Open AccessNGF‐Dependent Activation of TrkA Pathway: A Mechanism for the Neuroprotective Effect of Troxerutin in D‐Galactose‐Treated Mice
Author(s) -
Lu Jun,
Wu Dongmei,
Hu Bin,
Zheng Yuanlin,
Zhang Zifeng,
Wang Yongjian
Publication year - 2010
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/j.1750-3639.2010.00397.x
Subject(s) - tropomyosin receptor kinase a , neuroprotection , neurotoxicity , creb , trk receptor , pharmacology , nerve growth factor , protein kinase b , tropomyosin receptor kinase b , chemistry , neurotrophin , signal transduction , medicine , receptor , neurotrophic factors , biochemistry , toxicity , transcription factor , gene
D‐galactose‐(D‐gal)‐treated mouse, with cognitive impairment, has been used for neurotoxicity investigation and anti‐neurotoxicity pharmacology research. In this study, we investigated the mechanism underlying the neuroprotective effect of troxerutin. The results showed that troxerutin improved behavioral performance in D‐gal‐treated mice by elevating Cu, Zn‐superoxide dismutases (Cu, Zn‐SOD) activity and decreasing reactive oxygen species levels. Furthermore, our results showed that troxerutin significantly promoted nerve growth factor (NGF) mRNA expression which resulted in TrkA activation. On one hand, NGF/TrkA induced activation of Akt and ERK1/2, which led to neuronal survival; on the other hand, NGF/TrkA mediated CaMKII and CREB phosphorylation and increased PSD95 expression, which improved cognitive performance. However, the neuroprotective effect of troxerutin was blocked by treatment with K252a, an antagonist for TrkA. No neurotoxicity was observed in mice treated with K252a or troxerutin alone. In conclusion, administration of troxerutin to D‐gal‐injected mice attenuated cognitive impairment and brain oxidative stress through the activation of NGF/TrkA signaling pathway.