Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.
Laboratory of RNA and Major Diseases of Brain and Hearts, Sun Yat-Sen University, Guangzhou, 510120, China.
Neurotox Res. 2021 Apr;39(2):227-239. doi: 10.1007/s12640-020-00307-9. Epub 2020 Nov 7.
Considering the fact that melatonin acts as protective agent in various cognitive impairment, we decided to explore the precise effect of pretreatment with melatonin on cognitive function, mitochondrial activity, apoptosis and synaptic integrity in aged rats anesthetized by propofol. We first randomly allocated the thirty Sprague Dawley rats into three groups: Control vehicle-treated group (Con), Propofol-treated group (Pro) and Melatonin + Propofol group (Mel + Pro). The Barnes maze, open field and contextual fear conditioning test were employed to evaluate spatial memory, exploratory behavior and general locomotor activity, and hippocampus-dependent learning and memory ability, respectively. Moreover, mitochondrial function (including reactive oxygen species, mitochondrial membrane potential and ATP levels) and apoptosis were detected in the regions of hippocampus (HIP) and prefrontal cortex (PFC). The results of behavioral tests suggested that melatonin improved propofol-induced memory impairment in aged rats. Melatonin mitigated mitochondrial dysfunction and decreased the apoptotic cell counts in the regions of HIP and PFC. Furthermore, prophylactic melatonin treatment also reversed the propofol-induced inactivation of PKA/CREB/BDNF signaling and synaptic dysfunction. On the whole, our results indicated that melatonin ameliorated the propofol-induced cognitive disorders via attenuating mitochondrial dysfunction, apoptosis, inactivation of PKA/CREB/BDNF signaling and synaptic dysfunction.
鉴于褪黑素在各种认知障碍中作为保护剂的作用，我们决定探索褪黑素预处理对丙泊酚麻醉老年大鼠认知功能、线粒体活性、细胞凋亡和突触完整性的精确影响。我们首先将三十只 Sprague Dawley 大鼠随机分为三组：对照组（Con）、丙泊酚组（Pro）和褪黑素+丙泊酚组（Mel+Pro）。采用巴恩斯迷宫、旷场和情境恐惧条件反射测试分别评估空间记忆、探索行为和一般运动活动以及海马依赖性学习和记忆能力。此外，还检测了海马（HIP）和前额叶皮层（PFC）区域的线粒体功能（包括活性氧、线粒体膜电位和 ATP 水平）和细胞凋亡。行为测试的结果表明，褪黑素改善了丙泊酚诱导的老年大鼠记忆障碍。褪黑素减轻了线粒体功能障碍，并减少了 HIP 和 PFC 区域的凋亡细胞计数。此外，预防性褪黑素治疗还逆转了丙泊酚诱导的 PKA/CREB/BDNF 信号通路失活和突触功能障碍。总的来说，我们的结果表明，褪黑素通过减轻线粒体功能障碍、细胞凋亡、PKA/CREB/BDNF 信号通路失活和突触功能障碍改善了丙泊酚引起的认知障碍。
