Prophylactic Melatonin Attenuates Isoflurane-Induced Cognitive Impairment in Aged Rats through Hippocampal Melatonin Receptor 2-cAMP Response Element Binding Signalling
Prophylactic Melatonin Attenuates Isoflurane-Induced Cognitive Impairment in Aged Rats through Hippocampal Melatonin Receptor 2-cAMP Response Element Binding Signalling
复制标题
预防性褪黑激素通过海马褪黑激素受体 2 → cAMP 反应元件结合信号传导减轻老年大鼠异氟烷引起的认知障碍
DOI：
10.1111/bcpt.12652
复制
发表时间：
2017-03-01
影响因子：
3.1
通讯作者：
Guo, Xiangyang
中科院分区：
文献类型：
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作者：
Liu, Yajie;Ni, Cheng;Guo, Xiangyang
褪黑素通过褪黑素受体发挥多种生理作用，其中褪黑素-2受体（MT2）在昼夜节律障碍、阿尔茨海默病等神经系统疾病中发挥重要作用。褪黑激素替代策略之前已经测试过，MT2是这个过程中的一个关键目标。cAMP反应元件结合（CREB）是记忆形成的重要转录因子，可能参与MT2信号传导。因此，本研究旨在探讨预防性褪黑激素对吸入麻醉异氟醚诱导的认知障碍的影响，并确定褪黑激素的保护作用是否依赖于老年大鼠海马中MT2和下游CREB信号传导。结果表明，预防性褪黑素可减轻异氟醚引起的老年大鼠血浆/海马褪黑素水平下降和认知障碍。此外，选择性MT2拮抗剂4P-PDOT可阻断褪黑素对异氟醚诱导的海马MT2表达和下游CREB磷酸化降低的保护作用。4P-PDOT阻断褪黑素对异氟醚所致记忆损伤的抑制作用。总的来说，结果表明预防性褪黑激素的保护作用依赖于海马体MT2-CREB信号传导，这可能是麻醉引起的认知障碍的潜在治疗靶点。
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 MT2 was a critical target during the process. cAMP response element binding (CREB) is an essential transcription factor for memory formation and could be involved in MT2 signalling. 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 MT2 and 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 MT2 antagonist, blocked the protective effects of melatonin on isoflurane-induced decreases in both hippocampal MT2 expression 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.