GALACTOSPHINGOLIPIDS AND AXONO-GLIAL INTERACTION IN MYELIN OF THE CENTRAL-NERVOUS-SYSTEM

The myelin of central and peripheral nervous system of UDP-galactose-c eramide galactosyltransferase deficient mice (cgt(-/-) is completely d epleted of its major lipid constituents, galactocerebrosides and sulfa tides. The deficiency of these glycolipids affects the biophysical pro perties of the myelin sheath and causes the loss of the rapid saltator y conduction velocity of myelinated axons. With the onset of myelinati on, null mutant cgt(-/-) mice develop fatal neurological defects. CNS and PNS analysis of cgt(-/-) mice revealed (1) hypomyelination of axon s of the spinal cord and optic nerves, but no apoptosis of oligodendro cytes, (2) redundant myelin in younger mice leading to vacuolated nerv e fibers in cgt(-/-) mice, (3) the occurrence of multiple myelinated C NS axons, and (4) severely distorted lateral loops in CNS paranodes. T he loss of saltatory conduction is not associated with a randomization of voltage-gated sodium channels in the axolemma of PNS fibers. We co nclude that cerebrosides (GalC) and sulfatides (sGalC) play a major ro le in CNS axono-glial interaction. A close axono-glial contact is not a prerequisite for the spiraling and compaction process of myelin. Axo nal sodium channels remain clustered at the nodes of Ranvier independe nt of the change in the physical properties of myelin membrane devoid of galactosphingolipids. Increased intracellular concentrations of fre e ceramides do not trigger apoptosis of oligodendrocytes.