Glial GABA, synthesized by monoamine oxidase B, mediates tonic inhibition
Glial GABA, synthesized by monoamine oxidase B, mediates tonic inhibition
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DOI：
10.1113/jphysiol.2014.278754
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发表时间：
2014-11-15
影响因子：
5.5
通讯作者：
Lee, C. Justin
中科院分区：
文献类型：
--
作者：
Yoon, Bo-Eun;Woo, Junsung;Lee, C. Justin
GABA是大脑中主要的抑制性递质，不仅从神经元亚群中释放，也从神经胶质中释放。虽然神经元GABA是由谷氨酸脱羧酶（GAD）合成的，但神经胶质GABA的来源尚不清楚。在估计GABA在Bergmann神经胶质细胞中的浓度为5-10 mM左右，通过免疫金电子显微镜，我们证明，GABA的生产在神经胶质细胞需要MAOB，腐胺降解途径中的关键酶。在培养的小脑胶质细胞中，Ca 2+诱导和紧张性GABA释放显着减少MAOB和MAOB抑制剂司来吉兰的基因沉默。在成年小鼠的小脑和纹状体中，一般基因沉默、MAOB敲除或司来吉兰处理导致从颗粒神经元和中等多刺神经元记录的强直性GABA电流消除。MAOB的胶质细胞特异性救援导致强直性GABA电流的完全救援。我们的研究结果表明MAOB是神经胶质GABA合成的关键酶，它通过bestrophin 1（Best 1）通道释放，介导脑中的紧张性抑制。
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 Ca2+-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.