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.
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.
Authors: Graham R Campbell; Iryna Ziabreva; Amy K Reeve; Kim J Krishnan; Richard Reynolds; Owen Howell; Hans Lassmann; Doug M Turnbull; Don J Mahad Journal: Ann Neurol Date: 2010-11-08 Impact factor: 10.422