Treadmill exercise elevates striatal dopamine D2 receptor binding potential in patients with early Parkinson’s disease

Abstract

We have previously demonstrated changes in dopaminergic neurotransmission after intensive exercise in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse model of Parkinson’s disease (PD), including an increase in the dopamine D₂ receptor (DA-D₂R), using noninvasive PET imaging with the radioligand [¹⁸F]fallypride. The purpose of this feasibility and translational study was to examine whether intensive exercise leads to similar alterations in DA-D₂R expression using PET imaging with [¹⁸F]fallypride in individuals with early-stage PD. In this pilot study, four patients with early-stage PD were randomized to receive intensive exercise (treadmill training sessions three times/week for 8 weeks) or no exercise. Two healthy age-matched individuals participated in treadmill training. Alterations in the DA-D₂R binding potential (BP) as a marker for receptor expression were determined using PET imaging with [¹⁸F]fallypride. Turning performance in the patients with PD as a measure of postural control and the Unified Parkinson’s Disease Rating Scale scores pre-exercise and postexercise were determined. Our data showed an exercise-induced increase in [¹⁸F]fallypride BP as well as improved postural control in patients with PD who exercised. Changes in DA-D₂R BP were not observed in patients with PD who did not exercise. These results suggest that exercise can lead to neuroplasticity in dopaminergic signaling and contribute to improved function that may be task specific (postural control) in early-stage PD.