SIRT1 activation attenuates microglia-mediated synaptic engulfment in postoperative cognitive dysfunction.
SIRT1 activation attenuates microglia-mediated synaptic engulfment in postoperative cognitive dysfunction.
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SIRT1激活减弱术后认知功能障碍中小胶质细胞介导的突触吞噬
DOI：
10.3389/fnagi.2022.943842
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发表时间：
2022
影响因子：
4.8
通讯作者：
中科院分区：
文献类型：
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作者：
术后认知功能障碍（POCD）是外科手术患者的一种使人衰弱的神经系统并发症。目前的研究主要集中在小胶质细胞的激活，但很少有人知道由此产生的神经元突触的变化。最近的研究表明，Sirtuin-1（SIRT 1）通过参与小胶质细胞活化在几种不同的神经系统疾病中起着关键作用。在这项研究中，我们评估了SIRT 1激活在POCD小鼠模型中的作用。在七氟醚麻醉下对12-14月龄小鼠进行探索性剖腹手术，以建立我们的动物POCD模型。通过RNA测序评估麻醉和手术后海马的转录变化。通过Western Blot验证SIRT 1表达。在手术后用SIRT 1激动剂SRT 1720或媒介物处理小鼠。评价了小胶质细胞形态学、小胶质细胞吞噬作用、营养不良神经突的存在和树突棘密度的变化。采用Y迷宫和Morris水迷宫（MWM）评价认知能力。Sirtuin-1表达水平在POCD中下调。暴露于麻醉和手术导致小胶质细胞形态改变，突触吞噬增加，树突棘丢失和认知缺陷。这些作用通过SRT 1720给药减轻。这项研究表明SIRT 1在POCD发病机制中具有重要的神经保护作用。增加SIRT 1功能代表了预防和治疗POCD的有希望的治疗策略。
Postoperative cognitive dysfunction (POCD) is a debilitating neurological complication in surgical patients. Current research has focused mainly on microglial activation, but less is known about the resultant neuronal synaptic changes. Recent studies have suggested that Sirtuin-1 (SIRT1) plays a critical role in several different neurological disorders via its involvement in microglial activation. In this study, we evaluate the effects of SIRT1 activation in a POCD mouse model. Exploratory laparotomy was performed in mice aged 12–14 months under sevoflurane anesthesia to establish our animal POCD model. Transcriptional changes in the hippocampus after anesthesia and surgery were evaluated by RNA sequencing. SIRT1 expression was verified by Western Blot. Mice were treated with SIRT1 agonist SRT1720 or vehicle after surgery. Changes in microglia morphology, microglial phagocytosis, presence of dystrophic neurites, and dendritic spine density were evaluated. Cognitive performance was evaluated using the Y maze and Morris water maze (MWM). Sirtuin-1 expression levels were downregulated in POCD. Exposure to anesthesia and surgery lead to alteration in microglia morphology, increased synaptic engulfment, dendritic spine loss, and cognitive deficits. These effects were alleviated by SRT1720 administration. This study suggests an important neuroprotective role for SIRT1 in POCD pathogenesis. Increasing SIRT1 function represents a promising therapeutic strategy for prevention and treatment of POCD.
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影响因子：
6.1
作者：
Diaz-Aparicio I;Beccari S;Abiega O;Sierra A
通讯作者：
Sierra A
影响因子：
6.1
作者：
Li, Li;Tan, Hong-Ping;Gu, Zheng-Tao
通讯作者：
Gu, Zheng-Tao
影响因子：
2.9
作者：
Li, Zhe;Liu, Fang;Cao, Xuezhao
通讯作者：
Cao, Xuezhao
衰老对自闭症谱系障碍BTBR小鼠模型的影响。
影响因子：
4.8
作者：
Jasien JM;Daimon CM;Wang R;Shapiro BK;Martin B;Maudsley S
通讯作者：
Maudsley S
DOI：
10.1083/jcb.201709069
发表时间：
2018-02-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hansen DV;Hanson JE;Sheng M
通讯作者：
Sheng M