Fluoxetine Enhances APP/PS1 2×Tg Alzheimer’ Diseease Mice Cognition And Association Through Increased Exprease Of Brain-Derived Neurotropic Factor And Reduce The Neuron Apoptosis

Objective:To explore fluoxetine enhance the ability of learning and memory of APP/PS12×Tg Alzheimer’s Disease Mice. Further, to discuss whether the protective effect of fuoxetine through increase the expression of BDNF to reduce neuron apoptosis.Methods:In vivo experiment:experimental animals were divided into three groups:APP/PS1 AD model saline group (NSX APP/PS1 AD model Fluoxetine (10 mg/kg/d) group (FLX)、The Age-matched wild-type litter-mates as the WT group (WT) (n=12). NS and WT group injection of saline. Morris water maze test was used to assess the cognitive behaviorist in each group. ELLISA test was applied to quantify the BDNF concentration of blood and Hippocampus. Immunohistochemistrical staining was use to analysis the expression of BDNF in hippocampus neurons. Tunel staining used to assess apoptosis change in hippocampus.In vitro experiment:human neuroblastoma cells (SH-SY5Y) cultured for 48 hours were divided into four groups:normal, Aβ, fluoxetine, and fluoxetine+Aβ group. Except the normal group, cells in the other three groups were respectively cultured with DMEM containing 10 μmol/L β-amyloid/、100 nmol/L fluoxetine and 100 nmol/L fluoxetine+10 μmol/L β-amyloid for 48 hours. In situ apoptosis dyeing used to observe the cell apoptosis. Results:In vivo1. the FLX group had a significantly higher BDNF concentration in serum and Hippocampus than the NS group when fluoxetine administered 30 days and 60 days (p<0.01)2. In Morris water maze tests, the FLX group significantly reduces the average navigation time compared with the NS group (p<0.05). The average cross platform times FLX group significantly more than the NS group (p<0.05)3. Nissl staining shows that hippocampus neurons in FLX group were significantly more than that of NS group4. Tunel experiment shows that NS group have more apoptotic cells compared with FLX and NS groups (p<0.01)In vitroThe number of apoptotic neurons was significantly lower in the fluoxetine, and fluoxetine+Aβ group compared with the Aβ group (p<0.01)Conclusion:Long-term administration of fluoxetine significantly increased AD model mice both blood serum and the hippocampus BDNF concentration, reduced neuronal apoptosis and improved the APP/PS1 Alzheimer’s Disease Mice learning and memory ability.