Relationship between mitochondria and α-synuclein: a study of single substantia nigra neurons

Arch Neurol. 2012 Mar;69(3):385-93. doi: 10.1001/archneurol.2011.2675.

Abstract

Objective: To explore the relationship between α-synuclein pathology and mitochondrial respiratory chain protein levels within single substantia nigra neurons.

Design: We examined α-synuclein and mitochondrial protein expression in substantia nigra neurons of 8 patients with dementia with Lewy bodies, 5 patients with Parkinson disease, and 8 control subjects. Protein expression was determined using immunocytochemistry followed by densometric analysis.

Patients: We examined single substantia nigra neurons from 5 patients with idiopathic Parkinson disease (mean age, 81.2 years), 8 patients with dementia with Lewy bodies (mean age, 75 years), and 8 neurologically and pathologically normal control subjects (mean age, 74.5 years). The control cases showed minimal Lewy body pathology and cell loss. Patients with dementia with Lewy bodies and idiopathic Parkinson disease fulfilled the clinical and neuropathologic criteria for these diseases.

Results: Our results showed that mitochondrial density is the same in nigral neurons with and without α-synuclein pathology. However, there are significantly higher levels of the respiratory chain subunits in neurons containing α-synuclein pathology.

Conclusions: The finding of increased levels of respiratory chain complex subunits within neurons containing α-synuclein does not support a direct association between mitochondrial respiratory chain dysfunction and the formation of α-synuclein pathology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cell Count
  • Densitometry
  • Female
  • Humans
  • Image Processing, Computer-Assisted
  • Immunohistochemistry
  • Lewy Body Disease / pathology
  • Male
  • Mitochondria / metabolism*
  • Mitochondrial Diseases / metabolism*
  • Mitochondrial Proteins / metabolism
  • Neurons / metabolism*
  • Paraffin Embedding
  • Parkinson Disease / pathology
  • Reproducibility of Results
  • Substantia Nigra / metabolism*
  • Tissue Fixation
  • alpha-Synuclein / metabolism*

Substances

  • Mitochondrial Proteins
  • alpha-Synuclein