IL-6 knockout mice exhibit resistance to stress-induced development of depression-like behaviors
IL-6 knockout mice exhibit resistance to stress-induced development of depression-like behaviors
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DOI：
10.1016/j.nbd.2006.05.001
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发表时间：
2006-09-01
影响因子：
6.1
通讯作者：
Gass, Peter
中科院分区：
文献类型：
--
作者：
Chourbaji, Sabine;Urani, Alexandre;Gass, Peter
中枢神经系统中的细胞因子依赖性机制与抑郁症的发病机制有关。白细胞介素-6在抑郁症患者中上调，抗抑郁药下调。我们对IL-6缺陷小鼠（IL-6（-/-））进行了抑郁相关的测试（习得性无助、强迫游泳、悬尾、蔗糖偏好）。IL-6（-/-）小鼠在强迫游泳和悬尾实验中表现出较低的绝望感，而享乐行为则增强。此外，IL-6（-/-）小鼠表现出对无助的抵抗力。这种抗性可能是由于缺乏IL-6引起的，因为应激增加了野生型海马中IL-6的表达，这表明IL-6是抑郁症发病机制中的分子机制的一个组成部分。IL-6（-/-）小鼠代表了研究体内抑郁症病理生理学中IL-6依赖性信号传导途径的工具。此外，这些小鼠可以通过改变马槟榔碱介导的信号传导来支持用于抑郁症的化合物的筛选。(c)2006年爱思唯尔公司All rights reserved.
Cytokine-dependent mechanisms in the CNS have been implicated in the pathogenesis of depression. Interleukin-6 is upregulated in depressed patients and dowregulated by antidepressants. It is, however, unknown whether IL-6 is involved in the pathogenesis of depression.We subjected IL-6-deficient mice (IL-6(-/-)) to depression-related tests (learned helplessness, forced swimming, tail suspension, sucrose preference). We also investigated IL-6 in the hippocampus of stressed wild-type mice.IL-6(-/-) mice showed reduced despair in the forced swim, and tail suspension test, and enhanced hedonic behavior. Moreover, IL-6(-/-)mice exhibited resistance to helplessness. This resistance may be caused by the lack of IL-6, because stress increased IL-6 expression in wildtype hippocampi.This suggests that IL-6 is a component in molecular mechanisms in the pathogenesis of depression. IL-6(-/-) mice represent tools to study IL-6-dependent signaling pathways in the pathophysiology of depression in vivo. Moreover, these mice may support the screening of compounds for depression by altering cytokine-mediated signaling. (c) 2006 Elsevier Inc. All rights reserved.