Macrophage migration inhibitory factor is critically involved in basal and fluoxetine-stimulated adult hippocampal cell proliferation and in anxiety, depression, and memory-related behaviors
Macrophage migration inhibitory factor is critically involved in basal and fluoxetine-stimulated adult hippocampal cell proliferation and in anxiety, depression, and memory-related behaviors
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DOI：
10.1038/mp.2010.15
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发表时间：
2011-05-01
影响因子：
11
通讯作者：
Sandi, C.
中科院分区：
文献类型：
--
作者：
Conboy, L.;Varea, E.;Sandi, C.
深入的研究致力于揭示介导成年海马神经发生的神经生物学机制，抗抑郁药对其的调节及其行为后果。巨噬细胞移动抑制因子（MIF）是一种在CNS中表达的促炎细胞因子，其功能尚不清楚。在这里，我们显示，第一次，MIF表达的相关性成人海马神经发生。我们确定MIF表达的神经源性细胞（干细胞，细胞增殖，并在新增殖的细胞进行成熟）在啮齿动物齿状回的颗粒下区。使用遗传学（MIF基因缺失）和药理学（用MIF拮抗剂Iso-1治疗）方法显示了MIF在细胞增殖中的因果函数。从行为上看，MIF基因缺失导致焦虑和抑郁样行为增加，以及依赖于大脑的记忆受损。总之，我们的研究提供了证据支持MIF在基础和抗抑郁药刺激的成年海马细胞增殖中的关键功能。此外，丢失的MIF导致的行为表型，在很大程度上，对应于预测产生减少海马神经发生的改变。这些发现强调了MIF作为一个潜在的相关分子靶点，用于开发与神经发生缺陷相关的治疗，以及与焦虑，抑郁和认知相关的问题。Molecular Psychiatry（2011）16，533-547; doi：10.1038/mp.2010.15; 2010年2月23日在线发表
Intensive research is devoted to unravel the neurobiological mechanisms mediating adult hippocampal neurogenesis, its regulation by antidepressants, and its behavioral consequences. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that is expressed in the CNS, where its function is unknown. Here, we show, for the first time, the relevance of MIF expression for adult hippocampal neurogenesis. We identify MIF expression in neurogenic cells (in stem cells, cells undergoing proliferation, and in newly proliferated cells undergoing maturation) in the subgranular zone of the rodent dentate gyrus. A causal function for MIF in cell proliferation was shown using genetic (MIF gene deletion) and pharmacological (treatment with the MIF antagonist Iso-1) approaches. Behaviorally, genetic deletion of MIF resulted in increased anxiety-and depression-like behaviors, as well as of impaired hippocampus-dependent memory. Together, our studies provide evidence supporting a pivotal function for MIF in both basal and antidepressant-stimulated adult hippocampal cell proliferation. Moreover, loss of MIF results in a behavioral phenotype that, to a large extent, corresponds with alterations predicted to arise from reduced hippocampal neurogenesis. These findings underscore MIF as a potentially relevant molecular target for the development of treatments linked to deficits in neurogenesis, as well as to problems related to anxiety, depression, and cognition. Molecular Psychiatry (2011) 16, 533-547; doi:10.1038/mp.2010.15; published online 23 February 2010