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. Neurodegeneration: powering communication in the face of adversity Large numbers of healthy mitochondria are found along neuronal axons in postmortem brain tissue from patients with Parkinson’s disease (PD). Mitochondrial dysfunction is implicated in neurodegenerative diseases and is thought to precede neuronal loss. Although disrupted mitochondria have been reported in neuronal cell bodies, little is known about the mitochondria in axons and at synapses of substantia nigra neurons in PD. Amy Reeve at Newcastle University, UK, and colleagues found that although PD neurons have fewer synapses, their axons contained more mitochondria than age-matched controls. Moreover, there were fewer synapses devoid of mitochondria than in controls. Given that mitochondria power the movement and recycling of neurotransmitter containing vesicles at synapses, these findings suggest that in PD neurons attempt to compensate for the loss of synapses by maintaining neurotransmission in the remaining ones.