High Glucose Diet Attenuates Dopaminergic Neuronal Function in C. elegans Leading to Acceleration of Aging Process

Abstract Background: Environmental or exogenous factors that cause Parkinson’s disease have not been sufficiently elucidated. Here, we investigate a causative effect of high glucose diet on Parkinson’s disease-relevant dopaminergic neuronal system in C. elegans . Methods: Aging parameters were first observed by measuring the lifespan, body movement, and body sizes with and without background of high glucose. Toxic effect of high glucose diet was further explored by observing the dopaminergic neurons using transgenic dat-1 ::GFP strains, BZ555 under Zeiss microscope. And extended the experiments by assessing dopamine-related behavioral analysis including basal slowing response and alcohol avoidance. Aggregation on the α -synucleins were also assessed by observing the NL5901 worms. Results: . Worms fed with 250 mM glucose showed daf-2 -independent regulation of aging displaying short lifespan (≤15 days), long body size (max. 140%) and slow movement (min. 30%, 10 bends/min). Anterior dopaminergic neurons were rapidly inactivated (70%) by glucose-rich diet from 12 h of exposure suggesting specific degeneration in ADE neurons. The dysregulation of neurons led to deteriorations in dopaminergic behaviors including basal slowing response (BSR). High glucose diet decreased dopamine synthesis (40 vs. 15 pg/mg protein) and induced α-synuclein aggregation in the muscles. Conclusion: Results demonstrate a potential of high glucose diet as a trigger of dopaminergic neuronal dysregulation conjugating aging acceleration.