Study Of The Molecular Mechanism Of Neuroprotective Effect Of Fluoxetine On The APP/PS1 Double Transgenic AD Mice And In Vitro Experimental Study Of APP695swe Nerve Cell Model Of Alzheimer’s Disease

ObjectiveThe possible Molecular mechanism of neuroprotective effect of Fluoxetine(FLX) on the APP/PS1 double transgenic AD mice and in vitro experimental study of APP695 swe nerve cell model of Alzheimer’s Disease was preliminarily discussed. MethodsIn vivo experiments with APP / PS1 double transgenic AD mouse hippocampal neurons within the major object. Mice of APP/PS1 as AD patients were randomly divided into two groups. The experimental group was injected fluoxetine 10 mg / kg per day for each concentration mice. The control group was injected intraperitoneally with normal saline(NS) in place, others were the same as fluoxetine group. For another, the normal mouse as normal people as normal group. After 60 days in different areas of cells in the hippocampus of these three groups mice in TUNEL staining.In vitro experiments.The fluoxetine on the nerve cell model including N2A/WT cells and N2A/APP695 swe cells of Alzheimer’s disease. Firstly, the cell viability of APP695 cells was measured by CCK-8 experiment, and the suitable concentration of fluoxetine was selected as the drug concentration on the subsequent experiments. Secondly, WT group, APP695 + fluoxetine group, and APP695 group were divided, of which the cells were in Apoptosis staining experiments after being cultured for 48 hours. Finally, the expression of Aβ and BDNF was determined by Western-blot. ResultsThe result in vivo experiments showed that in cells TUNEL staining, apoptotic cells in the APP/PS1+fluoxetine group was less than the APP/PS1+NS group(p<0.05), but compared with the normal mouse NS group were no significant difference(p>0.05).The APP/PS1+NS group was different between normal mouse NS group(p<0.05).The result in vitro experiments of CCK-8 experiment showed the suitable concentration of fluoxetine concentration was 10-7 mol/L. The Situ apoptosis staining showed that apoptotic cells of APP695 group were significantly more than the other two groups(p<0.01), apoptotic cells increased(p<0.05) when compared with the APP695 + fluoxetine group, whereas, there was no significant difference between WT group and APP695+fluoxetine group(p>0.05). Western result showed that Aβ expression in APP695 group was more(p<0.05) while BDNF expression was significantly less(p<0.01) when compared with the other two groups, and Aβ expression increased(p<0.05) while of BDNF expression decreased(p<0.05) when compared with APP695+fluoxetine group, while there was no significant difference of Aβ and BDNF expression(p>0.05) between WT group and fluoxetine group. ConclusionThe results suggest that fluoxetine can reduce apoptosis in the APP / PS1 AD mouse hippocampal cells.Fluoxetine may inhibit APP695 overexpressing Aβ, thereby it might reduce the impact of toxic Aβ to APP695, reduce neuronal apoptosis and then increase the expression of BDNF to save nerve cell, which provided new ideas for treatment of Fluoxetine on Alzheimer’s disease.