The Effect And Possible Mechanism Of Gensenoside Rg1 And Rb1 On Abnormal Phosphorylation Of Tau In Hippocampal Neurons Of Alzheimer's Disease-like Rat Model

Objective To observe the expression of phosphorylating tau with ser199/ser202,ser396 and thr231 residues ,and the activation of GSK-3β in Alzheimer's disease-like rat model after aggregated Aβ25-35 were microinjected into hippocampus of rats,then explore the protective effect of Gensenoside Rg1 and Rb1 on the abnormal phosphorylation of tau in hippocampal neurons of this model ,and their possible mechanism .Methods:Dorsal hippocampus microinjection of 5nmol aggregated Aβ25-35 was performed by stereotaxic technique to establish the AD-like rat model. After 14 days,the pathological changes in rat's hippocampal neurons were observed by Bielschowsky stain; the expression of PS396-tau,PS199PS202-tau , PT231-tau and total tau(Tau5) were observed by immunohistochemical and Western botting detection; the expression of GSK-3β and phosphorylating GSK-3β were measured by western blot. Meanwhile,The rats were administered different doses of Rg1 and Rb1 (5.0mg,10.0mg,20.0mg/kg ,ip)for 14 consecutive days after Aβ25-35 were microinjected, to observe their effects on the above marks using the same techniques.Results: In Aβ25-35-induced AD-like rat model,The neurofibrils were fused,disordered,thickened and crowded together into broad band, and the neurites was deeply stained. The expression of phosphorylating tau with ser199/ser202,ser396 and thr231 residues in hippocampal neurons (p<0.01)were significantly increased compared with normal groups and saline microinjected groups. And the expression of GSK-3β and phosphorylating GSK-3β were obviously increased too.After aggregated Aβ25-35 were microinjected,Ginsenoside Rg1 and Rb1 were performed by coelio-injection. Ginsenoside Rg1 and Rb1 had the evident protective effect on the hippocampal neurons.Not only the expression of phosphorylating tau with ser199/ser202,ser396 and thr231 residues(p<0.01) ,but the GSK-3β and phosphorylating GSK-3β in Rg1 and Rb1 treatment groups were significantly decreased compared with aggregated Aβ25-35 microinjected groups. And the effective dose of Ginsenoside Rg1 and Rb1 had abbrevant difference ,the dose of 20mg/kg were especially significant in Rg1 treatment groups (p<0.01).however, the dose of 5mg/kg were most effective in Rb1 treatment groups(p<0.01),the dose of 20mg/kg were not effective(p>0.05).Conclusions:aggregated Aβ25-35 microinjected into dorsal hippocampus could take effect on inducing abnormal phosphorylation of tau by activating GSK-3β,And constructing the Alzheimer's disease-like rat model.Ginsenoside Rg1(20mg/kg) and Rb1(5mg/kg)had obvious protective effect on AD-like rat's hippocampal neurons, and the mechanism may be due to decrease the levels of phosphorylation of tau by inhibiting the GSK-3β' activation. Ginsenoside Rg1 and Rb1 may have potential benefit on the therapy of AD.