Neuroprotective effect of fluoxetine on the APP/PS1 transgenic mouse model of Alzheimer's disease

Abstract

Abstract: AIM: To study the neuroprotective effect of fluoxetine and its impact on learning and memory functions in aged APP/PS1 transgenic mouse model of Alzheimer's disease.METHODS: The experiments were performed both in vivo and in vitro. In the in vivo experiment, experimental animals were divided into three groups: APP/PSI AD model group was treated by intragastric injection of Fluoxetine (FLX)(n=8), APP/PS1 AD model saline group (NA)(n=8)and age-matched wild-type litter-mates as the WT group (WT) (n=10). FLX group was given fluoxetine 10 mg/kg by intraperitoneal injection. NA and WT groups were given saline solution. Morris water maze test was used to assess the cognitive behavioristics in each group. Tunel staining was used to assess apoptosis in the hippo campus. In the in vitro experiment, human neuroblastoma cells (SH-SY5Y) cultured for 48 hours were divided into four groups: normal, Aβ, fluoxetine, and fluoxetine + Aβ groups. 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.RESULTS: In Morris water maze tests, the average latency was significantly shorter in the FLX group compared with NS groups (P<0.01) and the average cross platform times in the FLX group was significantly more than the NA group (P<0.01). Tunel experiment showed that FLX group had less apoptotic cells compared with NA group (P<0.01). In the in vitro experiment, the number of apoptotic neurons was significantly lower in the fluoxetine group compared with the Aβ group (P<0.01).CONCLUSION: These findings indicate that fluoxetine has neuroprotective effects on the neurons and long-term administration of fluoxetine can improve the learning and memory ability of the APP/PS1 transgenic mouse model

Key words: Alzheimer's disease, fluoxetine, apoptosis, neuron, APP/PS1 transgenic mouse, cognition

CLC Number:

R965.2

LI Gang, KUANG Chao, MENG Zan, ZHOU Liang, MA Jing, LUO Yan-min, LI Zao, LIU Pin-yue, HE Jie, TANG Yong, LIU Yong-gang. Neuroprotective effect of fluoxetine on the APP/PS1 transgenic mouse model of Alzheimer's disease[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2015, 20(5): 514-519.

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