The Effects Of H102Upon APP Transgenic Mice’s Learning And Memory Ability And Its Mechanism

Objective:to observe the effect of H102on learning and memory function, cholinergic system, antioxidation and the expression of Aβ-degrading Enzyme of APP transgenicmiceMethods:The APP transgenic mice were randomly divided into model group, the H102treatment group, and a group of C57BL/6J mice with the same age and background was set as normal. Model group and the normal control group were treated with normal saline solution, while the H102treatment group was treated with compounds(H102in normal saline solution), medicine or saline was infused in lateral cerebral ventricle every day. The ability of spatial reference memory were determined by Morris Water Maze (MWM), Immunohistochemical stain was done with ChAT, IDE, NEP and biochemistry method was used to determine the activities of AChE, SODand the content of MDA.Results:1. The Morris water maze test includes two parts:Place Navigation Training and the Spatial Probe Test. The results were expressed as follows:①Place Navigation TrainingCompare with normal group, the escape latency of mice in AD model group was longer significantly(P<0.01). Compare with the H102treatment group, the escape latency of mice in AD model group was significantly shorter(P<0.01).②Spatial Probe TestCompare with normal group, the times of the mice of AD model group past the position of the platform were significantly less (P<0.05),and the initial angles were significantly larger(P<0.01). In addition,compared with the H102treatment group, the times of the mice of AD model group past the position of the platform were significantly longer (P<0.05),and the initial angles were significantly smaller (P<0.01).which elucidated that memory of searching for the position of the platform had been strengthened.These results concluded that H102could improve the cognition and memory ability of the APP transgenic mice to some extent. 2. The effect of H102on cholinergic system, and antioxidation of APPtransgenicmice(1) the effect of H102on cholinergic system①The ChAT staining results showed that there were generousl and orderly ChAT positive neuron in hippocampus CA3domain and Cortex of temporal lobe of mouse in H102treatment group,the ChAT positive staining in plasma was darker, and there were dense positive fibres. The number and rate of ChAT positive neuron in hippocampus CA3domain and Cortex of temporal lobe of mouse in H102treatment group were obviously higher than those of the model group (p<0.01)②The activity of hippocampal AChE of H102treatment group mice was obviously lower than that of the the model group (p<0.01)(2) Antioxidation:the activities of AChE in hippocampus and content of MDA in cortex of H102group were obviously lower than the model group (p<0.01/0.05), while the activity of SOD in cortex was higher than that of the modle group (p=0.01)(3) In model group, the expression of IDE,NEP was lower in Cortex and hippocampus than that in control group. HI02treatment group apparently normalize the expression of the targeted enzymes and proteins. Both of them were similar to normal control.Conclusions:H102can advance the ability of learning and memory, the might mechanism may be:1. H102can obviously improve the activities of ChAT and SOD. While lower the Activity of AChE and decrease the content of MDA, which might be the mechanism of H102to improve the cognitive impairment and dysmnesia of AD.2. H102can decrease the expression of Aβ, and decline the toxicity of A(3, so lead to the improvement of the ability of learning and memory. H102is a potential drug for AD.