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A melatonin replacement strategy has been tested previously, and <jats:styled-content style=\"fixed-case\">MT<\/jats:styled-content><jats:sub>2<\/jats:sub> was a critical target during the process. <jats:styled-content style=\"fixed-case\">cAMP<\/jats:styled-content> response element binding (<jats:styled-content style=\"fixed-case\">CREB<\/jats:styled-content>) is an essential transcription factor for memory formation and could be involved in <jats:styled-content style=\"fixed-case\">MT<\/jats:styled-content><jats:sub>2<\/jats:sub> signalling. Therefore, the present study was designed to investigate the effects of prophylactic melatonin on inhaled anaesthetic isoflurane\u2010induced cognitive impairment, and to determine whether the protective effects of melatonin are dependent on <jats:styled-content style=\"fixed-case\">MT<\/jats:styled-content><jats:sub>2<\/jats:sub> and downstream <jats:styled-content style=\"fixed-case\">CREB<\/jats:styled-content> signalling in the hippocampus of aged rats. The results showed that prophylactic melatonin attenuated isoflurane\u2010induced decreases in plasma\/hippocampal melatonin levels and cognitive impairment in aged rats. Furthermore, 4P\u2010<jats:styled-content style=\"fixed-case\">PDOT<\/jats:styled-content>, a selective <jats:styled-content style=\"fixed-case\">MT<\/jats:styled-content><jats:sub>2<\/jats:sub> antagonist, blocked the protective effects of melatonin on isoflurane\u2010induced decreases in both hippocampal <jats:styled-content style=\"fixed-case\">MT<\/jats:styled-content><jats:sub>2<\/jats:sub> expression and downstream <jats:styled-content style=\"fixed-case\">CREB<\/jats:styled-content> phosphorylation. And 4P\u2010<jats:styled-content style=\"fixed-case\">PDOT<\/jats:styled-content> blocked the attenuation of melatonin on isoflurane\u2010induced memory impairment. Collectively, the results suggest that the protective effects of prophylactic melatonin are dependent on hippocampal <jats:styled-content style=\"fixed-case\">MT<\/jats:styled-content><jats:sub>2<\/jats:sub>\u2010<jats:styled-content style=\"fixed-case\">CREB<\/jats:styled-content> signalling, which could be a potential therapeutic target for anaesthetic\u2010induced cognitive impairment.<\/jats:p>","DOI":"10.1111\/bcpt.12652","type":"journal-article","created":{"date-parts":[[2016,8,12]],"date-time":"2016-08-12T05:56:49Z","timestamp":1470981409000},"page":"219-226","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Prophylactic Melatonin Attenuates Isoflurane\u2010Induced Cognitive Impairment in Aged Rats through Hippocampal Melatonin Receptor 2 \u2013 cAMP Response Element Binding Signalling"],"prefix":"10.1111","volume":"120","author":[{"given":"Yajie","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Peking University Third Hospital Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Peking University Third Hospital Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhengqian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Peking University Third Hospital Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ning","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Peking University Third Hospital Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Peking University Third Hospital Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoying","family":"Rong","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Peking University Third Hospital Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Peking University Third Hospital Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dehua","family":"Chui","sequence":"additional","affiliation":[{"name":"Neuroscience Research Institute &amp; 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