{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:16:29Z","timestamp":1790266589598,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2018,5,2]],"date-time":"2018-05-02T00:00:00Z","timestamp":1525219200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81603336"],"award-info":[{"award-number":["81603336"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005349","name":"American Association of Colleges of Pharmacy","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005349","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Major depressive disorder (<jats:styled-content style=\"fixed-case\">MDD<\/jats:styled-content>) is a mental disease characterized by depressed mood, lifetime anxiety, and deficits of learning and memory. Inhibition of phosphodiesterase 9 (<jats:styled-content style=\"fixed-case\">PDE<\/jats:styled-content>9) has been reported to improve rodent cognitive and memory function. However, the role of <jats:styled-content style=\"fixed-case\">PDE<\/jats:styled-content>9 in <jats:styled-content style=\"fixed-case\">MDD<\/jats:styled-content>, in particular its manifestations of depression and anxiety, has not been investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We examined the protective effects of <jats:styled-content style=\"fixed-case\">WYQ<\/jats:styled-content>\u2010C36D (C36D), a novel <jats:styled-content style=\"fixed-case\">PDE<\/jats:styled-content>9 inhibitor, against corticosterone\u2010induced cytotoxicity, <jats:styled-content style=\"fixed-case\">pCREB<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">CREB<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">BDNF<\/jats:styled-content> expression by cell viability, and immunoblot assays in <jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content>\u201022 cells. The potential effects of C36D at doses of 0.1, 0.5, and 1\u00a0mg\/kg on stress\u2010induced depression\u2010 and anxiety\u2010like behaviors and memory deficits were also examined in mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>C36D significantly protected <jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content>\u201022 cells against corticosterone\u2010induced cytotoxicity and rescued corticosterone\u2010induced decreases in <jats:styled-content style=\"fixed-case\">cGMP<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> CREB<\/jats:styled-content> phosphorylation, and <jats:styled-content style=\"fixed-case\">BDNF<\/jats:styled-content> expression. All these effects were otherwise blocked by the <jats:styled-content style=\"fixed-case\">PKG<\/jats:styled-content> inhibitor Rp\u20108\u2010Br\u2010<jats:styled-content style=\"fixed-case\">PET<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">cGMPS<\/jats:styled-content> (Rp8). In addition, when tested in vivo in stressed mice, C36D produced antidepressant\u2010like effects on behavior, as shown by decreased immobility time both in the forced swimming and tail suspension tests. C36D also showed anxiolytic\u2010like and memory\u2010enhancing effects in the elevated plus\u2010maze and novel object recognition tests.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results show that inhibition of <jats:styled-content style=\"fixed-case\">PDE<\/jats:styled-content>9 by C36D produces antidepressant\u2010 and anxiolytic\u2010like behavioral effects and memory enhancement by activating <jats:styled-content style=\"fixed-case\">cGMP<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">PKG<\/jats:styled-content> signaling pathway. <jats:styled-content style=\"fixed-case\">PDE<\/jats:styled-content>9 inhibitors may have the potential as a novel class of drug to treat <jats:styled-content style=\"fixed-case\">MDD<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.12864","type":"journal-article","created":{"date-parts":[[2018,5,3]],"date-time":"2018-05-03T06:47:58Z","timestamp":1525330078000},"page":"889-896","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["A novel <scp>PDE<\/scp>9 inhibitor <scp>WYQ<\/scp>\u2010C36D ameliorates corticosterone\u2010induced neurotoxicity and depression\u2010like behaviors by <scp>cGMP<\/scp>\u2010<scp>CREB<\/scp>\u2010related signaling"],"prefix":"10.1111","volume":"24","author":[{"given":"Xian\u2010Feng","family":"Huang","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Engineering and Life Sciences Changzhou University  Changzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010Tao","family":"Jiang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Engineering and Life Sciences Changzhou University  Changzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Engineering and Life Sciences Changzhou University  Changzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang\u2010Chen","family":"Song","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Engineering and Life Sciences Changzhou University  Changzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Pharmacy Xuzhou Medical University  Xuzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gui\u2010Lan","family":"Shi","sequence":"additional","affiliation":[{"name":"Zibo Vocational Institute  Zibo Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu\u2010Ming","family":"Ding","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Engineering and Life Sciences Changzhou University  Changzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng\u2010Ming","family":"Ke","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center The University of North Carolina  Chapel Hill NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of New Mexico  Albuquerque NM USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James M.","family":"O'Donnell","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences School of Pharmacy and Pharmaceutical Sciences The State University of New York at Buffalo  Buffalo NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han\u2010Ting","family":"Zhang","sequence":"additional","affiliation":[{"name":"Departments of Behavioral Medicine &amp; 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