Exp Neurobiol 2021; 30(2): 113-119
Published online April 30, 2021
© The Korean Society for Brain and Neural Sciences
Heeyoung An1,2, Jun Young Heo3*, C. Justin Lee1,2* and Min-Ho Nam4*
1KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841,
2Center for Cognition and Sociality, Institute for Basic Science (IBS), Daejeon 34126,
3Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015,
4Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea
Correspondence to: *To whom correspondence should be addressed.
Jun Young Heo, TEL: 82-42-580-8221, FAX: 82-42-580-8121
C. Justin Lee, TEL: 82-42-878-9150, FAX: 82-42-878-9151
Min-Ho Nam, TEL: 82-2-958-6421, FAX: 82-2-958-7034
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
The cause of Parkinson’s disease has been traditionally believed to be the dopaminergic neuronal death in the substantia nigra pars compacta (SNpc). This traditional view has been recently challenged by the proposal that reactive astrocytes serve as key players in the pathology of Parkinson’s disease through excessive GABA release. This aberrant astrocytic GABA is synthesized by the enzymatic action of monoamine oxidase B (MAOB), whose pharmacological inhibition and gene-silencing are reported to significantly alleviate parkinsonian motor symptoms in animal models of Parkinson’s disease. However, whether genetic ablation and over-expression of MAOB can bidirectionally regulate parkinsonian motor symptoms has not been tested. Here we demonstrate that genetic ablation of MAOB blocks the MPTP-induced augmentation of astrocytic GABA-mediated tonic inhibition of neighboring dopaminergic neurons as well as parkinsonian motor symptoms, indicating the necessity of MAOB for parkinsonian motor symptoms. Furthermore, we demonstrate that GFAP-MAOB transgenic mice, in which MAOB is over-expressed under the GFAP promoter for astrocyte-specific over-expression, display exacerbated MPTP-induced tonic inhibition and parkinsonian motor symptoms compared to wild-type mice, indicating the importance of astrocytic MAOB for parkinsonian motor symptoms. Our study provides genetic pieces of evidence for the causal link between the pathological role of astrocytic MAOB-dependent tonic GABA synthesis and parkinsonian motor symptoms.