A history of depression is a risk factor for Alzheimer's disease (AD), suggesting the possibility that antidepressants administered prophylactically might retard the disease process and preserve cognitive function. Here we report that pre-symptomatic treatment with the antidepressant paroxetine attenuates the disease process and improves cognitive performance in the 3xTgAD mouse model of AD. Five-month-old male and female 3xTgAD and non-transgenic mice were administered either paroxetine or saline daily for 5 months. Open-field activity was tested in 7-month-old mice and performance in passive avoidance and Morris swim tasks were evaluated at 10 months. 3xTgAD mice exhibited reduced exploratory activity, increased transfer latency in the passive avoidance test and impaired performance in the Morris spatial navigation task compared to nontransgenic control mice. Paroxetine treatment ameliorated the spatial navigation deficit in 3xTgAD male and female mice, without affecting swim speed or distance traveled, suggesting a preservation of cognitive function. Levels of amyloid beta-peptide (Abeta) and numbers of Abeta immunoreactive neurons were significantly reduced in the hippocampus of male and female paroxetine-treated 3xTgAD mice compared to saline-treated 3xTgAD mice. Female 3xTgAD mice exhibited significantly less tau pathology in the hippocampus and amygdala compared to male 3xTgAD mice, and paroxetine lessened tau pathology in male 3xTgAD mice. The ability of a safe and effective antidepressant to suppress neuropathological changes and improve cognitive performance in a mouse model suggests that such drugs administered prophylactically might retard the development of AD in humans.

译文

抑郁症病史是阿尔茨海默氏病 (AD) 的危险因素,表明预防性服用抗抑郁药可能会延缓疾病进程并保留认知功能。在这里,我们报告了抗抑郁药帕罗西汀的对症前治疗可以减轻疾病过程并改善AD的3xtgad小鼠模型的认知能力。每天给五个月大的雄性和雌性3xtgad和非转基因小鼠服用帕罗西汀或生理盐水,持续5个月。在7个月大的小鼠中测试了野外活动,并在10个月时评估了被动回避和莫里斯游泳任务的表现。与非转基因对照小鼠相比,3xtgad小鼠的探索活性降低,被动回避测试中的转移潜伏期增加,Morris空间导航任务的性能受损。帕罗西汀治疗改善了3xTgAD雄性和雌性小鼠的空间导航缺陷,而不影响游泳速度或行进距离,表明可以保留认知功能。与生理盐水处理的3xTgAD小鼠相比,雄性和雌性帕罗西汀处理的3xTgAD小鼠的海马中淀粉样 β 肽 (Abeta) 的水平和Abeta免疫反应性神经元的数量显着降低。与雄性3xtgad小鼠相比,雌性3xtgad小鼠在海马和杏仁核中的tau病理明显减少,帕罗西汀减轻了雄性3xtgad小鼠的tau病理。在小鼠模型中,安全有效的抗抑郁药抑制神经病理变化并改善认知能力的能力表明,预防性施用的此类药物可能会阻止人类AD的发展。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录