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学科主题: 临床医学
题名:
Duration-dependent regulation of autophagy by isoflurane exposure in aged rats
作者: 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
发表日期: 2015-08-01
DOI: 10.1007/s12264-015-1549-1
卷: 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
所属项目编号: 81371205 ; 2012CB911000 ; 2012CB911004
项目资助者: National Natural Science Foundation of China ; National Basic Research Development Program (973 Program) of China
WOS记录号: WOS:000361452400014
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/65295
Appears in Collections:北京大学第三临床医学院_麻醉科_期刊论文

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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

Recommended Citation:
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.
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