Astrocytic GABA Receptors in Mouse Hippocampus Control Responses to Behavioral Challenges through Astrocytic BDNF.
10.1007/s12264-020-00474-x
- Author:
Ji-Hong LIU
1
;
Ze-Lin LI
1
;
Yi-Si LIU
1
;
Huai-De CHU
1
;
Neng-Yuan HU
1
;
Ding-Yu WU
1
;
Lang HUANG
1
;
Shu-Ji LI
1
;
Xiao-Wen LI
1
;
Jian-Ming YANG
1
;
Tian-Ming GAO
2
Author Information
1. State Key Laboratory of Organ Failure Research, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong Key Laboratory of Psychiatric Disorders, Collaborative Innovation Center for Brain Science, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
2. State Key Laboratory of Organ Failure Research, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong Key Laboratory of Psychiatric Disorders, Collaborative Innovation Center for Brain Science, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China. tgao@smu.edu.cn.
- Publication Type:Journal Article
- Keywords:
Astrocyte;
Brain-derived neurotrophic factor;
Depression;
Forced swimming test;
Gamma-aminobutyric acid receptor
- From:
Neuroscience Bulletin
2020;36(7):705-718
- CountryChina
- Language:English
-
Abstract:
Major depressive disorder (MDD) is a common mood disorder that affects almost 20% of the global population. In addition, much evidence has implicated altered function of the gamma-aminobutyric acid (GABAergic) system in the pathophysiology of depression. Recent research has indicated that GABA receptors (GABARs) are an emerging therapeutic target in the treatment of stress-related disorders such as MDD. However, which cell types with GABARs are involved in this process is unknown. As hippocampal dysfunction is implicated in MDD, we knocked down GABARs in the hippocampus and found that knocking down these receptors in astrocytes, but not in GABAergic or pyramidal neurons, caused a decrease in immobility in the forced swimming test (FST) without affecting other anxiety- and depression-related behaviors. We also generated astrocyte-specific GABAR-knockout mice and found decreased immobility in the FST in these mice. Furthermore, the conditional knockout of GABARs in astrocytes selectively increased the levels of brain-derived neurotrophic factor protein in hippocampal astrocytes, which controlled the decrease in immobility in the FST. Taken together, our findings contribute to the current understanding of which cell types expressing GABARs modulate antidepressant activity in the FST, and they may provide new insights into the pathological mechanisms and potential targets for the treatment of depression.
