Protective Effect And Possible Mechanism Of Ginsenoside Rg1 And Rb1 On AD-Like Tau Hyperphosphorylation Induced By Okadaic Acid In The Hippocampal Neurons Of SD Rats

Protective effect and possible mechanism of Ginsenoside Rg1 and Rb1 on AD-Like Tau hyperphosphorylation induced by Okadaic Acid in the hippocampal neurons of SD RatsPostgraduate: Li YongkunSupervisor: Chen XiaochunOBJECTIVE To establish AD-like tau hyperphosphorylation rat models by injecting Okadaic Acid (OA) into Sprauge-Dawley (SD) rat hippocampus, then explore the effect and its possible mechanism of Ginsenoside Rg1 and Rb1 on Tau hyperphosphorylation of the rat models.METHODS OA in a 1.5μl volume was injected into one of the dorsal hippocampus of rats that had been pretreated with some certain dosage (5mg/Kg, 10mg/Kg or 20mg/Kg, i.p. qd, respectively) of Ginsenoside Rg1 or Rb1 for 12 days. The pathological changes of neurofibrils, axons and dendrite were observed by Bielschowski's staining. The level of tau phosphorylation was investigated by immunohistochemistry and Western-blot with a panel of phosphorylation-dependent antibodies (Tau-pSer199/202, Tau-pThr231, Tau-pSer396) and non-phosphorylation- dependent antibody (Tau-5). The activity of PP2A and TchE were detected by non- radioimmunoassay.RESULTS After OA injection, the neuronal axons of hippocampus became anachromasis, and the fused, twisted, disordered and thickened neurofibrils were observed, and the axons and dendrites were disjuncted, which indicate that the neuron axons and microtubule system were disintegration. However, neither SP nor NFTs were observed. The numbers of immuno-positive stained cells markedly increased with Tau-pSer199/202 and Tau-pThr231 antibody (p<0.01vs control). According to Western-blot, tau protein was highly phosphorylated in the sites of Ser199/202, Thr231and Ser396. The activity of PP2A significantly decreased (P<0.01vs control), but the activity of TchE had no obvious changes. After 2-week pretretment with ginsenoside Rg1 or ginsenoside Rb1, the neurofibrils and axons kept regular, and the level of tau phosphorylation decreased, especially in the Rg20mg/Kg and Rb5mg/Kg groups. Meanwhile,the activity of PP2A increased significantly compared with model group(P<0.01) and control group(P<0.01), but there is no obvious changes for TchE.CONCLUSION Ginsenoside Rg1 and Rb1 can attenuate Tau hyperphosphorylation induced by Okadaic acid in SD rats' hippocampal neurons. The probable mechanism may relate to their up-regulation activity of PP2A.