Acta Neuropathologica

, Volume 120, Issue 5, pp 623–631 | Cite as

Mitochondrial abnormalities in the putamen in Parkinson’s disease dyskinesia

  • Alipi V. Naydenov
  • Fair Vassoler
  • Andrew S. Luksik
  • Joanna Kaczmarska
  • Christine Konradi
Original Paper


Prolonged treatment of Parkinson’s disease (PD) with levodopa leads to disabling side effects collectively referred to as ‘dyskinesias’. We hypothesized that bioenergetic function in the putamen might play a crucial role in the development of dyskinesias. To test this hypothesis, we used post mortem samples of the human putamen and applied real time–PCR approaches and gene expression microarrays. We found that mitochondrial DNA (mtDNA) levels are decreased in patients who have developed dyskinesias, and mtDNA damage is concomitantly increased. These pathologies were not observed in PD subjects without signs of dyskinesias. The group of nuclear mRNA transcripts coding for the proteins of the mitochondrial electron transfer chain was decreased in patients with dyskinesias to a larger extent than in patients who had not developed dyskinesias. To examine whether dopamine fluctuations affect mtDNA levels in dopaminoceptive neurons, rat striatal neurons in culture were repeatedly exposed to levodopa, dopamine or their metabolites. MtDNA levels were reduced after treatment with dopamine, but not after treatment with dopamine metabolites. Levodopa led to an increase in mtDNA levels. We conclude that mitochondrial susceptibility in the putamen plays a role in the development of dyskinesias.


Parkinson’s disease Dyskinesia Putamen Mitochondria Respiratory chain 



The authors are indebted to the staff of the Harvard Brain Tissue Resource Center at McLean Hospital, who provided all tissues and to the study subjects. Angela Cenci, MD, provided helpful discussions. Melissa Hodges provided technical support in the laboratory. This work was supported by the National Institutes of Health [NS48235 to C.K.; MH068855 to HBTRC]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding institutes or the National Institutes of Health.

Supplementary material

401_2010_740_MOESM1_ESM.doc (121 kb)
Demographic data of all samples. Not all samples were available for each experiment. Duration of disease and L-dopa levels were significantly different in the entire group. Thus, subgroups of samples were used which were controlled for these parameters. (DOC 121 kb)
401_2010_740_MOESM2_ESM.doc (79 kb)
Sequences of primer pairs for PCR reactions (DOC 79 kb)
401_2010_740_MOESM3_ESM.doc (131 kb)
Detailed gene expression data of electron transport proteins. ‘Mean’ data are natural values; p-values were obtained from log2 –transformed data to ensure normal distribution. (DOC 131 kb)


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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Alipi V. Naydenov
    • 1
  • Fair Vassoler
    • 1
  • Andrew S. Luksik
    • 1
  • Joanna Kaczmarska
    • 1
  • Christine Konradi
    • 1
    • 2
    • 3
  1. 1.Department of Pharmacology and PsychiatryVanderbilt UniversityNashvilleUSA
  2. 2.Center for Molecular NeuroscienceVanderbilt UniversityNashvilleUSA
  3. 3.Kennedy Center for Research on Human DevelopmentVanderbilt UniversityNashvilleUSA

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