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Cited 46 time in webofscience Cited 47 time in scopus
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Aberrant Tonic Inhibition of Dopaminergic Neuronal Activity Causes Motor Symptoms in Animal Models of Parkinson's Disease

Authors
Heo, Jun YoungNam, Min-HoYoon, Hyung HoKim, JeongyeonHwang, Yu JinWon, WoojinWoo, Dong HoLee, Ji AePark, Hyun-JungJo, SeonmiLee, Min JoungKim, SunpilShim, Jeong-EunJang, Dong-PyoKim, Kyoung I.Huh, Sue H.Jeong, Jae Y.Kowall, Neil W.Lee, JungheeIm, HyeonjooPark, Jong HyunJang, Bo KoPark, Ki DukLee, Hyunjoo J.Shin, HyogeunCho, Il-JooHwang, Eun MiKim, YoungSooKim, Hye YunOh, Soo-JinLee, Seung EunPaek, Sun HaYoon, Jong HyukJin, Byung K.Kweon, Gi RyangShim, InsopHwang, OnyouRyu, HoonJeon, Sang RyongLee, C. Justin
Issue Date
Jan-2020
Publisher
CELL PRESS
Citation
CURRENT BIOLOGY, v.30, no.2, pp.276 - +
Journal Title
CURRENT BIOLOGY
Volume
30
Number
2
Start Page
276
End Page
+
URI
http://scholarworks.bwise.kr/kbri/handle/2023.sw.kbri/651
DOI
10.1016/j.cub.2019.11.079
ISSN
0960-9822
Abstract
Current pharmacological treatments for Parkinson's disease (PD) are focused on symptomatic relief, but not on disease modification, based on the strong belief that PD is caused by irreversible dopaminergic neuronal death. Thus, the concept of the presence of dormant dopaminergic neurons and its possibility as the disease-modifying therapeutic target against PD have not been explored. Here we show that optogenetic activation of substantia nigra pars compacta (SNpc) neurons alleviates parkinsonism in acute PD animal models by recovering tyrosine hydroxylase (TH) from the TH-negative dormant dopaminergic neurons, some of which still express DOPA decarboxylase (DDC). The TH loss depends on reduced dopaminergic neuronal firing under aberrant tonic inhibition, which is attributed to excessive astrocytic GABA. Blocking the astrocytic GABA synthesis recapitulates the therapeutic effect of optogenetic activation. Consistently, SNpc of postmortem PD patients shows a significant population of TH-negative/DDC-positive dormant neurons surrounded by numerous GABA-positive astrocytes. We propose that disinhibiting dormant dopaminergic neurons by blocking excessive astrocytic GABA could be an effective therapeutic strategy against PD.
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연구본부 > 퇴행성 뇌질환 연구그룹 > 1. Journal Articles
연구본부 > 정서·인지 질환 연구그룹 > 1. Journal Articles

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Kim, Jeong yeon
연구본부 (정서·인지질환 연구그룹)
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