Study On The Relationship Between Gut Microbiota And Alzheimer’s Disease In Mice Model

Alzheimer’s disease(AD)is the main type of dementia and has become a global social and economic burden.The pathological characteristics mainly for cranial nerve cells gathered a large number of amyloid beta peptide tau protein aggregate abnormal in cell and lead to neurofibrillary tangle,it eventually leads to neuronal atrophy and destruction,synaptic loss and cognitive impairment.The relationship between gut microbiota and host had become a hot issue.A large number of research shown a strong relationship between gut microbiota and mulitiple disease.In recent years,many studies have shown that the pathogenesis of AD is related to gut microbiota imbalance,which provides a new idea for the treatment of AD.In order to further explore the causal relationship between gut microbiota and AD,fecal microbe transplantation(FMT)from old-month-old mice model to low-month-old mice model,from old-month-old mice model to wild-type mice and from wild-type mice to low-month-old mice model to study the effects of FMT on neurobehavioral,pathological and gut bacterial composition related to AD.In this thesis,4-month-old APP/PS1 double transgenic mice and 6-week-old male C57 mice were used as recipient mice,and 8-month-old APP/PS1 double transgenic mice were used as old-month-old APP/PS1 donor mice.The control group C57 mice were used as wildtype C57 fecal donor mice.APP/PS1 transgenic mice are widely used in AD research because of the typical AD characteristics,such as the appearance of senile plaque in the brain,the spatial memory and the memory capacity disorder.The feces of old-month-old APP/PS1 mice model were transplanted into low-month-old APP/PS1 mice model and wild-type C57 mice,transplantation of wild-type C57 mice faces into low-month-old APP/PS1 mice model.The differences of behavioral cognitive memory,pathology,gut microbiota composition and different bacteria in recipient mice were analyzed.The main findings of this thesis are as follows:(1)Transplantation of feces from old-month-old APP/PS1 mice reduced the percentage of time spent in the target quadrant,increased the time that needed to search for the platform,reduced the targeting of mice,and reduced the spatial memory and spatial discrimination ability of mice.(2)Transplantation of feces from old-month-old APP/PS1 mice increased the damage of recipient mice cells and decreased the ability of scavenging free radicals,and the level of Aβ1-42 increased significantly.(3)Transplantation of feces from old-month-old APP/PS1 mice increased the relative abundance of gut microbiota in recipient mice,increased the species diversity of gut microbiota in wild-type C57 mice,destroyed the gut microbiota homeostasis of recipient mice and caused gut microbiota imbalance,significantly reduced the relative abundance of beneficial bacteria Prevotella and Akkermansia,and increased the relative abundance of Barnesiella in C57+H＿FMT mice.(4)The feces of wild-type C57 mice transplanted into low-month-old APP/PS1 mice model could improve the gut microbiota imbalance caused by AD in recipient mice,including the gut microbiota abundance,species diversity,gut microbiota composition and relative abundance of beneficial flora,and improve the spatial learning and memory ability of recipient mice,but had no significant effect on the free radical scavenging ability and the level of Aβ1-42 in recipient mice.In this thesis,FMT was used to find that gut microbiota was closely related to AD,transplanting feces from old-month-old AD mice model to low-month-old AD mice model accelerated the pathogenesis of AD,transplanting feces from old-month-old AD mice model to wild-type mice showed cognitive impairment in recipient mice,transplanting feces from wild-type mice to low-month-old AD model mice alleviated cognitive impairment in mice and slowed down the pathogenesis of AD.This thesis provides theoretical clues for the prevention and treatment of AD with gut microbiota as the target,however,the molecular mechanism of the relevance between gut microbiota and AD still need to be studied.