Reduced Oligodendrocyte Precursor Cell Impairs Astrocytic Development in Early Life Stress.
Reduced Oligodendrocyte Precursor Cell Impairs Astrocytic Development in Early Life Stress.
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DOI：
10.1002/advs.202101181
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发表时间：
2021-08
期刊：
影响因子：
--
通讯作者：
Niu J
中科院分区：
文献类型：
--
作者：
Wang Y;Su Y;Yu G;Wang X;Chen X;Yu B;Cheng Y;Li R;Sáez JC;Yi C;Xiao L;Niu J
星形胶质细胞发育不良与早期生活应激相关的各种神经精神疾病有关。然而，可能导致精神症状的潜在星形细胞病变机制仍不清楚。在这项研究中，研究表明，在改进的亲代隔离小鼠模型中，少突胶质前体细胞(OPC)数量的减少伴随着海马星形细胞的发育受阻，OPC的丢失抑制了星形胶质细胞网络的形成和活动。进一步证明，OPC来源的Wnt配体，尤其是Wnt7b，是Wnt/β-catenin途径介导的星形胶质细胞发育及其与神经元功能相关的后续效应所必需的。此外，Wnt7a/b的局部补充足以挽救星形细胞发育不良。这些结果阐明了OPC对星形胶质细胞发育的调控作用依赖于Wnt旁分泌，但不依赖髓鞘，这为早期生活应激中星形细胞病变的机制提供了独特的见解，并可能参与人类早期生活应激相关神经精神疾病的发病机制。星形胶质细胞发育不良，包括星形胶质细胞网络形成缺陷，与早期生活应激引起的神经精神疾病有关。研究表明，在生命早期，少突胶质前体细胞(OPC)数量减少，应激通过OPC衍生的Wnt配体水平降低而导致星形胶质细胞发育不良，从而导致神经元功能障碍和神经精神症状。
Astrocyte maldevelopment is implicated in various neuropsychiatric diseases associated with early life stress. However, the underlying astrocytopathy mechanism, which can result in the psychiatric symptoms, remains unclear. In this study, it is shown that a reduced oligodendrocyte precursor cell (OPC) population accompanies hindered hippocampal astrocytic development in an improved parental isolation mouse model, and that the loss of OPCs suppresses astrocytic network formation and activity. It is further demonstrated that OPC‐derived Wnt ligands, in particular Wnt7b, are required for Wnt/β‐catenin pathway‐mediated astrocytic development and subsequent effects related to neuronal function. In addition, focal replenishment of Wnt7a/b is sufficient to rescue astrocytic maldevelopment. These results elucidate a Wnt‐paracrine‐dependent but myelin‐independent role of OPCs in regulating astrocytic development, which provides a unique insight into the astrocytopathy mechanism in early life stress, and can be implicated in the pathogenesis of human early life stress‐related neuropsychiatric disorders. Astrocyte maldevelopment, including defective astrocytic network formation, is implicated in neuropsychiatric diseases induced by early life stress. It is shown that reduced oligodendrocyte precursor cell (OPC) number occurred in early life stress causes astrocyte maldevelopment through decreased level of OPC‐derived Wnt ligands, which subsequently elicits neuronal dysfunction and neuropsychiatric symptoms.
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影响因子：
16.2
作者：
Kang, Shin H.;Fukaya, Masahiro;Yang, Jason K.;Rothstein, Jeffrey D.;Bergles, Dwight E.
通讯作者：
Bergles, Dwight E.
影响因子：
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作者：
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通讯作者：
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影响因子：
6.2
作者：
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通讯作者：
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成熟髓鞘神经胶质细胞中切丁酶的缺失会导致成年小鼠进行性轴突变性，但不会导致明显的脱髓鞘
影响因子：
6.2
作者：
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通讯作者：
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影响因子：
3.5
作者：
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通讯作者：
Reynolds, R