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

FRANCO DIANA LORENA; BAIER CARLOS JAVIER; GALLEGOS CRISTINA EUGENIA; MONGIAT LUCAS ALBERTO; DIONISIO L; BAUZAT CECILIA; CAVIEDES PABLO; BARRANTES FJ

NEUROSCIENCE

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2014

0306-4522

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 a7-type neuronal AChR and, to a lesser extent, of a4-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 a7-AChR-GFP abolished the CORT effects on the cell cycle and the specific a7-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 a7-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.