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

• 作者: Dong-Fu Feng Nan-Jie Xu Peng-Hui Ai Shengdi Chen Si Chen Suya Sun Xian-Dong Liu Xiao-Na Zhu Yuan-Bo Pan
• 来源期刊: 转化神经变性病(英文)
• 学科: 地球科学
• 关键词: Alzheimer's disease Paroxetine treatment Glutamate receptor Memory deficit
• 年，卷（期）: zhsjbxbyw,（2）
• 页码范围: 203-213
• 页数: 11页
• 分类号: X70

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.