Open AccessReduced Oligodendrocyte Precursor Cell Impairs Astrocytic Development in Early Life Stress
Author(s) -
Wang Yuxin,
Su Yixun,
Yu Guangdan,
Wang Xiaorui,
Chen Xiaoying,
Yu Bin,
Cheng Yijun,
Li Rui,
Sáez Juan C.,
Yi Chenju,
Xiao Lan,
Niu Jianqin
Publication year - 2021
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.202101181
Subject(s) - maldevelopment , wnt signaling pathway , astrocyte , neuroscience , oligodendrocyte , population , neurogenesis , biology , mechanism (biology) , microbiology and biotechnology , myelin , medicine , signal transduction , central nervous system , anatomy , philosophy , environmental health , epistemology
Abstract 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.