The Effects Of Statins Or Low-fat Diet Intervention Started From Juvenile Or Youth On Aβ Plaques And GFAP Expressions Of Astrocytes In Brain Of Middle-aged Tg2576 Mice

Objective To investigate the effects of low-fat diet or statins intervention started from juvenile or youth on periodon Aβ plaques and GFAP of astrocytes expressions in brain of middle-aged Tg2576 mice.Methods Thirty-five two-month-old model mice with double transgenic APP/PS1 gene of human(Tg2576mice)were selected,and all experimental mice were randomly divided into 5 groups according to the intervention initiation time and intervention methods9n=7).They were blank control group,juvenile statins group,juvenile low-fat group,young statins group,and young low-fat group.The interventionrespectively was initiated at2-month-old(juvenile group)and 6-month-old(youth group).The intervention methods were low-fat diet and statin,meanwhile,one group just feed with regular diet as blank control group,atorvastatin [17mg/(kg·d)] and standard low-fat diet used as the intervention means.until all mice were sacrificed at 10-month-age after they carried out Morris water maze test.The right brain tissue was left to prepare standard paraffin serial sections.Polyclonal anti-Aβ antibody(Ab71-5800,1:100)and monoclonal anti-GFAP antibody(ab7260,1:2000)were used to immune-pathologically stain the five groups of mouse brain.In the Image J mapping software,the positive staining area methodwas used to semi-quantitatively determine the positive Aβ plaque area ratio and staining positive area ratio by anti-GFAP in the cortex and hippocampus of mouse brain tissue sections in each group.Results(1)In cortexes,the area ratios of positive Aβ plaques and staining positive area ratio by anti-GFAP except for the youth low-fat group in the intervention groups were significantly higher than those in the blank control group(P=0.000;P=0.003)。But in the hippocampus,the area ratios of positive Aβ plaques and staining positive area ratio by anti-GFAP were slightly higher than those in the blank control group(P=0.602;P=0.093),which but did not reach a statistical difference.(2)Factorial analysis of 2 by 2 showed that only the onset times of interventions showed significant influences on the positive Aβplaque(P=0.026)and staining positive area ratio by anti-GFAP(P=0.034)in cortexes.Two intervention initiation time and two intervention methods had no significant influences on the positive Aβ plaque(P=0.787;P=0.934)and staining positive area ratio by anti-GFAP(P=0.787;P=0.934)in hippocampus.(3)The linear regression analysis suggested a positive correlation between staining positive area ratio by anti-GFAP and the area ratios of positive Aβ plaques(R2=0.142;P=0.034)in the whole brain.The linear regression analysis suggested a positive correlation between staining positive area ratio by anti-GFAP and the concentrations of Aβ40 in serum(R2=0.0001;P=0.000).The linear regression analysis suggested a negative correlation between the area ratio of GFAP receptors and the concentrations of LDL-C(R2=0.317;P=0.001).Conclusion(1)All AD mice by intervened had been discovered the phenomenon that Aβ plaques(mainly in cortexes)were increased in brain,and the earlier the initiation,the more obvious the tendency of Aβaggregation.model mice with two intervention methods and different times of interventions showed increased Aβ plaque deposition in the brain,and the earlier the initiation,the more obvious the tendency of Aβ aggregation.(2)AD model mice by intervened simultaneously observed that the trend of enhanced GFAP expression with similar trend of Aβ plaques in brain,which in cortexes was apparent than in hippocampus,but there was no significant influence in GFAP expression between the two intervention methods.These had suggested that the trend of GFAP expression enhancement may only be related to the consequent reaction with increase of Aβdeposition,and not directly related to the intervention methods.(3)The level of GFAP expression in the brain and Aβ deposition on the whole were statistically significant positive correlation,but there are large regional differences,and the former had a positive correlation with the concentrations of LDL-C,which suggested the trend of increased of GFAP expression and Aβ deposition in the brain tissue probably due to the combined lipid-lowering effects of the two interventions.