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Burtscher 2020 Int J Mol Sci

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Burtscher J, Di Pardo A, Maglione V, Schwarzer C, Squitieri F (2020) Mitochondrial respiration changes in R6/2 Huntington's Disease model mice during aging in a brain region specific manner. Int J Mol Sci 21:5412.

Β» PMID: 32751413 Open Access

Burtscher J, Di Pardo A, Maglione V, Schwarzer C, Squitieri F (2020) Int J Mol Sci

Abstract: 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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Labels: MiParea: Respiration 





HRR: Oxygraph-2k 

2021-12