Reduced Oligodendrocyte Precursor Cell Impairs Astrocytic Development in Early Life Stress

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.