The Effects of Exercise on Dopamine Neurotransmission in Parkinson’s Disease: Targeting Neuroplasticity to Modulate Basal Ganglia Circuitry

TLDR

Animal studies demonstrate that exercise induces neuroplasticity in corticostriatal circuits affected by Parkinson’s disease, modulating dopamine and glutamate transmission, synaptogenesis, and cerebral blood flow, with skilled exercise producing greater regional effects on frontal‑striatal circuits than aerobic exercise. This review investigates how exercise may drive circuit‑specific neuroplasticity in dopamine‑depleted models, focusing on the dorsal lateral striatum and prefrontal circuitry underlying motor and cognitive deficits, and hypothesizes that increased neuronal metabolic demand coupled with enhanced blood flow could be key mechanisms for brain repair and disease modification. The authors analyze how exercise modulates neuroplasticity in the dorsal lateral striatum and prefrontal circuitry, proposing that synergistic increases in metabolic demand and cerebral blood flow underlie the observed circuit‑specific effects.

Abstract

Animal studies have been instrumental in providing evidence for exercise-induced neuroplasticity of corticostriatal circuits that are profoundly affected in Parkinson's disease. Exercise has been implicated in modulating dopamine and glutamate neurotransmission, altering synaptogenesis, and increasing cerebral blood flow. In addition, recent evidence supports that the type of exercise may have regional effects on brain circuitry, with skilled exercise differentially affecting frontal-striatal related circuits to a greater degree than pure aerobic exercise. Neuroplasticity in models of dopamine depletion will be reviewed with a focus on the influence of exercise on the dorsal lateral striatum and prefrontal related circuitry underlying motor and cognitive impairment in PD. Although clearly more research is needed to address major gaps in our knowledge, we hypothesize that the potential effects of exercise on inducing neuroplasticity in a circuit specific manner may occur through synergistic mechanisms that include the coupling of an increasing neuronal metabolic demand and increased blood flow. Elucidation of these mechanisms may provide important new targets for facilitating brain repair and modifying the course of disease in PD.