Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 장동표 | - |
dc.date.accessioned | 2021-03-16T01:28:54Z | - |
dc.date.available | 2021-03-16T01:28:54Z | - |
dc.date.issued | 2020-01 | - |
dc.identifier.citation | CURRENT BIOLOGY, v. 30, no. 2, page. 276-291 | en_US |
dc.identifier.issn | 0960-9822 | - |
dc.identifier.issn | 1879-0445 | - |
dc.identifier.uri | https://www.sciencedirect.com/science/article/pii/S0960982219315817?via%3Dihub | - |
dc.identifier.uri | https://repository.hanyang.ac.kr/handle/20.500.11754/160581 | - |
dc.description.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. | en_US |
dc.description.sponsorship | The AAV-A53T viral vector was kindly provided by Dr. Jun-ichi Miyazaki at Kumamoto University. This work was supported by the Creative Research Initiative Program (2015R1A3A2066619) of the National Research Foundation (NRF) of Korea funded by the Ministry of Science and ICT of Korea and Institute for Basic Science (IBS), Center for Cognition and Sociality (IBS-R001-D2) to C.J. L.; Asan Life Science Institute grants (18-241 and 19-241) funded by the Asan Medical Center to S.R.J.; Brain Science Program (2018M3C7A1056894) funded by NRF of Korea to H.R.; KIST institutional program (Project No. 2E29221) and Brain Science Program (2018M3C7A1056897) funded by the NRF of Korea to M.H.N.; MRC program (2017R1A5A2015385) funded by the Ministry of Science and ICT of Korea to J.Y.H.; and KBRI basic research program (20-BR-02-05) through Korea Brain Research Institute funded by the Ministry of Science and ICT of Korea to J.K. | en_US |
dc.language.iso | en | en_US |
dc.publisher | CELL PRESS | en_US |
dc.subject | MONOAMINE-OXIDASE-B | en_US |
dc.subject | REVERSIBLE PARKINSONISM | en_US |
dc.subject | TYROSINE-HYDROXYLASE | en_US |
dc.subject | REACTIVE ASTROCYTES | en_US |
dc.subject | SUBSTANTIA-NIGRA | en_US |
dc.subject | ALPHA-SYNUCLEIN | en_US |
dc.subject | RAT MODEL | en_US |
dc.subject | INFLAMMATORY RESPONSES | en_US |
dc.subject | GABA RELEASE | en_US |
dc.subject | NEURODEGENERATION | en_US |
dc.title | Aberrant Tonic Inhibition of Dopaminergic Neuronal Activity Causes Motor Symptoms in Animal Models of Parkinson's Disease | en_US |
dc.type | Article | en_US |
dc.relation.no | 2 | - |
dc.relation.volume | 30 | - |
dc.identifier.doi | 10.1016/j.cub.2019.11.079 | - |
dc.relation.page | 276-291 | - |
dc.relation.journal | CURRENT BIOLOGY | - |
dc.contributor.googleauthor | Heo, Jun Young | - |
dc.contributor.googleauthor | Nam, Min-Ho | - |
dc.contributor.googleauthor | Yoon, Hyung Ho | - |
dc.contributor.googleauthor | Kim, Jeongyeon | - |
dc.contributor.googleauthor | Hwang, Yu Jin | - |
dc.contributor.googleauthor | Won, Woojin | - |
dc.contributor.googleauthor | Woo, Dong Ho | - |
dc.contributor.googleauthor | Lee, Ji Ae | - |
dc.contributor.googleauthor | Park, Hyun-Jung | - |
dc.contributor.googleauthor | Jang, Dong-Pyo | - |
dc.relation.code | 2020051959 | - |
dc.sector.campus | S | - |
dc.sector.daehak | GRADUATE SCHOOL OF BIOMEDICAL SCIENCE AND ENGINEERING[S] | - |
dc.identifier.pid | dongpjang | - |
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