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

Bibliographic

Year of Publication:
2006
Contact PI Name:
Lin Li
Contact PI Affiliation:
Department of Pharmacology, Xuanwu Hospital of Capital University of Medical Sciences, Education Ministry Key Laboratory for Neurodegenerative Disease, Beijing, China
Co-Authors:
Lan Zhang, Ying Xing, Cui-Fei Ye, Hou-Xi Ai, Hai-Feng
Primary Reference (PubMED ID):
Funding Source:
Capital Medical Development Foundation of China
Beijing Municipal Science and Technology Commission
National Natural Science Foundation of China
National Key Basic Research 973 Program of China
Study Goal and Principal Findings:

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-β-d-glucoside (TSG), which is the main component of Polygonum multiflorum, on learning-memory abilities. 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 240μmol/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 they 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). 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. 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.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Natural Product
Therapeutic Agent:
2,3,5,4'-tetrahydroxystilbene-2-O-β-d-glucoside
Therapeutic Target:
Multi Target
Therapeutic Notes:
2,3,4′,5-tetrahydroxystilbene-2-O-β-D-glucoside (TSG) is the main active compound in Polygonum multiflorum Thunb.

Animal Model

Model Information:
Species:
Mouse
Model Type:
APP
Strain/Genetic Background:
C57BL/6

Experimental Design

Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Biomarkers
Dose
Formulation
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest

Outcomes

Outcome Measured
Outcome Parameters
Behavioral
Morris Water Maze
Novel Object Recognition Test (NORT)