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

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.