Oncotarget

Research Papers: Gerotarget (Focus on Aging):

Fluoxetine attenuates the impairment of spatial learning ability and prevents neuron loss in middle-aged APPswe/PSEN1dE9 double transgenic Alzheimer’s disease mice

Jing Ma, Yuan Gao, Lin Jiang, Feng-lei Chao, Wei Huang, Chun-ni Zhou, Wei Tang, Lei Zhang, Chun-xia Huang, Yi Zhang, Yan-min Luo, Qian Xiao, Hua-rong Yu, Rong Jiang and Yong Tang _

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Oncotarget. 2017; 8:27676-27692. https://doi.org/10.18632/oncotarget.15398

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Abstract

Jing Ma1,2, Yuan Gao3, Lin Jiang1,2, Feng-lei Chao1,2, Wei Huang1,2, Chun-ni Zhou1,2, Wei Tang1,2, Lei Zhang1,2, Chun-xia Huang4, Yi Zhang1,2, Yan-min Luo1,2, Qian Xiao1,2, Hua-rong Yu4, Rong Jiang1,2 and Yong Tang1,2

1 Department of Histology and Embryology, Chongqing Medical University, Chongqing, P. R. China

2 Laboratory of Stem Cells and Tissue Engineering, Chongqing Medical University, Chongqing, P. R. China

3 Department of Geriatrics, The First Affiliated Hospital, Chongqing Medical University, Chongqing, P. R. China

4 Department of Physiology, Chongqing Medical University, Chongqing, P. R. China

Correspondence to:

Yong Tang, email:

Keywords: fluoxetine, Alzheimer’s disease, cognition, neuron, APP/PS1 mice, Gerotarget

Received: July 04, 2016 Accepted: January 31, 2017 Published: February 16, 2017

Abstract

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-3β activity and increased the level of β-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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