Oligodendrocyte Egr2 Mediates the Beneficial Effect of Resocialization on the Social Ability of Socially Isolated Mice

Early social isolation (SI) impairs social ability, which can be partially rescued after resocialization, but the underlying mechanisms have been rarely addressed. This study reported that adolescent SI mice resocialized with group housing (GH) mice, but not with SI mice, showed improved social behavior performances, increased myelination in the medial prefrontal cortex (mPFC), and upregulated Egr2 expression in oligodendrocytes (OLs). Specific down-regulation of OL Egr2 in GH companions or overexpression of OL Egr2 in SI peers abolished or rescued their repair effects on mPFC hypomyelination and social ability defects in SI mice, respectively. Furthermore, the improving effect of GH companions on OL Egr2 expression and myelinogenesis in the mPFC of SI mice was abolished when GH mice were treated with corticosterone. RNA-sequencing analysis showed that Egr2 enhanced myelination by inhibiting PDGFRα. Together, these results revealed that the Egr2/PDGFRα axis mediates distinct peer effects in rescuing SI-induced hypomyelination and social ability impairment.