Alterations in mitochondrial membrane potential in peripheral blood mononuclear cells in Parkinson's Disease: Potential for a novel biomarker

Background: Progressive apoptosis in the dopaminergic neurons of substantia nigra lead to Parkinson's disease. Since neurons require substantially higher supply of energy, their mitochondria have a pivotal status in neuronal survival. These organelles have a key role to play in apoptosis and any impairment thereof may lead to apoptosis mediated cell death. Objectives: To evaluate and compare the mitochondrial membrane potential (Delta psi) in Parkinson's disease patients and healthy controls. Methods: We evaluated the mitochondrial membrane potential (Delta psi) in the peripheral blood mononuclear cells by Flow cytometry using a lipophillic cationic dye JC-1 in Parkinson's disease patients (N = 61) and healthy controls (N = 37). Results: JC-1 fluorescence was measured and represented as percentage positivity i.e., Mean +/- SEM in FL-2 (representing non-apoptotic aggregates) and FL-1 (indicating apoptotic cell population having depolarized or damaged mitochondria) channels. The ratio of % FL-2 and % FL-1, which is an indicator of cellular mitochondrial membrane potential, was found to be significantly higher in healthy controls (Mean +/- SEM = 60.48 +/- 18.42) as compared to patients (Mean +/- SEM = 24.30 +/- 4.671) in both stimulated and unstimulated conditions. Conclusions: Mitochondrial membrane potential is altered and hence its evaluation in peripheral blood mononuclear cells may serve as an early marker of apoptosis in PD and, therefore, may pave way for early interventions. Since Delta Psi has a role in the maintenance of electrochemical gradient, the disruption of which may lead to neuronal apoptosis, Delta psi is intricately nested within etiopathogenesis of PD and may prove to be useful in design of diagnostics, prognostics and therapeutics for PD.