Role of AMPA Receptor Signalling in Remyelination

Abstract

Myelin and myelin repair is crucial for normal nervous system function. Myelin enables fast communication between neurons while also providing protection and trophic support. In the central nervous system (CNS), myelin is produced by oligodendrocytes. Oligodendrocytes are derived from oligodendrocyte progenitor cells (OPCs). During development, most OPCs differentiate into myelinating oligodendrocyte while some are kept into adulthood. Both during development and following injury, OPCs express glutamate receptors which enables them to receive and respond to glutamate released from active axons. Damage to the myelin and oligodendrocytes results in white matter lesions in which the transmission of information is impaired. This is commonly found in patients with multiple sclerosis (MS) and may cause various neurological problems. While myelin repair is known to occur spontaneously following demyelination, this process becomes less efficient with age and disease progression and ultimately fails. Accumulating evidences indicate that neuronal activity is crucial for myelination and remyelination. In this study, the role of glutamate signalling during remyelination was examined by blocking the AMPA glutamate receptor through the use of NBQX, an AMPA receptor antagonist. The results showed that blocking AMPA receptors dramatically reduced remyelination, suggesting that glutamatergic signalling from active neurons plays a crucial role in remyelination by oligodendrocytes.