Citalopram restores short-term memory deficit and non-cognitive behaviors in APP/PS1 mice while halting the advance of Alzheimer's disease-like pathology.
Citalopram restores short-term memory deficit and non-cognitive behaviors in APP/PS1 mice while halting the advance of Alzheimer's disease-like pathology.
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西酞普兰可以恢复 APP/PS1 小鼠的短期记忆缺陷和非认知行为，同时阻止阿尔茨海默病样病理的进展。
DOI：
10.1016/j.neuropharm.2017.12.021
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发表时间：
2017
影响因子：
4.7
通讯作者：
Fan Xiaotang
中科院分区：
文献类型：
--
作者：
Zhang Qin;Yang Chen;Liu Tianyao;Liu Liang;Li Fen;Cai Yulong;Lv Keyi;Li Xin;Gao Junwei;Sun Dayu;Xu Haiwei;Yang Qingwu;Fan Xiaotang
阿尔茨海默病（AD）是痴呆症最常见的原因。除了认知障碍外，非认知行为缺陷也是 AD 常见的神经系统后遗症。在这里，我们发现 7 个月大的 APPswe/PSEN1dE9 (APP/PS1) 小鼠存在复杂的行为缺陷，包括物体识别障碍、社交互动不足、抑郁增加和埋弹珠。西酞普兰是一种选择性血清素再摄取抑制剂 (SSRI)，可改善 AD 患者和转基因动物模型中的淀粉样蛋白沉积。治疗 4 周后，西酞普兰挽救了这些小鼠的短期记忆、社交能力和抑郁症缺陷。进一步的免疫组织化学分析表明，如前所述，长期西酞普兰治疗显着减弱了 APP/PS1 小鼠大脑中的 β-淀粉样蛋白沉积和小胶质细胞活化。小清蛋白 (PV) 中间神经元是 GABA 能神经元的主要细胞亚型，被认为对于短期记忆和社交互动不可或缺，也促进了抑郁症的进展。此外，我们发现西酞普兰可以显着增加 APP/PS1 小鼠皮质中的 PV 阳性神经元，而不改变海马体，这可能有助于改善行为表现。我们的研究结果表明，西酞普兰可能是 AD 早期治疗的潜在候选者。
Alzheimer's disease (AD) is the most common cause of dementia. In addition to cognitive impairments, deficits in non-cognitive behaviors are also common neurological sequelae in AD. Here, we show that complex behavioral deficits in 7-month-old APPswe/PSEN1dE9 (APP/PS1) mice include impairments in object recognition, deficient social interaction, increased depression and buried marbles. Citalopram, one of the selective serotonin reuptake inhibitors (SSRIs), ameliorated the amyloid deposition in AD patients and transgenic animal models. After treatment for 4 weeks, citalopram rescued the deficits in short-term memory, sociability and depression in these mice. Further immunohistochemical analysis showed chronic citalopram treatment significantly attenuated β-amyloid deposition and microglial activation in the brains of APP/PS1 mice as demonstrated previously. Parvalbumin (PV) interneurons, which are the primary cellular subtype of GABAergic neurons and considered indispensable for short-term memory and social interaction, also contributed to the progress of depression. Additionally, we found the citalopram could significantly increase the PV-positive neurons in the cortex of APP/PS1 mice without alteration in the hippocampus, which might contribute to the improvement of behavioral performance. Our findings suggest that citalopram might be a potential candidate for the early treatment of AD.