摘要
背景:淀粉样β抑制嗅球功能。这种作用的机制必须包括网络兴奋性的改变,炎症和不同转运体的激活。功能通路。因此,我们在这里测试了托非那莫酸,一种调节这些病理过程的药物,是否能预防淀粉样β诱导的嗅球功能障碍。 目的:探讨托芬那酸对淀粉样β诱导的嗅球网络功能、嗅觉功能及GSK 3β活性的影响。 方法:在成年小鼠嗅球切片上观察托芬那酸对淀粉样β诱导的群体活性抑制的保护作用,同时观察托芬那酸和淀粉样蛋白的作用。采用沐浴法。我们还测试了长期(21天)用托芬那酸处理动物切片中淀粉样β的影响。淀粉样β微注射两周后,对照组和托芬那莫酸长期处理的动物的嗅球种群活动和嗅觉进行了测试。嗅觉用气味回避和习惯性/交叉习惯性测试。Westernblot检测GSK 3β的活化情况。 结果:急性沐浴液中托芬那酸对淀粉样β诱导的嗅球网络活性的抑制作用无明显影响。相比之下,用托非那莫酸治疗慢性对β淀粉样蛋白诱导的神经网络活性抑制的抑制作用与抑制gsk 3β激活和保护淀粉样蛋白有关。β诱发的嗅觉障碍。 结论:我们的数据进一步支持使用托芬那酸预防淀粉样蛋白β诱导的病理和阿尔茨海默病的早期症状。
关键词: 淀粉样蛋白-β蛋白,嗅觉,习惯性,网络活性,磷酸化,甲磺酸。
Current Alzheimer Research
Title:Tolfenamic Acid Prevents Amyloid β-induced Olfactory Bulb Dysfunction In Vivo
Volume: 15 Issue: 8
关键词: 淀粉样蛋白-β蛋白,嗅觉,习惯性,网络活性,磷酸化,甲磺酸。
摘要: Background: Amyloid beta inhibits olfactory bulb function. The mechanisms involved in this effect must include alterations in network excitability, inflammation and the activation of different transduction pathways. Thus, here we tested whether tolfenamic acid, a drug that modulates several of these pathological processes, could prevent amyloid beta-induced olfactory bulb dysfunction.
Objective: To test whether tolfenamic acid prevents amyloid beta-induced alterations in olfactory bulb network function, olfaction and GSK3β activity.
Method: The protective effects of tolfenamic acid against amyloid beta-induced population activity inhibition were tested in olfactory bulb slices from adult mice, while tolfenamic acid and amyloid beta were bath-applied. We also tested the effects of amyloid-beta in slices obtained from animals pre-treated chronically (21 days) with tolfenamic acid. The effects of amyloid beta micro-injected into the olfactory bulbs were also tested, after two weeks, on olfactory bulb population activity and olfaction in control and tolfenamic acid chronically treated animals. Olfaction was assessed with the odor-avoidance and the habituation/cross-habituation tests. GSK3β activation was evaluated with Western-blot.
Results: Acute bath application of tolfenamic acid does not prevent amyloid beta-induced inhibition of olfactory bulb network activity in vitro. In contrast, chronic treatment with tolfenamic acid renders the olfactory bulb resistant to amyloid beta-induced network activity inhibition in vitro and in vivo, which correlates with the inhibition of GSK3β activation and the protection against amyloid beta-induced olfactory dysfunction.
Conclusion: Our data further support the use of tolfenamic acid to prevent amyloid beta-induced pathology and the early symptoms of Alzheimer Disease.
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Tolfenamic Acid Prevents Amyloid β-induced Olfactory Bulb Dysfunction In Vivo, Current Alzheimer Research 2018; 15 (8) . https://dx.doi.org/10.2174/1567205015666180223091233
DOI https://dx.doi.org/10.2174/1567205015666180223091233 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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