Open AccessAquaporin‐4 Knockout Exacerbates Corticosterone‐Induced Depression by Inhibiting Astrocyte Function and Hippocampal Neurogenesis
Author(s) -
Kong Hui,
Zeng XiaoNing,
Fan Yi,
Yuan SongTao,
Ge Song,
Xie WeiPing,
Wang Hong,
Hu Gang
Publication year - 2014
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12222
Subject(s) - neurogenesis , corticosterone , knockout mouse , astrocyte , tail suspension test , endocrinology , hippocampal formation , medicine , hippocampus , glial cell line derived neurotrophic factor , behavioural despair test , neural stem cell , neurotrophic factors , synapsin i , biology , neuroscience , microbiology and biotechnology , central nervous system , stem cell , receptor , biochemistry , hormone , vesicle , synaptic vesicle , antidepressant , membrane
Summary Aims The predominant expression of aquaporin‐4 ( AQP 4) in the brain implies that this water channel may be involved in a range of brain disorders. This study was designed to investigate the role of AQP 4 in the pathogenesis of depression, and related possible biological mechanism. Methods and Results Wild‐type ( AQP 4 +/+ ) and AQP 4 knockout ( AQP 4 −/− ) mice were given daily subcutaneous injections of corticosterone (20 mg/kg) for consecutive 21 days. Forced swimming test ( FST ) and tail suspension test ( TST ) showed longer immobility times in corticosterone‐treated AQP 4 −/− genotype, indicating AQP 4 knockout exacerbated depressive‐like behaviors in mice. Using immunohistological staining, western blot, and enzyme‐linked immunosorbent assay ( ELISA ), we found a significant loss of astrocytes, aggravated downregulation of excitatory amino acid transporter 2 ( EAAT 2), synapsin‐1, and glial cell line‐derived neurotrophic factor ( GDNF ) in the hippocampus of AQP 4 −/− mice. Moreover, even less hippocampal neurogenesis was identified in corticosterone‐treated AQP 4 −/− mice in vivo and hippocampus‐derived adult neural stem cells ( ANSC s) in vitro . Conclusions The present findings suggest AQP 4 involves the pathogenesis of depression by modulating astrocytic function and adult neurogenesis, highlighting a novel profile of AQP 4 as a potential target for the treatment for depression.