Ketone ester-enriched diet ameliorates motor and dopamine release deficits in MitoPark mice

Background: Parkinson's disease is a progressive, neurodegenerative disease characterized by motor dysfunction and dopamine deficits. The MitoPark mouse recapitulates several facets of Parkinson's disease, including gradual development of motor deficits, which enables the study of potential therapeutic interventions. One therapeutic strategy involves decreasing the mitochondrial metabolic load by inducing ketosis and providing an alternative energy source for neurons, leading to decreased neuronal oxidative stress. Objective: We assessed whether administration of a ketone ester-enriched diet would improve motor and dopamine release deficits in MitoPark mice. Methods: Motor function (rotarod and open field tests), dopamine release (fast-scan cyclic voltammetry), tissue dopamine levels (GC-MS), and dopamine neurons and axons (immunofluorescence) were assessed in MitoPark and control mice fed either the standard or ketone ester-enriched diets. Results: When started on the ketone diet before motor dysfunction onset, MitoPark mice had preserved motor function relative to standard diet MitoPark mice. While the ketone ester enriched diet did not preserve dopamine neurons or striatal dopamine axons, dopamine release in ketone diet MitoPark mice was greater than standard diet MitoPark mice but less than control mice. In a follow up experiment, we began the ketone diet after motor dysfunction onset and observed a modest preservation of motor function in ketone diet MitoPark mice relative to standard diet MitoPark mice. Conclusion: The improvement in motor dysfunction indicates that a ketone ester enriched diet or ketone supplement may represent a promising adjunct treatment for Parkinson's disease. ### Competing Interest Statement The authors have declared no competing interest.