GETO Extract On The APP / PS1 Double Transgenic Protective Effect Of The Ultrastructure Of Hippocampus Of Mice

Background:Alzheimer’s disease is the most common disease of dementia in elderly people, it has a high morbidity but no effective therapy. Alzheimer’s disease is an irreversible neurodegenerative disease, thus it is important to prevent it at its early stage. Neuron damage and synaptic pathology have been identified as early events in AD pathogenesis. Pharmacological studies and clinical trials confirmed that Chinese medicine can improve cognitive function safely and effectively, but studies about Chinese medicine protecting neurons and synapses in AD like animals are rare. In this study, the author investigated the effect of compound Chinese herbs in protecting neurons and synapse in APP/PS1transgenic mice.Objective:To observe the effect of GEPT on ultrastrue ture of hippocampus CA1area in APP/PS1double transgenic mice. Explore the possible target of GEPT on the treatment of Alzheimer’s disease. Investigate the benefit of long-period applying of GEPT at early-stage and the correlation of curative effect and GEPT dosage.Methods:15six-month-old APP/PS1double transgenic mice were randomly divided into five groups, namely model group, GEPTlow-dosage(G1) group, GEPT medium-dosage (Gm) group, GEPT high-dosage (Gh) group and donepezil group. With3six-month-old wild type C57mice as normal control group, these6groups of mice were the short-treatment-period group (STP).15three-month-old APP/PS1double transgenic mice were randomly divided into five groups, namely model group, GEPT low-dosage group, GEPT medium-dosage group, GEPT high-dosage group and donepezil group. With3three-month-old wild type C57mice as normal control group, these6groups were the long-treatment-period group (LTP). Mice of normal control groups and model groups were given a gavage of sodium carboxyme thylcellu lose every day, and mice of GEPT groups were given a gavage of GEPT solution of different dosage, respectively0.075,0.15,0.3g·kg-1·d-1every day. Donepezil groups were given a gavage of donepezil solution with a dosage of0.92mg· kg-1·d-1every day. The gavage of the short-treatment-period group lasted3months, and the long-treatment-period6months. After treatment, the changes in ultrastrueture of hippocampus CA1area were observed using transmission electron microscope and the synapses numbers under the same amplification factor were counted. Results:The neurons of hippocampus CA1area in the normal control groups are basically normal, the neuron membrane are smooth without defects.The cell organelle structures are clear and complete. The neurons of hippocampus CA1area in the model groups are degenerated or shrank and necrosed. The cell organelle are swelling with normal structures disappeared. The nucleus are out of normal shape and chromatin pyknosed. The neurons of the GEPT groups and the donepezil groups are similar to the normal control group, except the low-dosage GEPT group of short-treatment-period group, which has a high percentage of neurons degenerated or necrosed. There are also some neuron degeneration and necrosis existed in the GEPT medium-dosage group of short-treatment-period group, but the percentage is much lower and the cell organelle structure is ultimately normal. The synapses numbers counted shows that under the same area, the synapses number of the model group is much lower than normal control(STP and LTP groups, p=0.000), GEPT low-dosage groups (STP group, p=0.015, LTP group, p=0.000), GEPT medium-dosage groups (STP group, p=0.009,LTP group, p=0.000), GEPT high-dosage groups (STP group, p=0.030, LTP group,p=0.000) and LTP donepezil groups (p=0.000). There are no dose-dependency found in synapse number of the GEPT groups, that is, the synapses number is not growing larger as the dosage of GEPT is growing higher. When compared between the same GEPT dosage groups of STP group and LTP group, the synapses number of the LTP group is much higher than that of the STP group(G1group, p=0.013, Gm group, p-0.009, Gh group, p=0.017). The synapses number of the LTP donepezil group is much higher than the STP donepezil group (p=0.025).Conclusion:GEPT is able to improve learning and memorizing capacity in the early stages of Alzheimer’s disease in APP/PS1mice by repairing the neurons and synapse in hippocampus CA1area. This might be one of the possible mechanisms of GEPT treating AD. The repairing effect of GEPT is more obvious when applied in early stage and long period, and the improvement degree of neurons is positively correlated with GEPT dosage. GEPT is also protective in synapses numbers of hippocampus CA1area and the protective effect is better when used in early stage and long period, but no dose-dependence is found in GEPT protecting synapse numbers in this study.