An, Heeyoung Koh, Wuhyun Kang, SeungHee Nam, Min-Ho Lee, C. Justin 2024-01-19T14:32:22Z 2024-01-19T14:32:22Z 2021-10-21 2021-06 1226-2560 https://pubs.kist.re.kr/handle/201004/116913 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 3Drendering 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. English KOREAN SOC BRAIN & NEURAL SCIENCE, KOREAN SOC NEURODEGENERATIVE DISEASE REACTIVE ASTROCYTES GABA RELEASE CHANNEL 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 Article 10.5607/en21015 1 EXPERIMENTAL NEUROBIOLOGY, v.30, no.3, pp.213 - 221 EXPERIMENTAL NEUROBIOLOGY 30 3 213 221 scie scopus kci ART002736103 000670453200002 2-s2.0-85111088816 Medicine, Research & Experimental Neurosciences Research & Experimental Medicine Neurosciences & Neurology Article REACTIVE ASTROCYTES GABA RELEASE CHANNEL Best1 MAOB Channel distribution Proximity vGAT vGLUT2