Journal Article

High cholesterol level is essential for myelin membrane growth

Wehr, Michael C, Brügger, Britta, Saher, Gesine, Möbius, Wiebke, Nave, Klaus-Armin, Ishibashi, Shun, Wieland, Felix, Lappe-Siefke, Corinna, Tozawa, Ryu-ichi

2005

Overview

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.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 2',3'-Cyclic-Nucleotide Phosphodiesterases - metabolism / Age Factors / Animal Genetics and Genomics / Animals / Animals, Newborn / Apolipoproteins E - metabolism / Behavior, Animal / Behavioral Sciences / Biological Techniques / Biomedical and Life Sciences / Biomedicine / Blotting, Northern - methods / Blotting, Southern - methods / Blotting, Western - methods / Cell Membrane - metabolism / Central Nervous System - metabolism / Cholesterol - deficiency / Cholesterol - physiology / Chromatography, Thin Layer - methods / Cloning, Molecular / Creatine - metabolism / Farnesyl-Diphosphate Farnesyltransferase - deficiency / Farnesyl-Diphosphate Farnesyltransferase - genetics / Farnesyl-Diphosphate Farnesyltransferase - metabolism / Gene Expression Regulation, Developmental - physiology / Hypercholesterolemia / In Situ Hybridization - methods / Lipid Metabolism / Mass Spectrometry - methods / Mice / Mice, Inbred C57BL / Mice, Mutant Strains - physiology / Microscopy, Electron, Transmission - methods / Microsomes - metabolism / Myelin Proteolipid Protein - metabolism / Myelin sheath / Myelin Sheath - metabolism / Myelin Sheath - ultrastructure / Neurobiology / Neurosciences / Oligodendroglia - metabolism / Oligodendroglia - ultrastructure / Phenotype / Physiological aspects / Psychomotor Performance - physiology / Receptors, LDL - metabolism / RNA - analysis / Silver Staining - methods / Spinal Cord - metabolism / Spinal Cord - ultrastructure