Effects Of Fornix Deep Brain Stimulation On Learning And Memory In 1-42βamyloid-induced Alzheimer’s Disease Model Rats

Background:Alzheimer’s disease(AD)is the most common neurodegenerative disease caused by memory impairment in the elderly.It is mainly characterized by chronic progressive cognitive loss,often accompanied by mental symptoms,decreased neurological function and personality changes.Eventually lead to a decline in social skills and quality of life.The conventional treatment methods are mainly symptomatic treatment using cholinesterase inhibitors and excitatory amino acid receptor antagonists,and the curative effect is unsatisfactory.Deep brain stimulation(DBS)is a surgical treatment for acupuncturing dyskinesia diseases such as Parkinson’s disease,dystonia,and idiopathic tremor.In recent years,some scholars have proposed to treat AD with DBS,and there have been preliminary clinical trials.Animal experiments have shown that DBS can improve the symptoms of AD,but the specific mechanism of action is still unclear.In this experiment,we were treated with 7-day short-term sputum fornix-DBS(f-DBS)stimulation in 1-42βAmyloid-induced AD model rats to observe the spatial localization learning ability of AD model rats after DBS stimulation.Changes in the pathological morphology of the hippocampus,and attempts to discuss the short-term f-DBS neurological improvement and potential mechanisms of AD.Objective:Thirty-two healthy 8-week-old male Sprague-Dawley rats were randomly divided into four groups:(1)Sham group;(2)Sham+DBS group;(3)AD group;(4)AD+DBS group.After 7 days of short-term DBS,water maze test,sub-positioning navigation experiment and space exploration experiment were carried out to observe the changes of learning and memory ability of experimental animals,and the possible mechanism of action of DBS was observed through pathological experiments.Result:A total of 24 rats,such as the group,were excluded from the behavioral bias and experimentally shed individuals.Sham=5;N=6 in Sham+DBS group;N=5 in AD group;N=8 in AD+DBS group.Morris water maze test results suggest that after four days of training,AD group had the lowest behavioral score,AD+DBS group behavioral scores were not statistically different from Sham group and Sham+DBS group(P>0.05),and AD group behavioral score.There was a statistical difference(P<0.01);there was no statistical difference in swimming speed between the groups.HE staining and Nissl staining of hippocampal CA1 and DG suggest that AD rats may have neuronal loss after DBS treatment.Conclusion:Through 7 days of short-term deep brain stimulation,the cognitive memory function of the AD rat model induced by injection of 1-42β amyloid in the bilateral hippocampal CA1 region was improved.In the Morris water maze training experiment,DBS treatment can significantly improve the incubation period of animal training after AD modeling and return to near normal level.This means that DBS treatment can improve the cognitive and learning ability of AD experimental animals.However,there was no statistical difference between the swimming speed scores of the experimental animals and the AD model after DBS treatment,suggesting that DBS treatment may have limited improvement in motor neuron lesions caused by AD.The short-term DBS post-AD model rat neuronal apoptosis ratio is reduced,suggesting that early DBS intervention may protect neurons in the hippocampus,and have a certain recovery effect on cognitive and memory impairment caused by disease.This provides a preliminary experimental support for the clinical use of DBS in the treatment of AD to improve the learning and cognitive function of patients.