Estimates of Intracellular Dopamine in Parkinson’s Disease: A Systematic Review and Meta-Analysis

Abstract

Background: The hallmark of Parkinson’s disease is depletion of dopamine in the basal ganglia. Models of Parkinson’s disease include dopamine as a contributor to disease progression. However, intraneuronal levels of dopamine have not been reported. Objective: Meta-analytic methods were utilized to determine intracellular dopamine levels in Parkinson’s disease. Methods: A systematic review of the literature and frequentist meta-analyses were performed. Dopamine levels were scaled for cell and axon numbers as well as VMAT2 protein levels. Results: Reduced tissue dopamine, dopaminergic cell bodies and VMAT2 protein were confirmed. The ratio of Parkinson’s to normal brain intracellular dopamine scaled for either cell or axon number, each with VMAT2 level in the caudate ranged from 1.49 to 1.87 (p\u200a=\u200a0.51 and p\u200a=\u200a0.12, respectively) and in the putamen from 0.75 to 4.61 (p\u200a=\u200a0.40 and 0.001, respectively). Conclusion: Free, intracellular dopamine levels are not reduced in Parkinson’s disease compared to normals to a similar degree as are total tissue concentrations, supporting the relevance of modulating VMAT2, neuromelanin and/or dopamine synthesis as rational neuroprotective strategies.