Repairing CNS myelin—astrocytes have to do their jobs

Abstract

Chronic and progressive demyelination is a feature of a wide range of CNS disorders. Demyelination is a hallmark of multiple sclerosis (MS), and is commonly considered the major cause of symptoms in this disease, at least in its earlier phases. Demyelination is widespread also following compression injuries to the brain or spinal cord. This pathology may have a particularly heavy impact on the human spinal cord white matter with its large numbers of heavily myelinated axons. Recent findings indicate that demyelination may contribute to functional deteriorations associated with aging (Davatzikos and Resnick, 2002; Kovari et al., 2004), and to the pathogenesis of psychiatric disorders, notably schizophrenia (Davis et al., 2003; Flynn et al., 2003). The impact of demyelination pathology for the functional disturbances is more difficult to assess in these conditions because of the many other simultaneously ongoing or temporally overlapping pathological processes. In any case, demyelination is a pathological process with implications for diseases causing serious disability and distress, and affecting large numbers of patients. At the same time, restoring action potential conduction in demyelinated axons may lead to rapid recovery of functions. If demyelinated axons maintain functional synaptic target contacts, the return of impulse conduction in these axons may lead to functional improvement more or less immediately. Even if synaptic contacts have been lost, e.g., as a result of absence of activity, there may be rapid return of such contacts through terminal sprouting after action potential propagation has been resumed. Thus, the clinical benefits may be substantial from therapies leading to rapid and efficient remyelination of demyelinated axons. The myelinated axon is a highly elaborate structure, built to ensure faithful saltatory propagation of action potentials