BROWSE

Related Scientist

Moonsun, Sa's photo.

Moonsun, Sa
인지 및 사회성 연구단
more info

ITEM VIEW & DOWNLOAD

Unaltered Tonic Inhibition in the Arcuate Nucleus of Diet-induced Obese Mice

Cited 0 time in webofscience Cited 0 time in scopus
205 Viewed 0 Downloaded
Title
Unaltered Tonic Inhibition in the Arcuate Nucleus of Diet-induced Obese Mice
Author(s)
Moonsun Sa; Jung Moo Lee; Mingu Gordon Park; Jiwoon Lim; Kim, Jong Min Joseph; Wuhyun Koh; Yoon, Bo-Eun; C. Justin Lee
Publication Date
2022-06
Journal
Experimental Neurobiology, v.31, no.3, pp.147 - 157
Publisher
Korean Society for Neurodegenerative Disease
Abstract
Copyright © Experimental Neurobiology 2022.The principal inhibitory transmitter, γ-aminobutyric acid (GABA), is critical for maintaining hypothalamic homeostasis and released from neurons phasically, as well as from astrocytes tonically. Although astrocytes in the arcuate nucleus (ARC) of the hypothalamus are shown to transform into reactive astrocytes, the tonic inhibition by astrocytic GABA has not been adequately investigated in diet-induced obesity (DIO). Here, we investigated the expression of monoamine oxidase- B (MAOB), a GABA-synthesizing enzyme, in reactive astrocytes in obese mice. We observed that a chronic high-fat diet (HFD) significantly increased astrocytic MAOB and cellular GABA content, along with enhanced hypertrophy of astrocytes in the ARC. Unexpectedly, we found that the level of tonic GABA was unaltered in chronic HFD mice using whole-cell patch-clamp recordings in the ARC. Furthermore, the GABA-induced current was increased with elevated GABAA receptor α5 (GABRA5) expression. Surprisingly, we found that a nonselective GABA transporter (GAT) inhibitor, nipecotic acid (NPA)-induced current was significantly increased in chronic HFD mice. We observed that GAT1 inhibitor, NO711-induced current was significantly increased, whereas GAT3 inhibitor, SNAP5114-induced current was not altered. The unexpected unaltered tonic inhibition was due to an increase of GABA clearance in the ARC by neuronal GAT1 rather than astrocytic GAT3. These results imply that increased astrocytic GABA synthesis and neuronal GABAA receptor were compensated by GABA clearance, resulting in unaltered tonic GABA inhibition in the ARC of the hypothalamus in obese mice. Taken together, GABA-related molecular pathways in the ARC dynamically regulate the tonic inhibition to maintain hypothalamic homeostasis against the HFD challenge.
URI
https://pr.ibs.re.kr/handle/8788114/12784
DOI
10.5607/en22014
ISSN
1226-2560
Appears in Collections:
Center for Cognition and Sociality(인지 및 사회성 연구단) > 1. Journal Papers (저널논문)
Files in This Item:
There are no files associated with this item.

qrcode

  • facebook

    twitter

  • Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.
해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse