Glial GABA, synthesized by monoamine oxidase B, mediates tonic inhibition. (21st October 2014)

• Record Type: Journal Article
• Authors: Yoon, Bo‐Eun; Woo, Junsung; Chun, Ye‐Eun; Chun, Heejung; Jo, Seonmi; Bae, Jin Young; An, Heeyoung; Min, Joo Ok; Oh, Soo‐Jin; Han, Kyung‐Seok; Kim, Hye Yun; Kim, Taekeun; Kim, Young Soo; Bae, Yong Chul; Lee, C. Justin
• Is Part Of: Journal of physiology. Volume 592:Number 22(2014:Nov.)
• Page Start: 4951
• Page End: 4968
• Publication Date: 2014-10-21
• Subjects: Physiology -- Periodicals; 612.005
• DOI: 10.1113/jphysiol.2014.278754
• Languages: English
• ISSNs: 0022-3751

Abstract

Abstract : Key points: Here 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 mm 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.