title: Selective striatal mtDNA depletion in end-stage Huntington's disease R6/2 mice.
abstract: In Huntington's disease (HD) the striatum and cortex seem particularly vulnerable. Mitochondrial dysfunction can also cause neurodegeneration with prominent striatal involvement very similar to HD. We first examined if mitochondrial biogenesis, mitochondrial DNA (mtDNA) transcription, and the implications for mitochondrial respiratory chain (MRC) assembly and function differ between the striatum and cortex compared with the whole brain average in the healthy mouse brain. We then examined the effects of the mutant huntingtin transgene in end-stage R6/2 mice. In wild-type mice, mitochondrial mass (citrate synthase levels, mtDNA copy number) was higher in the striatum than in the cortex or whole brain average. PGC-1α and TFAM mRNA levels were also higher in the striatum than the whole brain average and cortex. mRNA reserve for MRC Complex proteins was higher in the striatum and cortex. In addition, in the cortex a greater part of mitochondrial mass was dedicated to the generation of ATP by oxidative phosphorylation than in the striatum or on average in the brain. In the HD transgenic striatum there was selective mtDNA depletion without evidence that this translated to abnormalities of steady-state MRC function. Our data indicate that in mice the striatum differs from the cortex, or whole brain average, in potentially important aspects of mitochondrial biology. This may contribute to the increased vulnerability of the striatum to insults such as the HD mutation, causing selective striatal mtDNA depletion in end-stage R6/2 mice.
authors: Department of Neurology, Ulm University, Germany.
authors: Tanja
authors: T
authors: Hering
authors: Department of Neurology, Ulm University, Germany.
authors: Nathalie
authors: N
authors: Birth
authors: Department of Clinical Neurosciences, Institute of Neurology, University College London, London, UK.
authors: Jan-Willem
authors: JW
authors: Taanman
authors: Department of Neurology, Ulm University, Germany.
authors: Michael
authors: M
authors: Orth
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002950:Citrate (si)-Synthase / Q000096:biosynthesis; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism*; D004579:Electron Transport / Q000187:drug effects / Q000235:genetics; D018628:Gene Dosage; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009154:Mutation / Q000235:genetics; D017072:Neostriatum / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D004272:DNA, Mitochondrial; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D000255:Adenosine Triphosphate; D002950:Citrate (si)-Synthase
keywords: Mitochondrial biogenesis; Mitochondrial respiratory chain assembly; PGC-1α; TFAM; mtDNA depletion