Aquaporin-4 knockout exacerbates corticosterone-induced depression by inhibiting astrocyte function and hippocampal neurogenesis.
نویسندگان
چکیده
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.
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ورودعنوان ژورنال:
- CNS neuroscience & therapeutics
دوره 20 5 شماره
صفحات -
تاریخ انتشار 2014