Effect of ostholon memory and tau protein phosphorylation in brain of AD mice

OBJECTIVE To investigate the effects of osthole on learning and memory impairment of AD mice induced by injection of Aβ_(25-35) and effects of aspartate proteolytic enzymes(caspase 3, 6, 8) containing cysteine on the phosphorylation of tau protein. METHODS Mice were randomly assigned to sham operation, Aβ_(25-35), Aβ_(25-35)+Ost-L, Aβ_(25-35)+Ost-M, and Aβ_(25-35)+Ost-H group. The learning ability of mice was evaluated by behavioral dark avoidance experiment. The protein expression of tau and p-tau in brain tissue of AD rats was detected by Western blotting.The levels of apoptotic proteins in brain tissues were detected by the kit. HE staining was used to detect the pathological changes of neurons in brain slices.RESULTS(1) Effects of osthole on learning and memory:the results of behavior avoidance experiments showed that: compared with the model group, the dark avoidance latency of osthole(OST) increased in the low, medium and high dose groups. The difference was statistically significant(P<0.05). The dark incubation period of mice in the low-dose OST group was the longest, followed by those in the medium-dose OST group, and was the shortest in the high-dose OST group.(2) Effects on tau and p-tau expression in AD mice: the main pathological features of AD are senile plaque deposition with Aβ as the core,neuronal fiber tangles formed by tau protein phosphorylation, and neuronal death. Western blotting was used to detect the protein expression of tau and p-tau in brain tissue of AD rats. The test results show that: compared with the sham group, tau and p-tau expression in the model group were significantly increased. Compared with the model group, tau and p-tau expression of OST decreased significantly in brain tissues of the low, medium and high dose groups. In addition, the decreased expression of tau and p-tau in brain tissues of mice in the low-dose group of OST was the most significant, followed by the mice in the medium-dose group of OST, and the decreased expression of tau and p-tau in brain tissues of the high-dose group of OST was the least.(3) Effects on apoptotic protein levels in brain tissue: caspase is closely related to eukaryotic apoptosis and is involved in the regulation of cell growth, differentiation and apoptosis. The level of apoptotic protein in brain tissue was detected by the kit. Experimental results show that: the activity of aspartate proteolytic enzyme(caspase 3, 6, 8) of cysteine in the model group was significantly increased compared with that of the sham group. Compared with the model group, aspartate proteolytic enzyme(caspase 3, 6, 8)activity of cysteine in the low-dose, medium-dose and high-dose OST groups was significantly decreased. In addition, the decrease of OST was the most significant in the low-dose group, followed by that in the medium-dose group, and the decrease was the least in the high-dose group. CONCLUSION OST significantly improved the learning and memory of dementia model mice injected into bilateral hippocampus of Aβ_(25-35). Experimental studies have shown that OST can regulate the expression of brain tissue proteins tau and p-tau in AD mice, and the levels of apoptotic proteins in brain tissues to varying degrees, thus improving the pathological changes of multiple AD and delaying the pathogenesis of neurodegenerative diseases.