Galactosylceramide (galactocerebroside) is highly enriched in myelin, comprising about 20% of the total myelin lipid. Antibodies to this lipid have been shown to cause demyelination as well as an acute conduction block in nerve. However, little is known about the role of galactosylceramide in myelin and its interaction with other myelin components. Myelin proteins and lipids are believed to be arranged in a manner coinciding with the fluid mosaic membrane model that implies extensive interaction among the lipid and protein components to stabilize myelin structure. Although in vitro experiments support this hypothesis, to our knowledge, no in vivo experiments have been published that demonstrate role of specific lipid myelin components in the assembly and/or stabilization of myelin. We hypothesize that galactosylceramide interacts with myelin protein and lipid to stabilize the myelin and that a substantial decrease of galactosylceramide will effect composition and/or turnover and/or incorporation of myelin components. Our experimental paradigm utilizes the observation that cycloserine substantially decreases rat brain galactosylceramide without significantly affecting the relative composition of other myelin components. Cycloserine will be administered to rats and the most effective route of administration and dosage established for reduction of brain galactosylceramide. We will then determine the alteration of my myelin composition. [3H]Precursors will be used to monitor the effects of decreased brain galactosylceramide on assembly and turnover of myelin proteins. Results from these experiments will reveal the role of galactosylceramide in stabilizing my myelin. Furthermore, these experiments will serve to establish the experimental methods for investigating any nonstructural role of galactosylceramide in oligodendrocytes and as a prototype to investigate interactions in vivo in other membrane systems.
| Miller, S L; Denisova, L (1998) Cycloserine-induced decrease of cerebroside in myelin. Lipids 33:441-3 |
