Memantine improves cognitive deficits by activiating NGF/TrkA signaling in APP/PS1 transgenic mice
10.3969/j.issn.1001-1978.2016.04.007
- VernacularTitle: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
- Author:
Weifan YAO
;
Mingyan LIU
;
Xin ZHONG
;
Shilun YANG
;
Ke DU
;
Ruikun MAO
;
Minjie WEI
- Publication Type:Journal Article
- Keywords:
memantine;
NGF;
TrkA;
cognitive deficits;
Alzheimer′s disease;
Aβ
- From:
Chinese Pharmacological Bulletin
2016;32(4):473-479,480
- CountryChina
- Language:Chinese
-
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.
