Study On The Functional Connectivity Of Senescence-accelerated Mouse Prone 8 Strain Based On Functional Magnetic Resonance Imaging

Alzheimer's disease(AD)is a complex neurodegenerative disease of the nervous system,whose etiology is still unknown.As the main research model of Alzheimer's disease,senescence-accelerated mouse prone 8 strain(SAMP8)mice have been widely studied in behavioral and neuropathological aspects.However,there is still a lack of research on the brain functional connectivity patterns in senescence-accelerated mouse prone 8 strain mice.The purpose of this study was to(1)based on the functional magnetic resonance imaging(f MRI)to study the distribution patterns and variation patterns of hippocampal subfield functional connectivity in senescence-accelerated mouse prone 8 strain mice,(2)with the disease progress,senescence-accelerated mouse prone 8 strain,the change rule of hippocampal subfield functional connectivity,(3)combined with behavioral experiment and protein content detection,research the relationship between the functional connectivity-behavior,functional connectivity-protein.In this study,the resting state functional magnetic resonance imaging data of mice with different months(3-6 months,9-12 months,15-18 months)in the senescence-accelerated mouse prone 8 strain and the control group in the senescence-accelerated mouse resistant 1strain were collected,using the method of functional connectivity analysis,get two groups of mice were left and the right side of the CA1 subfield,right and left of CA3/DG subfield of the functional connectivity,Firstly,the functional connectivity of the hippocampal subfield was tested by in-group single sample T test in the two groups of mice at different month,respectively,and the one-way(months)ANOVA was performed to compare months respectively on two groups of mice hippocampal subfield functional connectivity;The contents of memory-related proteins in the hippocampus were detected by ELISA and the shuttle chamber experiment was conducted on two groups of mice.Two-way(disease ×hemispheric)ANOVA was performed in two groups of mice of the same month to study the interaction between disease and hemisphere.First,we obtained the distribution pattern of functional connectivity in the hippocampal subfield of the two groups of mice with the change of monthly age.And then we found that,at the age of 3-6 months,the functional connectivity between the CA3/DG subfield and the anterior cingulate gyrus/prelimbic area(ACC/PL)were significantly decreased compared with the control group.With the increase of monthly age,the differences in functional connectivitybetween the right CA3/DG subfield and anterior cingulate gyrus/prelimbic area in the senescence-accelerated mouse prone 8 strain mice and the control group of the same age were gradually reduced.The influence of month age on behavioral indicators and protein levels in the control group was extremely significant,and the functional connectivity between CA3/DG subfield and anterior cingulate gyrus/prefrontal lobe in the control group was significantly correlated with behavioral indicators and protein levels,but such correlation did not exist in the senescence-accelerated mouse prone 8 strain mice.To sum up,this article first discovered senescence-accelerated mouse prone 8 strain mice hippocampal subfield abnormal distribution of functional connectivity,as well as its changing with the disease progression,and the functional connectivity of hippocampal subfield combined with learning and memory behavior experiment and memory related proteins,reveal the relationship between the functional connectivity with the behavior index and protein content in two groups of mice.This study not only provides a new perspective for understanding the pathophysiological mechanism of Alzheimer's disease progression,but also provides a new means for early clinical diagnosis and disease progression monitoring of Alzheimer's disease.