Paroxetine ameliorates prodromal emotional dysfunction and late-onset memory deficit in Alzheimer’s disease mice  

作　　者：Peng-Hui Ai Si Chen Xian-Dong Liu Xiao-Na Zhu Yuan-Bo Pan Dong-Fu Feng Shengdi Chen Nan-Jie Xu Suya Sun 

机构地区：[1]Department of Neurology and Institute of Neurology,Rui-jin Hospital Shanghai Jiao Tong University School of Medicine,Shanghai,200025,China [2]Collaborative Innovation Center for Brain Science,Department of Anatomy and Physiology,Shanghai Jiao Tong University School of Medicine,Shanghai,200025,China [3]Department of Neurosurgery,Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,200025,China [4]Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education,Shanghai Jiao Tong University School of Medicine,Shanghai,200025,China [5]Shanghai Key Laboratory of Reproductive Medicine,Shanghai Jiao Tong University School of Medicine,Shanghai,200025,China

出　　处：《Translational Neurodegeneration》2020年第2期203-213,共11页转化神经变性病（英文）

基　　金：This research was supported by the National Natural Science Foundation of China(81870820 and 31671062 to N.-J.X.,81671047 to S.S.);Grants of Shanghai Brain-Intelligence Project from STCSM(16JC1420500);the Science and Technology Commission of Shanghai Municipality(18JC1420302);Innovation Program of Shanghai Municipal Education Commission(2017-01-07-00-01-E00046).

摘　　要：Background Neuropsychiatric symptoms(NPS)such as depression,anxiety,apathy,and irritability occur in prodromal phases of clinical Alzheimer’s disease(AD),which might be an increased risk for later developing AD.Here we treated young APP/PS1 AD model mice prophylactically with serotonin-selective re-uptake inhibitor(SSRI)paroxetine and investigated the protective role of anti-depressant agent in emotional abnormalities and cognitive defects during disease progress.Methods To investigate the protective role of paroxetine in emotional abnormalities and cognitive defects during disease progress,we performed emotional behaviors of 3 months old APP/PS1 mouse following oral administration of paroxetine prophylactically starting at 1 month of age.Next,we tested the cognitive,biochemical and pathological,effects of long term administration of paroxetine at 6 months old.Results Our results showed that AD mice displayed emotional dysfunction in the early stage.Prophylactic administration of paroxetine ameliorated the initial emotional abnormalities and preserved the eventual memory function in AD mice.Conclusion Our data indicate that prophylactic administration of paroxetine ameliorates the emotional dysfunction and memory deficit in AD mice.These neuroprotective effects are attributable to functional restoration of glutamate receptor(GluN2A)in AD mice.

关 键 词：Alzheimer's disease Paroxetine treatment Glutamate receptor Memory deficit 

分 类 号：R749.16[医药卫生—神经病学与精神病学]