Learning-memory deficit with aging in APP transgenic mice of Alzheimer's disease and intervention by using tetrahydroxystilbene glucoside

Behav Brain Res. 2006 Oct 16;173(2):246-54. doi: 10.1016/j.bbr.2006.06.034. Epub 2006 Aug 9.

Abstract

Objective: To investigate learning-memory deficit in different ages of AD-like APP transgenic mice and to observe the protective effects of 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside (TSG), which is the main component of Polygonum multiflorum, on learning-memory abilities.

Methods: PDAPPV717I transgenic (Tg) mice were randomly divided into 3 model groups (4, 10 and 16 months old mice) and TSG treated (at doses 120 and 240 micromol/kg/d) groups. TSG was administered to some Tg mice with an age range 4-10 months. In untreated 10 months old Tg mice, the TSG was administrated to those falling in the age range 10-16 months. For the control group we adopted the same age and background C57BL/6J mice. The learning-memory ability was measured by applying Morris water maze (MWM) and object recognition test (ORT).

Results: In the 4 months old PDAPPV717I Tg mice, the learning-memory deficit was detected. The escape latency in MWM was prolonged, and the discrimination index decreased in ORT. In the 10 months old Tg mice, the learning-memory deficit was aggravated. TSG improved all spatial learning-memory impairment in MWM as well as the object recognition impairment in ORT. In the 16 months old Tg mice, the learning-memory deficit remained to exist but abated a lot. TSG showed significant improvement in learning-memory ability in both MWM and ORT.

Conclusion: PDAPPV717I transgenic mice with an age range 4-16 months revealed the existence of learning-memory deficit compared with the control group. Tetrahydroxystilbene glucoside not only prevents, i.e. at an early stage, the learning-memory deficit in AD-like model, but also can reverse the learning-memory deficit in the late stage of AD-like model. Thus, TSG could be considered among the future therapeutic drugs indicated for the treatment of AD.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aging*
  • Alzheimer Disease / complications
  • Alzheimer Disease / genetics*
  • Amyloid beta-Protein Precursor / genetics*
  • Analysis of Variance
  • Animals
  • Disease Models, Animal
  • Glucosides / therapeutic use*
  • Learning Disabilities / drug therapy*
  • Learning Disabilities / etiology
  • Learning Disabilities / genetics
  • Maze Learning / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Pattern Recognition, Visual / drug effects
  • Stilbenes / therapeutic use*

Substances

  • Amyloid beta-Protein Precursor
  • Glucosides
  • Stilbenes
  • 2,3,5,4'-tetrahydroxystilbene 2-O-glucopyranoside