From adaptive to maladaptive myelination: White matter dynamics in cognition and neurologic disorders

Myelin is a fatty substance formed by processes of mature oligodendrocytes, which wrap around neuronal axons. Previously, myelin was believed to be important solely for the rapid conduction of electrical signals. However, over the past decade, research has revealed that its role goes far beyond this, including providing metabolic support to neurons and exhibiting significant plasticity. Myelin has also been thought to play a role in the pathogenesis of several neurodegenerative diseases. Furthermore, myelin has been implicated in various psychiatric disorders, including anxiety, depression, and schizophrenia, stimulating investigations into its involvement in normal cognitive function, learning, and memory. Understanding the intricate processes involved in myelin formation, damage, and repair is important in elucidating its contribution to neural circuit functions in health and disease. In this review, we discussed the unique structure of myelin and its contributions to the pathogenesis of neurological disorders such as Alzheimer's disease, epilepsy, multiple sclerosis, traumatic brain injury, schizophrenia, and stroke. Furthermore, we discuss the precise mechanisms by which myelin alterations in these disorders affect the synchronization and integration of neural activity, and how these changes impair executive functions such as learning, memory, attention, and decision-making. Additionally, we highlight recent findings of de novo myelination and myelin plasticity while identifying key knowledge gaps that need to be addressed to advance therapies to promote myelin repair in disease states.