Cotinine and 6-Hydroxy-L-Nicotine Reverses Memory Deficits and Reduces Oxidative Stress in Aβ25-35-Induced Rat Model of Alzheimer's Disease
Cotinine and 6-Hydroxy-L-Nicotine Reverses Memory Deficits and Reduces Oxidative Stress in Aβ25-35-Induced Rat Model of Alzheimer's Disease
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DOI：
10.3390/antiox9080768
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发表时间：
2020-08-01
期刊：
影响因子：
7
通讯作者：
Hritcu, Lucian
中科院分区：
文献类型：
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作者：
Boiangiu, Razvan Stefan;Mihasan, Marius;Hritcu, Lucian
尼古丁衍生物可替宁（COT）和6-羟基-L-尼古丁（6 HLN）显示出有希望的认知改善作用，而没有表现出尼古丁的副作用。在这里，我们研究了COT和6 HLN对A β（25-35）诱导的阿尔茨海默病（AD）大鼠模型中记忆障碍和氧化应激的影响。将COT和6 HLN长期给予A β（25-35）处理的大鼠，并使用体内任务（Y-迷宫、新物体识别和径向臂迷宫）评估其记忆表现。通过使用计算机模拟工具，我们试图将行为结果与这些烟碱化合物在烟碱乙酰胆碱受体（nAChR）的α 7和α 4 β 2亚型的变构位点中的计算结合潜力相关联。测定海马组织的氧化状态和乙酰胆碱酯酶（AChE）活性。RT-qPCR评估dbdnf、arc和il-1 β mRNA水平。我们的数据显示，COT和6 HLN可以与α 7和α 4 β 2 nAChR结合，其亲和力与尼古丁相似甚至更高。因此，该治疗在A β（25-35）诱导的AD大鼠模型中显示出促认知、抗氧化和抗AChE特征。最后，RT-qPCR分析显示COT和6 HLN正调控bdnf、arc和il-1 β基因的表达。因此，这些作用于胆碱能系统的烟碱衍生物可能是改善AD状况的有希望的选择。
The nicotinic derivatives, cotinine (COT), and 6-hydroxy-L-nicotine (6HLN), showed promising cognitive-improving effects without exhibiting the nicotine's side-effects. Here, we investigated the impact of COT and 6HLN on memory impairment and the oxidative stress in the A beta(25-35)-induced rat model of Alzheimer's disease (AD). COT and 6HLN were chronically administered to A beta(25-35)-treated rats, and their memory performances were assessed using in vivo tasks (Y-maze, novel object recognition, and radial arm maze). By using in silico tools, we attempted to associate the behavioral outcomes with the calculated binding potential of these nicotinic compounds in the allosteric sites of alpha 7 and alpha 4 beta 2 subtypes of the nicotinic acetylcholine receptors (nAChRs). The oxidative status and acetylcholinesterase (AChE) activity were determined from the hippocampal tissues. RT-qPCR assessedbdnf, arc, and il-1 beta mRNAlevels. Our data revealed that COT and 6HLN could bind to alpha 7 and alpha 4 beta 2 nAChRs with similar or even higher affinity than nicotine. Consequently, the treatment exhibited a pro-cognitive, antioxidant, and anti-AChE profile in the A beta(25-35)-induced rat model of AD. Finally, RT-qPCR analysis revealed that COT and 6HLN positively modulated the bdnf, arc, and il-1 beta genes expression. Therefore, these nicotinic derivatives that act on the cholinergic system might represent a promising choice to ameliorate AD conditions.