期刊
ADVANCED SCIENCE
卷 8, 期 16, 页码 -出版社
WILEY
DOI: 10.1002/advs.202101181
关键词
astrocytic network; connexin; glial interaction; neuropsychiatric disorder; parental isolation
资金
- National Nature Science Foundation of China [NSFC 31871045, 31970921, 81971309, 31921003]
- Chongqing and Guangdong Basic and Applied Basic Research Foundation [cstc2018jcyjAX0702, 2019A1515011333]
- Shenzhen Fundamental Research Program [JCYJ20190809161405495, RCYX20200714114644167]
- Fundamental Research Funds for the Central Universities [19ykzd04]
- Centro Interdisciplinario de Neurociencias de Valparaiso (ICM-ANID) [P09-022]
This study demonstrates that reduced oligodendrocyte precursor cells (OPCs) are associated with hindered hippocampal astrocytic development in an improved parental isolation mouse model, and loss of OPCs suppresses astrocytic network formation and activity. Moreover, OPC-derived Wnt ligands, particularly Wnt7b, are essential for Wnt/beta-catenin pathway-mediated astrocytic development and neuronal function. Local replenishment of Wnt7a/b is sufficient to rescue astrocytic maldevelopment.
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/beta-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.
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