title: Corticosterone affects the differentiation of a neuronal cerebral cortex-derived cell line through modulation of the nicotinic acetylcholine receptor.
abstract: 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 α7-type neuronal AChR and, to a lesser extent, of α4-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 α7-AChR-GFP abolished the CORT effects on the cell cycle and the specific α7-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 α7-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.
authors.affiliation: Laboratory of Molecular Neurobiology, Institute of Biomedical Research (BIOMED)-UCA-CONICET, Faculty of Medical Sciences, Pontifical Catholic University of Argentina, and CONICET, Buenos Aires, Argentina; Instituto de Investigaciones Bioquímicas de Bahía Blanca, Argentina.
authors.forename: C J
authors.initials: CJ
authors.lastname: Baier
authors.affiliation: Laboratory of Molecular Neurobiology, Institute of Biomedical Research (BIOMED)-UCA-CONICET, Faculty of Medical Sciences, Pontifical Catholic University of Argentina, and CONICET, Buenos Aires, Argentina.
authors.forename: D L
authors.initials: DL
authors.lastname: Franco
authors.affiliation: Laboratorio de Toxicología, Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, Bahía Blanca, Argentina.
authors.forename: C E
authors.initials: CE
authors.lastname: Gallegos
authors.affiliation: Laboratorio de Plasticidad Neuronal, Fundación Instituto Leloir-CONICET, Buenos Aires, Argentina.
authors.forename: L A
authors.initials: LA
authors.lastname: Mongiat
authors.affiliation: Laboratorio de Neurofisiología y Farmacología Molecular, Instituto de Investigaciones Bioquímicas de Bahía Blanca, B8000FWB Bahía Blanca, Argentina.
authors.forename: L
authors.initials: L
authors.lastname: Dionisio
authors.affiliation: Laboratorio de Neurofisiología y Farmacología Molecular, Instituto de Investigaciones Bioquímicas de Bahía Blanca, B8000FWB Bahía Blanca, Argentina.
authors.forename: C
authors.initials: C
authors.lastname: Bouzat
authors.affiliation: Program of Molecular and Clinical Pharmacology, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile. Electronic address: pcaviede@med.uchile.cl.
authors.forename: P
authors.initials: P
authors.lastname: Caviedes
authors.affiliation: Laboratory of Molecular Neurobiology, Institute of Biomedical Research (BIOMED)-UCA-CONICET, Faculty of Medical Sciences, Pontifical Catholic University of Argentina, and CONICET, Buenos Aires, Argentina. Electronic address: rtfjb1@yahoo.com.
authors.forename: F J
authors.initials: FJ
authors.lastname: Barrantes
mesh_terms: D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D003345:Corticosterone / Q000378:metabolism*; D051379:Mice; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*
chemical_list: D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; C054634:methyllycaconitine; D009538:Nicotine; D003345:Corticosterone; D000157:Aconitine
keywords: cell cycle; glucocorticoids; ion channel; nicotine; stress