title: Prophylactic Melatonin Attenuates Isoflurane-Induced Cognitive Impairment in Aged Rats through Hippocampal Melatonin Receptor 2 - cAMP Response Element Binding Signalling.
abstract: Melatonin exerts many physiological effects via melatonin receptors, among which the melatonin-2 receptor (MT2) plays a critical role in circadian rhythm disorders, Alzheimer's disease and other neurological disorders. A melatonin replacement strategy has been tested previously, and MT2was a critical target during the process. cAMP response element binding (CREB) is an essential transcription factor for memory formation and could be involved in MT2signalling. Therefore, the present study was designed to investigate the effects of prophylactic melatonin on inhaled anaesthetic isoflurane-induced cognitive impairment, and to determine whether the protective effects of melatonin are dependent on MT2and downstream CREB signalling in the hippocampus of aged rats. The results showed that prophylactic melatonin attenuated isoflurane-induced decreases in plasma/hippocampal melatonin levels and cognitive impairment in aged rats. Furthermore, 4P-PDOT, a selective MT2antagonist, blocked the protective effects of melatonin on isoflurane-induced decreases in both hippocampal MT2expression and downstream CREB phosphorylation. And 4P-PDOT blocked the attenuation of melatonin on isoflurane-induced memory impairment. Collectively, the results suggest that the protective effects of prophylactic melatonin are dependent on hippocampal MT2-CREB signalling, which could be a potential therapeutic target for anaesthetic-induced cognitive impairment.
authors: Department of Anesthesiology, Peking University Third Hospital, Beijing, China.
authors: Yajie
authors: Y
authors: Liu
authors: Department of Anesthesiology, Peking University Third Hospital, Beijing, China.
authors: Cheng
authors: C
authors: Ni
authors: Department of Anesthesiology, Peking University Third Hospital, Beijing, China.
authors: Zhengqian
authors: Z
authors: Li
authors: Department of Anesthesiology, Peking University Third Hospital, Beijing, China.
authors: Ning
authors: N
authors: Yang
authors: Department of Anesthesiology, Peking University Third Hospital, Beijing, China.
authors: Yang
authors: Y
authors: Zhou
authors: Department of Anesthesiology, Peking University Third Hospital, Beijing, China.
authors: Xiaoying
authors: X
authors: Rong
authors: Department of Anesthesiology, Peking University Third Hospital, Beijing, China.
authors: Min
authors: M
authors: Qian
authors: Neuroscience Research Institute & Department of Neurobiology, Peking University, Beijing, China.
authors: Dehua
authors: D
authors: Chui
authors: Department of Anesthesiology, Peking University Third Hospital, Beijing, China.
authors: Xiangyang
authors: X
authors: Guo
mesh_terms: D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D060825:Cognitive Dysfunction / Q000139:chemically induced / Q000517:prevention & control; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007530:Isoflurane / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008550:Melatonin / Q000008:administration & dosage*; D008569:Memory Disorders / Q000139:chemically induced* / Q000517:prevention & control*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D044123:Receptor, Melatonin, MT2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
chemical_list: C114459:4-phenyl-2-propionamidotetraline; D018685:Anesthetics, Inhalation; D017362:Cyclic AMP Response Element-Binding Protein; D044123:Receptor, Melatonin, MT2; D013764:Tetrahydronaphthalenes; D007530:Isoflurane; D008550:Melatonin