| Cholesterol defect is marked across multiple rodent models of Huntington's disease and is manifest in astrocytes. | |
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MedLine Citation:
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PMID: 20702713 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Brain cholesterol, which is synthesized locally, is a major component of myelin and cell membranes and participates in neuronal functions, such as membrane trafficking, signal transduction, neurotransmitter release, and synaptogenesis. Here we show that brain cholesterol biosynthesis is reduced in multiple transgenic and knock-in Huntington's disease (HD) rodent models, arguably dependent on deficits in mutant astrocytes. Mice carrying a progressively increased number of CAG repeats show a more evident reduction in cholesterol biosynthesis. In postnatal life, the cholesterol-dependent activities of neurons mainly rely on the transport of cholesterol from astrocytes on ApoE-containing particles. Our data show that mRNA levels of cholesterol biosynthesis and efflux genes are severely reduced in primary HD astrocytes, along with impaired cellular production and secretion of ApoE. Consistently, in CSF of HD mice, ApoE is mostly associated with smaller lipoproteins, indicating reduced cholesterol transport on ApoE-containing lipoproteins circulating in the HD brain. These findings indicate that cholesterol defect is robustly marked in HD animals, implying that strategies aimed at selectively modulating brain cholesterol metabolism might be of therapeutic significance. |
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Authors:
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Marta Valenza; Valerio Leoni; Joanna M Karasinska; Lara Petricca; Jianjia Fan; Jeffrey Carroll; Mahmoud A Pouladi; Elisa Fossale; Huu Phuc Nguyen; Olaf Riess; Marcy MacDonald; Cheryl Wellington; Stefano DiDonato; Michael Hayden; Elena Cattaneo |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of neuroscience : the official journal of the Society for Neuroscience Volume: 30 ISSN: 1529-2401 ISO Abbreviation: J. Neurosci. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-08-12 Completed Date: 2010-09-03 Revised Date: 2011-11-24 |
Medline Journal Info:
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Nlm Unique ID: 8102140 Medline TA: J Neurosci Country: United States |
Other Details:
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Languages: eng Pagination: 10844-50 Citation Subset: IM |
Affiliation:
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Department of Pharmacological Sciences and Centre for Stem Cell Research, Università degli Studi di Milano, 20133 Milan, Italy. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Analysis of Variance Animals Animals, Genetically Modified Animals, Newborn Apolipoproteins E / cerebrospinal fluid Astrocytes / metabolism* Brain / metabolism*, pathology Cells, Cultured Cholesterol / biosynthesis, metabolism* Disease Models, Animal Female Huntington Disease / cerebrospinal fluid, genetics, metabolism*, pathology* Male Mice Myelin Basic Proteins / metabolism Myelin Sheath / metabolism, pathology Rats Sterols / metabolism Synaptosomal-Associated Protein 25 / metabolism Synaptosomes / metabolism, pathology Trinucleotide Repeat Expansion / genetics |
| Grant Support | |
ID/Acronym/Agency:
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GGP06250//Telethon; NS32765/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Apolipoproteins E; 0/Myelin Basic Proteins; 0/Sterols; 0/Synaptosomal-Associated Protein 25; 57-88-5/Cholesterol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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