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Long-term Effects of Recurrent Neonatal Seizures on Neurobehavioral Function and Related Gene Expression and Its Intervention by Inhibitor of Cathepsin B
Ni, Hong1,2; Yan, Jian-zhen1,2; Zhang, Le-ling1,2; Feng, Xing1,2; Wu, Xi-ru3
关键词Cathepsin B Autophagy bcl-2 PRG-1 Seizure
刊名NEUROCHEMICAL RESEARCH
2012
DOI10.1007/s11064-011-0578-z
37期:1页:31-39
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology ; Neurosciences
研究领域[WOS]Biochemistry & Molecular Biology ; Neurosciences & Neurology
关键词[WOS]BRAIN-INJURY ; CELL-DEATH ; UP-REGULATION ; WISTAR RAT ; AUTOPHAGY ; HIPPOCAMPUS ; APOPTOSIS ; ISCHEMIA ; PRG-1 ; MITOCHONDRIA
英文摘要

Cathepsins are families of proteases that have been reported to play the key roles in neuroexcitotoxicity. The present study was sought to determine the effect of CBI, a cathepsin B inhibitor, in the prevention of neurobehavioral deficits after inhalant flurothyl-induced recurrent neonatal seizures in rats. We examined the expression pattern of autophagy-related genes at acute phase after the last seizures using western blot method, and evaluated behavioral deficits during postnatal day 28 (P28) to P35. The results showed improved neurological scores and learning ability in CBI-treated rats compared with the nontreated control. Flurothyl-induced increases in the ratio of LC3-II/LC3-I, Beclin-1 and Cathepsin-B were blocked by pre-treatment with CBI at 1.5, 3, 6 and 24 h after the last seizures in hippocampus and cerebral cortex by western blot analysis. Meanwhile, CBI also reversed flurothyl-induced down-regulation of Bcl-2 protein levels. Furthermore, in the long-term time point of 35 days (P35), PRG-1 mRNA and protein level in hippocampus and cerebral cortex of recurrent seizure group were up-regulated when compared to the control rats; meanwhile, the up-regulated expression of PRG-1 were robustly inhibited by CBI. These date demonstrated, for the first time, that lysosomal enzymes participate in neonatal seizure-induced brain damage and that modulation of cathepsin B may offer a new strategy for the development of therapeutic interventions for treatment of developmental seizure-induced brain damage.

语种英语
WOS记录号WOS:000302404000006
项目编号30470555 ; 30870808 ; BK2007509 ; BK2010233
资助机构National Natural Science Foundation of China ; Natural Science Foundation of Jiangsu Province of China ; Saxon State Ministry of Social Affairs and Consumer Protection/Germany ; Health Department of the Jiangsu Province/China
引用统计
被引频次:18[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/400002259/61439
专题北京大学第一临床医学院_儿科
作者单位1.Soochow Univ, Affiliated Childrens Hosp, Neurol Lab, Suzhou 215003, Peoples R China
2.Soochow Univ, Inst Neurosci, Suzhou 215003, Peoples R China
3.Peking Univ, Hosp 1, Dept Pediat, Beijing 100034, Peoples R China
推荐引用方式
GB/T 7714
Ni, Hong,Yan, Jian-zhen,Zhang, Le-ling,et al. Long-term Effects of Recurrent Neonatal Seizures on Neurobehavioral Function and Related Gene Expression and Its Intervention by Inhibitor of Cathepsin B[J]. NEUROCHEMICAL RESEARCH,2012,37(1):31-39.
APA Ni, Hong,Yan, Jian-zhen,Zhang, Le-ling,Feng, Xing,&Wu, Xi-ru.(2012).Long-term Effects of Recurrent Neonatal Seizures on Neurobehavioral Function and Related Gene Expression and Its Intervention by Inhibitor of Cathepsin B.NEUROCHEMICAL RESEARCH,37(1),31-39.
MLA Ni, Hong,et al."Long-term Effects of Recurrent Neonatal Seizures on Neurobehavioral Function and Related Gene Expression and Its Intervention by Inhibitor of Cathepsin B".NEUROCHEMICAL RESEARCH 37.1(2012):31-39.
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