title: Fluoxetine improves behavioral performance by suppressing the production of soluble β-amyloid in APP/PS1 mice.
abstract: 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.
authors.forename: Junhui
authors.initials: J
authors.lastname: Wang
authors.forename: Yanbo
authors.initials: Y
authors.lastname: Zhang
authors.forename: Haiyun
authors.initials: H
authors.lastname: Xu
authors.forename: Shenghua
authors.initials: S
authors.lastname: Zhu
authors.forename: Hongxing
authors.initials: H
authors.lastname: Wang
authors.forename: Jue
authors.initials: J
authors.lastname: He
authors.forename: Handi
authors.initials: H
authors.lastname: Zhang
authors.forename: Huining
authors.initials: H
authors.lastname: Guo
authors.forename: Jiming
authors.initials: J
authors.lastname: Kong
authors.forename: Qingjun
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Mental Health Center Shantou University, North Taishan Road, Shantou, Guangdong 515063, China. huangqj@stumhc.cn.
authors.forename: Xin-Min
authors.initials: XM
authors.lastname: Li
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology* / Q000523:psychology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004644:Emotions / Q000187:drug effects / Q000502:physiology; D005473:Fluoxetine / Q000494:pharmacology*; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D018697:Nootropic Agents / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D058225:Plaque, Amyloid / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D065853:Spatial Learning / Q000187:drug effects / Q000502:physiology; D065852:Spatial Memory / Q000187:drug effects / Q000502:physiology; D016708:Synaptophysin / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; D018697:Nootropic Agents; D016708:Synaptophysin; C569015:Syp protein, mouse; D005473:Fluoxetine