Aquaporin-4 knockout exacerbates corticosterone-induced depression by inhibiting astrocyte function and hippocampal neurogenesis.

Abstract

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.

• Authors: Hui Kong, Xiao-Ning Zeng, Yi Fan, Song-Tao Yuan, Song Ge, Wei-Ping Xie, Hong Wang, Gang Hu
• Journal: CNS neuroscience & therapeutics (CNS Neurosci Ther) Vol. 20 Issue 5 Pg. 391-402 (May 2014) ISSN: 1755-5949 [Electronic] England
• PMID: 24422972 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 John Wiley & Sons Ltd.

Chemical References

• Aqp4 protein, mouse
• Aquaporin 4
• Excitatory Amino Acid Transporter 2
• Gdnf protein, mouse
• Glial Cell Line-Derived Neurotrophic Factor
• Slc1a2 protein, mouse
• Synapsins
• Corticosterone

Topics

• Animals
• Aquaporin 4 (genetics, metabolism)
• Astrocytes (physiology)
• Cell Death (physiology)
• Cells, Cultured
• Corticosterone
• Depressive Disorder (physiopathology)
• Disease Models, Animal
• Down-Regulation
• Excitatory Amino Acid Transporter 2 (metabolism)
• Glial Cell Line-Derived Neurotrophic Factor (metabolism)
• Hippocampus (physiopathology)
• Male
• Mice, Inbred Strains
• Mice, Knockout
• Neurogenesis (physiology)
• Synapsins (metabolism)