Antisera to different glycolipids induce myelin alterations in mouse spinal cord tissue cultures.
To study the demyelinative effects of antibodies to glycolipids, well-myelinated cultures of mouse spinal cord tissue were exposed to antisera against galactocerebroside and two gangliosides (GM1 and GM4), as well as to anti-white matter antiserum. The demyelinative process was evaluated by morphologic and biochemical techniques. Cultures exposed to anti-white matter and anti-galactocerebroside antisera showed the most marked changes. These consisted of a decrease in the number of oligodendroglial cells and dissolution and phagocytosis of myelin. Concomitantly, the activity of 2',3'-cyclic nucleotide-3'-phosphohydrolase (CNPase) was decreased by 60-70%. This occurred within 24 h of exposure to a relatively low concentration of serum (10%). Cultures exposed to anti-GM1 and anti-GM4 antisera showed similar changes but to a lesser degree. The CNPase activity was decreased about 30% within 48 h of exposure to a 25% concentration of these antisera. This diminution represents about a 20% loss of myelin, an observation corroborated by electron microscopy where myelin but not oligodendroglial cell loss was observed. Therefore, in addition to anti-galactocerebroside activity, which was previously found to be the major antibody responsible for the demyelinating activity induced by anti-whole CNS tissue antiserum, these data suggest that antibodies to gangliosides like GM1 and GM4 might also play a role in immune-mediated demyelination, including perhaps, the human demyelinating diseases.
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D046508:Culture Techniques; D003711:Demyelinating Diseases / Q000276:immunology*; D005677:G(M1) Ganglioside / Q000276:immunology; D005699:Galactosylceramides / Q000276:immunology; D005732:Gangliosides / Q000276:immunology; D006017:Glycolipids / Q000276:immunology*; D007106:Immune Sera / Q000633:toxicity; D051379:Mice; D008854:Microscopy, Electron; D013116:Spinal Cord / Q000276:immunology*
D005699:Galactosylceramides; D005732:Gangliosides; D006017:Glycolipids; D007106:Immune Sera; C002454:galactocerebroside; D005677:G(M1) Ganglioside; C028253:ganglioside, GM4