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

被引：4

作者：

姚维范

刘明妍

钟欣

杨时伦

杜可

毛瑞琨

魏敏杰

机构：

[1] 中国医科大学药学院药理学教研室

来源：

中国药理学通报 | 2016年 / 04期

关键词：

美金刚; NGF; TrkA; 学习记忆障碍; 阿尔茨海默病; Aβ;

D O I：

暂无

中图分类号：

R749.94 [儿童精神病];

学科分类号：

100204 [神经病学];

摘要：

目的考察NGF/TrkA信号通路在美金刚(memantine,MEM)改善APP/PS1转基因小鼠的学习记忆障碍中的作用及其相关机制。方法以Morris水迷宫、被动避暗试验及自主活动试验观察动物行为学变化,免疫组化检测小鼠脑内Aβ1-42表达水平,ELISA法及比色法考察其脑内ChAT及AChE活性,并用Western blot法检测小鼠海马NGF的水平及其特异性受体TrkA下游ERK通路相关蛋白的表达水平。结果 MEM明显改善APP/PS1转基因小鼠的学习记忆障碍,并明显降低其脑内Aβ1-42蛋白沉积。MEM可上调NGF表达水平,继而激活NGF-TrkA通路,明显增加TrkA、c-raf、ERK1/2及其下游效应蛋白CREB的磷酸化水平;同时,增强其脑内ACh生成酶ChAT并降低其水解酶AChE活性。结论 MEM可能通过增加NGF的表达,激活TrkA信号通路,降低APP/PS1转基因小鼠脑内Aβ1-42蛋白沉积,从而改善其学习记忆障碍。

引用

收藏

页码：473 / 480

页数：8

相关论文

共 19 条

[1]

EGCG通过抑制p75NTR通路对APP/PS1小鼠学习记忆障碍的改善作用 [J].

杨时伦 ;

刘明妍 ;

钟欣 ;

杜可 ;

姚维范 ;

赵海山 ;

魏敏杰 .

中国药理学通报, 2014, 30 (10) :1419-1424

[2]

Characterization of cognitive deficits in a transgenic mouse model of Alzheimer's disease and effects of donepezil and memantine[J] Akira Nagakura;Yoshitsugu Shitaka;Junko Yarimizu;Nobuya Matsuoka European Journal of Pharmacology 2013,

[3]

Once-Daily Memantine[J] Katherine A. Lyseng-Williamson;Kate McKeage Drugs & Aging 2013,

[4]

Memantine in Alzheimer’s disease: experience in an Alzheimer’s disease assessment unit[J] Elena Sinforiani;Chiara Pasotti;Laura Chiapella;Paola Malinverni;Chiara Zucchella Aging Clinical and Experimental Research 2012,

[5]

Acetylcholinesterase inhibitors rapidly activate Trk neurotrophin receptors in the mouse hippocampus[J] Neuropharmacology 2011,

[6]

In vivo evidence for functional NMDA receptor blockade by memantine in rat hippocampal neurons[J] Viktor Szegedi;Gábor Juhász;Chris G. Parsons;Dénes Budai Journal of Neural Transmission 2010,

[7]

Memantine Improves Cognition and Reduces Alzheimer’s-Like Neuropathology in Transgenic Mice[J] Hilda Martinez-Coria;Kim N. Green;Lauren M. Billings;Masashi Kitazawa;Miriam Albrecht;Gerhard Rammes;Chris G. Parsons;Sandeep Gupta;Pradeep Banerjee;Frank M. LaFerla The American Journal of Pathology 2010,

[8]

The basal forebrain cholinergic system in aging and dementia. Rescuing cholinergic neurons from neurotoxic amyloid-β42 with memantine[J] Csaba Nyakas;Ivica Granic;László G. Halmy;Pradeep Banerjee;Paul G.M. Luiten Behavioural Brain Research 2010,

[9]

Memantine Normalizes Several Phenotypic Features in the Ts65DnMouse Model of Down Syndrome[J] Noemí Rueda;María Llorens-Martín;Jesús Flórez;Elsa Valdizán;Pradeep Banerjee;Jose Luis Trejo;Carmen Martínez-Cué Journal of Alzheimer's Disease 2010,

[10]

Memantine lowers amyloid‐β peptide levels in neuronal cultures and in APP/PS1 transgenic mice[J] George M.Alley;Jason A.Bailey;DeMaoChen;BalmikiRay;Lakshman K.Puli;HeikkiTanila;Pradeep K.Banerjee;Debomoy K.Lahiri J. Neurosci. Res. 2009,