Nicotine exacerbates tau phosphorylation and cognitive impairment induced by amyloid-beta 25-35 in rats
Nicotine exacerbates tau phosphorylation and cognitive impairment induced by amyloid-beta 25-35 in rats
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DOI：
10.1016/j.ejphar.2010.03.029
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发表时间：
2010-07-10
影响因子：
5
通讯作者：
Zhou, Hua-Dong
中科院分区：
文献类型：
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作者：
Deng, Juan;Shen, Cheng;Zhou, Hua-Dong
据报道，尼古丁可减少斑块负担，并可用作可能的抗阿尔茨海默病药物。然而，尼古丁对阿尔茨海默病的记忆和tau病理学的影响研究较少。本研究调查了尼古丁对海马注射淀粉样蛋白β（A β）25-35诱导的tau磷酸化和认知障碍的影响。大鼠用尼古丁酒石酸氢盐溶于生理盐水皮下注射，每天两次，持续14天。以年龄、性别相匹配的大鼠给予等量生理盐水作为对照。Morris水迷宫检测A β 25-35所致大鼠认知功能损害。与假手术大鼠相比，A β 25-35注射显著延长了Morris水迷宫试验中溶剂处理大鼠的平均逃避潜伏期，并增加了tau（pS202）和tau（pT 231）免疫反应性细胞的数量。数据显示，在阿尔茨海默病的A β大鼠模型中，与A β 25-35注射组相比，尼古丁（1 mg/kg基础体重）治疗显著加剧了认知障碍和海马中Ser-202和Thr-231处的tau磷酸化。应重新评估尼古丁用于治疗阿尔茨海默病。(C)2010 Elsevier B. V.保留所有权利。
Nicotine was reported to reduce the plaque burden and could be used as a possible anti-Alzheimer's disease agent. However, the effect of nicotine on memory and tau pathology in Alzheimer's disease has been less studied. The present study investigated the effect of nicotine on tau phosphorylation and cognitive impairment induced by hippocampus injections of amyloid-beta (A beta) 25-35. Rats were treated with nicotine hydrogen tartrate salt dissolved in normal saline by subcutaneous injection twice per day for 14 days. The age and gender matched rats treated with same amount of normal saline were used as the control. Morris water maze was used to detect the cognitive impairment induced by A beta 25-35. Compared to the sham-operated rats, A beta 25-35 injection significantly prolonged the mean escape latency in vehicle-treated rats in the Morris water maze test and increased the number of tau(pS202) and tau(pT231) immunoreactive cells. The data show that nicotine (1 mg/kg in base weight) treatment significantly exacerbates cognitive impairment and tau phosphorylation at Ser-202 and Thr-231 in the hippocampus compared with A beta 25-35 injection groups in the A beta rat model of Alzheimer's disease. The use of nicotine for treatment of Alzheimer's disease should be reassessed. (C) 2010 Elsevier B.V. All rights reserved.