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- Title
NGF-Dependent Activation of TrkA Pathway: A Mechanism for the Neuroprotective Effect of Troxerutin in D-Galactose-Treated Mice.
- Authors
Jun Lu; Dong-mei Wu; Bin Hu; Yuan-lin Zheng; Zi-feng Zhang; Yong-jian Wang
- Abstract
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.
- Subjects
PHYSIOLOGICAL effects of galactose; NEUROPROTECTIVE agents; NEUROTOXICOLOGY; THERAPEUTICS; NEUROLOGICAL disorders; LABORATORY mice; CHEMICAL reactions
- Publication
Brain Pathology, 2010, Vol 20, Issue 5, p952
- ISSN
1015-6305
- Publication type
Article
- DOI
10.1111/j.1750-3639.2010.00397.x