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Short Communication

Exp Neurobiol 2021; 30(3): 213-221

Published online June 16, 2021

© The Korean Society for Brain and Neural Sciences

Differential Proximity of Perisynaptic Astrocytic Best1 at the Excitatory and Inhibitory Tripartite Synapses in APP/PS1 and MAOB-KO Mice Revealed by Lattice Structured Illumination Microscopy

Heeyoung An1,2, Wuhyun Koh2, SeungHee Kang2, Min-Ho Nam3,4* and C. Justin Lee1,2*

1KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841,
2Center for Cognition and Sociality, Institute for Basic Science (IBS), Daejeon 34126,
3Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792,
4Department of KHU-KIST Convergence Science and Technology, Kyung Hee University, Seoul 02453, Korea

Correspondence to: *To whom correspondence should be addressed.
C. Justin Lee, TEL: 82-42-878-9150, FAX: 82-42-878-9151
Min-Ho Nam, TEL: 82-2-958-6421, FAX: 82-2-958-7034

Received: May 24, 2021; Revised: May 28, 2021; Accepted: May 30, 2021

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Bestrophin-1 (Best1) is a GABA- and glutamate-permeable, Ca2+-activated Cl- channel, which is mainly expressed in astrocytes and localized at the microdomain or perisynaptic junction of the tripartite synapse. Distribution of Best1 is dramatically changed in pathological conditions such as Alzheimer’s disease. However, it is still unknown whether Best1 is located at the glutamatergic or GABAergic tripartite synapses. Here, we utilized the Lattice structured illumination microscopy (Lattice SIM) to visualize Best1 expression at the perisynaptic junctions of the tripartite synapses in CA1 of mouse hippocampus. We performed co-labeling with antibodies against 1) Best1 and vesicular glutamate transporter-2 (vGLUT2) or 2) Best1 and vesicular GABA transporter (vGAT) to measure the proximity of Best1-containing perisynapse to glutamatergic or GABAergic presynapse, respectively. In addition, we examined two transgenic mouse lines of 1) APP/PS1 mouse showing high astrocytic MAOB activity and cytosolic GABA and 2) MAOB-KO mouse showing low astrocytic GABA. Lattice SIM images were further processed by Imaris, which allowed 3D-rendering and spot identification. We found that astrocytic Best1 was distributed closer to the glutamatergic synapses than GABAergic synapses in the wild-type mice. In APP/PS1 mice, Best1 distribution was significantly changed by moving away from the glutamatergic synapses while moving closer to the GABAergic synapses. On the contrary, in MAOB-KO mice, the Best1 distribution was dramatically changed by moving closer to the glutamatergic synapses and moving far away from the GABAergic synapses. Our findings propose that the proximity of Best1-containing perisynapses to presynapses dynamically changes according to the level of astrocytic cytosolic GABA.

Graphical Abstract

Keywords: Best1, MAOB, Channel distribution, Proximity, vGAT, vGLUT2