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Dopaminergic midbrain neurons are the prime target for mitochondrial DNA deletions

Lookup NU author(s): Dr Matthias Elstner, Emeritus Professor Doug Turnbull

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Abstract

Mitochondrial dysfunction is a consistent finding in neurodegenerative disorders like Alzheimer's (AD) or Parkinson's disease (PD) but also in normal human brain aging. In addition to respiratory chain defects, damage to mitochondrial DNA (mtDNA) has been repeatedly reported in brains from AD and PD patients. Most studies though failed to detect biologically significant point mutation or deletion levels in brain homogenate. By employing quantitative single cell techniques, we were recently able to show significantly high levels of mtDNA deletions in dopaminergic substantia nigra (SN) neurons from PD patients and age-matched controls. In the present study we used the same approach to quantify the levels of mtDNA deletions in single cells from three different brain regions (putamen, frontal cortex, SN) of patients with AD (n = 9) as compared to age-matched controls (n = 8). There were no significant differences between patients and controls in either region but in both groups the deletion load was markedly higher in dopaminergic SN neurons than in putamen or frontal cortex (p

Publication metadata

Author(s): Bender A, Schwarzkopf RM, McMillan A, Krishnan KJ, Rieder G, Neumann M, Elstner M, Turnbull DM, Klopstock T

Publication type: Article

Publication status: Published

Journal: Journal of Neurology

Year: 2008

Volume: 255

Issue: 8

Pages: 1231-1235

ISSN (print): 0340-5354

ISSN (electronic): 1432-1459

Publisher: Steinkopff

URL: http://dx.doi.org/10.1007/s00415-008-0892-9

DOI: 10.1007/s00415-008-0892-9

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