Corticosterone halts differentiation of a neuronal cell line via acetylcholine receptor modulation

Abstract

In previous work we determined that prenatal stress affects the expression of α7 nicotinic acetylcholine receptor (α7-AChR) in the frontal cortex of adult rat offspring. The aim of the present study was to investigate whether corticosterone (CORT) affects the biology of AChRs. A neuronal cell line (CNh) derived from cerebral cortex and exhibiting a cholinergic phenotype was treated with CORT (1μM). Whole-cell voltage-clamp recordings showed functional AChR expression at the plasma membrane. Upon treatment with CORT, CNh cells expressed lower levels of α7- AChR (~60% of that in control cells). As a control, α4-AChR was found not to be affected. Morphometric analyses showed that CORT delayed the acquisition of the mature CNh cell phenotype. After 48 h in differentiation medium, cell cycle analysis using flow cytometry showed that control CNh cells were arrested in the G0/ G1 phase (~65-70%), whereas cells grown in the presence of CORT remained undifferentiated (G0/G1<60%). Nicotine treatment affected the differentiation of CNh cells and exerted a synergistic effect together with CORT (G0/G1~40%, G2/M~55-60%). Transfection of CNh cells with GFP-tagged α7-AChR abolished the alterations in the cell cycle in CORT-treated cells. Thus, α7- AChR could act as a modulator of the differentiation of CNh cells and CORT, through this receptor, could impair the acquisition of a mature phenotype.