| First Author | Kong H | Year | 2014 |
| Journal | CNS Neurosci Ther | Volume | 20 |
| Issue | 5 | Pages | 391-402 |
| PubMed ID | 24422972 | Mgi Jnum | J:323031 |
| Mgi Id | MGI:6875054 | Doi | 10.1111/cns.12222 |
| Citation | Kong H, et al. (2014) Aquaporin-4 knockout exacerbates corticosterone-induced depression by inhibiting astrocyte function and hippocampal neurogenesis. CNS Neurosci Ther 20(5):391-402 |
| abstractText | 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. |
