Duration-dependent regulation of autophagy by isoflurane exposure in aged rats  

作　　者：Zheng-Qian Li Lun-Xu Li Na Mo Yi-Yun Cao Bolati Kuerban Yao-Xian Liang Dong-Sheng Fan De-Hua Chui Xiang-Yang Guo 

机构地区：[1]Department of Anesthesiology,Peking University Third Hospital [2]Cancer Hospital and Institute,Chinese Academy of Medical Sciences and Peking Union Medical College [3]Department of Neurology,Peking University Third Hospital [4]Department of Nephrology,Peking University Third Hospital

出　　处：《Neuroscience Bulletin》2015年第4期505-513,共9页神经科学通报（英文版）

基　　金：supported by grants from the National Natural Science Foundation of China (81371205);the National Basic Research Development Program (973 Program) of China (2012CB911000 and 2012CB911004)

摘　　要：Current evidence suggests a central role for autophagy in many inflammatory brain disorders, including Alzheimer＇s disease （AD）. Furthermore, it is also well accepted that some inhalation anesthetics, such as isoflurane, may cause AD- like neuropathogenesis and resultant postoperative cognitive dysfunction, especially in the elderly population. However, the impact of inhalation anesthetics on autophagic components in the brain remains to be documented. Hence, our objective was to investigate the effects of different durations of isoflurane exposure on hippocampus-dependent learning and hippocarnpal autophagy in aged rats. Aged Sprague-Dawley rats （20 months old） were randomly exposed to 1.5% isoflurane or 100% oxygen for 1 or 4 h. Animals were then trained in the Morris water maze （4 trials/day for 5 consecutive days）. Hippocampal phagophore formation markers, beclin 1 and protein microtubule-associated protein 1 light chain-3B （LC3B）, as well as p62, an indicator of autophagic flux, were quantified by western blotting. There was no significant difference in the escape latencies and time spent in the target quadrant, as well as hippocampal expression of beclin 1, LC3B- II, and p62 at 24 h post-anesthesia between the 1-h isoflurane-exposed rats and their controls （P 〉0.05）. Four-hour exposure to isoflurane resulted in spatial learning and memory deficits, as evidenced by prolonged escape latencies on days 4 and 5 post- anesthesia and less time spent in the target quadrant than sham-exposed animals （P 〈0.05）. These events were accompanied by a decline in hippocampal expression of LC3B-I, LC3B-II, and beclin 1 24 h after isoflurane （P 〈0.01 and P 〈0.05）. Nevertheless, no significant change in p62 expression was found. Further kinetics study of autophagic changes induced by 4 h of isoflurane showed a transient upregulation of LC3B-I, LC3B-II, and beclin 1 at the end of exposure and a subsequent striking decrease within 12-24 h post-anesthesia （P 〈0.05）. Hippocampal p62 peakCurrent evidence suggests a central role for autophagy in many inflammatory brain disorders, including Alzheimer＇s disease （AD）. Furthermore, it is also well accepted that some inhalation anesthetics, such as isoflurane, may cause AD- like neuropathogenesis and resultant postoperative cognitive dysfunction, especially in the elderly population. However, the impact of inhalation anesthetics on autophagic components in the brain remains to be documented. Hence, our objective was to investigate the effects of different durations of isoflurane exposure on hippocampus-dependent learning and hippocarnpal autophagy in aged rats. Aged Sprague-Dawley rats （20 months old） were randomly exposed to 1.5% isoflurane or 100% oxygen for 1 or 4 h. Animals were then trained in the Morris water maze （4 trials/day for 5 consecutive days）. Hippocampal phagophore formation markers, beclin 1 and protein microtubule-associated protein 1 light chain-3B （LC3B）, as well as p62, an indicator of autophagic flux, were quantified by western blotting. There was no significant difference in the escape latencies and time spent in the target quadrant, as well as hippocampal expression of beclin 1, LC3B- II, and p62 at 24 h post-anesthesia between the 1-h isoflurane-exposed rats and their controls （P 〉0.05）. Four-hour exposure to isoflurane resulted in spatial learning and memory deficits, as evidenced by prolonged escape latencies on days 4 and 5 post- anesthesia and less time spent in the target quadrant than sham-exposed animals （P 〈0.05）. These events were accompanied by a decline in hippocampal expression of LC3B-I, LC3B-II, and beclin 1 24 h after isoflurane （P 〈0.01 and P 〈0.05）. Nevertheless, no significant change in p62 expression was found. Further kinetics study of autophagic changes induced by 4 h of isoflurane showed a transient upregulation of LC3B-I, LC3B-II, and beclin 1 at the end of exposure and a subsequent striking decrease within 12-24 h post-anesthesia （P 〈0.05）. Hippocampal p62 peak

关 键 词：AUTOPHAGY phagophore formation cognitive dysfunction 

分 类 号：R614[医药卫生—麻醉学]