Document Detail


High cholesterol level is essential for myelin membrane growth.
MedLine Citation:
PMID:  15793579     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Gesine Saher; Britta Brügger; Corinna Lappe-Siefke; Wiebke Möbius; Ryu-ichi Tozawa; Michael C Wehr; Felix Wieland; Shun Ishibashi; Klaus-Armin Nave
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-03-27
Journal Detail:
Title:  Nature neuroscience     Volume:  8     ISSN:  1097-6256     ISO Abbreviation:  Nat. Neurosci.     Publication Date:  2005 Apr 
Date Detail:
Created Date:  2005-03-29     Completed Date:  2005-06-13     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9809671     Medline TA:  Nat Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  468-75     Citation Subset:  IM    
Affiliation:
Department of Neurogenetics, Max Planck Institute of Experimental Medicine, 37075 Goettingen, Germany.
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MeSH Terms
Descriptor/Qualifier:
2',3'-Cyclic-Nucleotide Phosphodiesterases / metabolism
Age Factors
Animals
Animals, Newborn
Apolipoproteins E / metabolism
Behavior, Animal
Blotting, Northern / methods
Blotting, Southern / methods
Blotting, Western / methods
Cell Membrane / metabolism
Central Nervous System / metabolism
Cholesterol / deficiency,  physiology*
Chromatography, Thin Layer / methods
Cloning, Molecular
Creatine / metabolism
Farnesyl-Diphosphate Farnesyltransferase / deficiency,  genetics,  metabolism
Gene Expression Regulation, Developmental / physiology*
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 / metabolism*,  ultrastructure
Oligodendroglia / metabolism*,  ultrastructure
Phenotype
Psychomotor Performance / physiology
RNA / analysis
Receptors, LDL / metabolism
Silver Staining / methods
Spinal Cord / metabolism,  ultrastructure
Chemical
Reg. No./Substance:
0/Apolipoproteins E; 0/Myelin Proteolipid Protein; 0/Receptors, LDL; 57-00-1/Creatine; 57-88-5/Cholesterol; 63231-63-0/RNA; EC 2.5.1.21/Farnesyl-Diphosphate Farnesyltransferase; EC 3.1.4.-/2',3'-Cyclic-Nucleotide Phosphodiesterases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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