Tau hyperphosphorylation: A downstream effector of isoflurane-induced neuroinflammation in aged rodents
Tau hyperphosphorylation: A downstream effector of isoflurane-induced neuroinflammation in aged rodents
复制标题
Tau 蛋白过度磷酸化：老年啮齿动物异氟烷诱导的神经炎症的下游效应器
DOI：
10.1016/j.mehy.2013.11.015
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发表时间：
2014-01-01
影响因子：
4.7
通讯作者：
Li, Shiyong
中科院分区：
文献类型：
--
作者：
Luo, Xiaoxiao;Yang, Liu;Li, Shiyong
术后认知功能障碍（POCD）是麻醉和手术后严重的神经系统后遗症。高龄、麻醉时间等多种危险因素与POCD相关，但其病理生理机制有待进一步阐明。迄今为止，有大量证据表明，神经炎症细胞因子和随后的神经炎症反应有助于暴露于异氟醚（一种常用的全身麻醉剂）的老年啮齿动物的认知障碍。有趣的是，即使在异氟烷暴露14天后，这种认知障碍也会通过抗炎剂得到缓解。此外，异氟醚诱导的神经炎性细胞因子上调仅局限于48小时内。因此，首先考虑的可能是异氟醚诱导的神经炎性细胞因子的下游效应，它有助于长期的认知功能障碍。在阿尔茨海默病（AD）模型中，促炎细胞因子可诱导tau蛋白过度磷酸化，这与突触异常和进一步的认知障碍有关。目前尚不清楚异氟醚诱导的神经炎性细胞因子是否会引发tau蛋白过度磷酸化。综上所述，我们假设tau过度磷酸化是异氟醚诱导的神经炎症反应的下游靶点，因此将异氟醚诱导的相对短暂的神经炎症过程与长期认知障碍联系起来。(C) 2013 Elsevier Ltd.版权所有。
Postoperative cognitive dysfunction (POCD) is a severe neurological sequela after anesthesia and surgery. Multiple risk factors, such as advanced age and anesthesia duration, relevant to POCD have been made out, although the pathophysiological mechanisms of this complication need to be further elucidated. To date, there is a substantial body of evidence implicating that neuroinflammatory cytokines and the subsequent neuroinflammatory response contribute to the cognitive impairment in aged rodents exposed to isoflurane, a commonly used general anesthetic. Interestingly, this cognitive disorder is mitigated by anti-inflammatory agents even 14 days after isoflurane exposure. In addition, isoflurane-induced upregulation of neuroinflammatory cytokines is only limited within 48 h. So a first possibility to consider is a downstream effector of isoflurane-induced neuroinflammatory cytokines which contributes to the long-lasting cognitive dysfunction. In Alzheimer's disease (AD) models, proinflammatory cytokines can induce tau hyperphosphorylation which is associated with synaptic abnormality and further cognitive impairment. It is unknown whether isoflurane-induced neuroinflammatory cytokines can trigger tau hyperphosphorylation. Taken together, we hypothesize that tau hyperphosphorylation is a downstream target of isoflurane-induced neuroinflammatory response and thus bridges the isoflurane-induced relatively transient neuroinflammatory process to the long-term cognitive impairment. (C) 2013 Elsevier Ltd. All rights reserved.