Surgery/Anesthesia disturbs mitochondrial fission/fusion dynamics in the brain of aged mice with postoperative delirium
Surgery/Anesthesia disturbs mitochondrial fission/fusion dynamics in the brain of aged mice with postoperative delirium
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DOI：
10.18632/aging.102659
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发表时间：
2020-01-15
期刊：
影响因子：
5.2
通讯作者：
Peng, Mian
中科院分区：
文献类型：
--
作者：
Lu, Yayuan;Chen, Lei;Peng, Mian
术后谵妄（POD）是手术和麻醉（手术/麻醉）后的常见并发症。线粒体功能障碍，这是证明了能源赤字和过度激活的氧化应激，已被报道有助于POD。线粒体融合和分裂过程之间的动态平衡对于调节线粒体功能至关重要。然而，手术/麻醉对线粒体融合/裂变动力学的影响仍不清楚。在这里，我们评估了1.4%异氟烷麻醉下剖腹手术2小时对老年小鼠脑中线粒体分裂/融合动力学的影响。手术/麻醉组小鼠表现出不平衡的分裂/融合动力学，线粒体部分中DISC 1表达降低，Drp 1和Mfn 2表达增加，导致海马和前额叶皮质中线粒体过度分裂和线粒体形态发生紊乱。此外，手术小鼠表现出线粒体功能障碍，表现为异常激活的氧化应激（ROS水平升高，SOD水平降低）和能量缺乏（ATP和MMP水平降低）。手术/麻醉还降低了神经元/突触可塑性相关蛋白（如PSD-95和BDNF）的表达。此外，手术/麻醉诱导老年小鼠的谵妄样行为。总之，手术/麻醉扰乱了老年小鼠脑中线粒体分裂/融合动力学，从而损害了线粒体功能;这些影响可能参与了POD的潜在机制。
Postoperative delirium (POD) is a common complication following surgery and anesthesia (Surgery/Anesthesia). Mitochondrial dysfunction, which is demonstrated by energy deficits and excessively activated oxidative stress, has been reported to contribute to POD. The dynamic balance between mitochondrial fusion and fission processes is critical in regulating mitochondrial function. However, the impact of Surgery/Anesthesia on mitochondrial fusion/fission dynamics remains unclear. Here, we evaluate the effects of laparotomy under 1.4% isoflurane anesthesia for 2 hours on mitochondrial fission/fusion dynamics in the brain of aged mice. Mice in Surgery/Anesthesia group showed unbalanced fission/fusion dynamics, with decreased DISC1 expression and increased expression of Drp1 and Mfn2 in the mitochondrial fraction, leading to excessive mitochondrial fission and disturbed mitochondrial morphogenesis in the hippocampus and prefrontal cortex. In addition, surgical mice presented mitochondrial dysfunction, demonstrated by abnormally activated oxidative stress (increased ROS level, decreased SOD level) and energy deficits (decreased levels of ATP and MMP). Surgery/Anesthesia also decreased the expression of neuronal/synaptic plasticity-related proteins such as PSD-95 and BDNF. Furthermore, Surgery/Anesthesia induced delirium-like behavior in aged mice. In conclusion, Surgery/Anesthesia disturbed mitochondrial fission/fusion dynamics and then impaired mitochondrial function in the brain of aged mice; these effects may be involved in the underlying mechanism of POD.