Discussion Of Mechanism About Early Application Of Fluoxetine To Alleviate Depression-like Behavior In APP/PS1 Double Transgenic Mice

backgroundAlzheimer’s disease has become a public health concern of global concern.Studies have shown that depression is one of the most common mental illnesses in Alzheimer’s disease.This study examined whether APP/PS1 double transgenic mice had anxiety and depression-like behavior in the early stage of Alzheimer’s disease.Using fluoxetine(FLX)as an intervention method and hippocampus as the target brain region,the early application of FLX was explored.The effect of APP/PS1 double transgenic mouse behavior and hippocampal myelin basic protein(MBP).ObjectiveTo investigate the presence of anxiety and depression-like behavioral disorder in 3 month old APP/PS1 double transgenic mice and the effects of FLX on anxiety and depression-like behavior in 3 month old APP/PS1 double transgenic mice and the effect on hippocampal MBP.To explore whether FLX can play a neuroprotective role in the early stage of Alzheimer’s disease.MethodsAnimals were divided into four groups.Twenty female 3 month old APP/PS1 double transgenic mice were divided into APP/PS1+FLX group and APP/PS1 group.Twenty female wild-type(Wild type,WT)mice were randomly divided into WT+FLX group and WT group.The APP/PS1+FLX group mice and the WT+FLX group mice were intraperitoneally injected with FLX 10 mg/kg/d,and the APP/PS1 group mice and the WT group mice were intraperitoneally injected with an equal amount of 0.9% sodium chloride injection.It is administered every day from 9:00 am to 10:00 pm for a total of 4 weeks.Through the open field experiment,the elevated plus maze test was used to test whether the mice had anxiety-like behavior;forced swimming test and tail suspension test to detect whether there was depression-like behavior in mice.The expression of MBP in hippocampus of APP/PS1 double transgenic mice was analyzed by Western blotting.Statistical analysis of all experimental data was performed using SPSS 22.0 statistical software.The experimental data obey the normal distribution,and the two-way comparison is performed by LSR by single factor ANOVA.If the data does not obey the normal distribution,the data is statistically analyzed by nonparametric test.The significance level was set to P < 0.05.ResultIn the open field test,there was no significant difference in the proportion of total crossings in the central region,the ratio of total time in the central region to the total time,and the distance in the central region(P>0.05);in the elevated plus maze test,there were no significant differences in the retention time of the four arms and the number of open arms(P>0.05).In the tail suspension test,compared with the WT group,the APP/PS1 group had a prolonged immobility time in the tail suspension experiment(P<0.05);compared with the APP/PS1+FLX group,the APP/PS1 group The immobility time of the mouse tail suspension experiment was significantly prolonged(P<0.05).There was no significant difference in the immobility time between the WT group and the WT+FLX group(P>0.05).In the forced swimming test,compared with the WT group,the forced swimming time in the APP/PS1 group was significantly prolonged(P<0.05);compared with the APP/PS1+FLX group,the APP/PS1 group was compared with the APP/PS1+FLX group.The time of forced swimming was significantly prolonged(P<0.05).There was no significant difference in forced swimming time between WT group and WT+FLX group(P>0.05).The expression of MBP in hippocampus of mice was detected by Western blotting.Compared with WT group,the relative expression of MBP protein in hippocampus of APP/PS1 group was significantly decreased(P<0.001);and mice with APP/PS1+FLX group.Compared with APP/PS1 group,the relative expression of MBP protein in hippocampus of mice was significantly decreased(P<0.05).There was no significant difference in the expression of MBP protein in hippocampus between WT group and WT+FLX group(P>0.05).Conclusion1.3 months old APP/PS1 double transgenic mice showed depression-like behavior without anxiety-like behavior.2.Early application of FLX can alleviate the depression-like behavior of 3 month old APP/PS1 double transgenic mice.3.Early application of FLX can increase the expression of MBP protein in hippocampus of 3 month old APP/PS1 double transgenic mice.