Glial GABA, synthesized by monoamine oxidase B, mediates tonic inhibition

Bo Eun Yoon, Junsung Woo, Ye Eun Chun, Heejung Chun, Seonmi Jo, Jin Young Bae, Heeyoung An, Joo Ok Min, Soo Jin Oh, Kyung Seok Han, Hye Yun Kim, Taekeun Kim, YoungSoo Kim, Yong Chul Bae, C. Justin Lee

Research output: Contribution to journalArticle

41 Citations (Scopus)

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 andmedium 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 tomediate tonic inhibition in the brain.

Original languageEnglish
Pages (from-to)4951-4968
Number of pages18
JournalJournal of Physiology
Volume592
Issue number22
DOIs
Publication statusPublished - 2014 Jan 1

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Monoamine Oxidase
Neuroglia
gamma-Aminobutyric Acid
Selegiline
Gene Silencing
Neurons
Gene Knockout Techniques
Glutamate Decarboxylase
Putrescine
Brain
Enzymes
Cerebellum
Electron Microscopy

All Science Journal Classification (ASJC) codes

  • Physiology

Cite this

Yoon, B. E., Woo, J., Chun, Y. E., Chun, H., Jo, S., Bae, J. Y., ... Lee, C. J. (2014). Glial GABA, synthesized by monoamine oxidase B, mediates tonic inhibition. Journal of Physiology, 592(22), 4951-4968. https://doi.org/10.1113/jphysiol.2014.278754
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, YoungSoo ; Bae, Yong Chul ; Lee, C. Justin. / Glial GABA, synthesized by monoamine oxidase B, mediates tonic inhibition. In: Journal of Physiology. 2014 ; Vol. 592, No. 22. pp. 4951-4968.
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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 andmedium 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 tomediate tonic inhibition in the brain.",
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Yoon, BE, Woo, J, Chun, YE, Chun, H, Jo, S, Bae, JY, An, H, Min, JO, Oh, SJ, Han, KS, Kim, HY, Kim, T, Kim, Y, Bae, YC & Lee, CJ 2014, 'Glial GABA, synthesized by monoamine oxidase B, mediates tonic inhibition', Journal of Physiology, vol. 592, no. 22, pp. 4951-4968. https://doi.org/10.1113/jphysiol.2014.278754

Glial GABA, synthesized by monoamine oxidase B, mediates tonic inhibition. / 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, YoungSoo; Bae, Yong Chul; Lee, C. Justin.

In: Journal of Physiology, Vol. 592, No. 22, 01.01.2014, p. 4951-4968.

Research output: Contribution to journalArticle

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T1 - Glial GABA, synthesized by monoamine oxidase B, mediates tonic inhibition

AU - Yoon, Bo Eun

AU - Woo, Junsung

AU - Chun, Ye Eun

AU - Chun, Heejung

AU - Jo, Seonmi

AU - Bae, Jin Young

AU - An, Heeyoung

AU - Min, Joo Ok

AU - Oh, Soo Jin

AU - Han, Kyung Seok

AU - Kim, Hye Yun

AU - Kim, Taekeun

AU - Kim, YoungSoo

AU - Bae, Yong Chul

AU - Lee, C. Justin

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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 andmedium 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 tomediate tonic inhibition in the brain.

AB - 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 andmedium 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 tomediate tonic inhibition in the brain.

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