| High cholesterol level is essential for myelin membrane growth. | |
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MedLine Citation:
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PMID: 15793579 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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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:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't Date: 2005-03-27 |
Journal Detail:
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Title: Nature neuroscience Volume: 8 ISSN: 1097-6256 ISO Abbreviation: Nat. Neurosci. Publication Date: 2005 Apr |
Date Detail:
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Created Date: 2005-03-29 Completed Date: 2005-06-13 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9809671 Medline TA: Nat Neurosci Country: United States |
Other Details:
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Languages: eng Pagination: 468-75 Citation Subset: IM |
Affiliation:
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Department of Neurogenetics, Max Planck Institute of Experimental Medicine, 37075 Goettingen, Germany. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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2',3'-Cyclic-Nucleotide Phosphodiesterases
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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:
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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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