Mechanism of Dihuang Drink(地黄饮子)Regulating Synaptic Plasticity in Hippocampus
Objective:To observe the effect of Dihuang Drink(地黄饮子)on improving learning and memory ability and hippocampal synaptic plasticity in model mice with Alzheimer's disease(AD),and to explore the mechanism of AD treatment.Methods:Total 50 6-month-old SAMP8 mice were selected to construct AD animal model,and they were divided into model group,memantine hydrochloride group,Dihuang Drink low-dose,medium-dose and high-dose groups by RANDBETWEEN random function,and 10 SAMR1 mice of the same age were selected as normal group.Dihuang Drink groups and memantine hydrochloride group were given corresponding drugs by gavage,and normal group and model group were given equal volume of pure water by gavage for 12 weeks.The learning and memory ability of mice was detected by new object recognition,Morris water maze and Barnes maze respectively.The long-term potentiation(LTP)effect of hippocampus was recorded by field potential experiment.The changes of postsynaptic density protein-95(PSD-95)and synapsin(SYN)protein levels were detected by immunohistochemical experiment.The protein expression of NMDAR1,NMDAR2B and Ca2+-binding calmodulin-dependent protein kinase Ⅱ(CaMKⅡ)in hippocampal neurons were detected by Western blotting method.Results:Compared with the model group,the new object recognition coefficient of mice in the Dihuang Drink groups was increased,and the difference was statistically significant(P＜0.001);the time of staying in the target quadrant was significantly increased,and the difference was statistically significant(P＜0.05,P＜0.01),and the number of platform crossing was increased,and the escape latency was decreased;the time required to enter the escape box was reduced,but the difference was not statistically significant(P＞0.05),and the time of staying in the quadrant of the escape box was significantly increased,and the difference was statistically significant(P＜0.05).The in vivo hippocampal field potential recording experiment showed that there was no significant difference in the slope of fEPSPs in each group of mice before high frequency stimulation,and the slope of the Dihuang Drink groups was significantly higher than that of the model group 30 min and 60 min after high frequency stimulation(P＜0.05).Compared with the model group,the expression levels of PSD-95 protein and SYN protein in hippocampal neurons in CA1 region of the Dihuang Drink groups were increased;the expression levels of PSD-95 protein and SYN protein in hippocampal neurons in CA3 region of the Dihuang Drink groups were increased.Compared with the model group,the expression levels of CaMKⅡ,NMDAR1,NMDAR2B protein in hippocampal neurons in the Dihuang Drink groups were increased.Conclusions:Dihuang Drink can improve the learning and memory ability of AD model mice,and the mechanism may be through regulating the Ca2+in hippocampal neurons to maintain synaptic plasticity.
Alzheimer's diseaseDihuang Drink(地黄饮子)hippocampussynaptic plasticitylong-term poten-tiationcalcium ionmicelearning and memory ability
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