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High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease

Nature Genetics volume 38, pages 515–517 (2006)Cite this article

Abstract

Here we show that in substantia nigra neurons from both aged controls and individuals with Parkinson disease, there is a high level of deleted mitochondrial DNA (mtDNA) (controls, 43.3% ± 9.3%; individuals with Parkinson disease, 52.3% ± 9.3%). These mtDNA mutations are somatic, with different clonally expanded deletions in individual cells, and high levels of these mutations are associated with respiratory chain deficiency. Our studies suggest that somatic mtDNA deletions are important in the selective neuronal loss observed in brain aging and in Parkinson disease.

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Figure 1: Respiratory chain deficiency and analysis of mtDNA deletions in substantia nigra neurons.
Figure 2: Characterization and quantification of mtDNA deletion in substantia nigra neurons from individuals with Parkinson disease and from age-matched controls.

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References

  1. Taylor, R.W. & Turnbull, D.M. Nat. Rev. Genet. 6, 389–402 (2005).

    Article  CAS  Google Scholar 

  2. Johnson, M.A., Turnbull, D.M., Dick, D.J. & Sherratt, H.S. J. Neurol. Sci. 60, 31–53 (1983).

    Article  CAS  Google Scholar 

  3. Sciacco, M., Bonilla, E., Schon, E.A., DiMauro, S. & Moraes, C.T. Hum. Mol. Genet. 3, 13–19 (1994).

    Article  CAS  Google Scholar 

  4. Cortopassi, G.A. & Arnheim, N. Nucleic Acids Res. 18, 6927–6933 (1990).

    Article  CAS  Google Scholar 

  5. Müller-Höcker, J. Am. J. Pathol. 134, 1167–1173 (1989).

    PubMed  PubMed Central  Google Scholar 

  6. Taylor, R.W. et al. J. Clin. Invest. 112, 1351–1360 (2003).

    Article  CAS  Google Scholar 

  7. Fearnley, J.M. & Lees, A.J. Brain 114, 2283–2301 (1991).

    Article  Google Scholar 

  8. Greene, J.G., Dingledine, R. & Greenamyre, J.T. Neurobiol. Dis. 18, 19–31 (2005).

    Article  CAS  Google Scholar 

  9. Smeyne, R.J. & Jackson-Lewis, V. Brain Res. Mol. Brain Res. 134, 57–66 (2005).

    Article  CAS  Google Scholar 

  10. Itoh, K., Weis, S., Mehraein, P. & Muller-Hocker, J. Neurobiol. Aging 17, 843–848 (1996).

    Article  CAS  Google Scholar 

  11. Cottrell, D.A. et al. Neurobiol. Aging 22, 265–272 (2001).

    Article  CAS  Google Scholar 

  12. He, L. et al. Nucleic Acids Res. 30, e68 (2002).

    Article  Google Scholar 

  13. Trifunovic, A. et al. Nature 429, 417–423 (2004).

    Article  CAS  Google Scholar 

  14. Kraytsberg, Y. et al. Nat. Genet., advance online publication 2 April 2006 (doi: 10.1038/ng1778).

  15. Luoma, P. et al. Lancet 364, 875–882 (2004).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work has been supported by Alzheimer's Research Trust, Wellcome Trust, Medical Research Council UK and European Neurological Society.

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Author notes

  1. Andreas Bender and Kim J Krishnan: These authors contributed equally to this work.

Authors and Affiliations

  1. Mitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, The Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne, NE2 4HH, UK

    Andreas Bender, Kim J Krishnan, Geoffrey A Taylor, Amy K Reeve, Joshua S Hersheson, Joanne Betts, Robert W Taylor & Douglass M Turnbull

  2. MRC Building, Institute for the Health of the Elderly, Newcastle General Hospital, Newcastle upon Tyne, NE4 6BE, UK

    Christopher M Morris

  3. Department of Neuropathology, Institute for the Health of the Elderly, Newcastle General Hospital, Newcastle upon Tyne, NE4 6BE, UK

    Robert H Perry & Evelyn Jaros

  4. Department of Neurology, University of Munich, Klinikum Grosshadern, Marchioninistr. 15, Munich, 81377, Germany

    Andreas Bender & Thomas Klopstock

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  1. Andreas Bender
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  2. Kim J Krishnan
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Corresponding author

Correspondence to Douglass M Turnbull.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Characterization of real-time PCR assay. (PDF 54 kb)

Supplementary Table

Primers used. (PDF 73 kb)

Supplementary Methods (PDF 108 kb)

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Bender, A., Krishnan, K., Morris, C. et al. High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease. Nat Genet 38, 515–517 (2006). https://doi.org/10.1038/ng1769

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