| Alzheimer’s disease, a central, primary, progressive and degenerative disease,is a relatively common form of senile dementia patients. Its clinical performanceis the cognitive disabilities, learning and memory recession, often accompaniedby exception of the language, spirit and personality. While its basic pathology ischaracterized by the senile plaques formed by Aβ deposition, neurofibrillarytangles formed by phosphorylated Tau protein deposition as well as a largenumber of cholinergic neurons lost. The incidence of AD patients is affected bymany factors and etiology and pathological mechanism is very complex.Therefore, nowadays the treatment of AD has no significant breakthroughs andthe effective and safe therapy and means are lacking.Our research group has found that ginsenoside Rd could inhibit theinflammatory response in hippocampus of AD rat model, inhibit oxidative stressdamage in cultured hippocampal neurons and protect neurons. Based on thoseresults, we observed neuroprotective effect of Rd on the experimental model ofAD and its mechanism from three aspects: in vitro, in vivo and pure in vitro chemical experiments. It can provide a basis for the development of safe andeffective prevention and a new drug of treatment of AD.Objective: To study protective effects of learning and memory in theexperimental models of AD, impact of Rd on pathological features and theirmechanisms of neuroprotection, it provide some experimental basis to search forthe protective drug of AD.Methods:(1) Objects of study: acute brain injury model: SD rats with bilateralhippocampal CA1region of stereotactic micro-injection of Aβ1-40; chronic ADanimal model: APP transgenic mice; cell model in vitro: cortical neurons treatedby Aβ25-35.(2) Morris water maze was used to observe the effects of Rd onlearning and memory capacity in the rats of model about acute brain injury andAPP transgenic mice, and nissl staining was used to observe histological changes.MTT method was used to observe the survival of Aβ25-35treated cortical neuronsand immunofluorescence staining were used to observe the morphologicalchanges.(3) Western blot was used to detect the expression of phosphorylatedTau protein and the expression of kinase and phosphatase regulatingphosphorylated Tau protein was also observed. Those results discussed theprotective mechanisms of Rd in animal models of AD.(4) to further rule out thevarious environmental impacts in vitro and in vivo, pure chemical experiments invitro were used to detect the expression changes of phosphorylated Tau proteinby Western blot method after chemical reactions. It further explored theprotection mechanism of Rd in animal models of AD and the target of Rd.Results:(1) Rd (5,10,30mg/kg) on learning and memory functions in Aβ1-40induced rats showed some improvements: the time of escape latency wasshortened in Aβ1-40induced rats, the number of crossing over the originalplatform was increased, and the loss of hippocampal CA1neurons of rat model was reduced; Rd (10mg/kg) could significantly improve learning and memory inAPP transgenic mice: Shortened the time of escape latency and increased thenumber of crossing over the original platform; Rd (2.5,5μM) could improve thesurvival of cultured cortical neurons;(2) Rd was able to reduce the expression ofphosphorylated Tau protein, inhibit expression of GSK-3β and improve thePP-2A activity;(3) Pure chemistry experiment results showed that Rd was able toreduce the phosphorylated Tau protein after chemical reaction.Conclusion: Rd could enhance the abilities of learning and memory inexperimental AD animal models and the survival rate of the cellular model of AD.The mechanism of Rd may be related to inhibiting GSK-3β expression andactivity of PP-2A. Therefore Rd could reduce the formation and deposition ofexcessive phosphorylation of Tau protein and play a neuroprotective effect on theAD model. |
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