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 ...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.展开更多
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)+1 种基金the Science and Technology Commission of Shanghai Municipality(18JC1420302)Innovation Program of Shanghai Municipal Education Commission(2017-01-07-00-01-E00046).
文摘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.
