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Mitochondrial Respiration Changes in R6/2 Huntington’s Disease Model Mice during Aging in a Brain Region Specific Manner

Mitochondrial dysfunction is crucially involved in aging and neurodegenerative diseases, such as Huntington’s Disease (HD). How mitochondria become compromised in HD is poorly understood but instrumental for the development of treatments to prevent or reverse resulting deficits. In this paper, we in...

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Autores principales: Burtscher, Johannes, Di Pardo, Alba, Maglione, Vittorio, Schwarzer, Christoph, Squitieri, Ferdinando
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432063/
https://www.ncbi.nlm.nih.gov/pubmed/32751413
http://dx.doi.org/10.3390/ijms21155412
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author Burtscher, Johannes
Di Pardo, Alba
Maglione, Vittorio
Schwarzer, Christoph
Squitieri, Ferdinando
author_facet Burtscher, Johannes
Di Pardo, Alba
Maglione, Vittorio
Schwarzer, Christoph
Squitieri, Ferdinando
author_sort Burtscher, Johannes
collection PubMed
description Mitochondrial dysfunction is crucially involved in aging and neurodegenerative diseases, such as Huntington’s Disease (HD). How mitochondria become compromised in HD is poorly understood but instrumental for the development of treatments to prevent or reverse resulting deficits. In this paper, we investigate whether oxidative phosphorylation (OXPHOS) differs across brain regions in juvenile as compared to adult mice and whether such developmental changes might be compromised in the R6/2 mouse model of HD. We study OXPHOS in the striatum, hippocampus, and motor cortex by high resolution respirometry in female wild-type and R6/2 mice of ages corresponding to pre-symptomatic and symptomatic R6/2 mice. We observe a developmental shift in OXPHOS-control parameters that was similar in R6/2 mice, except for cortical succinate-driven respiration. While the LEAK state relative to maximal respiratory capacity was reduced in adult mice in all analyzed brain regions, succinate-driven respiration was reduced only in the striatum and cortex, and NADH-driven respiration was higher as compared to juvenile mice only in the striatum. We demonstrate age-related changes in respirational capacities of different brain regions with subtle deviations in R6/2 mice. Uncovering in situ oxygen conditions and potential substrate limitations during aging and HD disease progression are interesting avenues for future research to understand brain-regional vulnerability in HD.
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spelling pubmed-74320632020-08-24 Mitochondrial Respiration Changes in R6/2 Huntington’s Disease Model Mice during Aging in a Brain Region Specific Manner Burtscher, Johannes Di Pardo, Alba Maglione, Vittorio Schwarzer, Christoph Squitieri, Ferdinando Int J Mol Sci Article Mitochondrial dysfunction is crucially involved in aging and neurodegenerative diseases, such as Huntington’s Disease (HD). How mitochondria become compromised in HD is poorly understood but instrumental for the development of treatments to prevent or reverse resulting deficits. In this paper, we investigate whether oxidative phosphorylation (OXPHOS) differs across brain regions in juvenile as compared to adult mice and whether such developmental changes might be compromised in the R6/2 mouse model of HD. We study OXPHOS in the striatum, hippocampus, and motor cortex by high resolution respirometry in female wild-type and R6/2 mice of ages corresponding to pre-symptomatic and symptomatic R6/2 mice. We observe a developmental shift in OXPHOS-control parameters that was similar in R6/2 mice, except for cortical succinate-driven respiration. While the LEAK state relative to maximal respiratory capacity was reduced in adult mice in all analyzed brain regions, succinate-driven respiration was reduced only in the striatum and cortex, and NADH-driven respiration was higher as compared to juvenile mice only in the striatum. We demonstrate age-related changes in respirational capacities of different brain regions with subtle deviations in R6/2 mice. Uncovering in situ oxygen conditions and potential substrate limitations during aging and HD disease progression are interesting avenues for future research to understand brain-regional vulnerability in HD. MDPI 2020-07-30 /pmc/articles/PMC7432063/ /pubmed/32751413 http://dx.doi.org/10.3390/ijms21155412 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Burtscher, Johannes
Di Pardo, Alba
Maglione, Vittorio
Schwarzer, Christoph
Squitieri, Ferdinando
Mitochondrial Respiration Changes in R6/2 Huntington’s Disease Model Mice during Aging in a Brain Region Specific Manner
title Mitochondrial Respiration Changes in R6/2 Huntington’s Disease Model Mice during Aging in a Brain Region Specific Manner
title_full Mitochondrial Respiration Changes in R6/2 Huntington’s Disease Model Mice during Aging in a Brain Region Specific Manner
title_fullStr Mitochondrial Respiration Changes in R6/2 Huntington’s Disease Model Mice during Aging in a Brain Region Specific Manner
title_full_unstemmed Mitochondrial Respiration Changes in R6/2 Huntington’s Disease Model Mice during Aging in a Brain Region Specific Manner
title_short Mitochondrial Respiration Changes in R6/2 Huntington’s Disease Model Mice during Aging in a Brain Region Specific Manner
title_sort mitochondrial respiration changes in r6/2 huntington’s disease model mice during aging in a brain region specific manner
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432063/
https://www.ncbi.nlm.nih.gov/pubmed/32751413
http://dx.doi.org/10.3390/ijms21155412
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