Paroxetine ameliorates prodromal emotional dysfunction and late-onset memory deficit in Alzheimer's disease mice
Paroxetine ameliorates prodromal emotional dysfunction and late-onset memory deficit in Alzheimer's disease mice
复制标题
帕罗西汀改善阿尔茨海默病小鼠的前驱情绪功能障碍和迟发性记忆缺陷
DOI：
10.1186/s40035-020-00194-2
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发表时间：
2020-05-12
影响因子：
12.6
通讯作者：
Sun, Suya
中科院分区：
文献类型：
--
作者：
Ai, Peng-Hui;Chen, Si;Sun, Suya
临床阿尔茨海默病（AD）的前驱期出现抑郁、焦虑、冷漠和易怒等神经精神症状（NPS），这可能会增加后期发展为AD的风险。本研究以5 -羟色胺选择性再摄取抑制剂（SSRI）帕罗西汀（paroxetine）预防年轻APP/PS1 AD模型小鼠，探讨抗抑郁药对疾病进展过程中情绪异常和认知缺陷的保护作用。方法研究帕罗西汀对疾病进展过程中情绪异常和认知缺陷的保护作用，从1月龄开始预防性口服帕罗西汀，观察3月龄APP/PS1小鼠的情绪行为。接下来，我们测试了长期服用帕罗西汀对6个月大婴儿的认知、生化和病理影响。结果我们的研究结果表明，AD小鼠在早期就表现出情绪障碍。预防性给予帕罗西汀可改善AD小鼠最初的情绪异常，并保留最终的记忆功能。结论预防性给予帕罗西汀可改善AD小鼠的情绪功能障碍和记忆缺陷。这些神经保护作用可归因于AD小鼠谷氨酸受体（GluN2A）的功能恢复。
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.