GABA, but Not Bestrophin-1, Is Localized in Astroglial Processes in the Mouse Hippocampus and the Cerebellum

Lasse Ormel; Knut H Lauritzen; Rainer Schreiber; Karl Kunzelmann; Vidar Gundersen

doi:10.3389/fnmol.2020.00135

GABA, but Not Bestrophin-1, Is Localized in Astroglial Processes in the Mouse Hippocampus and the Cerebellum

Front Mol Neurosci. 2020 Jul 28:13:135. doi: 10.3389/fnmol.2020.00135. eCollection 2020.

Authors

Lasse Ormel^{1

2}, Knut H Lauritzen^{1

3}, Rainer Schreiber⁴, Karl Kunzelmann⁴, Vidar Gundersen^{1

5}

Affiliations

¹ Section of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
² Department of Neurology, Oslo University Hospital, Ullevål, Oslo, Norway.
³ Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
⁴ Department of Physiology, University of Regensburg, Regensburg, Germany.
⁵ Section for Movement Disorders, Department of Neurology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.

Abstract

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 Ca²⁺ 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.

Keywords: Bergman glia; astrocyte; electron microscopy; immunohistochemistry; rodent.