Dopaminergic Neurons Exhibit an Age-Dependent Decline in Electrophysiological Parameters in the MitoPark Mouse Model of Parkinson's Disease.

Abstract

Parkinson's disease (PD) is the second most diagnosed neurodegenerative disorder, and the classic motor symptoms of the disease are attributed to selective loss of dopaminergic neurons of the substantia nigra. The MitoPark mouse is a genetic model of PD that mimics many of the key characteristics of the disease and enables the study of progressive neurodegeneration in parkinsonism. Here we have identified functional deficits in the ion channel physiology of dopaminergic neurons from MitoPark mice that both precede and are concurrent with the time course of behavioral symptomatology. Because PD is a progressive disease with a long asymptomatic phase, identification of early functional adaptations could lay the groundwork to test therapeutic interventions that halt or reverse disease progression.