Potential of Theobromine in the Reduction of L-Dopainduced Dyskinesia in Caenorhabditis Elegans Model of Parkinson’s Disease

Abstract

Chronic L-DOPA therapy, currently the most effective PD treatment, eventually leads to L-DOPA-induced dyskinesia. Literature has revealed that caffeine, as an L-DOPA adjunct, lessens locomotion and mechanosensation impairments in Caenorhabditis elegans (UA57), though data on other methylxanthines’ potential regarding the same is scarce. This study investigated locomotion, basal slowing response (BSR), and mechanosensation of C. elegans UA57 overexpressing CAT-2 when treated with theobromine, L-DOPA, and their combinations. Transgenic C. elegans were treated with vehicle (0.1% DMSO), L-DOPA (20 or 60 mM), theobromine (62.5 or 125 μg/mL), and 60 mM L-DOPA + 62.5 or 125 μg/mL theobromine (60LC10 and 60LC20), then subjected to the assays for 4 days with a phenotypic control (n = 30). Chronic exposure to 125 μg/mL theobromine alone and in combination with 60 mM L-DOPA improved locomotion body bends on day 3.. Meanwhile, exposure to 62.5 μg/mL and 125 μg/mL theobromine conferred acute protection of reversals (day 1) and chronic protection of the basal slowing response (days 2-3). In contrast, mechanosensory responses to nose, head, tail, and harsh touch appear to be unprotected by theobromine, but are still inconclusive due to the low sensitivity scoring method used. This study shows potential for theobromine in PD therapy and warrants further investigation.