Chronic Social Stress Impairs Prefrontal Cortical Myelination And Cognitive Functions In Juvenile Mice

Children and adolescents face significant social challenge.Studies on school bully indicated that social defeated primary and middle school students showed impaired cognitive functions associated with prefrontal cortex(PFC).However,the underlying mechanism remains unclear.Prefrontal cortex is the last completely myelinated brain area,which is particularly vulnerable to negative social experience.In this work,the male C57BL/6mice(Postnatal 21 days)were subjected to repeated social defeat by different aggressive CD-1 mice in 10 consecutive days.We used chronic social defeat(CSD)model to examine whether chronic social stress impairs prefrontal cortical myelination and cognitive functions,and analyze its underlying mechanism.Results:1)We found that postnatal 10 to 30 days is a rapid growth period of oligodendrogenesis and myelination in PFC.During the critical period,juvenile mice were exposed to chronic social stress.Behavioral tests showed that CSD induced anxiety-like behaviors and impaired PFC-depended cognitive functions.2)We found that CSD reduced the myelin basic protein(MBP)staining area in the PFC,but not affected the MBP level of the motor cortex,striatum,hippocampus and corpus callosum.We observed a significant decreased number of mature oligodendrocytes(CC1~+/OLIG2~+cells)and increased number of oligodendrocyte precursor cells(PDGRF?~+cells)in the CSD mice compared with CON mice.The present results suggest that chronic social stress impairs cognitive functions associated with the prefrontal cortex,at least in part,through regulation of oligodendrogenesis and myelination.