Aidt 2013 PLoS Curr: Difference between revisions
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{{Publication | {{Publication | ||
|title=Aidt FH, Nielsen SM, Kanters J, Pesta D, Nielsen TT, NΓΈrremΓΈlle A, Hasholt L, Christiansen M, Hagen CM (2013) Dysfunctional mitochondrial respiration in the striatum of the Huntington's disease transgenic R6/2 mouse model. PLoS Curr 5 | |title=Aidt FH, Nielsen SM, Kanters J, Pesta D, Nielsen TT, NΓΈrremΓΈlle A, Hasholt L, Christiansen M, Hagen CM (2013) Dysfunctional mitochondrial respiration in the striatum of the Huntington's disease transgenic R6/2 mouse model. PLoS Curr 5. pii:ecurrents.hd.d8917b4862929772c5a2f2a34ef1c201. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed/23568011 PMID:23568011 Open Access] | |info=[http://www.ncbi.nlm.nih.gov/pubmed/23568011 PMID:23568011 Open Access] | ||
|authors=Aidt FH, Nielsen SM, Kanters J, Pesta D, Nielsen TT, Noerremoelle A, Hasholt L, Christiansen M, Hagen CM | |authors=Aidt FH, Nielsen SM, Kanters J, Pesta D, Nielsen TT, Noerremoelle A, Hasholt L, Christiansen M, Hagen CM | ||
|year=2013 | |year=2013 | ||
|journal=PLoS Curr | |journal=PLoS Curr | ||
|abstract=Metabolic dysfunction and mitochondrial involvement are recognised as part of the pathology in Huntington's Disease (HD). Post-mortem examinations of the striatum from end-stage HD patients have shown a decrease in the in vitro activity of Complexes II, III and IV of the electron transfer system (ETS). In different models of HD, evidence of enzyme defects have been reported in Complex II and Complex IV using enzyme assays. However, such assays are highly variable and results have been inconsistent. We investigated the integrated ETS function ex vivo using a sensitive high-resolution respirometric (HRR) method. The O2 flux in a whole-cell sample combined with the addition of mitochondrial substrates, uncouplers and inhibitors enabled us to accurately quantitate the function of individual mitochondrial complexes in intact mitochondria, while retaining mitochondrial regulation and compensatory mechanisms. We used HRR to examine the mitochondrial function in striata from 12-week old R6/2 mice expressing exon 1 of human HTT with 130 CAG repeats. A significant reduction in Complex II and Complex IV flux control ratios was found in the R6/2 mouse striatum at 12 weeks of age compared to controls, confirming previous findings obtained with spectrophotometric enzyme assays. | |abstract=Metabolic dysfunction and mitochondrial involvement are recognised as part of the pathology in Huntington's Disease (HD). Post-mortem examinations of the striatum from end-stage HD patients have shown a decrease in the ''in vitro'' activity of Complexes II, III and IV of the electron transfer system (ETS). In different models of HD, evidence of enzyme defects have been reported in Complex II and Complex IV using enzyme assays. However, such assays are highly variable and results have been inconsistent. We investigated the integrated ETS function ex vivo using a sensitive high-resolution respirometric (HRR) method. The O2 flux in a whole-cell sample combined with the addition of mitochondrial substrates, uncouplers and inhibitors enabled us to accurately quantitate the function of individual mitochondrial complexes in intact mitochondria, while retaining mitochondrial regulation and compensatory mechanisms. We used HRR to examine the mitochondrial function in striata from 12-week old R6/2 mice expressing exon 1 of human HTT with 130 CAG repeats. A significant reduction in Complex II and Complex IV flux control ratios was found in the R6/2 mouse striatum at 12 weeks of age compared to controls, confirming previous findings obtained with spectrophotometric enzyme assays. | ||
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Revision as of 13:59, 31 March 2015
Aidt FH, Nielsen SM, Kanters J, Pesta D, Nielsen TT, NΓΈrremΓΈlle A, Hasholt L, Christiansen M, Hagen CM (2013) Dysfunctional mitochondrial respiration in the striatum of the Huntington's disease transgenic R6/2 mouse model. PLoS Curr 5. pii:ecurrents.hd.d8917b4862929772c5a2f2a34ef1c201. |
Aidt FH, Nielsen SM, Kanters J, Pesta D, Nielsen TT, Noerremoelle A, Hasholt L, Christiansen M, Hagen CM (2013) PLoS Curr
Abstract: Metabolic dysfunction and mitochondrial involvement are recognised as part of the pathology in Huntington's Disease (HD). Post-mortem examinations of the striatum from end-stage HD patients have shown a decrease in the in vitro activity of Complexes II, III and IV of the electron transfer system (ETS). In different models of HD, evidence of enzyme defects have been reported in Complex II and Complex IV using enzyme assays. However, such assays are highly variable and results have been inconsistent. We investigated the integrated ETS function ex vivo using a sensitive high-resolution respirometric (HRR) method. The O2 flux in a whole-cell sample combined with the addition of mitochondrial substrates, uncouplers and inhibitors enabled us to accurately quantitate the function of individual mitochondrial complexes in intact mitochondria, while retaining mitochondrial regulation and compensatory mechanisms. We used HRR to examine the mitochondrial function in striata from 12-week old R6/2 mice expressing exon 1 of human HTT with 130 CAG repeats. A significant reduction in Complex II and Complex IV flux control ratios was found in the R6/2 mouse striatum at 12 weeks of age compared to controls, confirming previous findings obtained with spectrophotometric enzyme assays.
Labels: MiParea: Respiration, Genetic knockout;overexpression
Pathology: Neurodegenerative
Organism: Mouse Tissue;cell: Nervous system Preparation: Homogenate Enzyme: TCA cycle and matrix dehydrogenases Regulation: Uncoupler Coupling state: LEAK, OXPHOS, ETS"ETS" is not in the list (LEAK, ROUTINE, OXPHOS, ET) of allowed values for the "Coupling states" property.
HRR: Oxygraph-2k