Chronic hyperactivation of midbrain dopamine neurons causes preferential dopamine neuron degeneration.

ABSTRACT: Parkinson's disease (PD) is characterized by the death of substantia nigra (SNc) dopamine (DA) neurons, but the pathophysiological mechanisms that precede and drive their death remain unknown. The activity of DA neurons is likely altered in PD, but we understand little about if or how chronic changes in activity may contribute to degeneration. To address this question, we developed a chemogenetic (DREADD) mouse model to chronically increase DA neuron activity, and confirmed this increase using ex vivo electrophysiology. Chronic hyperactivation of DA neurons resulted in prolonged increases in locomotor activity during the light cycle and decreases during the dark cycle, consistent with chronic changes in DA release and circadian disturbances. We also observed early, preferential dege

SUBMITTER: Rademacher K 

PROVIDER: S-EPMC11030348 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature