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Mitochondrial dysfunction within the synapses of substantia nigra neurons in Parkinson's disease


Mitochondrial dysfunction within the cell bodies of substantia nigra neurons is prominent in both ageing and Parkinson's disease. The loss of dopaminergic substantia nigra neurons in Parkinson's disease is associated with loss of synapses within the striatum, and this may precede neuronal loss. We investigated whether mitochondrial changes previously reported within substantia nigra neurons were also seen within the synapses and axons of these neurons. Using high resolution quantitative fluorescence immunohistochemistry we determined mitochondrial density within remaining dopaminergic axons and synapses, and quantified deficiencies of mitochondrial Complex I and Complex IV in these compartments. In Parkinson's disease mitochondrial populations were increased within axons and the mitochondria expressed higher levels of key electron transport chain proteins compared to controls. Furthermore we observed synapses which were devoid of mitochondrial proteins in all groups, with a significant reduction in the number of these 'empty' synapses in Parkinson's disease. This suggests that neurons may attempt to maintain mitochondrial populations within remaining axons and synapses in Parkinson's disease to facilitate continued neural transmission in the presence of neurodegeneration, potentially increasing oxidative damage. This compensatory event may represent a novel target for future restorative therapies in Parkinson's disease.

Type Journal
ISBN 2373-8057 (Print) 2373-8057 (Linking)
Authors Reeve, A. K.; Grady, J. P.; Cosgrave, E. M.; Bennison, E.; Chen, C.; Hepplewhite, P. D.; Morris, C. M.
Responsible Garvan Author Dr John Grady
Publisher Name NPJ Parkinson's Disease
Published Date 2018-03-01
Published Volume 4
Published Pages 9
Status Published in-print
DOI 10.1038/s41531-018-0044-6
URL link to publisher's version