中国药理学通报2016，Vol.32Issue(4)：473-479,480,8.DOI:10.3969/j.issn.1001-1978.2016.04.007
美金刚激活NGF/TrkA信号通路改善APP/PS1转基因小鼠学习记忆障碍
Memantine improves cognitive deficits by activiating NGF/TrkA signaling in APP/PS1 transgenic mice
摘要
Abstract
Aims To study the role of NGF/Trk A sig-naling pathway in Memantine ( MEM) improving APP/PS1 transgenic mice cognitive deficits and to explore its possible mechanisms. Methods Cognitive perform-ance was assessed by Morris water maze( MWM) , pas-sive avoidance test( PAT) and locomotivity test. Aβ1-42 protein levels were determined by immunohistochemis-try. The activities of AChE and ChAT were also exam-ined by ELISA and colorimetry. Western blot was used to detect the expression levels of NGF and its receptor TrkA and the downstream ERK pathway. Results MEM treatment significantly ameliorated the cognitive deficits, dramatically reduced the Aβ1-42 overexpres-sion. MEM increased the activity of choline acetyl-transferase( ChAT) , while decreased that of acetylcho-line esterase( AChE) . Moreover, MEM activiated NGF signaling by increasing the phosphorylation of TrkA fol-lowing the increased phosphorylation of c-Raf, ERK1/2 and downstream effector CREB after MEM treatment. Conclusion MEM treatment may activate the NGF/TrkA signaling in APP/PS1 mice to reduce amyloidosis and cognitive deficits.关键词
美金刚/NGF/TrkA/学习记忆障碍/阿尔茨海默病/AβKey words
memantine/NGF/TrkA/cognitive deficits/Alzheimer′s disease/Aβ分类
医药卫生引用本文复制引用
姚维范,刘明妍,钟欣,杨时伦,杜可,毛瑞琨,魏敏杰..美金刚激活NGF/TrkA信号通路改善APP/PS1转基因小鼠学习记忆障碍[J].中国药理学通报,2016,32(4):473-479,480,8.基金项目
国家科技部“重大新药创制”科技重大专项子课题( No 2013ZX09103001-003),国家自然科学基金资助项目(No 81501098),辽宁省教育厅科学研究一般项目( No L2012279),辽宁省科学技术计划项目(No 2013225079) （ No 2013ZX09103001-003）
