Fluoxetine Improves Behavioral Performance by Suppressing the Production of Soluble β-Amyloid in APP/PS1 Mice

Author(s): Junhui Wang, Yanbo Zhang, Haiyun Xu, Shenghua Zhu, Hongxing Wang, Jue He, Handi Zhang, Huining Guo, Jiming Kong, Qingjun Huang, Xin-Min Li

Journal Name: Current Alzheimer Research

Volume 11 , Issue 7 , 2014

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Alzheimer’s disease (AD) is the most common neurodegenerative disorder of the central nervous system. Current approaches for AD treatment only ameliorate symptoms. Therapeutic strategies that target the pathological processes of the disease remain elusive. Fluoxetine (FLX) is one of the most widely used antidepressants for the treatment of depression and anxiety associated with AD, however, it is unknown if the drug affects the pathogenesis of the disease. We showed that FLX improved spatial memory, learning and emotional behaviors of APP/PS1 mice, a well characterized model of AD. In the same mice, FLX effectively prevented the protein loss of synaptophysin (SYP) and microtubuleassociated protein 2 (MAP2). FLX was unable to prevent plaque formation, but significantly lowered high levels of soluble β-amyloid (Aβ) in brain tissue, cerebrospinal fluid (CSF) and blood sera. FLX also effectively inhibited the phosphorylation of amyloid precursor protein (APP) at T668, which may be a possible mechanism of the reduced Aβ production in APP/PS1 mouse after treatment.

Keywords: Amyloid precursor protein (APP), Alzheimer’s disease (AD), behavior, fluoxetine, soluble Aβ.

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Article Details

Year: 2014
Published on: 12 August, 2014
Page: [672 - 680]
Pages: 9
DOI: 10.2174/1567205011666140812114715
Price: $65

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