Baier C J, Franco D L, Gallegos C E, Mongiat L A, Dionisio L, Bouzat C, Caviedes P, Barrantes F J
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.
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.
Neuroscience. 2014 Aug 22;274:369-82. doi: 10.1016/j.neuroscience.2014.05.049. Epub 2014 Jun 4.
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.
长期暴露于应激激素会对与认知相关的脑结构产生影响。烟碱型乙酰胆碱受体（AChRs）参与包括学习和记忆形成在内的众多认知过程。为了更好地理解慢性应激引发精神疾病的分子机制，我们在神经元细胞系CNh中研究了皮质酮（CORT）对AChRs生物学特性的影响。我们发现，用CORT进行长期处理会降低α7型神经元AChR的表达水平，对α4 - AChR表达水平的影响则较小。CORT还延迟了CNh细胞中成熟细胞表型的获得。长期尼古丁处理影响了CNh细胞的分化，并与CORT发挥协同作用，这表明AChR可能参与了控制细胞周期的信号通路。α7 - AChR - GFP的过表达消除了CORT对细胞周期的影响，而特异性α7 - AChR抑制剂甲基lycaconitine模拟了CORT所发挥的增殖作用。全细胞电压钳记录显示，在CORT处理的细胞中，尼古丁诱发的电流显著降低。综上所述，这些观察结果表明，AChRs，尤其是α7 - AChR，可能作为CNh细胞分化的调节因子，并且CORT可能通过影响这种AChR亚型的功能来损害成熟表型的获得。
