Endogenous ciliary neurotrophic factor modulates anxiety and depressive-like behavior
Endogenous ciliary neurotrophic factor modulates anxiety and depressive-like behavior
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DOI：
10.1016/j.bbr.2012.01.020
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发表时间：
2012-04
影响因子：
2.7
通讯作者：
Isabella Peruga;S. Hartwig;D. Merkler;J. Thöne;B. Hovemann;G. Juckel;R. Gold;R. Linker
中科院分区：
文献类型：
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作者：
Isabella Peruga;S. Hartwig;D. Merkler;J. Thöne;B. Hovemann;G. Juckel;R. Gold;R. Linker
在分子水平上，抑郁症的特征在于改变的单胺能神经传递以及中枢神经系统中细胞因子和其他介质的调节。特别是，神经营养因子可能会影响情感行为，包括抑郁和焦虑。睫状神经营养因子（CNTF）在神经元发育调控、神经保护和认知过程中起重要作用。在这里，我们研究了10-20周龄的CNTF缺陷小鼠（CNTF-/-小鼠）的情感行为。CNTF −/−小鼠表现出焦虑样行为增加，在亮/暗箱的亮室中花费的时间减少了30%，惊吓反应也显著增加。在习得性无助模式中，CNTF-/-小鼠更容易出现抑郁样行为。在20周龄而非10周龄的CNTF-/-小鼠海马中，这些变化与小清蛋白免疫反应性GABA能中间神经元的丢失、5-羟色胺水平以及5-HT受体1A表达的降低相关。通过长期应用抗抑郁药阿米替林和西酞普兰来调节单胺能神经递质水平并没有产生有益的效果。这些数据表明，内源性CNTF在海马功能的结构维持中起着关键作用，因此对焦虑和抑郁的啮齿动物模型中的情感行为的调制具有重要影响。
On a molecular level, depression is characterized by an altered monoaminergic neurotransmission as well as a modulation of cytokines and other mediators in the central nervous system. In particular, neurotrophic factors may influence affective behavior including depression and anxiety. Ciliary neurotrophic factor (CNTF) plays an important role in the regulation of neuronal development, neuroprotection and may also influence cognitive processes. Here we investigate the affective behavior in mice deficient for CNTF (CNTF −/− mice) at young age of 10–20 weeks. CNTF −/− mice displayed an increased anxiety-like behavior with a 30% reduction of the time spent in the bright compartment of the light/dark box as well as a significantly increased startle response. In the learned helplessness paradigm, CNTF −/− mice are more prone to depressive-like behavior. In the hippocampus of 20 weeks old, but not 10 weeks old, CNTF −/− mice, these changes correlated with a loss of parvalbumin immunoreactive GABAergic interneurons and a reduction of serotonin levels as well as 5-HT receptor 1A expression. Modulation of monoaminergic neurotransmitter levels via chronic application of the antidepressants amitriptyline and citalopram did not exert beneficial effects. These data imply that endogenous CNTF plays a pivotal role for the structural maintenance of hippocampal functions and thus has an important impact on the modulation of affective behavior in rodent models of anxiety and depression.