Promoting neurogenesis via Wnt/beta-catenin signaling pathway accounts for the neurorestorative effects of morroniside against cerebral ischemia injury
机构:[a]Department of Pharmacology, Xuanwu Hospital of Capital Medical University, 45 Chang-chun Street, Beijing 100053, China首都医科大学宣武医院药学部[b]Department of Physiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China[c]Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, No.10 Xitoutiao, You An Men Beijing 100069, China[d]Department of Neurosurgery, Xuanwu Hospital of Capital Medical University. 45 Chang-chun Street, Beiing 100053, China神经外科首都医科大学宣武医院
Ischemic stroke is a leading cause of mortality and permanent disability in adults worldwide. Neurogenesis triggered by ischemia in the adult mammalian brain may provide insights into stroke treatment. Morroniside is an active component of sarcocarp of C. officinalis that have shown neuroprotective effects. The aim of the present study is to test whether morroniside promotes neurogenesis via Wnt/beta-catenin signaling pathway for brain recovery in a rat model of focal cerebral ischemia. Morroniside was administered intragastrically once daily at the concentrations of 30, 90 and 270 mg/kg for 7 days post-ischemia. Neurological functions were detected by Ludmila Belayev score tests. Endogenous neural stem cells responses were investigated with immunofluorescence staining of Ki-67 and Nestin to identify the neurogenesis in the subventricular zone (SVZ). The expression of proteins involved in and related to Wnt/beta-catenin signaling pathway was detected by western blotting analysis. Morroniside significantly promoted neurogenesis for brain recovery 7 days post-ischemia. Increased expression of Writ 3a, P-catenin and T-cell transcription factor-4 (Tcf-4), along with activation of downstream transcription factors Pax6 and neurogenin2 (Ngn2), indicated that the neurorestorative effects of morroniside may be associated with Wnt/beta-catenin signaling pathway. These data provide support for understanding the mechanisms of morroniside in neurorestorative effects and suggest a potential new strategy for ischemic stroke treatment. (C) 2014 Elsevier B.V. All rights reserved.
基金:
the National Science and Technol-ogy Major Project (201 2ZX09102201-106);
National NaturalScience Foundation of China (81173575, 81373994, 30973893 and 81274173);
Beijing Natural Science Foundation ( 7102077 and7211017);
Beijing Municipal Commission of Education & CapitalMedical University Base-Technological Innovation Platform Fund(112216);
Beijing Health System Experts of High-level grant (2011-3- O97);
China Postdoctoral Science Foundation funded project(2012M520330)
Beijing Postdoctoral Science Foundationfunded project
第一作者机构:[a]Department of Pharmacology, Xuanwu Hospital of Capital Medical University, 45 Chang-chun Street, Beijing 100053, China
通讯作者:
通讯机构:[a]Department of Pharmacology, Xuanwu Hospital of Capital Medical University, 45 Chang-chun Street, Beijing 100053, China[c]Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, No.10 Xitoutiao, You An Men Beijing 100069, China
推荐引用方式(GB/T 7714):
Fang-Ling Sun,Wen Wang,Wei Zuo,et al.Promoting neurogenesis via Wnt/beta-catenin signaling pathway accounts for the neurorestorative effects of morroniside against cerebral ischemia injury[J].EUROPEAN JOURNAL OF PHARMACOLOGY.2014,738:214-221.doi:10.1016/j.ejphar.2014.05.019.
APA:
Fang-Ling Sun,Wen Wang,Wei Zuo,Jin-Long Xue,Jing-dong Xu...&Xun-Ming Ji.(2014).Promoting neurogenesis via Wnt/beta-catenin signaling pathway accounts for the neurorestorative effects of morroniside against cerebral ischemia injury.EUROPEAN JOURNAL OF PHARMACOLOGY,738,
MLA:
Fang-Ling Sun,et al."Promoting neurogenesis via Wnt/beta-catenin signaling pathway accounts for the neurorestorative effects of morroniside against cerebral ischemia injury".EUROPEAN JOURNAL OF PHARMACOLOGY 738.(2014):214-221