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

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.

• Authors: Lan Zhang, Ying Xing, Cui-Fei Ye, Hou-Xi Ai, Hai-Feng Wei, Lin Li
• Journal: Behavioural brain research (Behav Brain Res) Vol. 173 Issue 2 Pg. 246-54 (Oct 16 2006) ISSN: 0166-4328 [Print] Netherlands
• PMID: 16901557 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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