Mitochondrial Complex 1 Activity Measured by Spectrophotometry Is Reduced across All Brain Regions in Ageing and More Specifically in Neurodegeneration
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Mitochondrial function, in particular complex 1 of the electron transport chain (ETC), has been shown to decrease during normal ageing and in neurodegenerative disease. However, there is some debate concerning which area of the brain has the greatest complex 1 activity. It is important to identify the pattern of activity in order to be able to gauge the effect of age or disease related changes. We determined complex 1 activity spectrophotometrically in the cortex, brainstem and cerebellum of middle aged mice (70-71 weeks), a cerebellar ataxic neurodegeneration model (pcd5J) and young wild type controls. We share our updated protocol on the measurements of complex1 activity and find that mitochondrial fractions isolated from frozen tissues can be measured for robust activity. We show that complex 1 activity is clearly highest in the cortex when compared with brainstem and cerebellum (p<0.003). Cerebellum and brainstem mitochondria exhibit similar levels of complex 1 activity in wild type brains. In the aged brain we see similar levels of complex 1 activity in all three-brain regions. The specific activity of complex 1 measured in the aged cortex is significantly decreased when compared with controls (p<0.0001). Both the cerebellum and brainstem mitochondria also show significantly reduced activity with ageing (p<0.05). The mouse model of ataxia predictably has a lower complex 1 activity in the cerebellum, and although reductions are measured in the cortex and brain stem, the remaining activity is higher than in the aged brains. We present clear evidence that complex 1 activity decreases across the brain with age and much more specifically in the cerebellum of the pcd5j mouse. Mitochondrial impairment can be a region specific phenomenon in disease, but in ageing appears to affect the entire brain, abolishing the pattern of higher activity in cortical regions.
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Complex 1 activity significantly decreased in mitochondria isolated from the aged mouse cortex when compared to young controls.
“Complex 1 activity in particular significantly decreased in mitochondria isolated from the aged mouse cortex when compared to young controls.80”
From Uncovering the signatures of aging and senescence in the human dorsolateral prefrontal cortex (2026) · cites this paper as [80]
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- Authors
- Pollard, A. K., Craig, E. L., & Chakrabarti, L.
- Affiliations
- University of Nottingham (GB)
- Corresponding author
- Chakrabarti, Lisa
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2016-06-22
- Volume
- 11
- Issue
- 6
- Pages
- e0157405
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4917223
- OpenAlex
- W2468126113
- Cited by
- 94
- References
- 34
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 13 · 2023: 14 · 2022: 15 · 2021: 17 · 2020: 6 · 2019: 2 · 2018: 7 · 2017: 3 · 2016: 2
- FWCI
- 2.43
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Repository@Nottingham (University of Nottingham) (publishedVersion, cc-by)
- Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Nottingham ePrints (University of Nottingham) (submittedVersion, cc-by)
- Funders
- Biotechnology and Biological Sciences Research Council
- University of Nottingham
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- mitochondrial complex I, electron transport chain, brain aging, neurodegeneration, cerebellar ataxia, brain regions, mitochondrial function, cortex, brainstem, cerebellum, spectrophotometric assay
- MeSH terms
- Aging, Animals, Brain, Brain Stem, Cerebral Cortex, Frozen Sections, Mice, Inbred C57BL, Mitochondria, Nerve Degeneration, Specimen Handling, Spectrophotometry, Electron Transport Complex I
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