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Increase of deleted mitochondrial DNA in the striatum in Parkinson's disease and senescence
1Department of Biomedical Chemistry, Faculty of Medicine, University of Nagoya, Japan.
Abstract:
A mutant mitochondrial DNA (mtDNA) with a 4,977-bp deletion was detected in the parkinsonian brain by using the polymerase chain reaction. Although the deleted mtDNA was detectable even in the brain of aged controls, the proportion of deleted mtDNA to normal mtDNA in the striatum was higher in the parkinsonian patients than in the controls. In both the parkinsonian patients and the aged controls, the proportion was higher in the striatum than in the cerebral cortex. These results indicate that age-related accumulation of deleted mtDNA is accelerated in the parkinsonian striatum and suggest that the deletion contributes to pathophysiological processes underlying Parkinson's disease.
Insights
Parkinson's disease brains show higher levels of deleted mitochondrial DNA (mtDNA) in the striatum compared to controls. This age-related mtDNA deletion accumulation may contribute to Parkinson's disease pathology.
Area of Science:
- Neuroscience
- Genetics
- Cell Biology
Background:
- Mitochondrial dysfunction is implicated in neurodegenerative diseases.
- Mutant mitochondrial DNA (mtDNA) deletions are associated with aging and disease.
Purpose of the Study:
- To investigate the presence and proportion of a specific 4,977-bp mtDNA deletion in the brains of Parkinson's disease patients.
- To compare the levels of deleted mtDNA in different brain regions (striatum and cerebral cortex) between patients and controls.
Main Methods:
- Polymerase chain reaction (PCR) was used to detect and quantify the 4,977-bp deleted mtDNA.
- Brain tissue samples from Parkinson's disease patients and aged controls were analyzed.
Main Results:
- The 4,977-bp deleted mtDNA was detected in both parkinsonian and control brains.
- The proportion of deleted mtDNA to normal mtDNA was significantly higher in the striatum of Parkinson's disease patients compared to controls.
- In both groups, the striatum showed a higher proportion of deleted mtDNA than the cerebral cortex.
Conclusions:
- Age-related accumulation of deleted mtDNA is accelerated in the parkinsonian striatum.
- The 4,977-bp mtDNA deletion may play a role in the pathophysiology of Parkinson's disease.