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


CONCLUSIONS
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.
Zhang
Lan
L
Department of Pharmacology, Xuanwu Hospital of Capital University of Medical Sciences, Education Ministry Key Laboratory for Neurodegenerative Disease, Beijing 100053, PR China. lanizhg@hotmail.com
Xing
Ying
Y
Ye
Cui-Fei
CF
Ai
Hou-Xi
HX
Wei
Hai-Feng
HF
Li
Lin
L
D000367:Age Factors; D000375:Aging; D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D005960:Glucosides / Q000627:therapeutic use*; D007859:Learning Disabilities / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010364:Pattern Recognition, Visual / Q000187:drug effects; D013267:Stilbenes / Q000627:therapeutic use*
D016564:Amyloid beta-Protein Precursor; D005960:Glucosides; D013267:Stilbenes; C093026:2,3,5,4'-tetrahydroxystilbene 2-O-glucopyranoside