RESUMO
Prenatal stress (PS) strongly impacts fetal brain development and function in adulthood. In normal aging and Alzheimer's disease, there is hypothalamic-pituitary-adrenal axis dysfunction and loss of cholinergic neurons and neuronal nicotinic acetylcholine receptors (nAChRs). This study investigated whether prenatal restraint stress affects nAChR expression in the brain of adult offspring. For PS, pregnant dams were placed in a plastic restrainer for 45 min, three times daily during the last week of pregnancy; controls were undisturbed. Male offspring were analyzed at postnatal day (PND) 60 (n = 4 rats per group). Western blot (WB) and fluorescence microscopy showed that PS decreased α7-AChR subunit expression (â¼50%) in the frontal cortex in the adult offspring. PS decreased significantly the number of α7-AChR-expressing cells in the medial prefrontal cortex (by â¼25%) and in the sensory-motor cortex (by â¼20%) without affecting the total cell number in those areas. No alterations were found in the hippocampus by quantitative polymerase chain reaction (qPCR), or WB analysis, but a detailed fluorescence microscopy analysis showed that PS affected α7-AChR mainly in the CA3 and dentate gyrus subfields: PS decreased α7-AChR subunit expression by â¼25 and â¼30%, respectively. Importantly, PS decreased the number of α7-AChR-expressing cells and the total cell number (by â¼15 and 20%, respectively) in the dentate gyrus. PS differently affected α4-AChR: PS impaired its mRNA expression in the frontal cortex (by â¼50%), without affecting protein levels. These results demonstrate that disturbances during gestation produce long-term alterations in the expression pattern of α7-AChR in rat brain.
Assuntos
Encéfalo/metabolismo , Complicações na Gravidez/genética , Efeitos Tardios da Exposição Pré-Natal/genética , RNA Mensageiro/metabolismo , Estresse Psicológico/genética , Receptor Nicotínico de Acetilcolina alfa7/genética , Doença de Alzheimer , Animais , Feminino , Hipocampo/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Sistema Hipófise-Suprarrenal/metabolismo , Córtex Pré-Frontal/metabolismo , Gravidez , Complicações na Gravidez/metabolismo , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Ratos , Restrição Física , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Córtex Sensório-Motor/metabolismo , Estresse Psicológico/metabolismo , Receptor Nicotínico de Acetilcolina alfa7/metabolismoRESUMO
Stressor presence during the last weeks of gestation has been associated with behavioral disorders in later life. In this study we support further research on the long term effects of prenatal stress on Swiss mice descendant's behavior. Prenatal stress procedure consisted on restraining the dams under bright light for 45 min, three times per day from the 15th day of pregnancy, until birth. After weaning, offspring's motor performance and spontaneous exploratory behavior were measured by the tight-rope and T-maze tests, respectively. We also evaluated anxiety behavior using elevated plus maze test. We found that maternal stress improves the performance of the animals in the tight rope test and that this effect was sex and age dependent: prenatal stressed males obtained the best scores during the first month of life, while in females the same was achieved at the second month. Spontaneous exploratory behavior analysis revealed that it was elevated in prenatal stressed males and that this effect persisted on time. However, we did not find significant differences on this behavioral response among both females groups. Finally, differences on anxiety behavior were found only in females: prenatally stressed animals showed a higher proportion of entries into the open arms of a plus maze (reduced anxiety) compared to the control group. Our results show that prenatal stress modifies the normal behavior of the progeny: prenatal stressed animals have a better performance in the carried out test. These notably results suggest the existence of an adaptive response to prenatal stress.