Reduced Oligodendrocyte Precursor Cell Impairs Astrocytic Development in Early Life Stress,Advanced Science

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Reduced Oligodendrocyte Precursor Cell Impairs Astrocytic Development in Early Life Stress
Advanced Science ( IF 14.3 ) Pub Date : 2021-06-21 , DOI: 10.1002/advs.202101181
Yuxin Wang ₁ , Yixun Su _{1,

2} , Guangdan Yu ₁ , Xiaorui Wang ₁ , Xiaoying Chen ₁ , Bin Yu _{1,

3} , Yijun Cheng ₁ , Rui Li ₁ , Juan C Sáez ₄ , Chenju Yi ₂ , Lan Xiao _{1,

3} , Jianqin Niu ₁

Affiliation

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.

中文翻译：

少突胶质细胞前体细胞减少会损害早期生活压力下的星形胶质细胞发育

星形胶质细胞发育不良与早期生活压力相关的各种神经精神疾病有关。然而，导致精神症状的星形细胞病的潜在机制仍不清楚。本研究表明，在改进的亲本隔离小鼠模型中，少突胶质细胞前体细胞 (OPC) 数量的减少会阻碍海马星形胶质细胞的发育，并且 OPC 的缺失会抑制星形胶质细胞网络的形成和活动。进一步证明 OPC 衍生的 Wnt 配体，特别是 Wnt7b，是 Wnt/ β-连环蛋白途径介导的星形胶质细胞发育以及随后与神经元功能相关的效应所必需的。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OPCs在调节星形胶质细胞发育中的Wnt旁分泌依赖性但不依赖于髓磷脂的作用，这为了解早期生活应激中的星形细胞病变机制提供了独特的见解，并且可能涉及人类早期生活应激相关的神经精神疾病的发病机制。失调。

更新日期：2021-08-19

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