Effects Of Statins Or Low-fat Diet Intervention Started From Early Period On Aβ Plaques And The Expression Of CHRNA7 In Brain Tissues Of Middle-aged Tg2576 Mice

Objective This experiment was designed to investigate the effects of statins or low-fat diet intervention started from early period onβ-amyloid（Aβ）plaques and the expression of nicotinic acetylcholine receptorα7（CHRNA7）in brain tissues of middle-aged Tg2576 mice,combined with semi-quantitative analysis to understand the interaction of different intervention types and intervention timing,and tried to decipher the effect of early intervention on Aβpathology in the brain of model mice about Alzheimer’s disease（AD）and the effects of behavioral science of AD model mice from the level of cholinergic receptor expression.Methods Thirty-five Tg2576 mice were randomly divided into five groups,four groups of which,named as the juvenile statin group,the juvenile low-fat group,the youth statin group,the youth low-fat group,were treated with Lipitor^?（17 mg/（kg*d））or fed with standard low-fat diet at 2 months or at 6 months respectively.And the fifth group was the blank control group,fed with common forage throughout the process.The above five groups of mice were fed to 9.5 months of age,completed seven times of Morris water maze cognitive behavioral tests,and were butchered at 10 months of age.Their left cerebral hemisphere was prepared as pathological specimens.The brain tissue sections of above five groups were immunostained with polyclonal anti-Aβantibody（Ab71-5800,1:100）and polyclonal anti-CHRNA7 antibody（also known as anti-α7n ACh R antibody,21379-1-AP,1:100）,respectively.The ratio of positive area about Aβplaques and CHRNA7 in the cortex and hippocampus of mice brain tissues was semi-quantitatively determined by image processing software Image J.The effects of two intervention methods and two intervention timings on Aβpathology and CHRNA7 expression in the mice brain,as well as the association between CHRNA7expression and the behavioral test results of the Morris water maze in mice were analyzed.Results（1）Compared with the control group,the positive area ratio of Aβplaques in the cortex of mice in the four experimental group was significantly higher than in the blank control group（F=3.646,P=0.016）.Among which the juvenile statin group（P=0.002）and the juvenile low-fat group（P=0.004）showed a statistically significant increase trend;However,the positive area ratio of Aβplaques in the hippocampus showed a slight upward trend（F=0.857,P=0.502）;（2）Except for the hippocampus in the juvenile statin group（P=0.066）,the expression of CHRNA7 in the cortex（F=18.298,P=0.000）and hippocampus（F=3.289,P=0.026）of mice in other experimental groups had statistical down-regulation compared with the blank control group in the corresponding brain region;（3）Factorial Design showed that neither the type of intervention nor the timing of intervention had an interaction effect on the semi-quantitative expression of Aβplaques and CHRNA7（P>0.05）;Pearson correlation analysis showed that there was a significant negative correlation between CHRNA7 and Aβplaques in the cortex（r=-0.383,P=0.030）,whose linear regression equation could be written as y=-10.864x+15.807（R²=0.147,t=2.27,P=0.030）;But there was a negative correlation trend between the two in the hippocampus（r=-0.158,P=0.386）.（4）Pearson correlation analysis showed that the expression levels of CHRNA7 in the cortex（r=-0.128,P=0.484）and hippocampus（r=-0.221,P=0.225）of five groups and the mean escape latency of mice in Morris water maze test were negatively correlated without statistical significance.Conclusion（1）Early intervention of statins or low-fat diet could aggravate Aβpathology in the brain tissues of the middle-aged Tg2576 model mice,and the earlier the intervention,the more obvious the Aβaccumulation;（2）The intervention not only down-regulated the expression of CHRNA7 in the cortex and hippocampus of middle-aged Tg2576mice,but also resulted in an overall negative correlation between the expression of CHRNA7 and the deposition of Aβ,but the degree of association varies in different brain regions.Furthermore,there was no significant correlation between intervention effects and intervention methods.（3）As observed in this study,there was a causal relationship that could be reasonably speculated between the increase of Aβplaques in brain tissues,the decrease of CHRNA7 expression in brain tissues,and the cognitive decline in mice.