Somatic mitochondrial DNA mutations in single neurons and glia

Ippolita Cantuti-Castelvetri, Michael T. Lin, Kangni Zheng, Christine E. Keller-McGandy, Rebecca A. Betensky, Donald R. Johns, M. Flint Beal, David G. Standaert, David K. Simon

Research output: Contribution to journalArticlepeer-review

Abstract

Somatic mitochondrial DNA (mtDNA) point mutations reach high levels in the brain. However, the cell types that accumulate mutations and the patterns of mutations within individual cells are not known. We have quantified somatic mtDNA mutations in 28 single neurons and in 18 single glia from post-mortem human substantia nigra of six control subjects. Both neurons and glia contain mtDNA with somatic mutations. Single neurons harbor a geometric mean (95% CI) of 200.3 (152.9-262.4) somatic mtDNA point mutations per million base pairs, compared to 133.8 (97.5-184.9) for single glia (p = 0.0251). If mutations detected multiple times in the same cell are counted only once, the mean mutation level per million base pairs remains elevated in single neurons (146.9; 124.0-174.2) compared to single glia (100.5; 81.5-126.5; p = 0.009). Multiple distinct somatic point mutations are present in different cells from the same subject. Most of these mutations are individually present at low levels (less than 10-20% of mtDNA molecules), but with high aggregate mutation levels, particularly in neurons. These mutations may contribute to changes in brain function during normal aging and neurodegenerative disorders.

Original languageEnglish (US)
Pages (from-to)1343-1355
Number of pages13
JournalNeurobiology of Aging
Volume26
Issue number10
DOIs
StatePublished - Nov 2005

Keywords

  • Acquired
  • Aging
  • Allele-specific PCR
  • Dopaminergic
  • Laser capture microdissection
  • Mitochondria
  • Mutation
  • Oxidative stress
  • Parkinson's disease
  • Single cell
  • Somatic

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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