Prefrontal Cortical Demyelination Seriously Impairs Cognitive Functions In Adolescent Mice

Myelin is a substance with multilayer insulating membrane that surrounds the axon of neurons.In the central nervous system,myelin is formatted by the outgrowth of oligodendrocyte.Myelination is essential for rapid transmission of action potentials and provides axons with nutrition and protection.Demyelination could lead to a series of diseases,including multiple sclerosis,schizophrenia,depression and cognitive disorders.The prefrontal cortex(PFC)is the last matured cortex in the central nervous system,and is also the last structure that completes myelination.The PFC plays decisive roles in many cognitive functions,including attention regulation,inhibitory control of behavior,social behaviors,decision making,and reasoning,and so on.It is documented that PFC demyelination impairs working memory and attention regulation.The present work aims to further elucidate the importance of PFC myelination on cognitive functions of PFC,especially the adolescent PFC.To do this,we first developed demyelination mouse model by infusing lysolecithin(LPC)into the bilateral medial PFC(mPFC)of mice.Myelination level of mPFC was measured with immunohistochemistry and western blotting.PFC-dependent cognitive functions including anxiety,social communication,spatial learning/memory and fear conditioning,were evaluated by using open-field,elevated plus maze,social interaction,Barnes maze and fear conditioning tasks.Results show that,1)mPFC myelination demonstrated an inverted-U profile with age;2)Intra-mPFC infusion of LPC induced demyelination in both adolescent and adult mice;3)Intra-mPFC infusion of LPC produced locomotion hyperactivity and anxiety-like behaviors,and impaired social interaction,spatial learning/memory and fear learning/memory in adolescent mice,while only locomotion hyperactivity was observed upon LPC infusion in adult mice.The present results indicate that,myelination is extremely important for mPFC cognitive functions.Compared with adulthood,cognitive function execution relies more on PFC myelination in the adolescent.