期刊
STEREOTACTIC AND FUNCTIONAL NEUROSURGERY
卷 96, 期 1, 页码 22-32出版社
KARGER
DOI: 10.1159/000486644
关键词
Animal model; Halorhodopsin; Optogenetics; Parkinson's disease
资金
- Korea Health Technology R&D Project through the Korea Health Industry Development Institute - Ministry of Health & Welfare, Republic of Korea [HI16C2188]
- Asan Life Science Institute Grant from the Asan Medical Center, Seoul, Republic of Korea [16-241]
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 x 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. (c) 2018 S. Karger AG, Basel.
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