Intense exercise increases dopamine transporter and neuromelanin concentrations in the substantia nigra in Parkinson's disease

Abstract

Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons. Exercise has been reported to slow the clinical progression of PD. We evaluated the dopaminergic system of patients with mild and early PD before and after a six-month program of intense exercise. Using ¹⁸F-FE-PE2I PET imaging, we measured dopamine transporter (DAT) availability in the striatum and substantia nigra. Using NM-MRI, we evaluated the neuromelanin content in the substantia nigra. Exercise reversed the expected decrease in DAT availability into a significant increase in both the substantia nigra and putamen. Exercise also reversed the expected decrease in neuromelanin concentration in the substantia nigra into a significant increase. These findings suggest improved functionality in the remaining dopaminergic neurons after exercise. Further research is needed to validate our findings and to pinpoint the source of any true neuromodulatory and neuroprotective effects of exercise in PD in large clinical trials.

Fig. 1. Dopamine Transporter Levels Pre- and Post-Exercise.

A Average ¹⁸F-FE-PE2I DAT BP_ND images before and after six months of exercise. The red box including the midbrain and SN is enlarged. Note: The left side of the color bar (0.0–3.0) corresponds to the DAT BP_ND in the striatum and the right side (0.0–1.0) to the DAT BP_ND in the SN shown in the inset images. BP_ND is unitless. Orientation is axial. B ¹⁸F-FE-PE2I BP_ND in the SN pre- and post-exercise by study participant. Individual lines are red if an increase was observed, blue if a decrease was observed. The solid black line represents the mean of our cohort, the dashed black line represents the expected decrease from the pre-exercise average in the absence of intervention.

Fig. 2. Neuromelanin Levels Pre- and Post-Exercise.

A Average NM-MRI pre- and post-exercise. Axial image on the left shows the acquired NM image and the red box locates the cut-out sections shown. Top row shows the raw T1-weighted NM image (T1w NM), the bottom row shows the corresponding CR values. B CR in the SNc pre- and post-exercise by study participant. Individual lines are red if an increase was observed, blue if a decrease was observed. The solid black line represents the mean of our cohort, the dashed black line represents the baseline average multiplied by the expected decrease without intervention.