Prenatal restraint stress decreases the expression of alpha-7 nicotinic receptor in the brain of adult rat offspring

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 alpha 7-AChR subunit expression (similar to 50%) in the frontal cortex in the adult offspring. PS decreased significantly the number of alpha 7-AChR-expressing cells in the medial prefrontal cortex (by similar to 25%) and in the sensory-motor cortex (by similar to 20%) 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 alpha 7-AChR mainly in the CA3 and dentate gyrus subfields: PS decreased alpha 7-AChR subunit expression by similar to 25 and similar to 30%, respectively. Importantly, PS decreased the number of alpha 7-AChR-expressing cells and the total cell number (by similar to 15 and 20%, respectively) in the dentate gyrus. PS differently affected alpha 4-AChR: PS impaired its mRNA expression in the frontal cortex (by similar to 50%), without affecting protein levels. These results demonstrate that disturbances during gestation produce long-term alterations in the expression pattern of alpha 7-AChR in rat brain.