Mechanism of tenuigenin ameliorating cognitive impairment of APP/PS1 transgenic mice / 解放军医学杂志

ABSTRACT

Objective To explore the effect and potential mechanism of tenuigenin (TEN) treatment on ameliorating cognitive impairment of Alzheimer's disease (AD) model mice. Methods 6-month-old APP/PS1 transgenic mice (n=18) were randomly divided into the saline group and TEN group (9 each), 9 wild-type mice of the same age were selected as control group. Mice in TEN group were intraperitoneally injected with TEN at a dose of 8 mg/(kg.d) for 8 weeks, those in both saline group and control group were intraperitoneally injected with same dose of saline for 8 weeks. The Morris water maze test was carried out with all the mice of the three groups to assess the spatial memory level, and immunohistochemistry was performed to detect the distribution and expression of postsynaptic density protein 95 (PSD-95) in hippocampal area of brain, and thioflavin staining was performed to check the senile plaque in hippocampus. ELISA was used to assess the Aβ42 level. Western blotting was used to detect the levels of PSD-95 and p-tau protein (Ser231, Ser214, Ser396) in brain. Results In the Morris water maze test, mice in saline group exhibited greater escape latency compared with that of mice in control group after the second day, the difference was statistically significant (P0.05); mice in TEN group exhibited longer escape latency compared with that of control group at the 5th day. Space search trial found that mice in saline group spent obviously longer time to find the original position of the platforms than those in control group [(40.428±3.408) s vs. (14.142±7.289) s, P0.05). It was found that mice in saline group exhibited fewer times of crossing platform than those in control group (0.428±0.035 vs. 2.285±1.380, P0.05). The relative amount of PSD-95 was lower in mice of saline group than that in control group (0.570±0.700 vs. 0.740±0.054), the difference was statistically significant (P0.05). The number of plaques and Aβ42 level in hippocampus decreased significantly in TEN group than those in saline group [(8.889±1.692 vs. 18.000±2.000) and (2.859±0.864) ng/mg vs. (5.154±0.735) ng/mg, P<0.05]. As to the expression level of protein p-tau Ser231, Ser214 and Ser396 in mice hippocampus, they were higher significantly in saline group than those in control group (0.947±0.131 vs. 0.540±0.076, 0.832±0.161 vs. 0.305±0.088 and 0.819±0.053 vs. 0.338±0.052, P<0.05), while they were obviously lower in TEN group than in saline group (0.568±0.051 vs. 0.947±0.131, 0.472±0.094 vs. 0.832±0.161 and 0.452±0.071 vs. 0.819±0.053, P<0.05). The expression levels of protein p-tau Se214 and Ser396 in mice hippocampus of TEN group were higher than those in control group with statistical significance (0.472±0.094 vs. 0.305±0.088 and 0.452±0.071 vs. 0.338±0.052, P<0.05), but the expression level of p-tau Ser231 showed no significant difference between TEN group and control group (0.568±0.051 vs. 0.540±0.076). Conclusion Tenuigenin may attenuate cognitive deficits by up-regulating the PSD-95 level in APP/PS1 mice, decrease Aβ deposition and excessive phosphorylation of protein p-tau, and might be a potential therapeutic agent for Alzheimer's disease.