| Mitochondrial dysfunction in Huntington's disease: the bioenergetics of isolated and in situ mitochondria from transgenic mice. | |
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MedLine Citation:
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PMID: 17394466 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Mitochondrial dysfunction is believed to participate in Huntington's disease (HD) pathogenesis. Here we compare the bioenergetic behavior of forebrain mitochondria isolated from different transgenic HD mice (R6/2, YAC128 and Hdh150 knock-in) and wild-type littermates with the first determination of in situ respiratory parameters in intact HD striatal neurons. We assess the Ca2+-loading capacity of isolated mitochondria by steady Ca2+-infusion. Mitochondria from R6/2 mice (12-13 weeks) and 12 months YAC128, but not homozygous or heterozygous Hdh150 knock-in mice (15-17 weeks), exhibit increased Ca2+-loading capacity when compared with respective wild-type littermates. In situ mitochondria in intact striatal neurons show high respiratory control. Moreover, moderate expression of full-length mutant huntingtin (in Hdh150 knock-in heterozygotes) does not significantly impair mitochondrial respiration in unstimulated neurons. However, when challenged with energy-demanding stimuli (NMDA-receptor activation in pyruvate-based media to accentuate the mitochondria role in Ca2+-handling), Hdh150 neurons are more vulnerable to Ca2+-deregulation than neurons from their wild-type littermates. These results stress the importance of assessing HD mitochondrial function in the cellular context. |
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Authors:
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Jorge M A Oliveira; Mika B Jekabsons; Sylvia Chen; Amy Lin; A Cristina Rego; Jorge Gonçalves; Lisa M Ellerby; David G Nicholls |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of neurochemistry Volume: 101 ISSN: 0022-3042 ISO Abbreviation: J. Neurochem. Publication Date: 2007 Apr |
Date Detail:
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Created Date: 2007-03-30 Completed Date: 2007-05-29 Revised Date: 2012-07-11 |
Medline Journal Info:
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Nlm Unique ID: 2985190R Medline TA: J Neurochem Country: England |
Other Details:
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Languages: eng Pagination: 241-9 Citation Subset: IM |
Affiliation:
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Buck Institute for Age Research, Novato, California, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Brain / metabolism, physiopathology Brain Chemistry / genetics* Calcium Signaling / genetics Cell Respiration / genetics Disease Models, Animal Energy Metabolism / genetics* Genetic Predisposition to Disease / genetics* Humans Huntington Disease / genetics*, metabolism, physiopathology Mice Mice, Transgenic Mitochondria / genetics*, metabolism Mitochondrial Diseases / genetics*, metabolism, physiopathology Mutation / genetics Nerve Tissue Proteins / genetics Nuclear Proteins / genetics Receptors, N-Methyl-D-Aspartate / metabolism Synaptic Transmission / drug effects, physiology |
| Grant Support | |
ID/Acronym/Agency:
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NS40251A/NS/NINDS NIH HHS; R01 NS041908/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/HTT protein, human; 0/Nerve Tissue Proteins; 0/Nuclear Proteins; 0/Receptors, N-Methyl-D-Aspartate |
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