Clemastine enhances myelin formation in the striatum and medial prefrontal cortex and improves sociability in a neonatal rat hypoxic-ischemic model

Neonatal hypoxia-ischemia (HI) results in gray and white matter injuries, leading to impairments in social behavior and severe neurological deficits. Clemastine treatment has demonstrated efficacy in alleviating behavioral deficits in various neurological disorders by improving myelin formation. It has been suggested that the medial prefrontal cortex (mPFC) and the striatum play a key role in human social behaviors. To test whether clemastine can mitigate sociability deficits by rescuing the myelin damage in these key brain areas, we administered clemastine orally for two weeks following HI insult in neonatal rats. We demonstrated that clemastine successfully ameliorated HI-induced social deficits during adolescence, attenuated hypomyelination and promoted oligodendrocyte maturation in the striatum and mPFC. We also observed that clementine reduced proliferation and apoptosis of oligodendrocyte progenitor cells (OPCs), decreased myelin debris induced by HI in the striatum, and was accompanied by microglia morphological changes in the striatum. Furthermore, our findings revealed a positive correlation between sociability and myelin formation in the striatum and mPFC. In conclusion, our data indicate that clemastine attenuates HI-induced sociability impairments during adolescence, potentially through its role in promoting myelin formation in the striatum and mPFC.