A Novel Animal Model of Parkinson's Disease Using Optogenetics: Representation of Various Disease Stages by Modulating the Illumination Parameter.

Abstract

BACKGROUND: The classic animal model of Parkinson's disease (PD) using neurotoxin can only simulate fixed stages of the disease by causing irreversible damage to the nigrostriatal system. OBJECTIVES: To develop an optogenetic PD model that can modulate the severity of disease by optical stimulation by introducing the halorhodopsin (NpHR) gene into the substantia nigra compacta. METHODS: Fifteen rats received injections of engineered AAV with NpHR-YFP gene into the substantia nigra. They were then subjected to illumination of 590-nm light wavelengths with 3 optical stimulation conditions, i.e., frequency-width: 5 Hz-10 ms (n = 5), 5 Hz-100 ms (n = 5), and 50 Hz-10 ms (n = 5). Eleven rats received 6-hydroxydopamine injections to establish the conventional PD model. RESULTS: The optogenetic models showed characteristic PD manifestations, similar to those of the conventional models; the severity of forelimb akinesia correlated with the total illumination value (frequency × width). The group with a low illumination value (5 Hz-10 ms) was comparable to the conventional partial model whereas the groups with high illumination values (5 Hz-100 ms and 50 Hz-10 ms) were similar to the conventional complete model. CONCLUSIONS: An optogenetic PD model has the advantage of more appropriately representing various PD stages by controlling illumination parameters.