Glial interaction in demyelination and remyelination processes in the corpus callosum

The corpus callosum (CC)—the largest commissural fiber system connecting the two hemispheres—is considered essential for bilateral sensory integration and higher cognitive functions. Multiple sclerosis (MS), an autoimmune-mediated degenerative disease of the central nervous system, and other neurological disorders impair oligodendrocyte function, leading to destruction or loss of the myelin coating of callosal fibers. Most studies exploring the CC by immunocytochemical, neurochemical, and ablation techniques of specific glial cells have made remarkable progress in understanding the functions of the different glial populations (microglia, astrocytes, and oligodendrocytes), their interrelations, and the molecular and cellular mechanisms that underlie de/remyelination mechanisms. We review the information on the processes that take place in the CC during de/remyelination in sections that discuss: (I) demyelinating factors, by describing the cuprizone-induced demyelination mouse model; (II) glial cells, the molecular and cellular mechanisms underlying the biology of de/remyelination; (III) the exogenous factors influencing remyelination. Taken together, findings from cuprizone models suggest that endogenous remyelination may contribute to the functional recovery of callosal transfer, highlighting the importance of further elucidating these mechanisms to inform therapeutic strategies for callosal damage in multiple sclerosis and other neurodegenerative disorders.