Protective effect of dapsone on cognitive impairment induced by propofol involves hippocampal autophagy
Protective effect of dapsone on cognitive impairment induced by propofol involves hippocampal autophagy
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氨苯砜对丙泊酚所致认知障碍的保护作用涉及海马自噬
DOI：
10.1016/j.neulet.2017.04.019
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发表时间：
2017-05-10
影响因子：
2.5
通讯作者：
Guo, Xiangyang
中科院分区：
文献类型：
--
作者：
Yang, Ning;Li, Lunxu;Guo, Xiangyang
术后认知功能障碍（POCD）是老年患者常见的术后并发症，其发生机制尚不清楚。自噬是一种细胞成分的降解机制，是细胞生存和许多生理过程所必需的。丙泊酚是最常用的静脉麻醉药之一，但其作用机制和对老年啮齿动物认知功能的影响研究相对较少。在这项研究中，我们评估异丙酚对学习和记忆的影响，并确定海马自噬在异丙酚诱导的老年大鼠认知改变中的潜在作用。结果表明，4小时异丙酚暴露显着损害认知能力，通过抑制海马自噬。二氨基二苯砜（dapsone，DDS）是一种抗麻风药物，具有神经保护作用。我们以前已经证明，DDS可以改善手术应激诱导的抑郁和焦虑样行为。因此，我们的目的是研究DDS对丙泊酚诱导的认知功能障碍和相关的海马自噬反应的影响。5 mg/kg或10 mg/kg DDS预处理可显著改善老年大鼠的行为障碍，并上调抑制的自噬反应。我们的探索是第一个建立中枢自噬和丙泊酚麻醉后老年海马认知功能障碍之间的体内联系，并证明DDS对丙泊酚诱导的认知功能障碍的预防作用涉及自噬。这些发现可能意味着一个潜在的新靶点，用于治疗丙泊酚麻醉诱导的认知障碍患者。(C)2017爱思唯尔B. V.保留所有权利。
Post-operative cognitive dysfunction (POCD) is a commonly seen postoperative complication in elderly patients and its underlying mechanisms are still unclear. Autophagy, a degradation mechanism of cellular components, is required for cell survival and many physiological processes. Although propofol is one of the most commonly used intravenous anesthetics, investigations into its mechanisms and effects on cognition in aged rodents are relatively scarce. In this study, we evaluate the influence of propofol on learning and memory, and identify the potential role of hippocampal autophagy in propofol-induced cognitive alterations in aged rats. The results demonstrate that 4 h propofol exposure significantly impaired cognitive performance through the inhibition of hippocampal autophagy. Diaminodiphenyl sulfone (dapsone, DDS), which was used as an anti-leprosy drug, has been found to have neuroprotective effects. We have previously demonstrated that DDS can improve surgical stress induced depression- and anxiety-like behavior. We therefore aimed to investigate the effects of DDS on propofol-induced cognitive dysfunction and associated hippocampal autophagy responses. Pretreatment with 5 mg/kg or 10 mg/kg body weight DDS significantly improved the behavioral disorder and upregulated the inhibited autophagic response in aged rats. Our exploration is the first to establish an in vivo link between central autophagy and cognitive dysfunction in aged hippocampus after propofol anesthesia and demonstrate that the prophylactic effect of DDS on the cognitive impairment induced by propofol involves autophagy. These findings may imply a potential novel target for the treatment in patients with propofol anesthesia-induced cognitive impairment. (C) 2017 Elsevier B.V. All rights reserved.