title: Aquaporin-4 knockout exacerbates corticosterone-induced depression by inhibiting astrocyte function and hippocampal neurogenesis.
abstract: OBJECTIVE
  The predominant expression of aquaporin-4 (AQP4) 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 AQP4 in the pathogenesis of depression, and related possible biological mechanism.
  
  
  RESULTS
  Wild-type (AQP4(+/+) ) and AQP4 knockout (AQP4(-/-) ) 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 AQP4(-/-) genotype, indicating AQP4 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 (EAAT2), synapsin-1, and glial cell line-derived neurotrophic factor (GDNF) in the hippocampus of AQP4(-/-) mice. Moreover, even less hippocampal neurogenesis was identified in corticosterone-treated AQP4(-/-) mice in vivo and hippocampus-derived adult neural stem cells (ANSCs) in vitro.
  
  
  CONCLUSIONS
  The present findings suggest AQP4 involves the pathogenesis of depression by modulating astrocytic function and adult neurogenesis, highlighting a novel profile of AQP4 as a potential target for the treatment for depression.
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Kong
authors.forename: Xiao-Ning
authors.initials: XN
authors.lastname: Zeng
authors.forename: Yi
authors.initials: Y
authors.lastname: Fan
authors.forename: Song-Tao
authors.initials: ST
authors.lastname: Yuan
authors.forename: Song
authors.initials: S
authors.lastname: Ge
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Xie
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Gang
authors.initials: G
authors.lastname: Hu
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics / Q000378:metabolism*; D001253:Astrocytes / Q000502:physiology*; D016923:Cell Death / Q000502:physiology; D002478:Cells, Cultured; D003345:Corticosterone; D003866:Depressive Disorder / Q000503:physiopathology*; D004195:Disease Models, Animal; D015536:Down-Regulation; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D006624:Hippocampus / Q000503:physiopathology*; D008297:Male; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D055495:Neurogenesis / Q000502:physiology*; D016704:Synapsins / Q000378:metabolism
chemical_list: C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D027342:Excitatory Amino Acid Transporter 2; C495040:Gdnf protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; C493396:Slc1a2 protein, mouse; D016704:Synapsins; D003345:Corticosterone
keywords: Aquaporin-4; Astrocyte function; Depression; Neurogenesis