Dehydroevodiamine attenuates tau hyperphosphorylation and spatial memory deficit induced by activation of glycogen synthase kinase-3 in rats.

Abstract

Tau hyperphosphorylation and memory deficit are characteristic alterations of Alzheimer's disease (AD), and glycogen synthase kinase-3 (GSK-3) plays a crucial role in these AD-like changes. We have reported that activation of GSK-3 through ventricular injection of wortmannin and GF-109203X (WT/GFX, 100 microM each) induces tau hyperphosphorylation and memory impairment of rats [Liu, S.J. et al., 2003. Overactivation of glycogen synthase kinase-3 by inhibition of phosphoinositol-3 kinase and protein kinase C leads to hyperphosphorylation of tau and impairment of spatial memory. J. Neurochem. 87, 1333-1344]. By using this model, we explored in the present study the effects of dehydroevodiamine (DHED), a quinazoline alkaloid isolated from Evodia rutaecarpa Bentham, on the memory retention, tau phosphorylation and the activity of GSK-3. We found that pre-administration of DHED through vena caudalis for 1 week efficiently improved the WT/GFX-induced spatial memory retention impairment of the rats; it also antagonized tau hyperphosphorylation at multiple AD sites and arrested the overactivation of GSK-3 induced by WT/GFX. Our study gave the first in vivo evidence that DHED could suppress the overactivation of GSK-3 and improve tau hyperphosphorylation and spatial memory deficit of the rats, suggesting that this chemical may be served as a candidate for arresting AD-like pathological and behavioral alterations.

• Authors: Jun-Hua Peng, Chang-E Zhang, Wei Wei, Xiao-Ping Hong, Xi-Ping Pan, Jian-Zhi Wang
• Journal: Neuropharmacology (Neuropharmacology) Vol. 52 Issue 7 Pg. 1521-7 (Jun 2007) ISSN: 0028-3908 [Print] England
• PMID: 17434540 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Alkaloids
• Indoles
• Maleimides
• tau Proteins
• dehydroevodiamine
• Glycogen Synthase Kinase 3
• bisindolylmaleimide I

Topics

• Alkaloids (therapeutic use)
• Animals
• Behavior, Animal (drug effects)
• Dose-Response Relationship, Drug
• Drug Interactions
• Enzyme Activation (drug effects)
• Gene Expression Regulation (drug effects)
• Glycogen Synthase Kinase 3 (metabolism)
• Hippocampus (drug effects, metabolism)
• Indoles
• Male
• Maleimides
• Memory Disorders (chemically induced, metabolism, prevention & control)
• Phosphorylation (drug effects)
• Rats
• Rats, Wistar
• tau Proteins (metabolism)