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This study was designed to investigate the role of <jats:styled-content style=\"fixed-case\">AQP<\/jats:styled-content>4 in the pathogenesis of depression, and related possible biological mechanism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p>Wild\u2010type (<jats:styled-content style=\"fixed-case\">AQP<\/jats:styled-content>4<jats:sup>+\/+<\/jats:sup>) and <jats:styled-content style=\"fixed-case\">AQP<\/jats:styled-content>4 knockout (<jats:styled-content style=\"fixed-case\">AQP<\/jats:styled-content>4<jats:sup>\u2212\/\u2212<\/jats:sup>) mice were given daily subcutaneous injections of corticosterone (20\u00a0mg\/kg) for consecutive 21\u00a0days. Forced swimming test (<jats:styled-content style=\"fixed-case\">FST<\/jats:styled-content>) and tail suspension test (<jats:styled-content style=\"fixed-case\">TST<\/jats:styled-content>) showed longer immobility times in corticosterone\u2010treated <jats:styled-content style=\"fixed-case\">AQP<\/jats:styled-content>4<jats:sup>\u2212\/\u2212<\/jats:sup> genotype, indicating <jats:styled-content style=\"fixed-case\">AQP<\/jats:styled-content>4 knockout exacerbated depressive\u2010like behaviors in mice. Using immunohistological staining, western blot, and enzyme\u2010linked immunosorbent assay (<jats:styled-content style=\"fixed-case\">ELISA<\/jats:styled-content>), we found a significant loss of astrocytes, aggravated downregulation of excitatory amino acid transporter 2 (<jats:styled-content style=\"fixed-case\">EAAT<\/jats:styled-content>2), synapsin\u20101, and glial cell line\u2010derived neurotrophic factor (<jats:styled-content style=\"fixed-case\">GDNF<\/jats:styled-content>) in the hippocampus of <jats:styled-content style=\"fixed-case\">AQP<\/jats:styled-content>4<jats:sup>\u2212\/\u2212<\/jats:sup> mice. Moreover, even less hippocampal neurogenesis was identified in corticosterone\u2010treated <jats:styled-content style=\"fixed-case\">AQP<\/jats:styled-content>4<jats:sup>\u2212\/\u2212<\/jats:sup> mice <jats:italic>in vivo<\/jats:italic> and hippocampus\u2010derived adult neural stem cells (<jats:styled-content style=\"fixed-case\">ANSC<\/jats:styled-content>s) <jats:italic>in vitro<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The present findings suggest <jats:styled-content style=\"fixed-case\">AQP<\/jats:styled-content>4 involves the pathogenesis of depression by modulating astrocytic function and adult neurogenesis, highlighting a novel profile of <jats:styled-content style=\"fixed-case\">AQP<\/jats:styled-content>4 as a potential target for the treatment for depression.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.12222","type":"journal-article","created":{"date-parts":[[2014,1,15]],"date-time":"2014-01-15T06:57:24Z","timestamp":1389769044000},"page":"391-402","source":"Crossref","is-referenced-by-count":66,"title":["Aquaporin\u20104 Knockout Exacerbates Corticosterone\u2010Induced Depression by Inhibiting Astrocyte Function and Hippocampal Neurogenesis"],"prefix":"10.1111","volume":"20","author":[{"given":"Hui","family":"Kong","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine The First Affiliated Hospital of Nanjing Medical University Nanjing China"},{"name":"Jiangsu Key Laboratory of Neurodegeneration Department of Pharmacology Nanjing Medical University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010Ning","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine The First Affiliated Hospital of Nanjing Medical University Nanjing 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