Optogenetic inactivation of the entopeduncular nucleus improves forelimb akinesia in a Parkinson's disease model.

Autor: Yoon HH; Department of Neurological Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea., Nam MH; Center for Neuroscience, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea., Choi I; Department of Neurosurgery, Hallym University, Dongtan Sacred Heart Hospital, 7, Keunjaebong-gil, Hwaseong-si, Gyeonggi-do 445-907, Republic of Korea., Min J; Department of Neurological Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea., Jeon SR; Department of Neurological Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea. Electronic address: srjeon@amc.seoul.kr.
Jazyk: angličtina
Zdroj: Behavioural brain research [Behav Brain Res] 2020 May 27; Vol. 386, pp. 112551. Date of Electronic Publication: 2020 Feb 10.
DOI: 10.1016/j.bbr.2020.112551
Abstrakt: We performed optogenetic inactivation of rats' entopeduncular nucleus (EP, homologous to primates' globus pallidus interna (GPi)) and investigated the therapeutic effect in a rat model of PD. 6-Hydroxydopamine (6-OHDA)-induced hemiparkinsonian rats were injected with either a virus for halorhodopsin expression that is used to inactivate GABAergic neurons or a control virus injection and received optic fiber insertion. All the rats were illuminated by 590 nm of light. Each rat was then subjected to sequential sessions of stepping tests under controlled illumination patterns. The stepping test is a reliable evaluation method for forelimb akinesia. The number of adjusting steps was significantly higher in experimental (optogene with reporter gene expression) (5Hz - 10ms: 15.7 ± 1.9, 5Hz - 100ms: 16.0 ± 1.8, continuous: 21.6 ± 1.9) than control rats (reporter gene expression) (5Hz-10ms: 1.9 ± 1.1, 5Hz-100ms: 2.6 ± 1.0, continuous: 2.5 ± 1.2) (p < 0.001). Continuous EP illumination showed a significantly higher improvement of forelimb akinesia than other illumination patterns (p < 0.01). Optogene expression in the GABAergic neurons of the EP was confirmed by immunohistochemistry. Optogenetic inhibition of EP was effective to improve contralateral forelimb akinesia. However, further studies using prolonged illumination are needed to investigate the best illumination pattern for optogenetic stimulation.
Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest.
(Copyright © 2020. Published by Elsevier B.V.)
Databáze: MEDLINE
Externí odkaz: