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学科主题临床医学
Duration-dependent regulation of autophagy by isoflurane exposure in aged rats
Li, Zheng-Qian1; Li, Lun-Xu1; Mo, Na2,3; Cao, Yi-Yun1; Kuerban, Bolati4; Liang, Yao-Xian5; Fan, Dong-Sheng4; Chui, De-Hua4; Guo, Xiang-Yang1
关键词autophagy phagophore formation cognitive dysfunction
刊名NEUROSCIENCE BULLETIN
2015-08-01
DOI10.1007/s12264-015-1549-1
31期:4页:505-513
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Neurosciences
研究领域[WOS]Neurosciences & Neurology
关键词[WOS]POSTOPERATIVE COGNITIVE DYSFUNCTION ; KAPPA-B PATHWAY ; ALZHEIMERS-DISEASE ; ANESTHETIC ISOFLURANE ; GENERAL-ANESTHETICS ; CELL-DEATH ; BETA ; HIPPOCAMPUS ; APOPTOSIS ; BRAIN
英文摘要

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 hippocampal 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 isofl urane (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 isofl urane 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 peaked at 6 h but subsequently resolved. These results from our pilot in vivo study support a duration-dependent relationship between 1.5% isoflurane exposure, and spatial cognitive function as well as hippocampal phagophore formation.

语种英语
WOS记录号WOS:000361452400014
项目编号81371205 ; 2012CB911000 ; 2012CB911004
资助机构National Natural Science Foundation of China ; National Basic Research Development Program (973 Program) of China
引用统计
被引频次:8[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/65295
专题北京大学第三临床医学院_麻醉科
北京大学第二临床医学院_肾内科
北京大学第三临床医学院_神经内科
作者单位1.Peking Univ, Hosp 3, Dept Anesthesiol, Beijing 100191, Peoples R China
2.Chinese Acad Med Sci, Canc Hosp & Inst, Beijing 100021, Peoples R China
3.Peking Union Med Coll, Beijing 100021, Peoples R China
4.Peking Univ, Hosp 3, Dept Neurol, Beijing 100191, Peoples R China
5.Peking Univ, Hosp 3, Dept Nephrol, Beijing 100191, Peoples R China
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Li, Zheng-Qian,Li, Lun-Xu,Mo, Na,et al. Duration-dependent regulation of autophagy by isoflurane exposure in aged rats[J]. NEUROSCIENCE BULLETIN,2015,31(4):505-513.
APA Li, Zheng-Qian.,Li, Lun-Xu.,Mo, Na.,Cao, Yi-Yun.,Kuerban, Bolati.,...&Guo, Xiang-Yang.(2015).Duration-dependent regulation of autophagy by isoflurane exposure in aged rats.NEUROSCIENCE BULLETIN,31(4),505-513.
MLA Li, Zheng-Qian,et al."Duration-dependent regulation of autophagy by isoflurane exposure in aged rats".NEUROSCIENCE BULLETIN 31.4(2015):505-513.
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