3
Department of Cell Biology, Universitair Medisch Centrum Utrecht, 3584 CX Utrecht, The Netherlands.
4
Department of Metabolic Diseases, University of Tokyo, Tokyo 113-8655, Japan.
5
Department of Medicine, Jichi Medical School, Tochigi 329-0498, Japan.
6
Hertie Institute of Multiple Sclerosis Research, 37075 Goettingen, Germany.
Correspondence should be addressed to Klaus-Armin Nave nave@em.mpg.de
Cholesterol in the mammalian brain is a risk factor for certain neurodegenerative diseases, raising the question of its normal function. In the mature brain, the highest cholesterol content is found in myelin. We therefore created mice that lack the ability to synthesize cholesterol in myelin-forming oligodendrocytes. Mutant oligodendrocytes survived, but CNS myelination was severely perturbed, and mutant mice showed ataxia and tremor. CNS myelination continued at a reduced rate for many months, and during this period, the cholesterol-deficient oligodendrocytes actively enriched cholesterol and assembled myelin with >70% of the cholesterol content of wild-type myelin. This shows that cholesterol is an indispensable component of myelin membranes and that cholesterol availability in oligodendrocytes is a rate-limiting factor for brain maturation.
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