CORTICOSTERONE AFFECTS THE DIFFERENTIATION OF A NEURONAL CEREBRAL CORTEX-DERIVED CELL LINE THROUGH MODULATION OF THE NICOTINIC ACETYLCHOLINE RECEPTOR

Chronic exposure to stress hormones has an impact on brain structures relevant to cognition. Nicotinic acetylcholine receptors (AChRs) are involved in numerous cognitive processes including learning and memory formation. In order to better understand the molecular mechanisms of chronic stress-triggered mental disease, the effect of corticosterone (CORT) on the biology of AChRs was studied in the neuronal cell line CNh. We found that chronic treatment with CORT reduced the expression levels of the alpha 7-type neuronal AChR and, to a lesser extent, of alpha 4-AChR. CORT also delayed the acquisition of the mature cell phenotype in CNh cells. Chronic nicotine treatment affected the differentiation of CNh cells and exerted a synergistic effect with CORT, suggesting that AChR could participate in signaling pathways that control the cell cycle. Overexpression of alpha 7-AChR-GFP abolished the CORT effects on the cell cycle and the specific alpha 7-AChR inhibitor, methyllycaconitine, mimicked the proliferative action exerted by CORT. Whole-cell voltage-clamp recordings showed a significant decrease in nicotine-evoked currents in CORT-treated cells. Taken together, these observations indicate that AChRs, and the alpha 7-AChR in particular, could act as modulators of the differentiation of CNh cells and that CORT could impair the acquisition of a mature phenotype by affecting the function of this AChR subtype. (C) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.