Motor and Cognitive Deficits Accompanied by Progressive Microstructural and Metabolic Deterioration in a Mouse Model of Parkinson’s Disease

Motivation: The MitoPark mouse model, induced by mitochondrial dysfunction, has been confirmed to exhibit both motor and cognitive impairments resembling Parkinson's disease. However, further research is needed to delve into the mechanisms underlying these changes. Goal(s): Ｗe aimed to explore age-related changes in behavioral performances, brain microstructure, and metabolic functions in MitoPark mice. Approach: Every four weeks, a battery of tests including behavioral assessments, DTI scanning, and respiratory assays were performed on 8-week-old experimental mice. Results: MitoPark mice showed progressive degeneration in both motor and cognitive functions and impairments of microstructure and energy metabolism in dopaminergic pathways with increasing age. Impact: Progressively deteriorating mitochondrial respiration and glycolysis, impaired neural integrity, and demyelination in dopaminergic pathways in MitoPark mice may provide potential mechanisms underlying motor and non-motor deficits during the aging process of Parkinson's disease.