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BRAIN BEHAV IMMUN:研究揭示炎性免疫致抑郁症的新机制和治疗新途径

2017-07-04 佚名 中国科学院心理健康重点实验室

抑郁症是现代社会严重危害人类健康的身心疾病。关于抑郁症发病机理的假说有多种,目前具有潜力的是细胞因子假说或称炎性免疫假说。该假说认为抑郁症是一种心理-神经-免疫紊乱性疾病,机体的免疫系统在抑郁症中具有重要作用。研究组在以往研究中,证明中枢炎性免疫导致的抑郁行为与慢性应激所导致的抑郁行为类同,海马炎性细胞因子升高是两个抑郁模型的共同特征。这些研究发现表明炎性免疫是致抑郁症的关键因素。但脑内炎性免疫致

抑郁症是现代社会严重危害人类健康的身心疾病。关于抑郁症发病机理的假说有多种,目前具有潜力的是细胞因子假说或称炎性免疫假说。该假说认为抑郁症是一种心理-神经-免疫紊乱性疾病,机体的免疫系统在抑郁症中具有重要作用。研究组在以往研究中,证明中枢炎性免疫导致的抑郁行为与慢性应激所导致的抑郁行为类同,海马炎性细胞因子升高是两个抑郁模型的共同特征。这些研究发现表明炎性免疫是致抑郁症的关键因素。但脑内炎性免疫致抑郁症的机理迄今尚无清晰的阐释。

近年来研究发现炎性免疫对大脑,特别是海马的神经发生有抑制作用。神经发生(neurogenesis)也称神经元再生,是指大脑神经细胞能够自发地产生,经历发育、分化及迁移等过程,最终成为具有功能的成熟神经细胞加入原有神经网络。大脑的神经发生是大脑的自我更新、生理性稳态维持和神经可塑性的结构基础。传统观点认为,成年后的神经细胞不具有再生能力。各种原因导致的成年后神经元死亡被认为是不可逆的。随着科学技术的发展,人们开始认识到成年后大脑中新神经元仍不断地自发地产生于至少两个脑区:其一是海马的颗粒下层区域,新细胞产生后向齿状回颗粒细胞层迁移;其二是室管膜下层区域,新细胞产生后迁移至嗅球。然而,成年神经发生在炎性所致抑郁行为中究竟起什么作用并不清楚。

为弄清成年神经发生在炎性免疫所致抑郁症中扮演什么角色,中国科学院心理健康重点实验室林文娟研究员及其博士生汤明明等研究者,采用中枢炎性免疫应答造模,系统探讨炎性细胞因子调控抑郁行为与海马神经发生的关系。并采用补充外源性成纤维细胞生长因子2(Fibroblast growth factor 2,FGF2)改善或促进神经发生、观察被调控的海马神经发生与炎性免疫所致的抑郁行为的关系。研究发现,中枢炎性免疫导致神经发生的信号分子-细胞外信号调节激酶(Extracellular signal-regulated kinase ,ERK)下调,海马齿状回神经发生抑制。海马的神经发生抑制(包括神经元的增殖,新生神经元的生存和不成熟细胞数)与抑郁行为的各项指标如快感缺失,自主活动和探索行为减少,绝望情绪等显着相关。外源性FGF2能调节和提高ERK信号分子的水平, 改善了炎性免疫导致的神经发生的抑制,逆转了中枢炎性免疫所引起的抑郁样行为。这些结果表明神经发生是中枢炎性免疫诱发抑郁症状的重要机制。从调控或促进神经发生的角度,为防治炎性所致的抑郁症提供了新的途径。

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