronic stress and anxiety-like tendencies both at weaning and in adulthood probably as a consequence of reduced ACTH rise immediately after MD in pups. This finding suggests that postnatal stress-induced ACTH rise may have long-term developmental consequences.

  12. Metyrapone Blocks Maternal Food Restriction-Induced Changes in Female Rat Offspring Lung Development

    PubMed Central

    Li, Yishi; Corral, Julia; Saraswat, Aditi; Husain, Sumair; Dhar, Ankita; Sakurai, Reiko; Khorram, Omid; Torday, John S.

    2014-01-01

    Maternal food restriction (MFR) during pregnancy affects pulmonary surfactant production in the intrauterine growth-restricted (IUGR) offspring through unknown mechanisms. Since pulmonary surfactant production is regulated by maternal and fetal corticosteroid levels, both known to be increased in IUGR pregnancies, we hypothesized that metyrapone (MTP), a glucocorticoid synthesis inhibitor, would block the effects of MFR on surfactant production in the offspring. Three groups of pregnant rat dams were used (1) control dams fed ad libitum; (2) MFR (50% reduction in calories) from days 10 to 22 of gestation; and (3) MFR + MTP in drinking water (0.5 mg/mL), days 11 to 22 of gestation. At 5 months, the MFR offspring weighed significantly more, had reduced alveolar number, increased septal thickness, and decreased surfactant protein and phospholipid synthesis. These MFR-induced effects were normalized by the antiglucocorticoid MTP, suggesting that the stress of MFR causes hypercorticoidism, altering lung structure and function in adulthood. PMID:24023031

  13. Maternal consumption of Lake Ontario salmon in rats produces behavioral changes in the offspring.

    PubMed

    Daly, H B; Stewart, P W; Lunkenheimer, L; Sargent, D

    1998-01-01

    The current study assessed the effects of maternal, paternal, or combined parental consumption of Lake Ontario salmon in rats on the behavior of their offspring. Adult female Sprague-Dawley rats were put on a 30 day diet of either ground rat chow containing 30% Lake Ontario salmon (LAKE) or 30% Pacific Ocean salmon (OCEAN). These females were then mated with adult male rats similarly exposed (LAKE or OCEAN). An additional control group of males and females who were fed ground rat chow (MASH) only were also mated. These pairing combinations resulted in five offspring groups: LAKE-LAKE, LAKE-OCEAN, OCEAN-LAKE, OCEAN-OCEAN, MASH-MASH. When the offspring reached 80 days of age, they were tested for reactivity to frustrative nonreward using runway successive negative contrast, which has been repeatedly shown to be increased in adult rats fed Ontario salmon. Consistent with previous work, results showed that the behavior of the OCEAN-OCEAN rats did not differ from the MASH-MASH group, indicating that a salmon diet per se does not cause behavioral change. However, the offspring of dams who consumed Lake Ontario salmon (LAKE-LAKE and OCEAN-LAKE) showed an increased depression effect relative to controls. There was little evidence of a paternal effect. A follow-up experiment employed cross-fostering to determine the relative contribution of pre- and/or postnatal exposure to Lake Ontario salmon consumption on offspring behavior. Rat pups were cross-fostered to or from dams who consumed Lake Ontario salmon during gestation and parturition. Results from two separate replications indicated that prenatal (LAKE to OCEAN) exposure alone or postnatal (OCEAN to LAKE) exposure alone produced a large increase in successive negative contrast relative to controls (OCEAN to OCEAN). These data are strong evidence of behavioral changes produced by maternal consumption of Lake Ontario salmon in the offspring rat. Further, they indicate that either prenatal or postnatal exposure alone is

  14. Citrinin and endosulfan induced maternal toxicity in pregnant Wistar rats: pathomorphological study.

    PubMed

    Singh, Nittin D; Sharma, Anil K; Dwivedi, Prabhaker; Patil, Rajendra D; Kumar, Manoj

    2007-01-01

    Dietary exposures to environmental food pollutants such as mycotoxin(s) or pesticide(s) have gained immense significance due to their adverse effects on production and reproduction in animal and human populations. The present investigation was conducted to evaluate the maternal toxicity of citrinin (CIT) and endosulfan administered per os either alone or in combination in pregnant rats during gestational days 6-20. CIT (group I, 10 mg kg(-1) feed, through diet) and endosulfan (group II, 1 mg kg(-1) body weight, by oral intubation) when administered either alone or in combination (group III) in Wistar rats caused clinical signs of toxicity and pathomorphological changes in all the toxin treated groups, the severity being more pronounced in the combination treatment compared with that observed in the control (group IV). The rate of fetal resorptions was highest (22.22%) in the combination treatment followed by endosulfan (16.48%) and CIT (12.50%) treatment groups compared with the control group (3.86%). The histopathological changes such as engorged vasculature, vacuolar degeneration and karyomegaly in liver; congestion, tubular degeneration and cast formation in kidneys; vascular changes and hemosiderosis in uterus and lymphocytic depletion and apoptosis in the lymphoid organs were recorded in the animals of the toxin treated groups. The lesions were consistent and more severe in the combination treatment group compared with the individual treatment groups, suggesting an additive interaction of CIT and endosulfan in inducing maternal toxicity in Wistar rats.

  15. Effects of maternal ethanol ingestion on uptake of glucose alanine analogs in fetal rats

    SciTech Connect

    Snyder, A.K.; Singh, S.P.; Pullen, G.L.

    1986-05-01

    The distribution of maternally-derived glucose and alanine has been studied in selected tissues of fetuses from ethanol-fed (EF) rats (30% of caloric intake throughout gestation). Controls received diet without ethanol by pair-feeding (PF) or ad libitum (AF). On the 22nd day of gestation, 2 ..mu..Ci /sup 3/H 2-deoxyglucose (DG) and 1 ..mu..Ci /sup 14/C ..cap alpha..-aminoisobutyric acid (AIB) were administered i.v. to each rat. One hour later, maternal blood, placenta, and fetal blood, liver, lung and brain were sampled for /sup 3/H and /sup 14/C activities. When compared to either control group, the mean /sup 14/C AIB activities of tissues from EF animals were reduced from 19 to 46%, with the greatest effect seen in the brain (3.7 +/- 0.1, 7.2 +/- 0.3 and 6.9 +/- 1.3 dpm/mg in EF, PF and AF fetuses respectively). In addition, the ratios of tissue:plasma /sup 14/C were reduced (p < 0.01 or lower) in the EF fetal tissues and placenta. Maternal ethanol ingestion reduced the /sup 3/H 2-DG content of placenta (p < 0.05) and of brain (38.6 + 1.2, 48.1 +/- 1.2 and 47.2 +/- 1.2 in EF, PF and AF, p < 0.001). Brain weight showed significant positive correlations with AIB content (r = 0.466, p < 0.001) and with 2-DG content (r = 0.267, p < 0.01). Impaired uptake of maternally-derived nutrients may play a significant role in the effects of ethanol in utero.

  16. Effect of maternal ethanol consumption on foetal and neonatal rat hepatic protein synthesis.

    PubMed Central

    Rawat, A K

    1976-01-01

    Effects of maternal ethanol consumption were investigated on the rates of protein synthehsis by livers of foetal and neonatal rats both in vivo and in vitro, and on the activities of enzymes involved in protein synthesis and degradation. The rates of general protein synthesis by ribosomes in vitro studied by measuring the incorporation of [14C]leucine into ribosomal protein showed that maternal ethanol consumption resulted in an inhibition of the rates of protein synthesis by both foetal and neonatal livers from the ethanol-fed group. The rates of incorporation of intravenously injected [14C]leucine into hepatic proteins were also significantly lower in the foetal, neonatal and adult livers from the ethanol-fed group. Incubation of adult-rat liver slices with ethanol resulted in an inhibition of the incorporation of [14C]leucine into hepatic proteins; however, this effect was not observed in the foetal liver slices. This effect of externally added ethanol was at least partially prevented by the addition of pyrazole to the adult liver slices. Pyrazole addition to foetal liver slices was without significant effect on the rates of protein synthesis. Cross-mixing experiments showed that the capacity of both hepatic ribosomes and pH5 enzyme fractions to synthesize proteins was decreased in the foetal liver from the ethanol-fed group. Maternal ethanol consumption resulted in a decrease in hepatic total RNA content, RNA/DNA ratio and ribosomal protein content in the foetal liver. Foetal hepatic DNA content was not significantly affected. Ethanol consumption resulted in a significant decrease in proteolytic activity and the activity of tryptophan oxygenase in the foetal, neonatal and adult livers. It is possible that the mechanisms of inhibition of protein synthesis observed here in the foetal liver after maternal ethanol consumption may be responsible for at least some of the changes observed in 'foetal alcohol syndrome'. PMID:1016246

  17. Maternal hypoxia alters matrix metalloproteinase expression patterns and causes cardiac remodeling in fetal and neonatal rats.

    PubMed

    Tong, Wenni; Xue, Qin; Li, Yong; Zhang, Lubo

    2011-11-01

    Fetal hypoxia leads to progressive cardiac remodeling in rat offspring. The present study tested the hypothesis that maternal hypoxia results in reprogramming of matrix metalloproteinase (MMP) expression patterns and fibrillar collagen matrix in the developing heart. Pregnant rats were treated with normoxia or hypoxia (10.5% O(2)) from day 15 to 21 of gestation. Hearts were isolated from 21-day fetuses (E21) and postnatal day 7 pups (PD7). Maternal hypoxia caused a decrease in the body weight of both E21 and PD7. The heart-to-body weight ratio was increased in E21 but not in PD7. Left ventricular myocardium wall thickness and cardiomyocyte proliferation were significantly decreased in both fetal and neonatal hearts. Hypoxia had no effect on fibrillar collagen content in the fetal heart, but significantly increased the collagen content in the neonatal heart. Western blotting revealed that maternal hypoxia significantly increased collagen I, but not collagen III, levels in the neonatal heart. Maternal hypoxia decreased MMP-1 but increased MMP-13 and membrane type (MT)1-MMP in the fetal heart. In the neonatal heart, MMP-1 and MMP-13 were significantly increased. Active MMP-2 and MMP-9 levels and activities were not altered in either fetal or neonatal hearts. Hypoxia significantly increased tissue inhibitors of metalloproteinase (TIMP)-3 and TIMP-4 in both fetal and neonatal hearts. In contrast, TIMP-1 and TIMP-2 were not affected. The results demonstrate that in utero hypoxia reprograms the expression patterns of MMPs and TIMPs and causes cardiac tissue remodeling with the increased collagen deposition in the developing heart.

  18. Maternal Deprivation of Lewis Rat Pups Increases the Severity of Experi-mental Periodontitis in Adulthood

    PubMed Central

    Breivik, Torbjørn; Gundersen, Yngvar; Murison, Robert; Turner, Jonathan D; Muller, Claude P; Gjermo, Per; Opstad, Kristian

    2015-01-01

    Background and Objective: Early life adverse events may influence susceptibility/resistance to chronic inflammatory diseases later in life by permanently dysregulating brain-controlled immune-regulatory systems. We have investigated the impact of infant-mother separation during early postnatal life on the severity of experimental periodontitis, as well as systemic stress and immune responses, in adulthood. Material and Methods: Pups of periodontitis resistant Lewis rats were separated from their mothers for 3 h daily during postnatal days 2-14 (termed maternal deprivation; MD), separated for 15 min daily during the same time period (termed handling; HD), or left undisturbed. As adults, their behaviour was tested in a novel stressful situation, and ligature-induced periodontitis applied for 21 days. Two h before sacrifice all rats were exposed to a gram-negative bacterial lipopolysaccharide (LPS) challenge to induce a robust immune and stress response. Results: Compared to undisturbed controls, MD rats developed significantly more periodontal bone loss as adults, whereas HD rats showed a tendency to less disease. MD and HD rats exhibited depression-like behaviour in a novel open field test, while MD rats showed higher glucocorticoid receptor (Gr) expression in the hippocampus, and HD rats had altered methylation of genes involved in the expression of hippocampal Gr. LPS provoked a significantly lower increase in circulating levels of the cytokine TGF-1β in MD and HD rats, but there were no significant differences in levels of the stress hormone corticosterone. Conclusion: Stressful environmental exposures in very early life may alter immune responses in a manner that influences susceptibility/resistance to periodontitis. PMID:25713634

  19. Protein restriction in early life is associated with changes in insulin sensitivity and pancreatic β-cell function during pregnancy.

    PubMed

    Ignácio-Souza, Letícia Martins; Reis, Sílvia Regina; Arantes, Vanessa Cristina; Botosso, Bárbara Laet; Veloso, Roberto Vilela; Ferreira, Fabiano; Boschero, Antonio Carlos; Carneiro, Everardo Magalhães; Reis, Marise Auxiliadora de Barros; Latorraca, Márcia Queiroz

    2013-01-28

    Malnutrition in early life impairs glucose-stimulated insulin secretion in adulthood. Conversely, pregnancy is associated with a significant increase in glucose-stimulated insulin secretion under conditions of normoglycaemia. A failure in β-cell adaptive changes may contribute to the onset of diabetes. Thus, glucose homeostasis and β-cell function were evaluated in control-fed pregnant (CP) and non-pregnant (CNP) or protein-restricted pregnant (LPP) and non-pregnant (LPNP) rats, from fetal to adult life, and in protein-restricted rats that were recovered after weaning (RP and RNP). The typical insulin resistance of pregnancy was not observed in the RP rats, nor did pregnancy increase the insulin content/islet in the LPP group. The glucose dose-response curves from pregnant rats were shifted to the left in relation to the non-pregnant rats, except in the recovered group. Glucose utilisation but not oxidation in islets from the RP and LPP groups was reduced at a concentration of 8.3 mm-glucose compared with islets from the CP group. Cyclic AMP content and the potentiation of glucose-stimulated insulin secretion by isobutylmethylxanthine at a concentration of 2.8 mm-glucose indicated increased adenylyl cyclase 3 activity but reduced protein kinase A-α activity in islets from the RP and LPP rats. Protein kinase C (PKC)-α but not phospholipase C (PLC)-β1 expression was reduced in islets from the RP group. Phorbol-12-myristate 13-acetate produced a less potent stimulation of glucose-stimulated insulin secretion in the RP group. Thus, the alterations exhibited by islets from the LPP group appeared to be due to reduced islet mass and/or insulin biosynthesis. In the RP group the loss of the adaptive capacity apparently resulted from uncoupling between glucose metabolism and the amplifying signals of the secretory process, as well as a severe attenuation of the PLC/PKC pathway. PMID:22475371

  20. Protein restriction in early life is associated with changes in insulin sensitivity and pancreatic β-cell function during pregnancy.

    PubMed

    Ignácio-Souza, Letícia Martins; Reis, Sílvia Regina; Arantes, Vanessa Cristina; Botosso, Bárbara Laet; Veloso, Roberto Vilela; Ferreira, Fabiano; Boschero, Antonio Carlos; Carneiro, Everardo Magalhães; Reis, Marise Auxiliadora de Barros; Latorraca, Márcia Queiroz

    2013-01-28

    Malnutrition in early life impairs glucose-stimulated insulin secretion in adulthood. Conversely, pregnancy is associated with a significant increase in glucose-stimulated insulin secretion under conditions of normoglycaemia. A failure in β-cell adaptive changes may contribute to the onset of diabetes. Thus, glucose homeostasis and β-cell function were evaluated in control-fed pregnant (CP) and non-pregnant (CNP) or protein-restricted pregnant (LPP) and non-pregnant (LPNP) rats, from fetal to adult life, and in protein-restricted rats that were recovered after weaning (RP and RNP). The typical insulin resistance of pregnancy was not observed in the RP rats, nor did pregnancy increase the insulin content/islet in the LPP group. The glucose dose-response curves from pregnant rats were shifted to the left in relation to the non-pregnant rats, except in the recovered group. Glucose utilisation but not oxidation in islets from the RP and LPP groups was reduced at a concentration of 8.3 mm-glucose compared with islets from the CP group. Cyclic AMP content and the potentiation of glucose-stimulated insulin secretion by isobutylmethylxanthine at a concentration of 2.8 mm-glucose indicated increased adenylyl cyclase 3 activity but reduced protein kinase A-α activity in islets from the RP and LPP rats. Protein kinase C (PKC)-α but not phospholipase C (PLC)-β1 expression was reduced in islets from the RP group. Phorbol-12-myristate 13-acetate produced a less potent stimulation of glucose-stimulated insulin secretion in the RP group. Thus, the alterations exhibited by islets from the LPP group appeared to be due to reduced islet mass and/or insulin biosynthesis. In the RP group the loss of the adaptive capacity apparently resulted from uncoupling between glucose metabolism and the amplifying signals of the secretory process, as well as a severe attenuation of the PLC/PKC pathway.

  1. Effects of maternal deprivation on adrenal and behavioural responses in rats with anterodorsal thalami nuclei lesions.

    PubMed

    Suárez, M; Molina, S; Rivarola, M A; Perassi, N I

    2002-07-26

    There is evidence that repeated maternal isolation of neonatal rats may influence both emotional behavior and Hypothalamic-Pituitary Adrenal (HPA) activity. On the other hand the Anterodorsal Thalami Nuclei (ADTN) exerts an inhibitory influence on the hypophyso-adrenal system under basal and stressful conditions. In the present work we investigated whether neonatal maternal deprivation produces long term effects on the ADTN regulation of behavioral patterns (open field test) and on HPA axis activity. Specifically, we sought to determine whether adult female rats with ADTN lesions, previously isolated for 4.5 hours daily during the first 3 weeks of life, react in endocrinologically and behaviourally distinct manner as compared to controls. The examined groups were: non maternally deprived (NMD)/sham lesioned, NMD/lesioned, maternally deprived (MD)/sham lesioned, MD/lesioned with and without the open field test. At 3 months MD/sham lesioned animals showed a marked decrease in ambulation (P < 0.01), and with ADTN lesion, the rearing values were lower (P < 0.01) and grooming higher (P < 0.05) than NMD. This last data would indicate a high emotional index. Regarding the activity of the HPA axis, maternal deprivation induced a significant decrease in plasma ACTH concentration both in sham and lesioned animals (P < 0.001), and plasma Corticosterone (C) increased in sham animals (P < 0.001). This data would indicate a higher sensitivity of the adrenal glands. After the open field test ACTH and C were different between deprived and non-deprived animals depending on the ADTN lesion. Taking into consideration the increase of ACTH levels in sham lesioned MD animals exposed to the test, we could conclude that this new situation was a stressful situation. Finally in the present work, it was very difficult to relate the behavioral parameters with the endocrine data. It is known that depending on the context, corticosteroids may produce opposite effects on emotional behavior via

  2. Effects of maternal deprivation on adrenal and behavioural responses in rats with anterodorsal thalami nuclei lesions.

    PubMed

    Suárez, M; Molina, S; Rivarola, M A; Perassi, N I

    2002-07-26

    There is evidence that repeated maternal isolation of neonatal rats may influence both emotional behavior and Hypothalamic-Pituitary Adrenal (HPA) activity. On the other hand the Anterodorsal Thalami Nuclei (ADTN) exerts an inhibitory influence on the hypophyso-adrenal system under basal and stressful conditions. In the present work we investigated whether neonatal maternal deprivation produces long term effects on the ADTN regulation of behavioral patterns (open field test) and on HPA axis activity. Specifically, we sought to determine whether adult female rats with ADTN lesions, previously isolated for 4.5 hours daily during the first 3 weeks of life, react in endocrinologically and behaviourally distinct manner as compared to controls. The examined groups were: non maternally deprived (NMD)/sham lesioned, NMD/lesioned, maternally deprived (MD)/sham lesioned, MD/lesioned with and without the open field test. At 3 months MD/sham lesioned animals showed a marked decrease in ambulation (P < 0.01), and with ADTN lesion, the rearing values were lower (P < 0.01) and grooming higher (P < 0.05) than NMD. This last data would indicate a high emotional index. Regarding the activity of the HPA axis, maternal deprivation induced a significant decrease in plasma ACTH concentration both in sham and lesioned animals (P < 0.001), and plasma Corticosterone (C) increased in sham animals (P < 0.001). This data would indicate a higher sensitivity of the adrenal glands. After the open field test ACTH and C were different between deprived and non-deprived animals depending on the ADTN lesion. Taking into consideration the increase of ACTH levels in sham lesioned MD animals exposed to the test, we could conclude that this new situation was a stressful situation. Finally in the present work, it was very difficult to relate the behavioral parameters with the endocrine data. It is known that depending on the context, corticosteroids may produce opposite effects on emotional behavior via

  3. Evidence for active maternal-fetal transport of Na+ across the placenta of the anaesthetized rat.

    PubMed

    Stulc, J; Stulcová, B; Sibley, C P

    1993-10-01

    1. In order to investigate mechanisms of Na+ transfer, the unidirectional maternal-fetal clearance (Kmf) of 22Na+ and of 51Cr-EDTA (a marker of paracellular diffusion) was measured across the intact or umbilically or dually perfused placenta of the anaesthetized rat. 2. The Kmf of 22Na+ in the intact preparation (18.5 +/- 2.7 microliters min-1, mean +/- S.D., n = 105 placentas) exceeded that of 51Cr-EDTA in the same experiments (1.4 +/- 0.3 microliters min-1) by more than ten times, whereas the difference in their diffusion coefficients in water was only 2-fold. In the perfused preparations the difference in the Kmf values was 6-fold. 3. Assuming that a simple model of paracellular diffusion through wide pores was one component of transfer, the Kmf of 51Cr-EDTA and the diffusion coefficients were used to calculate a component of 22Na+ clearance (Kmf,residual) and of Na+ flux (Jmf,residual) across the perfused placentas which could not be accounted for by transfer through the paracellular route. 4. Kmf,residual of 22Na+ across the dually perfused placenta was significantly lower when temperature was reduced, the temperature quotient (Q10) of the transfer being about 2. Kmf,residual was also significantly lower when 0.1 mM ouabain was perfused on the fetal side. Jmf,residual exhibited saturation kinetics characterized by an apparent Michaelis constant (Km) of 90 mM. Kmf,residual was not influenced by 0.5 mM frusemide, 0.5 mM amiloride or by 0.5 mM hydrochlorothiazide administered to the maternal side. It was significantly increased by 1 mM alanine on the maternal side suggesting that the coupled transfer of Na+ and amino acids may contribute significantly to the maternal-fetal flux of Na+. 5. These observations suggest that most (80%) of the maternal-fetal flux of Na+ across the rat placenta is effected by active transcellular transport. This transport involves passive entry of Na+ into the trophoblast from the maternal side by a largely unknown saturable mechanism

  4. Differences in maternal behavior of rats and the sociosexual development of the offspring.

    PubMed

    Birke, L I; Sadler, D

    1987-01-01

    This paper describes experiments designed to investigate long-term behavioral consequences for offspring of changes in maternal behavior directed toward them as pups. Specifically, the hypothesis was considered that experimentally induced alterations in maternal behavior would result in general and wide-ranging effects on offspring development, including effects on later social and sexual behavior. The first experiment looked at the effects of changing pup odors on maternal responsiveness toward the pups, and showed that the application of perfume, particularly to the anogenital region, resulted in significant lowering of maternal anogenital licking of pups. Non-pup-directed behavior did not differ between groups. The behavior of those pups that had thus differed in infant experience was then followed in three subsequent experiments. In Experiment 2, social behavior during the juvenile period was investigated, focusing particularly on the expression of social play. The most noticeable difference to emerge in this experiment was that male pups that had been anogenitally perfumed as infants showed much higher levels of social play than male or female pups from other treatment groups. The last two experiments considered adult behavior. Experiment 3 showed that there are no lasting effects of the neonatal treatment on the attractiveness an animal has for its conspecifics. In the final experiment, "masculine" sexual behavior of males (mounts with intromission), and "feminine" sexual behavior of females (i.e., lordosis and proceptive behavior) were investigated. This confirmed previous reports by Moore (1984) (Moore, C. L. (1984). Maternal contributions to the development of masculine sexual behavior in laboratory rats. Dev. Psychobiol., 17:347-363) that those male pups that had received lower rates of anogenital licking as pups showed longer intermount intervals, when tested as adults. The results are discussed in relation to the development of sexually differentiated

  5. Maternal molecular hydrogen treatment attenuates lipopolysaccharide-induced rat fetal lung injury.

    PubMed

    Hattori, Y; Kotani, T; Tsuda, H; Mano, Y; Tu, L; Li, H; Hirako, S; Ushida, T; Imai, K; Nakano, T; Sato, Y; Miki, R; Sumigama, S; Iwase, A; Toyokuni, S; Kikkawa, F

    2015-01-01

    Maternal inflammation is associated with spontaneous preterm birth and respiratory impairment among premature infants. Recently, molecular hydrogen (H2) has been reported to have a suppressive effect on oxidative stress and inflammation. The aim of this study was to evaluate the effects of H2 on fetal lung injury caused by maternal inflammation. Cell viability and the production of interleukin-6 (IL-6) and reactive oxygen species (ROS) were examined by treatment with lipopolysaccharide (LPS) contained in ordinal or H2-rich medium (HM) using a human lung epithelial cell line, A549. Pregnant Sprague Dawley rats were divided into three groups: Control, LPS, and HW + LPS groups. Rats were injected with phosphate-buffered saline (Control) or LPS intraperitoneally (LPS) on gestational day 19 and provided H2 water (HW) ad libitum for 24 h before LPS injection (HW + LPS). Fetal lung samples were collected on day 20, and the levels of apoptosis, oxidative damage, IL-6, and vascular endothelial growth factor (VEGF) were evaluated using immunohistochemistry. The number of apoptotic cells, and levels of ROS and IL-6 were significantly increased by LPS treatment, and repressed following cultured with HM in A549 cells. In the rat models, the population positive for cleaved caspase-3, 8-hydroxy-2'-deoxyguanosine, IL-6, and VEGF was significantly increased in the LPS group compared with that observed in the Control group and significantly decreased in the HW + LPS group. In this study, LPS administration induced apoptosis and oxidative damage in fetal lung cells that was ameliorated by maternal H2 intake. Antenatal H2 administration may decrease the pulmonary mobility associated with inflammation in premature infants.

  6. [Pup-Associated Conditioned Place Preference and Maternal Behavior in Depressive WAG/Rij Rats].

    PubMed

    Sarkisova, K Yu; Tanaeva, K K; Dobryakova, Yu V

    2016-01-01

    Elaboration of conditioned place preference (CPP) associated with own and foster pups, and maternal behavior were compared in females of WAG/Rij and Wistar rats. In addition, behavior of females in the open field, elevated plus-maze and forced swimming tests were investigated before pregnancy and after pup delivery. In has been found that females of WAG/Rij rats elaborate worse CPP task associated with both their own (WAG/Rij) and foster (Wistar) pups. Thus, the number of females that increase time spent in initially non-preferred compartment after its association with pups and the number of females that reach criterion of CPP elaboration in WAG/Rij rats were less than in Wistar controls. WAG/Rij females exhibited less maternal care in the place preference test both to their own and foster pups: less number of approaches to pups, pups carrying and the time spent in contact with pups non-associated with feeding. In WAG/Rij females compared with Wistar controls immobility time in the forced swimming test was higher both before pregnancy and after pup delivery indicating a stable depression-like state. Before pregnancy, statistically significant inter-strain differences in the anxiety level have not been revealed. After pup delivery, in WAG/Rij females anxiety level decreased but in Wistar females didn't substantially change. Results suggest that worse elaboration of CPP task and reduced maternal care in depressive WAG/Rij females are not associated with specific features of their own pups but are due to their depression-like state. Put into other words, pups for depressive mothers are less potent reinforcer than for "normal" (non-depressive) mothers. PMID:27538286

  7. Brief neonatal maternal separation alters extinction of conditioned fear and corticolimbic glucocorticoid and NMDA receptor expression in adult rats.

    PubMed

    Wilber, Aaron A; Southwood, Christopher J; Wellman, Cara L

    Neonatal maternal separation alters adult HPA axis responsiveness to stress, adult emotionality, and glucocorticoid receptor (GR) concentrations in forebrain regions such as hippocampus. To investigate effects of neonatal maternal separation on emotion regulation and its neural substrates, we assessed acquisition and extinction of conditioned fear in adult rats that underwent neonatal maternal separation. Corticolimbic structures including basolateral amygdala and medial prefrontal cortex are critical for acquisition and extinction of conditioned fear, and such learning is N-methyl-D-aspartic acid (NMDA) receptor-dependent. Thus, we used immunohistochemistry to assess expression of the GR and the NR1 subunit of the NMDA receptor in basolateral amygdala and medial prefrontal cortex. On postnatal days 2-14, pups underwent control rearing or maternal separation for 15 min per day. Fear conditioning and extinction in adulthood were then assessed in male rats. Rats received five tone-alone habituation trials, then seven tone/footshock pairings. After 1 h, rats received tone-alone extinction trials to criterion, and 15 recall of extinction trials the next day. Brains were processed for immunohistochemical labeling of GR and NR1, and staining was quantified. Brief maternal separation did not alter acquisition or initial extinction, but impaired extinction recall. Brief maternal separation did not alter GR or NR1 expression in basolateral amygdala. However, brief maternal separation increased GR and decreased NR1 expression specifically in the infralimbic region of medial prefrontal cortex, consistent with work implicating this area in extinction recall. Thus, brief maternal separation impaired extinction recall and altered GR and NR1 expression in its neural substrate in adults.

  8. Maternal and fetal toxicity of N-methylmorpholine by oral administration in rats.

    PubMed

    Sitarek, K

    1999-01-01

    N-methylmorpholine, which is used as a catalyst in polyurethane foams producing, in solvents, stabilizing agents, and corrosion inhibitors, was administered to female rats by gavage at 100, 200, 600, and 900 mg/kg during organogenesis. It did not exhibit selective toxicity toward the developing conceptus. This compound administered to pregnant females was fetotoxic and teratogenic in the presence of maternal toxicity. N-methylmorpholine induced anophthalmia, internal hydrocephalus, and hydronephrosis but only at one dose which was also maternotoxic. Teratogenesis Carcinog. Mutagen. 19:369-376, 1999. PMID:10587407

  9. Maternal separation enhances object location memory and prevents exercise-induced MAPK/ERK signalling in adult Sprague–Dawley rats

    PubMed Central

    Bugarith, Kishor; Russell, Vivienne A

    2012-01-01

    Early life stress increases the risk of developing psychopathology accompanied by reduced cognitive function in later life. Maternal separation induces anxiety-like behaviours and is associated with impaired memory. On the other hand, exercise has been shown to diminish anxiety-like behaviours and improve cognitive function. The effects of maternal separation and exercise on anxiety, memory and hippocampal proteins were investigated in male Sprague–Dawley rats. Maternal separation produced anxiety-like behaviours which were reversed by exercise. Maternal separation also enhanced object location memory which was not affected by exercise. Exercise did, however, increase synaptophysin and phospho-extracellular signal-regulated kinase (p-ERK) in the hippocampus of non-separated rats and this effect was not observed in maternally separated rats. These findings show that maternal separation selectively enhanced n memory and prevented activation of the MAPK/ERK signalling pathway in the adult rat hippocampus. PMID:22476924

  10. Maternal separation enhances object location memory and prevents exercise-induced MAPK/ERK signalling in adult Sprague-Dawley rats.

    PubMed

    Makena, Nokuthula; Bugarith, Kishor; Russell, Vivienne A

    2012-09-01

    Early life stress increases the risk of developing psychopathology accompanied by reduced cognitive function in later life. Maternal separation induces anxiety-like behaviours and is associated with impaired memory. On the other hand, exercise has been shown to diminish anxiety-like behaviours and improve cognitive function. The effects of maternal separation and exercise on anxiety, memory and hippocampal proteins were investigated in male Sprague-Dawley rats. Maternal separation produced anxiety-like behaviours which were reversed by exercise. Maternal separation also enhanced object location memory which was not affected by exercise. Exercise did, however, increase synaptophysin and phospho-extracellular signal-regulated kinase (p-ERK) in the hippocampus of non-separated rats and this effect was not observed in maternally separated rats. These findings show that maternal separation selectively enhanced n memory and prevented activation of the MAPK/ERK signalling pathway in the adult rat hippocampus.

  11. Early deprivation alters the vocalization behavior of neonates directing maternal attention in a rat model of child neglect.

    PubMed

    Zimmerberg, Betty; Kim, Ju H; Davidson, Abigail N; Rosenthal, Abigail J

    2003-12-01

    Animal models of child neglect (known as maternal separation or early deprivation) have suggested a causal link to subsequent depression and/or anxiety in children. In this experiment, the acoustical features of the ultrasonic calls emitted by a rat pup when separated from its dam were analyzed as well as the maternal behavior when the dam was allowed to retrieve the pup. Bout structure and harmonic double shifts did differ between controls and "neglected" pups, as did maternal attention. This model will be used to determine neural mechanisms underlying deficits in attachment behavior. PMID:14998903

  12. Tianeptine influence on plasmatic catecholamine levels and anxiety index in rats under variable chronic stress after early maternal separation.

    PubMed

    Trujillo, Verónica; Masseroni, María Lujan; Levin, Gloria; Suárez, Marta Magdalena

    2009-01-01

    The aim of this work was to determine the effect of chronic treatment with 5 mg/kg of tianeptine in male adult Wistar rats separated from the mother as neonates and submitted to variable chronic stress, plasma catecholamines, and anxiety. The plus maze test was performed in order to calculate the anxiety index and catecholamine levels were determined by high-pressure liquid chromatography. Both stress and maternal separation elevated catecholamine levels without affecting anxiety. In the maternally separated stress group, tianeptine decreased epinephrine. Anxiety was reduced in the maternally separated unstressed tianeptine group. Also, all groups showed a tendency to lower anxiety index.

  13. Effects of maternal deprivation and the duration of reunion time on rat pup ultrasonic vocalization responses to isolation: possible implications for human infant studies.

    PubMed

    Shair, Harry N; Rupert, Deborah D; Rosko, Lauren M; Hofer, Myron A; Myers, Michael M; Welch, Martha G

    2015-01-01

    In a paradigm that may serve as a translational model for maternal separation experiences of human infants in neonatal intensive care units, we examined how the duration of reunion with the dam influenced the phenomenon of maternal potentiation of ultrasonic vocalizations, in which isolated rat pups increase rates of vocalization following brief interactions with dams. We report that maternal potentiation in 12-13 day-old rats did not occur after reunions with their anesthetized dam that lasted longer than 15-min. However, after 18 hr maternal separation, isolated pups given reunions with their anesthetized dam increased vocalization rate even with reunions as long as 3 hr. Using a split-cage apparatus that prevented physical contact, the impact of 18 hr separations on maternal potentiation was partially offset by experiencing olfactory and/or auditory stimuli of the mother. These results suggest that maintaining partial maternal sensory exposure during prolonged maternal separation can reduce responses elicited by subsequent maternal separation.

  14. Effect of Bauhinia forficata extract in diabetic pregnant rats: maternal repercussions.

    PubMed

    Damasceno, D C; Volpato, G T; Calderon, I de Mattos Paranhos; Aguilar, R; Rudge, M V Cunha

    2004-02-01

    Bauhinia forficata, commonly known as "paw-of-cow", is widely used in Brazil folk medicine for the treatment of Diabetes mellitus. The purposes of present study were to determine the repercussions of diabetes on the defense system against oxidative stress in pregnant female rats and to characterize the influence of the treatment with Bauhinia forficata extract on the antioxidant system, glycemic control, hepatic glycogen, cholesterol, triglycerides, total proteins and lipids. Virgin female Wistar rats were injected with 40 mg/kg streptozotocin (STZ) before mating. Oral administration of an aqueous extract of Bauhinia forficata leaves was given to non-diabetic and diabetic pregnant rats in 3 doses: 500 mg/kg from 0 to 4th day of pregnancy, 600 mg/kg from 5th to 14th day and 1000 mg/kg from 15th to 20th day. All the females were killed on the day 21 of pregnancy. A maternal blood sample was collected by venous puncture and the maternal liver was removed for biochemical measurement. The diabetic pregnant rats presented hyperglycemia, hyperlipemia, hypertriglyceridemia, hypercholesterolemia, hyperuricemia, decreased determinations of reduced glutathione (GSH) and superoxide dismutase (SOD). Treatment with B. forficata extract did not interfere in the albumin, total protein and lipid, triglyceride, cholesterol and SOD determinations. Increased hepatic glycogen, decreased uric acid concentration and increased GSH activity was observed. This last fact suggests that the plant may have some action on antioxidant defense system. However, the demonstration of the active component present in B. forficata responsible for its antioxidant effect and the increase in hepatic glycogen deserve further investigation.

  15. Increased affective ultrasonic communication during fear learning in adult male rats exposed to maternal immune activation.

    PubMed

    Yee, Nicole; Schwarting, Rainer K W; Fuchs, Eberhard; Wöhr, Markus

    2012-09-01

    Maternal exposure to infection during pregnancy greatly increases the risk of psychopathology in the offspring. In support of clinical findings, rodent models of maternal immune activation (MIA) show that prenatal exposure to pathogens can induce phenotypic changes in the offspring associated with schizophrenia, autism, depression and anxiety. In the current study, we investigated the effects of MIA via polyinosinic:polycytidylic acid (poly I:C) on emotional behavior and communication in rats. Pregnant rats were administered poly I:C or saline on gestation day 15 and male offspring were tested in an auditory fear conditioning paradigm in early adulthood. We found that prenatal poly I:C exposure significantly altered affective signaling, namely, the production of aversive 22-kHz ultrasonic vocalizations (USVs), in terms of call number, structure and temporal patterning. MIA led to an increase in aversive 22-kHz USVs to 300% of saline controls. Offspring exposed to MIA not only emitted more 22-kHz USVs, but also emitted calls that were shorter in duration and occurred in bouts containing more calls. The production of appetitive 50-kHz USVs and audible calls was not affected. Intriguingly, alterations in aversive 22-kHz USV emission were observed despite no obvious changes in overt defensive behavior, which highlights the importance of assessing USVs as an additional measure of fear. Aversive 22-kHz USVs are a prominent part of the rat's defensive behavioral repertoire and serve important communicative functions, most notably as alarm calls. The observed changes in aversive 22-kHz USVs show that MIA has long-term effects on emotional behavior and communication in exposed rat offspring.

  16. Impairment of Central Chemoreception in Neonatal Rats Induced by Maternal Cigarette Smoke Exposure during Pregnancy.

    PubMed

    Lei, Fang; Yan, Xiang; Zhao, Fusheng; Zhang, Senfeng; Zhang, Qilan; Zhou, Hua; Zheng, Yu

    2015-01-01

    It has been postulated that prenatal cigarette smoke exposure (CSE) increases the risk for sudden infant death syndrome. The victims of infant death syndrome suffer from respiratory abnormalities, such as central apnea, diminished chemoreflex and alteration in respiratory pattern during sleep. However, no experimental evidence on CSE model exists to confirm whether prenatal CSE gives rise to reduction of neonatal central chemoreception in in vitro preparations in absence of peripheral sensory feedback. The aim of the present study was to test the hypothesis that maternal CSE during pregnancy depresses central chemoreception of the neonatal rats. The pregnant rats were divided into two groups, control (n = 8) and CSE (n = 8). Experiments were performed on neonatal (0-3days) rat pups. Fictive respiratory activity was monitored by recording the rhythmic discharge from the hypoglossal rootlets of the medullary slices obtained from the neonatal rats. The burst frequency (BF) and integrated amplitude (IA) of the discharge were analyzed. Their responses to acidified artificial cerebrospinal fluid (aCSF) were tested to indicate the change of the central chemosensitivity. Under condition of perfusing with standard aCSF (pH 7.4), no significant difference was detected between the two groups in either BF or IA (P>0.05). Under condition of perfusing with acidified aCSF (pH 7.0), BF was increased and IA was decreased in both groups (P<0.01). However, their change rates in the CSE group were obviously smaller than that in the control group, 66.98 ± 10.11% vs. 143.75 ± 15.41% for BF and -22.38 ± 2.51% vs. -44.90 ± 3.92% for IA (P<0.01). In conclusion, these observations, in a prenatal CSE model, provide important evidence that maternal smoking during pregnancy exerts adverse effects on central chemoreception of neonates. PMID:26333001

  17. Rat visceral yolk sac cells: viability and expression of cell markers during maternal diabetes.

    PubMed

    Aires, M B; Santos, J R A; Souza, K S; Farias, P S; Santos, A C V; Fioretto, E T; Maria, D A

    2015-08-01

    The function of the visceral yolk sac (VYS) is critical for embryo organogenesis until final fetal development in rats, and can be affected by conditions such as diabetes. In view of the importance of diabetes during pregnancy for maternal and neonatal health, the objective of this study was to assess fetal weight, VYS cell markers, and viability in female Wistar rats (200-250 g) with induced diabetes (alloxan, 37 mg/kg) on the 8th gestational day (gd 8). At gd 15, rats from control (n=5) and diabetic (n=5) groups were anesthetized and laparotomized to remove the uterine horns for weighing of fetuses and collecting the VYS. Flow cytometry was used for characterizing VYS cells, and for determining mitochondrial activity, cell proliferation, DNA ploidy, cell cycle phases, and caspase-3 activity. Fetal weight was reduced in the diabetic group. Expression of the cell markers CD34, VEGFR1, CD115, CD117, CD14, CCR2, CD90, CD44, STRO-1, OCT3/4, and Nanog was detected in VYS cells in both groups. In the diabetic group, significantly decreased expression of CD34 (P<0.05), CCR2 (P<0.001), and OCT3/4 (P<0.01), and significantly increased expression of CD90 (P<0.05), CD117 (P<0.01), and CD14 (P<0.05) were observed. VYS cells with inactive mitochondria, activated caspase-3, and low proliferation were present in the rats with diabetes. Severe hyperglycemia caused by maternal diabetes had negative effects on pregnancy, VYS cell viability, and the expression of cell markers. PMID:26176314

  18. Changes in behavior and ultrasonic vocalizations during antidepressant treatment in the maternally separated Wistar-Kyoto rat model of depression.

    PubMed

    van Zyl, P J; Dimatelis, J J; Russell, V A

    2014-06-01

    Genetic predisposition and stress are major factors in depression. The objective of this study was to establish a robust animal model of depression by selecting the appropriate substrain of the Wistar-Kyoto (WKY) rat, and subjecting these rats to the stress of maternal separation during the early stages of development. The initial experiment identified WKY/NCrl as the appropriate substrain of WKY to use for the study. In the second part of the study, depression-like behavior and ultrasonic vocalizations (USVs) were recorded in WKY/NCrl and maternally separated WKY/NCrl rats during the course of reversal of depression-like behavior. Wistar rats served as the reference strain. In adulthood, non-separated WKY/NCrl, maternally separated WKY/NCrl and Wistar rats were injected intraperitoneally with either saline or desipramine (15 mg/kg/day) for 15 days and their behavior recorded. Desipramine decreased immobility and increased active swimming and struggling behavior of WKY/NCrl in the FST and also decreased their USVs in response to removal of cage mates. The USVs in this study appeared to signal an attempt to re-establish social contact with cage mates and provided a measure of social dependence. Maternally separated WKY/NCrl rats displayed more anxiety than normally reared WKY/NCrl rats and responded to the anxiolytic effects of desipramine. The present findings support the use of WKY/NCrl as an animal model of depression. Maternal separation increased the anxiety-like behavior of the WKY/NCrl, thus providing a robust model to study depression- and anxiety-related behavior.

  19. Nicotine ameliorates schizophrenia-like cognitive deficits induced by maternal LPS exposure: a study in rats

    PubMed Central

    Waterhouse, Uta; Roper, Vic E.; Brennan, Katharine A.

    2016-01-01

    ABSTRACT Maternal exposure to infectious agents is a predisposing factor for schizophrenia with associated cognitive deficits in offspring. A high incidence of smoking in these individuals in adulthood might be, at least in part, due to the cognitive-enhancing effects of nicotine. Here, we have used prenatal exposure to maternal lipopolysaccharide (LPS, bacterial endotoxin) at different time points as a model for cognitive deficits in schizophrenia to determine whether nicotine reverses any associated impairments. Pregnant rats were treated subcutaneously with LPS (0.5 mg/kg) at one of three neurodevelopmental time periods [gestation days (GD) 10-11, 15-16, 18-19]. Cognitive assessment in male offspring commenced in early adulthood [postnatal day (PND) 60] and included: prepulse inhibition (PPI), latent inhibition (LI) and delayed non-matching to sample (DNMTS). Following PND 100, daily nicotine injections (0.6 mg/kg, subcutaneously) were administered, and animals were re-tested in the same tasks (PND 110). Only maternal LPS exposure early during fetal neurodevelopment (GD 10-11) resulted in deficits in all tests compared to animals that had been prenatally exposed to saline at the same gestational time point. Repeated nicotine treatment led to global (PPI) and selective (LI) improvements in performance. Early but not later prenatal LPS exposure induced consistent deficits in cognitive tests with relevance for schizophrenia. Nicotine reversed the LPS-induced deficits in selective attention (LI) and induced a global enhancement of sensorimotor gating (PPI). PMID:27483346

  20. Adaptive significance of natural variations in maternal care in rats: a translational perspective

    PubMed Central

    Beery, Annaliese K.; Francis, Darlene D.

    2011-01-01

    A wealth of data from the last fifty years documents the potency of early life experiences including maternal care on developing offspring. A majority of this research has focused on the developing stress axis and stress-sensitive behaviors in hopes of identifying factors impacting resilience and risk-sensitivity. The power of early life experience to shape later development is profound and has the potential to increase fitness of individuals for their environments. Current findings in a rat maternal care paradigm highlight the complex and dynamic relation between early experiences and a variety of outcomes. In this review we propose adaptive hypotheses for alternate maternal strategies and resulting offspring phenotypes, and ways to distinguish between these hypotheses. We also provide evidence underscoring the critical role of context in interpreting the adaptive significance of early experiences. If our goal is to identify risk-factors relevant to humans, we must better explore the role of the social and physical environment in our basic animal models. PMID:21458485

  1. Preimplantation embryo-secreted factors modulate maternal gene expression in rat uterus.

    PubMed

    Yamagami, Kazuki; Islam, M Rashedul; Yoshii, Yuka; Mori, Kazuki; Tashiro, Kosuke; Yamauchi, Nobuhiko

    2016-05-01

    In mammalian reproduction, embryo implantation into the uterus is spatiotemporally regulated by a complex process triggered by a number of factors. Although previous studies have suggested that uterine receptivity is mediated by blastocyst-derived factors, specific functions of embryos remain to be defined during preimplantation. Therefore, the present study was conducted to identify the maternal genes regulated by embryo-secreted factors in the rat uterus. RNA-sequencing (RNA-seq) data revealed that 10 genes are up-regulated in the delayed implantation uterus compared with the pseudopregnancy uterus. The RNA-seq results were further verified by real-time quantitative polymerase chain reaction. Sulf1 expression is significantly (P < 0.05) induced in the delayed implantation uterus, although Areg, Calca, Fxyd4 and Lamc3 show a definite but non-statistically significant increase in their expression levels. During early pregnancy, the levels of Areg, Calca, Fxyd4, Lamc3 and Sulf1 expression at 3.5 days post coitus (dpc) are significantly (P < 0.05) higher than those at 1.5 dpc. Treatment with embryo-conditioned media revealed that Lamc3 and Sulf1 are up-regulated compared with the other genes studied. Thus, embryo-derived factors regulate maternal gene expression, with Lamc3 and Sulf1 possibly being suitable markers for a response study of embryo-secreted factors to improve our understanding of embryo-maternal communication.

  2. Preimplantation embryo-secreted factors modulate maternal gene expression in rat uterus.

    PubMed

    Yamagami, Kazuki; Islam, M Rashedul; Yoshii, Yuka; Mori, Kazuki; Tashiro, Kosuke; Yamauchi, Nobuhiko

    2016-05-01

    In mammalian reproduction, embryo implantation into the uterus is spatiotemporally regulated by a complex process triggered by a number of factors. Although previous studies have suggested that uterine receptivity is mediated by blastocyst-derived factors, specific functions of embryos remain to be defined during preimplantation. Therefore, the present study was conducted to identify the maternal genes regulated by embryo-secreted factors in the rat uterus. RNA-sequencing (RNA-seq) data revealed that 10 genes are up-regulated in the delayed implantation uterus compared with the pseudopregnancy uterus. The RNA-seq results were further verified by real-time quantitative polymerase chain reaction. Sulf1 expression is significantly (P < 0.05) induced in the delayed implantation uterus, although Areg, Calca, Fxyd4 and Lamc3 show a definite but non-statistically significant increase in their expression levels. During early pregnancy, the levels of Areg, Calca, Fxyd4, Lamc3 and Sulf1 expression at 3.5 days post coitus (dpc) are significantly (P < 0.05) higher than those at 1.5 dpc. Treatment with embryo-conditioned media revealed that Lamc3 and Sulf1 are up-regulated compared with the other genes studied. Thus, embryo-derived factors regulate maternal gene expression, with Lamc3 and Sulf1 possibly being suitable markers for a response study of embryo-secreted factors to improve our understanding of embryo-maternal communication. PMID:26685865

  3. Maternal hyperglycemia leads to fetal cardiac hyperplasia and dysfunction in a rat model.

    PubMed

    Lehtoranta, Lara; Vuolteenaho, Olli; Laine, V Jukka; Koskinen, Anna; Soukka, Hanna; Kytö, Ville; Määttä, Jorma; Haapsamo, Mervi; Ekholm, Eeva; Räsänen, Juha

    2013-09-01

    Accelerated fetal myocardial growth with altered cardiac function is a well-documented complication of human diabetic pregnancy, but its pathophysiology is still largely unknown. Our aim was to explore the mechanisms of fetal cardiac remodeling and cardiovascular hemodynamics in a rat model of maternal pregestational streptozotocin-induced hyperglycemia. The hyperglycemic group comprised 107 fetuses (10 dams) and the control group 219 fetuses (20 dams). Fetal cardiac function was assessed serially by Doppler ultrasonography. Fetal cardiac to thoracic area ratio, newborn heart weight, myocardial cell proliferative and apoptotic activities, and cardiac gene expression patterns were determined. Maternal hyperglycemia was associated with increased cardiac size, proliferative, apoptotic and mitotic activities, upregulation of genes encoding A- and B-type natriuretic peptides, myosin heavy chain types 2 and 3, uncoupling proteins 2 and 3, and the angiogenetic tumor necrosis factor receptor superfamily member 12A. The genes encoding Kv channel-interacting protein 2, a regulator of electrical cardiac phenotype, and the insulin-regulated glucose transporter 4 were downregulated. The heart rate was lower in fetuses of hyperglycemic dams. At 13-14 gestational days, 98% of fetuses of hyperglycemic dams had holosystolic atrioventricular valve regurgitation and decreased outflow mean velocity, indicating diminished cardiac output. Maternal hyperglycemia may lead to accelerated fetal myocardial growth by cardiomyocyte hyperplasia. In fetuses of hyperglycemic dams, expression of key genes that control and regulate cardiomyocyte electrophysiological properties, contractility, and metabolism are altered and may lead to major functional and clinical implications on the fetal heart. PMID:23839525

  4. Acute cocaine alters oxytocin levels in the medial preoptic area and amygdala in lactating rat dams: implications for cocaine-induced changes in maternal behavior and maternal aggression.

    PubMed

    Elliott, J C; Lubin, D A; Walker, C H; Johns, J M

    2001-04-01

    Acute cocaine administration has been correlated with disruptions in the onset and maintenance of maternal behavior as well as decreases in maternal aggressive behavior in rat dams. A growing body of evidence suggests that cocaine may alter oxytocin levels leading to impairments in maternal behavior and aggression. The current study assessed whether acute cocaine injections alter oxytocin (OT) levels in the medial preoptic area (MPOA), ventral tegmental area (VTA), amygdala (AMY), and hippocampus (HIP) on postpartum day (PPD) 1 or PPD 6. On PPD 1, 30 mg/kg cocaine reduced OT levels by approximately 26.9% (picograms/milligram) in the MPOA (t (18) = 3.44, P<.01) compared to saline. On PPD 6, 30 mg/kg cocaine significantly increased OT levels by approximately 20.9% (picograms/brain area) in the AMY (F (2,25) = 3.44, P=.05) relative to saline. These findings suggest that acute cocaine may disrupt maternal behavior and maternal aggression at least in part through its action on the oxytocinergic system. PMID:11384208

  5. Swim test immobility in a genetic rat model of depression is modified by maternal environment: a cross-foster study.

    PubMed

    Friedman, Elliot; Berman, Marissa; Overstreet, David

    2006-03-01

    The Flinders sensitive line (FSL) genetic animal model of depression exhibits marked immobility during forced swimming, an accepted index of depressive like behavior in rodent depression models. The present experiment tested the hypothesis that swim test behavior in the FSL rats is influenced in part by early experience, specifically maternal environment. Male FSL and control Flinders resistant line (FRL) pups were cross fostered onto dams of the same or complementary strain. Nest quality and dam behavior during pup retrieval were measured on PN5 and PN8, and swim test behavior assessed in the adult males on PN60. FSL rats reared by foster FRL dams were significantly less immobile than FSL rats raised by FSL dams, but still significantly more immobile that the two FRL groups, which did not differ from each other. FSL dams took significantly longer to retrieve their pups and dropped them more often than the FRL control dams. Moreover, strain differences in maternal retrieval behavior significantly predicted later swim test immobility in the FSL animals. These findings suggest that swim test immobility in the FSL rats is modified by maternal environment. In contrast, the FRL control rats were relatively insensitive to the influence of maternal environment. The FSL model offers promise for understanding the interactions of genetic vulnerabilities and environmental influences in the etiology of clinical depression.

  6. Placental HSD2 Expression and Activity Is Unaffected by Maternal Protein Consumption or Gender in C57BL/6 Mice

    PubMed Central

    Garbrecht, Mark R.; Lamb, Fred S.

    2013-01-01

    The placenta acts as a physiological barrier, preventing the transfer of maternal glucocorticoids to the developing fetus. This is accomplished via the oxidation, and subsequent inactivation, of endogenous glucocorticoids by the 11-β hydroxysteroid dehydrogenase type 2 enzyme (HSD2). Maternal protein restriction during pregnancy has been shown to result in a decrease in placental HSD2 expression and fetal glucocorticoid overexposure, especially late in gestation, resulting in low birth weight and “fetal programming” of the offspring. This dietary intervention impairs fetal growth and cardiovascular function in adult C57BL/6 offspring, but the impact on placental HSD2 has not been defined. The goal of the current study was to examine the effects of a maternal low-protein diet (18% versus 9% protein) on placental HSD2 gene expression and enzyme activity in mice during late gestation. In contrast to previous studies in rats, a maternal low-protein diet did not affect HSD2 protein or enzyme activity levels in the placentas of C57BL/6 mice and this was irrespective of the gender of the offspring. These data suggest that the effects of maternal protein restriction on adult phenotypes in C57BL/6 mice depend upon a mechanism that may be independent of placental HSD2 or possibly occurs earlier in gestation. PMID:23781346

  7. Environmental prenatal stress alters sexual dimorphism of maternal behavior in rats.

    PubMed

    Pérez-Laso, Carmen; Segovia, Santiago; Martín, José Luis R; Ortega, Esperanza; Gómez, Francisco; Del Cerro, M Cruz R

    2008-03-01

    The prenatal external environment can affect fetuses, altering the maternal behavior that they express when mature. In the present study, environmental prenatal stress (EPS) was applied to pregnant rats in their final week of gestation, and when their female offspring reached maturity, the long latency effect of the stress on those offspring was ascertained on their induced maternal behavior (MB), accessory olfactory bulb (AOB) morphology and plasma levels of ACTH and corticosterone (Cpd B). EPS reduced: the percentage of these virgins that showed induced MB, their retrieval of foster pups, the time spent crouching, and the quality of nest building; it also increased the incidence of their cannibalism of foster pups. The EPS-treated females presented a male-like pattern of induced MB. They showed increased plasma levels of ACTH and Cpd B and increased numbers of mitral cells in the AOB. These findings provide evidence that stress applied to the pregnant rat produces long-lasting behavioral, neuroanatomical and hormonal alterations in the female offspring that can be observed when they reach maturity.

  8. Embryotoxic effects of brief maternal insulin-hypoglycemia during organogenesis in the rat.

    PubMed Central

    Buchanan, T A; Schemmer, J K; Freinkel, N

    1986-01-01

    To test whether maternal hypoglycemia can impair organogenesis, we induced brief glucopenia with insulin in conscious pregnant rats during either the headfold stage or the early neural tube closure stage of embryogenesis. At each time, 10 pairs of animals received identical insulin infusions for 1 h. Half the animals were maintained at euglycemia during the infusions, while the others were allowed to become hypoglycemic. Euglycemia was maintained or restored in all animals immediately after the insulin was stopped. Spontaneous activity was diminished during the hypoglycemia but consciousness was preserved. Embryos were removed from mothers and examined 2 d later. This examination revealed that embryos from the hypoglycemic mothers were growth-retarded and displayed a small but significant incidence of gross developmental anomalies compared with embryos from the insulin-infused euglycemic mothers. Thus, brief, mild maternal hypoglycemia during early organogenesis can disrupt normal embryo development in the rat. The effect is due to the hypoglycemia per se rather than to the insulin employed for its induction. PMID:3528219

  9. Neonatal Maternal Separation Augments Carotid Body Response to Hypoxia in Adult Males but Not Female Rats

    PubMed Central

    Soliz, Jorge; Tam, Rose; Kinkead, Richard

    2016-01-01

    Perinatal exposure to adverse experiences disrupts brain development, including the brainstem network that regulates breathing. At adulthood, rats previously subjected to stress (in the form of neonatal maternal separation; NMS) display features reported in patients suffering from sleep disordered breathing, including an increased hypoxic ventilatory response and hypertension. This effect is also sex-specific (males only). Based on these observations, we hypothesized that NMS augments the carotid body's O2-chemosensitivity. Using an isolated and perfused ex vivo carotid body preparation from adult rats we compared carotid sinus nerve (CSN) responses to hypoxia and hypercapnia in carotid bodies harvested from adult rats that either experienced control conditions (no experimental manipulation) or were subjected to NMS (3 h/day from postnatal days 3 to 12). In males, the CSN response to hypoxia measured in preparations from NMS males was 1.5 fold higher than controls. In control rats, the female's response was similar to that of males; however, the increase in CSN activity measured in NMS females was 3.0 times lower than controls. The CSN response to hypercapnia was not influenced by stress or sex. We conclude that NMS is sufficient to have persistent and sex-specific effects on the carotid body's response to hypoxia. Because NMS also has sex-specific effects on the neuroendocrine response to stress, we propose that carotid body function is influenced by stress hormones. This, in turn, leads to a predisposition toward cardio-respiratory disorders. PMID:27729873

  10. Maternal dietary omega-3 fatty acid intake increases resolvin and protectin levels in the rat placenta

    PubMed Central

    Jones, Megan L.; Mark, Peter J.; Keelan, Jeffrey A.; Barden, Anne; Mas, Emilie; Mori, Trevor A.; Waddell, Brendan J.

    2013-01-01

    Placental inflammation is associated with several pregnancy disorders. Inflammation is limited by anti-inflammatory and proresolving mechanisms, the latter partly mediated by resolvins and protectins derived from omega-3 polyunsaturated fatty acids (n-3PUFA). We examined effects of dietary n-3PUFAs on levels of resolvins, protectins, and lipoxygenase (ALOX) enzymes in the rat placenta. Rats consumed standard (Std) or high n-3PUFA (Hn3) diets from day 1 of pregnancy; tissues were collected on day 17 or 22 (term = day 23). Maternal Hn3 diet increased resolvin and protectin precursors, 18R/S-HEPE (P < 0.001), and 17R/S-HDHA (P < 0.01) at both days. Resolvins (17R-RvD1 and RvD1) increased at day 22 (P < 0.001) after Hn3 consumption, coincident with higher Alox15b and Alox5 mRNA expression, while RvD2 increased at both days (P < 0.05). Protectins, PD1, and 10S,17S-DiHDHA increased over late gestation (P < 0.001), coincident with higher Alox15 mRNA expression (P < 0.001) and further increased with Hn3 diet (P < 0.05). Maternal systemic and placental proinflammatory mediators were not suppressed by Hn3 diet; systemic IL1β, placental Il1β, and Il6 mRNA expression increased marginally with Hn3 at day 22 (P < 0.001), while Ptgs1 (Cox1) expression increased both days (P < 0.05). Our data indicate that maternal n-3PUFA supplementation enhances expression of enzymes in the n-3PUFA metabolic pathway and increases placental levels of resolvins and protectins. PMID:23723388

  11. Limited Nesting Stress Alters Maternal Behavior and In Vivo Intestinal Permeability in Male Wistar Pup Rats

    PubMed Central

    Moussaoui, Nabila; Larauche, Muriel; Biraud, Mandy; Molet, Jenny; Million, Mulugeta; Mayer, Emeran; Taché, Yvette

    2016-01-01

    A few studies indicate that limited nesting stress (LNS) alters maternal behavior and the hypothalamic pituitary adrenal (HPA) axis of dams and offspring in male Sprague Dawley rats. In the present study, we evaluated the impact of LNS on maternal behavior in Wistar rats, and on the HPA axis, glycemia and in vivo intestinal permeability of male and female offspring. Intestinal permeability is known to be elevated during the first week postnatally and influenced by glucocorticoids. Dams and neonatal litters were subjected to LNS or normal nesting conditions (control) from days 2 to 10 postnatally. At day 10, blood was collected from pups for determination of glucose and plasma corticosterone by enzyme immunoassay and in vivo intestinal permeability by oral gavage of fluorescein isothiocyanate–dextran 4kDa. Dams exposed to LNS compared to control showed an increase in the percentage of time spent building a nest (118%), self-grooming (69%), and putting the pups back to the nest (167%). LNS male and female pups exhibited a reduction of body weight by 5% and 4%, adrenal weights/100g body weight by 17% and 18%, corticosterone plasma levels by 64% and 62% and blood glucose by 11% and 12% respectively compared to same sex control pups. In male LNS pups, intestinal permeability was increased by 2.7-fold while no change was observed in females compared to same sex control. There was no sex difference in any of the parameters in control pups except the body weight. These data indicate that Wistar dams subjected to LNS during the first postnatal week have an altered repertoire of maternal behaviors which affects the development of the HPA axis in both sexes and intestinal barrier function in male offspring. PMID:27149676

  12. Chronic Nicotine Exposure Abolishes Maternal Systemic and Renal Adaptations to Pregnancy in Rats.

    PubMed

    Ferreira, Vanessa Meira; Passos, Clevia Santos; Maquigussa, Edgar; Pontes, Roberto Braz; Bergamaschi, Cassia Toledo; Campos, Ruy Ribeiro; Boim, Mirian Aparecida

    2016-01-01

    Pregnancy is characterized by maternal systemic and intrarenal vasodilation, leading to increases in the renal plasma flow (RPF) and glomerular filtration rate (GFR). These responses are mainly mediated by nitric oxide (NO) and relaxin. The impact of cigarette smoking on the maternal adaptations to pregnancy is unclear. Here we evaluated the effects of chronic exposure to nicotine on systemic and intrarenal parameters in virgin (V) and 14-day pregnant (P) Wistar rats. V and P groups received saline or nicotine (6 mg·kg(-1)·day(-1)) respectively, via osmotic minipumps for 28 days, starting 14 days before pregnancy induction. Nicotine induced a 10% increase in blood pressure in the V group and minimized the characteristic pregnancy-induced hypotension. Renal sympathetic nerve activity (rSNA) and baroreflex sensitivity were impaired by nicotine mainly in the P group, indicating that the effect of nicotine on blood pressure was not mediated by nervous system stimulation. Nicotine had no effect on GFR in the V rats but reduced GFR of the P group by 30%. Renal expression of sodium and water transporters was downregulated by nicotine, resulting in increased fractional sodium excretion mainly in the P group, suggesting that nicotine compromised the sodium and water retention required for normal gestation. There was a reduction in the expression of inducible NO synthase (iNOS) in both the kidney tissue and renal artery, as well as in the expression of the relaxin receptor (LGR7). These results clearly show that nicotine induced deleterious effects in both virgin and pregnant animals, and abolished the maternal capacity to adapt to pregnancy.

  13. Effect of maternal exercise on biochemical parameters in rats submitted to neonatal hypoxia-ischemia.

    PubMed

    Marcelino, Thiago Beltram; de Lemos Rodrigues, Patrícia Idalina; Miguel, Patrícia Maidana; Netto, Carlos Alexandre; Pereira Silva, Lenir Orlandi; Matté, Cristiane

    2015-10-01

    Pregnancy is a critical period for brain metabolic programming, being affected by individual environment, such as nutrition, stress, and physical exercise. In this context, we previously reported a cerebral antioxidant upregulation and mitochondrial biogenesis in the offspring delivered from exercised mothers, which could provide neuroprotection against neonatal insults. Hypoxia-ischemia (HI) encephalopathy is one of the most studied models of neonatal brain injury; disrupting motor, cognitive, and learning abilities. Physiopathology includes oxidative stress, allied to mitochondria energy production failure, glutamatergic excitotoxicity, and cell death. In this study we evaluated the effect of maternal swimming during pregnancy on offspring׳s brain oxidative status evaluated fourteen days after HI stablishment. Swimming exercise was performed by female adult rats one week before and during pregnancy, in controlled environment. Their offspring was submitted to HI on postnatal day 7, and the brain samples for biochemical assays were obtained in the weaning. Contrary to our expectations, maternal exercise did not prevent the oxidative alterations observed in brain from HI-rats. In a general way, we found a positive modulation in the activities of antioxidant enzymes, measured two weeks after HI, in hippocampus, striatum, and cerebellum of pups delivered from exercised mothers. Reactive species levels were modulated differently in each structure evaluated. Considering the scenery presented, we concluded that HI elicited a neurometabolic adaptation in both brain hemispheres, particularly in hippocampus, parietal cortex, and cerebellum; while striatum appears to be most damaged. The protocol of aerobic maternal exercise was not enough to fully prevent HI-induced brain damages. PMID:26119914

  14. Sex-dependent effects of maternal deprivation and adolescent cannabinoid treatment on adult rat behaviour.

    PubMed

    Llorente-Berzal, Alvaro; Fuentes, Sílvia; Gagliano, Humberto; López-Gallardo, Meritxell; Armario, Antonio; Viveros, María-Paz; Nadal, Roser

    2011-10-01

    Early life experiences such as maternal deprivation (MD) exert long-lasting changes in adult behaviour and reactivity to stressors. Adolescent exposure to cannabinoids is a predisposing factor in developing certain psychiatric disorders. Therefore, the combination of the two factors could exacerbate the negative consequences of each factor when evaluated at adulthood. The objective of this study was to investigate the long-term effects of early MD [24 hours at postnatal day (PND) 9] and/or an adolescent chronic treatment with the cannabinoid agonist CP-55,940 (0.4 mg/kg, PND 28-42) on diverse behavioural and physiological responses of adult male and female Wistar rats. We tested them in the prepulse inhibition (PPI) of the startle response and analysed their exploratory activity (holeboard) and anxiety (elevated plus maze, EPM). In addition, we evaluated their adrenocortical reactivity in response to stress and plasma leptin levels. Maternal behaviour was measured before and after deprivation. MD induced a transient increase of maternal behaviour on reuniting. In adulthood, maternally deprived males showed anxiolytic-like behaviour (or increased risk-taking behaviour) in the EPM. Adolescent exposure to the cannabinoid agonist induced an impairment of the PPI in females and increased adrenocortical responsiveness to the PPI test in males. Both, MD and adolescent cannabinoid exposure also induced sex-dependent changes in plasma leptin levels and body weights. The present results indicate that early MD and adolescent cannabinoid exposure exerted distinct sex-dependent long-term behavioural and physiological modifications that could predispose to the development of certain neuropsychiatric disorders, though no synergistic effects were found.

  15. Prenatal exposure to integerrimine N-oxide impaired the maternal care and the physical and behavioral development of offspring rats.

    PubMed

    Sandini, Thaísa M; Udo, Mariana S B; Reis-Silva, Thiago M; Bernardi, Maria Martha; Spinosa, Helenice de S

    2014-08-01

    Plants that contain pyrrolizidine alkaloids (PAs) have been reported as contaminants of pastures and food, as well as being used in herbal medicine. PAs are responsible for poisoning events in livestock and human beings. The aim of this present study was to evaluate effects of prenatal exposure to integerrimine N-oxide, the main PA found in the butanolic residue (BR) of Senecio brasiliensis, on both physical and behavioral parameters of Wistar rat offspring. The toxicity and maternal behavior were also evaluated. For this, pregnant Wistar rats received integerrimine N-oxide from the BR of Senecio brasiliensis, by gavage, on gestational days 6-20 (during organogenesis and fetal development period) at doses of 3, 6 and 9 mg/kg. During treatment, maternal body weight gain, and food and water intake were evaluated. After parturition, maternal behavior and aggressive maternal behavior were analyzed. In addition, physical development and behavioral assessments were observed in both male and female pups. Results showed that prenatal exposure to integerrimine N-oxide of S. brasiliensis induced maternal toxicity, impairment in maternal behavior and aggressive maternal behavior, mainly in the highest dose group. Between sexes comparison of pups showed loss of body weight, delayed physical development such as pinna detachment, hair growth, eruption of incisor teeth, eye and vaginal openings. These pups also showed a delay of palmar grasp, surface righting reflex, negative geotaxis and auditory startle reflexes. Thus, prenatal exposure to integerrimine N-oxide induces maternal toxicity, impairment of maternal care and delayed in physical and behavioral development of the offspring.

  16. Prenatal exposure to integerrimine N-oxide impaired the maternal care and the physical and behavioral development of offspring rats.

    PubMed

    Sandini, Thaísa M; Udo, Mariana S B; Reis-Silva, Thiago M; Bernardi, Maria Martha; Spinosa, Helenice de S

    2014-08-01

    Plants that contain pyrrolizidine alkaloids (PAs) have been reported as contaminants of pastures and food, as well as being used in herbal medicine. PAs are responsible for poisoning events in livestock and human beings. The aim of this present study was to evaluate effects of prenatal exposure to integerrimine N-oxide, the main PA found in the butanolic residue (BR) of Senecio brasiliensis, on both physical and behavioral parameters of Wistar rat offspring. The toxicity and maternal behavior were also evaluated. For this, pregnant Wistar rats received integerrimine N-oxide from the BR of Senecio brasiliensis, by gavage, on gestational days 6-20 (during organogenesis and fetal development period) at doses of 3, 6 and 9 mg/kg. During treatment, maternal body weight gain, and food and water intake were evaluated. After parturition, maternal behavior and aggressive maternal behavior were analyzed. In addition, physical development and behavioral assessments were observed in both male and female pups. Results showed that prenatal exposure to integerrimine N-oxide of S. brasiliensis induced maternal toxicity, impairment in maternal behavior and aggressive maternal behavior, mainly in the highest dose group. Between sexes comparison of pups showed loss of body weight, delayed physical development such as pinna detachment, hair growth, eruption of incisor teeth, eye and vaginal openings. These pups also showed a delay of palmar grasp, surface righting reflex, negative geotaxis and auditory startle reflexes. Thus, prenatal exposure to integerrimine N-oxide induces maternal toxicity, impairment of maternal care and delayed in physical and behavioral development of the offspring. PMID:24881561

  17. Treadmill exercise during pregnancy ameliorates post‑traumatic stress disorder‑induced anxiety‑like responses in maternal rats.

    PubMed

    Seo, Jin-Hee; Kim, Tae-Woon; Kim, Chang-Ju; Sung, Yun-Hee; Lee, Sam-Jun

    2013-02-01

    Post‑traumatic stress disorder (PTSD) is an anxiety disorder triggered by life‑threatening events that cause intense fear. Exercise is known to have protective effects on neuropsychiatric diseases. The present study investigated whether treadmill exercise during pregnancy reduced or alleviated symptoms of PTSD in maternal rats. To induce predator stress in pregnant rats, rats were exposed to a hunting dog in an enclosed room. Exposure time was three 10‑min daily sessions separated by 1 h, starting at week 1 of pregnancy until delivery. Pregnant rats in the exercise group were forced to run on a treadmill for 30 min once a day, starting one week following pregnancy until delivery. Rats receiving predator stress during pregnancy exhibited PTSD anxiety‑like behaviors following delivery. Expression of 5‑hydroxytryptamine (5‑HT) and its synthesizing enzyme tryptophan hydroxylase (TPH) in the dorsal raphe was increased compared with unstressed rats. Expression of c‑Fos and neuronal nitric oxide synthases (nNOS) in the hypothalamus and locus coeruleus were higher in the rats receiving stress during pregnancy compared with unstressed rats. By contrast, treadmill exercise during pregnancy ameliorated anxiety‑like behaviors and reduced the expression of 5‑HT, TPH, c‑Fos and nNOS in the PTSD maternal rats. The results of the present study indicate that exercise during pregnancy is suitable for use as a therapeutic strategy to reduce anxiety‑related disorders, including PTSD.

  18. Effects of genistein in the maternal diet on reproductive development and spatial learning in male rats

    PubMed Central

    Ball, Evan R.; Caniglia, Mary Kay; Wilcox, Jenna L.; Overton, Karla A.; Burr, Marra J.; Wolfe, Brady D.; Sanders, Brian J.; Wisniewski, Amy B.; Wrenn, Craige C.

    2010-01-01

    Endocrine disruptors, chemicals that disturb the actions of endogenous hormones, have been implicated in birth defects associated with hormone-dependent development. Phytoestrogens are a class of endocrine disruptors found in plants. In the current study we examined the effects of exposure at various perinatal time periods to genistein, a soy phytoestrogen, on reproductive development and learning in male rats. Dams were fed genistein-containing (5 mg/kg feed) food during both gestation and lactation, during gestation only, during lactation only, or during neither period. Measures of reproductive development and body mass were taken in the male offspring during postnatal development, and learning and memory performance was assessed in adulthood. Genistein exposure via the maternal diet decreased body mass in the male offspring of dams fed genistein during both gestation and lactation, during lactation only, but not during gestation only. Genistein decreased anogenital distance when exposure was during both gestation and lactation, but there was no effect when exposure was limited to one of these time periods. Similarly, spatial learning in the Morris water maze was impaired in male rats exposed to genistein during both gestation and lactation, but not in rats exposed during only one of these time periods. There was no effect of genistein on cued or contextual fear conditioning. In summary, the data indicate that exposure to genistein through the maternal diet significantly impacts growth in male offspring if exposure is during lactation. The effects of genistein on reproductive development and spatial learning required exposure throughout the pre- and postnatal periods. PMID:20053350

  19. Long Lasting Microvascular Tone Alteration in Rat Offspring Exposed In Utero to Maternal Hyperglycaemia

    PubMed Central

    Vessières, Emilie; Dib, Abdallah; Bourreau, Jennifer; Lelièvre, Eric; Custaud, Marc-Antoine; Lelièvre-Pégorier, Martine; Loufrani, Laurent; Henrion, Daniel; Fassot, Céline

    2016-01-01

    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. PMID:26756337

  20. Neonatal maternal separation up-regulates protein signalling for cell survival in rat hypothalamus.

    PubMed

    Irles, Claudine; Nava-Kopp, Alicia T; Morán, Julio; Zhang, Limei

    2014-05-01

    We have previously reported that in response to early life stress, such as maternal hyperthyroidism and maternal separation (MS), the rat hypothalamic vasopressinergic system becomes up-regulated, showing enlarged nuclear volume and cell number, with stress hyperresponsivity and high anxiety during adulthood. The detailed signaling pathways involving cell death/survival, modified by adverse experiences in this developmental window remains unknown. Here, we report the effects of MS on cellular density and time-dependent fluctuations of the expression of pro- and anti-apoptotic factors during the development of the hypothalamus. Neonatal male rats were exposed to 3 h-daily MS from postnatal days 2 to 15 (PND 2-15). Cellular density was assessed in the hypothalamus at PND 21 using methylene blue staining, and neuronal nuclear specific protein and glial fibrillary acidic protein immunostaining at PND 36. Expression of factors related to apoptosis and cell survival in the hypothalamus was examined at PND 1, 3, 6, 9, 12, 15, 20 and 43 by Western blot. Rats subjected to MS exhibited greater cell-density and increased neuronal density in all hypothalamic regions assessed. The time course of protein expression in the postnatal brain showed: (1) decreased expression of active caspase 3; (2) increased Bcl-2/Bax ratio; (3) increased activation of ERK1/2, Akt and inactivation of Bad; PND 15 and PND 20 were the most prominent time-points. These data indicate that MS can induce hypothalamic structural reorganization by promoting survival, suppressing cell death pathways, increasing cellular density which may alter the contribution of these modified regions to homeostasis.

  1. Escitalopram improves memory deficits induced by maternal separation in the rat.

    PubMed

    Couto, Frederico Simões do; Batalha, Vânia L; Valadas, Jorge S; Data-Franca, João; Ribeiro, Joaquim A; Lopes, Luísa V

    2012-11-15

    Maternal separation (MS) induces depressive-like behavior and long-term changes in cognition in rats. Escitalopram is an antidepressant drug shown to reverse the depressive-like features caused by this stress model. However, it is not known if it can ameliorate the affected cognition. We now characterized the effect of escitalopram on hippocampal-dependent memory in rats submitted to the MS protocol. Male Wistar rats were assigned either to control (CTR) or maternal separated (MS) group. MS were separated from their dams between 2-14 postnatal days (PND) for 180min daily. Escitalopram was given in food pellets (0.34g/kg/day first 2 weeks and 0.41g/kg/day the subsequent period, average dose 25mg/kg) from PND 43 onwards, during 1 month. Depressive behavior was assessed in the forced swimming test (FST), and memory performance in the Morris water maze (MWM). Escitalopram significantly improved the FST's latency to despair in the MS group (n=6), but did not change the immobility time. All groups showed a significant learning effect in the MWM over time, but no differences have been found upon treatment (n=6). However, escitalopram treatment significantly increased the time spent on the platform quadrant in the probe trial in the MS group. We report here that chronic treatment with escitalopram is able to improve hippocampal dependent memory in a chronic stress model, while not changing the learning ability. Moreover, this is accompanied by an amelioration of the depressive like behavior. These results support the use of escitalopram to tackle underlying cognitive deficits caused by stress in early-life.

  2. Could maternal exposure to the antidepressants fluoxetine and St. John's Wort induce long-term reproductive effects on male rats?

    PubMed

    Vieira, Milene Leivas; Hamada, Renata Yumi; Gonzaga, Natalia Ignácio; Bacchi, Andre Demambre; Barbieri, Mainara; Moreira, Estefânia Gastaldello; Mesquita, Suzana de Fátima Paccola; Gerardin, Daniela Cristina Ceccatto

    2013-01-01

    Based on the limited number of studies that have investigated the adverse effects of maternal treatment with antidepressants on the development of male descendents, this study was carried out in rat in order to evaluate if maternal exposure to fluoxetine (FLX) or St. John's Wort (SJW) could disrupt the development of male offspring. The dams were treated daily, by gavage, with 7.5 mg/kg of FLX or 100 mg/kg SJW during pregnancy and lactation. The reproductive and behavior parameters were analyzed in male pups. Results showed decreases in the weight of the full seminal vesicle and in the number of spermatozoa. Moreover, FLX-exposed pups presented reduced seminiferous epithelium height and diameter of seminiferous tubules. The present study shows that maternal exposure to FLX, but not SJW could interfere on reproductive parameters in adult male rats.

  3. Maternal obesity characterized by gestational diabetes increases the susceptibility of rat offspring to hepatic steatosis via a disrupted liver metabolome.

    PubMed

    Pereira, Troy J; Fonseca, Mario A; Campbell, Kristyn E; Moyce, Brittany L; Cole, Laura K; Hatch, Grant M; Doucette, Christine A; Klein, Julianne; Aliani, Michel; Dolinsky, Vernon W

    2015-07-15

    Maternal obesity is associated with a high risk for gestational diabetes mellitus (GDM), which is a common complication of pregnancy. The influence of maternal obesity and GDM on the metabolic health of the offspring is poorly understood. We hypothesize that GDM associated with maternal obesity will cause obesity, insulin resistance and hepatic steatosis in the offspring. Female Sprague-Dawley rats were fed a high-fat (45%) and sucrose (HFS) diet to cause maternal obesity and GDM. Lean control pregnant rats received low-fat (LF; 10%) diets. To investigate the interaction between the prenatal environment and postnatal diets, rat offspring were assigned to LF or HFS diets for 12 weeks, and insulin sensitivity and hepatic steatosis were evaluated. Pregnant GDM dams exhibited excessive gestational weight gain, hyperinsulinaemia and hyperglycaemia. Offspring of GDM dams gained more weight than the offspring of lean dams due to excess adiposity. The offspring of GDM dams also developed hepatic steatosis and insulin resistance. The postnatal consumption of a LF diet did not protect offspring of GDM dams against these metabolic disorders. Analysis of the hepatic metabolome revealed increased diacylglycerol and reduced phosphatidylethanolamine in the offspring of GDM dams compared to offspring of lean dams. Consistent with altered lipid metabolism, the expression of CTP:phosphoethanolamine cytidylyltransferase, and peroxisomal proliferator activated receptor-α mRNA was reduced in the livers of GDM offspring. GDM exposure programs gene expression and hepatic metabolite levels and drives the development of hepatic steatosis and insulin resistance in young adult rat offspring.

  4. Maternal obesity during gestation impairs fatty acid oxidation and mitochondrial SIRT3 expression in rat offspring at weaning

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In utero exposure to maternal obesity increases the offspring’s risk of obesity in later life. We have also previously reported that offspring of obese rat dams develop hepatic steatosis, mild hyperinsulinemia, and a lipogenic gene signature in the liver at postnatal day (PND) 21. In the current s...

  5. Ultrasonic vocalization responses of rat pups to acute separation and contact comfort do not depend on maternal thermal cues.

    PubMed

    Hofer, M A; Brunelli, S A; Shair, H N

    1993-03-01

    In order to assess the importance of maternal thermal cues in controlling the acute USV responses of rat pups to contact with her body (the contact comfort response) and to separation from her, we drastically altered maternal temperature by inducing severe hypothermia so that maternal rectal and flank temperatures averaged more than 20 degrees C below normal and 10 degrees C below ambient levels during testing. Isolated 12- to 13-day-old pups showed reductions in USV when these cold dams were presented and brisk USV accelerations when the cold dams were removed from the test chamber. These responses closely resembled those of other pups tested with warm (36 degrees C) anesthetized dams. No significant differences were found in pups' USV contact comfort responses to cold and warm dams. For acute separation, prior maternal thermal properties and other factors were found to modulate the relative intensity of the marked USV increase elicited by this event.

  6. Maternal age effects on myometrial expression of contractile proteins, uterine gene expression, and contractile activity during labor in the rat

    PubMed Central

    Elmes, Matthew; Szyszka, Alexandra; Pauliat, Caroline; Clifford, Bethan; Daniel, Zoe; Cheng, Zhangrui; Wathes, Claire; McMullen, Sarah

    2015-01-01

    Advanced maternal age of first time pregnant mothers is associated with prolonged and dysfunctional labor and significant risk of emergency cesarean section. We investigated the influence of maternal age on myometrial contractility, expression of contractile associated proteins (CAPs), and global gene expression in the parturient uterus. Female Wistar rats either 8 (YOUNG n = 10) or 24 (OLDER n = 10) weeks old were fed laboratory chow, mated, and killed during parturition. Myometrial strips were dissected to determine contractile activity, cholesterol (CHOL) and triglycerides (TAG) content, protein expression of connexin-43 (GJA1), prostaglandin-endoperoxide synthase 2 (PTGS2), and caveolin 1 (CAV-1). Maternal plasma concentrations of prostaglandins PGE2, PGF2α, and progesterone were determined by RIA. Global gene expression in uterine samples was compared using Affymetrix Genechip Gene 2.0 ST arrays and Ingenuity Pathway analysis (IPA). Spontaneous contractility in myometrium exhibited by YOUNG rats was threefold greater than OLDER animals (P < 0.027) but maternal age had no significant effect on myometrial CAP expression, lipid profiles, or pregnancy-related hormones. OLDER myometrium increased contractile activity in response to PGF2α, phenylephrine, and carbachol, a response absent in YOUNG rats (all P < 0.002). Microarray analysis identified that maternal age affected expression of genes related to immune and inflammatory responses, lipid transport and metabolism, steroid metabolism, tissue remodeling, and smooth muscle contraction. In conclusion YOUNG laboring rat myometrium seems primed to contract maximally, whereas activity is blunted in OLDER animals and requires stimulation to meet contractile potential. Further work investigating maternal age effects on myometrial function is required with focus on lipid metabolism and inflammatory pathways. PMID:25876907

  7. The Effects of L-arginine on the Hippocampus of Male Rat Fetuses under Maternal Stress

    PubMed Central

    Mahmoudi, Reza; Enant, Elham; Delaviz, Hamdollah; Rad, Parastou; Roozbehi, Amrollah; Jafari Barmak, Mehrzad; Azizi, Arsalan

    2016-01-01

    Introduction: Prenatal stress has deleterious effects on the development of the brain and is associated with behavioral and psychosocial problems in childhood and adulthood. This study aimed to determine the protective effect of L-arginine on fetal brain under maternal stress. Methods: Twenty pregnant Wistar rats (weighting 200–230 g) were randomly divided into 4 groups (n=5 for each group). The first nonstress and stress groups received 2 mL of normal saline and the other nonstress and stress two groups received L-arginine (200 mg/kg, IP) from their 5th to 20th days of pregnancy. The pregnant rats were killed on 20th day and the brain fetuses removed and prefrontal cortical thickness, total neurons in the prefrontal cortex and in the areas of CA1, CA2, and CA3 of the hippocampus were measured and counted. Nitrite levels in the brain were measured as an indicator for nitric oxide (NO) level. Results: There was a significant decrease of mean number of pyramidal cells in the CA1 in prenatal stress group compared to nonstress and nonstress plus arginine groups. The NO level in brain tissue increased significantly in the stress plus arginine (3.8±0.4 nmol/mg) and in nonstress rats (2.9±0.3 nmol/mg) compared to the stress group (1.8±0.1 nmol/mg). Prefrontal cortical thickness decreased significantly in stress rats (1.2±0.09 mm) compared to the nonstress plus arginine (1.7±0.15 mm) and nonstress (1.6±0.13 mm) groups. Discussion: Results indicated that prenatal stress could lead to neurodegeneration of hippocampus and prefrontal cortex of rat fetuses. L-arginine as a precursor of NO synthesis had neuroprotective effect during prenatal stress and could be used an effective treatment for stress. PMID:27303594

  8. Effects of running wheel training on adult obese rats programmed by maternal prolactin inhibition.

    PubMed

    Boaventura, G; Casimiro-Lopes, G; Pazos-Moura, C C; Oliveira, E; Lisboa, P C; Moura, E G

    2013-10-01

    The inhibition of maternal prolactin production in late lactation leads to metabolic syndrome and hypothyroidism in adult offspring. Physical training is a therapeutic strategy that could prevent or reverse this condition. We evaluated the effects of a short-duration low-intensity running wheel training program on the metabolic and hormonal alterations in rats. Lactating Wistar rats were treated with bromocriptine (Bro, 1 mg twice a day) or saline on days 19, 20, and 21 of lactation, and the training of offspring began at 35 days of age. Offspring were divided into sedentary and trained controls (C-Sed and C-Ex) and sedentary and trained Bro-treated rats (Bro-Sed and Bro-Ex). Chronic exercise delayed the onset of weight gain in Bro-Ex offspring, and the food intake did not change during the experimental period. At 180 days, visceral fat mass was higher (+46%) in the Bro-Sed offspring than in C-Sed and Bro-Ex rats. As expected, running capacity was higher in trained animals. Most parameters observed in the Bro-Sed offspring were consistent with hypothyroidism and metabolic syndrome and were reversed in the Bro-Ex group. Chronic exercise did not influence the muscle glycogen in the C-Ex group; however, liver glycogen was higher (+30%) in C-Ex group and was unchanged in both Bro offspring groups. Bro-Ex animals had higher plasma lactate dehydrogenase levels, indicating skeletal muscle damage and intolerance of the training program. Low-intensity chronic training is able to normalize many clinical aspects in Bro animals; however, these animals might have had a lower threshold for exercise adaptation than the control rats. PMID:23863192

  9. Female rats are resistant to developing the depressive phenotype induced by maternal separation stress.

    PubMed

    Dimatelis, J J; Vermeulen, I M; Bugarith, K; Stein, D J; Russell, V A

    2016-02-01

    Many stress-related psychiatric disorders are more common in women than in men. We aimed to determine how female rats respond to maternal separation (MS; removal of the dam from the litter for 3 h/day from postnatal day (P) 2-14)). A subset of MS females were also exposed to chronic constant light for 3 weeks during adolescence (P42-63) to investigate whether the antidepressant effect of light treatment, previously observed in male rats, could be seen in female rats. Ultrasonic vocalizations (22 kHz) were recorded and the forced swim test was conducted immediately after light exposure (P65-67) and 33 days later (P98-99) to determine depressive-like behaviour. Key proteins in the MAPK signal transduction pathway (MKP-1, phospho-ERK, total ERK) and a synaptosomal marker (synaptophysin) were measured in the ventral hippocampus. We found that MS decreased the duration of 22 kHz vocalizations at P65 which was reversed by subsequent light. Light exposure increased time spent in the inner zone of the open field and the number of 22 kHz calls in response to novelty at P98. MS decreased the time females spent immobile and increased time actively swimming in the forced swim test at P67 but not at P99. MKP-1 and synaptophysin levels remained unchanged while MS decreased phospho-ERK levels in the ventral hippocampus. In contrast to clinical findings, the results suggest that female rats may be resistant to MS-induced depression-like behaviour. The behavioural effects of MS and light treatment in female rats may involve the MAPK/ERK signal transduction pathway.

  10. Maternal Omega-3 Supplementation Increases Fat Mass in Male and Female Rat Offspring

    PubMed Central

    Muhlhausler, Beverly Sara; Miljkovic, Dijana; Fong, Laura; Xian, Cory J.; Duthoit, Emmanuelle; Gibson, Robert A.

    2011-01-01

    Adipogenesis and lipogenesis are highly sensitive to the nutritional environment in utero and in early postnatal life. Omega-3 long chain polyunsaturated fatty acids (LCPUFA) inhibit adipogenesis and lipogenesis in adult rats, however it is not known whether supplementing the maternal diet with omega-3 LCPUFA results in reduced fat deposition in the offspring. Female Albino Wistar rats were fed either a standard chow (Control, n = 10) or chow designed to provide ∼15 mg/kg/day of omega-3 LCPUFA, chiefly as docosahexaenoic acid (DHA), throughout pregnancy and lactation (Omega-3, n = 11) and all pups were weaned onto a commercial rat chow. Blood and tissues were collected from pups at 3 and 6 weeks of age and weights of visceral and subcutaneous fat depots recorded. The expression of adipogenic and lipogenic genes in the subcutaneous and visceral fat depots were determined using quantitative real time reverse transcription-PCR. Birth weight and postnatal growth were not different between groups. At 6 weeks of age, total percentage body fat was significantly increased in both male (5.09 ± 0.32% vs. 4.56 ± 0.2%, P < 0.04) and female (5.15 ± 0.37% vs. 3.89 ± 0.36%, P < 0.04) offspring of omega-3 dams compared to controls. The omega-3 LCPUFA content of erythrocyte phospholipids (as a% of total fatty acids) was higher in omega-3 offspring (6.7 ± 0.2% vs. 5.6 ± 0.2%, P < 0.001). There was no effect of maternal omega-3 LCPUFA supplementation on the expression of adipogenic or lipogenic genes in the offspring in either the visceral or subcutaneous fat depots. We have therefore established that an omega-3 rich environment during pregnancy and lactation in a rodent model increases fat accumulation in both male and female offspring, particularly in subcutaneous depots, but that this effect is not mediated via upregulation adipogenic/lipogenic gene transcription. These data suggest that maternal n−3 LCPUFA

  11. Effect of maternal deprivation on N-acetyltransferase activity rhythm in blinded rat pups.

    PubMed

    Katoh, Y; Takeuchi, Y; Yamazaki, K; Takahashi, K

    1998-02-15

    It has been reported that the rhythms of infant rats synchronize with the mother's rhythm until the light-dark cycle comes and has strong effects on their endogenous clocks. We found that periodic maternal deprivation (PMD) was able to cause a phase shift of serotonin N-acetyltransferase (NAT) in neonatal blinded rat pups. PMD in which contact with the mother was allowed for only 4 h caused a phase shift of NAT rhythm, irrespective of the timing of contact with the mother in a day. Acute single mother deprivation caused an excess of NAT activity for more hours than usual and contact with the mother prevented such an excessive response. Mother deprivation may act as a cold stress, since artificial warming of pups gave the same results as contact with the mother. When the pups were artificially warmed by a heater during a 1-week deprivation period, a flat 24-h pattern of NAT was observed. The mechanism causing a phase shift of NAT activity rhythm of rat pups may be complicated. PMID:9523895

  12. Postnatal maternal separation modifies the response to an obesogenic diet in adulthood in rats

    PubMed Central

    Paternain, Laura; Martisova, Eva; Milagro, Fermín I.; Ramírez, María J.; Martínez, J. Alfredo; Campión, Javier

    2012-01-01

    SUMMARY An early-life adverse environment has been implicated in the susceptibility to different diseases in adulthood, such as mental disorders, diabetes and obesity. We analyzed the effects of a high-fat sucrose (HFS) diet for 35 days in adult female rats that had experienced 180 minutes daily of maternal separation (MS) during lactancy. Changes in the obesity phenotype, biochemical profile, levels of glucocorticoid metabolism biomarkers, and the expression of different obesity- and glucocorticoid-metabolism-related genes were analyzed in periovaric adipose tissue. HFS intake increased body weight, adiposity and serum leptin levels, whereas MS decreased fat pad masses but only in rats fed an HFS diet. MS reduced insulin resistance markers but only in chow-fed rats. Corticosterone and estradiol serum levels did not change in this experimental model. A multiple gene expression analysis revealed that the expression of adiponutrin (Adpn) was increased owing to MS, and an interaction between HFS diet intake and MS was observed in the mRNA levels of leptin (Lep) and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (Ppargc1a). These results revealed that early-life stress affects the response to an HFS diet later in life, and that this response can lead to phenotype and transcriptomic changes. PMID:22773756

  13. Sex-dependent maternal deprivation effects on brain monoamine content in adolescent rats.

    PubMed

    Llorente, Ricardo; O'Shea, Esther; Gutierrez-Lopez, M Dolores; Llorente-Berzal, Alvaro; Colado, María Isabel; Viveros, María-Paz

    2010-07-26

    Rats subjected to a single prolonged episode of maternal deprivation (MD) [24h, postnatal days 9-10] show, later in life, behavioural alterations that resemble specific signs of schizophrenia and other neuropsychiatric signs including increased levels of impulsivity and an apparent difficulty to cope with stressful situations. Some of these behavioural modifications are observable in the periadolescent period. However there is no previous information regarding the possible underlying neurochemical correlates at this critical developmental period. In this study we have addressed the effects of MD on the levels of serotonin (5-HT), dopamine (DA) and their respective metabolites in prefrontal cortex, hippocampus, striatum, midbrain and cerebellum of male and female periadolescent Wistar rats. MD rats showed significantly increased levels of 5-HT in all regions studied with the exception of cerebellum. In addition, MD animals showed increased levels of DA in PFC as well as increased levels of DA and a decrease of DOPAC/DA and HVA/DA ratios in striatum. The effect of MD on the monoaminergic systems was in several cases sex-dependent.

  14. Effects of maternal stress on development and behaviour in rat offspring.

    PubMed

    Weinstock, M

    2001-09-01

    Retrospective studies suggest that gestational stress in humans can delay the attainment of developmental milestones, increase the incidence of allergic reactions and respiratory infections and cause behavioural abnormalities in the children. Our studies and others have shown that prenatal stress in rats can mimic several of these developmental and behavioural alterations. These include a suppression of immune function, but also enhanced sensitivity to allergens. Prenatally-stressed rats, like children, show a reduced propensity for social interaction and increased anxiety in intimidating or novel situations. They have physiological and behavioural alterations consistent with depressive symptoms, including a phase-shift in their circadian rhythm for corticosterone, sleep abnormalities, and greater acquisition of learned helplessness under appropriate conditions. Prenatally-stressed male rats also show demasculinisation and feminisation of their sexual behaviour. The developmental and behavioural abnormalities in prenatally-stressed offspring may be mediated by alterations in the activity of endogenous opioids or neurosteroids, since several of them can be corrected by maternal administration of an opioid antagonist or by drugs like diazepam and allopregnanolone that modulate GABA transmission. PMID:22432137

  15. Maternal separation is associated with DNA methylation and behavioural changes in adult rats.

    PubMed

    Anier, Kaili; Malinovskaja, Kristina; Pruus, Katrin; Aonurm-Helm, Anu; Zharkovsky, Alexander; Kalda, Anti

    2014-03-01

    Early life stress is known to promote long-term neurobiological changes, which may underlie the increased risk of psychopathology. Maternal separation (MS) is used as an early life stressor that causes profound neurochemical and behavioural changes in the pups that persist into adulthood. However, the exact mechanism of how MS alters these behavioural changes is not yet understood. Epigenetic modifications, such as DNA methylation, are critical regulators of persistent gene expression changes and may be related to behavioural disorders. The aim of the present study was to investigate whether early life stress on rats could alter cocaine-induced behavioural sensitisation in adulthood via aberrant DNA methylation. We have three main findings: (1) MS increased DNA methyltransferases (DNMTs) expression in the nucleus accumbens (NAc) of infant and adult rats; (2) MS induced DNA hypomethylation on a global level in the NAc, and hypermethylation of the promoter regions of the protein phosphatase 1 catalytic subunit (PP1C) and adenosine A2Areceptor (A2AR) genes, which was associated with their transcriptional downregulation in the NAc; (3) MS-induced molecular changes paralleled an increased response to cocaine-induced locomotor activity and exploratory behaviour in adult rats. Thus, our results suggest that stressful experiences in early life may create a background, via aberrant DNA methylation, which promotes the development of cocaine-induced behavioural sensitisation in adulthood. PMID:23972903

  16. Maternal metallothionein and zinc after acute ethanol exposure during gestation in the rat

    SciTech Connect

    Harris, J.E. )

    1992-02-26

    Acute exposure of the rat fetus to ethanol at critical periods can cause growth retardation and brain damage; the mechanism(s) is not known. Ethanol may cause redistribution of maternal zinc which results in fetal zinc deficiency and subsequent interruption of growth and development. The purpose was to determine if acute ethanol administration to the pregnant rat alters Zn and the Zn binding protein metallothionein (MT) in selected tissues. On gestational day (gd) 14, eighteen pregnant Sprague-Dawley rats were divided into groups. By intragastric tube, ethanol treated dams were given ethanol and pairfed controls were given a 0.85% NaCl solution. On gd 15, intragastric feedings were repeated. Throughout, the Lieber-DeCarli control diet was fed (adlibitum to untreated controls and ethanol treated dams and in appropriate quantities to pair fed controls). Blood ethanol concentrations at 90 minutes after the ethanol dose were 154 {plus minus} 46 and 265 {plus minus} 110 mg% on gd 14 and 15, respectively.

  17. Maternal behavior induced in male rats by bilateral lesions of the bed nucleus of the accessory olfactory tract.

    PubMed

    Izquierdo, M A; Collado, P; Segovia, S; Guillamón, A; del Cerro, M C

    1992-10-01

    In the present study, we investigate the effect of bilateral electrolytic lesions of the bed nucleus of the accessory olfactory tract (BAOT) in male Wistar rats that did not have care-pups experience, using a test of induced maternal behavior. Consistent with our previous findings in virgin female rats (10), there was a significantly shorter sensitization (3 days) and retrieval (2 days) latencies in the BAOT-lesioned group than in the sham-lesioned and intact-control male groups (12 days for both). Based on these findings, we propose that BAOT, a sexually dimorphic nucleus of the vomeronasal system, exerts an inhibitory modulation in the expression of parental behavior in male and female virgin rats. It may do so by maintaining an olfactory-based tonic inhibition of maternal behavior, thereby resulting in the adults' tonic avoidance of the pups until this inhibition is abolished by lesion, or reduced or overridden by appropriate hormonal and/or sensory influences.

  18. Combined Norepinephrine/Serotonergic Reuptake Inhibition: Effects on Maternal Behavior, Aggression, and Oxytocin in the Rat

    PubMed Central

    Cox, Elizabeth Thomas; Jarrett, Thomas Merryfield; McMurray, Matthew Stephen; Greenhill, Kevin; Hofler, Vivian E.; Williams, Sarah Kaye; Joyner, Paul Wayland; Middleton, Christopher L.; Walker, Cheryl H.; Johns, Josephine M.

    2011-01-01

    Background: Few systematic studies exist on the effects of chronic reuptake of monoamine neurotransmitter systems during pregnancy on the regulation of maternal behavior (MB), although many drugs act primarily through one or more of these systems. Previous studies examining fluoxetine and amfonelic acid treatment during gestation on subsequent MB in rodents indicated significant alterations in postpartum maternal care, aggression, and oxytocin levels. In this study, we extended our studies to include chronic gestational treatment with desipramine or amitriptyline to examine differential effects of reuptake inhibition of norepinephrine and combined noradrenergic and serotonergic systems on MB, aggression, and oxytocin system changes. Methods: Pregnant Sprague-Dawley rats were treated throughout gestation with saline or one of three doses of either desipramine, which has a high affinity for the norepinephrine monoamine transporter, or amitriptyline, an agent with high affinity for both the norepinephrine and serotonin monoamine transporters. MB and postpartum aggression were assessed on postpartum days 1 and 6 respectively. Oxytocin levels were measured in relevant brain regions on postpartum day 7. Predictions were that amitriptyline would decrease MB and increase aggression relative to desipramine, particularly at higher doses. Amygdaloidal oxytocin was expected to decrease with increased aggression. Results: Amitriptyline and desipramine differentially reduced MB, and at higher doses reduced aggressive behavior. Hippocampal oxytocin levels were lower after treatment with either drug but were not correlated with specific behavioral effects. These results, in combination with previous findings following gestational treatment with other selective neurotransmitter reuptake inhibitors, highlight the diverse effects of multiple monoamine systems thought to be involved in maternal care. PMID:21713063

  19. Exposure to low levels of hydrogen sulfide elevates circulating glucose in maternal rats

    SciTech Connect

    Hayden, L.J.; Goeden, H.; Roth, S.H. )

    1990-09-01

    Although the lethal effect of hydrogen sulfide (H{sub 2}S) has long been known, the results of exposure to low levels of H{sub 2}S have not been well documented. Rat dams and pups were exposed to low levels of H{sub 2}S (less than or equal to 75 ppm) from d 1 of gestation until d 21 postpartum and analyzed for changes in circulating enzymatic activity and metabolites. Blood glucose was significantly elevated in maternal blood on d 21 postpartum at all exposure levels. This increase in glucose was accompanied by a possible decrease in serum triglyceride in the pups and in the dams on d 21 postpartum. There was no evidence of alterations in serum alkaline phosphatase, lactate dehydrogenase, or serum glutamate oxaloacetate transaminase.

  20. Maternal Hyperglycemia Directly and Rapidly Induces Cardiac Septal Overgrowth in Fetal Rats

    PubMed Central

    Gordon, Erin E.; Reinking, Benjamin E.; Hu, Shanming; Yao, Jianrong; Kua, Kok L.; Younes, Areej K.; Wang, Chunlin; Segar, Jeffrey L.; Norris, Andrew W.

    2015-01-01

    Cardiac septal overgrowth complicates 10–40% of births from diabetic mothers, but perplexingly hyperglycemia markers during pregnancy are not reliably predictive. We thus tested whether fetal exposure to hyperglycemia is sufficient to induce fetal cardiac septal overgrowth even in the absence of systemic maternal diabetes. To isolate the effects of hyperglycemia, we infused glucose into the blood supply of the left but not right uterine horn in nondiabetic pregnant rats starting on gestational day 19. After 24 h infusion, right-sided fetuses and dams remained euglycemic while left-sided fetuses were moderately hyperglycemic. Echocardiograms in utero demonstrated a thickened cardiac septum among left-sided (glucose-exposed, 0.592 ± 0.016 mm) compared to right-sided (control, 0.482 ± 0.016 mm) fetuses. Myocardial proliferation was increased 1.5 ± 0.2-fold among left-sided compared to right-sided fetuses. Transcriptional markers of glucose-derived anabolism were not different between sides. However, left-sided fetuses exhibited higher serum insulin and greater JNK phosphorylation compared to controls. These results show that hyperglycemic exposure is sufficient to rapidly induce septal overgrowth even in the absence of the myriad other factors of maternal diabetes. This suggests that even transient spikes in glucose may incite cardiac overgrowth, perhaps explaining the poor clinical correlation of septal hypertrophy with chronic hyperglycemia. PMID:26064981

  1. Early maternal deprivation in rats induces gender-dependent effects on developing hippocampal and cerebellar cells.

    PubMed

    Llorente, Ricardo; Gallardo, Meritxell López; Berzal, Alvaro Llorente; Prada, Carmen; Garcia-Segura, Luis Miguel; Viveros, María-Paz

    2009-05-01

    Adult animals submitted to a single prolonged episode of maternal deprivation [24h, postnatal day 9-10] show behavioral alterations that resemble specific symptoms of schizophrenia. According to the neurodevelopmental theory, these behavioral deficits might be mediated by detrimental neurodevelopmental processes that might be associated, at least partially, with stress-induced corticosterone responses. In order to address this hypothesis, we have focused on the hippocampus and cerebellar cortex, two brain regions that show high density of glucocorticoid receptors, and analyzed possible neuronal and glial alterations by immunohistochemical techniques. To evaluate the presence of degenerated neurons we used Fluoro-Jade-C (FJ-C) staining and for the study of astrocytes we employed glial fibrillary acidic protein (GFAP). Within control animals, females showed significantly more GFAP positive cells than males and a trend towards more FJ-C positive cells. Maternal deprivation induced neuronal degeneration and astroglial changes in the hippocampus and cerebellar cortex of neonatal rats that, in general, were more marked in males. This differential effect may be attributable to a greater vulnerability of males to this kind of early environmental insult and/or to sex-dependent differences in the onset and/or progression of the effects. The present experimental procedure may be instrumental in elucidating sex-dependent mechanisms of neurodevelopmental psychiatric disorders with a basis in early environmental insults.

  2. Power spectrum analysis of ultrasonic vocalization elicited by maternal separation in rat pups.

    PubMed

    Ise, Satoko; Ohta, Hisashi

    2009-08-01

    The present study investigated how frequency distribution of maternal separation-induced ultrasonic vocalization was altered by environmental stimuli and pharmacological agents. Sprague-Dawley rat pups at 10 days were used to measure numbers and frequencies of the ultrasonic vocalizations under various ambient temperatures and with pharmacological manipulations of the corticotropin-releasing factor (CRF) and GABAergic systems. The ultrasonic vocalization consisted of two distinct peaks in the frequency range of 30 kHz to 50 kHz. The area under the curve (AUC) in the high-frequency range and the number of the ultrasonic vocalizations increased when ambient temperature was lowered. Systemic administration of a selective CRF1 receptor antagonist, NBI27914, and a typical anxiolytic, diazepam, decreased the AUC in the high-frequency range and the number of the ultrasonic vocalizations in a dose-dependent manner at an ambient temperature of 24 degrees C. The AUC in the low-frequency range did not change with an alteration in ambient temperature or treatment with NBI27914 and diazepam except a high dose (1 mg/kg) of diazepam. These results demonstrated that emotional levels of isolated pups reflected not only the number but also the frequency distribution of maternal separation-induced ultrasonic vocalizations. High-frequency components, but not low-frequency components, of the ultrasonic vocalization were sensitive to changes in negative affective state of isolated pups.

  3. Power spectrum analysis of ultrasonic vocalization elicited by maternal separation in rat pups.

    PubMed

    Ise, Satoko; Ohta, Hisashi

    2009-08-01

    The present study investigated how frequency distribution of maternal separation-induced ultrasonic vocalization was altered by environmental stimuli and pharmacological agents. Sprague-Dawley rat pups at 10 days were used to measure numbers and frequencies of the ultrasonic vocalizations under various ambient temperatures and with pharmacological manipulations of the corticotropin-releasing factor (CRF) and GABAergic systems. The ultrasonic vocalization consisted of two distinct peaks in the frequency range of 30 kHz to 50 kHz. The area under the curve (AUC) in the high-frequency range and the number of the ultrasonic vocalizations increased when ambient temperature was lowered. Systemic administration of a selective CRF1 receptor antagonist, NBI27914, and a typical anxiolytic, diazepam, decreased the AUC in the high-frequency range and the number of the ultrasonic vocalizations in a dose-dependent manner at an ambient temperature of 24 degrees C. The AUC in the low-frequency range did not change with an alteration in ambient temperature or treatment with NBI27914 and diazepam except a high dose (1 mg/kg) of diazepam. These results demonstrated that emotional levels of isolated pups reflected not only the number but also the frequency distribution of maternal separation-induced ultrasonic vocalizations. High-frequency components, but not low-frequency components, of the ultrasonic vocalization were sensitive to changes in negative affective state of isolated pups. PMID:19523931

  4. Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood

    PubMed Central

    Krstew, Elena V.; Tait, Robert J.; Hulse, Gary K.

    2012-01-01

    Naltrexone is not recommended during pregnancy. However, sustained-release naltrexone implant use in humans has resulted in cases of inadvertent foetal exposure. Here, we used clinically relevant dosing to examine the effects of maternally administered sustained-release naltrexone on the rat brain by examining offspring at birth and in adulthood. Maternal treatment (naltrexone or placebo implant) started before conception and ceased during gestation, birth or weaning. Morphometry was assessed in offspring at birth and adulthood. Adult offspring were evaluated for differences in locomotor behaviour (basal and morphine-induced, 10 mg/kg, s.c.) and opioid neurochemistry, propensity to self-administer morphine and cue-induced drug-seeking after abstinence. Blood analysis confirmed offspring exposure to naltrexone during gestation, birth and weaning. Naltrexone exposure increased litter size and reduced offspring birth-weight but did not alter brain morphometry. Compared to placebo, basal motor activity of naltrexone-exposed adult offspring was lower, yet they showed enhanced development of psychomotor sensitization to morphine. Developmental naltrexone exposure was associated with resistance to morphine-induced down-regulation of striatal preproenkephalin mRNA expression in adulthood. Adult offspring also exhibited greater operant responding for morphine and, in addition, cue-induced drug-seeking was enhanced. Collectively, these data show pronounced effects of developmental naltrexone exposure, some of which persist into adulthood, highlighting the need for follow up of humans that were exposed to naltrexone in utero. PMID:23300784

  5. Behavioral and Pharmacological Investigation of Anxiety and Maternal Responsiveness of Postpartum Female Rats in a Pup Elevated Plus Maze

    PubMed Central

    Yang, Yu; Qin, Jingxue; Chen, Weihai; Sui, Nan; Chen, Hong; Li, Ming

    2015-01-01

    The present study investigated the validity of a novel pup-based repeated elevated plus maze task to detect reduced anxiety and increased maternal responsiveness in postpartum female rats and explored the roles of dopamine D2, serotonin transporter and GABA/benzodiazepine receptors in the mediation of these processes. Sprague-Dawley postpartum or nulliparous female rats were tested 4 times every other day on postpartum days 4, 6 and 8 in an elevated plus maze with 4 pups or 4 pup-size erasers placed on each end of the two open arms. When tested with erasers, untreated postpartum mother rats entered the open arms proportionally more than nulliparous rats. They also tended to spend more time in the open arms, indicating reduced anxiety. When tested with pups, postpartum rats retrieved pups into the closed arms, entered the open arms and closed arms more and had a higher moving speed than nulliparous rats, indicating increased maternal responsiveness. Both haloperidol (0.1 or 0.2 mg/kg, sc) and fluoxetine (5 or 10 mg/kg, ip) dose- and time-dependently decreased the percentage of time spent in the open arms and speed, but did not affect the percentage of open arm entries. Diazepam (1.0 or 2.0 mg/kg, ip) did not affect pup retrieval, open arm time/entry in lactating rats. Thus, the percentage of open arm entries appears to be the most sensitive measure of anxiety in postpartum female rats, while speed could be used to index maternal responsiveness to pups, which are likely mediated by the dopamine D2 and serotonin transporter systems. PMID:26159828

  6. Evaluation of neonatally-induced mild diabetes in rats: Maternal and fetal repercussions

    PubMed Central

    2010-01-01

    Many experimental studies have been performed to evaluate mild diabetes effects. However, results are divergent regarding glycemia and insulin measurement, fetal macrossomia, and placental weights. The aim was to investigate repercussions of neonatally-induced mild diabetes on the maternal organism and presence of congenital defects in their offspring in other mild diabetes model. On the day of birth, female offspring were distributed into two groups: Group streptozotocin (STZ): received 100 mg STZ/kg body weight, and Control Group: received vehicle in a similar time period. Maternal weights and glycemias were determined at days 0, 7, 14 and 21 of pregnancy. At day 21 of pregnancy, the rats were anesthetized and a laparotomy was performed to weigh and analyze living fetuses and placentas. The fetuses were classified as small (SPA), appropriate (APA) and large (LPA) for pregnancy age. Fetuses were also analyzed for the presence of external anomalies and processed for skeletal anomaly and ossification sites analysis. Statistical significance was considered as p < 0.05. In STZ group, there was increased glycemia at 0 and 14 days of pregnancy, lower weights throughout pregnancy, higher placental weight and index, an increased proportion of fetuses classified as SPA and LPA, and their fetuses presented with an increased frequency of abnormal sternebra, and absent cervical nuclei, which were not enough to cause the emergence of skeletal anomalies. Thus, this study shows that mild diabetes altered fetal development, characterized by intrauterine growth restriction. Further, the reached glycemia does not lead to any major congenital defects in the fetuses of streptozotocin-induced mild diabetic rats. PMID:20529353

  7. Anxiety-like behaviour in adult rats perinatally exposed to maternal calorie restriction.

    PubMed

    Levay, Elizabeth A; Paolini, Antonio G; Govic, Antonina; Hazi, Agnes; Penman, Jim; Kent, Stephen

    2008-08-22

    Environmental stimuli such as caloric availability during the perinatal period exert a profound influence on the development of an organism. Studies in this domain have focused on the effects of under- and malnutrition while the effects of more mild levels of restriction have not been delineated. Rat dams and their offspring were subjected to one of five dietary regimens: control, CR50% for 3 days preconception, CR25% during gestation, CR25% during lactation, and CR25% during gestation, lactation, and post-weaning (lifelong). The pup retrieval test and maternal observations were conducted during lactation to quantify maternal care. In the pup retrieval test, dams that were concurrently experiencing CR (i.e., from the lactation and lifelong groups) displayed shorter latencies to retrieve all pups than the control and preconception groups and the lactation group constructed better nests than all groups. Adult offspring were tested in three tests of anxiety: the elevated plus maze, open field, and emergence test. No differences were observed in the elevated plus maze; however, in the open field preconception animals made fewer entries and spent more time in the central zone than controls. In addition, preconception offspring exhibited longer latencies to full body emergence, spent less time fully emerged, and spent more time engaged in risk assessment behaviours than all other groups. Offspring from the preconception group were also on average 11% heavier than control rats throughout life and displayed 37% higher serum leptin concentrations than controls. A potential role for leptin in the anxiogenic effect of preconception CR is discussed.

  8. Maternal Oxytocin Administration Before Birth Influences the Effects of Birth Anoxia on the Neonatal Rat Brain.

    PubMed

    Boksa, Patricia; Zhang, Ying; Nouel, Dominique

    2015-08-01

    Ineffective contractions and prolonged labor are common birth complications in primiparous women, and oxytocin is the most common agent given for induction or augmentation of labor. Clinical studies in humans suggest oxytocin might adversely affect the CNS response to hypoxia at birth. In this study, we used a rat model of global anoxia during Cesarean section birth to test if administering oxytocin to pregnant dams prior to birth affects the acute neonatal CNS response to birth anoxia. Anoxic pups born from dams pre-treated with intravenous injections or infusions of oxytocin before birth showed significantly increased brain lactate, a metabolic indicator of CNS hypoxia, compared to anoxic pups from dams pre-treated with saline. Anoxic pups born from dams given oxytocin before birth also showed decreased brain ATP compared to anoxic pups from saline dams. Direct injection of oxytocin to postnatal day 2 rat pups followed by exposure to anoxia also resulted in increased brain lactate and decreased brain ATP, compared to anoxia exposure alone. Oxytocin pre-treatment of the dam decreased brain malondialdehyde, a marker of lipid peroxidation, as well as protein kinase C activity, both in anoxic pups and controls, suggesting oxytocin may reduce aspects of oxidative stress. Finally, when dams were pretreated with indomethacin, a cyclooxygenase (COX) inhibitor, maternal oxytocin no longer potentiated effects of anoxia on neonatal brain lactate, suggesting this effect of oxytocin may be mediated via prostaglandin production or other COX-derived products. The results indicate that maternal oxytocin administration may have multiple acute effects on CNS metabolic responses to anoxia at birth.

  9. Influence of maternal cadmium exposure or fetal cadmium injection on hepatic metallothionein concentrations in the fetal rat

    SciTech Connect

    Sasser, L.B.; Kelman, B.J.; Levin, A.A.; Miller, R.K.

    1985-01-01

    The ability of Cd to induce the synthesis of fetal hepatic metallothionein (MT) was investigated in rat fetuses exposed to Cd throughout gestation via the mother's drinking water or injected directly with Cd through the uterine wall on Day 18 of gestation. On Day 21 all dams were killed and fetal and maternal tissues were removed. Tissue MT, Zn, Cu, and Cd concentrations were measured. Fetal hepatic Cd concentration was increased only at the high maternal Cd exposure, whereas Zn concentration was significantly reduced by Cd exposure. Both fetal liver and kidney MT were reduced following maternal Cd exposure. Unlike maternal hepatic MT, fetal hepatic MT was not increased after maternal Cd exposure nor did the direct injection of Cd into the 18 days of gestation fetus induce fetal MT synthesis. These data suggest that fetal rat liver is incapable of synthesizing MT in response to Cd, possibly because Cd is not transported to the site of MT synthesis in the fetal system. Furthermore, neither the route of exposure, the duration of prenatal Cd exposure, nor the stage of gestation appear to account for the differences observed between fetal and adult hepatic MT induction by Cd. 47 references, 6 tables.

  10. Influence of maternal hyperthyroidism in the rat on the expression of neuronal and astrocytic cytoskeletal proteins in fetal brain.

    PubMed

    Evans, I M; Pickard, M R; Sinha, A K; Leonard, A J; Sampson, D C; Ekins, R P

    2002-12-01

    Maternal hypothyroidism during pregnancy impairs brain function in human and rat offspring, but little is known regarding the influence of maternal hyperthyroidism on neurodevelopment. We have previously shown that the expression of neuronal and glial differentiation markers in fetal brain is compromised in hypothyroid rat dam pregnancies and have now therefore extended this investigation to hyperthyroid rat dams. Study groups comprised partially thyroidectomised dams, implanted with osmotic pumps infusing either vehicle (TX dams) or a supraphysiological dose of thyroxine (T4) (HYPER dams), and euthyroid dams infused with vehicle (N dams). Cytoskeletal protein abundance was determined in fetal brain at 21 days of gestation by immunoblot analysis. Relative to N dams, circulating total T4 levels were reduced to around one-third in TX dams but were doubled in HYPER dams. Fetal brain weight was increased in HYPER dams, whereas litter size and fetal body weight were reduced in TX dams. Glial fibrillary acidic protein expression was similar in HYPER and TX dams, being reduced in both cases relative to N dams. alpha-Internexin (INX) abundance was reduced in HYPER dams and increased in TX dams, whereas neurofilament 68 (NF68) exhibited increased abundance in HYPER dams. Furthermore, INX was inversely related to - and NF68 directly related to - maternal serum total T4 levels, independently of fetal brain weight. In conclusion, maternal hyperthyroidism compromises the expression of neuronal cytoskeletal proteins in late fetal brain, suggestive of a pattern of accelerated neuronal differentiation.

  11. Maternal and Fetal Blood and Organ Toluene Levels in Rats Following Acute and Repeated Binge Inhalation Exposure

    PubMed Central

    Bowen, Scott E.; Hannigan, John H.; Irtenkauf, Susan

    2007-01-01

    Inhalation of organic solvents is a persistent form of drug abuse with particular concern being the abuse of inhalants by women of child-bearing age. While studies have begun assessing postnatal outcomes of offspring exposed prenatally to inhalants, relatively little is known about the distribution of toluene in blood and body tissues of pregnant, inhalant-abusing women, or in the fetuses. The present study assessed the tissue toluene levels attained following brief toluene exposures using a pre-clinical rat model of maternal inhalant abuse. Timed-pregnant Sprague-Dawley rats were exposed to toluene at 8,000 or 12,000 parts per million (ppm) for 15, 30 or 45 min/exposure. Exposures occurred twice each day from gestational day 8 (GD8) through GD20. Immediately following the second exposure on GD8, GD14 and GD20 blood was taken from the saphenous vein of the dams. Following saphenous vein blood collection on GD20, dams were sacrificed and trunk blood was collected along with maternal tissue specimens from cerebellum, heart, lung, kidney and liver. The placenta, amniotic fluid and fetal brain were also collected. Results demonstrated that maternal saphenous blood toluene levels increased as the inhaled concentration of toluene and duration of exposure increased. The maternal cerebellum, heart, kidney and liver appeared to be saturated after 30 min on GD20 such that toluene levels in those organs were equivalent across all ambient concentrations of inhaled toluene. Toluene levels also increased in fetal brain as the inhaled concentration of toluene increased and in placenta and amniotic fluid as the duration of exposure increased. Toluene levels in all tissues at GD20, except maternal lung and amniotic fluid, were higher than in maternal saphenous blood suggesting that toluene concentrated in those organs. Measurement of toluene levels in blood and other tissues following repeated toluene exposure demonstrated that toluene readily reaches a variety of potential sites

  12. Evidences that maternal swimming exercise improves antioxidant defenses and induces mitochondrial biogenesis in the brain of young Wistar rats.

    PubMed

    Marcelino, T B; Longoni, A; Kudo, K Y; Stone, V; Rech, A; de Assis, A M; Scherer, E B S; da Cunha, M J; Wyse, A T S; Pettenuzzo, L F; Leipnitz, G; Matté, C

    2013-08-29

    Physical exercise during pregnancy has been considered beneficial to mother and child. Recent studies showed that maternal swimming improves memory in the offspring, increases hippocampal neurogenesis and levels of neurotrophic factors. The objective of this work was to investigate the effect of maternal swimming during pregnancy on redox status and mitochondrial parameters in brain structures from the offspring. Adult female Wistar rats were submitted to five swimming sessions (30 min/day) prior to mating with adult male Wistar rats, and then trained during the pregnancy (five sessions of 30-min swimming/week). The litter was sacrificed when 7 days old, when cerebellum, parietal cortex, hippocampus, and striatum were dissected. We evaluated the production of reactive species and antioxidant status, measuring the activities of superoxide-dismutase (SOD), catalase (CAT) and glutathione-peroxidase (GPx), as well as non-enzymatic antioxidants. We also investigated a potential mitochondrial biogenesis regarding mitochondrion mass and membrane potential, through cytometric approaches. Our results showed that maternal swimming exercise promoted an increase in reactive species levels in cerebellum, parietal cortex, and hippocampus, demonstrated by an increase in dichlorofluorescein oxidation. Mitochondrial superoxide was reduced in cerebellum and parietal cortex, while nitrite levels were increased in cerebellum, parietal cortex, hippocampus, and striatum. Antioxidant status was improved in cerebellum, parietal cortex, and hippocampus. SOD activity was increased in parietal cortex, and was not altered in the remaining brain structures. CAT and GPx activities, as well as non-enzymatic antioxidant potential, were increased in cerebellum, parietal cortex, and hippocampus of rats whose mothers were exercised. Finally, we observed an increased mitochondrial mass and membrane potential, suggesting mitochondriogenesis, in cerebellum and parietal cortex of pups subjected to

  13. Effect of essential oil from Citrus aurantium in maternal reproductive outcome and fetal anomaly frequency in rats.

    PubMed

    Volpato, Gustavo T; Francia-Farje, Luis A D; Damasceno, Débora C; Oliveira, Renata V; Hiruma-Lima, Clélia A; Kempinas, Wilma G

    2015-03-01

    Citrus aurantium L., commonly known as bitter orange, is widely used in folk medicine, but there is little data in the literature about the effects on pregnancy. The aim of the present study was to evaluate the influence of essential oil obtained from fruits of Citrus aurantium on the maternal reproductive outcome and fetal anomaly incidence in rats. Pregnant Wistar rats were randomized into four groups (n minimum = 12 animals/group): G1 = control, G2 to G4 = treated with essential oil from C. aurantium at dose 125, 250 and 500 mg/kg, respectively. Rats were orally treated, by gavage, with plant essential oil or vehicle during pre-implantation and organogenic period (gestational day 0-14). On gestational day 20 the rats were anaesthetized and the gravid uterus was weighed with its contents and the fetuses were analyzed. Results showed that the treated group with 500 mg/kg presented decreased placental weights and placental index, although the treatment with bitter orange essential oil did not show any alteration in maternal reproductive performance, toxicological effect, changes in ossification sites, and malformation index. In conclusion, the treatment of Citrus aurantium essential oil was not teratogenic and did not alter the maternal reproductive outcome. PMID:25806990

  14. Effects of Maternal Dietary Restriction of Vitamin B-6 on Neocortex Development in Rats

    NASA Astrophysics Data System (ADS)

    Groziak, Susan Marie

    The aim of this investigation was to quantitate the effects of a dietary restriction in Vitamin B-6 during gestation or gestation and lactation on neurogenesis, neuron longevity and neuron differentiation in the neocortex of rats. Sprague Dawley female rats were fed, ad libitum, a Vitamin B-6 free diet (AIN 76) supplemented with 0.0 or 0.6 mg pyridoxine (PN)/kg diet during gestation followed by a control level of 7.0 mg PN/kg diet during lactation, or were fed the Vitamin B-6 free diet supplemented with 0.6 or 7.0 mg PN/kg diet throughout gestation and lactation. The neocortex of progeny of these animals were examined at 30 days of age employing light and electron microscopy. Analyses of neurogenesis, neuron longevity and differentiation of neurons (size of somata, dendritic arborization and spine density in Golgi Cox preparations, and synaptic density in E.M. preparations) were conducted. Each of the Vitamin B-6 restricted treatments adversely affected neurogenesis, neuron longevity and neuron differentiation. The degree of adverse effects paralleled the severity (dose or duration) of the restriction imposed. Expressed as percentage reduction from control values, the findings indicated that neuron longevity and differentiation of neurons in the neocortex were more severely affected than neurogenesis by a maternal dietary restriction in Vitamin B-6.

  15. Maternal separation increases methamphetamine-induced damage in the striatum in male, but not female rats.

    PubMed

    Hensleigh, Emily; Pritchard, Laurel M

    2015-12-15

    Methamphetamine abuse impacts the global economy through costs associated with drug enforcement, emergency room visits, and treatment. Previous research has demonstrated early life stress, such as childhood abuse, increases the likelihood of developing a substance abuse disorder. However, the effects of early life stress on neuronal damage induced by binge methamphetamine administration are unknown. We aimed to elucidate the effects of early life stress on methamphetamine induced dopamine damage in the striatum. Pups were separated from dams for 3h per day during the first two weeks of development or 15 min for control. In adulthood, rats received either subcutaneous 0.9% saline or 5.0mg/kg METH injections every 2h for a total of four injections. Rectal temperatures were taken before the first injection and 1h after each subsequent injection. Seven days after treatment, rats were euthanized and striatum was collected for quantification of tyrosine hydroxylase (TH) and dopamine transporters (DAT) content by Western blot. Methamphetamine significantly elevated core body temperature in males and decreased striatal DAT and TH content, and this effect was potentiated by early life stress. Females did not exhibit elevated core body temperatures or changes in DAT or TH in either condition. Results indicate maternal separation increases methamphetamine induced damage, and females are less susceptible to methamphetamine induced damage.

  16. Maternal green tea extract supplementation to rats fed a high-fat diet ameliorates insulin resistance in adult male offspring.

    PubMed

    Li, Shiying; Tse, Iris M Y; Li, Edmund T S

    2012-12-01

    Maternal overnutrition is associated with increased risk of metabolic disorders in the offspring. This study tested the hypothesis that maternal green tea (GT) supplementation can alleviate metabolic derangements in high-fat-diet-fed rats born of obese dams. Female Sprague-Dawley rats were fed low-fat (LF, 7%), high-fat (HF, 30%) or HF diet containing 0.75% or 1.0% GT extract (GT1, GT2) prior to conception and throughout gestation and lactation. Both doses of GT significantly improved metabolic parameters of HF-fed lactating dams (P<.05). Birth weight and litter size of offspring from HF dams were similar, but GT supplementation led to lighter pups on day 21 (P<.05). The weaned male pups received HF, GT1 or GT2 diet (dam/pup diet groups: LF/HF, HF/HF, HF/GT1, HF/GT2, GT1/HF and GT2/HF). At week 13, they had similar weight but insulin resistance index (IRI), serum nonesterified fatty acid (NEFA) and liver triglyceride of rats born to GT dams were 57%, 23% and 26% lower, accompanied by improved gene/protein expressions related to lipid and glucose metabolism, compared with the HF/HF rats (P<.05). Although HF/GT1 and HF/GT2 rats had lower serum NEFA, their insulin and IRI were comparable to HF/HF rats. This study shows that metabolic derangements induced by an overnourished mother could be offset by supplementing GT to the maternal diet and that this approach is more effective than giving GT to offspring since weaning. Hence, adverse effects of developmental programming are reversible, at least in part, by supplementing bioactive food component(s) to the mother's diet.

  17. Maternal Dietary Supplementation with Oligofructose-Enriched Inulin in Gestating/Lactating Rats Preserves Maternal Bone and Improves Bone Microarchitecture in Their Offspring.

    PubMed

    Bueno-Vargas, Pilar; Manzano, Manuel; Diaz-Castro, Javier; López-Aliaga, Inmaculada; Rueda, Ricardo; López-Pedrosa, Jose María

    2016-01-01

    Nutrition during pregnancy and lactation could exert a key role not only on maternal bone, but also could influence the skeletal development of the offspring. This study was performed in rats to assess the relationship between maternal dietary intake of prebiotic oligofructose-enriched inulin and its role in bone turnover during gestation and lactation, as well as its effect on offspring peak bone mass/architecture during early adulthood. Rat dams were fed either with standard rodent diet (CC group), calcium-fortified diet (Ca group), or prebiotic oligofructose-enriched inulin supplemented diet (Pre group), during the second half of gestation and lactation. Bone mineral density (BMD) and content (BMC), as well as micro-structure of dams and offspring at different stages were analysed. Dams in the Pre group had significantly higher trabecular thickness (Tb.Th), trabecular bone volume fraction (BV/TV) and smaller specific bone surface (BS/BV) of the tibia in comparison with CC dams. The Pre group offspring during early adulthood had an increase of the lumbar vertebra BMD when compared with offspring of CC and Ca groups. The Pre group offspring also showed significant increase versus CC in cancellous and cortical structural parameters of the lumbar vertebra 4 such as Tb.Th, cortical BMD and decreased BS/BV. The results indicate that oligofructose-enriched inulin supplementation can be considered as a plausible nutritional option for protecting against maternal bone loss during gestation and lactation preventing bone fragility and for optimizing peak bone mass and architecture of the offspring in order to increase bone strength.

  18. Maternal Dietary Supplementation with Oligofructose-Enriched Inulin in Gestating/Lactating Rats Preserves Maternal Bone and Improves Bone Microarchitecture in Their Offspring

    PubMed Central

    Diaz-Castro, Javier; López-Aliaga, Inmaculada; Rueda, Ricardo

    2016-01-01

    Nutrition during pregnancy and lactation could exert a key role not only on maternal bone, but also could influence the skeletal development of the offspring. This study was performed in rats to assess the relationship between maternal dietary intake of prebiotic oligofructose-enriched inulin and its role in bone turnover during gestation and lactation, as well as its effect on offspring peak bone mass/architecture during early adulthood. Rat dams were fed either with standard rodent diet (CC group), calcium-fortified diet (Ca group), or prebiotic oligofructose-enriched inulin supplemented diet (Pre group), during the second half of gestation and lactation. Bone mineral density (BMD) and content (BMC), as well as micro-structure of dams and offspring at different stages were analysed. Dams in the Pre group had significantly higher trabecular thickness (Tb.Th), trabecular bone volume fraction (BV/TV) and smaller specific bone surface (BS/BV) of the tibia in comparison with CC dams. The Pre group offspring during early adulthood had an increase of the lumbar vertebra BMD when compared with offspring of CC and Ca groups. The Pre group offspring also showed significant increase versus CC in cancellous and cortical structural parameters of the lumbar vertebra 4 such as Tb.Th, cortical BMD and decreased BS/BV. The results indicate that oligofructose-enriched inulin supplementation can be considered as a plausible nutritional option for protecting against maternal bone loss during gestation and lactation preventing bone fragility and for optimizing peak bone mass and architecture of the offspring in order to increase bone strength. PMID:27115490

  19. [Maternal methyl-containing dietary supplementation alters the ability to learn in adult rats in swimming Morris test].

    PubMed

    Pliusnina, I Z; Os'kina, I N; Shchepina, O A; Prasolova, L A; Trut, L N

    2006-01-01

    Maternal choline diet influences the spatial learning processes. In this work, the learning ability of adult progeny of mothers who had received methyl diet enriched with choline and betain during pregnancy and lactation was studied in Morris test. The introduction of the diet to pregnant rats resulted in an increase in the time of search for invisible platform and time of swimming near the pool walls in offsprings, which meant a worsening of their learning ability. It was also found that change in platform searching strategy was not associated with an increase in anxiety of male rats. Possible involvement of maternal methyl diet in the change of expression of genes which control development of the nervous system is discussed. PMID:16869262

  20. Maternal high-fat diet inversely affects insulin sensitivity in dams and young adult male rat offspring.

    PubMed

    Karbaschi, Roxana; Sadeghimahalli, Forouzan; Zardooz, Homeira

    2016-09-01

    This study attempts to further clarify the potential effects of maternal high-fat (HF) diet on glucose homeostasis in dams and young adult male rat offspring. Female rats were divided into control (CON dams) and HF (HF dams) diet groups, which received the diet 4 weeks prior to and through pregnancy and lactation periods. Blood samples were taken to determine metabolic parameters, then an intraperitoneal glucose tolerance test (IPGTT) was performed. Maternal HF diet increased intra-abdominal fat mass and plasma corticosterone level, but decreased leptin concentration in dams. In HF offspring intra-abdominal fat mass, plasma leptin, and corticosterone levels decreased. Following IPGTT, the plasma insulin level of HF dams was higher than the controls. In HF offspring plasma insulin level was not significantly different from the controls, but a steeper decrease of their plasma glucose concentration was observed. PMID:27604865

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

    SciTech Connect

    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 {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

  2. Maternal obesity characterized by gestational diabetes increases the susceptibility of rat offspring to hepatic steatosis via a disrupted liver metabolome

    PubMed Central

    Pereira, Troy J; Fonseca, Mario A; Campbell, Kristyn E; Moyce, Brittany L; Cole, Laura K; Hatch, Grant M; Doucette, Christine A; Klein, Julianne; Aliani, Michel; Dolinsky, Vernon W

    2015-01-01

    Maternal obesity is associated with a high risk for gestational diabetes mellitus (GDM), which is a common complication of pregnancy. The influence of maternal obesity and GDM on the metabolic health of the offspring is poorly understood. We hypothesize that GDM associated with maternal obesity will cause obesity, insulin resistance and hepatic steatosis in the offspring. Female Sprague-Dawley rats were fed a high-fat (45%) and sucrose (HFS) diet to cause maternal obesity and GDM. Lean control pregnant rats received low-fat (LF; 10%) diets. To investigate the interaction between the prenatal environment and postnatal diets, rat offspring were assigned to LF or HFS diets for 12 weeks, and insulin sensitivity and hepatic steatosis were evaluated. Pregnant GDM dams exhibited excessive gestational weight gain, hyperinsulinaemia and hyperglycaemia. Offspring of GDM dams gained more weight than the offspring of lean dams due to excess adiposity. The offspring of GDM dams also developed hepatic steatosis and insulin resistance. The postnatal consumption of a LF diet did not protect offspring of GDM dams against these metabolic disorders. Analysis of the hepatic metabolome revealed increased diacylglycerol and reduced phosphatidylethanolamine in the offspring of GDM dams compared to offspring of lean dams. Consistent with altered lipid metabolism, the expression of CTP:phosphoethanolamine cytidylyltransferase, and peroxisomal proliferator activated receptor-α mRNA was reduced in the livers of GDM offspring. GDM exposure programs gene expression and hepatic metabolite levels and drives the development of hepatic steatosis and insulin resistance in young adult rat offspring. Key points Gestational diabetes mellitus is a common complication of pregnancy, but its effects on the offspring are poorly understood. We developed a rat model of diet-induced gestational diabetes mellitus that recapitulates many of the clinical features of the disease, including excessive gestational

  3. [Comparative analysis of the maternal motivation expression in WAG/Rij and Wistar rats in the place preference and open field tests].

    PubMed

    Dobriakova, Iu V; Tanaeva, K K; Dubynin, V A; Sarkisova, K Iu

    2014-01-01

    Maternal behavior in females of WAG/Rij and Wistar rats was compared in the place preference test from 2 to 8 days after delivery, as well as in the open field test from 4 to 6 days after delivery. In females of WAG/Rij rats compared with females of Wistar rats weaker expression of maternal motivation has been revealed in both tests: they spend less time in the compartment associated with pups. Moreover, in females of WAG/Rij rats, number of approaches to pups, number of pup-carryings and time spent with pups (time of contacts) were less than in females of Wistar rats. Reduced maternal motivation in females of WAG/Rij rats in the place preference test persisted in repeated testing, while in the open field test it was detected only in the first testing, indicating higher reliability of the place preference test for revealing inter-strain differences in the expression of maternal motivation. It is supposed that weaker expression of maternal behavior and preference is due to hypo-function of the mesolimbic dopaminergic bran system in WAG/Rij rats as a genetic model of depression associated with absence epilepsy.

  4. Ventral Striatum Dopamine D2 Receptor Activity Inhibits Rat Pups’ Vocalization Response to Loss of Maternal Contact

    PubMed Central

    Muller, Jeff M.; Moore, Holly; Myers, Michael M.; Shair, Harry N.

    2010-01-01

    Most mammalian infants vocalize when isolated. The vocalization promotes caregiver proximity, which is critical to survival. If, before isolation, a rat pup has contact with its dam, its isolation vocalization rate is increased (maternal potentiation) relative to isolation preceded only by littermate contact. Prior work showed that systemic administration of a D2 receptor agonist blocks maternal potentiation at doses that do not alter baseline vocalization. In this study, infusion of quinpirole (2 µg/side) into the nucleus accumbens also blocks maternal potentiation. Infusion of the accumbens with the D2 antagonist raclopride (4 µg/side) prevents systemic quinpirole from blocking potentiation. Quinpirole infusion in the dorsal striatum did not affect maternal potentiation and infusion of raclopride in the dorsal striatum did not reverse the block of maternal potentiation by systemic quinpirole. Vocalization results after a second vehicle infusion on a given day are no different than the results following an initial vehicle infusion, so experimental design can not account for the effects of drug infusions. Because activity level was increased by both dorsal and ventral striatum infusions, activity level can not account for the results. PMID:18298255

  5. Environmental prenatal stress eliminates brain and maternal behavioral sex differences and alters hormone levels in female rats.

    PubMed

    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. PMID:26163152

  6. Environmental prenatal stress eliminates brain and maternal behavioral sex differences and alters hormone levels in female rats.

    PubMed

    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.

  7. Maternal Dexamethasone Exposure Alters Synaptic Inputs to Gonadotropin-Releasing Hormone Neurons in the Early Postnatal Rat.

    PubMed

    Lim, Wei Ling; Idris, Marshita Mohd; Kevin, Felix Suresh; Soga, Tomoko; Parhar, Ishwar S

    2016-01-01

    Maternal dexamethasone [(DEX); a glucocorticoid receptor agonist] exposure delays pubertal onset and alters reproductive behavior in the adult offspring. However, little is known whether maternal DEX exposure affects the offspring's reproductive function by disrupting the gonadotropin-releasing hormone (GnRH) neuronal function in the brain. Therefore, this study determined the exposure of maternal DEX on the GnRH neuronal spine development and synaptic cluster inputs to GnRH neurons using transgenic rats expressing enhanced green fluorescent protein (EGFP) under the control of GnRH promoter. Pregnant females were administered with DEX (0.1 mg/kg) or vehicle (VEH, water) daily during gestation day 13-20. Confocal imaging was used to examine the spine density of EGFP-GnRH neurons by three-dimensional rendering and synaptic cluster inputs to EGFP-GnRH neurons by synapsin I immunohistochemistry on postnatal day 0 (P0) males. The spine morphology and number on GnRH neurons did not change between the P0 males following maternal DEX and VEH treatment. The number of synaptic clusters within the organum vasculosum of the lamina terminalis (OVLT) was decreased by maternal DEX exposure in P0 males. Furthermore, the number and levels of synaptic cluster inputs in close apposition with GnRH neurons was decreased following maternal DEX exposure in the OVLT region of P0 males. In addition, the postsynaptic marker molecule, postsynaptic density 95, was observed in GnRH neurons following both DEX and VEH treatment. These results suggest that maternal DEX exposure alters neural afferent inputs to GnRH neurons during early postnatal stage, which could lead to reproductive dysfunction during adulthood. PMID:27630615

  8. In utero glucocorticoid exposure reduces fetal skeletal muscle mass in rats independent of effects on maternal nutrition.

    PubMed

    Gokulakrishnan, Ganga; Estrada, Irma J; Sosa, Horacio A; Fiorotto, Marta L

    2012-05-15

    Maternal stress and undernutrition can occur together and expose the fetus to high glucocorticoid (GLC) levels during this vulnerable period. To determine the consequences of GLC exposure on fetal skeletal muscle independently of maternal food intake, groups of timed-pregnant Sprague-Dawley rats (n = 7/group) were studied: ad libitum food intake (control, CON); ad libitum food intake with 1 mg dexamethasone/l drinking water from embryonic day (ED)13 to ED21 (DEX); pair-fed (PF) to DEX from ED13 to ED21. On ED22, dams were injected with [(3)H]phenylalanine for measurements of fetal leg muscle and diaphragm fractional protein synthesis rates (FSR). Fetal muscles were analyzed for protein and RNA contents, [(3)H]phenylalanine incorporation, and MuRF1 and atrogin-1 (MAFbx) mRNA expression. Fetal liver tyrosine aminotransferase (TAT) expression was quantified to assess fetal exposure to GLCs. DEX treatment reduced maternal food intake by 13% (P < 0.001) and significantly reduced placental mass relative to CON and PF dams. Liver TAT expression was elevated only in DEX fetuses (P < 0.01). DEX muscle protein masses were 56% and 70% than those of CON (P < 0.01) and PF (P < 0.05) fetuses, respectively; PF muscles were 80% of CON (P < 0.01). Muscle FSR decreased by 35% in DEX fetuses (P < 0.001) but were not different between PF and CON. Only atrogin-1 expression was increased in DEX fetus muscles. We conclude that high maternal GLC levels and inadequate maternal food intake impair fetal skeletal muscle growth, most likely through different mechanisms. When combined, the effects of decreased maternal intake and maternal GLC intake on fetal muscle growth are additive.

  9. Maternal Dexamethasone Exposure Alters Synaptic Inputs to Gonadotropin-Releasing Hormone Neurons in the Early Postnatal Rat

    PubMed Central

    Lim, Wei Ling; Idris, Marshita Mohd; Kevin, Felix Suresh; Soga, Tomoko; Parhar, Ishwar S.

    2016-01-01

    Maternal dexamethasone [(DEX); a glucocorticoid receptor agonist] exposure delays pubertal onset and alters reproductive behavior in the adult offspring. However, little is known whether maternal DEX exposure affects the offspring’s reproductive function by disrupting the gonadotropin-releasing hormone (GnRH) neuronal function in the brain. Therefore, this study determined the exposure of maternal DEX on the GnRH neuronal spine development and synaptic cluster inputs to GnRH neurons using transgenic rats expressing enhanced green fluorescent protein (EGFP) under the control of GnRH promoter. Pregnant females were administered with DEX (0.1 mg/kg) or vehicle (VEH, water) daily during gestation day 13–20. Confocal imaging was used to examine the spine density of EGFP–GnRH neurons by three-dimensional rendering and synaptic cluster inputs to EGFP–GnRH neurons by synapsin I immunohistochemistry on postnatal day 0 (P0) males. The spine morphology and number on GnRH neurons did not change between the P0 males following maternal DEX and VEH treatment. The number of synaptic clusters within the organum vasculosum of the lamina terminalis (OVLT) was decreased by maternal DEX exposure in P0 males. Furthermore, the number and levels of synaptic cluster inputs in close apposition with GnRH neurons was decreased following maternal DEX exposure in the OVLT region of P0 males. In addition, the postsynaptic marker molecule, postsynaptic density 95, was observed in GnRH neurons following both DEX and VEH treatment. These results suggest that maternal DEX exposure alters neural afferent inputs to GnRH neurons during early postnatal stage, which could lead to reproductive dysfunction during adulthood.

  10. Maternal Dexamethasone Exposure Alters Synaptic Inputs to Gonadotropin-Releasing Hormone Neurons in the Early Postnatal Rat

    PubMed Central

    Lim, Wei Ling; Idris, Marshita Mohd; Kevin, Felix Suresh; Soga, Tomoko; Parhar, Ishwar S.

    2016-01-01

    Maternal dexamethasone [(DEX); a glucocorticoid receptor agonist] exposure delays pubertal onset and alters reproductive behavior in the adult offspring. However, little is known whether maternal DEX exposure affects the offspring’s reproductive function by disrupting the gonadotropin-releasing hormone (GnRH) neuronal function in the brain. Therefore, this study determined the exposure of maternal DEX on the GnRH neuronal spine development and synaptic cluster inputs to GnRH neurons using transgenic rats expressing enhanced green fluorescent protein (EGFP) under the control of GnRH promoter. Pregnant females were administered with DEX (0.1 mg/kg) or vehicle (VEH, water) daily during gestation day 13–20. Confocal imaging was used to examine the spine density of EGFP–GnRH neurons by three-dimensional rendering and synaptic cluster inputs to EGFP–GnRH neurons by synapsin I immunohistochemistry on postnatal day 0 (P0) males. The spine morphology and number on GnRH neurons did not change between the P0 males following maternal DEX and VEH treatment. The number of synaptic clusters within the organum vasculosum of the lamina terminalis (OVLT) was decreased by maternal DEX exposure in P0 males. Furthermore, the number and levels of synaptic cluster inputs in close apposition with GnRH neurons was decreased following maternal DEX exposure in the OVLT region of P0 males. In addition, the postsynaptic marker molecule, postsynaptic density 95, was observed in GnRH neurons following both DEX and VEH treatment. These results suggest that maternal DEX exposure alters neural afferent inputs to GnRH neurons during early postnatal stage, which could lead to reproductive dysfunction during adulthood. PMID:27630615

  11. The mother as hunter: significant reduction in foraging costs through enhancements of predation in maternal rats.

    PubMed

    Kinsley, Craig Howard; Blair, Jamie C; Karp, Natalie E; Hester, Naomi W; McNamara, Ilan M; Orthmeyer, Angela L; McSweeney, Molly C; Bardi, Massimo M; Karelina, Kate; Christon, Lillian M; Sirkin, Maxwell R; Victoria, Lindsay W; Skurka, Danielle J; Fyfe, Christian R; Hudepohl, Margaret B; Felicio, Luciano F; Franssen, R Adam; Meyer, Elizabeth E A; da Silva, Ilton S; Lambert, Kelly G

    2014-09-01

    In previous laboratory investigations, we have identified enhanced cognition and reduced stress in parous rats, which are likely adaptations in mothers needing to efficiently exploit resources to maintain, protect and provision their immature offspring. Here, in a series of seven behavioral tests on rats, we examined a natural interface between cognition and resource gathering: predation. Experiment 1 compared predatory behavior (toward crickets) in age-matched nulliparous mothers (NULLs) and postpartum lactating mothers (LACTs), revealing a highly significant enhancement of predation in LACT females (mean = -65s in LACTs, vs. -270s in NULLs). Experiment 2 examined the possibility that LACTs, given their increased metabolic rate, were hungrier, and thus more motivated to hunt; doubling the length of time of food deprivation in NULLs did not decrease their predatory latencies. Experiments 3-5, which examined sensory regulation of the effect, indicated that olfaction (anosmia), audition (blockade with white noise), and somatosensation (trimming the vibrissae) appear to play little role in the behavioral enhancement observed in the LACTs; Experiment 6 examined the possibility that visual augmentations may facilitate the improvements in predation; testing LACTs in a 0-lux environment eliminated the behavioral advantage (increasing their latencies from -65s to -212s), which suggests that temporary augmentation to the visual system may be important, and with hormone-neural alterations therein a likely candidate for further study. In contrast, testing NULLS in the 0-lux environment had the opposite effect, reducing their latency to catch the cricket (from -270s to -200s). Finally, Experiment 7 examined the development of predatory behavior in Early-pregnant (PREG), Mid-PREG, and Late-PREG females. Here, we observed a significant enhancement of predation in Mid-PREG and Late-PREG females--at a time when maternity-associated bodily changes would be expected to diminish

  12. Maternal high fructose and low protein consumption during pregnancy and lactation share some but not all effects on early-life growth and metabolic programming of rat offspring.

    PubMed

    Arentson-Lantz, Emily J; Zou, Mi; Teegarden, Dorothy; Buhman, Kimberly K; Donkin, Shawn S

    2016-09-01

    Maternal nutritional stress during pregnancy acts to program offspring metabolism. We hypothesized that the nutritional stress caused by maternal fructose or low protein intake during pregnancy would program the offspring to develop metabolic aberrations that would be exacerbated by a diet rich in fructose or fat during adult life. The objective of this study was to characterize and compare the fetal programming effects of maternal fructose with the established programming model of a low-protein diet on offspring. Male offspring from Sprague-Dawley dams fed a 60% starch control diet, a 60% fructose diet, or a low-protein diet throughout pregnancy and lactation were weaned onto either a 60% starch control diet, 60% fructose diet, or a 30% fat diet for 15 weeks. Offspring from low-protein and fructose-fed dam showed retarded growth (P<.05) at weaning (50.3, 29.6 vs 59.1±0.8 g) and at 18 weeks of age (420, 369 vs 464±10.9 g). At 18 weeks of age, offspring from fructose dams expressed greater quantities (P<.05) of intestinal Pgc1a messenger RNA compared with offspring from control or low-protein dams (1.31 vs 0.89, 0.85; confidence interval, 0.78-1.04). Similarly, maternal fructose (P=.09) and low-protein (P<.05) consumption increased expression of Pgc1a in offspring liver (7.24, 2.22 vs 1.22; confidence interval, 2.11-3.45). These data indicate that maternal fructose feeding is a programming model that shares some features of maternal protein restriction such as retarded growth, but is unique in programming of selected hepatic and intestinal transcripts.

  13. Maternal high fructose and low protein consumption during pregnancy and lactation share some but not all effects on early-life growth and metabolic programming of rat offspring.

    PubMed

    Arentson-Lantz, Emily J; Zou, Mi; Teegarden, Dorothy; Buhman, Kimberly K; Donkin, Shawn S

    2016-09-01

    Maternal nutritional stress during pregnancy acts to program offspring metabolism. We hypothesized that the nutritional stress caused by maternal fructose or low protein intake during pregnancy would program the offspring to develop metabolic aberrations that would be exacerbated by a diet rich in fructose or fat during adult life. The objective of this study was to characterize and compare the fetal programming effects of maternal fructose with the established programming model of a low-protein diet on offspring. Male offspring from Sprague-Dawley dams fed a 60% starch control diet, a 60% fructose diet, or a low-protein diet throughout pregnancy and lactation were weaned onto either a 60% starch control diet, 60% fructose diet, or a 30% fat diet for 15 weeks. Offspring from low-protein and fructose-fed dam showed retarded growth (P<.05) at weaning (50.3, 29.6 vs 59.1±0.8 g) and at 18 weeks of age (420, 369 vs 464±10.9 g). At 18 weeks of age, offspring from fructose dams expressed greater quantities (P<.05) of intestinal Pgc1a messenger RNA compared with offspring from control or low-protein dams (1.31 vs 0.89, 0.85; confidence interval, 0.78-1.04). Similarly, maternal fructose (P=.09) and low-protein (P<.05) consumption increased expression of Pgc1a in offspring liver (7.24, 2.22 vs 1.22; confidence interval, 2.11-3.45). These data indicate that maternal fructose feeding is a programming model that shares some features of maternal protein restriction such as retarded growth, but is unique in programming of selected hepatic and intestinal transcripts. PMID:27632913

  14. Insulin Like Growth Factor 2 Expression in the Rat Brain Both in Basal Condition and following Learning Predominantly Derives from the Maternal Allele

    PubMed Central

    Ye, Xiaojing; Kohtz, Amy; Pollonini, Gabriella; Riccio, Andrea; Alberini, Cristina M.

    2015-01-01

    Insulin like growth factor 2 (Igf2) is known as a maternally imprinted gene involved in growth and development. Recently, Igf2 was found to also be regulated and required in the adult rat hippocampus for long-term memory formation, raising the question of its allelic regulation in adult brain regions following experience and in cognitive processes. We show that, in adult rats, Igf2 is abundantly expressed in brain regions involved in cognitive functions, like hippocampus and prefrontal cortex, compared to the peripheral tissues. In contrast to its maternal imprinting in peripheral tissues, Igf2 is mainly expressed from the maternal allele in these brain regions. The training-dependent increase in Igf2 expression derives proportionally from both parental alleles, and, hence, is mostly maternal. Thus, Igf2 parental expression in the adult rat brain does not follow the imprinting rules found in peripheral tissues, suggesting differential expression regulation and functions of imprinted genes in the brain. PMID:26495851

  15. Resveratrol partially prevents oxidative stress and metabolic dysfunction in pregnant rats fed a low protein diet and their offspring.

    PubMed

    Vega, Claudia C; Reyes-Castro, Luis A; Rodríguez-González, Guadalupe L; Bautista, Claudia J; Vázquez-Martínez, Magaly; Larrea, Fernando; Chamorro-Cevallos, Germán A; Nathanielsz, Peter W; Zambrano, Elena

    2016-03-01

    Protein restriction in pregnancy produces maternal and offspring metabolic dysfunction potentially as a result of oxidative stress. Data are lacking on the effects of inhibition of oxidative stress. We hypothesized that maternal resveratrol administration decreases oxidative stress, preventing, at least partially, maternal low protein-induced maternal and offspring metabolic dysfunction. In the present study, pregnant wistar rats ate control (C) (20% casein) or a protein-restricted (R) (10% casein) isocaloric diet. Half of each group received resveratrol orally, 20 mg kg(-1) day(-1), throughout pregnancy. Post-delivery, mothers and offspring ate C. Oxidative stress biomarkers and anti-oxidant enzymes were measured in placenta, maternal and fetal liver, and maternal serum corticosterone at 19 days of gestation (dG). Maternal (19 dG) and offspring (postnatal day 110) glucose, insulin, triglycerides, cholesterol, fat and leptin were determined. R mothers showed metabolic dysfunction, increased corticosterone and oxidative stress and reduced anti-oxidant enzyme activity vs. C. R placental and fetal liver oxidative stress biomarkers and anti-oxidant enzyme activity increased. R offspring showed higher male and female leptin, insulin and corticosterone, male triglycerides and female fat than C. Resveratrol decreased maternal leptin and improved maternal, fetal and placental oxidative stress markers. R induced offspring insulin and leptin increases were prevented and other R changes were offspring sex-dependent. Resveratrol partially prevents low protein diet-induced maternal, placental and sex-specific offspring oxidative stress and metabolic dysfunction. Oxidative stress is one mechanism programming offspring metabolic outcomes. These studies provide mechanistic evidence to guide human pregnancy interventions when fetal nutrition is impaired by poor maternal nutrition or placental function. PMID:26662841

  16. Windows of vulnerability: maternal separation, age, and fluoxetine on adolescent depressive-like behavior in rats.

    PubMed

    Freund, N; Thompson, B S; Denormandie, J; Vaccarro, K; Andersen, S L

    2013-09-26

    Early exposure to stressful life events plays a significant role in adolescent depression. Clinical studies have identified a number of factors that increase the risk of depression, including sex of the subject, duration of the stressor, and genetic polymorphisms that elevate serotonin levels. In this study we used the maternal separation (MS) model to investigate to what extent these factors interacted during development to manifest in depressive-like behavior in male and female rats. The triadic model of learned helplessness parses depressive-like behavior into aspects of controllable, uncontrollable, and motivational behaviors. This model was used to investigate how the timing of MS between the ages of postnatal day (P) 2-9 and P9-16 interacted with either simultaneous vehicle (saline; 1ml/kg; i.p.) or fluoxetine (10mg/kg) exposure, which was used to enhance serotonin levels; these experiments also compared the effect of a vehicle injection during these developmental periods to a no injection control. Vehicle injections alone increased helplessness in the controllable condition in male rats when injected between P9-16 only, and did not interact further with MS. MS at both ages decreased controllability in male adolescents; females demonstrated an increase in controllability after MS. Elevated serotonin at P2-9 increased escape latencies in male and female control and MS subjects. Fluoxetine exposure at P9-16 increased helplessness in controls. Fluoxetine decreased helplessness in MS males independent of age, but increases helplessness in MS females. This study highlights the importance of age of MS (MS between P2-9 increases helplessness in males more than females), the duration of the stressor (previous results show females are effected by longer MS [P2-20], but not shorter [this study]), and that elevated serotonin increases escape latencies to a greater extent in females. PMID:23850503

  17. Maternal obesity caused by overnutrition exposure leads to reversal learning deficits and striatal disturbance in rats.

    PubMed

    Wu, Ting; Deng, Shining; Li, Wei-Guang; Yu, Yongguo; Li, Fei; Mao, Meng

    2013-01-01

    Maternal obesity caused by overnutrition during pregnancy increases susceptibility to metabolic risks in adulthood, such as obesity, insulin resistance, and type 2 diabetes; however, whether and how it affects the cognitive system associated with the brain remains elusive. Here, we report that pregnant obesity induced by exposure to excessive high fatty or highly palatable food specifically impaired reversal learning, a kind of adaptive behavior, while leaving serum metabolic metrics intact in the offspring of rats, suggesting a much earlier functional and structural defects possibly occurred in the central nervous system than in the metabolic system in the offspring born in unfavorable intrauterine nutritional environment. Mechanically, we found that above mentioned cognitive inflexibility might be associated with significant striatal disturbance including impaired dopamine homeostasis and disrupted leptin signaling in the adult offspring. These collective data add a novel perspective of understanding the adverse postnatal sequelae in central nervous system induced by developmental programming and the related molecular mechanism through which priming of risk for developmental disorders may occur during early life. PMID:24223863

  18. Maternal Obesity Caused by Overnutrition Exposure Leads to Reversal Learning Deficits and Striatal Disturbance in Rats

    PubMed Central

    Wu, Ting; Deng, Shining; Li, Wei-Guang; Yu, Yongguo; Li, Fei; Mao, Meng

    2013-01-01

    Maternal obesity caused by overnutrition during pregnancy increases susceptibility to metabolic risks in adulthood, such as obesity, insulin resistance, and type 2 diabetes; however, whether and how it affects the cognitive system associated with the brain remains elusive. Here, we report that pregnant obesity induced by exposure to excessive high fatty or highly palatable food specifically impaired reversal learning, a kind of adaptive behavior, while leaving serum metabolic metrics intact in the offspring of rats, suggesting a much earlier functional and structural defects possibly occurred in the central nervous system than in the metabolic system in the offspring born in unfavorable intrauterine nutritional environment. Mechanically, we found that above mentioned cognitive inflexibility might be associated with significant striatal disturbance including impaired dopamine homeostasis and disrupted leptin signaling in the adult offspring. These collective data add a novel perspective of understanding the adverse postnatal sequelae in central nervous system induced by developmental programming and the related molecular mechanism through which priming of risk for developmental disorders may occur during early life. PMID:24223863

  19. Maternal Exercise During Pregnancy Reduces Risk of Mammary Tumorigenesis In Rat Offspring

    PubMed Central

    Camarillo, Ignacio; Clah, Leon; Zheng, Wei; Zhou, Xuanzhu; Larrick, Brienna; Blaize, Nicole; Breslin, Emily; Patel, Neal; Johnson, Diamond; Teegarden, Dorothy; Donkin, Shawn S.; Gavin, Timothy P.; Newcomer, Sean

    2015-01-01

    Breast cancer is the most common cancer among women. Emerging research indicates that modifying lifestyle factors during pregnancy may convey long-term health benefits to offspring. This study was designed to determine whether maternal exercise during pregnancy leads to reduced mammary tumorigenesis in female offspring. Pregnant rats were randomly assigned to exercised and sedentary groups, with the exercised group having free access to a running wheel and the sedentary group housed with a locked wheel during pregnancy. Female pups from exercised or sedentary dams were weaned at 21 days of age and fed a high fat diet without access to a running wheel. At 6 weeks, all pups were injected with the carcinogen N-methyl-N-nitrosourea (MNU). Mammary tumor development in all pups was monitored for 15 weeks. Pups from exercised dams had a substantially lower tumor incidence (42.9%) compared to pups from sedentary dams (100%). Neither tumor latency nor histological grade differed between the two groups. These data are the first to demonstrate that exercise during pregnancy potentiates reduced tumorigenesis in offspring. This study provides an important foundation towards developing more effective modes of behavior modification for cancer prevention. PMID:24950432

  20. Maternal exercise during pregnancy reduces risk of mammary tumorigenesis in rat offspring.

    PubMed

    Camarillo, Ignacio G; Clah, Leon; Zheng, Wei; Zhou, Xuanzhu; Larrick, Brienna; Blaize, Nicole; Breslin, Emily; Patel, Neal; Johnson, Diamond; Teegarden, Dorothy; Donkin, Shawn S; Gavin, Timothy P; Newcomer, Sean

    2014-11-01

    Breast cancer is the most common cancer among women. Emerging research indicates that modifying lifestyle factors during pregnancy may convey long-term health benefits to offspring. This study was designed to determine whether maternal exercise during pregnancy leads to reduced mammary tumorigenesis in female offspring. Pregnant rats were randomly assigned to exercised and sedentary groups, with the exercised group having free access to a running wheel and the sedentary group housed with a locked wheel during pregnancy. Female pups from exercised or sedentary dams were weaned at 21 days of age and fed a high fat diet without access to a running wheel. At 6 weeks, all pups were injected with the carcinogen N-methyl-N-nitrosourea. Mammary tumor development in all pups was monitored for 15 weeks. Pups from exercised dams had a substantially lower tumor incidence (42.9%) compared with pups from sedentary dams (100%). Neither tumor latency nor histological grade differed between the two groups. These data are the first to demonstrate that exercise during pregnancy potentiates reduced tumorigenesis in offspring. This study provides an important foundation towards developing more effective modes of behavior modification for cancer prevention. PMID:24950432

  1. Early maternal deprivation in rats: a proposed animal model for the study of developmental neuroimmunoendocrine interactions.

    PubMed

    De la Fuente, M; Llorente, R; Baeza, I; De Castro, N M; Arranz, L; Cruces, J; Viveros, M P

    2009-02-01

    Adult animals that had been subjected to a single prolonged episode of maternal deprivation (MD) [24 h, postnatal day (PND) 9-10] show long-term behavioral alterations that resemble specific symptoms of schizophrenia. Moreover, at adolescence MD rats showed depressive-like behavior and altered motor responses. According to the neurodevelopmental hypothesis, certain behavioral abnormalities observed in MD animals may be related to altered neurodevelopmental processes triggered by MD-induced elevated glucocorticoids in relevant specific brain regions. We review here these neuroendocrine effects and show new data indicating that the MD procedure induces diverse detrimental effects on the immune system that are already revealed in the short term (PND 13) and persist into adulthood. These long-lasting effects might be related to altered hypothalamus-pituitary-adrenal axis activity and to social as well as nutrition-related factors. In fact, MD induces long-lasting decreases in body weight. In view of our findings we propose the present MD procedure as a potentially useful model to analyze developmental interactions between early psychophysiological stress and immunodeficient states.

  2. Influence of the destabilisation of the maternal digestive microflora on that of the newborn rat.

    PubMed

    Brunel, A; Gouet, P

    1993-01-01

    By destabilising the digestive flora of pregnant rats by antibiotic treatment, it was shown that part of the digestive microflora of the neonate originated from the maternal faeces. A mixture of ampicillin, bacitracin neomycin and streptomycin associated with nystatin were administered ad libitum at three different times, 1-3, 3-5, and more than 5 days before the estimated date of littering. For each treatment, samples were taken from the faeces, teats, and vagina of dams and from the digestive tracts of neonates aged between 6 and 120 h, and analysed for the presence of staphylococci, enterococci, lactobacilli and coliform bacteria. Antibiotic treatment reduced digestive flora populations to levels lower than 10(2) g-1 but had less effect on the vaginal and cutaneous mammary flora. In the digestive microflora of the neonate, the enterococci were unevenly affected, whereas the staphylococci were considerably decreased and the lactobacilli almost completely eliminated; coliform bacteria were found sporadically and in small numbers. The traces of antibiotics found in milk are not sufficient to explain these modifications. Counts made in control animals on media fed the same antibiotic concentrations were not modified. This work underlined the awful consequences for the newborn of a serious perturbation of the mother flora and the necessity of its presence for a normal installation of the digestive microflora of the newborn.

  3. Global Histone H4 Acetylation in the Olfactory Bulb of Lactating Rats with Different Patterns of Maternal Behavior.

    PubMed

    de Moura, Ana Carolina; da Silva, Ivy Reichert Vital; Reinaldo, Gustavo; Dani, Caroline; Elsner, Viviane Rostirola; Giovenardi, Márcia

    2016-10-01

    In rats, variations in the levels of neuromodulatory molecules and in the expression of their receptors are observed during pregnancy and postpartum. These changes may contribute to the development and management of maternal behavior. The frequency of licking the pups is used to evaluate maternal care, having mothers with low licking (LL) and high licking (HL) frequencies. Previously, we found that HL had increased levels of transcriptional expression of the receptors for serotonin (HTR1a, HTR1b), estrogen (Erα), dopamine (D1a), and prolactin (Prlr) than LL in the olfactory bulb (OB); however, the molecular mechanisms behind this phenomenon are unknown. Since evidences pointed out that epigenetic marks, which may alter gene expression, are modulated by environmental factors such as exercise, diet, maternal care, and xenobiotic exposure, our objective was to verify the acetylation levels of histone-H4 in the OB of LL and HL rats. Maternal behavior was studied for the first 7 postpartum days. LL (n = 4) and HL (n = 5) mothers were selected according to the behavior of licking their pups. Acetylation levels of histone-H4 were determined using the Global Histone-H4 Acetylation Assay Kit and expressed as ng/mg protein (mean ± SD). Analysis revealed that HL (278.36 ± 68.95) had increased H4 acetylation levels than LL (183.24 ± 73.05; p = 0.045). The enhanced expression of the previously studied receptors in the OB could be related, at least in part, to the hyperacetylation status of histone-H4 here observed. Afterward, the modulation of histone acetylation levels could exert a pivotal role through molecular mechanisms involved in the different patterns of maternal behavior.

  4. Early postnatal maternal deprivation in rats induces memory deficits in adult life that can be reversed by donepezil and galantamine.

    PubMed

    Benetti, Fernando; Mello, Pâmela Billig; Bonini, Juliana Sartori; Monteiro, Siomara; Cammarota, Martín; Izquierdo, Iván

    2009-02-01

    Early postnatal maternal deprivation is known to cause long-lasting neurobiological effects. Here, we investigated whether some of the cognitive aspects of these deficits might be related to a disruption of the cholinergic system. Pregnant Wistar rats were individually housed and maintained on a 12:12h light/dark cycle with food and water freely available. The mothers were separated from their pups for 3h per day from postnatal day 1 (PND-1) to PND-10. To do that, the dams were moved to a different cage and the pups maintained in the original home cage, which was transferred to a different room kept at 32 degrees C. After they reached 120-150 days of age, maternal-deprived and non-deprived animals were either sacrificed for brain acetylcholinesterase measurement, or trained and tested in an object recognition task and in a social recognition task as described by Rossato et al. (2007) [Rossato, J.I., Bevilaqua, L. R.M., Myskiw, J.C., Medina, J.H., Izquierdo, I., Cammarota, M. 2007. On the role hippocampal synthesis in the consolidation and reconsolidation of object recognition memory. Learn. Mem. 14, 36-46] and Lévy et al. (2003) [Lévy, F., Melo. A.I., Galef. B.G. Jr., Madden, M., Fleming. A.S. 2003. Complete maternal deprivation affects social, but not spatial, learning in adult rats. Dev. Psychobiol. 43, 177-191], respectively. There was increased acetylcholinesterase activity in hippocampus and perirhinal cortex of the deprived animals. In addition, they showed a clear impairment in memory of the two recognition tasks measured 24h after training. Oral administration of the acetylcholinesterase inhibitors, donepezil or galantamine (1mg/kg) 30min before training reversed the memory impairments caused by maternal deprivation. The findings suggest that maternal deprivation affects memory processing at adulthood through a change in brain cholinergic systems.

  5. Maternal low-protein diet causes body weight loss in male, neonate Sprague-Dawley rats involving UCP-1-mediated thermogenesis.

    PubMed

    Claycombe, Kate J; Vomhof-DeKrey, Emilie E; Roemmich, James N; Rhen, Turk; Ghribi, Othman

    2015-07-01

    Brown adipose tissue (BAT) plays an important role in regulating body weight (BW) by modifying thermogenesis. Maternal low protein (LP) diets reduce offspring birth weight. Increased BAT thermogenesis in utero may be one mechanism for the lower BW. However, whether maternal LP nutrition alters BAT thermogenesis and BW of offspring in utero is not yet known. We fed obese-prone Sprague-Dawley dams 8% LP or 20% normal protein (NP) diets for 3 weeks prior to breeding and through pregnancy. BW and gene expression of interscapular BAT (iBAT) thermogenic markers were measured in male fetal (gestation day 18) and neonatal (day 0 or 1) offspring. BW of neonatal LP males was lower than NP males but no difference was observed in females. Gene and protein expression of UCP-1 and transcription factors PRDM16 and PPARα in iBAT were 2- to 6-fold greater in LP than in NP male neonatal offspring. FNDC5, a precursor of irisin and activator of thermogenesis, was expressed 2-fold greater in neonatal LP iBAT than NP males. However, fetal iBAT UCP-1, PRDM16, PPARα and irisin mRNA did not differ between LP and NP groups. Maternal LP diet had no effects on placental irisin and UCP-2 expression. These results suggest that prenatal protein restriction increases the risk for low BW through mechanisms affecting full-term offspring iBAT thermogenesis but not greatly altering fetal iBAT or placental thermogenesis.

  6. Intrauterine protein restriction combined with early postnatal overfeeding was not associated with adult-onset obesity but produced glucose intolerance by pancreatic dysfunction

    PubMed Central

    2013-01-01

    We investigated if whether intrauterine protein restriction in combination with overfeeding during lactation would cause adult-onset obesity and metabolic disorders. After birth, litters from dams fed with control (17% protein) and low protein (6% protein) diets were adjusted to a size of four (CO and LO groups, respectively) or eight (CC and LC groups, respectively) pups. All of the offspring were fed a diet containing 12% protein from the time of weaning until they were 90 d old. Compared to the CC and LC groups, the CO and LO groups had higher relative and absolute food intakes, oxygen consumption and carbon dioxide production; lower brown adipose tissue weight and lipid content and greater weight gain and absolute and relative white adipose tissue weight and absolute lipid content. Compared with the CO and CC rats, the LC and LO rats exhibited higher relative food intake, brown adipose tissue weight and lipid content, reduced oxygen consumption, carbon dioxide production and spontaneous activity, increased relative retroperitoneal adipose tissue weight and unaltered absolute white adipose tissue weight and lipid content. The fasting serum glucose was similar among the groups. The area under the glucose curve was higher in the LO and CO rats than in the LC and CC rats. The basal insulinemia and homeostasis model assessment of insulin resistance (HOMA-IR) were lower in the LO group than in the other groups. The total area under the insulin curve for the LO rats was similar to the CC rats, and both were lower than the CO and LC rats. Kitt was higher in the LO, LC and CO groups than in the CC group. Thus, intrauterine protein restriction followed by overfeeding during lactation did not induce obesity, but produced glucose intolerance by impairing pancreatic function in adulthood. PMID:23305533

  7. Intrauterine protein restriction combined with early postnatal overfeeding was not associated with adult-onset obesity but produced glucose intolerance by pancreatic dysfunction.

    PubMed

    Coutinho, Grazielle Vitória Ponti; Coutinho, Felipe Rodrigues; Faiad, Jaline Zandonato; Taki, Marina Satie; de Lima Reis, Silvia Regina; Ignácio-Souza, Letícia Martins; Paiva, Adriene Alexandra; Latorraca, Márcia Queiroz; Gomes-da-Silva, Maria Helena Gaíva; Martins, Maria Salete Ferreira

    2013-01-01

    We investigated if whether intrauterine protein restriction in combination with overfeeding during lactation would cause adult-onset obesity and metabolic disorders. After birth, litters from dams fed with control (17% protein) and low protein (6% protein) diets were adjusted to a size of four (CO and LO groups, respectively) or eight (CC and LC groups, respectively) pups. All of the offspring were fed a diet containing 12% protein from the time of weaning until they were 90 d old. Compared to the CC and LC groups, the CO and LO groups had higher relative and absolute food intakes, oxygen consumption and carbon dioxide production; lower brown adipose tissue weight and lipid content and greater weight gain and absolute and relative white adipose tissue weight and absolute lipid content. Compared with the CO and CC rats, the LC and LO rats exhibited higher relative food intake, brown adipose tissue weight and lipid content, reduced oxygen consumption, carbon dioxide production and spontaneous activity, increased relative retroperitoneal adipose tissue weight and unaltered absolute white adipose tissue weight and lipid content. The fasting serum glucose was similar among the groups. The area under the glucose curve was higher in the LO and CO rats than in the LC and CC rats. The basal insulinemia and homeostasis model assessment of insulin resistance (HOMA-IR) were lower in the LO group than in the other groups. The total area under the insulin curve for the LO rats was similar to the CC rats, and both were lower than the CO and LC rats. Kitt was higher in the LO, LC and CO groups than in the CC group. Thus, intrauterine protein restriction followed by overfeeding during lactation did not induce obesity, but produced glucose intolerance by impairing pancreatic function in adulthood. PMID:23305533

  8. Histamine acting on the basolateral amygdala reverts the impairment of aversive memory of rats submitted to neonatal maternal deprivation.

    PubMed

    Benetti, Fernando; da Silveira, Clarice Kras Borges; Rosa, Jessica; Izquierdo, Ivan

    2015-02-01

    Recent findings suggest a role of brain histamine in the regulation of memory consolidation, particularly in one-trial inhibitory avoidance (IA) learning and that disruption in the mother infant relationship i.e. maternal deprivation induces cognitive deficits. We investigate whether histamine itself, and histaminergic compounds given into the basolateral amygdala (BLA) immediately post-training can affect retention (24 h after training) of one-trial (IA) in rats submitted to early postnatal maternal deprivation. In all cases, deprived (Dep) animals had lower retention scores than non-deprived controls (N-dep). Histamine induced memory enhancement on its own in N-dep animals and was able to overcome the deleterious effect of Dep. The effects by SKF-91488 is similar to histamine. The H3 agonist, imetit mimetized the enhancing effects of histamine; neither agonist H1 pyridylethylamine nor the H2 dimaprit had any effect. Ranitidine and thioperamide (50 nmol) co-infused with histamine (10 nmol) fully blocked the restorative effect of histamine on retention in Dep animals. Thioperamide, in addition, blocked the enhancing effect of histamine on memory of the N-dep animals as well. None of the drugs used given into BLA had any effect on open-field or elevated plus-maze behavior in N-dep or Dep rats. Our results are limited to experimental design in rats. Extrapolation i.e. in humans requires further experimentations. The present results suggest that the memory deficit induced by early postnatal maternal deprivation in rats may at least in part be due to an impairment of histamine H3 receptor-mediated mediated mechanisms in the BLA.

  9. Social, thermal, and temporal influences on isolation-induced and maternally potentiated ultrasonic vocalizations of rat pups.

    PubMed

    Shair, Harry N; Brunelli, Susan A; Masmela, Jenny R; Boone, Emilie; Hofer, Myron A

    2003-03-01

    Sensory and temporal factors have been demonstrated to be involved in the regulation of isolation-induced ultrasonic vocalizations (USV) of young rats. Sensory cues include thermal, olfactory, and tactile modalities. Temporal factors include the time spent in isolation. The goal of the present research was to examine the interaction of these factors in both isolation-induced and maternally potentiated USV. Maternal potentiation of USV occurs when a brief interaction with the dam, even a passive (anesthetized) dam, elicits an augmented vocal response to a subsequent isolation, with rates of USV in rat pups well above those emitted in standard isolation tests. We found that passive maternal potentiation of USV did occur under all conditions tested. Neither a 30-min prior isolation nor high ambient temperature prevented an increase in USV rate over the rate of the original isolation. After 30-min isolation at warm temperatures when the rate of USV had fallen to zero, the pups increased vocalization in the presence of the dam as well as in the subsequent isolation. Temporal and thermal factors also interacted significantly in regulating the level of the USV emitted by the pups during the first isolation, in the presence of the anesthetized dam, and during the second isolation. PMID:12555284

  10. Maternal Stress Combined with Terbutaline Leads to Comorbid Autistic-Like Behavior and Epilepsy in a Rat Model.

    PubMed

    Bercum, Florencia M; Rodgers, Krista M; Benison, Alex M; Smith, Zachariah Z; Taylor, Jeremy; Kornreich, Elise; Grabenstatter, Heidi L; Dudek, F Edward; Barth, Daniel S

    2015-12-01

    Human autism is comorbid with epilepsy, yet, little is known about the causes or risk factors leading to this combined neurological syndrome. Although genetic predisposition can play a substantial role, our objective was to investigate whether maternal environmental factors alone could be sufficient. We examined the independent and combined effects of maternal stress and terbutaline (used to arrest preterm labor), autism risk factors in humans, on measures of both autistic-like behavior and epilepsy in Sprague-Dawley rats. Pregnant dams were exposed to mild stress (foot shocks at 1 week intervals) throughout pregnancy. Pups were injected with terbutaline on postnatal days 2-5. Either maternal stress or terbutaline resulted in autistic-like behaviors in offspring (stereotyped/repetitive behaviors and deficits in social interaction or communication), but neither resulted in epilepsy. However, their combination resulted in severe behavioral symptoms, as well as spontaneous recurrent convulsive seizures in 45% and epileptiform spikes in 100%, of the rats. Hippocampal gliosis (GFAP reactivity) was correlated with both abnormal behavior and spontaneous seizures. We conclude that prenatal insults alone can cause comorbid autism and epilepsy but it requires a combination of teratogens to achieve this; testing single teratogens independently and not examining combinatorial effects may fail to reveal key risk factors in humans. Moreover, astrogliosis may be common to both teratogens. This new animal model of combined autism and epilepsy permits the experimental investigation of both the cellular mechanisms and potential intervention strategies for this debilitating comorbid syndrome.

  11. Maternal dexamethasone exposure inhibits the gonadotropin-releasing hormone neuronal movement in the preoptic area of rat offspring.

    PubMed

    Lim, Wei Ling; Soga, Tomoko; Parhar, Ishwar S

    2014-01-01

    Migration and final positioning of gonadotropin-releasing hormone (GnRH) neurons in the preoptic area (POA) is critical for reproduction. It is known that maternal dexamethasone (DEX) exposure impairs reproductive function and behaviour in the offspring. However, it is still not known whether maternal DEX exposure affects the postnatal GnRH neurons in the offspring. This study determined the neuronal movement of enhanced green fluorescent protein (EGFP)-tagged GnRH neurons in slice culture of postnatal day 0 (P0), P5 and P50-60 transgenic male rats. Effect of maternal DEX treatment on EGFP-GnRH neuronal movement and F-actin distribution on GnRH neurons at P0 stage were studied. Time-lapse analysis of P0 and P5 EGFP-GnRH neurons displayed active cellular movement within the POA compared to young adult P50-60 stages, suggesting possible fine-tuning movement for positioning of early postnatal GnRH neurons. The DEX-treated EGFP-GnRH neurons demonstrated decreased motility in the POA and reduced F-actin distribution in the GnRH neurons at 60 h culture compared to the vehicle-treated. These results suggest that the P0 GnRH neuronal movement in the POA is altered by maternal DEX exposure, which possibly disrupts the fine-tuning process for positioning and development of early postnatal GnRH neurons in the brain, potentially linked to reproductive dysfunction in adulthood.

  12. Adolescent voluntary exercise attenuated hippocampal innate immunity responses and depressive-like behaviors following maternal separation stress in male rats.

    PubMed

    Sadeghi, Mahsa; Peeri, Maghsoud; Hosseini, Mir-Jamal

    2016-09-01

    Early life stressful events have detrimental effects on the brain and behavior, which are associated with the development of depression. Immune-inflammatory responses have been reported to contribute in the pathophysiology of depression. Many studies have reported on the beneficial effects of exercise against stress. However, underlying mechanisms through which exercise exerts its effects were poorly studied. Therefore, it applied maternal separation (MS), as a valid animal model of early-life adversity, in rats from postnatal day (PND) 2 to 14 for 180min per day. At PND 28, male Wistar albino rats were subjected to 5 experimental groups; 1) controls 2) MS rats 3) MS rats treated with fluoxetine 5mg/kg to PND 60, 4) MS rats that were subjected to voluntary running wheel (RW) exercise and 5) MS rats that were subjected to mandatory treadmill (TM) exercise until adulthood. At PND 60, depressive-like behaviors were assessed by using forced swimming test (FST), splash test, and sucrose preference test (SPT). Our results revealed that depressive-like behaviors following MS stress were associated with an increase in expression of toll-like receptor 4 (Tlr-4) and its main signaling protein, Myd88, in the hippocampal formation. Also, we found that voluntary (and not mandatory) physical exercise during adolescence is protected against depressant effects of early-life stress at least partly through mitigating the innate immune responses in the hippocampus. PMID:27184238

  13. Early maternal deprivation and neonatal single administration with a cannabinoid agonist induce long-term sex-dependent psychoimmunoendocrine effects in adolescent rats.

    PubMed

    Llorente, Ricardo; Arranz, Lorena; Marco, Eva-María; Moreno, Enrique; Puerto, Marta; Guaza, Carmen; De la Fuente, Mónica; Viveros, Maria-Paz

    2007-07-01

    Maternal deprivation [24h on postnatal day 9] might represent an animal model of schizophrenia and behavioural and neurochemical alterations observed in adulthood may be mediated by hippocampal impairments induced by abnormally increased glucocorticoids due to neonatal stress. We aimed to provide new data for psychoimmunoendocrine characterization of this animal model by evaluating its effects in adolescent rats of both genders. In previous studies we found that cannabinoid compounds counteracted the enhanced impulsivity of maternally deprived animals and that the cannabinoid receptor agonist WIN 55,212-2 showed neuroprotective properties in neonatal rats. So, we hypothesised that this compound could counteract at least some of the detrimental effects that we expected to find in maternally deprived animals. Accordingly, the drug was administered immediately after the maternal deprivation period. Maternally deprived males showed significantly decreased motor activity in the holeboard and the plus-maze. The cannabinoid agonist induced, exclusively in males, a significant anxiogenic-like effect, which was reversed by maternal deprivation. In the forced swimming test, both treatments independently induced depressive-like responses. Maternal deprivation reduced immunological function whereas the drug exerted tissue-dependent effects on the immune parameters analysed. Maternally deprived females showed reduced corticosterone levels whereas the cannabinoid agonist increased hormone concentration in all groups. In general, the results show detrimental effects of both treatments as well as intriguing interactions, notably in relation to emotional behaviour and certain immunological responses.

  14. Effects of Oral Maternal Administration of Caffeine on Reproductive Functions of Male Offspring of Wistar Rats.

    PubMed

    Ogunwole, Eunice; Akindele, Opeyemi O; Oluwole, Omobola F; Salami, S A; Raji, Y

    2015-12-20

    Caffeine was investigated for its possible fetal programming effects on reproductive function of male offspring. Sixty-five pregnant Wistar rats were grouped into four. Group 1 was control and received distilled water. Groups 2, 3 and 4 were treated orally with 1.14, 3.42 and 5.70 mg/kg body weight of caffeine respectively. Each group was subdivided into four based on gestation days (GD) 1-7, 8-14, 15-21 and 1-21. The day of parturition was taken as postnatal day zero (0). Male offspring were sacrificed on postnatal day 70. Parameters determined were: weight at birth, body weight at postnatal day 21 and 70, anogenital distance (AGD) index, sperm parameters, reproductive organ weight, histology and hormonal profile (testosterone, FSH and LH). Data were analyzed using Analysis of Variance. Level of significance was taken at P<0.05. Male offspring belonging to caffeine treated dams showed dose dependent significant decreases in birth weight. Male offspring from dams treated with caffeine during GD 1-7 and GD 1-21 had a significant increase in their AGD index. Also, male offspring from dams treated with 1.14 and 5.70 mg/kg body weight of caffeine during GD 8-14 had a significant increase in AGD index. Dams treated with 3.42 mg/kg body weight of caffeine during GD 15-21, had a significant increase in the AGD index of their male offspring. The sperm motility of offspring from dams treated with 5.70 mg/kg body weight of caffeine during GD 1-7 and GD 1-21 were significantly increased. Offspring of GD 8-14 and GD 15-21 dams treated with 3.42 and 5.70 mg/kg body weight of caffeine respectively, showed significantly reduced serum testosterone level. There was a significant decrease in the weight of testes of offspring from dams treated with caffeine during GD 8-14. Histological sections of testes of offspring from caffeine treated dams showed interstitial congestions, edema, reduced germinal epithelial height and detached basal membrane. Maternal caffeine exposure during

  15. Maternal deprivation effects on brain plasticity and recognition memory in adolescent male and female rats.

    PubMed

    Marco, Eva M; Valero, Manuel; de la Serna, Oscar; Aisa, Barbara; Borcel, Erika; Ramirez, Maria Javier; Viveros, María-Paz

    2013-05-01

    Data from both human and animal studies suggest that exposure to stressful life events at neonatal stages may increase the risk of psychopathology at adulthood. In particular, early maternal deprivation, 24 h at postnatal day (pnd) 9, has been associated with persistent neurobehavioural changes similar to those present in developmental psychopathologies such as depression and schizophrenic-related disorders. Most neuropsychiatric disorders first appear during adolescence, however, the effects of MD on adolescent animals' brain and behaviour have been scarcely explored. In the present study, we aimed to investigate the emotional and cognitive consequences of MD in adolescent male and female rats, as well as possible underlying neurobiological mechanisms within frontal cortex and hippocampus. Animals were exposed to a battery of behavioural tasks, from pnd 35 to 42, to evaluate cognitive [spontaneous alternation task (SAT) and novel object test (NOT)] and anxiety-related responses [elevated plus maze (EPM)] during adolescence. Changes in neuronal and glial cells, alterations in synaptic plasticity as well as modifications in cannabinoid receptor expression were investigated in a parallel group of control and adolescent (pnd 40) male and female animals. Notably, MD induced a significant impairment in recognition memory exclusively among females. A generalized decrease in NeuN expression was found in MD animals, together with an increase in hippocampal glial fibrillar acidic protein (GFAP) expression exclusively among MD adolescent males. In addition, MD induced in the frontal cortex and hippocampus of male and female adolescent rats a significant reduction in brain derived neurotrophic factor (BDNF) and postsynaptic density (PSD95) levels, together with a decrease in synaptophysin in frontal cortex and neural cell adhesion molecule (NCAM) in hippocampus. MD induced, in animals of both sexes, a significant reduction in CB1R expression, but an increase in CB2R that was

  16. Effects of Oral Maternal Administration of Caffeine on Reproductive Functions of Male Offspring of Wistar Rats.

    PubMed

    Ogunwole, Eunice; Akindele, Opeyemi O; Oluwole, Omobola F; Salami, S A; Raji, Y

    2015-01-01

    Caffeine was investigated for its possible fetal programming effects on reproductive function of male offspring. Sixty-five pregnant Wistar rats were grouped into four. Group 1 was control and received distilled water. Groups 2, 3 and 4 were treated orally with 1.14, 3.42 and 5.70 mg/kg body weight of caffeine respectively. Each group was subdivided into four based on gestation days (GD) 1-7, 8-14, 15-21 and 1-21. The day of parturition was taken as postnatal day zero (0). Male offspring were sacrificed on postnatal day 70. Parameters determined were: weight at birth, body weight at postnatal day 21 and 70, anogenital distance (AGD) index, sperm parameters, reproductive organ weight, histology and hormonal profile (testosterone, FSH and LH). Data were analyzed using Analysis of Variance. Level of significance was taken at P<0.05. Male offspring belonging to caffeine treated dams showed dose dependent significant decreases in birth weight. Male offspring from dams treated with caffeine during GD 1-7 and GD 1-21 had a significant increase in their AGD index. Also, male offspring from dams treated with 1.14 and 5.70 mg/kg body weight of caffeine during GD 8-14 had a significant increase in AGD index. Dams treated with 3.42 mg/kg body weight of caffeine during GD 15-21, had a significant increase in the AGD index of their male offspring. The sperm motility of offspring from dams treated with 5.70 mg/kg body weight of caffeine during GD 1-7 and GD 1-21 were significantly increased. Offspring of GD 8-14 and GD 15-21 dams treated with 3.42 and 5.70 mg/kg body weight of caffeine respectively, showed significantly reduced serum testosterone level. There was a significant decrease in the weight of testes of offspring from dams treated with caffeine during GD 8-14. Histological sections of testes of offspring from caffeine treated dams showed interstitial congestions, edema, reduced germinal epithelial height and detached basal membrane. Maternal caffeine exposure during

  17. Importance of Maternal Diabetes on the Chronological Deregulation of the Intrauterine Development: An Experimental Study in Rat

    PubMed Central

    Salazar García, Marcela; Reyes Maldonado, Elba; Revilla Monsalve, María Cristina; Villavicencio Guzmán, Laura; Reyes López, Alfonso; Sánchez-Gómez, Concepción

    2015-01-01

    We investigated whether maternal diabetes induced in rats using streptozotocin (STZ) on Day 5 of pregnancy affects the intrauterine developmental timeline. A total of 30 pregnant Sprague-Dawley diabetic rats (DRs) and 20 control rats (CRs) were used to obtain 21-day fetuses (F21) and newborn (NB) pups. Gestational age, weight, and body size were recorded as were the maxillofacial morphometry and morphohistological characteristics of the limbs. In DRs, pregnancy continued for ∼1.7 days, and delivery occurred 23 days postcoitus (DPC). In this group, the number of pups was lower, and 13% had maxillofacial defects. F21 in the DR group had lower weights and were smaller; moreover, the morphological characteristics of the maxillofacial structures, derived from the neural crest, were discordant with their chronological gestational age, resembling 18- to 19-day-old fetuses. These deficiencies were counterbalanced in NB pups. We conclude that hyperglycemia, which results from maternal diabetes and precedes embryo implantation, deregulates the intrauterine developmental timeline, restricts embryo-fetal growth, and primarily delays the remodeling and maturation of the structures derived from neural crest cells. PMID:25756053

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

    SciTech Connect

    Ronco, Ana Maria; Montenegro, Marcela; Castillo, Paula; Urrutia, Manuel; Saez, Daniel; Hirsch, Sandra; Zepeda, Ramiro; Llanos, Miguel N.

    2011-03-01

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

  19. Increased white matter neuron density in a rat model of maternal immune activation - Implications for schizophrenia.

    PubMed

    Duchatel, Ryan J; Jobling, Phillip; Graham, Brett A; Harms, Lauren R; Michie, Patricia T; Hodgson, Deborah M; Tooney, Paul A

    2016-02-01

    Interstitial neurons are located among white matter tracts of the human and rodent brain. Post-mortem studies have identified increased interstitial white matter neuron (IWMN) density in the fibre tracts below the cortex in people with schizophrenia. The current study assesses IWMN pathology in a model of maternal immune activation (MIA); a risk factor for schizophrenia. Experimental MIA was produced by an injection of polyinosinic:polycytidylic acid (PolyI:C) into pregnant rats on gestational day (GD) 10 or GD19. A separate control group received saline injections. The density of neuronal nuclear antigen (NeuN(+)) and somatostatin (SST(+)) IWMNs was determined in the white matter of the corpus callosum in two rostrocaudally adjacent areas in the 12week old offspring of GD10 (n=10) or GD19 polyI:C dams (n=18) compared to controls (n=20). NeuN(+) IWMN density trended to be higher in offspring from dams exposed to polyI:C at GD19, but not GD10. A subpopulation of these NeuN(+) IWMNs was shown to express SST. PolyI:C treatment of dams induced a significant increase in the density of SST(+) IWMNs in the offspring when delivered at both gestational stages with more regionally widespread effects observed at GD19. A positive correlation was observed between NeuN(+) and SST(+) IWMN density in animals exposed to polyI:C at GD19, but not controls. This is the first study to show that MIA increases IWMN density in adult offspring in a similar manner to that seen in the brain in schizophrenia. This suggests the MIA model will be useful in future studies aimed at probing the relationship between IWMNs and schizophrenia.

  20. Increased white matter neuron density in a rat model of maternal immune activation - Implications for schizophrenia.

    PubMed

    Duchatel, Ryan J; Jobling, Phillip; Graham, Brett A; Harms, Lauren R; Michie, Patricia T; Hodgson, Deborah M; Tooney, Paul A

    2016-02-01

    Interstitial neurons are located among white matter tracts of the human and rodent brain. Post-mortem studies have identified increased interstitial white matter neuron (IWMN) density in the fibre tracts below the cortex in people with schizophrenia. The current study assesses IWMN pathology in a model of maternal immune activation (MIA); a risk factor for schizophrenia. Experimental MIA was produced by an injection of polyinosinic:polycytidylic acid (PolyI:C) into pregnant rats on gestational day (GD) 10 or GD19. A separate control group received saline injections. The density of neuronal nuclear antigen (NeuN(+)) and somatostatin (SST(+)) IWMNs was determined in the white matter of the corpus callosum in two rostrocaudally adjacent areas in the 12week old offspring of GD10 (n=10) or GD19 polyI:C dams (n=18) compared to controls (n=20). NeuN(+) IWMN density trended to be higher in offspring from dams exposed to polyI:C at GD19, but not GD10. A subpopulation of these NeuN(+) IWMNs was shown to express SST. PolyI:C treatment of dams induced a significant increase in the density of SST(+) IWMNs in the offspring when delivered at both gestational stages with more regionally widespread effects observed at GD19. A positive correlation was observed between NeuN(+) and SST(+) IWMN density in animals exposed to polyI:C at GD19, but not controls. This is the first study to show that MIA increases IWMN density in adult offspring in a similar manner to that seen in the brain in schizophrenia. This suggests the MIA model will be useful in future studies aimed at probing the relationship between IWMNs and schizophrenia. PMID:26385575

  1. Effects of maternal nicotine exposure on thyroid hormone metabolism and function in adult rat progeny.

    PubMed

    Lisboa, P C; de Oliveira, E; Manhães, A C; Santos-Silva, A P; Pinheiro, C R; Younes-Rapozo, V; Faustino, L C; Ortiga-Carvalho, T M; Moura, E G

    2015-03-01

    Postnatal nicotine exposure leads to obesity and hypothyroidism in adulthood. We studied the effects of maternal nicotine exposure during lactation on thyroid hormone (TH) metabolism and function in adult offspring. Lactating rats received implants of osmotic minipumps releasing nicotine (NIC, 6 mg/kg per day s.c.) or saline (control) from postnatal days 2 to 16. Offspring were killed at 180 days. We measured types 1 and 2 deiodinase activity and mRNA, mitochondrial α-glycerol-3-phosphate dehydrogenase (mGPD) activity, TH receptor (TR), uncoupling protein 1 (UCP1), hypothalamic TRH, pituitary TSH, and in vitro TRH-stimulated TSH secretion. Expression of deiodinase mRNAs followed the same profile as that of the enzymatic activity. NIC exposure caused lower 5'-D1 and mGPD activities; lower TRβ1 content in liver as well as lower 5'-D1 activity in muscle; and higher 5'-D2 activity in brown adipose tissue (BAT), heart, and testis, which are in accordance with hypothyroidism. Although deiodinase activities were not changed in the hypothalamus, pituitary, and thyroid of NIC offspring, UCP1 expression was lower in BAT. Levels of both TRH and TSH were lower in offspring exposed to NIC, which presented higher basal in vitro TSH secretion, which was not increased in response to TRH. Thus, the hypothyroidism in NIC offspring at adulthood was caused, in part, by in vivo TRH-TSH suppression and lower sensitivity to TRH. Despite the hypothyroid status of peripheral tissues, these animals seem to develop an adaptive mechanism to preserve thyroxine to triiodothyronine conversion in central tissues. PMID:25653393

  2. Toxic Effects of Maternal Zearalenone Exposure on Intestinal Oxidative Stress, Barrier Function, Immunological and Morphological Changes in Rats

    PubMed Central

    Liu, Min; Gao, Rui; Meng, Qingwei; Zhang, Yuanyuan; Bi, Chongpeng; Shan, Anshan

    2014-01-01

    The present study was conducted to investigate the effects of maternal zearalenone (ZEN) exposure on the intestine of pregnant Sprague-Dawley (SD) rats and its offspring. Ninety-six pregnant SD rats were randomly divided into four groups and were fed with diets containing ZEN at concentrations of 0.3 mg/kg, 48.5 mg/kg, 97.6 mg/kg or 146.0 mg/kg from gestation days (GD) 1 to 7. All rats were fed with mycotoxin-free diet until their offspring were weaned at three weeks of age. The small intestinal fragments from pregnant rats at GD8, weaned dams and pups were collected and studied for toxic effects of ZEN on antioxidant status, immune response, expression of junction proteins, and morphology. The results showed that ZEN induced oxidative stress, affected the villous structure and reduced the expression of junction proteins claudin-4, occludin and connexin43 (Cx43) in a dose-dependent manner in pregnant rats. Different effects on the expression of cytokines were also observed both in mRNA and protein levels in these pregnant groups. Ingestion of high levels of ZEN caused irreversible damage in weaned dams, such as oxidative stress, decreased villi hight and low expression of junction proteins and cytokines. Decreased expression of jejunal interleukin-8 (IL-8) and increased expression of gastrointestinal glutathione peroxidase (GPx2) mRNA were detected in weaned offspring, indicating long-term damage caused by maternal ZEN. We also found that the Nrf2 expression both in mRNA and protein levels were up-regulated in the ZEN-treated groups of pregnant dams and the high-dose of ZEN group of weaned dams. The data indicate that modulation of Nrf2-mediated pathway is one of mechanism via which ZEN affects gut wall antioxidant and inflammatory responses. PMID:25180673

  3. Inulin supplementation during gestation mitigates acrylamide-induced maternal and fetal brain oxidative dysfunctions and neurotoxicity in rats.

    PubMed

    Krishna, Gokul; Muralidhara

    2015-01-01

    Accumulating evidence suggests that the developing brain is more susceptible to a variety of chemicals. Recent studies have shown a link between the enteric microbiota and brain function. While supplementation of non-digestible oligosaccharides during pregnancy has been demonstrated to positively influence human health mediated through stimulation of beneficial microbiota, our understanding on their neuromodulatory propensity is limited. In the present study, our primary focus was to examine whether supplementation of inulin (a well known fructan) during gestation can abrogate acrylamide (ACR)-induced oxidative impairments and neurotoxicity in maternal and fetal brain of rats. Initially, in a dose-determinative study, we recapitulated the impact of ACR exposure during gestation days (GD 6-19) on gestational parameters, extent of oxidative impairments in brain (maternal/fetal), cholinergic function and neurotoxicity. Subsequently, pregnant rats orally (gavage) administered with inulin (IN, 2 g/kg/day in two equal installments) supplements during gestation days (GD 0-19) were exposed to ACR (200 ppm) in drinking water. IN supplements significantly attenuated ACR-induced changes in exploratory activity (reduced open field exploration) measured on GD 14. Further, IN restored the placental weights among ACR exposed dams. Analysis of biochemical markers revealed that IN supplements effectively offset ACR associated oxidative stress not only in the maternal brain, but in the fetal brain as well. Elevated levels of protein carbonyls in maternal brain regions were completely normalized with IN supplements. More importantly, IN supplements significantly augmented the number of Bifidobacteria in the cecum of ACR rats which correlated well with the neurorestorative effect as evidenced by restored dopamine levels in the maternal cortex and fetal brain acetylcholinesterase activity among ACR-exposed dams. Further, IN supplements also conferred significant protection against

  4. Maternal presence and rearing condition affect responses to a live predator in kangaroo rats (Dipodomys heermanni arenae).

    PubMed

    Yoerg, S I; Shier, D M

    1997-12-01

    Experiment 1 compared the responses of wild-caught adult and captive-born adult and juvenile kangaroo rats (Dipodomys heermanni arenae) to a live snake. Wild-caught adult rats were less active and monitored the snake more than during a control condition; captive-born juvenile rats did not behave differently during snake and control tests. Snake-naive adult rats behaved more like the wild-caught adult rats, but not on all measures. In Experiment 2, pups were tested at 25 and 50 days of age in 4 conditions: no-snake control, alone with the snake, with a sibling and the snake, and with the mother and the snake. Pups did not behave differently during control and snake tests, but during tests with the mother, pups faced the snake less and followed the mother. Younger pups were more often near the mother than a sibling and followed the mother more when the snake was present. Development of defensive behavior may depend on both predator experience and maternal influence.

  5. COCAINE-ASSOCIATED ODOR CUE RE-EXPOSURE INCREASES BLOOD OXYGENATION LEVEL DEPENDENT SIGNAL IN MEMORY AND REWARD REGIONS OF THE MATERNAL RAT BRAIN*

    PubMed Central

    Caffrey, Martha K.; Febo, Marcelo

    2013-01-01

    BACKGROUND Cue triggered relapse during the postpartum period can negatively impact maternal care. Given the high reward value of pups in maternal rats, we designed an fMRI experiment to test whether offspring presence reduces the neural response to a cocaine associated olfactory cue. METHODS Cocaine conditioned place preference was carried out before pregnancy in the presence of two distinct odors that were paired with cocaine or saline (+Cue and −Cue). The BOLD response to +Cue and −Cue was measured in dams on postpartum days 2–4. Odor cues were delivered to dams in the absence and then the presence of pups. RESULTS Our data indicate that several limbic and cognitive regions of the maternal rat brain show a greater BOLD signal response to a +Cue versus −Cue. These include dorsal striatum, prelimbic cortex, parietal cortex, habenula, bed nucleus of stria terminalis, lateral septum and the mediodorsal and the anterior thalamic nucleus. Of the aforementioned brain regions, only the parietal cortex of cocaine treated dams showed a significant modulatory effect of pup presence. In this area of the cortex, cocaine exposed maternal rats showed a greater BOLD activation in response to the +Cue in the presence than in the absence of pups. CONCLUSIONS Specific regions of the cocaine exposed maternal rat brain are strongly reactive to drug associated cues. The regions implicated in cue reactivity have been previously reported in clinical imaging work, and previous work supports their role in various motivational and cognitive functions. PMID:24183499

  6. Treatment with tianeptine induces antidepressive-like effects and alters the neurotrophin levels, mitochondrial respiratory chain and cycle Krebs enzymes in the brain of maternally deprived adult rats.

    PubMed

    Della, Franciela P; Abelaira, Helena M; Réus, Gislaine Z; Santos, Maria Augusta B dos; Tomaz, Débora B; Antunes, Altamir R; Scaini, Giselli; Morais, Meline O S; Streck, Emilio L; Quevedo, João

    2013-03-01

    Maternally deprived rats were treated with tianeptine (15 mg/kg) once a day for 14 days during their adult phase. Their behavior was then assessed using the forced swimming and open field tests. The BDNF, NGF and energy metabolism were assessed in the rat brain. Deprived rats increased the immobility time, but tianeptine reversed this effect and increased the swimming time; the BDNF levels were decreased in the amygdala of the deprived rats treated with saline and the BDNF levels were decreased in the nucleus accumbens within all groups; the NGF was found to have decreased in the hippocampus, amygdala and nucleus accumbens of the deprived rats; citrate synthase was increased in the hippocampus of non-deprived rats treated with tianeptine and the creatine kinase was decreased in the hippocampus and amygdala of the deprived rats; the mitochondrial complex I and II-III were inhibited, and tianeptine increased the mitochondrial complex II and IV in the hippocampus of the non-deprived rats; the succinate dehydrogenase was increased in the hippocampus of non-deprived rats treated with tianeptine. So, tianeptine showed antidepressant effects conducted on maternally deprived rats, and this can be attributed to its action on the neurochemical pathways related to depression.

  7. Treatment with tianeptine induces antidepressive-like effects and alters the neurotrophin levels, mitochondrial respiratory chain and cycle Krebs enzymes in the brain of maternally deprived adult rats.

    PubMed

    Della, Franciela P; Abelaira, Helena M; Réus, Gislaine Z; Santos, Maria Augusta B dos; Tomaz, Débora B; Antunes, Altamir R; Scaini, Giselli; Morais, Meline O S; Streck, Emilio L; Quevedo, João

    2013-03-01

    Maternally deprived rats were treated with tianeptine (15 mg/kg) once a day for 14 days during their adult phase. Their behavior was then assessed using the forced swimming and open field tests. The BDNF, NGF and energy metabolism were assessed in the rat brain. Deprived rats increased the immobility time, but tianeptine reversed this effect and increased the swimming time; the BDNF levels were decreased in the amygdala of the deprived rats treated with saline and the BDNF levels were decreased in the nucleus accumbens within all groups; the NGF was found to have decreased in the hippocampus, amygdala and nucleus accumbens of the deprived rats; citrate synthase was increased in the hippocampus of non-deprived rats treated with tianeptine and the creatine kinase was decreased in the hippocampus and amygdala of the deprived rats; the mitochondrial complex I and II-III were inhibited, and tianeptine increased the mitochondrial complex II and IV in the hippocampus of the non-deprived rats; the succinate dehydrogenase was increased in the hippocampus of non-deprived rats treated with tianeptine. So, tianeptine showed antidepressant effects conducted on maternally deprived rats, and this can be attributed to its action on the neurochemical pathways related to depression. PMID:23325329

  8. Generational reproductive outcomes in Wistar rats maternally exposed to Ricinus communis oil at different stages of gestation.

    PubMed

    Salami, S A; Raji, Y

    2015-10-01

    Fetal programming hypothesis presupposes that stimulus or insult acting during critical periods of uterine growth and development may permanently alter tissue structure and function. Ricinus communis oil (RCO) has been reported to possess/used as laxative, labor-inducing and estrogenic properties. Generational reproductive effects of maternal exposure to RCO was investigated in rats. A total of 25 pregnant rats randomly assigned to five equal groups were treated with distilled water (control, group 1), RCO (950 mg/kg p.o.) during gestation days (GD) 1-7, 7-14, 14-21 and 1-21, respectively. Birth weight, morphometric data, anogenital distance (AGD), pubertal age, sperm parameters, hormonal profile, organ weight and histopathology were determined in the first (F1) and second (F2) filial generations. Results showed a significant decrease (P<0.05) in birth weight/morphometric data in male pups from the GD 1-7 and 7-14 groups. AGD decreased significantly in RCO-treated F1 males. Pubertal age of F1 females decreased significantly (P<0.05) compared with controls. At postnatal day 90, F1 males from the RCO-treated group showed significant decrease in testis weight, body weight, sperm count, motility and normal morphology. Testosterone levels were significantly decreased in RCO-treated F1 males, which also showed testicular interstitial edema and epididymal hypospermia. Only pubertal indexes were altered in F2 rats. Maternal exposure to RCO at early gestation periods impaired androgen-mediated reproductive end points in the first generation of rats. RCO exhibits endocrine disrupting capabilities.

  9. Maternal Nicotine Exposure During Late Gestation and Lactation Increases Anxiety-Like and Impulsive Decision-Making Behavior in Adolescent Offspring of Rat

    PubMed Central

    Lee, Hyunchan; Chung, Sooyeon; Noh, Jihyun

    2016-01-01

    Prenatal nicotine exposure over an entire pregnancy has been associated with an increased prevalence of hyperactivity, anxiety-like behavior and depression-like behavior in mature rats. However, the effects of maternal nicotine exposure in late gestation and lactation on the psychology and behavior of adolescent rat offspring are unclear. Thus, we investigated the effect of nicotine exposure during late gestation and lactation on anxiety-like and impulsive decision-making behavior in adolescent offspring of rat. Female rats were orally exposed to nicotine which is within range of plasma level of human chronic smokers during the period of third last period of gestation and lactation. When the offspring were weaned, we observed alterations in the anxiety-like behavior and decision-making ability of adolescent rat offspring using light/dark box test and T-maze delay-based cost-benefit decision-making task. The maternal consumption of nicotine reduced both the time spent in the light compartment and the number of transitions compared to nicotine-free rats. Moreover, such nicotine exposed adolescent offspring rats showed impulsive decision making which chose the instant reward in a decision-making situation. We found that nicotine exposure during late gestation and lactation induces an increase in anxiety-like and impulsive decision-making behavior at this developmental stage. These findings suggest that maternal nicotine-exposed offspring are at an increased risk of developing anxious and impulsive behavior.

  10. Maternal exposure to environmental enrichment before and during gestation influences behaviour of rat offspring in a sex-specific manner.

    PubMed

    Zuena, Anna Rita; Zinni, Manuela; Giuli, Chiara; Cinque, Carlo; Alemà, Giovanni Sebastiano; Giuliani, Alessandro; Catalani, Assia; Casolini, Paola; Cozzolino, Roberto

    2016-09-01

    The beneficial effects of Environmental Enrichment (EE) applied immediately after weaning or even in adulthood have been widely demonstrated. Less is known about the possible changes in behaviour and brain development of the progeny following the exposure of dams to EE. In order to further investigate this matter, female rats were reared in EE for 12weeks, from weaning until delivery. After having confirmed the presence of relevant behavioural effects of EE, both control and EE females underwent mating. Maternal behaviour was observed and male and female offspring were then administered a battery of behavioural test at different ages. EE mothers showed a decreased frequency of total nursing and, during the first 2days of lactation, an increase in licking/grooming behaviour. Maternal exposure to EE affected offspring behaviour in a sex-specific manner: social play behaviour and anxiety-like behaviour were increased in males but not in females and learning ability was improved only in females. As a general trend, maternal EE had a marked influence on motility in male and female offspring in both locomotor activity and swimming speed. Overall, this study highlights the importance of environmental stimulation, not only in the animals directly experiencing EE, but for their progeny too, opening the way to new hypothesis on the heritability mechanisms of behavioural traits.

  11. Effects of environmental stress during pregnancy on maternal and fetal plasma corticosterone and progesterone in the rat

    SciTech Connect

    Fleming, D.E.; Rhees, R.W.; Williams, S.R.; Kurth, S.M.

    1986-03-01

    Prenatal stress applied during a presumed critical period (third trimester) for sexual differentiation of the brain has been shown to alter development and influence sexual behavior. This experiment was designed to study the effects of environmental stress (restraint/illumination/heat) on maternal and fetal plasma corticosterone and progesterone titers. These hormones were studied since corticosterone has been shown to alter brain differentiation and progesterone has anti-androgen properties and since the secretion of both from the adrenal cortex is stimulated by ACTH. Plasma corticosterone and progesterone titers of both stressed and control gravid rats and their fetuses were measured on gestational days 18 and 20 by radioimmunoassay. Prenatal stress significantly reduced fetal body weight and fetal adrenal weight. Maternal pituitary weight was significantly increased. Prenatal stress caused a significant elevation in maternal corticosterone and progesterone titers and in fetal corticosterone titers. There was no difference between prenatal stressed and control fetal plasma progesterone levels. These data demonstrate that environmental stress significantly increases adrenal activity beyond that brought about naturally by pregnancy, and therefore may modify sequential hormonal events during fetal development.

  12. Maternal high-fat diet induces obesity and adrenal and thyroid dysfunction in male rat offspring at weaning.

    PubMed

    Franco, J G; Fernandes, T P; Rocha, C P D; Calviño, C; Pazos-Moura, C C; Lisboa, P C; Moura, E G; Trevenzoli, I H

    2012-11-01

    Maternal nutritional status affects the future development of offspring. Both undernutrition and overnutrition in critical periods of life (gestation or lactation) may cause several hormonal changes in the pups and programme obesity in the adult offspring. We have shown that hyperleptinaemia during lactation results in central leptin resistance, higher adrenal catecholamine secretion, hyperthyroidism, and higher blood pressure and heart rate in the adult rats. Here, we evaluated the effect of a maternal isocaloric high-fat diet on breast milk composition and its impact on leptinaemia, energy metabolism, and adrenal and thyroid function of the offspring at weaning. We hypothesised that the altered source of fat in the maternal diet even under normal calorie intake would disturb the metabolism of the offspring. Female Wistar rats were fed a normal (9% fat; C group) or high-fat diet (29% fat as lard; HF group) for 8 weeks before mating and during pregnancy and lactation. HF mothers presented increased total body fat content after 8 weeks (+27%, P < 0.05) and a similar fat content at the end of lactation. In consequence, the breast milk from the HF group had higher concentration of protein (+18%, P < 0.05), cholesterol (+52%, P < 0.05) and triglycerides (+86%, P < 0.05). At weaning, HF offspring had increased body weight (+53%, P < 0.05) and adiposity (2 fold, P < 0.05), which was associated with lower β3-adrenoreceptor content in adipose tissue (-40%, P < 0.05). The offspring also presented hyperglycaemia (+30%, P < 0.05) and hyperleptinaemia (+62%, P < 0.05). In the leptin signalling pathway in the hypothalamus, we found lower p-STAT3/STAT3 (-40%, P < 0.05) and SOCS3 (-55%, P < 0.05) content in the arcuate nucleus, suggesting leptin resistance. HF offspring also had higher adrenal catecholamine content (+17%, P < 0.05), liver glycogen content (+50%, P < 0.05) and hyperactivity of the thyroid axis at weaning. Our results suggest that a high fat diet increases

  13. Long term sex-dependent psychoneuroendocrine effects of maternal deprivation and juvenile unpredictable stress in rats.

    PubMed

    Llorente, R; Miguel-Blanco, C; Aisa, B; Lachize, S; Borcel, E; Meijer, O C; Ramirez, M J; De Kloet, E R; Viveros, M P

    2011-04-01

    We have analysed the long-term psychoneuroendocrine effects of maternal deprivation (MD) [24 h at postnatal day (PND) 9] and/or exposure to chronic unpredictable stress (CUS) during the periadolescent period (PND 28 to PND 43) in male and female Wistar rats. Animals were tested in the elevated plus maze (EPM, anxiety) at PND 44 and in two memory tests, spontaneous alternation and novel object recognition (NOT) in adulthood. The expression of hippocampal glucocorticoid (GR) and mineralocorticoid (MR) receptors, as well as of synaptophysin, neural cell adhesion molecule and brain-derived neurotrophic factor, was analysed by in situ hybridisation in selected hippocampal regions. Endocrine determinations of leptin, testosterone and oestradiol plasma levels were carried out by radioimmunoassay. Young CUS animals showed decreased anxiety behaviour in the EPM (increased percentage of time and entries in the open arms) irrespective of neonatal treatment. Memory impairments were induced by the two stressful treatments as was revealed by the NOT, with males being most clearly affected. Although each stressful procedure, when considered separately, induced different (always decrements) effects on the three synaptic molecules analysed and affected males and females differently, the combination of MD and CUS induced an unique disruptive effect on the three synaptic plasticity players. MD induced a long-term significant decrease in hippocampal GR only in males, whereas CUS tended to increase MR in males and decrease MR in females. Both neonatal MD and periadolescent CUS induced marked reductions in testosterone and oestradiol in males, whereas MD male animals also showed significantly decreased leptin levels. By contrast, in females, none of the hormones analysed was altered by any of the stressful procedures. Taking our data together in support of the 'two-hit' hypothesis, MD during neonatal life and/or exposure to CUS during the periadolescent period induced a permanent

  14. Mitochondrial dysmorphology in the neuroepithelium of rat embryos following a single dose of maternal hyperthermia during gestation.

    PubMed

    Padmanabhan, Rengasamy; Al-Menhali, Noura Musaed; Tariq, Saeed; Shafiullah, Mohamed

    2006-08-01

    Hyperthermia is teratogenic to human and animal embryos and induces mainly anomalies of the nervous system. However, the teratogenic mechanism is poorly understood. Mammalian embryos are known to switch from anaerobic to aerobic metabolism around the time of neural tube closure. This critical event might be sensitive to hyperthermia. The objective of the present study was to evaluate the ultrastructural changes of the mitochondria of the neuroepithelium (NE) of rat embryos following maternal exposure to hyperthermia. Pregnant rats were heat stressed for an hour on gestation day (GD) 9 and embryos were examined by electron microscopy on GD 10. NE presented extensive apoptosis. Intercellular junctions were weakened and copious cellular debris projected into the ventricle. The mitochondria were of diverse size and shape. Most of them were swollen and had short cristae and electron dense matrix. Hydropic changes were also observed in numerous mitochondria. Lipid-laden mitochondria were found in the apical portions of neuroblasts. The mesenchyme (ME) of heat-treated embryos showed paucity of cells and only as frequent apoptosis as the controls. Their mitochondria also showed changes similar to those of the NE. Additionally extensive lipid accumulation was observed in and in the vicinity of mitochondria, often surrounded by short strands of endoplasmic reticulum. Whereas mitochondrial pathology was associated with profound apoptosis in the NE, growth restriction and lipid accumulation accompanied mitochondrial changes in the ME. The results of this study indicate that the embryonic response to maternal heat shock is tissue-specific and morphologically distinct in this species. PMID:16847614

  15. Effect of maternal alcohol and nicotine intake, individually and in combination, on fetal growth in the rat

    SciTech Connect

    Leichter, J. )

    1991-03-15

    The effect of maternal ethanol and nicotine administration, separately and in combination, on fetal growth of rats was studied. Nicotine was administered by gavage for the entire gestational period. Alcohol was given in drinking water for 4 weeks prior to mating and 30% throughout gestation. Appropriate pair-fed and ad libitum control animals were included to separate the effect of ethanol and nicotine on the outcome of pregnancy from those produced by the confounding variables of malnutrition. Body weights of fetuses exposed to alcohol alone or in combination with nicotine were significantly lower than those of the pair-fed and ad libitum controls. However, the difference in fetal body weight between the alcohol plus nicotine and the alcohol alone group was not significant. Similarly, in the rats administered nicotine only, fetal weight was not significantly different compared to control animals. The results of this study indicate that maternal alcohol intake impairs fetal growth and nicotine does not, regardless whether it is administered separately or in combination with alcohol for the entire gestational period.

  16. Effects of Maternal Marginal Iodine Deficiency on Dendritic Morphology in the Hippocampal CA1 Pyramidal Neurons in Rat Offspring.

    PubMed

    Min, Hui; Wang, Yi; Dong, Jing; Wang, Yuan; Yu, Ye; Shan, Zhongyan; Xi, Qi; Teng, Weiping; Chen, Jie

    2016-06-01

    Although the salt iodization programmes are taken to control iodine deficiency (ID), some regions are still suffering from marginal ID. During pregnancy, marginal ID frequently leads to subtle insufficiency of thyroid hormones, characterized as low serum T4 levels. Therefore, the present research was to explore the effects of maternal marginal ID exposure on dendritic arbor growth in the hippocampal CA1 region and the underlying mechanisms. We established Wistar rat models with ID diet during pregnancy and lactation. The overall daily iodine intakes of the rats were estimated as 7.0, 5.0 and 1.5 μg/day in the control, marginal ID and severe ID groups, respectively. To study the morphological alterations of pyramidal neurons, Golgi-Cox procedure was conducted in the hippocampus. Sholl analyses demonstrated a slight decrease in the total length and branching numbers of basal dendrites on postnatal day (PN) 7, PN14 and PN21 in marginal ID group relative to the controls. However, there was no overt morphological change observed in apical dendrites. Immunofluorescence and Western blot analysis indicated that phosphorylation of MAP2, stathmin and JNK1 was down-regulated in marginal ID group. We speculate that the pups treated with maternal marginal ID subjected to subtle changes in dendritic growth of CA1 pyramidal neurons, which may be associated with the dysregulation of MAP2 and stathmin in a JNK1-dependent manner. PMID:27017219

  17. Structural equation modeling and nested ANOVA: Effects of lead exposure on maternal and fetal growth in rats

    SciTech Connect

    Hamilton, J.D. ); O'Flaherty, E.J.; Shukla, R.; Gartside, P.S. ); Ross, R. )

    1994-01-01

    This study provided an assessment of the effects of lead on early growth in rats based on structural equation modeling and nested analysis of variance (ANOVA). Structural equation modeling showed that lead in drinking water (250, 500, or 1000 ppm) had a direct negative effect on body weight and tail length (i.e., growth) in female rats during the first week of exposure. During the following 2 weeks of exposure, high correlation between growth measurements taken over time resulted in reduced early postnatal growth. By the fourth week of exposure, reduced growth was not evident. Mating began after 8 weeks of exposure, and exposure continued during gestation. Decreased fetal body weight was detected when the effects of litter size, intrauterine position, and sex were controlled in a nested ANOVA. Lead exposure did not appear to affect fetal skeletal development, possibly because lead did not alter maternal serum calcium and phosphorus levels. The effect of lead on individual fetal body weight suggests that additional studies are needed to examine the effect of maternal lead exposure on fetal development and early postnatal growth. 24 refs., 4 figs., 6 tabs.

  18. Outcome of pregnancy in the rat with mild hyperphenylalaninaemia and hypertyrosinaemia: implications for the management of "human maternal PKU".

    PubMed

    Lewis, S A; Lyon, I C; Elliott, R B

    1985-01-01

    In attempting to determine the effects of mildly elevated maternal phenylalanine (Phe) blood levels on the developing fetal rat brain, a dietary supplement of Phe was given, under taste cover of Aspartame. Phe and tyrosine (Tyr) levels were mildly elevated throughout pregnancy without evidence of malnutrition. Mild hyperphenylalaninaemia with concurrent hypertyrosinaemia induced in rats prior to conception resulted in microcephaly and lasting behavioural problems in the offspring, specifically hyperactivity and learning difficulties. Dams fed Tyr to produce Tyr levels equivalent to the Phe-fed animals showed only the learning difficulties among the offspring. alpha-Methyl Phe, a Phe hydroxylase inhibitor, fed in conjunction with Phe, at the level relevant to these experiments, resulted in raised Tyr levels and does not provide a better method of determining whether mildly elevated maternal Phe levels alone, or Phe and Tyr in combination, cause the abnormality found in the offspring of Phe-supplemented dams. Therapeutic addition of Tyr to diets of mothers with even mild hyperphenylalaninaemia should be approached with caution as mild co-elevation of Phe and Tyr in the fetus may be harmful. In the face of such a possible therapeutic dilemma alternatives, such as dietary additions of other essential amino acids to limit fetal brain damage, need to be explored.

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

    PubMed

    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.

  20. TRPV1-mediated presynaptic transmission in basolateral amygdala contributes to visceral hypersensitivity in adult rats with neonatal maternal deprivation

    PubMed Central

    Xiao, Ying; Chen, Xiaoqi; Zhang, Ping-An; Xu, Qiya; Zheng, Hang; Xu, Guang-Yin

    2016-01-01

    The central mechanisms of visceral hypersensitivity remain largely unknown. It’s reported that there are highest densities of TRPV1 labeled neurons within basolateral amygdala (BLA). The aim of this study was to explore the role and mechanisms of TRPV1 in BLA in development of visceral hypersensitivity. Visceral hypersensitivity was induced by neonatal maternal deprivation (NMD) and was quantified by abdominal withdrawal reflex. Expression of TRPV1 was determined by Western blot. The synaptic transmission of neurons in BLA was recorded by patch clamping. It was found that the expression of TRPV1 in BLA was significantly upregulated in NMD rats; glutamatergic synaptic activities in BLA were increased in NMD rats; application of capsazepine (TRPV1 antagonist) decreased glutamatergic synaptic activities of BLA neurons in NMD slices through a presynaptic mechanism; application of capsaicin (TRPV1 agonist) increased glutamatergic synaptic activities of BLA neurons in control slices through presynaptic mechanism without affecting GABAergic synaptic activities; microinjecting capsazepine into BLA significantly increased colonic distension threshold both in control and NMD rats. Our data suggested that upregulation of TRPV1 in BLA contributes to visceral hypersensitivity of NMD rats through enhancing excitation of BLA, thus identifying a potential target for treatment of chronic visceral pain. PMID:27364923

  1. Disruptions in the hypothalamic-pituitary-gonadal axis in rat offspring following prenatal maternal exposure to lipopolysaccharide.

    PubMed

    Izvolskaia, Marina S; Tillet, Yves; Sharova, Viktoria S; Voronova, Svetlana N; Zakharova, Lyudmila A

    2016-01-01

    Postnatal treatment with bacterial endotoxin lipopolysaccharide (LPS) changes the activity of the hypothalamic-pituitary-gonadal (HPG) axis and the gonadotropin-releasing hormone (GnRH) surge in rats. Exposure to an immune challenge in the critical periods of development has profound and long-lasting effects on the stress response, immune, metabolic, and reproductive functions. Prenatal LPS treatment delays the migration of GnRH neurons associated with increased cytokine release in maternal and fetal compartments. We investigated the effects of a single maternal exposure to LPS (18 μg/kg, i.p.) on day 12 (embryonic day (E)12) of pregnancy on reproductive parameters in rat offspring. Hypothalamic GnRH content, plasma luteinizing hormone (LH), testosterone, and estradiol concentrations were measured in both male and female offsprings at different stages of postnatal development by RIA and ELISA (n = 10 each per group). Body weight and in females day of vaginal opening (VO) were recorded. In offspring exposed to LPS prenatally, compared with controls, body weight was decreased in both sexes at P5 and P30; in females, VO was delayed; hypothalamic GnRH content was decreased at postnatal days 30-60 (P30-P60) in both sexes; plasma LH concentration was decreased at P14-P60 in females; plasma concentrations of testosterone/estradiol were increased at P14 in females, and plasma estradiol was increased at P14 in males. Hence activation of the maternal immune system by LPS treatment at a prenatal critical period leads to decreased GnRH and LH levels in pre- and postpubertal life and sex steroid imbalance in the prepubertal period, and delayed sexual maturation of female offspring.

  2. Treatment with a monoclonal antibody against methamphetamine and amphetamine reduces maternal and fetal rat brain concentrations in late pregnancy.

    PubMed

    White, Sarah J; Hendrickson, Howard P; Atchley, William T; Laurenzana, Elizabeth M; Gentry, W Brooks; Williams, D Keith; Owens, S Michael

    2014-08-01

    We hypothesized that treatment of pregnant rat dams with a dual reactive monoclonal antibody (mAb4G9) against (+)-methamphetamine [METH; equilibrium dissociation rate constant (KD) = 16 nM] and (+)-amphetamine (AMP; KD = 102 nM) could confer maternal and fetal protection from brain accumulation of both drugs of abuse. To test this hypothesis, pregnant Sprague-Dawley rats (on gestational day 21) received a 1 mg/kg i.v. METH dose, followed 30 minutes later by vehicle or mAb4G9 treatment. The mAb4G9 dose was 0.56 mole-equivalent in binding sites to the METH body burden. Pharmacokinetic analysis showed baseline METH and AMP elimination half-lives were congruent in dams and fetuses, but the METH volume of distribution in dams was nearly double the fetal values. The METH and AMP area under the serum concentration-versus-time curves from 40 minutes to 5 hours after mAb4G9 treatment increased >7000% and 2000%, respectively, in dams. Fetal METH serum did not change, but AMP decreased 23%. The increased METH and AMP concentrations in maternal serum resulted from significant increases in mAb4G9 binding. Protein binding changed from ∼15% to > 90% for METH and AMP. Fetal serum protein binding appeared to gradually increase, but the absolute fraction bound was trivial compared with the dams. mAb4G9 treatment significantly reduced METH and AMP brain values by 66% and 45% in dams and 44% and 46% in fetuses (P < 0.05), respectively. These results show anti-METH/AMP mAb4G9 therapy in dams can offer maternal and fetal brain protection from the potentially harmful effects of METH and AMP.

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

    PubMed

    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. PMID:27469996

  4. Contribution of maternal thyroxine to fetal thyroxine pools in normal rats near term

    SciTech Connect

    Morreale de Escobar, G.; Calvo, R.; Obregon, M.J.; Escobar Del Rey, F. )

    1990-05-01

    Normal dams were equilibrated isotopically with ({sup 125}I)T4 infused from 11 to 21 days of gestation, at which time maternal and fetal extrathyroidal tissues were obtained to determine their ({sup 125}I)T4 and T4 contents. The specific activity of the ({sup 125}I)T4 in the fetal tissues was lower than in maternal T4 pools. The extent of this change allows evaluation of the net contribution of maternal T4 to the fetal extrathyroidal T4 pools. At 21 days of gestation, near term, this represents 17.5 +/- 0.9% of the T4 in fetal tissues, a value considerably higher than previously calculated. The methodological approach was validated in dams given a goitrogen to block fetal thyroid function. The specific activities of the ({sup 125}I)T4 in maternal and fetal T4 pools were then similar, confirming that in cases of fetal thyroid impairment the T4 in fetal tissues is determined by the maternal contribution. Thus, previous statements that in normal conditions fetal thyroid economy near term is totally independent of maternal thyroid status ought to be reconsidered.

  5. Maternal Glucocorticoid Deficit Affects Hypothalamic-Pituitary-Adrenal Function and Behavior of Rat Offspring

    PubMed Central

    Wilcoxon, Jennifer Slone; Redei, Eva E.

    2007-01-01

    Detrimental consequences of prenatal stress include increased hypothalamic-pituitary-adrenal (HPA) function, anxiety and depression-like behavior in adult offspring. To identify the role of maternal corticosterone milieu in the fetal programming of adult function, we measured these same behavioral and hormonal endpoints after maternal adrenalectomy (ADX) and replacement with normal or moderately high levels of corticosterone (CORT). Adult male and female offspring exhibited differing HPA responses to maternal ADX. In female offspring of ADX mothers, exaggerated plasma ACTH stress responses were reversed by the higher, but not the lower, dose of maternal CORT. In contrast, male offspring of both ADX and ADX dams with higher CORT replacement showed exaggerated ACTH stress responses. Hypothalamic glucocorticoid receptor (GR) expression was decreased in these latter groups, while hippocampal GR increased only in the ADX offspring. Activity of young offspring of ADX dams replaced with the higher dose of CORT decreased in the open field test of exploration/anxiety, while immobility behavior of adult offspring in the forced swim test of depression increased following maternal ADX or higher levels of CORT replacement. Interestingly, for some measures, none or moderately high CORT replacement resulted in similar deficits in this study. These findings are in accord with consequences of prenatal stress or prenatal dexamethasone exposure, suggesting that a common mechanism may underlie the effects of too low or too high maternal glucocorticoids on adult HPA function and behavior. PMID:17275820

  6. High Fat Diet Administration during Specific Periods of Pregnancy Alters Maternal Fatty Acid Profiles in the Near-Term Rat.

    PubMed

    Cerf, Marlon E; Herrera, Emilio

    2016-01-01

    Excessive fat intake is a global health concern as women of childbearing age increasingly ingest high fat diets (HFDs). We therefore determined the maternal fatty acid (FA) profiles in metabolic organs after HFD administration during specific periods of gestation. Rats were fed a HFD for the first (HF1), second (HF2), or third (HF3) week, or for all three weeks (HFG) of gestation. Total maternal plasma non-esterified fatty acid (NEFA) concentrations were monitored throughout pregnancy. At day 20 of gestation, maternal plasma, liver, adipose tissue, and placenta FA profiles were determined. In HF3 mothers, plasma myristic and stearic acid concentrations were elevated, whereas docosahexaenoic acid (DHA) was reduced in both HF3 and HFG mothers. In HF3 and HFG mothers, hepatic stearic and oleic acid proportions were elevated; conversely, DHA and linoleic acid (LA) proportions were reduced. In adipose tissue, myristic acid was elevated, whereas DHA and LA proportions were reduced in all mothers. Further, adipose tissue stearic acid proportions were elevated in HF2, HF3, and HFG mothers; with oleic acid increased in HF1 and HFG mothers. In HF3 and HFG mothers, placental neutral myristic acid proportions were elevated, whereas DHA was reduced. Further, placental phospholipid DHA proportions were reduced in HF3 and HFG mothers. Maintenance on a diet, high in saturated fat, but low in DHA and LA proportions, during late or throughout gestation, perpetuated reduced DHA across metabolic organs that adapt during pregnancy. Therefore a diet, with normal DHA proportions during gestation, may be important for balancing maternal FA status.

  7. Periaqueductal gray μ and κ opioid receptors determine behavioral selection from maternal to predatory behavior in lactating rats.

    PubMed

    Klein, Marianne Orlandini; Cruz, Aline de Mello; Machado, Franciele Corrêa; Picolo, Gisele; Canteras, Newton Sabino; Felicio, Luciano Freitas

    2014-11-01

    Every mother must optimize her time between caring for her young and her subsistence. The rostro lateral portion of the periaqueductal grey (rlPAG) is a critical site that modulates the switch between maternal and predatory behavior. Opioids play multiple roles in both maternal behavior and this switching process. The present study used a pharmacological approach to evaluate the functional role of rlPAG μ and κ opioid receptors in behavioral selection. Rat dams were implanted with a guide cannula in the rlPAG and divided into three experiments in which we tested the role of opioid agonists (Experiment 1), the influence of μ and κ opioid receptor blockade in the presence of morphine (Experiment 2), and the influence of μ and κ opioid receptor blockade (Experiment 3). After behavioral test, in Experiment 4, we evaluated rlPAG μ and κ receptor activation in all Experiments 1-3. The results showed that massive opioidergic activation induced by morphine in the rlPAG inhibited maternal behavior without interfering with predatory hunting. No behavioral changes and no receptor activation were promoted by the specific agonist alone. However, κ receptor blockade increased hunting behavior and increased the level of μ receptor activation in the rlPAG. Thus, endogenous opioidergic tone might be modulated by a functional interaction between opioid receptor subtypes. Such a compensatory receptor interaction appears to be relevant for behavioral selection among motivated behaviors. These findings indicate a role for multiple opioid receptor interactions in the modulation of behavioral selection between maternal and predatory behaviors in the PAG.

  8. 1,25(OH) sub 2 D sub 3 and Ca-binding protein in fetal rats: Relationship to the maternal vitamin D status

    SciTech Connect

    Verhaeghe, J.; Thomasset, M.; Brehier, A.; Van Assche, F.A.; Bouillon, R. Institut National de la Sante et de la Recherche Medical )

    1988-04-01

    The autonomy and functional role of fetal 1,25-dihydroxyvitamin D{sub 3} (1,25(OH){sub 2}D{sub 3}) were investigated in nondiabetic and diabetic BB rats fed diets containing 0.85% calcium-0.7% phosphorus or 0.2% calcium and phosphorus and in semistarved rats on the low calcium-phosphorus diet. The changes in maternal and fetal plasma 1,25(OH){sub 2}D{sub 3} were similar: the levels were increased by calcium-phosphorus restriction and decreased by diabetes and semistarvation. Maternal and fetal 1,25(OH){sub 2}D{sub 3} levels were correlated. The vitamin D-dependent calcium-binding proteins (CaBP{sub 9K} and CaBP{sub 28K}) were measured in multiple maternal and fetal tissues and in the placenta of nondiabetic, diabetic, and calcium-phosphorus-restricted rats. The distributions of CaBP{sub 9K} and CaBP{sub 28K} in the pregnant rat were similar to that of the growing rat. The increased maternal plasma 1,25(OH){sub 2}D{sub 3} levels in calcium-phosphorus-restricted rats were associated with higher duodenal CaBP{sub 9K} and renal CaBPs, but placental CaBP{sub 9K} was not different. In diabetic pregnant rats, duodenal CaBP{sub 9K} was not different. In diabetic pregnant rats, duodenal CaBP{sub 9K} tended to be lower, while renal CaBPs were normal; placental CaBP{sub 9K} was decreased. The results indicate that in the rat fetal 1,25(OH){sub 2}D{sub 3} depends on maternal 1,25(OH){sub 2}D{sub 3} or on factors regulating maternal 1,25(OH){sub 2}D{sub 3}. The lack of changes in fetal CaBP in the presence of altered fetal plasma 1,25(OH){sub 2}D{sub 3} levels confirms earlier data showing that 1,25(H){sub 2}D{sub 3} has a limited hormonal function during perinatal development in the rat.

  9. Effect of maternal separation and chronic stress on hippocampal-dependent memory in young adult rats: evidence for the match-mismatch hypothesis.

    PubMed

    Zalosnik, M I; Pollano, A; Trujillo, V; Suárez, M M; Durando, P E

    2014-09-01

    Adverse experiences early in life may sensitize the hippocampus to subsequent stressors throughout the individual's life. We analyzed in male rats, whether, the interaction between early maternal separation and chronic stress affects: (1) the volume of the dorsal hippocampus, (2) CA1, CA2/3 and dentate gyrus (DG) and (3) hippocampal-dependent memory in adulthood. Male Wistar rats were subjected to daily maternal separation for 4.5 h between postnatal days 1-21. From postnatal day 50, animals were exposed to a chronic unpredictable stress paradigm during 24 days. The volumes of the dorsal hippocampus, their areas or strata did not reveal significant differences between treatments. Non-maternally separated and stressed animals showed poor hippocampal performance in a contextual fear conditioning test, with a significant reduction in freezing behavior during post-conditioning compared with control and maternally separated and stressed animals. Also, memory retrieval 24 h after conditioning was significantly weaker in this group than in control animals. Memory performance in maternally separated and stressed rats was similar to control animals. Our results show an interaction between early environment experiences and chronic variable stress in young adulthood as evidence that early stressful experiences do not necessarily lead to a negative outcome but can help in maintaining brain plasticity and increase fitness when animals reach adulthood.

  10. High fat diet and in utero exposure to maternal obesity disrupts circadian rhythm and leads to metabolic programming of liver in rat offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The risk of obesity in adulthood is subject to programming beginning at conception. In animal models, exposure to maternal obesity and high fat diets influences the risk of obesity in the offspring. Among other long-term changes, offspring from obese rats develop hyperinsulinemia, hepatic steatosi...

  11. Maternal low protein diet leads to placental angiogenic compensation via dysregulated M1/M2 macrophages and TNFa expression in Sprague-Dawley rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A maternal low-protein (LP) diet results in low birth weight, increased offspring rapid adipose tissue catch-up growth, adult obesity, and insulin resistance in Sprague-Dawley rats. The placenta functions to fulfill the fetus’ nutrient demands. Placental function is dependent on regulation of immune...

  12. Maternal low protein diet leads to placental angiogenic compensation via dysregulated M1/M2 macrophages and TNFa expression in Sprague-Dawley rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A maternal low-protein (LP) diet results in low birth weight, increased offspring rapid adipose tissue catch-up growth, adult obesity, and insulin resistance in Sprague-Dawley rats. The placenta plays key roles in nutrient transport and fetal growth. Placental function is dependent on regulation of ...

  13. Effects of rifampicin, dexamethasone, St. John's Wort and Thyroxine on maternal and foetal expression of Abcb1 and organ distribution of talinolol in pregnant rats.

    PubMed

    Saljé, Karen; Lederer, Kirstin; Oswald, Stefan; Dazert, Eike; Warzok, Rolf; Siegmund, Werner

    2012-08-01

    It is well accepted that ABCB1 plays a critical role in absorption, distribution and elimination of many xenobiotics and drugs. Only little is known about the regulation and function of ABCB1 during pregnancy. Thus, the aim of this study is to investigate maternal, placental and foetal Abcb1 expression and function in pregnant rats after induction with rifampicin, dexamethasone, St. John's wort (SJW) or thyroxine. Wistar rats were orally treated with rifampicin (250 mg/kg), SJW (1.0 g/kg), thyroxine (9 μg/kg), dexamethasone (1 mg/kg) or 0.5% methylcellulose suspension (control) for 9 days during late pregnancy (each N = 5). Afterwards, organ mRNA expression and protein content of Abcb1a were determined. Tissue concentrations of the ABCB1 probe drug talinolol were measured after repeated administration of the drug (100 mg/kg, 9 days) and after induction with oral rifampicin (250 mg/kg, 9 days, N = 5). Abcb1 expression was substantially lower in foetal than in maternal organs. Abcb1 was significantly induced by SJW in the maternal jejunum and placenta, by dexamethasone in foetal brain and liver and by thyroxine in the placenta and maternal and foetal brain. Rifampicin induced Abcb1 in all maternal and foetal organs. However, organ distribution of talinolol was not influenced by comedication of rifampicin. In conclusion, maternal and foetal Abcb1 organ expression in pregnant rats is inducible by nuclear receptor agonists. Although rifampicin regulates maternal and foetal Abcb1 expression, organ distribution of talinolol remains unchanged most likely caused by the known inhibitory effect of rifampicin on Abcb1 function.

  14. Long Term Hippocampal and Cortical Changes Induced by Maternal Deprivation and Neonatal Leptin Treatment in Male and Female Rats.

    PubMed

    Mela, Virginia; Díaz, Francisca; Borcel, Erika; Argente, Jesús; Chowen, Julie A; Viveros, Maria-Paz

    2015-01-01

    Maternal deprivation (MD) during neonatal life has diverse long-term behavioral effects and alters the development of the hippocampus and frontal cortex, with several of these effects being sexually dimorphic. MD animals show a marked reduction in their circulating leptin levels, not only during the MD period, but also several days later (PND 13). A neonatal leptin surge occurs in rodents (beginning around PND 5 and peaking between PND 9 and 10) that has an important neurotrophic role. We hypothesized that the deficient neonatal leptin signaling of MD rats could be involved in the altered development of their hippocampus and frontal cortex. Accordingly, a neonatal leptin treatment in MD rats would at least in part counteract their neurobehavioural alterations. MD was carried out in Wistar rats for 24 h on PND 9. Male and female MD and control rats were treated from PND 9 to 13 with rat leptin (3 mg/kg/day sc) or vehicle. In adulthood, the animals were submitted to the open field, novel object memory test and the elevated plus maze test of anxiety. Neuronal and glial population markers, components of the glutamatergic and cannabinoid systems and diverse synaptic plasticity markers were evaluated by PCR and/or western blotting. Main results include: 1) In some of the parameters analyzed, neonatal leptin treatment reversed the effects of MD (eg., mRNA expression of hippocampal IGF1 and protein expression of GFAP and vimentin) partially confirming our hypothesis; 2) The neonatal leptin treatment, per se, exerted a number of behavioral (increased anxiety) and neural effects (eg., expression of the following proteins: NG2, NeuN, PSD95, NCAM, synaptophysin). Most of these effects were sex dependent. An adequate neonatal leptin level (avoiding excess and deficiency) appears to be necessary for its correct neuro-programing effect. PMID:26382238

  15. Long Term Hippocampal and Cortical Changes Induced by Maternal Deprivation and Neonatal Leptin Treatment in Male and Female Rats.

    PubMed

    Mela, Virginia; Díaz, Francisca; Borcel, Erika; Argente, Jesús; Chowen, Julie A; Viveros, Maria-Paz

    2015-01-01

    Maternal deprivation (MD) during neonatal life has diverse long-term behavioral effects and alters the development of the hippocampus and frontal cortex, with several of these effects being sexually dimorphic. MD animals show a marked reduction in their circulating leptin levels, not only during the MD period, but also several days later (PND 13). A neonatal leptin surge occurs in rodents (beginning around PND 5 and peaking between PND 9 and 10) that has an important neurotrophic role. We hypothesized that the deficient neonatal leptin signaling of MD rats could be involved in the altered development of their hippocampus and frontal cortex. Accordingly, a neonatal leptin treatment in MD rats would at least in part counteract their neurobehavioural alterations. MD was carried out in Wistar rats for 24 h on PND 9. Male and female MD and control rats were treated from PND 9 to 13 with rat leptin (3 mg/kg/day sc) or vehicle. In adulthood, the animals were submitted to the open field, novel object memory test and the elevated plus maze test of anxiety. Neuronal and glial population markers, components of the glutamatergic and cannabinoid systems and diverse synaptic plasticity markers were evaluated by PCR and/or western blotting. Main results include: 1) In some of the parameters analyzed, neonatal leptin treatment reversed the effects of MD (eg., mRNA expression of hippocampal IGF1 and protein expression of GFAP and vimentin) partially confirming our hypothesis; 2) The neonatal leptin treatment, per se, exerted a number of behavioral (increased anxiety) and neural effects (eg., expression of the following proteins: NG2, NeuN, PSD95, NCAM, synaptophysin). Most of these effects were sex dependent. An adequate neonatal leptin level (avoiding excess and deficiency) appears to be necessary for its correct neuro-programing effect.

  16. Long Term Hippocampal and Cortical Changes Induced by Maternal Deprivation and Neonatal Leptin Treatment in Male and Female Rats

    PubMed Central

    Mela, Virginia; Díaz, Francisca; Borcel, Erika; Argente, Jesús; Chowen, Julie A.; Viveros, Maria-Paz

    2015-01-01

    Maternal deprivation (MD) during neonatal life has diverse long-term behavioral effects and alters the development of the hippocampus and frontal cortex, with several of these effects being sexually dimorphic. MD animals show a marked reduction in their circulating leptin levels, not only during the MD period, but also several days later (PND 13). A neonatal leptin surge occurs in rodents (beginning around PND 5 and peaking between PND 9 and 10) that has an important neurotrophic role. We hypothesized that the deficient neonatal leptin signaling of MD rats could be involved in the altered development of their hippocampus and frontal cortex. Accordingly, a neonatal leptin treatment in MD rats would at least in part counteract their neurobehavioural alterations. MD was carried out in Wistar rats for 24 h on PND 9. Male and female MD and control rats were treated from PND 9 to 13 with rat leptin (3 mg/kg/day sc) or vehicle. In adulthood, the animals were submitted to the open field, novel object memory test and the elevated plus maze test of anxiety. Neuronal and glial population markers, components of the glutamatergic and cannabinoid systems and diverse synaptic plasticity markers were evaluated by PCR and/or western blotting. Main results include: 1) In some of the parameters analyzed, neonatal leptin treatment reversed the effects of MD (eg., mRNA expression of hippocampal IGF1 and protein expression of GFAP and vimentin) partially confirming our hypothesis; 2) The neonatal leptin treatment, per se, exerted a number of behavioral (increased anxiety) and neural effects (eg., expression of the following proteins: NG2, NeuN, PSD95, NCAM, synaptophysin). Most of these effects were sex dependent. An adequate neonatal leptin level (avoiding excess and deficiency) appears to be necessary for its correct neuro-programing effect. PMID:26382238

  17. CRF-R1 activation in the anterior-dorsal BNST induces maternal neglect in lactating rats via an HPA axis-independent central mechanism

    PubMed Central

    Klampfl, Stefanie M.; Brunton, Paula J.; Bayerl, Doris S.; Bosch, Oliver J.

    2016-01-01

    Adequate maternal behavior in rats requires minimal corticotropin-releasing factor receptor (CRF-R) activation in the medial-posterior bed nucleus of the stria terminalis (mpBNST). Based on the architectural heterogeneity of the BNST and its distinct inter-neural connectivity, we tested whether CRF-R manipulation in another functional part, the anterior-dorsal BNST (adBNST), differentially modulates maternal behavior. We demonstrate that in the adBNST, activation of CRF-R1 reduced arched back nursing (ABN) and nursing, whereas activation of CRF-R2 resulted in an initial reduction in nursing but significantly increased the incidence of ABN 5 h after the treatment. Following stressor exposure, which is detrimental to maternal care, ABN tended to be protected by CRF-R1 blockade. Maternal motivation, maternal aggression, and anxiety were unaffected by any manipulation. Furthermore, under basal and stress conditions, activation of adBNST CRF-R1 increased plasma ACTH and corticosterone concentrations, whereas stimulation of adBNST CRF-R2 increased basal plasma ACTH and corticosterone concentrations, but blocked the stress-induced increase in plasma corticosterone secretion. Moreover, both the CRF-R1 and -R2 antagonists prevented the stress-induced increase in plasma corticosterone secretion. Importantly, elevated levels of circulating corticosterone induced by intra-adBNST administration of CRF-R1 or -R2 agonist did not impact maternal care. Finally, Crf mRNA expression in the adBNST was increased during lactation; however, Crfr1 mRNA expression was similar between lactating and virgin rats. In conclusion, maternal care is impaired by adBNST CRF-R1 activation, and this appears to be the result of a central action, rather than an effect of elevated circulating levels of CORT. These data provide new insights into potential causes of disturbed maternal behavior postpartum. PMID:26630389

  18. CRF-R1 activation in the anterior-dorsal BNST induces maternal neglect in lactating rats via an HPA axis-independent central mechanism.

    PubMed

    Klampfl, Stefanie M; Brunton, Paula J; Bayerl, Doris S; Bosch, Oliver J

    2016-02-01

    Adequate maternal behavior in rats requires minimal corticotropin-releasing factor receptor (CRF-R) activation in the medial-posterior bed nucleus of the stria terminalis (mpBNST). Based on the architectural heterogeneity of the BNST and its distinct inter-neural connectivity, we tested whether CRF-R manipulation in another functional part, the anterior-dorsal BNST (adBNST), differentially modulates maternal behavior. We demonstrate that in the adBNST, activation of CRF-R1 reduced arched back nursing (ABN) and nursing, whereas activation of CRF-R2 resulted in an initial reduction in nursing but significantly increased the incidence of ABN 5h after the treatment. Following stressor exposure, which is detrimental to maternal care, ABN tended to be protected by CRF-R1 blockade. Maternal motivation, maternal aggression, and anxiety were unaffected by any manipulation. Furthermore, under basal and stress conditions, activation of adBNST CRF-R1 increased plasma ACTH and corticosterone concentrations, whereas stimulation of adBNST CRF-R2 increased basal plasma ACTH and corticosterone concentrations, but blocked the stress-induced increase in plasma corticosterone secretion. Moreover, both the CRF-R1 and -R2 antagonists prevented the stress-induced increase in plasma corticosterone secretion. Importantly, elevated levels of circulating corticosterone induced by intra-adBNST administration of CRF-R1 or -R2 agonist did not impact maternal care. Finally, Crf mRNA expression in the adBNST was increased during lactation; however, Crfr1 mRNA expression was similar between lactating and virgin rats. In conclusion, maternal care is impaired by adBNST CRF-R1 activation, and this appears to be the result of a central action, rather than an effect of elevated circulating levels of CORT. These data provide new insights into potential causes of disturbed maternal behavior postpartum.

  19. Consequences of a Maternal High-Fat Diet and Late Gestation Diabetes on the Developing Rat Lung

    PubMed Central

    Forred, Benjamin J.; Larsen, Tricia D.; Jensen, Danielle N.; Wachal, Angela L.; Khan, Muhammad Ali; Vitiello, Peter F.

    2016-01-01

    Rationale Infants born to diabetic or obese mothers are at risk of respiratory distress and persistent pulmonary hypertension of the newborn (PPHN), conceivably through fuel-mediated pathogenic mechanisms. Prior research and preventative measures focus on controlling maternal hyperglycemia, but growing evidence suggests a role for additional circulating fuels including lipids. Little is known about the individual or additive effects of a maternal high-fat diet on fetal lung development. Objective The objective of this study was to determine the effects of a maternal high-fat diet, alone and alongside late-gestation diabetes, on lung alveologenesis and vasculogenesis, as well as to ascertain if consequences persist beyond the perinatal period. Methods A rat model was used to study lung development in offspring from control, diabetes-exposed, high-fat diet-exposed and combination-exposed pregnancies via morphometric, histologic (alveolarization and vasculogenesis) and physiologic (echocardiography, pulmonary function) analyses at birth and 3 weeks of age. Outcomes were interrogated for diet, diabetes and interaction effect using ANOVA with significance set at p≤0.05. Findings prompted additional mechanistic inquiry of key molecular pathways. Results Offspring exposed to maternal diabetes or high-fat diet, alone and in combination, had smaller lungs and larger hearts at birth. High-fat diet-exposed, but not diabetes-exposed offspring, had a higher perinatal death rate and echocardiographic evidence of PPHN at birth. Alveolar mean linear intercept, septal thickness, and airspace area (D2) were not significantly different between the groups; however, markers of lung maturity were. Both diabetes-exposed and diet-exposed offspring expressed more T1α protein, a marker of type I cells. Diet-exposed newborn pups expressed less surfactant protein B and had fewer pulmonary vessels enumerated. Mechanistic inquiry revealed alterations in AKT activation, higher endothelin-1

  20. Effects of swimming exercise on morphine-induced reward and behavioral sensitization in maternally-separated rat pups in the conditioned place preference procedure.

    PubMed

    Abad, Atiyeh Taghavi-Khalil; Miladi-Gorji, Hossein; Bigdeli, Imanollah

    2016-09-19

    This study was designed to examine the effects of swimming exercise during adolescence on morphine-induced conditioned place preference (CPP) and behavioral sensitization in maternally separated male and female rat pups. Male Wistar rats were allowed to mate with female virgin Wistar rats. Pups were separated from the dam daily for 180min during postnatal days 2-14. All pups were weaned on day 21.The exercising pups were allowed to swim (60min/d, five days per a week, for 30days) during adolescence. Then, rat pups were tested for behavioral sensitization and the CPP induced by morphine. Maternal separation produced a significant increase in morphine-induced CPP in both sexes, behavioral sensitization in male pups and tolerance to morphine-induced motor activity in female pups. Swimmer pups separated from the dam exhibited a decrease in morphine-induced CPP in both sexes and behavioral sensitization in male pups than those of their control pups. The present results have shown that swimming exercise during adolescence may exert a protective effect against morphine-induced reward and behavioral sensitization in adult male and female rats following maternal separation. PMID:27519931

  1. No effect of sustained systemic growth retardation on the distribution of Reelin-expressing interneurons in the neuron-producing hippocampal dentate gyrus in rats.

    PubMed

    Ohishi, Takumi; Wang, Liyun; Ogawa, Bunichiro; Fujisawa, Kenichi; Taniai, Eriko; Hayashi, Hitomi; Mitsumori, Kunitoshi; Shibutani, Makoto

    2010-12-01

    Reelin signaling plays a role in neuronal migration and positioning during brain development. To clarify the effect of systemic growth retardation on the distribution of Reelin-expressing interneurons in the hilus of the hippocampal dentate gyrus, pregnant rats were fed a synthetic diet with either a normal (20% casein) or low (10% casein) protein concentration from gestational day 10 to postnatal day (PND) 21 at weaning. Male offspring were immunohistochemically examined at PND 21 and on PND 77. Protein-restricted offspring displayed systemic growth retardation through PND 77 and had decreased absolute brain weights and an increased number of external granular cells in the cerebellar cortex, suggestive of retarded brain growth at weaning. However, maternal protein restriction did not change the cellular distribution of immunoreactivity for Reelin, Calbindin-D-28K, or glutamic acid decarboxylase 67 or of NeuN-positive postmitotic neurons in the dentate hilus either at PND 21 or PND 77, which suggests that the population of γ-aminobutyric acid-ergic interneurons involving synthesis of Reelin was not affected. Furthermore, as well as the distribution of hilar neurons expressing neurogenesis-related FoxG1, cell proliferation and apoptosis in the subgranular zone were unaffected through PND 77. These results suggest that systemic growth retardation caused by maternal protein restriction does not affect neuronal migration and postnatal neurogenesis of the dentate gyrus resulting in unaltered distribution of Reelin-synthesizing interneurons.

  2. Maternal obesity programs senescence signaling and glucose metabolism in osteo-progenitors from rat and human

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nutritional status during intrauterine and early postnatal life impacts the risk of chronic diseases, presumably via epigenetic mechanisms. However, evidence on the impact of gestational events on regulation of embryonic bone cell fate is sparse. We investigated the effects of maternal obesity on fe...

  3. Maternal obesity promotes a proinflammatory signature in rat uterus and blastocyst

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Maternal obesity at conception increases the risk of offspring obesity, thus propagating an intergenerational vicious cycle. Male offspring born to obese dams are hyper-responsive to high fat diets, gaining greater body weight, fat mass and additional metabolic sequelae compared to lean controls. ...

  4. Effect of maternal obesity on fetal bone development in the rat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Epidemiological studies show that quality of nutrition during intrauterine and postnatal early life impact the risk of low bone mass and fracture later in life. Maternal consumption of high-fat diets has been demonstrated to affect health outcomes, such as: brain development; obesity; insulin resist...

  5. Sex-dependent effects of an early life treatment in rats that increases maternal care: vulnerability or resilience?

    PubMed Central

    Fuentes, Sílvia; Daviu, Núria; Gagliano, Humberto; Garrido, Pedro; Zelena, Dóra; Monasterio, Nela; Armario, Antonio; Nadal, Roser

    2014-01-01

    Early life stress (ELS) in rodents has profound long-term effects that are partially mediated by changes in maternal care. ELS not only induces “detrimental” effects in adulthood, increasing psychopathology, but also promotes resilience to further stressors. In Long-Evans rats, we evaluated a combination of two procedures as a model of ELS: restriction of bedding during the first post-natal days and exposure to a “substitute” mother. The maternal care of biological and “substitute” mothers was measured. The male and female offspring were evaluated during adulthood in several contexts. Anxiety was measured by the elevated plus-maze (EPM), acoustic startle response (ASR) and forced swim test (FST). In other group of animals, novelty-seeking was measured (activity in an inescapable novel environment, preference for novel environments and exploration of novel objects). Plasmatic ACTH and corticosterone in basal conditions and in response to stress were also measured. Cognitive impulsivity was assessed by a delay-discounting paradigm, and impulsive action, attention and compulsive-like behavior by a five choice serial reaction time task (5CSRTT). ELS decreased pup body weight and increased the care of the biological mother; however, the “substitute” mother did not exhibit overt maltreatment. A mixture of “detrimental” and “beneficial” effects was shown. In the 5CSRTT, attention was impaired in both genders, and in females, ELS increased compulsive-like behavior. Novel object exploration was only increased by ELS in males, but the preference for novel spaces decreased in both genders. Baseline anxiety (EPM and ASR) and recognition memory were not affected. Unexpectedly, ELS decreased the ACTH response to novelty and swim stress and increased active coping in the FST in both genders. Cognitive impulsivity was decreased only in females, but impulsive action was not affected. The enhancement in maternal care may “buffer” the effects of ELS in a

  6. Maternal ethanol consumption during pregnancy enhances bile acid-induced oxidative stress and apoptosis in fetal rat liver.

    PubMed

    Perez, Maria J; Velasco, Elena; Monte, Maria J; Gonzalez-Buitrago, Jose M; Marin, Jose J G

    2006-08-15

    Ethanol is able to cross the placenta, which may cause teratogenicity. Here we investigated whether ethanol consumption during pregnancy (ECDP), even at doses unable to cause malformation, might increase the susceptibility of fetal rat liver to oxidative insults. Since cholestasis is a common condition in alcoholic liver disease and pregnancy, exposure to glycochenodeoxycholic acid (GCDCA) has been used here as the oxidative insult. The mothers received drinking water without or with ethanol from 4 weeks before mating until term, when placenta, maternal liver, and fetal liver were used. Ethanol induced a decreased GSH/GSSG ratio in these organs, together with enhanced gamma-glutamylcysteine synthetase and glutathione reductase activities in both placenta and fetal liver. Lipid peroxidation in placenta and fetal liver was enhanced by ethanol, although it had no effect on caspase-3 activity. Although the basal production of reactive oxygen species (ROS) was higher by fetal (FHs) than by maternal (AHs) hepatocytes in short-term cultures, the production of ROS in response to the presence of varying GCDCA concentrations was higher in AHs and was further increased by ECDP, which was associated to a more marked impairment in mitochondrial function. Moreover, GCDCA-induced apoptosis was increased by ECDP, as revealed by enhanced Bax-alpha/Bcl-2 ratio (both in AHs and FHs) and the activity of caspase-8 (only in AHs) and caspase-3. In sum, our results indicate that although AHs are more prone than FHs to producing ROS, at doses unable to cause maternal liver damage ethanol consumption causes oxidative stress and apoptosis in fetal liver.

  7. Periodic maternal deprivation induces gender-dependent alterations in behavioral and neuroendocrine responses to emotional stress in adult rats.

    PubMed

    Wigger, A; Neumann, I D

    1999-04-01

    There is evidence that stressful events during the neonatal "stress hyporesponsive period" may influence both emotional behavior and the maturation of the hypothalamic-pituitary-adrenal (HPA) axis in rats. We tested whether periodic maternal deprivation (180 min daily on postnatal days 3-10, PMD) caused chronic changes in emotional behavior and HPA axis activity in either male or female adult rats, or both. In addition, HPA secretory responses to human/rat corticotropin-releasing factor (CRH, 50 ng/kg i.v.) were determined in the adult males. In the elevated plus-maze test, adult (4-5 months of age) PMD-treated animals of both sexes displayed increased anxiety-related behavior compared to control rats. This was indicated by a reduction in the number of entries (male: 70% reduction, p < 0.01; female: 31% reduction, p < 0.01) and amount of time spent on the open arms (male: 86% reduction, p < 0.01; female: 40% reduction, NS). Neuroendocrine parameters were also altered in PMD-treated rats in a gender-dependent manner. Whereas basal plasma adrenocorticotropin (ACTH) and corticosterone levels did not differ significantly between PMD and control groups of either sex, the ACTH response to elevated plus-maze exposure, a predominantly emotional stressor, was higher in male (p < 0.01), but not female, PMD animals than in the respective controls. In contrast, PMD had no effect on behavioral (duration of struggling) or HPA axis responses to forced swimming (90 s, 19 degrees C), a complex and predominantly physical stressor, in either male or female rats. In response to CRH stimulation, PMD-treated males did not show differences in the ACTH secretion compared to controls, indicating alterations in HPA axis regulation at a suprapituitary level. Thus, PMD caused long-term changes in the emotional behavior of adult rats of both sexes, although to a differing degree in males and females, whereas it appeared to cause predominantly alterations in the HPA axis response in males

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

    PubMed

    Hallam, Megan C; Reimer, Raylene A

    2016-01-14

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

  9. Maternal immune activation produces neonatal excitability defects in offspring hippocampal neurons from pregnant rats treated with poly I:C

    PubMed Central

    Patrich, Eti; Piontkewitz, Yael; Peretz, Asher; Weiner, Ina; Attali, Bernard

    2016-01-01

    Maternal immune activation (MIA) resulting from prenatal exposure to infectious pathogens or inflammatory stimuli is increasingly recognized to play an important etiological role in neuropsychiatric disorders with neurodevelopmental features. MIA in pregnant rodents induced by injection of the synthetic double-stranded RNA, Poly I:C, a mimic of viral infection, leads to a wide spectrum of behavioral abnormalities as well as structural and functional defects in the brain. Previous MIA studies using poly I:C prenatal treatment suggested that neurophysiological alterations occur in the hippocampus. However, these investigations used only juvenile or adult animals. We postulated that MIA-induced alterations could occur earlier at neonatal/early postnatal stages. Here we examined the neurophysiological properties of cultured pyramidal-like hippocampal neurons prepared from neonatal (P0-P2) offspring of pregnant rats injected with poly I:C. Offspring neurons from poly I:C-treated mothers exhibited significantly lower intrinsic excitability and stronger spike frequency adaptation, compared to saline. A similar lower intrinsic excitability was observed in CA1 pyramidal neurons from hippocampal slices of two weeks-old poly I:C offspring. Cultured hippocampal neurons also displayed lower frequency of spontaneous firing, higher charge transfer of IPSCs and larger amplitude of miniature IPSCs. Thus, maternal immune activation leads to strikingly early neurophysiological abnormalities in hippocampal neurons. PMID:26742695

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

    PubMed Central

    Hallam, Megan C.; Reimer, Raylene A.

    2016-01-01

    The Thrifty Phenotype Hypothesis proposes that the fetus takes cues from the maternal environment to predict its postnatal environment. A mismatch between the predicted and actual environments precipitates an increased risk of chronic disease. Our objective was to determine if, following a high fat, high sucrose (HFS) diet challenge in adulthood, re-matching offspring to their maternal gestational diet would improve metabolic health more so than if there was no previous exposure to that diet. Animals re-matched to a high prebiotic fiber diet (HF) had lower body weight and adiposity than animals re-matched to a high protein (HP) or control (C) diet and also had increased levels of the satiety hormones GLP-1 and PYY (p < 0.05). Control animals, whether maintained throughout the study on AIN-93M, or continued on HFS rather than reverting back to AIN-93M, did not differ from each other in body weight or adiposity. Overall, the HF diet was associated with the most beneficial metabolic phenotype (body fat, glucose control, satiety hormones). The HP diet, as per our previous work, had detrimental effects on body weight and adiposity. Findings in control rats suggest that the obesogenic potential of the powdered AIN-93 diet warrants investigation. PMID:26784224

  11. Adolescent olanzapine sensitization is correlated with hippocampal stem cell proliferation in a maternal immune activation rat model of schizophrenia.

    PubMed

    Chou, Shinnyi; Jones, Sean; Li, Ming

    2015-08-27

    Previous work established that repeated olanzapine (OLZ) administration in normal adolescent rats induces a sensitization effect (i.e. increased behavioral responsiveness to drug re-exposure) in the conditioned avoidance response (CAR) model. However, it is unclear whether the same phenomenon can be detected in animal models of schizophrenia. The present study explored the generalizability of OLZ sensitization from healthy animals to a preclinical neuroinflammatory model of schizophrenia in the CAR. Maternal immune activation (MIA) was induced via polyinosinic:polycytidylic acid (PolyI:C) administration into pregnant dams. Behavioral assessments of offspring first identified decreased maternal separation-induced pup ultrasonic vocalizations and increased amphetamine-induced hyperlocomotion in animals prenatally exposed to PolyI:C. In addition, repeated adolescent OLZ administration confirmed the generalizability of the sensitization phenomenon. Using the CAR test, adolescent MIA animals displayed a similar increase in behavioral responsiveness after repeated OLZ exposure during both the repeated drug test days as well as a subsequent challenge test. Neurobiologically, few studies examining the relationship between hippocampal cell proliferation and survival and either antipsychotic exposure or MIA have incorporated concurrent behavioral changes. Thus, the current study also sought to reveal the correlation between OLZ behavioral sensitization in the CAR and hippocampal cell proliferation and survival. 5'-bromodeoxyuridine immunohistochemistry identified a positive correlation between the magnitude of OLZ sensitization (i.e. change in avoidance suppression induced by OLZ across days) and hippocampal cell proliferation. The implications of the relationship between behavioral and neurobiological results are discussed.

  12. SENSITIVITY OF FETAL RAT TESTICULAR STEROIDOGENESIS TO MATERNAL PROCHLORAZ EXPOSURE AND THE UNDERLYING MECHANISM OF INHIBITION

    EPA Science Inventory

    Since prochloraz (PCZ) is an imidazole fungicide that inhibits gonadal steroidogenesis and antagonizes the androgen receptor (AR), we hypothesized that pubertal exposure to PCZ would delay male rat reproductive development. Sprague Dawley rats were dosed by gavage with 0, 31.3, ...

  13. Maternal mobile phone exposure alters intrinsic electrophysiological properties of CA1 pyramidal neurons in rat offspring.

    PubMed

    Razavinasab, Moazamehosadat; Moazzami, Kasra; Shabani, Mohammad

    2016-06-01

    Some studies have shown that exposure to electromagnetic field (EMF) may result in structural damage to neurons. In this study, we have elucidated the alteration in the hippocampal function of offspring Wistar rats (n = 8 rats in each group) that were chronically exposed to mobile phones during their gestational period by applying behavioral, histological, and electrophysiological tests. Rats in the EMF group were exposed to 900 MHz pulsed-EMF irradiation for 6 h/day. Whole cell recordings in hippocampal pyramidal cells in the mobile phone groups did show a decrease in neuronal excitability. Mobile phone exposure was mostly associated with a decrease in the number of action potentials fired in spontaneous activity and in response to current injection in both male and female groups. There was an increase in the amplitude of the afterhyperpolarization (AHP) in mobile phone rats compared with the control. The results of the passive avoidance and Morris water maze assessment of learning and memory performance showed that phone exposure significantly altered learning acquisition and memory retention in male and female rats compared with the control rats. Light microscopy study of brain sections of the control and mobile phone-exposed rats showed normal morphology.Our results suggest that exposure to mobile phones adversely affects the cognitive performance of both female and male offspring rats using behavioral and electrophysiological techniques.

  14. Oxytocin mediates the acquisition of filial, odor-guided huddling for maternally-associated odor in preweanling rats

    PubMed Central

    Kojima, Sayuri; Alberts, Jeffrey R.

    2011-01-01

    The present study was designed to examine possible roles of oxytocin (OT) in the acquisition of a filial huddling preference in preweanling rats. We used a procedure in which a scented, foster mother can induce an odor-guided huddling preference in preweanling pups, following a single, 2-h-long co-habitation (Kojima & Alberts, 2009, 2011). This single, discrete period for preference learning enables us to observe the mother-pup interactions that establish the pups’ preferences and to intervene with experimental manipulations. Four, 14-day-old littermates interacted with a scented foster mother that provided maternal care during a 2-h session. Two of the pups were pretreated with an intracerebroventricular injection of OT or an oxytocin antagonist (OTA), and the others received a vehicle injection. Filial preference for a maternally-paired odor was measured in a huddling test the next day. OT is necessary for acquisition of the filial preference: Odor learning was blocked in the pups treated with OTA, but not in their vehicle-treated littermates who experienced the same mother at the same time. Injection with exogenous OT did not augment the pups’ preference. Manipulating pups’ central OT also altered the contact interactions of the mother and pups. When some pups received OT, mother-litter aggregations formed as frequently and with similar combinations of bodies, but contact aggregations were significantly more cohesive than when some pups in the litter received OTA. We discuss dual, behavioral and neuroendocrine roles of OT in social learning by preweanling rats. PMID:21872599

  15. Maternal dietary omega-3 fatty acid supplementation reduces placental oxidative stress and increases fetal and placental growth in the rat.

    PubMed

    Jones, Megan L; Mark, Peter J; Mori, Trevor A; Keelan, Jeffrey A; Waddell, Brendan J

    2013-02-01

    Placental oxidative stress plays a key role in the pathophysiology of several placenta-related disorders including intrauterine growth restriction. Oxidative stress occurs when accumulation of reactive oxygen species damages DNA, proteins, and lipids, an outcome normally limited by antioxidant defenses. Dietary supplementation with omega-3 polyunsaturated fatty acids (n-3 PUFAs) may limit oxidative stress by increasing antioxidant capacity, but n-3 PUFAs are also highly susceptible to lipid peroxidation; so n-3 PUFA supplementation is potentially harmful. Here we examined the effect of n-3 PUFAs on placental oxidative stress and on placental and fetal growth in the rat. We also investigated whether diet-induced changes in maternal plasma fatty acid profiles are associated with comparable changes in placental and fetal tissues. Rats were fed either standard or high n-3 PUFA diets from Day 1 of pregnancy, and tissues were collected on Day 17 or 22 (term = Day 23). Dietary supplementation with n-3 PUFAs increased fetal (6%) and placental (12%) weights at Day 22, the latter attributable primarily to growth of the labyrinth zone (LZ). Increased LZ weight was accompanied by reduced LZ F(2)-isoprostanes (by 31% and 11% at Days 17 and 22, respectively), a marker of oxidative damage. Maternal plasma PUFA profiles were altered by dietary fatty acid intake and were strongly predictive of corresponding profiles in placental and fetal tissues. Our data indicate that n-3 PUFA supplementation reduces placental oxidative stress and enhances placental and fetal growth. Moreover, fatty acid profiles in the mother, placenta, and fetus are highly dependent on dietary fatty acid intake.

  16. Maternal Hypoxia Increases the Activity of MMPs and Decreases the Expression of TIMPs in the Brain of Neonatal Rats

    PubMed Central

    Tong, Wenni; Chen, Wanqiu; Ostrowski, Robert P.; Ma, Qingyi; Souvenir, Rhonda; Zhang, Lubo; Zhang, John H.; Tang, Jiping

    2010-01-01

    A recent study has shown that increased activity of matrix metalloproteinases-2 and metalloproteinases-9 (MMP-2 and MMP-9) has detrimental effect on the brain after neonatal hypoxia. The present study determined the effect of maternal hypoxia on neuronal survivability and the activity of MMP-2 and MMP-9, as well as the expression of tissue inhibitors of metalloproteinase 1 and 2 (TIMP-1 and TIMP-2) in the brain of neonatal rats. Pregnant rats were exposed to 10.5% oxygen for 6 days from the gestation day 15 to day 21. Pups were sacrificed at day 0, 4, 7, 14, and 21 after birth. Body weight and brain weight of the pups were measured at each time point. The activity of MMP-2 and MMP-9 and the protein abundance of TIMP-1 and TIMP-2 were determined by zymography and Western blotting, respectively. The tissue distribution of MMPs was examined by immunofluorescence staining. The neuronal death was detected by Nissl staining. Maternal hypoxia caused significant decreases in body and brain size, increased activity of MMP-2 at day 0, and increased MMP-9 at day 0 and 4. The increased activity of the MMPs was accompanied by an overall tendency towards a reduced expression of TIMPs at all ages with the significance observed for TIMPs at day 0, 4, and 7. Immunofluorescence analysis showed an increased expression of MMP-2, MMP-9 in the hippocampus at day 0 and 4. Nissl staining revealed significant cell death in the hippocampus at day 0, 4, and 7. Functional tests showed worse neurobehavioral outcomes in the hypoxic animals. PMID:20017119

  17. Experimentally-induced maternal hypothyroidism alters crucial enzyme activities in the frontal cortex and hippocampus of the offspring rat.

    PubMed

    Koromilas, Christos; Tsakiris, Stylianos; Kalafatakis, Konstantinos; Zarros, Apostolos; Stolakis, Vasileios; Kimpizi, Despoina; Bimpis, Alexios; Tsagianni, Anastasia; Liapi, Charis

    2015-02-01

    Thyroid hormone insufficiency during neurodevelopment can result into significant structural and functional changes within the developing central nervous system (CNS), and is associated with the establishment of serious cognitive impairment and neuropsychiatric symptomatology. The aim of the present study was to shed more light on the effects of gestational and/or lactational maternal exposure to propylthiouracil (PTU)-induced hypothyroidism as a multilevel experimental approach to the study of hypothyroidism-induced changes on crucial brain enzyme activities of 21-day-old Wistar rat offspring in a brain region-specific manner. This experimental approach has been recently developed and characterized by the authors based on neurochemical analyses performed on newborn and 21-day-old rat offspring whole brain homogenates; as a continuum to this effort, the current study focused on two CNS regions of major significance for cognitive development: the frontal cortex and the hippocampus. Maternal exposure to PTU in the drinking water during gestation and/or lactation resulted into changes in the activities of acetylcholinesterase and two important adenosinetriphosphatases (Na(+),K(+)- and Mg(2+)-ATPase), that seemed to take place in a CNS-region-specific manner and that were dependent upon the PTU-exposure timeframe followed. As these findings are analyzed and compared to the available literature, they: (i) highlight the variability involved in the changes of the aforementioned enzymatic parameters in the studied CNS regions (attributed to both the different neuroanatomical composition and the thyroid-hormone-dependent neurodevelopmental growth/differentiation patterns of the latter), (ii) reveal important information with regards to the neurochemical mechanisms that could be involved in the way clinical hypothyroidism could affect optimal neurodevelopment and, ultimately, cognitive function, as well as (iii) underline the need for the adoption of more consistent

  18. Changes in Astroglial Markers in a Maternal Immune Activation Model of Schizophrenia in Wistar Rats are Dependent on Sex

    PubMed Central

    de Souza, Daniela F.; Wartchow, Krista M.; Lunardi, Paula S.; Brolese, Giovana; Tortorelli, Lucas S.; Batassini, Cristiane; Biasibetti, Regina; Gonçalves, Carlos-Alberto

    2015-01-01

    Data from epidemiological studies suggest that prenatal exposure to bacterial and viral infection is an important environmental risk factor for schizophrenia. The maternal immune activation (MIA) animal model is used to study how an insult directed at the maternal host can have adverse effects on the fetus, leading to behavioral and neurochemical changes later in life. We evaluated whether the administration of LPS to rat dams during late pregnancy affects astroglial markers (S100B and GFAP) of the offspring in later life. The frontal cortex and hippocampus were compared in male and female offspring on postnatal days (PND) 30 and 60. The S100B protein exhibited an age-dependent pattern of expression, being increased in the frontal cortex and hippocampus of the MIA group at PND 60, while at PND 30, male rats presented increased S100B levels only in the frontal cortex. Considering that S100B secretion is reduced by elevation of glutamate levels, we may hypothesize that this early increment in frontal cortex tissue of males is associated with elevated extracellular levels of glutamate and glutamatergic hypofunction, an alteration commonly associated with SCZ pathology. Moreover, we also found augmented GFAP in the frontal cortex of the LPS group at PND 30, but not in the hippocampus. Taken together data indicate that astroglial changes induced by MIA are dependent on sex and brain region and that these changes could reflect astroglial dysfunction. Such alterations may contribute to our understanding of the abnormal neuronal connectivity and developmental aspects of SCZ and other psychiatric disorders. PMID:26733814

  19. Intrauterine growth restriction combined with a maternal high-fat diet increases hepatic cholesterol and low-density lipoprotein receptor activity in rats.

    PubMed

    Zinkhan, Erin K; Zalla, Jennifer M; Carpenter, Jeanette R; Yu, Baifeng; Yu, Xing; Chan, Gary; Joss-Moore, Lisa; Lane, Robert H

    2016-07-01

    Intrauterine growth restriction (IUGR) and maternal consumption of a high-saturated-fat diet (HFD) increase the risk of hypercholesterolemia, a leading cause of morbidity and mortality. Many pregnant women eat a HFD, thus exposing the fetus to a HFD in utero. The cumulative effect of in utero exposure to IUGR and a HFD on offspring cholesterol levels remains unknown. Furthermore, little is known about the mechanism through which IUGR and maternal HFD consumption increase cholesterol. We hypothesize that IUGR combined with a maternal HFD would increase offspring serum and hepatic cholesterol accumulation via alteration in levels of key proteins involved in cholesterol metabolism. To test our hypothesis we used a rat model of surgically induced IUGR and fed the dams a regular diet or a HFD HFD-fed dams consumed the same kilocalories as regular diet-fed dams, with no difference between surgical intervention groups. In the offspring, IUGR combined with a maternal HFD increased hepatic cholesterol levels, low-density lipoprotein (LDL) receptor protein levels, and Ldlr activity in female rat offspring at birth and both sexes at postnatal day 14 relative to non-IUGR offspring both from regular diet- and HFD-fed dams. These findings suggest that IUGR combined with a maternal HFD increases hepatic cholesterol accumulation via increased LDL cholesterol uptake into the liver with resulting persistent increases in hepatic cholesterol accumulation.

  20. Neonatal maternal deprivation sensitizes voltage-gated sodium channel currents in colon-specific dorsal root ganglion neurons in rats.

    PubMed

    Hu, Shufen; Xiao, Ying; Zhu, Liyan; Li, Lin; Hu, Chuang-Ying; Jiang, Xinghong; Xu, Guang-Yin

    2013-02-15

    Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by abdominal pain in association with altered bowel movements. The underlying mechanisms of visceral hypersensitivity remain elusive. This study was designed to examine the role for sodium channels in a rat model of chronic visceral hyperalgesia induced by neonatal maternal deprivation (NMD). Abdominal withdrawal reflex (AWR) scores were performed on adult male rats. Colon-specific dorsal root ganglion (DRG) neurons were labeled with DiI and acutely dissociated for measuring excitability and sodium channel current under whole-cell patch-clamp configurations. The expression of Na(V)1.8 was analyzed by Western blot and quantitative real-time PCR. NMD significantly increased AWR scores, which lasted for ~6 wk in an association with hyperexcitability of colon DRG neurons. TTX-resistant but not TTX-sensitive sodium current density was greatly enhanced in colon DRG neurons in NMD rats. Compared with controls, activation curves showed a leftward shift in NMD rats whereas inactivation curves did not differ significantly. NMD markedly accelerated the activation time of peak current amplitude without any changes in inactivation time. Furthermore, NMD remarkably enhanced expression of Na(V)1.8 at protein levels but not at mRNA levels in colon-related DRGs. The expression of Na(V)1.9 was not altered after NMD. These data suggest that NMD enhances TTX-resistant sodium activity of colon DRG neurons, which is most likely mediated by a leftward shift of activation curve and by enhanced expression of Na(V)1.8 at protein levels, thus identifying a specific molecular mechanism underlying chronic visceral pain and sensitization in patients with IBS. PMID:23139220

  1. Effects of endurance exercise on expressions of glial fibrillary acidic protein and myelin basic protein in developing rats with maternal infection-induced cerebral palsy.

    PubMed

    Kim, Kijeong; Shin, Mal-Soon; Cho, Han-Sam; Kim, Young-Pyo

    2014-02-01

    Periventricular leukomalacia (PVL) is a common white matter lesion affecting the neonatal brain. PVL is closely associated with cerebral palsy (CP) and characterized by increase in the number of astrocytes, which can be detected by positivity for glial fibrillary acidic protein (GFAP). Change in myelin basic protein (MBP) is an early sign of white matter abnormality. Maternal or placental infection can damage the neonatal brain. In the present study, we investigated the effects of treadmill walking exercise on GFAP and MBP expressions in rats with maternal lipopolysaccharide (LPS)-induced PVL. Immunohistochemistry was performed for the detection of GFAP and MBP. The present results showed that intracervical maternal LPS injection during pregnancy increased GFAP expression in the striatum and decreased MBP expression in the corpus callosum of rats. The results also showed that treadmill walking exercise suppressed GFAP expression and enhanced MBP expression in the brains of rats with maternal LPS-induced PVL. The present study revealed that treadmill walking exercise is effective for the suppressing astrogliosis and hypomyelination associated with PVL. Here in this study, we showed that treadmill walking exercise may be effective therapeutic strategy for alleviating the detrimental effects of CP.

  2. Maternal and postweaning folic acid supplementation interact to influence body weight, insulin resistance, and food intake regulatory gene expression in rat offspring in a sex-specific manner.

    PubMed

    Huot, Pedro S P; Ly, Anna; Szeto, Ignatius M Y; Reza-López, Sandra A; Cho, Daniel; Kim, Young-In; Anderson, G Harvey

    2016-04-01

    Maternal intake of multivitamins or folic acid above the basal dietary requirement alters the growth and metabolic trajectory of rat offspring. We hypothesized that a modest increase in the folic acid content of maternal diets would alter the offspring's metabolic phenotype, and that these effects could be corrected by matching the folic acid content of the offspring's diet with that of the maternal diet. Female Sprague-Dawley rats were placed on a control or a 2.5× folic acid-supplemented diet prior to mating and during pregnancy and lactation. At weaning, pups from each maternal diet group were randomized to the control or to the 2.5× folic acid-supplemented diet for 25 weeks. Male pups from dams fed the folic acid-supplemented diet were 3.7% heavier than those from control-fed dams and had lower mRNA expression for leptin receptor Obrb isoform (Lepr) (11%) and Agouti-related protein (Agrp) (14%). In contrast, female pups from folic acid-supplemented dams were 5% lighter than those from control-fed dams and had lower proopiomelanocortin (Pomc) (42%), Lepr (32%), and Agrp (13%), but higher neuropeptide Y (Npy) (18%) mRNA expression. Folic acid supplementation ameliorated the alterations induced by maternal folic acid supplementation in male pups and led to the lowest insulin resistance, but the effects were smaller in female pups and led to the highest insulin resistance. In conclusion, maternal folic acid supplementation at 2.5× the control level was associated with alterations in body weight and hypothalamic gene expression in rat offspring in a sex-specific manner, and some of these effects were attenuated by postweaning folic acid supplementation.

  3. Maternal restraint stress delays maturation of cation-chloride cotransporters and GABAA receptor subunits in the hippocampus of rat pups at puberty.

    PubMed

    Veerawatananan, Bovorn; Surakul, Pornprom; Chutabhakdikul, Nuanchan

    2016-06-01

    The GABAergic synapse undergoes structural and functional maturation during early brain development. Maternal stress alters GABAergic synapses in the pup's brain that are associated with the pathophysiology of neuropsychiatric disorders in adults; however, the mechanism for this is still unclear. In this study, we examined the effects of maternal restraint stress on the development of Cation-Chloride Cotransporters (CCCs) and the GABAA receptor α1 and α5 subunits in the hippocampus of rat pups at different postnatal ages. Our results demonstrate that maternal restraint stress induces a transient but significant increase in the level of NKCC1 (Sodium-Potassium Chloride Cotransporter 1) only at P14, followed by a brief, yet significant increase in the level of KCC2 (Potassium-Chloride Cotransporter 2) at P21, which then decreases from P28 until P40. Thus, maternal stress alters NKCC1 and KCC2 ratio in the hippocampus of rat pups, especially during P14 to P28. Maternal restraint stress also caused biphasic changes in the level of GABAA receptor subunits in the pup's hippocampus. GABAA receptor α1 subunit gradually increased at P14 then decreased thereafter. On the contrary, GABAA receptor α5 subunit showed a transient decrease followed by a long-term increase from P21 until P40. Altogether, our study suggested that the maternal restraint stress might delay maturation of the GABAergic system by altering the expression of NKCC1, KCC2 and GABAA receptor α1 and α5 subunits in the hippocampus of rat pups. These changes demonstrate the dysregulation of inhibitory neurotransmission during early life, which may underlie the pathogenesis of psychiatric diseases at adolescence. PMID:26844244

  4. Maternal restraint stress delays maturation of cation-chloride cotransporters and GABAA receptor subunits in the hippocampus of rat pups at puberty

    PubMed Central

    Veerawatananan, Bovorn; Surakul, Pornprom; Chutabhakdikul, Nuanchan

    2015-01-01

    The GABAergic synapse undergoes structural and functional maturation during early brain development. Maternal stress alters GABAergic synapses in the pup's brain that are associated with the pathophysiology of neuropsychiatric disorders in adults; however, the mechanism for this is still unclear. In this study, we examined the effects of maternal restraint stress on the development of Cation-Chloride Cotransporters (CCCs) and the GABAA receptor α1 and α5 subunits in the hippocampus of rat pups at different postnatal ages. Our results demonstrate that maternal restraint stress induces a transient but significant increase in the level of NKCC1 (Sodium–Potassium Chloride Cotransporter 1) only at P14, followed by a brief, yet significant increase in the level of KCC2 (Potassium-Chloride Cotransporter 2) at P21, which then decreases from P28 until P40. Thus, maternal stress alters NKCC1 and KCC2 ratio in the hippocampus of rat pups, especially during P14 to P28. Maternal restraint stress also caused biphasic changes in the level of GABAA receptor subunits in the pup's hippocampus. GABAA receptor α1 subunit gradually increased at P14 then decreased thereafter. On the contrary, GABAA receptor α5 subunit showed a transient decrease followed by a long-term increase from P21 until P40. Altogether, our study suggested that the maternal restraint stress might delay maturation of the GABAergic system by altering the expression of NKCC1, KCC2 and GABAA receptor α1 and α5 subunits in the hippocampus of rat pups. These changes demonstrate the dysregulation of inhibitory neurotransmission during early life, which may underlie the pathogenesis of psychiatric diseases at adolescence. PMID:26844244

  5. Hypoactivation of CRF receptors, predominantly type 2, in the medial-posterior BNST is vital for adequate maternal behavior in lactating rats.

    PubMed

    Klampfl, Stefanie M; Brunton, Paula J; Bayerl, Doris S; Bosch, Oliver J

    2014-07-16

    Maternal behavior ensures the proper development of the offspring. In lactating mammals, maternal behavior is impaired by stress, the physiological consequence of central corticotropin-releasing factor receptor (CRF-R) activation. However, which CRF-R subtype in which specific brain area(s) mediates this effect is unknown. Here we confirmed that an intracerebroventricularly injected nonselective CRF-R antagonist enhances, whereas an agonist impairs, maternal care. The agonist also prolonged the stress-induced decrease in nursing, reduced maternal aggression and increased anxiety-related behavior. Focusing on the bed nucleus of the stria terminalis (BNST), CRF-R1 and CRF-R2 mRNA expression did not differ in virgin versus lactating rats. However, CRF-R2 mRNA was more abundant in the posterior than in the medial BNST. Pharmacological manipulations within the medial-posterior BNST showed that both CRF-R1 and CRF-R2 agonists reduced arched back nursing (ABN) rapidly and after a delay, respectively. After stress, both antagonists prevented the stress-induced decrease in nursing, with the CRF-R2 antagonist actually increasing ABN. During the maternal defense test, maternal aggression was abolished by the CRF-R2, but not the CRF-R1, agonist. Anxiety-related behavior was increased by the CRF-R1 agonist and reduced by both antagonists. Both antagonists were also effective in virgin females but not in males, revealing a sexual dimorphism in the regulation of anxiety within the medial-posterior BNST. In conclusion, the detrimental effects of increased CRF-R activation on maternal behavior are mediated via CRF-R2 and, to a lesser extent, via CRF-R1 in the medial-posterior BNST in lactating rats. Moreover, both CRF-R1 and CRF-R2 regulate anxiety in females independently of their reproductive status.

  6. FIRING PATTERNS OF MATERNAL RAT PRELIMBIC NEURONS DURING SPONTANEOUS CONTACT WITH PUPS

    PubMed Central

    Febo, Marcelo

    2012-01-01

    Extracellular single unit activity was recorded from medial prefrontal cortex (mPFC) of postpartum dams over the course of 3 days while they engaged in spontaneous pup-directed behaviors and non-specific exploratory behavior. Out of 109 units identified over the course of the experiment, 15 units were observed to be pup-responsive and 15 increased their discharge rates non-specifically while not attending to pups. An association between neuronal activity and typical maternal behaviors (e.g., retrieval, pup-grooming, nursing) was not observed. Instead, brief bouts of snout contact with pups were accompanied by phasic increases and decreases in spike rates. The observed pup contact responsive cells might play a role in processing of sensory feedback from pups or the transmission of modulatory output to other subcortical maternal brain areas. PMID:22643133

  7. Maternal obesity promotes a proinflammatory signature in rat uterus and blastocyst.

    PubMed

    Shankar, Kartik; Zhong, Ying; Kang, Ping; Lau, Franchesca; Blackburn, Michael L; Chen, Jin-Ran; Borengasser, Sarah J; Ronis, Martin J J; Badger, Thomas M

    2011-11-01

    Maternal obesity at conception increases the risk of offspring obesity, thus propagating an intergenerational vicious cycle. Male offspring born to obese dams are hyperresponsive to high fat-diets, gaining greater body weight, fat mass, and additional metabolic sequelae compared to lean controls. In this report, we identify the impact of maternal obesity before conception, on the embryo, and intrauterine milieu during the periimplantation period. We conducted global transcriptomic profiling in the uterus and periimplantation blastocyst, gene/protein expression analyses of inflammatory pathways in conjunction with endocrine and metabolic characterization in the dams at implantation. Uterine gene expression profiles of lean and obese dams revealed distinct signatures for genes regulating inflammation and lipid metabolism. Both pathway and gene-set enrichment analysis revealed uterine nuclear factor-κB and c-Jun N-terminal kinase signaling to be up-regulated in the uterus of obese dams, which was confirmed via immunoblotting. Obese uteri also evidenced an inflammatory secretome with higher chemokine mRNA abundance (CCL2, CCL5, CCL7, and CxCL10) and related regulators (TLR2, CD14, and Ccr1). Increased inflammation in the uterus was associated with ectopic lipid accumulation and expression of lipid metabolic genes. Gene expression in sex-identified male periimplantation blastocyst at day postcoitum 4.5 was clearly influenced by maternal obesity (359 transcripts, ±1.4-fold), including changes in developmental and epigenetic regulators. Akin to the uterus, nuclear factor-κB-regulated proinflammatory genes (CCL4 and CCL5) increased and expression of antioxidant (GPx3) and mitochondrial (TFAM and NRF1) genes decreased in the obese embryos. Our results suggest that ectopic lipid and inflammation may link maternal obesity to increased predisposition of offspring to obesity later in life.

  8. Prenatal exposure of a novel antipsychotic aripiprazole: impact on maternal, fetal and postnatal body weight modulation in rats.

    PubMed

    Singh, K P; Tripathi, Nidhi

    2014-03-01

    Nearly all atypical antipsychotic drugs (AAPDs) of second- generation are associated with body weight gain in adults with prolonged exposure; but reports on third-generation AAPDs like Aripiprazole (ARI) and weight gain are scanty and ambiguous. This may be attributed to some unknown mechanism of action, the study of which is essential to investigate gestational exposure of equivalent therapeutic doses of ARI on maternal and fetal weight gain and its longlasting impact on postnatal development and growth of offspring in rodent model. 30 pregnant Wistar rats were exposed to selected doses (2mg, 3mg and 5mg/kg BW) of ARI from GD3-21 orally, with control subjects. Half of the pregnant subjects of each group were sacrificed at GD22 and rest dams were allowed to deliver normally and pups were reared postnatally up to 10 weeks of age. In ARI treated groups, there was no substantial alteration of body weight gain and food intake in pregnant subjects while significant reduction was found in fetal and postnatal (pre-and post weaning) body weight gain. ARI was found neutral for substantial weight gain in pregnant rats but may induce significant weight loss in fetuses, creating long-lasting negative impact on offspring growth (in weight) till PND70. Therefore, ARI could be a good alternative of second- generation AAPDs for adult females but may not be safe for developing fetuses and offspring.

  9. Maternal obesity disturbs the postnatal development of gonocytes in the rat without impairment of testis structure at prepubertal age.

    PubMed

    Christante, Caroline Maria; Taboga, Sebastião Roberto; Pinto-Fochi, Maria Etelvina; Góes, Rejane Maira

    2013-12-01

    In this study, we evaluated whether maternal obesity (MO) affects testis development and gonocyte differentiation in the rat from 0.5 to 14.5 postnatal days. Male Wistar rats were used at 0.5, 4.5, 7.5, and 14.5 days post partum (dpp). These rats were born from obese mothers, previously fed with a high-fat diet (20% saturated fat), for 15 weeks, or normal mothers that had received a balanced murine diet (4% lipids). MO did not affect testis weight or histology at birth but changed the migratory behavior of gonocytes. The density of relocated cells was higher in MO pups at 0.5 dpp, decreased at 4.5 dpp, and differed from those of control pups, where density increased exponentially from 0.5 to 7.5 dpp. The numerical density of gonocytes within seminiferous cords did not vary in MO, in relation to control neonates, for any age considered, but the testis weight was 50% lower at 4.5 dpp. A wide variation in plasmatic testosterone and estrogen levels was observed among the groups during the first week of age and MO pups exhibited higher steroid concentrations at 4.5 dpp, in comparison with controls. At this age, higher estrogen levels of MO pups impaired the gonocyte proliferation. At 7.5 dpp, the testicular size and other parameters of gonocyte development are retrieved. In conclusion, MO and saturated lipid diets disturb gonocyte development and sexual steroid levels during the first days of life, with recovery at prepubertal age.

  10. Early maternal deprivation induces changes on the expression of 2-AG biosynthesis and degradation enzymes in neonatal rat hippocampus.

    PubMed

    Suárez, Juan; Rivera, Patricia; Llorente, Ricardo; Romero-Zerbo, Silvana Y; Bermúdez-Silva, Francisco J; de Fonseca, Fernando Rodríguez; Viveros, María-Paz

    2010-08-19

    Early maternal deprivation (MD) in rats (24h, PND 9-10) is a model for neurodevelopmental stress. Our previous data showed that MD altered the hippocampal levels of the endocannabinoid 2-AG and the expression of hippocampal cannabinoid receptors in 13-day-old rats, with males being more markedly affected. The aim of this study was to analyze the impact of MD on the enzymes involved in 2-AG biosynthesis (DAGLalpha and DAGLbeta) and degradation (MAGL) in relevant areas (DG, CA1, CA3) of the hippocampus in 13-day-old neonatal rats. The expression of the enzymes was evaluated by quantitative RT-PCR, immunohistochemistry, and densitometry. MD induced a significant increase in DAGLalpha immunoreactivity in both males and females, which was mainly associated with fibers in the polymorphic cell layer of the dentate gyrus and in the stratum pyramidale of CA3. In contrast, the molecular layer of the dentate gyrus showed a significant decrease in DAGLalpha immunoreactivity in MD males and females. No changes were observed in DAGLbeta immunoreactivity. MD induced a significant decrease in MAGL immunoreactivity in hippocampal CA3 and CA1 areas, more marked in males than in females, and that was mainly associated with fibers in all strata of CA3 and CA1. The results also showed a significant decrease of MAGL mRNA levels in MD males. These data support a clear association between neurodevelopmental stress and dysregulation of the endocannabinoid system. This association may be relevant for schizophrenia and other neurodevelopmental psychiatric disorders.

  11. Sex, but not maternal protein or folic acid intake, determines the fatty acid composition of hepatic phospholipids, but not of triacylglycerol, in adult rats.

    PubMed

    Burdge, G C; Slater-Jefferies, J L; Grant, R A; Chung, W-S; West, A L; Lillycrop, K A; Hanson, M A; Calder, P C

    2008-01-01

    The aim of the study was to investigate whether the protein and folic acid content of the maternal diet and the sex of the offspring alter the polyunsaturated fatty acid content of hepatic phospholipids and triacylglycerol (TAG). Pregnant rats were fed diets containing 18% or 9% protein with either 1 or 5mg/kg folic acid. Maternal diet did not alter hepatic lipid composition in the adult offspring. Data from each maternal dietary group were combined and reanalysed. The proportion of 18:0, 20:4n-6 and 22:6n-3 in liver phospholipids was higher in females than in males, while hepatic TAG composition did not differ between sexes. Delta5 Desaturase expression was higher in females than in males. Neither Delta5 nor Delta6 desaturase expression was related to polyunsaturated fatty acid concentrations. These results suggest that sex differences in liver phospholipid fatty acid composition may reflect primary differences in the specificity of phospholipid biosynthesis.

  12. Effects in rats of maternal exposure to raspberry leaf and its constituents on the activity of cytochrome p450 enzymes in the offspring.

    PubMed

    Makaji, Emilija; Ho, Shirley H Y; Holloway, Alison C; Crankshaw, Denis J

    2011-03-01

    The goal of our study was to determine whether maternal exposure to red raspberry leaf (RRL) and its constituents can permanently alter biotransformation of fluorogenic substrates by cytochrome P450 (CYP) in the livers of male and female offspring. Nulliparous female rats received vehicle, raspberry leaf, kaempferol, quercetin, or ellagic acid orally once breeding had been confirmed until parturition. Hepatic microsomes were prepared from animals at birth (postnatal day 1 [PND1]), weaning (PND21), PND65, and PND120 to determine the biotransformation of 8 fluorogenic substrates. The pattern of biotransformation of all but 2 of the substrates was gender specific. Maternal consumption of RRL increased biotransformation of 3 substrates by female offspring at PND120 resulting in a more masculine profile. Kaempferol and quercetin had a similar effect to RRL. These results suggest that maternal consumption of either RRL or some of its constituents leads to long-term alterations of CYP activity in female offspring.

  13. In utero exposure to prepregnancy maternal obesity and postweaning high-fat diet impair regulators of mitochondrial dynamics in rat placenta and offspring

    PubMed Central

    Borengasser, Sarah J.; Faske, Jennifer; Kang, Ping; Blackburn, Michael L.; Badger, Thomas M.

    2014-01-01

    The proportion of pregnant women who are obese at conception continues to rise. Compelling evidence suggests the intrauterine environment is an important determinant of offspring health. Maternal obesity and unhealthy diets are shown to promote metabolic programming in the offspring. Mitochondria are maternally inherited, and we have previously shown impaired mitochondrial function in rat offspring exposed to maternal obesity in utero. Mitochondrial health is maintained by mitochondrial dynamics, or the processes of fusion and fission, which serve to repair damaged mitochondria, remove irreparable mitochondria, and maintain mitochondrial morphology. An imbalance between fusion and fission has been associated with obesity, insulin resistance, and reproduction complications. In the present study, we examined the influence of maternal obesity and postweaning high-fat diet (HFD) on key regulators of mitochondrial fusion and fission in rat offspring at important developmental milestones which included postnatal day (PND)35 (2 wk HFD) and PND130 (∼16 wk HFD). Our results indicate HFD-fed offspring had reduced mRNA expression of presenilin-associated rhomboid-like (PARL), optic atrophy (OPA)1, mitofusin (Mfn)1, Mfn2, fission (Fis)1, and nuclear respiratory factor (Nrf)1 at PND35, while OPA1 and Mfn2 remained decreased at PND130. Putative transcriptional regulators of mitochondrial dynamics were reduced in rat placenta and offspring liver and skeletal muscle [peroxisome proliferator-activated receptor gamma coactivator (PGC1)α, PGC1β, and estrogen-related receptor (ERR)α], consistent with indirect calorimetry findings revealing reduced energy expenditure and impaired fat utilization. Overall, maternal obesity detrimentally alters mitochondrial targets that may contribute to impaired mitochondrial health and increased obesity susceptibility in later life. PMID:25336449

  14. Taurine supplementation preserves hypothalamic leptin action in normal and protein-restricted mice fed on a high-fat diet.

    PubMed

    Camargo, Rafael L; Batista, Thiago M; Ribeiro, Rosane A; Branco, Renato C S; Da Silva, Priscilla M R; Izumi, Clarice; Araujo, Thiago R; Greene, Lewis J; Boschero, Antonio C; Carneiro, Everardo M

    2015-11-01

    Malnutrition programs the neuroendocrine axis by disruption of food-intake control, leading to obesity. Taurine (Tau) is neuroprotective and improves anorexigenic actions in the hypothalamus. We evaluated the hypothalamic gene-expression profile and food-intake control in protein-restricted mice submitted to a high-fat diet (HFD) and Tau supplementation. Mice were fed on a control (14 % protein-C) or a protein-restricted diet (6 % protein-R) for 6 weeks. Thereafter, mice received, or not, HFD for 8 weeks (CH and RH) with or without 5 % Tau supplementation (CHT and RHT). Protein restriction led to higher food intake, but calories were matched to controls. Excessive calorie intake occurred in HFD mice and this was prevented by Tau supplementation only in the CH group. Additionally, RH and CH mice developed hypothalamic leptin resistance, which was prevented by Tau. Global alterations in the expressions of genes involved in hypothalamic metabolism, cellular defense, apoptosis and endoplasmic reticulum stress pathways were induced by dietary manipulations and Tau treatment. The orexigenic peptides NPY and AgRP were increased by protein restriction and lowered by the HFD. The anorexigenic peptide Pomc was increased by HFD, and this was prevented by Tau only in CH mice. Thus, food intake was disrupted by dietary protein restriction and obesity. HFD-induced alterations were not enhanced by previous protein deficiency, but the some beneficial effects of Tau supplementation upon food intake were blunted by protein restriction. Tau effects upon feeding behavior control are complex and involve interactions with a vast gene network, preventing hypothalamic leptin resistance. PMID:26133737

  15. Both long and brief maternal separation produces persistent changes in tissue levels of brain monoamines in middle-aged female rats.

    PubMed

    Arborelius, L; Eklund, M B

    2007-03-16

    Adverse experiences early in life are associated with an increased incidence of later psychopathology including depression. Based on evidence that dysfunction of central monoaminergic systems is involved in the pathophysiology of depression, we hypothesize that early adversity could negatively affect these systems. To test this we have investigated the effects of maternal separation, which has been suggested to model early-life stress and the development of a depression-like syndrome in the rat, on brain monoaminergic systems. Since depression is more common in women and the risk of developing this disorder appears to increase with age, we have studied such effects in middle-aged female rats. Rat pups were separated for 180 min (long maternal separation; LMS) or 15 min (brief maternal separation; BMS, often referred to as neonatal handling) twice daily for 2 weeks postpartum. An animal facility-reared (AFR) group was also included. At 15 months of age tissue levels of monoamines and their metabolites in several different brain regions were analyzed. In the LMS females tissue levels of both 5-HT and 5-hydroxyindole acetic acid (5-HIAA) were significantly increased in the dorsal raphe nucleus, and 5-HIAA and homovanillic acid levels were also elevated in the nucleus accumbens as compared with AFR and BMS rats. In the cingulate cortex both LMS and BMS decreased noradrenaline (NA) levels, although this effect was more pronounced in the LMS rats. On the other hand, BMS decreased 5-HT, 5-HIAA, dopamine (DA) as well as NA levels in the amygdala and produced an increase in DA levels in response to acute stress in the hypothalamus, an effect not seen in AFR rats. Our results demonstrate that LMS produced persistent alterations in both serotonergic, noradrenergic and dopaminergic systems in brain regions that have been suggested to be implicated in the pathophysiology of depression. In addition, BMS affected brain monoaminergic levels mainly in the amygdala.

  16. Highly Palatable Food during Adolescence Improves Anxiety-Like Behaviors and Hypothalamic-Pituitary-Adrenal Axis Dysfunction in Rats that Experienced Neonatal Maternal Separation

    PubMed Central

    Lee, Jong-Ho; Kim, Jin Young

    2014-01-01

    Background This study was conducted to examine the effects of ad libitum consumption of highly palatable food (HPF) during adolescence on the adverse behavioral outcome of neonatal maternal separation. Methods Male Sprague-Dawley pups were separated from dam for 3 hours daily during the first 2 weeks of birth (maternal separation, MS) or left undisturbed (nonhandled, NH). Half of MS pups received free access to chocolate cookies in addition to ad libitum chow from postnatal day 28 (MS+HPF). Pups were subjected to behavioral tests during young adulthood. The plasma corticosterone response to stress challenge was analyzed by radioimmunoassay. Results Daily caloric intake and body weight gain did not differ among the experimental groups. Ambulatory activities were decreased defecation activity and rostral grooming were increased in MS controls (fed with chow only) compared with NH rats. MS controls spent less time in open arms, and more time in closed arms during the elevated plus maze test, than NH rats. Immobility duration during the forced swim test was increased in MS controls compared with NH rats. Cookie access normalized the behavioral scores of ambulatory and defecation activities and grooming, but not the scores during the elevated plus maze and swim tests in MS rats. Stress-induced corticosterone increase was blunted in MS rats fed with chow only, and cookie access normalized it. Conclusion Prolonged access to HPF during adolescence and youth partly improves anxiety-related, but not depressive, symptoms in rats that experienced neonatal maternal separation, possibly in relation with improved function of the hypothalamic-pituitary-adrenal (HPA) axis. PMID:25031890

  17. Maternal dietary fat affects milk fatty acid profile and impacts on weight gain and thermogenic capacity of suckling rats.

    PubMed

    Priego, Teresa; Sánchez, Juana; García, Ana Paula; Palou, Andreu; Picó, Catalina

    2013-05-01

    We aimed to assess the effects of maternal supplementation with the main fat sources used in the human Western diet (olive oil, butter, margarine) on milk FA composition and on plasma FA profile of offspring, and to determine whether it may influence body-weight-gain (BWG) and adiposity of offspring during the suckling period. Wistar rats were supplemented with the different fat sources from day 14 of gestation and throughout lactation. Olive oil-supplemented dams showed the highest proportion of oleic-acid in milk, with no changes in plasma. Their offspring also showed the highest proportion of this FA in plasma, lower BWG during the suckling period, and higher levels of UCP1 in brown adipose tissue (BAT) at weaning. Margarine-supplemented dams showed the highest percentage of PUFA in milk, and a similar tendency was found in plasma of their offspring. Butter-supplemented dams displayed higher proportion of saturated FA (SFA) in milk compared to other fat-supplemented dams, but lower than controls. Control offspring also showed higher proportion of SFA in plasma and greater BWG during the suckling period than fat-supplemented groups. Significant correlations were found between the relative content of some milk FA and BWG of offspring, in particular, oleic-acid levels correlated negatively with BWG and positively with UCP1 levels. These results show that maternal dietary source of fat affects milk FA composition and circulating FA profile, as could be expected, but also BWG and thermogenic capacity of offspring during the suckling period. An effect of oleic-acid stimulating BAT thermogenic capacity of suckling pups is proposed.

  18. Maternal nicotine exposure during lactation alters hypothalamic neuropeptides expression in the adult rat progeny.

    PubMed

    Younes-Rapozo, Viviane; Moura, Egberto G; Manhães, Alex C; Pinheiro, Cintia R; Santos-Silva, Ana Paula; de Oliveira, Elaine; Lisboa, Patricia C

    2013-08-01

    Maternal exposure to nicotine during lactation causes hyperleptinemia in the pups and, at adulthood, these animals are overweight and hyperleptinemic, while, in their hypothalamus, the leptin signaling pathway is reduced, evidencing a central leptin resistance. Then, we evaluated the expression of pro-opiomelanocortin (POMC), alpha-melanocyte stimulating hormone (α-MSH), cocaine and amphetamine-regulated transcript (CART), neuropeptide Y (NPY), agouti-related peptide (AgRP) and others in different hypothalamic nuclei in order to better understand the mechanisms underlying the obese phenotype observed in these animals at adulthood. On the 2nd postnatal day (P2), dams were subcutaneously implanted with osmotic minipumps releasing nicotine (NIC-6 mg/kg/day) or saline for 14 days. Offspring were killed in P180 and immunohistochemistry and Western blot analysis were carried out. Significance data had p<0.05. Adult NIC offspring showed more intense NPY staining in the paraventricular nucleus (PVN) (+21%) and increased number of POMC-positive cells in the: arcuate nucleus (+33%), as an increase in fiber density of α-MSH in PVN (+85%). However, the number of CART-positive cells was reduced in the PVN (-25%). CRH staining was more intense in NIC offspring (+136%). Orexins and AgRP were not altered. Thus, maternal nicotine exposure changes hypothalamic neuropeptides in the adult progeny that is partially compatible with leptin resistance.

  19. Maternal saturated-fat-rich diet promotes leptin resistance in fetal liver lipid catabolism and programs lipid homeostasis impairments in the liver of rat offspring.

    PubMed

    Mazzucco, María Belén; Fornes, Daiana; Capobianco, Evangelina; Higa, Romina; Jawerbaum, Alicia; White, Verónica

    2016-01-01

    We aimed to analyze if an overload of saturated fat in maternal diet induced lipid metabolic impairments in livers from rat fetuses that persist in the offspring and to identify potential mechanisms involving fetal leptin resistance. Female rats were fed either a diet enriched in 25% of saturated fat (SFD rats) or a regular diet (controls). Fetuses of 21days of gestation and offspring of 21 and 140days of age were obtained and plasma and liver were kept for further analysis. Livers from a group of control and SFD fetuses were cultured in the presence or absence of leptin. Leptin or vehicle was administered to control fetuses during the last days of gestation and, on day 21, fetal livers and plasma were obtained. Lipid levels were assessed by thin-layer chromatography and mRNA gene expression of CPT1, ACO and PPARα by RT-PCR. Liver lipid levels were increased and CPT1 and ACO were down-regulated in fetuses and offspring from SFD rats compared to controls. After the culture with leptin, control fetal livers showed increased ACO and CPT1 expression and decreased lipid levels, while fetal livers from SFD rats showed no changes. Fetal administration of leptin induced a decrease in ACO and no changes in CPT1 expression. In summary, our results suggest that a saturated fat overload in maternal diet induces fetal leptin resistance in liver lipid catabolism, which might be contributing to liver lipid alterations that are sustained in the offspring.

  20. Maternal mobile phone exposure adversely affects the electrophysiological properties of Purkinje neurons in rat offspring.

    PubMed

    Haghani, M; Shabani, M; Moazzami, K

    2013-10-10

    Electromagnetic field (EMF) radiations emitted from mobile phones may cause structural damage to neurons. With the increased usage of mobile phones worldwide, concerns about their possible effects on the nervous system are rising. In the present study, we aimed to elucidate the possible effects of prenatal EMF exposure on the cerebellum of offspring Wistar rats. Rats in the EMF group were exposed to 900-MHz pulse-EMF irradiation for 6h per day during all gestation period. Ten offspring per each group were evaluated for behavioral and electrophysiological evaluations. Cerebellum-related behavioral dysfunctions were analyzed using motor learning and cerebellum-dependent functional tasks (Accelerated Rotarod, Hanging and Open field tests). Whole-cell patch clamp recordings were used for electrophysiological evaluations. The results of the present study failed to show any behavioral abnormalities in rats exposed to chronic EMF radiation. However, whole-cell patch clamp recordings revealed decreased neuronal excitability of Purkinje cells in rats exposed to EMF. The most prominent changes included afterhyperpolarization amplitude, spike frequency, half width and first spike latency. In conclusion, the results of the present study show that prenatal EMF exposure results in altered electrophysiological properties of Purkinje neurons. However, these changes may not be severe enough to alter the cerebellum-dependent functional tasks.

  1. Decreased basal insulin secretion from pancreatic islets of pups in a rat model of maternal obesity.

    PubMed

    Zambrano, Elena; Sosa-Larios, Tonantzin; Calzada, Lizbeth; Ibáñez, Carlos A; Mendoza-Rodríguez, Carmen A; Morales, Angélica; Morimoto, Sumiko

    2016-10-01

    Maternal obesity (MO) is a deleterious condition that enhances susceptibility of adult offspring to metabolic diseases such as type 2 diabetes. The objective is to study the effect of MO on in vitro insulin secretion and pancreatic cellular population in offspring. We hypothesize that a harmful antenatal metabolic environment due to MO diminishes the basal glucose-responsive secretory function of pancreatic beta cells in offspring. Mothers were fed a control (C) or high-fat diet from weaning through pregnancy (120 days) and lactation. At postnatal days (PNDs) 36 and 110, pups were killed, peripheral blood was collected and pancreatic islets were isolated. Basal insulin secretion was measured in vitro in islets for 60 min. It was found that blood insulin, glucose and homeostasis model assessment (HOMA) index were unaffected by maternal diet and age in females. However, male MO offspring at PND 110 showed hyperinsulinemia and insulin resistance compared with C. Body weight was not modified by MO, but fat content was higher in MO pups compared with C pups. Triglycerides and leptin concentrations were higher in MO than in C offspring in all groups except in females at PND 36. Pancreatic islet cytoarchitecture was unaffected by MO. At PND 36, islets of male and female C and MO offspring responded similarly to glucose, but at PND 110, male and female MO offspring islets showed a 50% decrease in insulin secretion. It was concluded that MO impairs basal insulin secretion of offspring with a greater impact on males than females, and this effect mainly manifests in adulthood. PMID:27496224

  2. Maternal obesity induced by diet in rats permanently influences central processes regulating food intake in offspring.

    PubMed

    Kirk, Shona L; Samuelsson, Anne-Maj; Argenton, Marco; Dhonye, Hannah; Kalamatianos, Theodosis; Poston, Lucilla; Taylor, Paul D; Coen, Clive W

    2009-06-11

    Hypothalamic systems which regulate appetite may be permanently modified during early development. We have previously reported hyperphagia and increased adiposity in the adult offspring of rodents fed an obesogenic diet prior to and throughout pregnancy and lactation. We now report that offspring of obese (OffOb) rats display an amplified and prolonged neonatal leptin surge, which is accompanied by elevated leptin mRNA expression in their abdominal white adipose tissue. At postnatal Day 30, before the onset of hyperphagia in these animals, serum leptin is normal, but leptin-induced appetite suppression and phosphorylation of STAT3 in the arcuate nucleus (ARC) are attenuated; the level of AgRP-immunoreactivity in the hypothalamic paraventricular nucleus (PVH), which derives from neurones in the ARC and is developmentally dependent on leptin, is also diminished. We hypothesise that prolonged release of abnormally high levels of leptin by neonatal OffOb rats leads to leptin resistance and permanently affects hypothalamic functions involving the ARC and PVH. Such effects may underlie the developmental programming of hyperphagia and obesity in these rats.

  3. Mifepristone Treatment during Early Adolescence Fails to Restore Maternal Deprivation-Induced Deficits in Behavioral Inhibition of Adult Male Rats

    PubMed Central

    Kentrop, Jiska; van der Tas, Liza; Loi, Manila; van IJzendoorn, Marinus H.; Bakermans-Kranenburg, Marian J.; Joëls, Marian; van der Veen, Rixt

    2016-01-01

    Early life adversity has a profound impact on brain development and later life health. Animal models have provided insight how early life stress programs stress responsiveness and might contribute to the development of psychiatric disorders. In the present study, the long-term effects of maternal deprivation (MD) on behavioral inhibition and attention were examined in adult male Wistar rats. To this end animals were tested in the 5-choice serial reaction time task (5-choice SRTT). We also explored the potential of a 3-day treatment with the glucocorticoid receptor (GR) antagonist mifepristone during early adolescence to normalize putative behavioral effects of early life stress. Deprivation of the mother for 24 h on postnatal day (PND) 3 led to a modest but significant increase in premature responses in the 5-choice SRTT, but did not affect measures of attention. Body weight was lower in deprived animals from weaning until the start of testing. Early adolescent mifepristone treatment (PND 26–28) did not influence performance on the 5-choice SRTT and did not mitigate the deprivation-related impairment in behavioral inhibition. Our results indicate that MD leads to impaired behavioral inhibition, and that mifepristone treatment during early adolescence does not normalize the behavioral changes caused by early life stress. PMID:27378873

  4. Maternal conjugated linoleic acid supplementation reverses high-fat diet-induced skeletal muscle atrophy and inflammation in adult male rat offspring.

    PubMed

    Pileggi, C A; Segovia, S A; Markworth, J F; Gray, C; Zhang, X D; Milan, A M; Mitchell, C J; Barnett, M P G; Roy, N C; Vickers, M H; Reynolds, C M; Cameron-Smith, D

    2016-03-01

    A high-saturated-fat diet (HFD) during pregnancy and lactation leads to metabolic disorders in offspring concomitant with increased adiposity and a proinflammatory phenotype in later life. During the fetal period, the impact of maternal diet on skeletal muscle development is poorly described, despite this tissue exerting a major influence on life-long metabolic health. This study investigated the effect of a maternal HFD on skeletal muscle anabolic, catabolic, and inflammatory signaling in adult rat offspring. Furthermore, the actions of maternal-supplemented conjugated linoleic acid (CLA) on these measures of muscle phenotype were investigated. A purified control diet (CD; 10% kcal fat), a CD supplemented with CLA (CLA; 10% kcal fat, 1% total fat as CLA), a high-fat (HFD; 45% kcal fat from lard), or a HFD supplemented with CLA (HFCLA; 45% kcal fat from lard, 1% total fat as CLA) was fed ad libitum to female Sprague-Dawley rats for 10 days before mating and throughout gestation and lactation. Male offspring received a standard chow diet from weaning, and the gastrocnemius was collected for analysis at day 150. Offspring from HF and HFCLA mothers displayed lower muscular protein content accompanied by elevated monocyte chemotactic protein-1, IL-6, and IL-1β concentrations. Phosphorylation of NF-κBp65 (Ser(536)) and expression of the catabolic E3 ligase muscle ring finger 1 (MuRF1) were increased in HF offspring, an effect reversed by maternal CLA supplementation. The present study demonstrates the importance of early life interventions to ameliorate the negative effects of poor maternal diet on offspring skeletal muscle development. PMID:26632603

  5. Early postnatal maternal separation causes alterations in the expression of β3-adrenergic receptor in rat adipose tissue suggesting long-term influence on obesity

    SciTech Connect

    Miki, Takanori; Liu, Jun-Qian; Ohta, Ken-ichi; Suzuki, Shingo; Kusaka, Takashi; Warita, Katsuhiko; Yokoyama, Toshifumi; Jamal, Mostofa; Ueki, Masaaki; Yakura, Tomiko; Tamai, Motoki; Sumitani, Kazunori; Hosomi, Naohisa; Takeuchi, Yoshiki

    2013-12-06

    Highlights: •High-fat diet intake following maternal separation did not cause body weight gain. •However, levels of metabolism-related molecules in adipose tissue were altered. •Increased levels of prohibitin mRNA in white fat were observed. •Attenuated levels of β3-adrenergic receptor mRNA were observed in brown fat. •Such alterations in adipose tissue may contribute to obesity later in life. -- Abstract: The effects of early postnatal maternal deprivation on the biological characteristics of the adipose tissue later in life were investigated in the present study. Sprague–Dawley rats were classified as either maternal deprivation (MD) or mother-reared control (MRC) groups. MD was achieved by separating the rat pups from their mothers for 3 h each day during the 10–15 postnatal days. mRNA levels of mitochondrial uncoupling protein 1 (UCP-1), β3-adrenergic receptor (β3-AR), and prohibitin (PHB) in the brown and white adipose tissue were determined using real-time RT-PCR analysis. UCP-1, which is mediated through β3-AR, is closely involved in the energy metabolism and expenditure. PHB is highly expressed in the proliferating tissues/cells. At 10 weeks of age, the body weight of the MRC and MD rats was similar. However, the levels of the key molecules in the adipose tissue were substantially altered. There was a significant increase in the expression of PHB mRNA in the white adipose tissue, while the β3-AR mRNA expression decreased significantly, and the UCP-1 mRNA expression remained unchanged in the brown adipose tissue. Given that these molecules influence the mitochondrial metabolism, our study indicates that early postnatal maternal deprivation can influence the fate of adipose tissue proliferation, presumably leading to obesity later in life.

  6. Specific neurotoxin lesions of median raphe serotonergic neurons disrupt maternal behavior in the lactating rat.

    PubMed

    Barofsky, A L; Taylor, J; Tizabi, Y; Kumar, R; Jones-Quartey, K

    1983-11-01

    Impairments in lactation after electrolytic lesions of the median raphe (MR) nucleus have been corrected by treatment with PRL. Specific serotonin neurotoxin lesions were used in the present study to determine whether decrements in litter growth after electrolytic lesions could be attributed to serotonergic neuron damage at the MR locus, and whether MR lesions (MRL) disrupted suckling-induced PRL release. Intracerebral microinjection of 5,7-dihydroxytryptamine (5,7-DHT) into the MR nucleus produced dose-related decrements in litter growth after either 4 micrograms (sham, 1.35 +/- 0.05; MRL, 1.04 +/- 0.05 g/pup X day; P less than 0.001) or 8 micrograms 5,7-DHT (sham, 1.35 +/- 0.06; MRL, 0.87 +/- 0.11 g/pup X day; P less than 0.001). Despite hypothalamic serotonin depletions of 15% and 55%, respectively, for the two doses of 5,7-DHT, there was no difference between sham and MRL animals in either basal or suckling-induced PRL release. When lesions were placed on day 1 of lactation (L) so that killing on day 7-L corresponded to the early maximal neurotoxin effect, MRL mothers still showed litter growth decrements (0.37 +/- 0.07; sham, 0.98 +/- 0.08 g/pup X day; P less than 0.001) and normal PRL values. When maternal behavior was examined, MRL animals exhibited a higher incidence of abnormal behaviors (failure to retrieve pups, cannibalism, and failure to initiate suckling during a 1-h test period; Fisher's exact P, Sham vs. MRL, less than 0.01, less than 0.05, and 0.15, respectively) than sham animals or animals with 5,7-DHT lesions in the dorsal raphe nucleus or superior colliculus. In addition, suckling behavior scores, determined from daily suckling behavior observations, were lowest in the MRL group and correlated with litter growth only in this group (r = 0.789; P less than 0.01). These data suggest that serotonergic elements in the MR nucleus play an obligatory role in maintaining normal maternal behavior during lactation, but they are not involved in suckling

  7. Effects of maternal oral administration of morphine sulfate on developing rat fetal cerebrum: a morphometrical evaluation.

    PubMed

    Sadraie, Seyed Homayoon; Kaka, Gholam Reza; Sahraei, Hedayat; Dashtnavard, Hosein; Bahadoran, Hosein; Mofid, Mahmood; Nasab, Hossein Mahdavi; Jafari, Fatemeh

    2008-12-15

    Intrauterine morphine exposure is a risk factor for neurological and behavioral deficit in children, although the precise underlying biological correlate for this is unclear. Female pregnant rats were orally treated with 0.1 mg/ml of morphine solution on the 21st day of gestation. Pregnant rats were killed on the 21st day of gestation and their fetuses were taken out and evaluated for growth and cerebral development. The fetuses were fixed and followed by dehydration through graded ethanol solutions and were then embedded and their heads were coronally sectioned through the frontal cerebral cortex. Quantitative computer-assisted morphometric study was done on the frontal cerebral cortex (FCC) which consists of cortical plate (CP), intermediate (migratory) zone (IZ) and matrix (proliferative) zone (MZ) in the rat embryos. The results showed that morphine exposure caused a significant reduction of fetal weight and crown-to-rump length in morphine exposure group. The present study showed that animals with intrauterine morphine exposure, induced by a period of reduced placental blood flow during the second week of pregnancy, demonstrate reduced both cortical thickness and the numbers of neurons in the developing fetal frontal cerebral cortex (FCC). Histomorphometric evaluation revealed that the thickness of the CP was significantly decreased in the morphine-exposed embryos. In addition, neuronal counting showed that cell proliferation in the CP was suppressed after morphine administration and that the migration of neurons from the matrix zone (MZ) to the cortex was decelerated. In conclusion, these results showed that morphine exposure during the second week of pregnancy could affect brain development in a way, which could lead to neurological and behavioral deficits in the postnatal animal.

  8. Maternal deprivation in neonatal rats of different conditions affects growth rate, circadian clock, and stress responsiveness differentially.

    PubMed

    Yamazaki, Ayano; Ohtsuki, Yoshio; Yoshihara, Toshihiro; Honma, Sato; Honma, Ken-Ichi

    2005-09-15

    Effects of periodic maternal deprivation (MD) were examined in rat pups on growth rate, circadian phase and period at weaning, and stress responsiveness in adulthood. MD was performed from postnatal day 1 to day 6 or day 7, with or without keeping ambient temperature at 37 degrees C and humidity at 70-80% during deprivation. Times of day and length of MD were also changed. Body weights were significantly reduced at weaning in MD12 (MD for 12 h) and MD6am (MD for 6 h in the morning) pups, whereas they were not changed in MD6pm (MD in the afternoon) and all MD3 groups. At 8 weeks old, body weight was still significantly lower in MD12 than the control, but not different from the control in other groups. Circadian phases of free-running locomotor rhythm at weaning were almost reversed in MD12, MD6am and MD6pm as compared with those in the control. Intermediate phase-shifts were observed in MD3Eam (3 h MD in the first quarter of the light phase; early am) and MD3Lam (late am; the second quarter), whereas no phase-shift was detected in MD3Epm (early pm; the third quarter) and MD3Lpm (late pm; the fourth quarter). Elevation of plasma corticosterone level after novelty exposure at 8 weeks old was more robustly in MD12 and MD3Lam than in the control, but the hormone response in MD3Lpm was not different from the control. Keeping ambient temperature at 37 degrees C during MD did not rescue the MD-induced body weight loss, but attenuated the phase-shifts of the circadian clock, and completely cancelled the stress-induced hormone response in MD12 rats. These findings indicate that MD in rat pups differentially affects growth rate, circadian clock, and stress responsiveness in adulthood, depending on time of day, length of MD and ambient temperature during MD. PMID:16126237

  9. Maternal nicotine exposure leads to higher liver oxidative stress and steatosis in adult rat offspring.

    PubMed

    Conceição, E P; Peixoto-Silva, N; Pinheiro, C R; Oliveira, E; Moura, E G; Lisboa, P C

    2015-04-01

    Early nicotine exposure causes future obesity and insulin resistance. We evaluated the long-term effect of the maternal nicotine exposure during lactation in liver oxidative status, insulin sensitivity and morphology in adult offspring. Two days after birth, osmotic minipumps were implanted in the dams: nicotine (N), 6 mg/kg/day for 14 days or saline (C). Offspring were killed at 180 days. Protein content of superoxide dismutase, glutathione peroxidase, catalase, nitrotyrosine, 4HNE, IRS1, Akt1 and PPARs were measured. MDA, bound protein carbonyl content, SOD, GPx and catalase activities were determined in liver and plasma. Hepatic morphology and triglycerides content were evaluated. Albumin and bilirubin were determined. In plasma, N offspring had higher catalase activity, and SOD/GPx ratio, albumin and bilirubin levels but lower MDA content. In liver, they presented higher MDA and 4HNE levels, bound protein carbonyl content, SOD activity but lower GPx activity. N offspring presented an increase of lipid droplet, higher triglyceride content and a trend to lower PPARα in liver despite unchanged insulin signaling pathway. Early nicotine exposure causes oxidative stress in liver at adulthood, while protect against oxidative stress at plasma level. In addition, N offspring develop liver microsteatosis, which is related to oxidative stress but not to insulin resistance. PMID:25662863

  10. Sex-dependent alterations in response to maternal deprivation in rats.

    PubMed

    Viveros, M P; Llorente, R; López-Gallardo, M; Suarez, J; Bermúdez-Silva, F; De la Fuente, M; Rodriguez de Fonseca, F; Garcia-Segura, L M

    2009-12-01

    We review here our latest results regarding short- and long-term effects of a neonatal maternal deprivation (MD) stress [24h at postnatal day (PND) 9] on diverse psychoneuroimmunoendocrine parameters, pointing out the existence of numerous sexual dimorphisms. Behavioral changes observed in MD animals might be at least in part attributable to neurodevelopmental effects of MD-induced elevated corticosterone levels. Our findings of short-term effects of MD on hippocampal and cerebellar neurons and glial cells appear to support this hypothesis. However, it is important to note that these cellular effects were more marked in males than in females. Moreover, in analyzing the effects of this neonatal stress on the endocannabinoid system (hippocampal endocannabinoid levels and CB1 receptors) we have also found that males were more affected by MD. Since all these sexual dimorphisms were found at an early neonatal age (PND 13), they are attributable to organizational effects of gonadal steroids. We discuss the potential implications of the elevated corticosterone and decreased leptin levels shown by MD animals in their diverse functional alterations, including the above mentioned neural effects as well as the intriguing persistent deficit in their immunological system. We also emphasize the necessity of analyzing the important influence of sex as regards the specific consequences of early life stress.

  11. Maternal micronutrients (folic acid and vitamin B(12)) and omega 3 fatty acids: implications for neurodevelopmental risk in the rat offspring.

    PubMed

    Roy, Suchitra; Kale, Anvita; Dangat, Kamini; Sable, Pratiksha; Kulkarni, Asmita; Joshi, Sadhana

    2012-01-01

    Altered maternal micronutrients (folic acid, vitamin B(12)) are suggested to be at the heart of intra-uterine programming of adult diseases. We have recently described interactions of folic acid, vitamin B(12) and docosahexaenoic acid in one carbon metabolism that is considered to play a key role in regulation oxidative stress and chromatin methylation. However its impact on fetal oxidative stress and brain fatty acid levels has been relatively unexplored. The present study examined the effect of imbalance in maternal micronutrients (folic acid and vitamin B(12)) and maternal omega 3 fatty acid supplementation on oxidative stress parameters and brain fatty acids and in the offspring at birth. Pregnant female rats were divided into six groups at two levels of folic acid both in the presence and absence of vitamin B(12). Both the vitamin B(12) deficient groups were supplemented with omega 3 fatty acid. Oxidative stress marker (malondialdehyde) and polyunsaturated fatty acid profiles in plasma and brain were analyzed in dam and offspring at d20. Our results for the first time indicate that imbalance in maternal micronutrients (excess maternal folic acid supplementation on a B(12) deficient diet) increases (p<0.01) oxidative stress in both mother and pups. This increased maternal oxidative stress resulted in lower (p<0.01) fetal brain DHA levels. Omega 3 fatty acid supplementation was able to restore (p<0.05) the levels of brain DHA in both the vitamin B(12) deficient groups. Our data has implications for implications for neurodevelopmental disorders since micronutrients and DHA are important modulators for neural functioning. PMID:21300490

  12. Maternal micronutrients (folic acid and vitamin B(12)) and omega 3 fatty acids: implications for neurodevelopmental risk in the rat offspring.

    PubMed

    Roy, Suchitra; Kale, Anvita; Dangat, Kamini; Sable, Pratiksha; Kulkarni, Asmita; Joshi, Sadhana

    2012-01-01

    Altered maternal micronutrients (folic acid, vitamin B(12)) are suggested to be at the heart of intra-uterine programming of adult diseases. We have recently described interactions of folic acid, vitamin B(12) and docosahexaenoic acid in one carbon metabolism that is considered to play a key role in regulation oxidative stress and chromatin methylation. However its impact on fetal oxidative stress and brain fatty acid levels has been relatively unexplored. The present study examined the effect of imbalance in maternal micronutrients (folic acid and vitamin B(12)) and maternal omega 3 fatty acid supplementation on oxidative stress parameters and brain fatty acids and in the offspring at birth. Pregnant female rats were divided into six groups at two levels of folic acid both in the presence and absence of vitamin B(12). Both the vitamin B(12) deficient groups were supplemented with omega 3 fatty acid. Oxidative stress marker (malondialdehyde) and polyunsaturated fatty acid profiles in plasma and brain were analyzed in dam and offspring at d20. Our results for the first time indicate that imbalance in maternal micronutrients (excess maternal folic acid supplementation on a B(12) deficient diet) increases (p<0.01) oxidative stress in both mother and pups. This increased maternal oxidative stress resulted in lower (p<0.01) fetal brain DHA levels. Omega 3 fatty acid supplementation was able to restore (p<0.05) the levels of brain DHA in both the vitamin B(12) deficient groups. Our data has implications for implications for neurodevelopmental disorders since micronutrients and DHA are important modulators for neural functioning.

  13. Induction of a rat T cell lymphoma-leukemia by magnesium deficiency--a study of fetal defense against maternal neoplasia.

    PubMed

    Hass, G M; Galt, R M; Laing, G H; Coogan, P S; Maganini, R O; Friese, J A

    1989-01-01

    If Sprague-Dawley rats, 25-30 days old, are fed a diet containing 4-5 mg% of Mg, about 25% of survivors develop a large tumor of the thymus within 6-12 weeks. The tumor is composed of lymphoblasts, which seem to arise from the thymic reticuloendothelial system and, at times, disseminate as an acute T cell lymphoma-leukemia of unknown etiology. If the tumor cells are transmitted intraperitoneally to rats, 14-16 days pregnant, a local invasive and generalized disease is established in the mother but not in the fetuses or their domain. However, if the neoplastic cells are injected into the fetal domain, they colonize the fetal tissues. The colonization by tumor cells is most impressive in the extravascular structure of the placental labyrinth but not in the placental syncytiotrophoblastic zone at the maternal-placental junction. This raises the question as to whether this zone may functionally mediate not only the well-known absolute intrauterine fetal defense against maternal metastatic neoplasia, but also the defense of the fetus against maternal immunologic rejection.

  14. Differential effects of neonatal maternal separation on the expression of neurotrophic factors in rat brain. II: Regional differences in the cerebellum versus the cerebral cortex.

    PubMed

    Miki, Takanori; Lee, Kyoung-Youl; Yokoyama, Toshifumi; Liu, Jun-Qian; Kusaka, Takashi; Suzuki, Shingo; Ohta, Ken-ichi; Warita, Katsuhiko; Jamal, Mostofa; Ueki, Masaaki; Yakura, Tomiko; Hosomi, Naohisa; Takeuchi, Yoshiki

    2013-01-01

    This study was conducted in order to examine the effects of early postnatal maternal separation stress on the age-dependent fluctuations in the expression levels of neurotrophic factor ligands and receptors in the developing cerebellum. Wistar rats were separated from their mothers for 3 h each day during postnatal days (PND) 10 to 15. The expression level of mRNA for brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor B (TrkB), insulin-like growth factor-1 (IGF-1), and type-1 IGF receptor (IGF-1R) were evaluated in the cerebellum on PND16, 20, 30, and 60 with real-time RT-PCR. The mRNA levels of cerebellar BDNF in maternally separated rats were increased on PND16, while the other variables showed no significant alterations at any of the time points examined. However, the effects of an identical maternal separation on the cerebral cortex were previously reported to be completely different. These results indicate regional differences in the responses of neurotrophic factor ligands/receptors between the cerebellum and cerebral cortex. Given that neurotrophic factors play important roles in brain development, alterations in these factors may interrupt normal brain development and ultimately, lead to functional disruptions.

  15. A mother's past can predict her offspring's future: Previous maternal separation leads to the early emergence of adult-like fear behavior in subsequent male infant rat offspring.

    PubMed

    Kan, Janice M; Callaghan, Bridget L; Richardson, Rick

    2016-10-01

    Recent evidence has shown that pups exposed to maternal separation exhibit profound changes in their emotional development, for example, early emergence of adult-like fear retention and fear inhibition (Callaghan & Richardson, 2011; Callaghan & Richardson, 2012). Numerous studies have shown that maternal separation is also a significant stressor for the mother. However, no studies have examined how a mother's prior parenting experience affects emotion development of pups in her subsequent litters. In this study female rats were bred and were then separated from their pups (maternal separation, MS) or remained with their pups (standard rearing, SR). After those pups were weaned, females were bred again with all pups from the subsequent litters being standard reared. Hence, these subsequent litter pups had mothers that were either previously separated (MS) or not (SR) from their prior litter. Those pups underwent fear conditioning at postnatal Day 17 and tested for fear retention, or had their fear extinguished and then tested for the renewal effect. The results show that the MS infants respond similarly to infants that had been directly exposed to MS. That is, the MS infants exhibited better retention of fear and more relapse after extinction compared with SR infants. Further experiments demonstrated that MS rats were not more anxious than SR infants. Taken together, these experiments are the first to demonstrate that infant offspring exhibit atypical emotional development of fear conditioning (but not anxiety) as a consequence of their mother's prior exposure to stress. (PsycINFO Database Record PMID:27537827

  16. Effects of altered maternal folic acid, vitamin B12 and docosahexaenoic acid on placental global DNA methylation patterns in Wistar rats.

    PubMed

    Kulkarni, Asmita; Dangat, Kamini; Kale, Anvita; Sable, Pratiksha; Chavan-Gautam, Preeti; Joshi, Sadhana

    2011-01-01

    Potential adverse effects of excess maternal folic acid supplementation on a vegetarian population deficient in vitamin B(12) are poorly understood. We have previously shown in a rat model that maternal folic acid supplementation at marginal protein levels reduces brain omega-3 fatty acid levels in the adult offspring. We have also reported that reduced docosahexaenoic acid (DHA) levels may result in diversion of methyl groups towards DNA in the one carbon metabolic pathway ultimately resulting in DNA methylation. This study was designed to examine the effect of normal and excess folic acid in the absence and presence of vitamin B(12) deficiency on global methylation patterns in the placenta. Further, the effect of maternal omega 3 fatty acid supplementation on the above vitamin B(12) deficient diets was also examined. Our results suggest maternal folic acid supplementation in the absence of vitamin B(12) lowers plasma and placental DHA levels (p<0.05) and reduces global DNA methylation levels (p<0.05). When this group was supplemented with omega 3 fatty acids there was an increase in placental DHA levels and subsequently DNA methylation levels revert back to the levels of the control group. Our results suggest for the first time that DHA plays an important role in one carbon metabolism thereby influencing global DNA methylation in the placenta. PMID:21423696

  17. Effect of voluntary alcohol consumption on Maoa expression in the mesocorticolimbic brain of adult male rats previously exposed to prolonged maternal separation

    PubMed Central

    Bendre, M; Comasco, E; Nylander, I; Nilsson, K W

    2015-01-01

    Discordant associations between monoamine oxidase A (MAOA) genotype and high alcohol drinking have been reported in human and non-human primates. Environmental influences likely moderate genetic susceptibility. The biological basis for this interplay remains elusive, and inconsistencies call for translational studies in which conditions can be controlled and brain tissue is accessible. The present study investigated whether early life stress and subsequent adult episodic alcohol consumption affect Maoa expression in stress- and reward-related brain regions in the rat. Outbred Wistar rats were exposed to rearing conditions associated with stress (prolonged maternal separation) or no stress during early life, and given free choice between alcohol and/or water in adulthood. Transcript levels of Maoa were assessed in the ventral tegmental area, nucleus accumbens (NAc), medial prefrontal cortex, cingulate cortex, amygdala and dorsal striatum (DS). Blood was collected to assess corticosterone levels. After alcohol consumption, lower blood corticosterone and Maoa expression in the NAc and DS were found in rats exposed to early life stress compared with control rats. An interaction between early life stress and voluntary alcohol intake was found in the NAc. Alcohol intake before death correlated negatively with Maoa expression in DS in high alcohol-drinking rats exposed to early life stress. Maoa expression is sensitive to adulthood voluntary alcohol consumption in the presence of early life stress in outbred rats. These findings add knowledge of the molecular basis of the previously reported associations between early life stress, MAOA and susceptibility to alcohol misuse. PMID:26645625

  18. Effect of voluntary alcohol consumption on Maoa expression in the mesocorticolimbic brain of adult male rats previously exposed to prolonged maternal separation.

    PubMed

    Bendre, M; Comasco, E; Nylander, I; Nilsson, K W

    2015-01-01

    Discordant associations between monoamine oxidase A (MAOA) genotype and high alcohol drinking have been reported in human and non-human primates. Environmental influences likely moderate genetic susceptibility. The biological basis for this interplay remains elusive, and inconsistencies call for translational studies in which conditions can be controlled and brain tissue is accessible. The present study investigated whether early life stress and subsequent adult episodic alcohol consumption affect Maoa expression in stress- and reward-related brain regions in the rat. Outbred Wistar rats were exposed to rearing conditions associated with stress (prolonged maternal separation) or no stress during early life, and given free choice between alcohol and/or water in adulthood. Transcript levels of Maoa were assessed in the ventral tegmental area, nucleus accumbens (NAc), medial prefrontal cortex, cingulate cortex, amygdala and dorsal striatum (DS). Blood was collected to assess corticosterone levels. After alcohol consumption, lower blood corticosterone and Maoa expression in the NAc and DS were found in rats exposed to early life stress compared with control rats. An interaction between early life stress and voluntary alcohol intake was found in the NAc. Alcohol intake before death correlated negatively with Maoa expression in DS in high alcohol-drinking rats exposed to early life stress. Maoa expression is sensitive to adulthood voluntary alcohol consumption in the presence of early life stress in outbred rats. These findings add knowledge of the molecular basis of the previously reported associations between early life stress, MAOA and susceptibility to alcohol misuse. PMID:26645625

  19. Effects of maternally exposed colouring food additives on cognitive performance in rats.

    PubMed

    Doguc, Duygu Kumbul; Ceyhan, Betul Mermi; Ozturk, Mustafa; Gultekin, Fatih

    2013-08-01

    Artificial food colourings and additives (AFCAs) have long been suggested to adversely affect the learning and behaviour in children. In this study, we aimed to provide additional data to clarify the possible side effects of colouring additives on behaviour and memory. We administered acceptable daily intake values of AFCAs as a mixture (Eritrosin, Ponceau 4R, Allura Red AC, Sunset Yellow FCF, Tartrazin, Amaranth, Brilliant Blue, Azorubin and Indigotin) to female rats before and during gestation and then tested their effects on behaviour and on spatial working memory in their offspring. Effects on spatial learning and memory were evaluated by Morris water maze, behavioural effects were evaluated by open-field test and forced swim test. Our results showed that commonly used artificial food colourings have no adverse effects on spatial working memory and did not create a depressive behaviour in offspring. But they showed a few significant effects on locomotor activity as AFCAs increased some parameters of locomotor activity. PMID:22323474

  20. Maternal Environmental Contribution to Adult Sensitivity and Resistance to Obesity in Long Evans Rats

    PubMed Central

    Schroeder, Mariana; Shbiro, Liat; Moran, Timothy H.; Weller, Aron

    2010-01-01

    Background The OLETF rat is an animal model of early onset hyperphagia induced obesity, presenting multiple pre-obese characteristics during the suckling period. In the present study, we used a cross-fostering strategy to assess whether interactions with obese dams in the postnatal environment contributed to the development of obesity. Methodology On postnatal Day (PND)-1 OLETF and control LETO pups were cross-fostered to same or opposite strain dams. An independent ingestion test was performed on PND11 and a nursing test on PND18. Rats were sacrificed at weaning or on PND90, and plasma leptin, insulin, cholesterol, triglycerides and alanine aminotransferase (ALT) were assayed. Fat pads were collected and weighed and adipocyte size and number were estimated. Body weight and intake, as well as the estrous cycle of the female offspring were monitored. Principal Findings During the suckling period, the pups' phenotype was almost completely determined by the strain of the mother. However, pups independently ingested food according to their genotype, regardless of their actual phenotype. At adulthood, cross fostered males of both strains and LETO females were affected in regard of their adiposity levels in the direction of the foster dam. On the other hand, OLETF females showed almost no alterations in adiposity but were affected by the strain of the dams in parameters related to the metabolic syndrome. Thus, OLETF females showed reduced liver adiposity and circulating levels of ALT, while LETO females presented a disrupted estrous cycle and increased cholesterol and triglycerides in the long term. Conclusions The present study provides further support for the early postnatal environment playing a sex-divergent role in programming later life phenotype. In addition, it plays a more central role in determining the functioning of mechanisms involved in energy balance that may provide protection from or sensitivity to later life obesity and pathologies related to the

  1. Maternal deprivation disrupts mitochondrial energy homeostasis in the brain of rats subjected to ketamine-induced schizophrenia.

    PubMed

    Zugno, Alexandra Ioppi; Pacheco, Felipe Damázio; Budni, Josiane; de Oliveira, Mariana Bittencourt; Canever, Lara; Heylmann, Alexandra Stephanie; Wessler, Patrícia Gomes; da Rosa Silveira, Flávia; Mastella, Gustavo Antunes; Gonçalves, Cinara Ludwig; Freitas, Karoline V; de Castro, Adalberto Alves; Streck, Emilio L; Quevedo, João

    2015-08-01

    Maternal deprivation (MD) appears to be one of the environmental factors involved in the pathophysiology of schizophrenia. A widely used animal model of the schizophrenia involves the administration of ketamine, a dissociative anesthetic, NMDA receptors noncompetitive antagonist, that induce symptoms such as schizophrenia. To clarify the molecular mechanism of schizophrenia induced by MD, we investigated alterations in energetic metabolism, oxidative stress and neurotrophic factor levels in the brain of rats following MD and/or a single administration of ketamine during adulthood. Male Wistar rats were subjected to MD for 10 days. Additionally, these animals received acute ketamine (5, 15 or 25 mg/kg by intraperitoneal route, i.p.) during adulthood, and 30 min later, they were killed and the prefrontal cortex (PFC), the hippocampus and the striatum were removed for molecular analyses. Ketamine 25 mg/kg and/or MD and Ketamine 15 and 5 mg/kg with MD decreased the creatine kinase (CK) activity in the hippocampus. The enzyme activity of succinate dehydrogenase (SDH) in the Krebs cycle had increased in the striatum following the administration of ketamine 25 mg/kg, MD per se or MD plus ketamine 5 and 15 mg/kg. MD per se or MD combined with ketamine in different doses increased the activity of mitochondrial complexes. The PFC of animals subjected to MD and administered with ketamine 5 mg/kg exhibited increased protein carbonyl content. In the hippocampus, ketamine 15 mg/kg, ketamine 25 mg/kg and MD each increased the carbonyl content. In the striatum, the TBARS levels were increased by the administration of ketamine 25 mg/kg. Finally, in the hippocampus, MD alone or in combination with ketamine reduced the Nerve Growth Factor (NGF) levels; however, the Brain-derived Neurotrophic Factor (BDNF) levels were unaltered. In the present study, we suggest that MD increased the risk of psychotic symptoms in adulthood, altering different parameters of energy and

  2. Maternal use of flaxseed oil during pregnancy and lactation prevents morphological alterations in pancreas of female offspring from rat dams with experimental diabetes.

    PubMed

    Correia-Santos, André Manoel; Vicente, Gabriela C; Suzuki, Akemi; Pereira, Aline D; dos Anjos, Juliana S; Lenzi-Almeida, Kátia C; Boaventura, Gilson T

    2015-04-01

    Nutritional recommendations have promoted the increased need to consume n-3 polyunsaturated fatty acids. Flaxseed is the richest dietary source of n-3 fatty acids among plant sources and is widely used for its edible oil. This study aimed to investigate whether maternal use of flaxseed oil has effects on pancreas morphology in the female offspring of diabetic mothers. Female Wistar rats (n = 12) were induced into diabetes by a high-fat diet and low dose of streptozotocin. After confirmation of the diabetes, rats were mated, and once pregnancy was confirmed, they were allocated into three groups (n = 6): high-fat group (HG); flaxseed oil group (FOG); and control group (CG) (non-diabetic rats). At weaning, female offspring (n = 6/group) received standard chow diet. The animals were euthanized at 180 days. Pancreas was collected for histomorphometric and immunohistochemistry analysis. HG showed hypertrophy of pancreatic islets (P < 0.0001), whereas FOG offspring had islets with smaller diameters compared to HG (P < 0.0001). HG offspring showed higher percentage of larger (P = 0.0061) and lower percentage of smaller islets (P = 0.0036). HG showed lower islet insulin immunodensity at 180 days (P < 0.0001), whereas FOG was similar to CG (P < 0.0001). Flaxseed oil reduced the damage caused by maternal hyperglycaemia, promoting normal pancreas histomorphometry and β-cell mass in female offspring.

  3. Peripheral and central alterations affecting spinal nociceptive processing and pain at adulthood in rats exposed to neonatal maternal deprivation.

    PubMed

    Juif, Pierre-Eric; Salio, Chiara; Zell, Vivien; Melchior, Meggane; Lacaud, Adrien; Petit-Demouliere, Nathalie; Ferrini, Francesco; Darbon, Pascal; Hanesch, Ulrike; Anton, Fernand; Merighi, Adalberto; Lelièvre, Vincent; Poisbeau, Pierrick

    2016-08-01

    The nociceptive system of rodents is not fully developed and functional at birth. Specifically, C fibers transmitting peripheral nociceptive information establish synaptic connections in the spinal cord already during the embryonic period that only become fully functional after birth. Here, we studied the consequences of neonatal maternal deprivation (NMD, 3 h/day, P2-P12) on the functional establishment of C fiber-mediated neurotransmission in spinal cord and of pain-related behavior. In vivo recording revealed that C fiber-mediated excitation of spinal cord neurons could be observed at P14 only in control but not in NMD rats. NMD was associated with a strong alteration in the expression of growth factors controlling C nociceptor maturation as well as two-pore domain K+ channels known to set nociceptive thresholds. In good agreement, C-type sensory neurons from NMD animals appeared to be hypoexcitable but functionally connected to spinal neurons, especially those expressing TRPV1 receptors. In vivo and in vitro recordings of lamina II spinal neurons at P14 revealed that the NMD-related lack of C fiber-evoked responses resulted from an inhibitory barrage in the spinal cord dorsal horn. Eventually, C-type sensory-spinal processing could be recovered after a delay of about 10 days in NMD animals. However, animals remained hypersensitive to noxious stimulus up to P100 and this might be due to an excessive expression of Nav1.8 transcripts in DRG neurons. Together, our data provide evidence for a deleterious impact of perinatal stress exposure on the maturation of the sensory-spinal nociceptive system that may contribute to the nociceptive hypersensitivity in early adulthood. PMID:27285721

  4. Effect of Caffeine Chronically Consumed During Pregnancy on Adenosine A1 and A2A Receptors Signaling in Both Maternal and Fetal Heart from Wistar Rats

    PubMed Central

    Iglesias, Inmaculada; Albasanz, Jose Luis

    2014-01-01

    Background: Caffeine is the most widely consumed psychoactive substance in the world, even during pregnancy. Its stimulatory effects are mainly due to antagonism of adenosine actions by blocking adenosine A1 and A2A receptors. Previous studies have shown that caffeine can cross the placenta and therefore modulate these receptors not only in the fetal brain but also in the heart. Methods: In the present work, the effect of caffeine chronically consumed during pregnancy on A1 and A2A receptors in Wistar rat heart, from both mothers and their fetuses, were studied using radioligand binding, Western-blotting, and adenylyl cyclase activity assays, as well as reverse transcription polymerase chain reaction. Results: Caffeine did not significantly alter A1R neither at protein nor at gene expression level in both the maternal and fetal heart. On the contrary, A2AR significantly decreased in the maternal heart, although mRNA was not affected. Gi and Gs proteins were also preserved. Finally, A1R-mediated inhibition of adenylyl cyclase activity did not change in the maternal heart, but A2AR mediated stimulation of this enzymatic activity significantly decreased according to the detected loss of this receptor. Conclusions: Opposite to the downregulation and desensitization of the A1R/AC pathway previously reported in the brain, these results show that this pathway is not affected in rat heart after caffeine exposure during pregnancy. In addition, A2AR is downregulated and desensitized in the maternal heart, suggesting a differential modulation of these receptor-mediated pathways by caffeine. PMID:25538864

  5. HPA and sympathoadrenal activity of adult rats perinatally exposed to maternal mild calorie restriction.

    PubMed

    Levay, Elizabeth A; Paolini, Antonio G; Govic, Antonina; Hazi, Agnes; Penman, Jim; Kent, Stephen

    2010-03-17

    Developmental programming of neuroendocrine systems is profoundly influenced by environmental cues such as caloric availability. The focus of investigations in this area has been on the effects of under- and malnutrition while there is a paucity of research examining the effects of more mild levels of calorie restriction (CR). Rat dams and their offspring were subjected to one of five dietary regimens: control, CR50% for 3 days preconception, CR25% during gestation, CR25% during lactation, and CR25% during gestation, lactation, and post-weaning (lifelong). Adult male offspring were decapitated and trunk blood collected to assay for basal concentrations of serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT), as well as plasma concentrations of adrenalin (A) and noradrenalin (NA). Basal serum ACTH was reduced by 35-43% in all dietary regimens except the lifelong group. Although a similar trend was observed in the concentrations of serum CORT, only the decrease in the lactation group attained statistical significance. A was reduced by 33-49% as a result of all dietary regimens and NA was reduced in the gestation and lifelong groups by 51% and 39%, respectively. The potential mechanisms underlying these neuroendocrine alterations are discussed.

  6. Low-Protein Diet during Lactation and Maternal Metabolism in Rats.

    PubMed

    Moretto, Vera L; Ballen, Marcia O; Gonçalves, Talita S S; Kawashita, Nair H; Stoppiglia, Luiz F; Veloso, Roberto V; Latorraca, Márcia Q; Martins, Maria Salete F; Gomes-da-Silva, Maria Helena G

    2011-01-01

    Some metabolic alterations were evaluated in Wistar rats which received control or low-protein (17%; 6%) diets, from the pregnancy until the end of lactation: control non-lactating (CNL), lactating (CL), low-protein non-lactating (LPNL) and lactating (LPL) groups. Despite the increased food intake by LPL dams, both LP groups reduced protein intake and final body mass was lower in LPL. Higher serum glucose occurred in both LP groups. Lactation induced lower insulin and glucagon levels, but these were reduced by LP diet. Prolactin levels rose in lactating, but were impaired in LPL, followed by losses of mammary gland (MAG) mass and, a fall in serum leptin in lactating dams. Lipid content also reduced in MAG and gonadal white adipose tissue of lactating and, in LPL, contributed to a decreased daily milk production, and consequent impairment of body mass gain by LPL pups. Liver mass, lipid content and ATP-citrate enzyme activity were increased by lactation, but malic enzyme and lipid: glycogen ratio elevated only in LPL. Conclusion. LP diet reduced the development of MAG and prolactin secretion which compromised milk production and pups growth. Moreover, this diet enhanced the store of lipid to glycogen ratio and suggests a higher risk of fatty liver development. PMID:21637364

  7. Low-Protein Diet during Lactation and Maternal Metabolism in Rats

    PubMed Central

    Moretto, Vera L.; Ballen, Marcia O.; Gonçalves, Talita S. S.; Kawashita, Nair H.; Stoppiglia, Luiz F.; Veloso, Roberto V.; Latorraca, Márcia Q.; Martins, Maria Salete F.; Gomes-da-Silva, Maria Helena G.

    2011-01-01

    Some metabolic alterations were evaluated in Wistar rats which received control or low-protein (17%; 6%) diets, from the pregnancy until the end of lactation: control non-lactating (CNL), lactating (CL), low-protein non-lactating (LPNL) and lactating (LPL) groups. Despite the increased food intake by LPL dams, both LP groups reduced protein intake and final body mass was lower in LPL. Higher serum glucose occurred in both LP groups. Lactation induced lower insulin and glucagon levels, but these were reduced by LP diet. Prolactin levels rose in lactating, but were impaired in LPL, followed by losses of mammary gland (MAG) mass and, a fall in serum leptin in lactating dams. Lipid content also reduced in MAG and gonadal white adipose tissue of lactating and, in LPL, contributed to a decreased daily milk production, and consequent impairment of body mass gain by LPL pups. Liver mass, lipid content and ATP-citrate enzyme activity were increased by lactation, but malic enzyme and lipid: glycogen ratio elevated only in LPL. Conclusion. LP diet reduced the development of MAG and prolactin secretion which compromised milk production and pups growth. Moreover, this diet enhanced the store of lipid to glycogen ratio and suggests a higher risk of fatty liver development. PMID:21637364

  8. Dynamic changes in lipids and proteins of maternal, fetal, and pup blood and milk during perinatal development in CD and Wistar rats.

    PubMed

    McMullin, Tami S; Lowe, Ezra R; Bartels, Michael J; Marty, Mary Sue

    2008-10-01

    An understanding of the physiological factors that regulate perinatal dosimetry is essential to improve the ability of physiologically based (PB) pharmacokinetic (PK) models to predict chemical risks to children. However, the impact of changing maternal/offspring physiology on PK during gestation and lactation remains poorly understood. This research determined lipid and protein changes in blood, milk and amniotic fluid of CD and Wistar dams, fetuses and neonates to improve the precision of perinatal PBPK modeling. Samples were collected from time-mated CD dams, fetuses, and pups on gestation day (GD) 18 and 20 (sperm positive = GD 0) or lactation day 0 (day of birth), 1, 3, 5, 10, 15, and 20 (n > or = 5 per time point). Fewer time points were sampled in Wistar rats, which showed similar patterns to CDs. Relative to nonpregnant dams, maternal serum protein levels (albumin, total protein and globulin) each decreased by approximately 20% during late gestation, whereas maternal serum lipids (triglycerides, low density lipoproteins, and phospholipids) increased up to fourfold. These physiological changes can impact maternal PK of both protein-bound and lipophilic chemicals. During lactation, triglycerides in milk were greater than 100-fold higher than maternal serum, favoring the disposition of lipophilic chemicals into milk and potentially increasing neonatal rodent exposure during critical stages of postnatal development. Serum protein levels in pups were two- to threefold lower than adults at birth, which may increase the bioavailability of protein-bound compounds. These data will aid in the interpretation of perinatal toxicity studies and improve the accuracy of predictive perinatal PBPK models. PMID:18593729

  9. Maternal Exposure of Rats to Isoflurane during Late Pregnancy Impairs Spatial Learning and Memory in the Offspring by Up-Regulating the Expression of Histone Deacetylase 2.

    PubMed

    Luo, Foquan; Hu, Yan; Zhao, Weilu; Zuo, Zhiyi; Yu, Qi; Liu, Zhiyi; Lin, Jiamei; Feng, Yunlin; Li, Binda; Wu, Liuqin; Xu, Lin

    2016-01-01

    Increasing evidence indicates that most general anesthetics can harm developing neurons and induce cognitive dysfunction in a dose- and time-dependent manner. Histone deacetylase 2 (HDAC2) has been implicated in synaptic plasticity and learning and memory. Our previous results showed that maternal exposure to general anesthetics during late pregnancy impaired the offspring's learning and memory, but the role of HDAC2 in it is not known yet. In the present study, pregnant rats were exposed to 1.5% isoflurane in 100% oxygen for 2, 4 or 8 hours or to 100% oxygen only for 8 hours on gestation day 18 (E18). The offspring born to each rat were randomly subdivided into 2 subgroups. Thirty days after birth, the Morris water maze (MWM) was used to assess learning and memory in the offspring. Two hours before each MWM trial, an HDAC inhibitor (SAHA) was given to the offspring in one subgroup, whereas a control solvent was given to those in the other subgroup. The results showed that maternal exposure to isoflurane impaired learning and memory of the offspring, impaired the structure of the hippocampus, increased HDAC2 mRNA and downregulated cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) mRNA, N-methyl-D-aspartate receptor 2 subunit B (NR2B) mRNA and NR2B protein in the hippocampus. These changes were proportional to the duration of the maternal exposure to isoflurane and were reversed by SAHA. These results suggest that exposure to isoflurane during late pregnancy can damage the learning and memory of the offspring rats via the HDAC2-CREB -NR2B pathway. This effect can be reversed by HDAC2 inhibition. PMID:27536989

  10. Maternal Exposure of Rats to Isoflurane during Late Pregnancy Impairs Spatial Learning and Memory in the Offspring by Up-Regulating the Expression of Histone Deacetylase 2

    PubMed Central

    Hu, Yan; Zhao, Weilu; Zuo, Zhiyi; Yu, Qi; Liu, Zhiyi; Lin, Jiamei; Feng, Yunlin; Li, Binda; Wu, Liuqin; Xu, Lin

    2016-01-01

    Increasing evidence indicates that most general anesthetics can harm developing neurons and induce cognitive dysfunction in a dose- and time-dependent manner. Histone deacetylase 2 (HDAC2) has been implicated in synaptic plasticity and learning and memory. Our previous results showed that maternal exposure to general anesthetics during late pregnancy impaired the offspring’s learning and memory, but the role of HDAC2 in it is not known yet. In the present study, pregnant rats were exposed to 1.5% isoflurane in 100% oxygen for 2, 4 or 8 hours or to 100% oxygen only for 8 hours on gestation day 18 (E18). The offspring born to each rat were randomly subdivided into 2 subgroups. Thirty days after birth, the Morris water maze (MWM) was used to assess learning and memory in the offspring. Two hours before each MWM trial, an HDAC inhibitor (SAHA) was given to the offspring in one subgroup, whereas a control solvent was given to those in the other subgroup. The results showed that maternal exposure to isoflurane impaired learning and memory of the offspring, impaired the structure of the hippocampus, increased HDAC2 mRNA and downregulated cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) mRNA, N-methyl-D-aspartate receptor 2 subunit B (NR2B) mRNA and NR2B protein in the hippocampus. These changes were proportional to the duration of the maternal exposure to isoflurane and were reversed by SAHA. These results suggest that exposure to isoflurane during late pregnancy can damage the learning and memory of the offspring rats via the HDAC2-CREB -NR2B pathway. This effect can be reversed by HDAC2 inhibition. PMID:27536989

  11. Maternal Flaxseed Oil During Lactation Enhances Bone Development in Male Rat Pups.

    PubMed

    Pereira, Aline D'Avila; Ribeiro, Danielle Cavalcante; de Santana, Fernanda Carvalho; de Sousa Dos Santos, Aline; Mancini-Filho, Jorge; do Nascimento-Saba, Celly Cristina Alves; Velarde, Luis Guillermo Coca; da Costa, Carlos Alberto Soares; Boaventura, Gilson Teles

    2016-08-01

    Flaxseed oil is an alpha linolenic acid source important in the growth and body development stage; furthermore, this acid acts on adipose tissue and bone health. The aim of this study was to evaluate body composition, fatty acid composition, hormone profile, retroperitoneal adipocyte area and femur structure of pups at weaning, whose mothers were fed a diet containing flaxseed oil during lactation. After birth, pups were randomly assigned: control (C, n = 12) and flaxseed oil (FO, n = 12), rats whose mothers were treated with diet containing soybean or flaxseed oil. At 21 days, the pups were weaned and body mass, length, body composition, biochemical parameter, leptin, osteoprotegerin, osteocalcin, fatty acids composition, intra-abdominal fat mass and femur structure were analyzed. FO showed (p < 0.05): higher body mass (+12 %) and length (+9 %); body fat mass (g, +45 %); bone mineral density (+8 %), bone mineral content (+55 %) and bone area (+35 %), osteocalcin (+173 %) and osteoprotegerin (+183 %). Arachidonic acid was lower (p < 0.0001), alpha-linolenic and eicosapentaenoic were higher (p < 0.0001). Intra-abdominal fat mass was higher (+25 %), however, the retroperitoneal adipocytes area was lower (-44 %). Femur mass (+10 %), distance between epiphyses (+4 %) and bone mineral density (+13 %) were higher. The study demonstrates that adequate flaxseed oil content during a lactation diet plays an important role in the development of pups. PMID:27256330

  12. Dietary protein and lifespan across the metamorphic boundary: protein-restricted larvae develop into short-lived adults.

    PubMed

    Runagall-McNaull, A; Bonduriansky, R; Crean, A J

    2015-06-29

    Restriction of nutrients in the adult diet extends lifespan across a diverse range of species, but less is known about the long-term effects of developmental dietary restriction. In particular, it is not known whether adult lifespan is influenced by developmental caloric restriction or macronutrient balance. We used the nutritional geometry approach to independently manipulate protein and carbohydrate contents of the larval diet in the neriid fly, Telostylinus angusticollis, and measured adult lifespan. We found that adult male and female lifespan was shortest when larvae were fed a protein restricted diet. Thus, protein restriction in the larval diet has the opposite effect of protein restriction in the adult diet (which prolongs life in this species and across a wide range of taxa). Adult lifespan was unaffected by larval dietary carbohydrate. These patterns persisted after controlling for larval diet effects on adult body size. We propose that larval and adult protein sources are used for distinct metabolic tasks: during development, dietary protein is used to build a durable soma that enhances adult lifespan, although excessive protein consumption partially reverses this effect.

  13. Maternal low protein diet causes body weight loss in male, neonate Sprague-Dawley rats involving UCP-1 mediated thermogenesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Brown adipose tissue (BAT) plays an important role in regulating body weight (BW) by modifying thermogenesis. Maternal low protein (LP) diets reduce offspring birth weight. Increased BAT thermogenesis in utero may be one mechanism for the lower BW. However, whether maternal LP nutrition alters BAT...

  14. Maternal obesity enhances white adipose tissue differentiation and alters genome-scale DNA methylation in male rat offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The risk of obesity in adulthood is strongly influenced by maternal body composition. Here we examined the hypothesis that maternal obesity influences white adipose tissue (WAT) transcriptome and increases propensity for adipogenesis in the offspring, prior to the development of obesity, using an es...

  15. In utero glucocorticoid (GLC) exposure and maternal undernutrition reduce fetal skeletal muscle mass by different mechanisms in rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Both maternal undernutrition and exposure of the fetus to above normal levels of GLC impair skeletal muscle growth. The degree to which the effects of maternal undernutrition on fetal skeletal muscle growth are a direct result of nutrient deficit or secondary to the presence of above normal GLC leve...

  16. The mTORC1-Signaling Pathway and Hepatic Polyribosome Profile Are Enhanced after the Recovery of a Protein Restricted Diet by a Combination of Soy or Black Bean with Corn Protein

    PubMed Central

    Márquez-Mota, Claudia C.; Rodriguez-Gaytan, Cinthya; Adjibade, Pauline; Mazroui, Rachid; Gálvez, Amanda; Granados, Omar; Tovar, Armando R.; Torres, Nimbe

    2016-01-01

    Between 6% and 11% of the world’s population suffers from malnutrition or undernutrition associated with poverty, aging or long-term hospitalization. The present work examined the effect of different types of proteins on the mechanistic target of rapamycin (mTORC1)-signaling pathway in: (1) healthy; and (2) protein restricted rats. (1) In total, 200 rats were divided into eight groups and fed one of the following diets: 20% casein (C), soy (S), black bean (B), B + Corn (BCr), Pea (P), spirulina (Sp), sesame (Se) or Corn (Cr). Rats fed C or BCr had the highest body weight gain; rats fed BCr had the highest pS6K1/S6K1 ratio; rats fed B, BCr or P had the highest eIF4G expression; (2) In total, 84 rats were fed 0.5% C for 21 day and protein rehabilitated with different proteins. The S, soy + Corn (SCr) and BCr groups had the highest body weight gain. Rats fed SCr and BCr had the highest eIF4G expression and liver polysome formation. These findings suggest that the quality of the dietary proteins modulate the mTORC1-signaling pathway. In conclusion, the combination of BCr or SCr are the best proteins for dietary protein rehabilitation due to the significant increase in body weight, activation of the mTORC1-signaling pathway in liver and muscle, and liver polysome formation. PMID:27657118

  17. Early administration of angiotensin-converting enzyme inhibitor captopril, prevents the development of hypertension programmed by intrauterine exposure to a maternal low-protein diet in the rat.

    PubMed

    Sherman, R C; Langley-Evans, S C

    1998-04-01

    1. Associations of intrauterine exposure to maternal undernutrition with later hypertension and coronary heart disease in the human population have been duplicated in the rat. Fetal exposure to low protein diets produces offspring that develop raised systolic blood pressure by the age of weaning. This animal model of 'programmed' hypertension was used to investigate the role of the renin-angiotensin system in the initiation and maintenance of high blood pressure. 2. Pregnant rats were fed diets containing 18 or 9% casein from conception until littering. The offspring from these pregnancies were administered captopril either between 2 and 4 weeks of age, or from 10 to 12 weeks of age. 3. The feeding of low protein diets in pregnancy had no effect upon the reproductive ability of female rats and the offspring generated were of normal birthweight. By 4 weeks of age the male and female offspring of low-protein-fed dams had systolic blood pressures that were 24-25 mmHg higher than those of rats exposed to a control diet in utero. 4. Treatment of 10-week-old female offspring with captopril for 2 weeks indicated that angiotensin II formation may play a role in the maintenance of high blood pressure in low-protein-exposed rats. While captopril had no significant effect upon systolic pressures of rats exposed to the control diet in intrauterine life, the systolic blood pressures of low-protein animals rapidly declined by 31 mmHg. 5. Administration of captopril to male and female offspring between 2 and 4 weeks of age exerted long-term effects upon systolic blood pressure. Eight weeks after cessation of treatment, at an age where maximal blood pressures are achieved, captopril-treated, low-protein-exposed rats had similar blood pressures to normotensive rats exposed to the protein-replete diet in utero. 6. In conclusion, we have demonstrated that the elevation of adult blood pressure associated with fetal exposure to a maternal low-protein diet, is prevented by early

  18. Effect of maternal micronutrients (folic acid, vitamin B12) and omega 3 fatty acids on liver fatty acid desaturases and transport proteins in Wistar rats.

    PubMed

    Wadhwani, Nisha S; Manglekar, Rupali R; Dangat, Kamini D; Kulkarni, Asmita V; Joshi, Sadhana R

    2012-01-01

    A disturbed fatty acid metabolism increases the risk of adult non-communicable diseases. This study examines the effect of maternal micronutrients on the fatty acid composition, desaturase activity, mRNA levels of fatty acid desaturases and transport proteins in the liver. Pregnant female rats were divided into 6 groups at 2 levels of folic acid both in the presence and absence of vitamin B(12). The vitamin B(12) deficient groups were supplemented with omega 3 fatty acid. An imbalance of maternal micronutrients reduces liver docosahexaenoic acid, increases Δ5 desaturase activity but decreases mRNA levels, decreases Δ6 desaturase activity but not mRNA levels as compared to control. mRNA level of Δ5 desaturase reverts back to the levels of the control group as a result of omega 3 fatty acid supplementation. Our data for the first time indicates that maternal micronutrients differentially alter the activity and expression of fatty acid desaturases in the liver.

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

    PubMed

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

    2016-01-01

    Clinical evidence has shown that physical exercise during pregnancy may alter brain development and improve cognitive function of offspring. However, the mechanisms through which maternal exercise might promote such effects are not well understood. The present study examined levels of brain-derived neurotrophic factor (BDNF) and absolute cell numbers in the hippocampal formation and cerebral cortex of rat pups born from mothers exercised during pregnancy. Additionally, we evaluated the cognitive abilities of adult offspring in different behavioral paradigms (exploratory activity and habituation in open field tests, spatial memory in a water maze test, and aversive memory in a step-down inhibitory avoidance task). Results showed that maternal exercise during pregnancy increased BDNF levels and absolute numbers of neuronal and non-neuronal cells in the hippocampal formation of offspring. No differences in BDNF levels or cell numbers were detected in the cerebral cortex. It was also observed that offspring from exercised mothers exhibited better cognitive performance in nonassociative (habituation) and associative (spatial learning) mnemonic tasks than did offspring from sedentary mothers. Our findings indicate that maternal exercise during pregnancy enhances offspring cognitive function (habituation behavior and spatial learning) and increases BDNF levels and cell numbers in the hippocampal formation of offspring. PMID:26771675

  20. Caffeine-induced fetal rat over-exposure to maternal glucocorticoid and histone methylation of liver IGF-1 might cause skeletal growth retardation.

    PubMed

    Tan, Yang; Liu, Jin; Deng, Yu; Cao, Hong; Xu, Dan; Cu, Fenglong; Lei, Youying; Magdalou, Jacques; Wu, Min; Chen, Liaobin; Wang, Hui

    2012-11-15

    Several epidemiological investigations, including previous work by our laboratory, indicate that maternal caffeine consumption is associated with intrauterine growth retardation and impaired fetal length growth. Skeletal development is critical for length growth. In the present study, our goals were to determine the effects of prenatal caffeine exposures on fetal skeletal growth and to investigate the mechanisms associated with such effects. Pregnant Wistar rats were injected intragastrically with 120mg/kg of caffeine intragastrically each day from gestational days 11-20. Maternal prenatal caffeine exposure was associated with decreased fetal femur lengths and inhibited of synthesis of extracellular matrices in fetal growth plates Moreover, caffeine exposure significantly increased the levels of fetal blood corticosterone and decreased IGF-1mRNA expression levels in the liver and growth plate. The expression levels of IGF-1 signaling pathway components (IGF-1R, IRS-1, AKT1/2 and Col2A1) were also reduced. In addition, the results of chromatin immunoprecipitation assays indicated that caffeine exposure down-regulated histone methylation of fetal IGF-1 in the liver. These results suggest that prenatal caffeine exposure may inhibit fetal skeletal growth through a mechanism that is associated with increased fetal exposure to maternal glucocorticoids and results in lower IGF-1 signaling pathway activity. Taken together, these results raise important concerns regarding the skeletal growth toxicity of caffeine and potentially indicate the intrauterine origins of adult osteoporosis and osteoarthritis.

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

    PubMed

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

    2016-01-01

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

  2. Analyzing the effects of a single episode of neonatal maternal deprivation on metabolite profiles in rat brain: a proton nuclear magnetic resonance spectroscopy study.

    PubMed

    Llorente, R; Villa, P; Marco, E M; Viveros, M P

    2012-01-10

    Animal models have greatly contributed to the understanding of neuropsychiatric disorders and have provided extensive evidence for the "neurodevelopmental hypothesis." In this regard, a single and prolonged episode (24 h) of early maternal deprivation early in life, on postnatal day 9, has been proposed as an animal model for the investigation of certain neuropsychiatric disorders, including schizophrenia. Since metabolic changes in hippocampus (HIP) and prefrontal cortex (PFC) have been described among schizophrenic patients by using ex vivo high-resolution magic angle spinning (HR-MAS) proton ((1)H) nuclear magnetic resonance spectroscopy, in the present study we aimed to investigate the effects of maternal deprivation (MD) on the metabolite profiles of the developing brain by using the HR-MAS technique. MD significantly altered the hippocampal and cortical metabolic profile of neonatal rats (PND 13) in a sex-dependent manner. Glutamine and glutamate (Glx) and taurine of male and female rat pups were altered in both brain areas analyzed. Differences in hippocampal phosphorylethanolamine have also been found as a function of the MD protocol. In addition, MD induced some other region- and sex-dependent effects, including changes in N-acetyl aspartate and total choline signals in the hippocampi of male pups. Present findings indicate a different brain metabolic profile in our animal model of early life stress suggesting its potential utility in the implementation of translational neuropsychiatric research.

  3. Maternal deprivation and early handling affect density of calcium binding protein-containing neurons in selected brain regions and emotional behavior in periadolescent rats.

    PubMed

    Giachino, C; Canalia, N; Capone, F; Fasolo, A; Alleva, E; Riva, M A; Cirulli, F; Peretto, P

    2007-03-16

    Adverse early life experiences can induce neurochemical changes that may underlie modifications in hypothalamic-pituitary-adrenal axis responsiveness, emotionality and cognition. Here, we investigated the expression of the calcium binding proteins (CBPs) calretinin, calbindin and parvalbumin, which identify subpopulations of GABAergic neurons and serve important functional roles by buffering intracellular calcium levels, following brief (early handling) and long (maternal deprivation) periods of maternal separation, as compared with non-handled controls. CBP-expressing neurons were analyzed in brain regions related to stress and anxiety. Emotionality was assessed in parallel using the social interaction test. Analyses were carried out at periadolescence, an important phase for the development of brain areas involved in stress responses. Our results indicate that density of CBP-immunoreactive neurons decreases in the paraventricular region of deprived rats but increases in the hippocampus and lateral amygdala of both early-handled and deprived rats when compared with controls. Emotionality is reduced in both early-handled and deprived animals. In conclusion, early handling and deprivation led to neurochemical and behavioral changes linked to stress-sensitive brain regions. These data suggest that the effects of early experiences on CBP containing neurons might contribute to the functional changes of neuronal circuits involved in emotional response.

  4. Maternal High-Fat Diet during Pregnancy and Lactation Influences Obestatin and Ghrelin Concentrations in Milk and Plasma of Wistar Rat Dams and Their Offspring

    PubMed Central

    Słupecka, Monika; Romanowicz, Katarzyna; Woliński, Jarosław

    2016-01-01

    The study aims to establish the effect of a maternal high-fat diet on obestatin concentration, total ghrelin, and ghrelin/obestatin ratio during pregnancy and lactation of Wistar rats and their offspring in the first 21 days of life. On the mating day, females were randomly allocated and fed either a high-fat diet (30% of fat; HF) or breeding diet (5% fat; BD) till the 21st day of lactation. Hormones were analyzed in the blood plasma and milk of rat dams as well as in the blood plasma of their offspring. HF resulted in a significant decrease in obestatin level on the 14th day of lactation and elevation on the 21st day. Plasma obestatin in HFD offspring was significantly higher than in BD ones. HF diet did not significantly affect dam plasma ghrelin until the 21st day of lactation. The ghrelin concentrations in milk after both diets were significantly lower than in blood plasma. Milk ghrelin in HF dams was significantly higher than in the BD ones. Plasma ghrelin from HF offspring was significantly higher than that from BD dams. Our results demonstrate that a maternal HF diet during pregnancy and lactation influences ghrelin and obestatin level in both dams and their offspring. PMID:27127509

  5. Maternal separation and early stress cause long-lasting effects on dopaminergic and endocannabinergic systems and alters dendritic morphology in the nucleus accumbens and frontal cortex in rats.

    PubMed

    Romano-López, Antonio; Méndez-Díaz, Mónica; García, Fabio García; Regalado-Santiago, Citlalli; Ruiz-Contreras, Alejandra E; Prospéro-García, Oscar

    2016-08-01

    A considerable amount experimental studies have shown that maternal separation (MS) is associated with adult offspring abnormal behavior and cognition disorder. Accordingly, this experimental procedure has been proposed as a predictor for alcohol and drug dependence based on the neurodevelopmental soon after birth. Endocannabinoid system (eCBs) has been implicated in reward processes, including drug abuse and dependence. MS and associated stress causes changes in the eCBs that seem to facilitate alcohol consumption. In this study, we seek to evaluate potential morphological changes in neurons of the frontal cortex (FCx) and nucleus accumbens (NAcc), in the expression of receptors and enzymes of the endocannabinoid and dopamine systems and in second messengers, such as Akt, in adult rats subjected to MS and early stress (MS + ES; 2 × 180 min daily) vs. nonseparated rats (NMS). Results showed that MS + ES induces higher D2R expression and lower D3R, FAAH, and MAGL expression compared with NMS rats. Alterations in total dendritic length were also detected and were characterized by increases in the NAcc while there were decreases in the FCx. We believe MS + ES-induced changes in the dopaminergic and endocannabinergic systems and in the neuronal microstructure might be contributing to alcohol seeking behavior and, potential vulnerability to other drugs in rats. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 819-831, 2016.

  6. Female-dependent impaired fear memory of adult rats induced by maternal separation, and screening of possible related genes in the hippocampal CA1.

    PubMed

    Sun, Xiu-Min; Tu, Wen-Qiang; Shi, Yan-Wei; Xue, Li; Zhao, Hu

    2014-07-01

    Early life stress is one of the major susceptible factors for stress-related pathologies like posttraumatic stress disorder (PTSD). Recent studies in rats suggest that rather than being overall unfavorable, early life stress may prepare the organism to perform optimally to stressful environments later in life. In this study, severely adverse early life stress was conducted by six consecutive hours of maternal separation (MS), from PND1 to PND21, and contextual fear conditioning model was used on PND90 to mimic the second stress in adulthood and the re-experiencing symptom of PTSD. It was observed that in this investigation pups experienced MS showed decreased sensibility to contextual fear conditioning in adulthood, and there sex plays an important role. For example, female rats suffered MS had much lower freezing than males and controls. Meanwhile, Morris water maze test indicated that MS did not impair rat's performance of spatial learning and memory. Furthermore, suppression subtractive hybridization (SSH) was used to screen the related genes of fear memory, by examining the changes of mRNA expression in CA1 area between female MS and control rats after contextual fear conditioning. Finally, nine up-regulated and one down-regulated genes, including β2-MG, MAF, Nd1-L, TorsinA and MACF1 gene were found in this study. It is assumed that the TorsinA, MACF1 and Nd1-L gene may contribute to the decreased sensitivity of PTSD induced by MS. PMID:24667363

  7. Maternal high-fat diet-induced programing of gut taste receptor and inflammatory gene expression in rat offspring is ameliorated by CLA supplementation.

    PubMed

    Reynolds, Clare M; Segovia, Stephanie A; Zhang, Xiaoyuan D; Gray, Clint; Vickers, Mark H

    2015-10-01

    Consumption of a high-fat (HF) diet during pregnancy and lactation influences later life predisposition to obesity and cardiometabolic disease in offspring. The mechanisms underlying this phenomenon remain poorly defined, but one potential target that has received scant attention and is likely pivotal to disease progression is that of the gut. The present study examined the effects of maternal supplementation with the anti-inflammatory lipid, conjugated linoleic acid (CLA), on offspring metabolic profile and gut expression of taste receptors and inflammatory markers. We speculate that preventing high-fat diet-induced metainflammation improved maternal metabolic parameters conferring beneficial effects on adult offspring. Sprague Dawley rats were randomly assigned to a purified control diet (CD; 10% kcal from fat), CD with CLA (CLA; 10% kcal from fat, 1% CLA), HF (45% kcal from fat) or HF with CLA (HFCLA; 45% kcal from fat, 1% CLA) throughout gestation and lactation. Plasma/tissues were taken at day 24 and RT-PCR was carried out on gut sections. Offspring from HF mothers were significantly heavier at weaning with impaired insulin sensitivity compared to controls. This was associated with increased plasma IL-1β and TNFα concentrations. Gut Tas1R1, IL-1β, TNFα, and NLRP3 expression was increased and Tas1R3 expression was decreased in male offspring from HF mothers and was normalized by maternal CLA supplementation. Tas1R1 expression was increased while PYY and IL-10 decreased in female offspring of HF mothers. These results suggest that maternal consumption of a HF diet during critical developmental windows influences offspring predisposition to obesity and metabolic dysregulation. This may be associated with dysregulation of taste receptor, incretin, and inflammatory gene expression in the gut. PMID:26493953

  8. Maternal diet during gestation and lactation modifies the severity of salt-induced hypertension and renal injury in Dahl salt-sensitive rats.

    PubMed

    Geurts, Aron M; Mattson, David L; Liu, Pengyuan; Cabacungan, Erwin; Skelton, Meredith M; Kurth, Theresa M; Yang, Chun; Endres, Bradley T; Klotz, Jason; Liang, Mingyu; Cowley, Allen W

    2015-02-01

    Environmental exposure of parents or early in life may affect disease development in adults. We found that hypertension and renal injury induced by a high-salt diet were substantially attenuated in Dahl SS/JrHsdMcwiCrl (SS/Crl) rats that had been maintained for many generations on the grain-based 5L2F diet compared with SS/JrHsdMcwi rats (SS/Mcw) maintained on the casein-based AIN-76A diet (mean arterial pressure, 116±9 versus 154±25 mm Hg; urinary albumin excretion, 23±12 versus 170±80 mg/d). RNAseq analysis of the renal outer medulla identified 129 and 82 genes responding to a high-salt diet uniquely in SS/Mcw and SS/Crl rats, respectively, along with minor genetic differences between the SS substrains. The 129 genes responding to salt in the SS/Mcw strain included numerous genes with homologs associated with hypertension, cardiovascular disease, or renal disease in human. To narrow the critical window of exposure, we performed embryo-transfer experiments in which single-cell embryos from 1 colony (SS/Mcw or SS/Crl) were transferred to surrogate mothers from the other colony, with parents and surrogate mothers maintained on their respective original diet. All offspring were fed the AIN-76A diet after weaning. Salt-induced hypertension and renal injury were substantially exacerbated in rats developed from SS/Crl embryos transferred to SS/Mcw surrogate mothers. Conversely, salt-induced hypertension and renal injury were significantly attenuated in rats developed from SS/Mcw embryos transferred to SS/Crl surrogate mothers. Together, the data suggest that maternal diet during the gestational-lactational period has substantial effects on the development of salt-induced hypertension and renal injury in adult SS rats.

  9. Maternal diet during gestation and lactation modifies the severity of salt-induced hypertension and renal injury in Dahl salt-sensitive rats.

    PubMed

    Geurts, Aron M; Mattson, David L; Liu, Pengyuan; Cabacungan, Erwin; Skelton, Meredith M; Kurth, Theresa M; Yang, Chun; Endres, Bradley T; Klotz, Jason; Liang, Mingyu; Cowley, Allen W

    2015-02-01

    Environmental exposure of parents or early in life may affect disease development in adults. We found that hypertension and renal injury induced by a high-salt diet were substantially attenuated in Dahl SS/JrHsdMcwiCrl (SS/Crl) rats that had been maintained for many generations on the grain-based 5L2F diet compared with SS/JrHsdMcwi rats (SS/Mcw) maintained on the casein-based AIN-76A diet (mean arterial pressure, 116±9 versus 154±25 mm Hg; urinary albumin excretion, 23±12 versus 170±80 mg/d). RNAseq analysis of the renal outer medulla identified 129 and 82 genes responding to a high-salt diet uniquely in SS/Mcw and SS/Crl rats, respectively, along with minor genetic differences between the SS substrains. The 129 genes responding to salt in the SS/Mcw strain included numerous genes with homologs associated with hypertension, cardiovascular disease, or renal disease in human. To narrow the critical window of exposure, we performed embryo-transfer experiments in which single-cell embryos from 1 colony (SS/Mcw or SS/Crl) were transferred to surrogate mothers from the other colony, with parents and surrogate mothers maintained on their respective original diet. All offspring were fed the AIN-76A diet after weaning. Salt-induced hypertension and renal injury were substantially exacerbated in rats developed from SS/Crl embryos transferred to SS/Mcw surrogate mothers. Conversely, salt-induced hypertension and renal injury were significantly attenuated in rats developed from SS/Mcw embryos transferred to SS/Crl surrogate mothers. Together, the data suggest that maternal diet during the gestational-lactational period has substantial effects on the development of salt-induced hypertension and renal injury in adult SS rats. PMID:25452472

  10. MATERNAL DIET DURING GESTATION AND LACTATION MODIFIES THE SEVERITY OF SALT-INDUCED HYPERTENSION AND RENAL INJURY IN DAHL SALT-SENSITIVE RATS

    PubMed Central

    Geurts, Aron M.; Mattson, David L.; Liu, Pengyuan; Cabacungan, Erwin; Skelton, Meredith M.; Kurth, Theresa M.; Yang, Chun; Endres, Bradley T.; Klotz, Jason; Liang, Mingyu; Cowley, Allen W.

    2014-01-01

    Environmental exposure of parents or early in life may affect disease development in adults. We found that hypertension and renal injury induced by a high-salt diet were substantially attenuated in Dahl SS/JrHsdMcwiCrl (SS/Crl) rats that had been maintained for many generations on the grain-based 5L2F diet compared to SS/JrHsdMcwi rats (SS/Mcw) maintained on the casein-based AIN-76A diet (mean arterial pressure 116±9 vs. 154±25 mmHg; urinary albumin excretion 23±12 vs. 170±80 mg/day). RNA-seq analysis of the renal outer medulla identified 129 and 82 genes responding to a high-salt diet uniquely in SS/Mcw and SS/Crl rats, respectively, along with minor genetic differences between the SS substrains. The 129 genes responding to salt in the SS/Mcw strain included numerous genes with homologs associated with hypertension, cardiovascular disease, or renal disease in human. To narrow the critical window of exposure, we performed embryo transfer experiments in which single-cell embryos from one colony (SS/Mcw or SS/Crl) were transferred to surrogate mothers from the other colony, with parents and surrogate mothers maintained on their respective original diet. All offspring were fed the AIN-76A diet after weaning. Salt-induced hypertension and renal injury were substantially exacerbated in rats developed from SS/Crl embryos transferred to SS/Mcw surrogate mothers. Conversely, salt-induced hypertension and renal injury were significantly attenuated in rats developed from SS/Mcw embryos transferred to SS/Crl surrogate mothers. Together, the data suggests that maternal diet during the gestational-lactational period has substantial effects on the development of salt-induced hypertension and renal injury in adult SS rats. PMID:25452472

  11. Maternal use of flaxseed oil during pregnancy and lactation prevents morphological alterations in pancreas of female offspring from rat dams with experimental diabetes

    PubMed Central

    Correia-Santos, André Manoel; Vicente, Gabriela C; Suzuki, Akemi; Pereira, Aline D; dos Anjos, Juliana S; Lenzi-Almeida, Kátia C; Boaventura, Gilson T

    2015-01-01

    Nutritional recommendations have promoted the increased need to consume n-3 polyunsaturated fatty acids. Flaxseed is the richest dietary source of n-3 fatty acids among plant sources and is widely used for its edible oil. This study aimed to investigate whether maternal use of flaxseed oil has effects on pancreas morphology in the female offspring of diabetic mothers. Female Wistar rats (n = 12) were induced into diabetes by a high-fat diet and low dose of streptozotocin. After confirmation of the diabetes, rats were mated, and once pregnancy was confirmed, they were allocated into three groups (n = 6): high-fat group (HG); flaxseed oil group (FOG); and control group (CG) (non-diabetic rats). At weaning, female offspring (n = 6/group) received standard chow diet. The animals were euthanized at 180 days. Pancreas was collected for histomorphometric and immunohistochemistry analysis. HG showed hypertrophy of pancreatic islets (P < 0.0001), whereas FOG offspring had islets with smaller diameters compared to HG (P < 0.0001). HG offspring showed higher percentage of larger (P = 0.0061) and lower percentage of smaller islets (P = 0.0036). HG showed lower islet insulin immunodensity at 180 days (P < 0.0001), whereas FOG was similar to CG (P < 0.0001). Flaxseed oil reduced the damage caused by maternal hyperglycaemia, promoting normal pancreas histomorphometry and β-cell mass in female offspring. PMID:25808815

  12. Maternal microchimerism

    PubMed Central

    Ye, Jody; Vives-Pi, Marta; Gillespie, Kathleen M

    2014-01-01

    Increased levels of non-inherited maternal HLA alleles have been detected in the periphery of children with type 1 diabetes and an increased frequency of maternal cells have been identified in type 1 diabetes pancreas. It is now clear that the phenotype of these cells is pancreatic,1 supporting the hypothesis that maternal cells in human pancreas are derived from multipotent maternal progenitors. Here we hypothesize how increased levels of maternal cells could play a role in islet autoimmunity. PMID:25093746

  13. Effect of maternal/fetal vitamin A deficiency on fetal rat lung surfactant protein expression and the response to prenatal dexamethasone.

    PubMed

    Zachman, R D; Grummer, M A

    1998-02-01

    The purpose of this work was to determine whether maternal/fetal vitamin A deficiency in vivo had an effect on fetal lung surfactant protein expression and its response to antenatal maternal dexamethasone (DEX). Weanling female rats at 21 d (30-35 g) were fed control (C) (4 mg of vitamin A/kg of diet) or a vitamin A-deficient (D) (0.06 of mg vitamin A/kg) diet. These females were mated, and at selected pregnancy dates fetal and maternal tissues were obtained. Control mothers had liver retinyl palmitate (RP) concentrations of 246 +/- 32 nmol/g of wet weight; those in the D group had 6.1 +/- 2.9 nmol/g of wet weight. Control fetal liver RP was 12-fold higher and control fetal lung RP was 3-fold higher than in the D group (liver: 18.5 +/- 0.4 nmol/g versus 1.5 +/- 0.25 nmol/g; lung: 1.8 +/- 0.98 nmol/g versus 0.6 +/- 0.2 nmol/g). Neither fetal lung surfactant protein (SP)-C mRNA nor SP-A mRNA was affected by vitamin A deficiency. In a second experiment, pregnant rats from both C and D groups were injected with either DEX (1 mg/kg) or an equal volume of saline on d 15-17, and killed on d 18. DEX increased fetal lung SP-C mRNA 2-fold over the level found in the saline-injected group (saline, 1.0 +/- 0.2 versus DEX, 2.1 +/- 0.2, p < 0.02). This increase in SP-C mRNA also occurred in fetal lungs from the D group (saline, 1.8 +/- 0.4 versus DEX 3.7 +/- 0.2, p < 0.01). Retinoic acid receptor-beta mRNA, which responds to vitamin A levels and DEX in many systems, was lower in fetal lungs of the D group that had been treated with DEX. We conclude that fetal rat lung development, as measured by SP-C mRNA and SP-A mRNA, and the SP-C mRNA response to DEX, was not affected by vitamin A deficiency. PMID:9475281

  14. EFFECT OF VARYING MATERNAL FOLATE STATUS AND DIETARY FOLATE INTAKE ON RESPONSE TO DIVERSE DEVELOPMENTAL TOXICANTS IN THE RAT

    EPA Science Inventory

    Periconceptional and early pregnancy folate supplements are associated with reduced recurrence and occurrence of birth defects in humans. This study was undertaken to assess the influence of maternal folate status and dietary folate intake on outcome of exposures to diverse terat...

  15. Postpartum Behavioral Profiles in Wistar Rats Following Maternal Separation - Altered Exploration and Risk-Assessment Behavior in MS15 Dams.

    PubMed

    Daoura, Loudin; Hjalmarsson, My; Oreland, Sadia; Nylander, Ingrid; Roman, Erika

    2010-01-01

    The rodent maternal separation (MS) model is frequently used to investigate the impact of early environmental factors on adult neurobiology and behavior. The majority of MS studies assess effects in the offspring and few address the consequences of repeated pup removal in the dam. Such studies are of interest since alterations detected in offspring subjected to MS may, at least in part, be mediated by variations in maternal behavior and the amount of maternal care provided by the dam. The aim of this study was to investigate how daily short (15 min; MS15) and prolonged (360 min; MS360) periods of MS affects the dam by examining postpartum behavioral profiles using the multivariate concentric square field (MCSF) test. The dams were tested on postpartum days 24-25, i.e., just after the end of the separation period and weaning. The results reveal a lower exploratory drive and lower risk-assessment behavior in MS15 dams relative to MS360 or animal facility reared dams. The present results contrast some of the previously reported findings and provide new information about early post-weaning behavioral characteristics in a multivariate setting. Plausible explanations for the results are provided including a discussion how the present results fit into the maternal mediation hypothesis.

  16. Inflammatory response and oxidative stress in developing rat brain and its consequences on motor behavior following maternal administration of LPS and perinatal anoxia.

    PubMed

    Stigger, Felipe; Lovatel, Gisele; Marques, Marília; Bertoldi, Karine; Moysés, Felipe; Elsner, Viviane; Siqueira, Ionara Rodrigues; Achaval, Matilde; Marcuzzo, Simone

    2013-12-01

    Cerebral palsy (CP) is a disorder of locomotion, posture and movement that can be caused by prenatal, perinatal or postnatal insults during brain development. An increased incidence of CP has been correlated to perinatal asphyxia and maternal infections during gestation. The effects of maternal exposure to low doses of bacterial endotoxin (lipopolysaccharide, LPS) associated or not with perinatal anoxia (PA) in oxidative and inflammatory parameters were examined in cerebral cortices of newborns pups. Concentrations of TNF-α, IL-1, IL-4, SOD, CAT and DCF were measured by the ELISA method. Other newborn rats were assessed for neonatal developmental milestones from day 1 to 21. Motor behavior was also tested at P29 using open-field and Rotarod. PA alone only increased IL-1 expression in cerebral cortex with no changes in oxidative measures. PA also induced a slight impact on development and motor performance. LPS alone was not able to delay motor development but resulted in changes in motor activity and coordination with increased levels of IL-1 and TNF-α expression associated with a high production of free radicals and elevated SOD activity. When LPS and PA were combined, changes on inflammatory and oxidative stress parameters were greater. In addition, greater motor development and coordination impairments were observed. Prenatal exposure of pups to LPS appeared to sensitize the developing brain to effects of a subsequent anoxia insult resulting in an increased expression of pro-inflammatory cytokines and increased free radical levels in the cerebral cortex. These outcomes suggest that oxidative and inflammatory parameters in the cerebral cortex are implicated in motor deficits following maternal infection and perinatal anoxia by acting in a synergistic manner during a critical period of development of the nervous system.

  17. Heterotic and maternal effects on body weight and the parameters of a logistic growth curve of LL and SS rats and their F1 offspring.

    PubMed

    Kasser, T G; Mabry, J W; Benyshek, L L; Campion, D J; Martin, R J

    1983-01-01

    Differences in growth curve parameters were evaluated on two growth strains of rats and their reciprocal crosses. Least squares analysis indicated differences (p less than .05) in asymptotic weight, age and weight at the inflection point, the rate parameter, and absolute growth rate. Significant paternal, maternal, and sex influences were evident for each of the four derived traits. Positive significant heterosis was exhibited for each of the parameters of the growth function. Analysis of least square means of body weight also indicated significant differences at all ages from 4 to 15 weeks. Significant line of sire, line of dam and sex effects were expressed for each week body weight was recorded. Although negative, significant heterosis was expressed for body weight at weeks 5 and 6. There was a tendency for heterosis in all other weekly body weight measurements to be positive. PMID:6642246

  18. Developmental stress and lead (Pb): Effects of maternal separation and/or Pb on corticosterone, monoamines, and blood Pb in rats.

    PubMed

    Amos-Kroohs, Robyn M; Graham, Devon L; Grace, Curtis E; Braun, Amanda A; Schaefer, Tori L; Skelton, Matthew R; Vorhees, Charles V; Williams, Michael T

    2016-05-01

    The level of lead (Pb) exposure in children has decreased dramatically since restrictions on its use were implemented. However, even with restrictions, children are exposed to Pb and still present with cognitive and behavioral deficits. One prominent aspect of the exposome of these children is that many come from low social economic status (SES) conditions, and low SES is associated with stress. In order to compare the combined effects of early stress and Pb, Sprague-Dawley rats were exposed to vehicle or Pb either alone or in combination with maternal separation stress during brain development (i.e., postnatal day (P)4-P11, P19, or P28). Maternally separated/isolated pups had lower body and thymus weights during exposure and had increased levels of blood Pb compared with vehicle controls. Isolation, but not Pb, affected the response to an acute stressor (standing in shallow water) when assessed on P19 and P29, but not earlier on P11. Interactions of Pb and isolation were found on monoamines in the neostriatum, hippocampus, and hypothalamus on turnover but not on levels, and most changes were on dopamine turnover. Isolation had greater short-term effects than Pb. Interactions were dependent on age, sex, and acute stress.

  19. The effects of maternal diabetes on expression of insulin-like growth factor-1 and insulin receptors in male developing rat hippocampus.

    PubMed

    Hami, Javad; Sadr-Nabavi, Ariane; Sankian, Mojtaba; Balali-Mood, Mehdi; Haghir, Hossein

    2013-01-01

    Diabetes during pregnancy causes neurodevelopmental and neurocognitive abnormalities in offspring. Insulin and insulin-like growth factor-1 (IGF-1) are important regulators of developmental and cognitive functions in the central nervous system. We examined the effects of maternal diabetes on insulin-like growth factor-1 receptor (IGF-1R) and insulin receptor (InsR) expression in the developing rat hippocampus. Female rats were maintained diabetic from a week before pregnancy through parturition and male offspring was killed at P0, P7, and P14. We found a significant bilateral upregulation of both IGF-1R and InsR transcripts in the hippocampus of pups born to diabetic mothers at P0, as compared to controls. However, at the same time point, the results of western blot analysis revealed only a slight change in their protein levels. At P7, there was a marked bilateral reduction in mRNA expression and protein levels of IGF-1R, although not of InsR in the diabetic group. We also found a downregulation in IGF1-R transcripts, especially in left hippocampus of the diabetic group at P14. Moreover, at the same time point, InsR expression was significantly decreased in both hippocampi of diabetic newborns. When compared with controls, we did not find any difference in hippocampal IGF-1R or InsR mRNA and protein levels in the insulin-treated group. The present study revealed that diabetes during pregnancy strongly influences the regulation of both IGF-1R and InsR in the right/left developing hippocampi. Furthermore, the rigid control of maternal glycaemia by insulin administration normalized these effects.

  20. Maternal exposure to hexachlorophene targets intermediate-stage progenitor cells of the hippocampal neurogenesis in rat offspring via dysfunction of cholinergic inputs by myelin vacuolation.

    PubMed

    Itahashi, Megu; Abe, Hajime; Tanaka, Takeshi; Mizukami, Sayaka; Kimura, Masayuki; Yoshida, Toshinori; Shibutani, Makoto

    2015-02-01

    Hexachlorophene (HCP) is known to induce myelin vacuolation corresponding to intramyelinic edema of nerve fibers in the central and peripheral nervous system in animals. This study investigated the effect of maternal exposure to HCP on hippocampal neurogenesis in rat offspring using pregnant rats supplemented with 0 (controls), 100, or 300 ppm HCP in the diet from gestational day 6 to day 21 after delivery. On postnatal day (PND) 21, the numbers of T box brain 2(+) progenitor cells and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling(+) apoptotic cells in the hippocampal subgranular zone (SGZ) decreased in female offspring at 300 ppm, which was accompanied by myelin vacuolation and punctate tubulin beta-3 chain staining of nerve fibers in the hippocampal fimbria. In addition, transcript levels of the cholinergic receptor, nicotinic beta 2 (Chrnb2) and B-cell CLL/lymphoma 2 (Bcl2) decreased in the dentate gyrus. HCP-exposure did not alter the numbers of SGZ proliferating cells and reelin- or calcium-binding protein-expressing γ-aminobutyric acid (GABA)-ergic interneuron subpopulations in the dentate hilus on PND 21 and PND 77. Although some myelin vacuolation remained, all other changes observed in HCP-exposed offspring on PND 21 disappeared on PND 77. These results suggest that maternal HCP exposure reversibly decreases type-2b intermediate-stage progenitor cells via the mitochondrial apoptotic pathway in offspring hippocampal neurogenesis at 300 ppm HCP. Neurogenesis may be affected by dysfunction of cholinergic inputs into granule cell lineages and/or GABAergic interneurons as indicated by decreased transcript levels of Chrnb2 and numbers of Chrnb2(+) interneurons caused by myelin vacuolation in the septal-hippocampal pathway.

  1. Gestational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin alters retinoid homeostasis in maternal and perinatal tissues of the Holtzman rat

    SciTech Connect

    Kransler, Kevin M. Tonucci, David A. McGarrigle, Barbara P. Napoli, Joseph L. Olson, James R.

    2007-10-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), one of the most widely studied environmental contaminants, causes a variety of adverse health effects including teratogenesis and altered development which may be related to disruptions in retinoid homeostasis. The purpose of this study was to determine the effect that gestational administration of TCDD has on retinoid homeostasis in both pregnant Holtzman rats and developing fetuses and neonates. A single oral dose of TCDD (0, 1.5, 3, or 6 {mu}g/kg) was administered to pregnant rats on gestation day 10, with fetuses analyzed on gestation days 17 and 20, and neonates analyzed on post natal day 7. Exposure to TCDD generally produced decreases in the concentrations of retinyl esters, such as retinyl palmitate, and retinol in maternal and perinatal liver and lung, while increasing levels in the maternal kidney. Additionally, perinatal hepatic retinol binding protein 1-dependent retinyl ester hydrolysis was also decrease by TCDD. Sensitivity of the developing perinates to TCDD appeared to have an age-related component demonstrated by an increased rate of mortality and significant alterations to body weight and length on post natal day 7 relative to that observed at gestation day 20. A unique observation made in this study was a significant decrease in lung weight observed in the perinates exposed to TCDD. Taken together, these data demonstrate that TCDD significantly alters retinoid homeostasis in tissues of the developing fetus and neonate, suggesting that their unique sensitivity to TCDD may at least be in part the result of altered retinoid homeostasis.

  2. Maternal exposure to fluoxetine during gestation and lactation affects the DNA methylation programming of rat's offspring: modulation by folic acid supplementation.

    PubMed

    Toffoli, L V; Rodrigues, G M; Oliveira, J F; Silva, A S; Moreira, E G; Pelosi, G G; Gomes, M V

    2014-05-15

    Fluoxetine is an antidepressant that has been largely used for treatment of depression in pregnancy. In the present study we evaluated the effects of the exposure to fluoxetine during gestation and lactation on DNA methylation of rat brain regions. Female Wistar rats were treated with 5mg/kg of fluoxetine during pregnancy and lactation. In order to assess the effects of fluoxetine in the context of maternal folic acid supplementation we performed an additional combined treatment composed by folic acid (8 mg/kg/day) and fluoxetine (5 mg/kg/day). On the postnatal day 22, male rats were euthanized and hippocampus, cortex, hypothalamus, and periaqueductal gray area were removed. Global DNA methylation was quantified using a high-throughput ELISA-based method. Neurofunctional changes were addressed using validated behavioral tests: hot plate, elevated plus maze and open field. A decrease in the global DNA methylation profile of hippocampus was associated to the exposure to fluoxetine, whereas an increase in methylation was observed in cortex. The combined treatment induced an increase in the methylation of hippocampus indicating the potential of folic acid to modulate this epigenetic alteration. Increase in the latency to the thermal nociceptive response was observed in animals exposed to fluoxetine whereas this effect was abolished in animals from the combined treatment. In summary we demonstrated that exposure to fluoxetine during gestation and lactation affect the DNA methylation of brain and the nociceptive response of rats. Furthermore our data reveal the potential of folic acid to modulate epigenetic and functional changes induced by early exposure to fluoxetine. PMID:24583191

  3. Maternal separation in early life modifies anxious behavior and Fos and glucocorticoid receptor expression in limbic neurons after chronic stress in rats: effects of tianeptine.

    PubMed

    Trujillo, Verónica; Durando, Patricia E; Suárez, Marta M

    2016-01-01

    Early-life adversity can lead to long-term consequence persisting into adulthood. Here, we assess the implications of an adverse early environment on vulnerability to stress during adulthood. We hypothesized that the interplay between early and late stress would result in a differential phenotype regarding the number of neurons immunoreactive for glucocorticoid receptor (GR-ir) and neuronal activity as assessed by Fos immunoreactivity (Fos-ir) in brain areas related to stress responses and anxiety-like behavior. We also expected that the antidepressant tianeptine could correct some of the alterations induced in our model. Male Wistar rats were subjected to daily maternal separation (MS) for 4.5 h during the first 3 weeks of life. As adults, the rats were exposed to chronic stress for 24 d and they were treated daily with tianeptine (10 mg/kg intraperitoneal) or vehicle (isotonic saline). Fos-ir was increased by MS in all structures analyzed. Chronic stress reduced Fos-ir in the hippocampus, but increased it in the paraventricular nucleus. Furthermore, chronic stress increased GR-ir in hippocampus (CA1) and amygdala in control non-MS rats. By contrast, when MS and chronic stress were combined, GR-ir was decreased in these structures. Additionally, whereas tianeptine did not affect Fos-ir, it regulated GR-ir in a region-dependent manner, in hippocampus and amygdala opposing in some cases the stress or MS effects. Furthermore, tianeptine reversed the MS- or stress-induced anxious behavior. The interplay between MS and chronic stress observed indicates that MS rats have a modified phenotype, which is expressed when they are challenged by stress in later life.

  4. Influence of maternal ingestion of Aroclor 1254[reg sign] (PCB) or FireMaster BP-6[reg sign] (PBB) on unstimulated and stimulated corticosterone levels in young rats

    SciTech Connect

    Meserve, L.A.; Murray, B.A.; Landis, J.A. )

    1992-05-01

    The organohalides polychlorinated biphenyl (PCB) and polybrominated biphenyl (PBB) remain troublesome environmental pollutants. For example, the percentage of the population in which PCB is detectable in adipose tissue remains high. These compounds are of particular interest to residents of the North Central United States, especially in regions surrounding the Great Lakes where contaminated fish may be a regular component of the diet. Additionally, PBB was mistakenly fed to cattle and chickens in Michigan during the early 1970s, products of which were ingested by humans. Among the physiological effects of ingestion of PCB or PBB is the depression of thyroid status, which has been reported in adult humans, in adult experimental animals, and in the offspring of these animals. In adult rats, circulating levels of thyroid hormones are inversely proportional to dose of PCB or PBB in the diet. On the other hand, reports of effects of these organohalides on adrenocortical function remain equivocal, describing both PCB- and PBB-induced depression, and absence of effect in rats and monkeys. Despite the possible consequences of maternal ingestion of PCB or PBB on future generations, little work has been done previously to determine whether consumption of these materials by pregnant and lactating animals confers hypothyroidism on their offspring, and/or influences other mechanisms of endocrine control in the young. Since early studies showed that hypothyroidism induced by feeding pregnant rats the goitrogen thiouracil altered the functional capabilities in their young of the hypothalamus-pituitary-adrenal (HPA) axis, as revealed by circulating corticosterone levels, the present study was done to determine whether ingestion of either PCB (Aroclor 1254[reg sign]) or PBB (FireMaster BP-6[reg sign]) by pregnant and lactating rats resulted in depressed thyroid status and/or modified HPA axis function in their 15 day old young. 19 refs., 1 fig., 1 tab.

  5. Early weaning by maternal prolactin inhibition leads to higher neuropeptide Y and astrogliosis in the hypothalamus of the adult rat offspring.

    PubMed

    Younes-Rapozo, Viviane; Moura, Egberto G; Manhães, Alex C; Peixoto-Silva, Nayara; de Oliveira, Elaine; Lisboa, Patricia C

    2015-02-14

    The suppression of prolactin production with bromocriptine (BRO) in the last 3 d of lactation reduces milk yield (early weaning) and increases the transfer of leptin through the milk, causing hyperleptinaemia in pups. In adulthood, several changes occur in the offspring as a result of metabolic programming, including overweight, higher visceral fat mass, hypothyroidism, hyperglycaemia, insulin resistance, hyperleptinaemia and central leptin resistance. In the present study, we investigated whether overweight rats programmed by early weaning with maternal BRO treatment have hypothalamic alterations in adulthood. We analysed the expression of neuropeptide Y (NPY), cocaine- and amphetamine-regulated transcript (CART), pro-opiomelanocortin (POMC) and α-melanocyte-stimulating hormone (α-MSH) by immunohistochemistry in the following hypothalamic nuclei: medial and lateral arcuate nucleus (ARC); paraventricular nucleus (PVN); lateral hypothalamus (LH). Additionally, we sought to determine whether these programmed rats exhibited hypothalamic inflammation as indicated by astrogliosis. NPY immunostaining showed a denser NPY-positive fibre network in the ARC and PVN (+82% in both nuclei) of BRO offspring. Regarding the anorexigenic neuropeptides, no difference was found for CART, POMC and α-MSH. The number of astrocytes was higher in all the nuclei of BRO rats. The fibre density of glial fibrillary acidic protein was also increased in both medial and lateral ARC (6·06-fold increase and 9·13-fold increase, respectively), PVN (5·75-fold increase) and LH (2·68-fold increase) of BRO rats. We suggest that early weaning has a long-term effect on the expression of NPY as a consequence of developmental plasticity, and the presence of astrogliosis indicates hypothalamic inflammation that is closely related to overweight and hyperleptinaemia observed in our model.

  6. Maternal separation in early life modifies anxious behavior and Fos and glucocorticoid receptor expression in limbic neurons after chronic stress in rats: effects of tianeptine.

    PubMed

    Trujillo, Verónica; Durando, Patricia E; Suárez, Marta M

    2016-01-01

    Early-life adversity can lead to long-term consequence persisting into adulthood. Here, we assess the implications of an adverse early environment on vulnerability to stress during adulthood. We hypothesized that the interplay between early and late stress would result in a differential phenotype regarding the number of neurons immunoreactive for glucocorticoid receptor (GR-ir) and neuronal activity as assessed by Fos immunoreactivity (Fos-ir) in brain areas related to stress responses and anxiety-like behavior. We also expected that the antidepressant tianeptine could correct some of the alterations induced in our model. Male Wistar rats were subjected to daily maternal separation (MS) for 4.5 h during the first 3 weeks of life. As adults, the rats were exposed to chronic stress for 24 d and they were treated daily with tianeptine (10 mg/kg intraperitoneal) or vehicle (isotonic saline). Fos-ir was increased by MS in all structures analyzed. Chronic stress reduced Fos-ir in the hippocampus, but increased it in the paraventricular nucleus. Furthermore, chronic stress increased GR-ir in hippocampus (CA1) and amygdala in control non-MS rats. By contrast, when MS and chronic stress were combined, GR-ir was decreased in these structures. Additionally, whereas tianeptine did not affect Fos-ir, it regulated GR-ir in a region-dependent manner, in hippocampus and amygdala opposing in some cases the stress or MS effects. Furthermore, tianeptine reversed the MS- or stress-induced anxious behavior. The interplay between MS and chronic stress observed indicates that MS rats have a modified phenotype, which is expressed when they are challenged by stress in later life. PMID:26452320

  7. Thrifty metabolic programming in rats is induced by both maternal undernutrition and postnatal leptin treatment, but masked in the presence of both: implications for models of developmental programming

    PubMed Central

    2014-01-01

    Background Maternal undernutrition leads to an increased risk of metabolic disorders in offspring including obesity and insulin resistance, thought to be due to a programmed thrifty phenotype which is inappropriate for a subsequent richer nutritional environment. In a rat model, both male and female offspring of undernourished mothers are programmed to become obese, however postnatal leptin treatment gives discordant results between males and females. Leptin treatment is able to rescue the adverse programming effects in the female offspring of undernourished mothers, but not in their male offspring. Additionally, in these rats, postnatal leptin treatment of offspring from normally-nourished mothers programmes their male offspring to develop obesity in later life, while there is no comparable effect in their female offspring. Results We show by microarray analysis of the female liver transcriptome that both maternal undernutrition and postnatal leptin treatment independently induce a similar thrifty transcriptional programme affecting carbohydrate metabolism, amino acid metabolism and oxidative stress genes. Paradoxically, however, the combination of both stimuli restores a more normal transcriptional environment. This demonstrates that “leptin reversal” is a global phenomenon affecting all genes involved in fetal programming by maternal undernourishment and leptin treatment. The thrifty transcriptional programme was associated with pro-inflammatory markers and downregulation of adaptive immune mediators, particularly MHC class I genes, suggesting a deficit in antigen presentation in these offspring. Conclusions We propose a revised model of developmental programming reconciling the male and female observations, in which there are two competing programmes which collectively drive liver transcription. The first element is a thrifty metabolic phenotype induced by early life growth restriction independently of leptin levels. The second is a homeostatic set point

  8. Can low-level ethanol exposure during pregnancy influence maternal care? An investigation using two strains of rat across two generations.

    PubMed

    Popoola, Daniel O; Borrow, Amanda P; Sanders, Julia E; Nizhnikov, Michael E; Cameron, Nicole M

    2015-09-01

    Gestational alcohol use is well documented as detrimental to both maternal and fetal health, producing an increase in offspring's tendency for alcoholism, as well as in behavioral and neuropsychological disorders. In both rodents and in humans, parental care can influence the development of offspring physiology and behavior. Animal studies that have investigated gestational alcohol use on parental care and/or their interaction mostly employ heavy alcohol use and single strains. This study aimed at investigating the effects of low gestational ethanol dose on parental behavior and its transgenerational transmission, with comparison between two rat strains. Pregnant Sprague Dawley (SD) and Long Evans (LE) progenitor dams (F0) received 1g/kg ethanol or water through gestational days 17-20 via gavage, or remained untreated in their home cages. At maturity, F1 female offspring were mated with males of the same strain and treatment and were left undisturbed through gestation. Maternal behavior was scored in both generations during the first six postnatal days. Arch-back nursing (ABN) was categorized as: 1, when the dam demonstrated minimal kyphosis; 2, when the dam demonstrated moderate kyphosis; and 3, when the dam displayed maximal kyphosis. Overall, SD showed greater amounts of ABN than LE dams and spent more time in contact with their pups. In the F0 generation, water and ethanol gavage increased ABN1 and contact with pups in SD, behaviors which decreased in treated LE. For ABN2, ethanol-treated SD dams showed more ABN2 than water-treated dams, with no effect of treatment on LE animals. In the F1 generation, prenatal exposure affected retrieval. Transgenerational transmission of LG was observed only in the untreated LE group. Strain-specific differences in maternal behavior were also observed. This study provides evidence that gestational gavage can influence maternal behavior in a strain-specific manner. Our results also suggest that the experimental procedure during

  9. Maternal ethanol ingestion effects on fetal rat brain vitamin A as a model for fetal alcohol syndrome.

    PubMed

    Grummer, M A; Langhough, R E; Zachman, R D

    1993-06-01

    Fetal embryo, head, and brain tissue from different gestational ages were analyzed for retinol content, nuclear retinoic acid receptor and cytosolic retinoic acid binding protein levels after maternal ethanol ingestion and compared with fetal levels in control diet pregnancies. Retinol levels in fetal embryo and brain of ethanol-ingesting pregnancies were 2- to 3-fold higher than fetal embryo and brain retinol of control pregnancies. Nuclear retinoic acid receptor was lower in 10-day embryo of ethanol pregnancies and apparently unaffected in fetal head and brain by maternal ethanol consumption at other days of gestation. In fetal head there was a significant overall ethanol effect on cytosolic retinoic acid binding protein, with increased levels in fetal tissue from ethanol-consuming pregnancies. These observations of altered embryo, fetal head, and fetal brain retinol and receptor protein levels support the hypothesis of a possible role of vitamin A in fetal alcohol syndrome. PMID:8333589

  10. Variable Maternal Stress in Rats Alters Locomotor Activity, Social Behavior, and Recognition Memory in the Adult Offspring

    PubMed Central

    Wilson, Christina A.; Terry, Alvin V.

    2013-01-01

    Rats repeatedly exposed to variable prenatal stress (PNS) exhibit behavioral signs that are similar to those manifested in several neuropsychiatric disorders such as deficits in attention and inhibitory control, and impairments in memory-related task performance. The purpose of the study described here was to conduct a comprehensive battery of tests to further characterize the behavioral phenotype of PNS rats as well as to evaluate the sensitivity of the model to therapeutic interventions (i.e., to compounds previously shown to have therapeutic potential in neuropsychiatric disorders). The results of this study indicated that PNS in rats is associated with: 1) increased locomotor activity and stereotypic behaviors, 2) elevated sensitivity to the psychostimulant amphetamine, 3) increased aggressive behaviors toward both adult and juvenile rats and 4) delay-dependent deficits in recognition memory. There was no evidence that PNS rats exhibited deficits in other areas of motor function/learning, sensorimotor gating, spatial learning and memory, social withdrawal, or anhedonia. In addition, the results revealed that the second generation antipsychotic risperidone attenuated amphetamine-related increases in locomotor activity in PNS rats; however, the effect was not sustained over time. Furthermore, deficits in recognition memory in PNS rats were attenuated by the norepinephrine reuptake inhibitor, atomoxetine, but not by the α7 nicotinic acetylcholine receptor partial agonist, GTS-21. This study supports the supposition that important phenomenological similarities exist between rats exposed to PNS and patients afflicted with neuropsychiatric disorders thus further establishing the face validity of the model for evaluating potential therapeutic interventions. PMID:23287801

  11. Specific effects of maternal zinc depletion or repletion on the deposition of zinc and metallothionein in newborn rat livers: a longitudinal study

    SciTech Connect

    Gallant, K.R.; Cherian, M.G.

    1986-03-05

    High levels of metallothionein (MT) have been reported in association with elevated zinc (Zn) in the livers of newborn rats. Previous studies in this laboratory have demonstrated that maternal Zn-deficiency (Zn-D) specifically reduces the storage of Zn as MT in one day old pup liver. To further investigate how dietary Zn levels influence the storage of Zn as MT, newborn Zn-D pups were allowed to suckle from Zn-sufficient (Zn-S) dams and vice versa. Pups were injected with 2.5 ..mu..Ci of Zn/sup 65/ and whole body retention monitored. Pups were sacrificed at varying time periods up to weaning and hepatic levels of Zn and MT were measured. A gradual increase in the abnormally low hepatic levels of Zn and MT was observed in Zn-D pups suckling from Zn-S dams up to about day 10. Zn-S pups suckling from Zn-D dams showed a much faster rate of decline of MT and Zn than in age-matched controls, suggesting a rapid turnover of Zn-MT. Whole body retention of Zn/sup 65/ was lower in the Zn-repleted pups than in the pups which were subjected to Zn-D postnatally. These results demonstrate that the Zn-MT levels fluctuate directly in response to the Zn status of the pups, supporting the role of MT as a Zn storage protein in newborn rats.

  12. Dietary n-3 polyunsaturated fatty acid deprivation together with early maternal separation increases anxiety and vulnerability to stress in adult rats.

    PubMed

    Mathieu, Géraldine; Oualian, Catherine; Denis, Isabelle; Lavialle, Monique; Gisquet-Verrier, Pascale; Vancassel, Sylvie

    2011-01-01

    Low concentrations of n-3 polyunsaturated fatty acid (PUFA) and chronic stress are implicated in susceptibility to mood disorders. We have investigated the combined effects of chronic n-3 PUFA dietary deficiency and early maternal separation (MS) stress on the reactivity to stressful situations of rats as adults. Pups fed a control or an n-3 PUFA deficient diet were daily separated for two weeks before weaning They were all tested at 3 month-old to determine their anxiety, and their ability to learn two aversive tasks differing in the control they could exert on the situation: auditory fear conditioning and brightness avoidance discrimination. Neither the n-3 PUFA-deficient diet nor MS alone significantly affected behavior. But n-3 PUFA-deficient rats that had been separated were more anxious and fearful in inescapable situations, while their ability to cope with an aversive avoidance task remained unaffected. These results support the notion that PUFA-unbalanced diet, together with stress, may be a determinant risk factor in emotional disorders.

  13. The effect of maternal malnutrition during lactation on the endometrial ERalpha expression, collagen type, and blood vessels in the rats offspring at puberty.

    PubMed

    Bittencourt Brasil, Flávia; Silva Faria, Tatiane; Barcellos Sampaio, Francisco José; da Fonte Ramos, Cristiane

    2010-01-01

    The aim of this manuscript was to evaluate the effects of maternal protein-energy-restriction and energy restriction during lactation on endometrial collagen and blood vessels, uterus Eralpha expression, and estradiol serum levels in the rats offspring at puberty. At parturition, dams were grouped as: control group (C), with free access to standard rat chow containing 23% protein and 17,038.7 KJ/Kg; protein-energy restricted group (PER), with free access to formulated chow containing 8% protein but made isoenergetic to the C diet (17,038.7 KJ/Kg); and energy-restricted group (ER), which received standard rat chow containing 23% protein based on the mean ingestion of the PER group corresponding to 60% of that consumed by the control group. After weaning, all female pups had free access to standard laboratory chow until puberty, when they were killed at the diestrum stage. The uterine ERalpha expression was determined by Western-Blot and estradiol serum levels by radioimmunoassay. Endometrial collagen and blood vessels were quantified by stereology. The volumetric density of blood vessels (C = 70.7 +/- 2.2; PER = 29.2 +/- 2.4; ER = 32.3 +/- 3.6; P < 0.001) and endometrial collagen (C = 31.1 +/- 1; PER = 26.9 +/- 1.0; ER = 26.5 +/- 0.7; P < 0.05) were significantly reduced in both malnourished groups. The ER group presented higher estradiol serum levels (C = 69.2 +/- 6.4; PER = 73.4 +/- 5.5; ER = 101.0 +/- 5.4; P < 0.01) in relation to C and PER groups. ERalpha expression was greater in both malnourished groups (C = 0.11 +/- 0.02; PER = 0.41 +/- 0.12; ER = 0.35 +/- 0.03; P < 0.05). In conclusion, maternal malnutrition during lactation caused changes in endometrial angiogenesis, collagen deposition, and Eralpha expression in female offspring that will appear in puberty and could affect the reproductive biology of the female offspring.

  14. Early maternal deprivation induces gender-dependent changes on the expression of hippocampal CB(1) and CB(2) cannabinoid receptors of neonatal rats.

    PubMed

    Suárez, Juan; Llorente, Ricardo; Romero-Zerbo, Silvana Y; Mateos, Beatriz; Bermúdez-Silva, Francisco J; de Fonseca, Fernando Rodríguez; Viveros, María-Paz

    2009-07-01

    Early maternal deprivation (MD) in rats (24 h, postnatal day 9-10) is a model for neurodevelopmental stress. There are some data proving that MD affects the endocannabinoid system (ECS) in a gender-dependent manner, and that these changes may account for the proposed schizophrenia-like phenotype of MD rats. The impact of MD on cannabinoid receptor distribution in the hippocampus is unknown. The aim of this study is to evaluate the expression of CB(1) and CB(2) receptors in diverse relevant subregions (DG, CA1, and CA3) of the hippocampus in 13-day-old rats by immunohistochemistry and densitometry. MD induced a significant decrease in CB(1) immunoreactivity (more marked in males than in females), which was mainly associated with fibers in the strata pyramidale and radiatum of CA1 and in the strata oriens, pyramidale, and radiatum of CA3. In contrast, MD males and females showed a significant increase in CB(2) immunoreactivity in the three hippocampal areas analyzed that was detected in neuropil and puncta in the stratum oriens of CA1 and CA3, and in the polymorphic cell layer of the dentate gyrus. A marked sex dimorphism was observed in CA3, with females exhibiting higher CB(1) immunoreactivity than males, and in dentate gyrus, with females exhibiting lower CB(2) immunoreactivity than males. These results point to a clear association between developmental stress and dysregulation of the ECS. The present MD procedure may provide an interesting experimental model to further address the role of the ECS in neurodevelopmental mental illnesses such as schizophrenia.

  15. Sex and age-dependent effects of a maternal junk food diet on the mu-opioid receptor in rat offspring.

    PubMed

    Gugusheff, Jessica R; Bae, Sung Eun; Rao, Alexandra; Clarke, Iain J; Poston, Lucilla; Taylor, Paul D; Coen, Clive W; Muhlhausler, Beverly S

    2016-03-15

    Perinatal junk food exposure increases the preference for palatable diets in juvenile and adult rat offspring. Previous studies have implicated reduced sensitivity of the opioid pathway in the programming of food preferences; however it is not known when during development these changes in opioid signalling first emerge. This study aimed to determine the impact of a maternal junk food (JF) diet on mu-opioid receptor (MuR) expression and ligand binding in two key regions of the reward pathway, the nucleus accumbens (NAc) and the ventral tegmental area (VTA) in rats during the early suckling (postnatal day (PND) 1 and 7) and late suckling/early post-weaning (PND 21 and 28) periods. Female rats were fed either a JF or a control diet for two weeks prior to mating and throughout pregnancy and lactation. MuR expression in the VTA was significantly reduced in female JF offspring on PND 21 and 28 (by 32% and 57% respectively, P<0.05), but not at earlier time points (PND 1 and 7). MuR ligand binding was also reduced (by 22%, P<0.05) in the VTA of female JF offspring on PND 28. No effects of perinatal junk food exposure on MuR mRNA expression or binding were detected at these time points in male offspring. These findings provide evidence that the opioid signalling system is a target of developmental programming by the end of the third postnatal week in females, but not in males. PMID:26718219

  16. Maternal separation enhances conditioned fear and decreases the mRNA levels of the neurotensin receptor 1 gene with hypermethylation of this gene in the rat amygdala.

    PubMed

    Toda, Hiroyuki; Boku, Shuken; Nakagawa, Shin; Inoue, Takeshi; Kato, Akiko; Takamura, Naoki; Song, Ning; Nibuya, Masashi; Koyama, Tsukasa; Kusumi, Ichiro

    2014-01-01

    Stress during postnatal development is associated with an increased risk for depression, anxiety disorders, and substance abuse later in life, almost as if mental illness is able to be programed by early life stressors. Recent studies suggest that such "programmed" effects can be caused by epigenetic regulation. With respect to conditioned fear, previous studies have indicated that early life stress influences its development in adulthood, whereas no potential role of epigenetic regulation has been reported. Neurotensin (NTS) is an endogenous neuropeptide that has receptors densely located in the amygdala and hippocampus. Recently, NTS systems have constituted an emerging target for the treatment of anxiety. The aim of the present work is to clarify whether the NTS system is involved in the disturbance of conditioned fear in rats stressed by maternal separation (MS). The results showed that MS enhanced freezing behaviors in fear-conditioned stress and reduced the gene expression of NTS receptor (NTSR) 1 but not of NTS or NTSR2 in the amygdalas of adult rats. The microinjection of a NTSR1 antagonist into the amygdala increased the percentage of freezing in conditioned fear, whereas the microinjection of NTSR1 agonist decreased freezing. These results suggest that NTSR1 in the amygdala may play a role in the effects of MS on conditioned fear stress in adult rats. Moreover, MS increased DNA methylation in the promoter region of NTSR1 in the amygdala. Taken together, MS may leave epigenetic marks in the NTSR1 gene in the amygdala, which may enhance conditioned fear in adulthood. The MS-induced alternations of DNA methylation in the promoter region of NTSR1 in the amygdala may be associated with vulnerability to the development of anxiety disorders and depression in adulthood. PMID:24831231

  17. Maternal Separation Enhances Conditioned Fear and Decreases the mRNA Levels of the Neurotensin Receptor 1 Gene with Hypermethylation of This Gene in the Rat Amygdala

    PubMed Central

    Toda, Hiroyuki; Boku, Shuken; Nakagawa, Shin; Inoue, Takeshi; Kato, Akiko; Takamura, Naoki; Song, Ning; Nibuya, Masashi; Koyama, Tsukasa; Kusumi, Ichiro

    2014-01-01

    Stress during postnatal development is associated with an increased risk for depression, anxiety disorders, and substance abuse later in life, almost as if mental illness is able to be programed by early life stressors. Recent studies suggest that such “programmed” effects can be caused by epigenetic regulation. With respect to conditioned fear, previous studies have indicated that early life stress influences its development in adulthood, whereas no potential role of epigenetic regulation has been reported. Neurotensin (NTS) is an endogenous neuropeptide that has receptors densely located in the amygdala and hippocampus. Recently, NTS systems have constituted an emerging target for the treatment of anxiety. The aim of the present work is to clarify whether the NTS system is involved in the disturbance of conditioned fear in rats stressed by maternal separation (MS). The results showed that MS enhanced freezing behaviors in fear-conditioned stress and reduced the gene expression of NTS receptor (NTSR) 1 but not of NTS or NTSR2 in the amygdalas of adult rats. The microinjection of a NTSR1 antagonist into the amygdala increased the percentage of freezing in conditioned fear, whereas the microinjection of NTSR1 agonist decreased freezing. These results suggest that NTSR1 in the amygdala may play a role in the effects of MS on conditioned fear stress in adult rats. Moreover, MS increased DNA methylation in the promoter region of NTSR1 in the amygdala. Taken together, MS may leave epigenetic marks in the NTSR1 gene in the amygdala, which may enhance conditioned fear in adulthood. The MS-induced alternations of DNA methylation in the promoter region of NTSR1 in the amygdala may be associated with vulnerability to the development of anxiety disorders and depression in adulthood. PMID:24831231

  18. Effects of maternal and lactational exposure to 2-hydroxy-4-methoxybenzone on development and reproductive organs in male and female rat offspring

    PubMed Central

    Nakamura, Noriko; Inselman, Amy L.; White, Gene A.; Chang, Ching-Wei; Trbojevich, Raul A.; Sepehr, Estatira; Voris, Kristie L.; Patton, Ralph E.; Bryant, Matthew S.; Harrouk, Wafa; McIntyre, Barry; Foster, Paul M.; Hansen, Deborah K.

    2015-01-01

    BACKGROUND 2-hydroxy-4-methoxybenzophenone (HMB) is an ultraviolet (UV)-absorbing compound used in many cosmetic products as a UV-protecting agent and in plastics for preventing UV-induced photodecomposition. HMB has been detected in over 95% of randomly collected human urine samples from adults and from premature infants, and it may have estrogenic potential. METHODS To determine the effects of maternal and lactational exposure to HMB on development and reproductive organs of offspring, time-mated female Harlan Sprague-Dawley rats were dosed with 0, 1,000, 3,000, 10,000, 25,000, or 50,000 ppm HMB (7-8 per group) added to chow from gestation day 6 until weaning on postnatal day (PND) 23. RESULTS AND CONCLUSION Exposure to HMB was associated with reduced body and organ weights in female and male offspring. No significant differences were observed in the number of implantation sites/litter, mean resorptions/litter, % litters with resorptions, number and weights of live fetuses, or sex ratios between the control and HMB dose groups. Normalized anogenital distance in male pups at PND 23 was decreased in the highest dose group. Spermatocyte development was impaired in testes of male offspring in the highest dose group. In females, follicular development was delayed in the highest dose group. However, by evaluating levels of the compound in rat serum, the doses at which adverse events occurred are much higher than usual human exposure levels. Thus, exposure to less than 10,000 ppm HMB does not appear to be associated with adverse effects on the reproductive system in rats. PMID:25707689

  19. Effects of maternal hypothyroidism during pregnancy on learning, memory and hippocampal BDNF in rat pups: Beneficial effects of exercise.

    PubMed

    Shafiee, Seyed Morteza; Vafaei, Abbas Ali; Rashidy-Pour, Ali

    2016-08-01

    Hypothyroidism during early development leads to numerous morphological, biochemical and functional changes in developing brain. In this study, we investigated the effects of voluntary and treadmill exercise on learning, memory and hippocampal BDNF levels in both hypothyroid male and female rat pups. To induce hypothyroidism in the mothers, 6-propyl-2-thiouracil (PTU) was added to their drinking water (100mg/L) from their embryonic day 6 to their postnatal day (PND) 21. For 14days, from PNDs 31 to 44, the rat pups were trained with one of the two different exercise protocols, namely the mild treadmill exercise and the voluntary wheel exercise. On PNDs 45-52, a water maze was used for testing their learning and memory ability. The rats were sacrificed one day later and their BDNF levels were then measured in the hippocampus. The findings of the present study indicate that hypothyroidism during the fetal period and the early postnatal period is associated with the impairment of spatial learning and memory and reduced hippocampal BDNF levels in both male and female rat offspring. Both the short-term treadmill exercise and the voluntary wheel exercise performed during the postnatal period reverse the behavioral and neurochemical deficits induced by developmental thyroid hormone insufficiency in both male and female rat offspring. The findings of this study thus demonstrate a marked reversibility of both behavioral and neurochemical disorders induced by developmental thyroid hormone insufficiency through the performance of exercise. PMID:27181637

  20. Effects of maternal hypothyroidism during pregnancy on learning, memory and hippocampal BDNF in rat pups: Beneficial effects of exercise.

    PubMed

    Shafiee, Seyed Morteza; Vafaei, Abbas Ali; Rashidy-Pour, Ali

    2016-08-01

    Hypothyroidism during early development leads to numerous morphological, biochemical and functional changes in developing brain. In this study, we investigated the effects of voluntary and treadmill exercise on learning, memory and hippocampal BDNF levels in both hypothyroid male and female rat pups. To induce hypothyroidism in the mothers, 6-propyl-2-thiouracil (PTU) was added to their drinking water (100mg/L) from their embryonic day 6 to their postnatal day (PND) 21. For 14days, from PNDs 31 to 44, the rat pups were trained with one of the two different exercise protocols, namely the mild treadmill exercise and the voluntary wheel exercise. On PNDs 45-52, a water maze was used for testing their learning and memory ability. The rats were sacrificed one day later and their BDNF levels were then measured in the hippocampus. The findings of the present study indicate that hypothyroidism during the fetal period and the early postnatal period is associated with the impairment of spatial learning and memory and reduced hippocampal BDNF levels in both male and female rat offspring. Both the short-term treadmill exercise and the voluntary wheel exercise performed during the postnatal period reverse the behavioral and neurochemical deficits induced by developmental thyroid hormone insufficiency in both male and female rat offspring. The findings of this study thus demonstrate a marked reversibility of both behavioral and neurochemical disorders induced by developmental thyroid hormone insufficiency through the performance of exercise.

  1. Effects of energy and protein restriction, followed by nutritional recovery on morphological development of the gastrointestinal tract of weaned kids.

    PubMed

    Sun, Z H; He, Z X; Zhang, Q L; Tan, Z L; Han, X F; Tang, S X; Zhou, C S; Wang, M; Yan, Q X

    2013-09-01

    Effects of energy, protein, or both energy and protein restriction on gastrointestinal morphological development were investigated in 60 Liuyang Black kids, which were sourced from local farms and weaned at 28 d of age. Weaned kids were randomly assigned to receive 1 of 4 dietary treatments (15 kids per treatment), which consisted of adequate nutrient supply (CON), energy restriction (ER), protein restriction (PR), or energy and protein restriction (EPR). The entire experiment included adaptation period (0 to 6 d), nutritional restriction period (7 to 48 d), and recovery period (49 to 111 d). Three kids from each group were killed at d 48 and 111, and the rumen, duodenum, jejunum, and ileum were harvested. On d 48 (end of nutritional restriction), lengths of the duodenum (P = 0.005), jejunum (P = 0.003), and ileum (P = 0.003), and weights of the rumen (P = 0.004), duodenum (P = 0.006), jejunum (P = 0.006), and ileum (P = 0.004) of kids in ER, PR, and EPR were less than those of kids in CON. Compared with CON, PR decreased papillae width (P = 0.03) and surface area (P = 0.05) of the rumen epithelium, villus surface area (P = 0.05), and N concentration (P = 0.02) of the jejunum mucosa on d 48. Compared with CON, EPR decreased papillae height (P = 0.001), width (P = 0.001), and surface area (P = 0.003), N concentration (P = 0.01), and the ratio of N to DNA (P = 0.03) of the rumen epithelium. Compared with CON, EPR also decreased villus height (P = 0.01), width (P = 0.006), and surface area (P = 0.006), N concentration (P < 0.001), and the ratio of N to DNA (P < 0.001) of the jejunum mucosa on d 48. On d 111 (end of nutritional recovery), lengths of the duodenum (P = 0.001), jejunum (P = 0.001), and ileum (P = 0.001), weights of the rumen (P < 0.001), duodenum (P = 0.001), jejunum (P < 0.001), and ileum (P < 0.001) of kids in ER, PR, and EPR were still less than those of kids in CON; N concentrations of rumen epithelium of kids in PR (P = 0.01) and EPR (P = 0.001), and

  2. Maternal folic acid supplementation modulates DNA methylation and gene expression in the rat offspring in a gestation period-dependent and organ-specific manner.

    PubMed

    Ly, Anna; Ishiguro, Lisa; Kim, Denise; Im, David; Kim, Sung-Eun; Sohn, Kyoung-Jin; Croxford, Ruth; Kim, Young-In

    2016-07-01

    Maternal folic acid supplementation can alter DNA methylation and gene expression in the developing fetus, which may confer disease susceptibility later in life. We determined which gestation period and organ were most sensitive to the modifying effect of folic acid supplementation during pregnancy on DNA methylation and gene expression in the offspring. Pregnant rats were randomized to a control diet throughout pregnancy; folic acid supplementation at 2.5× the control during the 1st, 2nd or 3rd week of gestation only; or folic acid supplementation throughout pregnancy. The brain, liver, kidney and colon from newborn pups were analyzed for folate concentrations, global DNA methylation and gene expression of the Igf2, Er-α, Gr, Ppar-α and Ppar-γ genes. Folic acid supplementation during the 2nd or 3rd week gestation or throughout pregnancy significantly increased brain folate concentrations (P<.001), while only folic acid supplementation throughout pregnancy significantly increased liver folate concentrations (P=.005), in newborn pups. Brain global DNA methylation incrementally decreased from early to late gestational folic acid supplementation and was the lowest with folic acid supplementation throughout pregnancy (P=.026). Folic acid supplementation in late gestation or throughout pregnancy significantly decreased Er-α, Gr and Ppar-α gene expression in the liver (P<.05). The kidney and colon were resistant to the effect of folic acid supplementation. Maternal folic acid supplementation affects tissue folate concentrations, DNA methylation and gene expression in the offspring in a gestation-period-dependent and organ-specific manner. PMID:27152636

  3. Maternal omega 3 fatty acid supplementation during pregnancy to a micronutrient-imbalanced diet protects postnatal reduction of brain neurotrophins in the rat offspring.

    PubMed

    Sable, P S; Dangat, K D; Joshi, A A; Joshi, S R

    2012-08-16

    An altered one carbon cycle (folic acid, vitamin B(12)) and omega 3 fatty acid metabolism during pregnancy can increase the risk for neurodevelopmental disorders in the offspring. Our earlier studies have shown that a maternal diet imbalanced with micronutrients like folic acid, vitamin B(12) reduces levels of brain docosahexaenoic acid (DHA) and neurotrophins in the offspring at birth. The present study examines whether these effects can be reversed by a postnatal diet. Pregnant female rats were divided into six treatment groups at two levels of folic acid both in the presence and absence of vitamin B(12). Omega 3 fatty acid supplementation was given to the vitamin B(12)-deficient groups. Following delivery, eight dams from each group were randomly shifted back to control and remaining eight continued on the same treatment diet. Plasma homocysteine levels could be normalized by a postnatal control diet. Brain DHA levels were similar in all the groups irrespective of the diet consumed during lactation. Brain-derived nerve growth factor (BDNF) and nerve growth factor (NGF) levels were lower in both the vitamin B(12)-deficient groups even after consuming a diet with normal levels of vitamin B(12) during lactation (p<0.05 for all) indicating that the effects of maternal programing with respect to neurotrophins cannot be reversed by a postnatal diet. Our findings for the first time suggest that omega 3 fatty acid supplementation to a micronutrient-imbalanced diet, during pregnancy and lactation protects the levels of BDNF and NGF. This may have significant implications in the development of psychiatric disorders/cognitive deficits in later life. PMID:22579981

  4. Maternal folic acid supplementation modulates DNA methylation and gene expression in the rat offspring in a gestation period-dependent and organ-specific manner.

    PubMed

    Ly, Anna; Ishiguro, Lisa; Kim, Denise; Im, David; Kim, Sung-Eun; Sohn, Kyoung-Jin; Croxford, Ruth; Kim, Young-In

    2016-07-01

    Maternal folic acid supplementation can alter DNA methylation and gene expression in the developing fetus, which may confer disease susceptibility later in life. We determined which gestation period and organ were most sensitive to the modifying effect of folic acid supplementation during pregnancy on DNA methylation and gene expression in the offspring. Pregnant rats were randomized to a control diet throughout pregnancy; folic acid supplementation at 2.5× the control during the 1st, 2nd or 3rd week of gestation only; or folic acid supplementation throughout pregnancy. The brain, liver, kidney and colon from newborn pups were analyzed for folate concentrations, global DNA methylation and gene expression of the Igf2, Er-α, Gr, Ppar-α and Ppar-γ genes. Folic acid supplementation during the 2nd or 3rd week gestation or throughout pregnancy significantly increased brain folate concentrations (P<.001), while only folic acid supplementation throughout pregnancy significantly increased liver folate concentrations (P=.005), in newborn pups. Brain global DNA methylation incrementally decreased from early to late gestational folic acid supplementation and was the lowest with folic acid supplementation throughout pregnancy (P=.026). Folic acid supplementation in late gestation or throughout pregnancy significantly decreased Er-α, Gr and Ppar-α gene expression in the liver (P<.05). The kidney and colon were resistant to the effect of folic acid supplementation. Maternal folic acid supplementation affects tissue folate concentrations, DNA methylation and gene expression in the offspring in a gestation-period-dependent and organ-specific manner.

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

    PubMed

    Wang, Hong; Gondré-Lewis, Marjorie C

    2013-01-01

    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 lab