Prenatal restraint stress affects the expression of neuronal nicotinic acetylcholine receptor in the brain of adult rat offspring

BAIER C.J.; FRANCO D.L.; PALLARÉS M.E.; ADROVER E.; ANTONELLI M.C.; CAVIEDES P.; BARRANTES FJ

Cancún

Congreso; 24th Biennial Meeting ISN/ASN 2013; 2013

International Society for Neurochemistry

In animal models, maternal disturbance can influence offspring?s brain chemistry, endocrine function, emotionality and learning ability. In particular, stress exposure has been shown to exacerbate Alzheimer´s disease (AD)-related cognitive deficits. In addition to the characteristic neuropathological findings -the presence of senile plaques and neurofibrillary tangles- the loss of cholinergic neurons and neuronal nicotinic acetylcholine receptors (AChR) are among the most significant changes occurring in AD. The relationship between maternal stress and development of AD in offspring remains to be elucidated. The aim of the present study was to investigate whether prenatal restrain stress affects the expression of AChR in the brain of adult offspring. Western blot assays showed that in the cortex of adult, prenatally stressed rats, the levels of a7 and a4 AChR subunits were lower (~30-40%) than in undisturbed animals. These results were confirmed by immunohistochemistry using anti-a7 and -a4 AChR subunit antibodies in serial coronal sections throughout the rostrocaudal extent of the structure. Stress during pregnancy results in activation of the hypothalamic-pituitary-adrenal (HPA) axis. Therefore, high levels of corticosterone secreted in response to stress by the gestant mother might be one of the predisposing factors for the changes observed in AChR in the adult rat brain. In order to determine whether corticosterone directly affected the expression of AChR we performed in vitro experiments using a cell line derived from cerebral cortex that exhibits a cholinergic phenotype (CNh cells). In agreement with in vivo results, Western blot and fluorescence microscopy experiments showed that CNh cells treated with exogenous corticosterone at different times express lower levels of AChR-containing a7 and a4 subunits. These results suggest that adverse, stressful conditions in utero might affect the development of the cholinergic system and that corticosterone could be directly involved in the observed changes in AChR expression.