Chronic models of the preclinical and early clinical stages of Parkinson’s disease in mice

Abstract

Degradation of the dopaminergic nigrostriatal system is a central process of the pathogenesis of Parkinson’s disease, which is a chronic neurodegenerative disorder. A specific feature of the disease is longterm asymptomatic progress over decades, which occurs due to the functioning of compensatory processes in the brain. Specific motor symptoms appear after substantial lesion of the nigrostriatal system and depletion of compensatory reserves. At this stage, traditional treatment of patients has low efficiency. In the present study, we developed new neurotoxic models of the maximally prolonged preclinical stage and early clinical stage of Parkinson’s disease in mice and performed a thorough evaluation of motor behavior and the morphofunctional state of the nigrostriatal system in these animals. Further comparative study of these models will help to identify: (a) specific peripheral biomarkers of each stage as a basis for the development of the early preclinical diagnostics of Parkinson’s disease; (b) the mechanisms of neuroplasticity that are responsible for asymptomatic progress of the disease; (c) molecular triggers of impaired motor behavior during the transition from the preclinical stage to the clinical stage.