Research On Improvement Of Active Avoidance Capacity Of AD Model Mice Via Conditioned Reflex Training

ObjectiveAlzheimer disease(AD)is a kind of common chronic neurodegenerative disease,and its basic pathological features include the deposition of β-amyloid protein outside the nerve cells,forming senile plaques(SP),and excessive phosphorylation of Tau protein in cells,causing neurofibrilarytangles(NFTs),thus leading to the decline in the number of neurons in brain and atrophy and dysfunction of brain tissues.Its main clinical features are the losses of patient’s memory,cognitive function,judgment,abstract thinking ability,emotion,personality and spatial relationship function.In this study,the changes in active avoidance capacity of AD model mice with and without receiving conditioned reflex training were observed and analyzed with cognitive stimulation,namely the conditioned reflex training,as an intervening measure.At the same time,the neurobiological experiment was performed to investigate the effects of cognitive stimulation on the growth of neurons and neuronal dendritic spines in subdentate gyrus zone and CA1 zone,and the effect of this intervention on the long-term potentiation(LTP)in hippocampus Schaffer collaterals-CA1 zone.This study investigated the effects of conditioned reflex training on behavioral changes of AD model and its neurobiological mechanisms,so as to provide the theoretical basis and reference for AD cognitive intervention and combined intervention.MethodsThe intraperitoneal injection of D-gal combined with gavage via aluminum trichloride was performed for 6 weeks to establish the model,followed by behavioral and neurobiological evaluation.In the behavioral experiment,Noldus mice activity box(behavioral analysis test system)was used for the relevant behavioral analysis,and the experimental region was divided into the safe region and stimulation region to understand the active avoidance capacity of the experimental animals in each group.In the neurobiological experiment,Golgi staining method(HITO Golgi staining kit)was used for staining,and the growth of neuronal dendritic spines in the hippocampal DG zone was observed under optical microscope.In the electrophysiological experiment,hippocampal slice LTP-induced experiment was performed to analyze the slope changes of excitatory postsynaptic potential(EPSP)of LTP in hippocampus Schaffer collaterals-CA1 zone.The experiment penetrated from the macroscopic behavioral manifestations into the neuronal morphological and electrophysiological changes.Test method:SPSS 16.0 statistical software and independent sample T test were used.ResultsThe experimental animal model was established successfully,which was verified from the behavioral and neurobiological perspectives.There was a significant difference in the underwater incubation between model group and normal group,and the number of hippocampal neuronal dendritic spine between model group and normal group was significantly different;there was a significant difference in the active avoidance capacity between AD model mice with and without receiving conditioned reflex training,and the preference in experimental region was significantly different between experimental animals in the two groups;Golgi staining showed that there was a significant difference in the growth of dendritic spines in subdentate gyrus zone between AD model mice with and without receiving conditioned reflex training,and the number of neuronal dendritic spines in the experimental animals receiving conditioned reflex training was significantly increased;there was a significant difference in LTP in the hippocampal DG-CA1 zone between AD model mice with and without receiving conditioned reflex training,and the postsynaptic potential of mice receiving conditioned reflex training was significantly increased;the study on the intervention of one memory form in another form was verified from the perspectives of behavior and neuronal morphology,which also affected the changes in LTP of neuronal transmission.ConclusionsIn this study,the active avoidance capacity of AD model mice was improved by conditioned reflex training,and it also promoted the development of neuronal dendritic spines.The study on the intervention of one memory form in another form was verified from the perspectives of behavior and neuronal morphology,which also affected the changes in LTP of neuronal transmission.Such an intervention means provides a certain theoretical basis and reference for the prevention,intervention and combined intervention in AD.