Related Experiment Video
Updated: Jul 7, 2026
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Lack of mitochondrial DNA deletions in lesions of multiple sclerosis
Andrei Blokhin1, Tamara Vyshkina, Samuel Komoly
1VA Medical Center, Research (151), Syracuse, NY, USA.
Objective:
To test if mitochondrial (mt)DNA deletions accumulate in brains of patients with multiple sclerosis (MS).
Background:
Previous studies demonstrated an accumulation of oxidative damage to mtDNA and decreased activity of mitochondrial enzymes in lesions of MS, where activated immune cells produce increased amounts of reactive oxygen species and nitric oxide. The unknown link between oxidative damage and decreased activity of mitochondrial enzymes may be the accumulation of deletions in mtDNA molecules. mtDNA deletions in the brain have been associated with neurodegeneration and aging.
Methods:
mtDNA deletions were quantified by using real-time PCR in laser-dissected, COX-positive and COX-negative single neuronal and glial cells from frozen postmortem brain tissue specimens including normal appearing gray (NAGM) and white matter (NAWM) regions and chronic active plaques of MS patients, and gray matter (GM) and white matter (WM) regions of age-matched controls. Three patients with advance Alzheimer's and Parkinson's diseases were included as positive controls. The proportion of deleted mtDNA molecules was correlated with pathology and age.
Results:
We detected no pathology-related accumulation of mtDNA deletions when comparisons were made among NAGM, NAWM, and plaque of MS brains, or between NAGM-GM and NAWM-WM of patients and age-matched controls. However, an accumulation of mtDNA deletions was noted in non-neurological controls beyond 60 years of age and in patients with Alzheimer's and Parkinson's diseases. As expected, the rate of mtDNA deletions was higher in COX- than in COX+ cells.
Conclusion:
While aging and neurodegeneration in PD and AD are associated with accumulation of COX- cells and mtDNA deletions, the pathology of MS is not.
Insights
Mitochondrial DNA deletions do not accumulate in multiple sclerosis (MS) brains, unlike in aging or neurodegenerative diseases like Alzheimer's and Parkinson's. This study clarifies the role of mtDNA deletions in MS pathology.
Area of Science:
- Neuroscience
- Genetics
- Cell Biology
Background:
- Multiple Sclerosis (MS) lesions show oxidative damage to mitochondrial DNA (mtDNA) and reduced enzyme activity.
- Reactive oxygen species and nitric oxide in MS lesions may link oxidative damage to mitochondrial dysfunction.
- mtDNA deletions in the brain are implicated in neurodegeneration and aging.
Purpose of the Study:
- To investigate the accumulation of mitochondrial DNA (mtDNA) deletions in the brains of multiple sclerosis (MS) patients.
- To determine if mtDNA deletions are a pathological feature of MS, distinct from aging and other neurodegenerative diseases.
Main Methods:
- Quantified mtDNA deletions using real-time PCR in laser-dissected neuronal and glial cells from postmortem MS brains and controls.
- Analyzed mtDNA deletions in normal-appearing gray and white matter, and active plaques of MS patients.
- Correlated mtDNA deletion proportions with age and pathology, including Alzheimer's and Parkinson's disease cases.
Main Results:
- No pathology-related accumulation of mtDNA deletions was found in MS brains compared to controls.
- mtDNA deletions accumulated in non-neurological individuals over 60 and in Alzheimer's/Parkinson's disease patients.
- Higher rates of mtDNA deletions were observed in COX-negative cells compared to COX-positive cells.
Conclusions:
- mtDNA deletions accumulate with aging and in neurodegenerative diseases (Parkinson's, Alzheimer's) but not in multiple sclerosis (MS).
- The accumulation of COX-negative cells and mtDNA deletions is not a hallmark of MS pathology.
Related Concept Videos
01:19Multiple Sclerosis l: Introduction
01:22Lysosomal Hydrolases