Abstract: Objective To investigate the deficit of extracellular-signal regulated kinase (ERK)1/2 activation in the different age of Alzheimer's disease (AD)-like animal model and the protective effect of 2,3,5,4′-tetrahydroxy stilbene-2-O-β-D-glucoside(TSG), which is the main component of Polygonum multiflorum, on ERK activation. Methods A generally accepted animal model of AD - PDAPPV717I transgenic (Tg) mouse was observed from 4 to 16 months old. Tg mice were randomly divided into 3 model groups(4, 10 and 16 months old mice)and TSG treated (at doses 120 and 240 μmol/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 ERK1/2 expression and phosphorylation were detected by Western blotting.Results In the 4-month-old PDAPPV717I Tg mice, phosphorylation of ERK1/2 decreased significantly in hippocampus and cortex compared with age matched control. In the 10-month-old Tg mice, decrease of ERK1/2 activation was aggravated in cortex but was less in hippocampus. The treatment of TSG at the doses of 120 and 240 μmol/kg for 6 months (from the age of 4 to 10 months) significantly up-regulated ERK1/2 activation in Tg mice. In the 16-month-old Tg mice, over-activation of ERK1/2 occurred in both hippocampus and cortex. The transgenic mice treated by TSG for 6 months (from the age of 10 months to 16 months) showed significant inhibition of over-activation of ERK1/2. Expression of total ERK1/2 showed no difference among control, Tg model and TSG treated groups.Conclusion PDAPPV717I transgenic mice with an age range from 4 to 16 months revealed the time-dependent deficit of ERK1/2 activation. TSG can bring the down or over activation of ERK1/2 into normal. Because ERK1/2 activation plays the crucial role in cellular signal transduction and learning-memory ability, TSG may have beneficial potential to the prevention and treatment of neurodegenerative diseases like AD.

Key words: Alzheimer's disease(AD), PDAPPV717I transgenic mice, extracellular-signal regulated kinase (ERK), signal transduction, tetrahydroxy stilbene glucoside