Behavioral And Electrophysiological Study Of Transgenic Monkeys In SOD1

Background: Amyotrophic lateral sclerosis of the spinal cord(amyotrophic lateral sclerosis,ALS),commonly known as "Frozen Man",is a kind of aggressive and lethal neurological degeneration characterized by muscular atrophy and medullary paralysis,which is listed as "the world's top five terminal diseases" by the World Health Organization is one of the most common types of motor neuron disease.According to an American epidemiological survey,the annual incidence of ALS is 1-5/100,000.ALS generally occurs in people over 40 years of age,its onset is characterized by hidden disease,rapid progress,most patients often die of respiratory failure within 3-5 years after the onset of disease,a serious threat to the health of the elderly,patients and families bring great mental trauma,but also to individuals and society to bring a heavy financial burden.At present,ALS treatment is still facing a serious situation,the only drug zolpidem and Edaravone Limited role,only some patients can play a role in delaying the disease,and there are side effects.Therefore,it is important to clarify the pathogenesis of ALS and preclinical pathology to become 10 minutes.At present,the research on ALS mainly depends on cell model and small animal model.The research based on cell model and small animal model has made an outstanding contribution to the study of the pathogenic mechanism of ALS.However,limited to the particularity of the model,the cell model failed to reflect the motor neurons in the body,such as the connection of the upper and lower motor neurons,the influence of glial cells on motor neurons,the structural differences of motor neuron axons and the transport of substances in axons.and existing animal models if flies,nematodes,rats and mice,etc.These model animals do not simulate the pathological symptoms of ALS well because of the differences in their genetic background and physiological structure,and the drugs developed based on such animal models lack effective clinical treatment effect.In the early stage of laboratory work,a model of 6 crab monkeys with hSOD1 gene was established by using slow virus as carrier,and this study was carried out on this basis.At present,the diagnosis of ALS in clinic mainly depends on electrophysiological diagnosis,but there is a lack of effective and uniform electrophysiological diagnosis methods in experimental animals.Therefore,this study referred to the clinical Electrophysiological research method,taking healthy crab monkeys as the object,established the Electrophysiological research method suitable for crab-eating monkeys and completed the collection of basic data.At the same time,early pathology and electrophysiological pathological changes were detected in 3 transgenic animals.In addition,the relevant behavioral assessment methods are established and the basic data is collected.Objective: Based on the model of six crab monkeys established in the early stage of the laboratory to express the mutant human source hSOD1 gene,this paper studies whether the Crab Monkey model expressing hSOD1 can simulate the clinical symptoms of ALS patients,and studies the early pathological manifestations of the Crab Monkey model expressing hSOD1.1.The early electrophysiological manifestations of crab-eating monkeys expressing the mutant human source hSOD1 gene were studied,and the relevant experimental standards and the collection of basic data were established.2.The early pathological manifestations of crab-eating monkeys expressing the mutant human source hSOD1 gene were studied.3.The early behavioral manifestations of crab monkeys expressing the mutant human source hSOD1 gene were studied,and the relevant experimental methods and the collection of basic data were established.Research methods:1.Refer to the clinical Electrophysiological research method,establish the Electrophysiological research method suitable for crab eating monkey.2.The pathological changes of transgenic animals were studied by using immunohistochemical techniques such as he staining,ATP staining and NSE staining.3.Based on the existing theoretical system of behavioral research,a behavioral evaluation method suitable for crab-eating monkeys is established.Results of the study:1.Establish relevant experimental standards and complete the collection of basic data,and detect the pathological changes of early clinical electrophysiology in 3 transgenic crab monkeys.2.Pathological changes in muscle tissue were found in 1 crab-eating monkeys.3.Establish relevant behavioral experimental methods and complete the collection of basic data.Data on animal behavioral differences between transgenic animals and control group were obtained.Conclusion:1.The results of this study show that the electrophysiological and pathological changes of transgenic animals are earlier than those of clinical symptoms,and this pathological change is slow,while showing a certain degree of extensibility.2.This study shows that transgenic crab monkey models can objectively simulate the clinical symptoms of ALS patients.3.The electrophysiological and behavioral research methods of crab monkeys established in this study will contribute to the study of diseases based on crab-eating monkeys.4.The findings of this study will provide a reference for the study of neurodegenerative diseases using crab-eating monkeys as models.