Redefining differential roles of MAO-A in dopamine degradation and MAO-B in tonic GABA synthesis |
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| Authors: | Hyun-U Cho Sunpil Kim Jeongeun Sim Seulkee Yang Heeyoung An Min-Ho Nam Dong-Pyo Jang C Justin Lee |
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| Institution: | 1.Department of Biomedical Engineering, Hanyang University, Seoul, Korea ;2.KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, Korea ;3.Center for Cognition and Sociality, Institute for Basic Science, Daejeon, Korea ;4.Center for Neuroscience, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, Korea ;5.Department of KHU-KIST Convergence Science and Technology, Kyung Hee University, Seoul, Korea |
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| Abstract: | Monoamine oxidase (MAO) is believed to mediate the degradation of monoamine neurotransmitters, including dopamine, in the brain. Between the two types of MAO, MAO-B has been believed to be involved in dopamine degradation, which supports the idea that the therapeutic efficacy of MAO-B inhibitors in Parkinson’s disease can be attributed to an increase in extracellular dopamine concentration. However, this belief has been controversial. Here, by utilizing in vivo phasic and basal electrochemical monitoring of extracellular dopamine with fast-scan cyclic voltammetry and multiple-cyclic square wave voltammetry and ex vivo fluorescence imaging of dopamine with GRABDA2m, we demonstrate that MAO-A, but not MAO-B, mainly contributes to striatal dopamine degradation. In contrast, our whole-cell patch-clamp results demonstrated that MAO-B, but not MAO-A, was responsible for astrocytic GABA-mediated tonic inhibitory currents in the rat striatum. We conclude that, in contrast to the traditional belief, MAO-A and MAO-B have profoundly different roles: MAO-A regulates dopamine levels, whereas MAO-B controls tonic GABA levels.Subject terms: Neurotransmitters, Biosensors, Astrocyte, Inhibition, Transporters in the nervous system |
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