PMID- 24422972
OWN - NLM
STAT- MEDLINE
DCOM- 20141208
LR  - 20211021
IS  - 1755-5949 (Electronic)
IS  - 1755-5930 (Print)
IS  - 1755-5930 (Linking)
VI  - 20
IP  - 5
DP  - 2014 May
TI  - Aquaporin-4 knockout exacerbates corticosterone-induced depression by inhibiting 
      astrocyte function and hippocampal neurogenesis.
PG  - 391-402
LID - 10.1111/cns.12222 [doi]
AB  - AIMS: 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. METHODS AND 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.
CI  - (c) 2014 John Wiley & Sons Ltd.
FAU - Kong, Hui
AU  - Kong H
AD  - 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.
FAU - Zeng, Xiao-Ning
AU  - Zeng XN
FAU - Fan, Yi
AU  - Fan Y
FAU - Yuan, Song-Tao
AU  - Yuan ST
FAU - Ge, Song
AU  - Ge S
FAU - Xie, Wei-Ping
AU  - Xie WP
FAU - Wang, Hong
AU  - Wang H
FAU - Hu, Gang
AU  - Hu G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140115
PL  - England
TA  - CNS Neurosci Ther
JT  - CNS neuroscience & therapeutics
JID - 101473265
RN  - 0 (Aqp4 protein, mouse)
RN  - 0 (Aquaporin 4)
RN  - 0 (Excitatory Amino Acid Transporter 2)
RN  - 0 (Gdnf protein, mouse)
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor)
RN  - 0 (Slc1a2 protein, mouse)
RN  - 0 (Synapsins)
RN  - W980KJ009P (Corticosterone)
SB  - IM
MH  - Animals
MH  - Aquaporin 4/genetics/*metabolism
MH  - Astrocytes/*physiology
MH  - Cell Death/physiology
MH  - Cells, Cultured
MH  - Corticosterone
MH  - Depressive Disorder/*physiopathology
MH  - Disease Models, Animal
MH  - Down-Regulation
MH  - Excitatory Amino Acid Transporter 2/metabolism
MH  - Glial Cell Line-Derived Neurotrophic Factor/metabolism
MH  - Hippocampus/*physiopathology
MH  - Male
MH  - Mice, Inbred Strains
MH  - Mice, Knockout
MH  - Neurogenesis/*physiology
MH  - Synapsins/metabolism
PMC - PMC6493035
OTO - NOTNLM
OT  - Aquaporin-4
OT  - Astrocyte function
OT  - Depression
OT  - Neurogenesis
COIS- The authors declare no conflict of interest.
EDAT- 2014/01/16 06:00
MHDA- 2014/12/15 06:00
PMCR- 2014/01/15
CRDT- 2014/01/16 06:00
PHST- 2013/11/16 00:00 [received]
PHST- 2013/12/03 00:00 [revised]
PHST- 2013/12/03 00:00 [accepted]
PHST- 2014/01/16 06:00 [entrez]
PHST- 2014/01/16 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
PHST- 2014/01/15 00:00 [pmc-release]
AID - CNS12222 [pii]
AID - 10.1111/cns.12222 [doi]
PST - ppublish
SO  - CNS Neurosci Ther. 2014 May;20(5):391-402. doi: 10.1111/cns.12222. Epub 2014 Jan 
      15.