| NGF-Dependent activation of TrkA pathway: A mechanism for the neuroprotective effect of troxerutin in D-galactose-treated mice. | |
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MedLine Citation:
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PMID: 20456366 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Jun Lu; Dong-mei Wu; Bin Hu; Yuan-lin Zheng; Zi-feng Zhang; Yong-jian Wang |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-03-19 |
Journal Detail:
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Title: Brain pathology (Zurich, Switzerland) Volume: 20 ISSN: 1750-3639 ISO Abbreviation: Brain Pathol. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-08-10 Completed Date: 2010-11-24 Revised Date: 2011-09-13 |
Medline Journal Info:
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Nlm Unique ID: 9216781 Medline TA: Brain Pathol Country: Switzerland |
Other Details:
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Languages: eng Pagination: 952-65 Citation Subset: IM |
Affiliation:
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Xuzhou Normal University, Jiangsu Province, China. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Analysis of Variance Animals Avoidance Learning / drug effects Behavior, Animal / drug effects Brain / metabolism CREB-Binding Protein / metabolism Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism Carbazoles / pharmacology Cognition Disorders / chemically induced, pathology, prevention & control* Disease Models, Animal Enzyme Inhibitors / pharmacology Galactose / toxicity Gene Expression Regulation / drug effects Hydroxyethylrutoside / analogs & derivatives*, therapeutic use Indole Alkaloids / pharmacology Intracellular Signaling Peptides and Proteins / metabolism Male Maze Learning / drug effects Membrane Proteins / metabolism Mice Nerve Growth Factor / genetics, pharmacology Neuroprotective Agents / therapeutic use* Reactive Oxygen Species / metabolism Receptor, trkA / metabolism* Signal Transduction / drug effects* Superoxide Dismutase / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Carbazoles; 0/Enzyme Inhibitors; 0/Hydroxyethylrutoside; 0/Indole Alkaloids; 0/Intracellular Signaling Peptides and Proteins; 0/Membrane Proteins; 0/Neuroprotective Agents; 0/Reactive Oxygen Species; 26566-61-0/Galactose; 7085-55-4/troxerutin; 9061-61-4/Nerve Growth Factor; 97161-97-2/K 252; EC 1.15.1.1/Superoxide Dismutase; EC 2.3.1.48/CREB-Binding Protein; EC 2.7.10.1/Receptor, trkA; EC 2.7.11.17/Calcium-Calmodulin-Dependent Protein Kinase Type 2; EC 2.7.4.8/Dlgh4 protein, mouse |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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