Approaches to the Study of Diseases Involving Oligodendroglial Death

Oligodendrocytes (OLs) are the myelin-producing cells of the central nervous system (CNS). Myelin is the compact, multilamellar, lipid-rich sheath that envelops axons. As a result of this membrane insulation, the rate of conduction of nerve action potentials down an axon is maximized while energy and space demands within the CNS are minimized. Disorders of myelin (i.e., white matter disorders) result from a variety of causes (see representative examples in Table 1). Extensive nervous system demyelination often has devastating consequences, including paralysis, dementia, or coma. These clinical sequelae reflect the marked reduction in the ability of the nervous system to conduct nerve impulses at a normal rate. Consider, for example, one form of the developmental disorder cerebral palsy (CP), in which injury to perinatal cerebral white matter results in decreased myelination of regions subserving such neurologic functions as motor control and vision. Around 5–15% of the nearly 50,000 preterm infants born in the US each year will acquire CP related to white matter damage, and manifesting as spastic motor deficits, and another 25–50% will show evidence of learning disabilities (1). The estimated economic cost to society of CP is in excess of five billion dollars annually.