Inflammation And Denervation In Skeletal Muscle Of Parkinson’S Disease Patients

Abstract

PURPOSE: Parkinson’s disease (PD) is a neurodegenerative condition that compromises skeletal muscle function in ~1% of the population over 60y. Increasing evidence indicates PD has an inflammatory component, which may contribute to denervation in skeletal muscle and eventual motor unit loss. However, while the effects of aging on muscle inflammation are reasonably well-studied, the effects of aging with PD are unclear. Compared to age-matched controls, we have previously shown exaggerated architectural changes in PD muscle (e.g., type I myofiber grouping resulting from dynamic denervation/renervation cycling) along with increased expression of indices of neuromuscular junction instability, and some signs of reversal with high intensity exercise training. The purpose of this study is to further investigate PD skeletal muscle pathology, examine the role of muscle inflammation, and explore the impact of exercise training. METHODS: Vastus lateralis skeletal muscle biopsies were obtained from three cohorts of individuals: PD patients (n=30, 67±7y, Hoehn & Yahr stage 2-3), age-matched older adults (OA) and young adults (YA). To assess the effect of exercise training, a subset of PD patients (n=16) underwent 16wk high intensity training. Markers of denervation (e.g., neural cell adhesion molecule (NCAM) and sodium channel Nav1.5) and inflammation [e.g., IL-1β, TNF-α, and TNF-like weak inducer of apoptosis (TWEAK)] are being assessed across the three groups and within the PD group pre- and post-training. RESULTS AND CONCLUSION: We expect the study findings to aid in differentiating the effects of primary aging vs. aging with PD in skeletal muscle. Further, we anticipate high intensity exercise training will improve the inflammatory profile of PD muscle. Complete results will be available for presentation at the 2018 ACSM national meeting.