Ormel Lasse, Lauritzen Knut H, Schreiber Rainer, Kunzelmann Karl, Gundersen Vidar
Section of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
Department of Neurology, Oslo University Hospital, Ullevål, Oslo, Norway.
Front Mol Neurosci. 2020 Jul 28;13:135. doi: 10.3389/fnmol.2020.00135. eCollection 2020.
GABA is proposed to act as a gliotransmitter in the brain. Differences in GABA release from astroglia are thought to underlie differences in tonic inhibition between the cerebellum and the CA1 hippocampus. Here we used quantitative immunogold cytochemistry to localize and compare the levels of GABA in astroglia in these brain regions. We found that the density of GABA immunogold particles was similar in delicate processes of Bergman glia in the cerebellum and astrocytes in the CA1 hippocampus. The astrocytic GABA release is proposed to be mediated by, among others, the Ca activated Cl channel bestrophin-1. The bestrophin-1 antibodies did not show any significant bestrophin-1 signal in the brain of wt mice, nor in bestrophin-1 knockout mice. The bestrophin-1 signal was low both on Western blots and immunofluorescence laser scanning microscopic images. These results suggest that GABA is localized in astroglia, but in similar concentrations in the cerebellum and CA1 hippocampus, and thus cannot account for differences in tonic inhibition between these brain regions. Furthermore, our data seem to suggest that the GABA release from astroglia previously observed in the hippocampus and cerebellum occurs via mechanisms other than bestrophin-1.
γ-氨基丁酸（GABA）被认为在大脑中作为一种胶质递质发挥作用。星形胶质细胞释放GABA的差异被认为是小脑和海马体CA1区之间紧张性抑制差异的基础。在这里，我们使用定量免疫金细胞化学来定位和比较这些脑区星形胶质细胞中GABA的水平。我们发现，小脑伯格曼胶质细胞的精细突起和海马体CA1区星形胶质细胞中GABA免疫金颗粒的密度相似。星形胶质细胞释放GABA的过程被认为是由多种因素介导的，其中包括钙激活氯离子通道Bestrophin-1。Bestrophin-1抗体在野生型小鼠的大脑中以及Bestrophin-1基因敲除小鼠的大脑中均未显示出任何明显的Bestrophin-1信号。在蛋白质免疫印迹和免疫荧光激光扫描显微镜图像上，Bestrophin-1信号均较低。这些结果表明，GABA定位于星形胶质细胞中，但在小脑和海马体CA1区中的浓度相似，因此不能解释这些脑区之间紧张性抑制的差异。此外，我们的数据似乎表明，先前在海马体和小脑中观察到的星形胶质细胞释放GABA是通过Bestrophin-1以外的机制发生的。
