Antisera to different glycolipids induce myelin alterations in mouse spinal cord tissue cultures

Abstract

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 (GM 1 and GM 4), 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 occured within 24 h of exposure to a relatively low concentration of serum (10%). Cultures exposed to anit-GM 1 and anti-GM 4 antisera showed similar changes but to a lasser 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 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 GM 1 and GM 4 might also play a role in immune-mediated demyelination, including perhaps, the human demyelinating diseases.