RESUMO
Intrauterine growth restriction (IUGR) is a risk factor for memory impairment and emotional disturbance during growth and adulthood. However, this risk might be modulated by environmental factors during development. Here we examined whether exposing adolescent male and female rats with thromboxane A2-induced IUGR to social defeat stress (SDS) affected their working memory and anxiety-like behavior in adulthood. We also used BrdU staining to investigate hippocampal cellular proliferation and BrdU and NeuN double staining to investigate neural differentiation in female IUGR rats. In the absence of adolescent stress, IUGR female rats, but not male rats, scored significantly lower in the T-maze test of working memory and exhibited higher anxiety-like behavior in the elevated-plus maze test compared with controls. Adolescent exposure to SDS abolished these behavioral impairments in IUGR females. In the absence of adolescent stress, hippocampal cellular proliferation was significantly higher in IUGR females than in non-IUGR female controls and was not influenced by adolescent exposure to SDS. Hippocampal neural differentiation was equivalent in non-stressed control and IUGR females. Neural differentiation was significantly increased by adolescent exposure to SDS in controls but not in IUGR females. There was no significant difference in the serum corticosterone concentrations between non-stressed control and IUGR females; however, adolescent exposure to SDS significantly increased serum corticosterone concentration in control females but not in IUGR females. These results demonstrate that adolescent exposure to SDS improves behavioral impairment independent of hippocampal neurogenesis in adult rats with IUGR.
Assuntos
Ansiedade/psicologia , Comportamento Animal/fisiologia , Retardo do Crescimento Fetal/psicologia , Hipocampo/crescimento & desenvolvimento , Memória de Curto Prazo/fisiologia , Meio Social , Estresse Psicológico/psicologia , Animais , Peso Corporal , Diferenciação Celular , Proliferação de Células , Corticosterona/sangue , Feminino , Hipocampo/embriologia , Gravidez , Ratos , Ratos Long-Evans , Ratos Sprague-DawleyRESUMO
Low birth weight due to intrauterine growth retardation (IUGR) is suggested to be a risk factor for various psychiatric disorders such as schizophrenia. It has been reported that developmental cortical dysfunction and neurocognitive deficits are observed in individuals with IUGR, however, the underlying molecular mechanisms have yet to be elucidated. Brain-derived neurotrophic factor (BDNF) and its receptor TrkB are associated with schizophrenia and play a role in cortical development. We previously demonstrated that BDNF induced glutamate release through activation of the TrkB/phospholipase C-γ (PLC-γ) pathway in developing cultured cortical neurons, and that, using a rat model for IUGR caused by maternal administration of thromboxane A2, cortical levels of TrkB were significantly reduced in IUGR rats at birth. These studies prompted us to hypothesize that TrkB reduction in IUGR cortex led to impairment of BDNF-dependent glutamatergic neurotransmission. In the present study, we found that BDNF-induced glutamate release was strongly impaired in cultured IUGR cortical neurons where TrkB reduction was maintained. Impairment of BDNF-induced glutamate release in IUGR neurons was ameliorated by transfection of human TrkB (hTrkB). Although BDNF-stimulated phosphorylation of TrkB and of PLC-γ was decreased in IUGR neurons, the hTrkB transfection recovered the deficits in their phosphorylation. These results suggest that TrkB reduction causes impairment of BDNF-stimulated glutamatergic function via suppression of TrkB/PLC-γ activation in IUGR cortical neurons. Our findings provide molecular insights into how IUGR links to downregulation of BDNF function in the cortex, which might be involved in the development of IUGR-related diseases such as schizophrenia.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/farmacologia , Córtex Cerebral/enzimologia , Retardo do Crescimento Fetal/enzimologia , Ácido Glutâmico/metabolismo , Fosfolipase C gama/metabolismo , Receptor trkB/metabolismo , Animais , Animais Recém-Nascidos , Linhagem Celular Tumoral , Células Cultivadas , Córtex Cerebral/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/fisiologia , Feminino , Humanos , Masculino , Neurônios/efeitos dos fármacos , Neurônios/enzimologia , Fosfolipase C gama/antagonistas & inibidores , Gravidez , Ratos , Ratos Long-Evans , Ratos Wistar , Receptor trkB/antagonistas & inibidoresRESUMO
Orexin A/hypocretin-1 inhibits pulsatile luteinizing hormone (LH) secretion in female rats. In this study, we investigated whether this inhibition was tied to the fasting state, as suggested by our previous study. We first examined whether orexin A inhibited pulsatile LH secretion when food was available ad libitumduring blood sampling. Next, we investigated the effect of intravenous administration of glucose (400 mg/kg) or lactic acid (negative control; 400 mg/kg) on orexin A-induced inhibition of pulsatile LH secretion. We found that orexin A did not affect pulsatile LH secretion in the presence of food, although it increased feeding behavior. Injection of orexin A significantly inhibited pulsatile LH secretion when food was withheld during blood sampling (p < 0.05); this inhibitory effect was rapidly reversed by intravenous injection of glucose but not lactic acid. Because orexin A did not seem to affect pulsatile LH secretion when food was available ad libitum, we speculate that orexin A has an effect on LH secretion when orexin A-induced hunger is accompanied by stress, such as the absence of food. Furthermore, glucose as well as food may act as a satiety factor in gonadotropin-releasing hormone pulse generation.
Assuntos
Jejum/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Hormônio Luteinizante/metabolismo , Neuropeptídeos/metabolismo , Animais , Jejum/sangue , Comportamento Alimentar/fisiologia , Feminino , Glucose/metabolismo , Ácido Láctico/metabolismo , Hormônio Luteinizante/sangue , Orexinas , Periodicidade , Ratos , Ratos Wistar , Resposta de Saciedade/fisiologia , Estresse Psicológico/sangue , Estresse Psicológico/metabolismo , Fatores de TempoRESUMO
Tuberoinfundibular dopaminergic (TIDA) neurons in the arcuate nucleus (ARC) of the hypothalamus play a role in inhibiting prolactin (PRL) secretion from the anterior pituitary. PRL is involved in a variety of behaviors, including feeding. Consequently, we hypothesized that fasting might reduce the activity of TIDA neurons, which might alter PRL secretion. However, direct examinations of TIDA neuron activity are difficult. Recently, transgenic mice were generated that expressed green fluorescent protein (GFP) under the control of the rat tyrosine hydroxylase gene. We first determined that GFP in the dorsomedial ARC was a reliable marker of TIDA neurons. Then, we performed electrophysiology and immunocytochemistry in GFP-labeled TIDA neurons to examine whether different feeding conditions could change their activity. Eight-week-old male mice were fed or fasted for 24â¯h. After sacrifice, we prepared acutely isolated brain slices for conducting whole-cell voltage-clamp recordings. TIDA neurons were identified with fluorescence microscopy. The mean amplitude of miniature excitatory postsynaptic currents (mEPSCs) was significantly reduced in fasting mice compared to fed mice, but different feeding conditions did not affect the mean mEPSC intervals. This result suggested that fasting reduced the number of excitatory synaptic inputs to TIDA neurons. To determine whether a reduction in excitatory synaptic inputs would cause a reduction in TIDA neuron activity, we examined the effect of 24-h fasting on c-Fos expression in the ARC. We found that fasting significantly reduced the number of Fos-positive TIDA neurons. In addition, serum PRL levels were significantly increased. Taken together, the present findings suggested that short-term fasting attenuated TIDA neuron activity.
Assuntos
Núcleo Arqueado do Hipotálamo/metabolismo , Neurônios Dopaminérgicos/metabolismo , Jejum/fisiologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Animais , Proteínas de Fluorescência Verde , Masculino , Camundongos , Camundongos Transgênicos , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
The states of pregnancy and lactation bring about a range of physiological and behavioral changes in the adult mammal that prepare the mother to care for her young. In the present study, the effects of pregnancy on cell proliferation in the subventricular zone (SVZ) in female rats were examined. This region has been identified as a site of neurogenesis in adult rodents. To examine the proliferating cell population, control and pregnant rats were injected with bromodeoxyuridine (BrdU, 90 mg/kg, i.v.) and euthanized 1 h following injection. BrdU was visualized using diaminobenzidine. Changes in BrdU-labeled cells occurred in the female rat brain over pregnancy with significant increases found in the SVZ on day 21 when compared with cycling diestrous females. No changes were evident in the dentate gyrus of the hippocampus as a function of gestation. These data demonstrate that, in the rat, as in mice, gestation stimulates an increase in the number of new cells in selected regions of the central nervous system.
Assuntos
Proliferação de Células , Ventrículos Laterais/citologia , Neurônios/citologia , Gravidez/fisiologia , Análise de Variância , Animais , Bromodesoxiuridina/metabolismo , Contagem de Células/métodos , Feminino , Imuno-Histoquímica/métodos , Ventrículos Laterais/crescimento & desenvolvimento , Fosfopiruvato Hidratase/metabolismo , Ratos , Ratos Sprague-Dawley , Fatores de TempoRESUMO
A ketogenic diet was recently shown to reduce glutamate accumulation in synaptic vesicles, decreasing glutamate transmission. We questioned whether a ketogenic diet affects hippocampal function, as glutamate transmission is critically involved in visuospatial ability. In the present study, male Wistar rats were maintained on a ketogenic diet containing 10% protein and 90% fat with complements for 3 weeks to change their energy expenditure from glucose-dependent to fat-dependent. Control rats were fed a diet containing 10% protein, 10% fat, and 80% carbohydrates. The fat-dependent energy expenditure induced by the ketogenic diet led to decreased body weight and increased blood ketone production, though the rats in the two groups consumed the same number of calories. The ketogenic diet did not alter food preferences for the control or high-fat diet containing 10% protein, 45% fat, and 45% carbohydrates. Anxiety in the open field was not altered by ingestion the ketogenic diet. However, rats fed the ketogenic diet performed better in the Y-maze test than rats fed the control diet. No difference was observed between the two groups in the Morris water maze test. Finally, Western blot revealed that the hippocampal expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptor subunit 1 (GluR1) was significantly increased in mice fed a ketogenic diet. These results suggest that hippocampal function is not impaired by a ketogenic diet and we speculate that the fat-dependent energy expenditure does not impair visuospatial ability.
Assuntos
Dieta Cetogênica , Hipocampo/fisiologia , Aprendizagem em Labirinto/fisiologia , Navegação Espacial/fisiologia , Ração Animal , Animais , Ansiedade/fisiopatologia , Glicemia/fisiologia , Western Blotting , Peso Corporal/fisiologia , Ácido Butírico/sangue , Comportamento de Escolha/fisiologia , Comportamento Alimentar/fisiologia , Masculino , Ratos , Ratos Wistar , Receptores de AMPA/metabolismo , Percepção GustatóriaRESUMO
It has been suspected that endocrine disrupters induce abnormal differentiation and development of reproductive organs. In the present study, we examined whether exposure to bisphenol A (BPA), a known endocrine disrupter, during gestation and lactation affects sex difference in the number of corticotropin-releasing hormone-immunoreactive neurons (CRH neurons) in the preoptic area (POA) and the bed nucleus of the stria terminalis (BST). For that purpose, pregnant female Wistar rats (n=8-11 per treatment group) were treated with either 0.1% ethanol (control group) or 10 mg/l BPA (BPA group) dissolved in their drinking water until their offspring were weaned. In the control group, we confirmed a previous report that the POA of female rats contained significantly more CRH neurons than that of male rats (p<0.05). This significant sex difference was also evident in the BPA group, indicating that BPA exposure used in the present study had no effect on the sex difference in CRH neurons in the POA. We also found in the control group that the BST of female rats contained significantly more CRH neurons (p<0.05) than that of male rats. However, this significant sex difference was not observed in the BPA group (p>0.05), suggesting that BPA exposure affected the sex difference in CRH neurons in the BST. Since there was no statistically significant difference in the number of CRH neurons between the control and the BPA group, irrespective of the sex, the results suggested that a loss of sex difference in CRH neurons was due to both an increase in CRH neurons in male rats and a decrease in CRH neurons in female rats. The present study indicates that there is a significant sex difference in the number of CRH neurons in the BST as well as in the POA and that exposure to BPA during gestation and lactation causes a loss of this sex difference in the rat BST, but not in the POA. We suggest that CRH neurons in the BST are more susceptible to endocrine disrupters than those in the POA, irrespective of the sex.
Assuntos
Hormônio Liberador da Corticotropina/efeitos dos fármacos , Fenóis/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Núcleos Septais/efeitos dos fármacos , Diferenciação Sexual/efeitos dos fármacos , Animais , Compostos Benzidrílicos , Hormônio Liberador da Corticotropina/metabolismo , Estrogênios não Esteroides/toxicidade , Feminino , Imuno-Histoquímica , Lactação , Masculino , Leite/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Gravidez , Área Pré-Óptica/citologia , Área Pré-Óptica/efeitos dos fármacos , Área Pré-Óptica/metabolismo , Ratos , Ratos Wistar , Núcleos Septais/citologia , Núcleos Septais/metabolismo , Caracteres SexuaisRESUMO
Increasing evidence demonstrates a connection between growth factor function (including brain-derived neurotrophic factor, BDNF), glucocorticoid levels (one of the steroid hormones), and the pathophysiology of depressive disorders. Because both BDNF and glucocorticoids regulate synaptic function in the central nervous system, their functional interaction is of major concern. Interestingly, alterations in levels of estrogen, another steroid hormone, may play a role in depressive-like behavior in postpartum females with fluctuations of BDNF-related molecules in the brain. BDNF and cytokines, which are protein regulators of inflammation, stimulate multiple intracellular signaling cascades involved in neuropsychiatric illness. Pro-inflammatory cytokines may increase vulnerability to depressive symptoms, such as the increased risk observed in patients with cancer and/or autoimmune diseases. In this review, we discuss the possible relationship between inflammation and depression, in addition to the cross-talk among cytokines, BDNF, and steroids. Further, since nutritional status has been shown to affect critical pathways involved in depression through both BDNF function and the monoamine system, we also review current evidence surrounding diet and supplementation (e.g., flavonoids) on BDNF-mediated brain functions.
RESUMO
We previously described sex differences in the number of corticotropin-releasing hormone-immunoreactive (CRH-ir) neurons in the dorsolateral division of the bed nucleus of the stria terminalis (BSTLD). Female rats were found to have more CRH neurons than male rats. We hypothesized that testosterone exposure during the critical period of sexual differentiation of the brain decreased the number of CRH-ir neurons in the hypothalamus, including the BSTLD and preoptic area. In the present study we confirm that testosterone exposure during the neonatal period results in changes to a variety of typical aspects of the female reproductive system, including estrous cyclicity as shown by virginal smear, the positive feedback effects of estrogen alone or combined with progesterone, luteinizing hormone secretions, and estrogen and progesterone-induced Fos expression in gonadotropin-releasing hormone neurons. The number of CRH-ir neurons in the preoptic area did not change, whereas CRH-ir neurons in the BSTLD significantly decreased in estrogen-primed ovariectomized rats exposed to testosterone during the neonatal period. These results suggest that the sexual differentiation of CRH neurons in the BSTLD is a result of testosterone exposure during the critical period and the BSTLD is more fragile than the preoptic area during sexual differentiation. Furthermore, sex differences in CRH in the preoptic area may not be caused by testosterone during this period.
Assuntos
Hormônio Liberador da Corticotropina/metabolismo , Neurônios/metabolismo , Núcleos Septais/efeitos dos fármacos , Testosterona/farmacologia , Animais , Animais Recém-Nascidos , Ciclo Estral/efeitos dos fármacos , Feminino , Hormônio Luteinizante/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Wistar , Reprodução/efeitos dos fármacos , Núcleos Septais/citologia , Núcleos Septais/metabolismo , Diferenciação SexualRESUMO
Contributions from estrogen receptor (ER) subtypes (ERα and ERß) to postpartum anxiogenic and depressive responses remain unresolved in rats. Using the elevated-plus maze (EPM) and forced swim (FS) tests, we confirmed that primiparous rats exhibited anxiogenic and depressive responses 3 weeks postpartum, improved 5 weeks postpartum (EPM), and recovered at 5 (FS) or 10 weeks postpartum (EPM) compared with diestrus nulliparous females. Immunohistochemistry suggested that these behavioral changes were temporally associated with decreased ERα but not ERß expression in the medial amygdala (MEA). Additionally, ERα expression in the medial preoptic area (MPOA) significantly increased 10 weeks postpartum. Brain-derived neurotrophic factor (BDNF) expression was significantly elevated in the MEA 3 weeks postpartum. BDNF receptor tropomyosin-related kinase expression was significantly elevated in the MEA at 3 and 10 weeks but not at 5 weeks postpartum. The phosphorylation of ERK (pERK)-2 in the MEA, MPOA, and hippocampal CA1 region was significantly elevated 3 and 5 weeks postpartum. The effects of single daily sc injections of the ERα-selective agonist, propyl pyrazoletriol (PPT); ERß-selective agonist, diarylpropionitrile; 17ß-estradiol (E2); and vehicle for 6 days in primiparous rats were assessed. PPT and E2 significantly produced anxiolytic and antidepressant actions in the EPM and FS tests but PPT to a lesser degree than E2 in the EPM test. Diarylpropionitrile affected the EPM test but was not significantly different from vehicle. BDNF expression was significantly increased 3 weeks postpartum by all treatments in the MPOA but not the CA1 and MEA. E2 and PPT treatment significantly increased tropomyosin-related kinase and pERK1/2 expression in the MEA and MPOA and increased pERK1/2 expression in the CA1. The onset of anxiety- and depression-like behaviors in postpartum rats may be partly caused by a complex estrogen-mediated mechanism; nevertheless, changes in the ERα-related system, likely in the MEA, are predominantly involved.
Assuntos
Tonsila do Cerebelo/efeitos dos fármacos , Ansiedade/tratamento farmacológico , Depressão Pós-Parto/tratamento farmacológico , Receptor alfa de Estrogênio/agonistas , Estrogênios/uso terapêutico , Neurônios/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Tonsila do Cerebelo/metabolismo , Animais , Ansiolíticos/uso terapêutico , Antidepressivos/uso terapêutico , Ansiedade/etiologia , Comportamento Animal/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Região CA1 Hipocampal/efeitos dos fármacos , Região CA1 Hipocampal/metabolismo , Estradiol/uso terapêutico , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/agonistas , Receptor beta de Estrogênio/metabolismo , Estrogênios/metabolismo , Feminino , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Neurônios/metabolismo , Fenóis , Área Pré-Óptica/efeitos dos fármacos , Área Pré-Óptica/metabolismo , Pirazóis/uso terapêutico , Ratos , Ratos Long-Evans , Receptor trkB/metabolismoRESUMO
In the present study, we examined sex-specific changes in luteinizing hormone (LH) secretion and Fos expression in gonadotropin-releasing hormone (GnRH) neurons in response to naloxone in young (3 months old) and old (24 months old), gonadectomized male and female rats. We revealed by immunocytochemistry that, regardless of age and sex, naloxone significantly increased the number of GnRH neurons expressing Fos, which was associated with increased LH secretion. Additionally, although the magnitude of the increase in Fos-expressing GnRH neurons did not change in old males compared to young males, it was attenuated by almost half in old females compared to young females. LH levels decreased 60% in old males compared to young males and 15% in old females compared to young females. These results suggest LH secretion is impaired with age, but the ability of GnRH neurons to be stimulated by naloxone is preserved. However, the opioid-controlling mechanism is more fragile in females than males during aging.
Assuntos
Hormônio Liberador de Gonadotropina/metabolismo , Hormônio Luteinizante/metabolismo , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Neurônios/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-fos/biossíntese , Envelhecimento/fisiologia , Animais , Retroalimentação Fisiológica , Feminino , Masculino , Neurônios/fisiologia , Orquiectomia , Ovariectomia , Ratos , Ratos Wistar , Fatores SexuaisRESUMO
Intrauterine growth retardation (IUGR) is putatively involved in the pathophysiology of schizophrenia. The animal model of IUGR induced by synthetic thromboxane A2 (TXA2) is useful to clarify the effect of IUGR on pups' brains, however, analysis at the cellular level is still needed. Brain-derived neurotrophic factor (BDNF), which plays a role in neuronal survival and synaptic plasticity in the central nervous system (CNS), may also be associated with schizophrenia. However, the possible relationship between IUGR and BDNF function remains unclear. Here, we examined how IUGR by TXA2 impacts BDNF function by using dissociated cortical neurons. We found that, although BDNF levels in cultured neurons from the cerebral cortex of low birth weight pups with IUGR were unchanged, TrkB (BDNF receptor) was decreased compared with control-rats. BDNF-stimulated MAPK/ERK1/2 and PI3K/Akt pathways, which are downstream intracellular signaling pathways of TrkB, were repressed in IUGR-rat cultures. Expression of glutamate receptors such as GluA1 and GluN2A was also suppressed in IUGR-rat cultures. Furthermore, in IUGR-rat cultures, anti-apoptotic protein Bcl2 was decreased and BDNF failed to prevent neurons from cell death caused by serum-deprivation. Taken together, IUGR resulted in reductions in cell viability and in synaptic function following TrkB down-regulation, which may play a role in schizophrenia-like behaviors.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/fisiologia , Córtex Cerebral/metabolismo , Retardo do Crescimento Fetal/metabolismo , Neurônios/metabolismo , Animais , Fator Neurotrófico Derivado do Encéfalo/farmacologia , Morte Celular , Sobrevivência Celular , Células Cultivadas , Córtex Cerebral/efeitos dos fármacos , Feminino , Retardo do Crescimento Fetal/patologia , Neurônios/efeitos dos fármacos , Neurônios/patologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Long-Evans , Receptor trkB/metabolismo , Receptores de AMPA/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismoRESUMO
Glucocorticoids are known to cause psychiatric disorders including depression. Prednisolone (PSL) is one of the most widely used synthetic glucocorticoids to treat various medical diseases; however, little is known about PSL-induced behavioral changes and its molecular basis in the brain. Growing evidence has implicated that hippocampal remodeling or damage play a role in the pathogenic effect of glucocorticoids. In this study, mice were administered PSL (50 or 100mg/kg) or vehicle for 6 or 7 days and subjected to a series of behavioral tests, i.e., open field, elevated plus maze, prepulse inhibition, forced swim, and tail suspension tests. Hippocampal tissues were subject to microarray analysis using the GeneChip Mouse Genome 430 2.0 Array (Affymetrix) containing 45,101 probes of transcripts. Increased anxiety- and depression-like behaviors assessed with open field, elevated plus maze, and tail suspension tests were observed. Microarray analysis detected 108 transcripts with a fold change of >2.0 or <0.5 in which many cell-death-related genes were found. The microarray data was validated by quantitative reverse transcriptase-polymerase chain reaction analysis. Our results demonstrated that PSL causes anxiety- and depression-like behaviors, and suggest that altered gene expressions related to hippocampal remodeling or damage are involved in the effect of PSL on such behaviors.
Assuntos
Ansiedade , Apoptose/genética , Depressão , Regulação da Expressão Gênica/efeitos dos fármacos , Hipocampo/metabolismo , Prednisolona , Estimulação Acústica/métodos , Animais , Ansiedade/induzido quimicamente , Ansiedade/metabolismo , Ansiedade/patologia , Apoptose/efeitos dos fármacos , Depressão/induzido quimicamente , Depressão/metabolismo , Depressão/patologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Comportamento Exploratório/efeitos dos fármacos , Perfilação da Expressão Gênica/métodos , Elevação dos Membros Posteriores/métodos , Hipocampo/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Inibição Neural/efeitos dos fármacos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Prednisolona/farmacologia , Reflexo de Sobressalto/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Natação/psicologiaRESUMO
We examined the induction of progesterone receptor-immunoreactive (PR-ir) cells by estrogen in the rat preoptic area and ventromedial hypothalamic nucleus. Ovariectomized young (3-month-old) and old (24-month-old) female rats were treated with estrogen or cholesterol for 4 days. Estrogen significantly increased PR-ir cells in the preoptic area and ventromedial hypothalamic nucleus in young rats. Cholesterol-treated old rats had very few PR-ir cells; estrogen treatment significantly increased the number of PR-ir cells in both the preoptic area and the ventromedial hypothalamic nucleus in old rats, although less than in young rats. Therefore, the ability of estrogen to induce PR immunoreactivity in the hypothalamus in ovariectomized rats is attenuated in old rats compared with young rats.
Assuntos
Envelhecimento/fisiologia , Encéfalo/metabolismo , Receptores de Progesterona/biossíntese , Animais , Encéfalo/efeitos dos fármacos , Estrogênios/farmacologia , Feminino , Imuno-Histoquímica , Ovariectomia , Ratos , Ratos Wistar , Receptores de Progesterona/efeitos dos fármacosRESUMO
The states of pregnancy and lactation bring about a range of physiological and behavioral changes in the adult mammal that prepare the mother to care for her young. Cell proliferation increases in the subventricular zone (SVZ) of the female rodent brain during both pregnancy and lactation when compared to that in cycling, diestrous females. In the present study, the effects of maternal behavior induction and pup exposure on neurogenesis in nulliparous rats were examined in order to determine whether maternal behavior itself, independent of pregnancy and lactation, might affect neurogenesis. Adult, nulliparous, Sprague-Dawley, female rats were exposed daily to foster young in order to induce maternal behavior. Following the induction of maternal behavior each maternal subject plus females that were exposed to pups for a comparable number of test days, but did not display maternal behavior, and subjects that had received no pup exposure were injected with bromodeoxyuridine (BrdU, 90 mg/kg, i.v.). Brain sections were double-labeled for BrdU and the neural marker, NeuN, to examine the proliferating cell population. Increases in the number of double-labeled cells were found in the maternal virgin brain when compared with the number of double-labeled cells present in non-maternal, pup-exposed nulliparous rats and in females not exposed to young. No changes were evident in the dentate gyrus of the hippocampus as a function of maternal behavior. These data indicate that in nulliparous female rats maternal behavior itself is associated with the stimulation of neurogenesis in the SVZ.
Assuntos
Encéfalo/fisiologia , Comportamento Materno/fisiologia , Neurogênese/fisiologia , Neurônios/fisiologia , Paridade/fisiologia , Animais , Bromodesoxiuridina , Contagem de Células , Proliferação de Células , Giro Denteado/fisiologia , Feminino , Imuno-Histoquímica , Gravidez , Ratos , Ratos Sprague-Dawley , Comportamento Sexual Animal , Nicho de Células-Tronco/fisiologia , Fatores de TempoAssuntos
Doenças Cardiovasculares/metabolismo , Deficiências de Ferro , Obesidade/metabolismo , Animais , Feminino , Humanos , GravidezRESUMO
p-Nonylphenol (NP) and 4-tert-octylphenol (OP) are known to mimic the action of estrogens as endocrine disruptors. However, their acute effects on the pituitary and the hypothalamus functions in vivo have been uncertain. We therefore determined their effects on the anterior pituitary, in particular, gonadotropin secretion. Two weeks after ovariectomy, the rats were given a subcutaneous injection of 10 mg NP, 10 mg OP, 10 mg bisphenol A, 1 microg 17beta-estradiol, or sesame oil alone as control. Twenty-four hours after the treatment, the expression of progesterone receptor mRNA in the anterior pituitary and the level of luteinizing hormone (LH), follicle-stimulating hormone, and prolactin were determined. The expression of progesterone receptor mRNA in the anterior pituitary was significantly increased by either NP, OP, bisphenol A, or estradiol, but bisphenol A was less effective. The level of LH was significantly decreased by either NP or OP, but not by bisphenol A and estradiol. Only estradiol significantly increased the level of prolactin. The level of follicle-stimulating hormone was unchanged by any of the treatments. To check the effects of NP and OP on pulsatile LH secretion, blood samplings were done at 6-min intervals for 3 h. Twenty-four hours after treatment in ovariectomized adult rats, we found that the injection of NP significantly decreased the amplitude of LH pulses and the mean LH concentrations, but not the frequency of LH pulses. The injection of OP significantly decreased the mean LH concentrations without affecting the frequency and amplitude of the LH pulses. Finally, the rats given an injection of NP or sesame oil were intravenously injected with 50 ng of gonadotropin-releasing hormone (GnRH) to check whether NP affected the LH secretory responsiveness of the anterior pituitary to GnRH. We found that the responsiveness to GnRH in NP-injected rats was significantly attenuated compared to the sesame oil-injected rats. The present study suggests that NP, even with a single injection, suppresses the pulsatile LH secretion in adult ovariectomized rats, probably by affecting the anterior pituitary level.
Assuntos
Ovariectomia , Fenóis/farmacologia , Adeno-Hipófise/efeitos dos fármacos , Adeno-Hipófise/fisiologia , Animais , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Prolactina/sangue , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismoRESUMO
Orexins are hypothalamic neuropeptides which stimulate luteinizing hormone (LH) secretion in estrogen- and progesterone-treated ovariectomized (OVX) rats and suppress it in OVX rats not treated with estrogen, suggesting a modulation by estrogen of the response to orexins. We examined the effects of orexin A on pulsatile LH secretion in OVX rats treated with a very small dose of estrogen so as to maintain the pulsatile secretion of LH. The estrogen treatment was done 24 h before the blood sampling by subcutaneously implanting a silicone tube (id = 1.5 mm, od = 2.5 mm, length = 25 mm) containing 17beta-estradiol (E(2)) dissolved in sesame oil at 20 microg/ml. In OVX rats treated with sesame oil as a control, the intracerebroventricular (icv) injection of orexin A (0.3 nmol, dissolved in 3 microl artificial cerebrospinal fluid) had no significant effect on the parameters of pulsatile LH secretion, i.e., pulse frequency and pulse amplitude, although it caused a small but statistically significant decrease in overall mean LH concentrations within 1 h. In OVX rats treated with E(2), the icv injection of orexin A significantly suppressed the pulsatile LH secretion; the frequency decreased for more than 2 h, inducing a rapid decline in overall mean LH concentrations. In view of the finding that a much higher dose of orexin A suppresses pulsatile LH secretion in OVX rats not treated with E(2), we suggest that the suppressive action of orexin A on pulsatile LH secretion is potentiated by estrogen.
Assuntos
Proteínas de Transporte/farmacologia , Estradiol/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular , Hormônio Luteinizante/metabolismo , Neuropeptídeos/farmacologia , Ovariectomia , Animais , Proteínas de Transporte/administração & dosagem , Implantes de Medicamento , Sinergismo Farmacológico , Estradiol/administração & dosagem , Feminino , Injeções Intraventriculares , Hormônio Luteinizante/sangue , Neuropeptídeos/administração & dosagem , Orexinas , Periodicidade , Ratos , Ratos WistarRESUMO
We examined the effects of intracerebroventricular injection of neuromedin U (NMU), at a dose that is reported to induce satiety in rats, on the pulsatile luteinizing hormone (LH) secretion in adult ovariectomized (OVX) rats under a normal feeding or a 48-h fasted condition. In OVX rats under the normal feeding condition, injection of NMU (1 nmol/3 microl) significantly decreased the mean LH concentration without affecting the frequency or amplitude of LH pulses, but under the 48-h fasted condition, it significantly decreased the mean LH concentration and the frequency of LH pulses without affecting the amplitude. The interpulse interval was significantly lengthened by NMU injection under the normal and the 48-h fasted condition, but the effect under the 48-h fasted condition was greater than under the normal feeding condition. We also confirmed that the 48-h fasted condition per se did not affect the pulsatile LH secretion in OVX rats. We suggest that NMU and fasting synergistically inhibit the pulsatile LH secretion, even though NMU has been said to act as a satiety factor.