Clomipramine treatment reversed the glial pathology in a chronic unpredictable stress-induced rat model of depression
Clomipramine treatment reversed the glial pathology in a chronic unpredictable stress-induced rat model of depression
复制标题
氯米帕明治疗逆转了慢性不可预测应激诱发的抑郁症大鼠模型中的神经胶质病理学
DOI：
10.1016/j.euroneuro.2009.06.010
复制
发表时间：
2009-11-01
影响因子：
5.6
通讯作者：
Wu, Gen-Cheng
中科院分区：
文献类型：
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作者：
Liu, Qiong;Li, Bing;Wu, Gen-Cheng
越来越多的证据表明，神经胶质病理有助于病理生理和抑郁症的病因可能。本研究探讨了慢性不可预测应激（CUS）后大鼠行为和海马神经胶质细胞相关蛋白（GFAP）的变化。此外，我们研究了氯丙咪嗪，三环类抗抑郁药（TCAs），已知调节5-羟色胺和去甲肾上腺素的摄取，对抑郁症诱导的抑郁样行为和GFAP水平的影响。CUS暴露组大鼠在物理状态、旷场实验和强迫游泳实验中表现出行为缺陷，海马GFAP表达显著降低。有趣的是，CUS诱导的行为和GFAP表达变化可被抗抑郁药氯丙咪嗪长期治疗逆转。氯丙咪嗪治疗对抑郁症诱导的抑郁样行为和GFAP表达的有益作用进一步验证了我们的假设，即胶质细胞功能障碍有助于抑郁症的病理生理学，胶质细胞成分可能是新的抗抑郁药物开发的可行靶点。(C)2009 Elsevier B.V.和ECNP。All rights reserved.
Growing evidence indicates that glia pathology contributes to the pathophysiology and possibly the etiology of depression. The study investigates changes in behaviors and glial fibrillary associated protein (GFAP) in the rat hippocampus after chronic unpredictable stress (CUS), a rat model of depression. Furthermore, we studied the effects of clomipramine, one of tricyclic antidepressants (TCAs), known to modulate serotonin and norepinephrine uptake, on CUS-induced depressive-like behaviors and GFAP levels. Rats exposed to CUS showed behavioral deficits in physical state, open field test and forced swimming test and exhibited a significant decrease in GFAP expression in the hippocampus. Interestingly, the behavioral and GFAP expression changes induced by CUS were reversed by chronic treatment with the antidepressant clomipramine. The beneficial effects of clomipramine treatment on CUS-induced depressive-like behavior and GFAP expression provide further validation of our hypothesis that glial dysfunction contributes to the pathophysiology of depression and that glial elements may represent viable targets for new antidepressant drug development. (C) 2009 Elsevier B.V. and ECNP. All rights reserved.