Microglia regulate hippocampal neurogenesis during chronic neurodegeneration.
Microglia regulate hippocampal neurogenesis during chronic neurodegeneration.
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DOI：
10.1016/j.bbi.2015.11.001
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发表时间：
2016-07
期刊：
影响因子：
--
通讯作者：
Gomez-Nicola D
中科院分区：
文献类型：
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作者：
De Lucia C;Rinchon A;Olmos-Alonso A;Riecken K;Fehse B;Boche D;Perry VH;Gomez-Nicola D
小胶质细胞在朊病毒病模型中是前神经原性的。阻断小胶质细胞的扩增可以防止新生神经元的异常分化。TGFβ在慢性神经变性期间主导小胶质细胞的前神经发生作用。神经发生在神经退行性疾病中改变，部分受炎症因子调节。我们已经研究了小胶质细胞，先天免疫脑细胞，是否调节神经退行性病变中海马神经发生。使用朊病毒疾病的ME 7模型，我们应用CSF 1 R功能的获得或丧失分别作为刺激或抑制小胶质细胞增殖的手段，以剖析这些细胞对神经发生的贡献。我们发现海马神经发生的增加与小胶质细胞数量的增加有关。小胶质细胞增殖的选择性抑制引起神经发生减少和正常神经元分化的恢复，支持小胶质细胞的促神经发生作用。使用基因筛选策略，我们确定TGFβ是控制慢性神经变性中小胶质细胞促神经原性反应的分子，并得到功能丧失机制实验的支持。通过选择性靶向小胶质细胞增殖，我们已经能够揭示小胶质细胞在慢性神经退行性变中的促神经发生作用，这表明在神经退行性变期间使神经发生性生态位正常化的有希望的治疗靶点。
Microglia are proneurogenic in a model of prion disease. Blocking the expansion of microglia prevents the aberrant differentiation of newborn neurons. TGFβ dominates the proneurogenic actions of microglia during chronic neurodegeneration. Neurogenesis is altered in neurodegenerative disorders, partly regulated by inflammatory factors. We have investigated whether microglia, the innate immune brain cells, regulate hippocampal neurogenesis in neurodegeneration. Using the ME7 model of prion disease we applied gain- or loss-of CSF1R function, as means to stimulate or inhibit microglial proliferation, respectively, to dissect the contribution of these cells to neurogenesis. We found that increased hippocampal neurogenesis correlates with the expansion of the microglia population. The selective inhibition of microglial proliferation caused a reduction in neurogenesis and a restoration of normal neuronal differentiation, supporting a pro-neurogenic role for microglia. Using a gene screening strategy, we identified TGFβ as a molecule controlling the microglial pro-neurogenic response in chronic neurodegeneration, supported by loss-of-function mechanistic experiments. By the selective targeting of microglial proliferation we have been able to uncover a pro-neurogenic role for microglia in chronic neurodegeneration, suggesting promising therapeutic targets to normalise the neurogenic niche during neurodegeneration.
DOI：
10.1093/database/bap011
发表时间：
2009
期刊：
Database : the journal of biological databases and curation
影响因子：
--
作者：
Gehlenborg N;Hwang D;Lee IY;Yoo H;Baxter D;Petritis B;Pitstick R;Marzolf B;Dearmond SJ;Carlson GA;Hood L
通讯作者：
Hood L