Effects Of GETO Extract On Generation And Degradation Of Beta-amyloid Protein And Neuron Plasticity In The Brain Of Model Murine Of Alzheimer's Disease

Objective: According to beta-amyloid (Aβ) cascade hypothesis in Alzheimer's disease(AD), this study is to observe effects of GETO (herbal extract) on generation and degradation of beta-amyloid protein and neuron plasticity, to look for effective target of GETO in the treating AD. Methods: APPV717I transgenic mouse and model rats with hippocampus injected by Aβ1-42, as AD models were used in this study. Morris water maze test was used to screen learning and memory impairmed animals. Congo red staining, immunohistochemistry(IHC), Western blot, electronmicroscope and system of image pro-plus were used to determine amyloid plaques, protein expression of APP,Aβ,BACE,PS1,IDE and NEP in the brain of APPV717I transgenic mouse, as well as ultramicro- structure of axons and protein expression ofβ-actin,β-tubulin,MBP,GAP43 and NGF in the hippocampus of model rats induced by Aβ1-42. Results: Morris water maze test showed that the escape latency and swimming distance of GETO group is significantly shorter than model group(p<0.05/0.01),but the times of crossing platform is much more than model group (p<0.05/0.01).Amyloid plaques in GETO group is significantly decreased compared to model group(p<0.05/0.01). Comparing to model group, the levels of expression of APP, Aβ, BACE and PS1 in the brain of mice in GETO group are significantly decreased (p<0.05/0.01); the levels of expression of IDE and NEP in the brain of mice in GETO group are significantly increased(p<0.05/0.01); And also the levels of expression ofβ-actin,β-tubulin, MBP,GAP43 and NGF in the hippocampus of rats in GETO group are significantly increased(p<0.05/0.01). Under electronmicroscope, there were obvious lysis of the axon microtubule, faintness of microfilamen and rarefaction of the synapsis of the neurophils of hippocampus CA1 in the model rats. In GETO group,the normal microfilament was clearly seen,the microtubule of the rats'hippocampus neuron axons was tidily arrayed; the increased synapsis of the neurophils could be seen. Conclusion: Mechanisms of GETO extract effective in the interventing AD are explained as follow. On the one hand,GETO can decreases the expression of APP and itsβ-andγ-secretase and increase the expression of IDE and NEP, to balance generation, accumulation and aggradation of Aβ, and to alleviate neuron toxicity in the AD brain.On the other hand,GETO can renovate damaged axons, improve neuroal nutrition, thereby ameliorate neuron plasticity and learning and memory peformance of AD models.