Galactosphingolipids and axono-glial interaction in myelin of the central nervous system.
The myelin of central and peripheral nervous system of UDP-galactose-ceramide galactosyltransferase deficient mice (cgt-/-) is completely depleted of its major lipid constituents, galactocerebrosides and sulfatides. The deficiency of these glycolipids affects the biophysical properties of the myelin sheath and causes the loss of the rapid saltatory conduction velocity of myelinated axons. With the onset of myelination, null mutant cgt-/- mice develop fatal neurological defects. CNS and PNS analysis of cgt-/- mice revealed (1) hypomyelination of axons of the spinal cord and optic nerves, but no apoptosis of oligodendrocytes, (2) redundant myelin in younger mice leading to vacuolated nerve fibers in cgt-/- mice, (3) the occurrence of multiple myelinated CNS axons, and (4) severely distorted lateral loops in CNS paranodes. The loss of saltatory conduction is not associated with a randomization of voltage-gated sodium channels in the axolemma of PNS fibers. We conclude that cerebrosides (GalC) and sulfatides (sGalC) play a major role in CNS axono-glial interaction. A close axono-glial contact is not a prerequisite for the spiraling and compaction process of myelin. Axonal sodium channels remain clustered at the nodes of Ranvier independent of the change in the physical properties of myelin membrane devoid of galactosphingolipids. Increased intracellular concentrations of free ceramides do not trigger apoptosis of oligodendrocytes.
Bosio
A
A
Molecular Neuroscience Laboratory, Institute of Biochemistry, Faculty of Medicine, University of Cologne, Joseph-Stelzmann-Strasse 52, D-50931 Cologne, Germany.
Büssow
H
H
Adam
J
J
Stoffel
W
W
D000818:Animals; D017209:Apoptosis; D001369:Axons / Q000378:metabolism / Q000648:ultrastructure*; D002490:Central Nervous System / Q000648:ultrastructure*; D003711:Demyelinating Diseases / Q000378:metabolism / Q000473:pathology; D005700:Galactosyltransferases / Q000235:genetics / Q000502:physiology*; D051147:Ganglioside Galactosyltransferase; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009186:Myelin Sheath / Q000502:physiology / Q000648:ultrastructure*; D009457:Neuroglia / Q000648:ultrastructure*; D009900:Optic Nerve / Q000648:ultrastructure; D017933:Peripheral Nervous System / Q000378:metabolism / Q000648:ultrastructure; D012584:Sciatic Nerve / Q000648:ultrastructure; D015222:Sodium Channels / Q000378:metabolism; D013116:Spinal Cord / Q000648:ultrastructure
D015222:Sodium Channels; D005700:Galactosyltransferases; D051147:Ganglioside Galactosyltransferase