BDNF-TrkB Signaling in Lifelong Central Nervous System Myelination and Myelin Repair

Myelin, the lipid membrane that wraps around nerves, is a critical component of the peripheral (PNS) and central nervous systems (CNS) that enables rapid neurotransmission and is critical for brain function, including motor skill acquisition and working memory. In the CNS, myelin acquisition occurs rapidly during development, and myelin sheaths are made by oligodendrocytes in response to a host of extracellular factors, including brain-derived neurotrophic factor (BDNF) and neuronal activity. BDNF promotes CNS myelination by activating its TrkB receptor expressed by oligodendrocytes, and loss of oligodendrocyte TrkB delays myelin acquisition and reduces myelin sheath thickness. Myelin acquisition continues throughout life, and activity-dependent myelination appears to underpin myelin acquisition in adulthood. As local release of BDNF by neurons occurs in response to neuronal activity, BDNF has been identified as a potential modulator of activity-dependent myelin acquisition in addition to its known developmental effects via oligodendrocyte TrkB. As BDNF-TrkB signaling is a robust potentiator of myelination, it has also been identified as a therapeutic target to promote myelin repair in demyelinating diseases including multiple sclerosis (MS). This chapter summarizes the development of CNS myelination, its importance throughout life, and the role of BDNF-TrkB signaling in myelin development and activity-dependent myelin plasticity. The potential for increasing endogenous BDNF levels or targeting TrkB activation as a therapeutic strategy to promote myelin repair for demyelinating diseases such as multiple sclerosis is also summarized.