The development and maturation of oligodendrocyte require complex mechanisms that interact at different levels to regulate neuronal activities. This review examines specific functions and critical roles of oligodendrocyte, regulatory factors involved in its differentiation, including the involvement of glutamate and reactive oxygen species (ROS). Olig2, Id4, Wnt/β-catenin and histone deacetylase (HDAC) appear to play crucial roles in spatio-temporal regulation of the differentiation of oligodendrocytes. Furthermore, HDAC appears to be the rate-limiting factor that may be manipulated to promote myelination as it simultaneously allays contact inhibition of Id4 in the intrinsic pathway and Wnt/β-catenin in the extrinsic pathway. ROS exhibit autocrine effect in enhancing functional activities of N-methyl-d-aspartate (NMDA) in neurogenesis and also play a secondary role in stimulating oligodendrocyte differentiation. It is concluded that the understanding of how regulators of oligodendrocyte interact may pave way for manipulation of oligodendrocytes in the management of neurodegenerative disorders.
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