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Glial GABA, synthesized by monoamine oxidase B, mediates tonic inhibition
Author(s) -
Yoon BoEun,
Woo Junsung,
Chun YeEun,
Chun Heejung,
Jo Seonmi,
Bae Jin Young,
An Heeyoung,
Min Joo Ok,
Oh SooJin,
Han KyungSeok,
Kim Hye Yun,
Kim Taekeun,
Kim Young Soo,
Bae Yong Chul,
Lee C. Justin
Publication year - 2014
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2014.278754
Subject(s) - monoamine oxidase b , glutamate decarboxylase , selegiline , chemistry , gamma aminobutyric acid , biology , monoamine oxidase , gaba receptor antagonist , neuroscience , biochemistry , microbiology and biotechnology , pharmacology , gabaa receptor , bicuculline , enzyme , medicine , receptor , disease , parkinson's disease
Key pointsHere we show that glial gamma aminobutyric acid (GABA) is produced by monoamine oxidase B (MAOB), utilizing a polyamine, putrescine. The concentration of GABA in Bergmann glial cells is estimated to be around 5–10 mM. General gene silencing of MAOB resulted in elimination of tonic GABA currents recorded from granule cells in the cerebellum and medium spiny neurons (MSN) in the striatum. Glial‐specific rescue of MAOB resulted in complete restoration of tonic GABA currents. Our results identify MAOB as a synthesizing enzyme of glial GABA, which is released to mediate tonic inhibition in the cerebellum and striatum.Abstract GABA is the major inhibitory transmitter in the brain and is released not only from a subset of neurons but also from glia. Although neuronal GABA is well known to be synthesized by glutamic acid decarboxylase (GAD), the source of glial GABA is unknown. After estimating the concentration of GABA in Bergmann glia to be around 5–10 m m by immunogold electron microscopy, we demonstrate that GABA production in glia requires MAOB, a key enzyme in the putrescine degradation pathway. In cultured cerebellar glia, both Ca 2+ ‐induced and tonic GABA release are significantly reduced by both gene silencing of MAOB and the MAOB inhibitor selegiline. In the cerebellum and striatum of adult mice, general gene silencing, knock out of MAOB or selegiline treatment resulted in elimination of tonic GABA currents recorded from granule neurons and medium spiny neurons. Glial‐specific rescue of MAOB resulted in complete rescue of tonic GABA currents. Our results identify MAOB as a key synthesizing enzyme of glial GABA, which is released via bestrophin 1 (Best1) channel to mediate tonic inhibition in the brain.