Heo, Jun Young Nam, Min-Ho Yoon, Hyung Ho Kim, Jeongyeon Hwang, Yu Jin Won, Woojin Woo, Dong Ho Lee, Ji Ae Park, Hyun-Jung Jo, Seonmi Lee, Min Joung Kim, Sunpil Shim, Jeong-Eun Jang, Dong-Pyo Kim, Kyoung I. Huh, Sue H. Jeong, Jae Y. Kowall, Neil W. Lee, Junghee Im, Hyeonjoo Park, Jong Hyun Jang, Bo Ko Park, Ki Duk Lee, Hyunjoo J. Shin, Hyogeun Cho, Il-Joo Hwang, Eun Mi Kim, YoungSoo Kim, Hye Yun Oh, Soo-Jin Lee, Seung Eun Paek, Sun Ha Yoon, Jong Hyuk Jin, Byung K. Kweon, Gi Ryang Shim, Insop Hwang, Onyou Ryu, Hoon Jeon, Sang Ryong Lee, C. Justin 2024-01-19T18:30:28Z 2024-01-19T18:30:28Z 2021-09-05 2020-01 0960-9822 https://pubs.kist.re.kr/handle/201004/119080 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. English Cell Press Aberrant Tonic Inhibition of Dopaminergic Neuronal Activity Causes Motor Symptoms in Animal Models of Parkinson's Disease Article 10.1016/j.cub.2019.11.079 1 Current Biology, v.30, no.2, pp.276 - 291 Current Biology 30 2 276 291 N scie scopus 000508195800025 2-s2.0-85077913662 Biochemistry & Molecular Biology Biology Cell Biology Biochemistry & Molecular Biology Life Sciences & Biomedicine - Other Topics Cell Biology Article MONOAMINE-OXIDASE-B REVERSIBLE PARKINSONISM TYROSINE-HYDROXYLASE REACTIVE ASTROCYTES SUBSTANTIA-NIGRA ALPHA-SYNUCLEIN RAT MODEL INFLAMMATORY RESPONSES GABA RELEASE NEURODEGENERATION astrocytes DOPA decarboxylase GABA MAO-B Parkinson&apos s disease substantia nigra pars compacta tonic inhibition tyrosine hydroxylase