【作者】 汤明明； 潘玉芹； 管西婷； 林文娟；

【Author】 TANG Mingming;PAN Yuqin;Guan Xiting;LIN Wenjuan;Key Laboratory of Mental Health,Institute of Psychology,Chinese Academy of Science;University of Chinese Academy of Sciences;

【机构】 中国科学院心理健康重点实验室中国科学院心理研究所；

【摘要】 抑郁症的动物行为模型有很多种,如慢性温和应激、习得性无助、强迫游泳应激、嗅球切除等。它们分别从不同的病因学角度模拟抑郁症的发生。本工作介绍本实验室新建立的中枢炎性免疫抑郁模型。证据表明免疫系统在一些心理精神障碍中具有作用,抑郁症可被看作是一种心理神经免疫紊乱性疾病。生理应激和心理应激能导致免疫激活和炎性细胞因子的产生,从而影响中枢神经系统的多个方面并导致抑郁行为的产生。细胞因子在抑郁症中的作用可视为近二十年来心理神经免疫学上最令人兴奋的新进展。国际上,脂多糖(lipopolysaccharide,LPS)免疫激活模型是研究抑郁症细胞因子假说的重要动物模型。常用的手段是外周单次LPS注射诱发抑郁样行为。但该模型中抑郁行为持续仅有数小时。为建立诱发较长时程抑郁行为的免疫激活动物模型,本研究考察侧脑室重复中枢LPS诱发的行为改变的时程和细胞因子的变化。结果发现:三次重复注射LPS注射后24 h,促炎性细胞因子IL-1β、IL-6、TNF-α在前额皮质和海马中的蛋白表达显著增加;LPS注射后7天,促炎性细胞因子恢复到正常的低水平。在行为上,LPS注射后24 h抑郁行为明显,即糖水偏好下降,自发活动和探索行为减少,悬尾不动时间增加等。且自发活动、探索行为减少和悬尾不动时间的增加能够延续至末次LPS注射后72 h。LPS注射后7天,动物行为恢复正常。这些结果表明侧脑室重复LPS注射可诱发较长时程的抑郁行为。抑郁行为的产生和消失与促炎性细胞因子在脑内的表达水平的时程变化一致。进一步的考察证明,中枢炎性免疫激活诱发的抑郁行为与慢性强迫游泳应激诱发的抑郁行为相似,其促炎性细胞因子在脑内的变化也有共同之处。更多还原

【Abstract】 Increasing evidence suggests that immune inflammation is involved in depressive disorders.The aim of the present study was to develop an animal model of depression induced by central inflammation. The central inflammation was induced by triple central lipopolysaccharide(LPS) administration. The neuroinflammatory state evoked by LPS was marked by an increased production of pro-inflammatory cytokines, including interleukin-1β, interleukin-6, and tumour necrosis factor-α. It was found that the rats in the neuroinflammatory state exhibited depressive-like behaviours, including decreased saccharin preference, reduced locomotor activity,increased immobility time in the tail suspension test, and increased latency to feed in the novelty suppressed feeding test. Different from the short term of depressive-like behaviours induced by peripheral administration of LPS, this triple central LPS administration model shows that the depressive-like behaviours were exhibited not only at 24 h, but also at 72 h after repeated central LPS administration. The level of brain pro-inflammatory cytokines were concomitantly synchronised with the exhibition of depressive –like behaviors and the recovery from the altered behaviors. It was further found that that chronic antidepressant Fluoxetine relived the depressive-like behavior induced by central LPS administration. The triple repeated central LPS administration induced depressive-like behaviors were also similar with the chronic swim stress induced depressive –like behaviors in a series of behavioral tests. Both models also share some common changes of pro-inflammatory cytokines in brain.更多还原