Journal
ONCOTARGET
Volume 8, Issue 17, Pages 27676-27692Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.15398
Keywords
fluoxetine; Alzheimer's disease; cognition; neuron; APP/PS1 mice; Gerotarget
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Funding
- Natural Science Foundation of China [NSFC 816171259, NSFC 81501101]
- Research Foundation for 100 Academic and Discipline Talented Leaders of Chongqing, PR China
- Foundation for the Excellent Young Scholars of Chongqing Medical University [CYYQ201509]
- Supporting Excellent Ph.D. Projects of Chongqing Medical University
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Selective serotonin reuptake inhibitors (SSRIs) have been reported to increase cognitive performance in some clinical studies of Alzheimer's disease (AD). However, there is a lack of evidence supporting the efficacy of SSRIs as cognition enhancers in AD, and the role of SSRIs as a treatment for AD remains largely unclear. Here, we characterized the impact of fluoxetine (FLX), a well-known SSRI, on neurons in the dentate gyrus (DG) and in CA1 and CA3 of the hippocampus of middle-aged (16 to 17 months old) APPswe/PSEN1dE9 (APP/PS1) transgenic AD model mice. We found that intraperitoneal (i.p.) injection of FLX (10 mg/kg/day) for 5 weeks effectively alleviated the impairment of spatial learning ability in middle-aged APP/PS1 mice as evaluated using the Morris water maze. More importantly, the number of neurons in the hippocampal DG was significantly increased by FLX. Additionally, FLX reduced the deposition of beta amyloid, inhibited GSK-3 beta activity and increased the level of beta-catenin in middle-aged APP/PS1 mice. Collectively, the results of this study indicate that FLX delayed the progression of neuronal loss in the hippocampal DG in middle-aged AD mice, and this effect may underlie the FLX-induced improvement in learning ability. FLX may therefore serve as a promising therapeutic drug for AD.
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