Neutralization of IL-17 rescues amyloid-β-induced neuroinflammation and memory impairment
Neutralization of IL-17 rescues amyloid-β-induced neuroinflammation and memory impairment
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DOI：
10.1111/bph.14586
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发表时间：
2019-09-01
影响因子：
7.3
通讯作者：
Maione, Francesco
中科院分区：
文献类型：
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作者：
Cristiano, Claudia;Volpicelli, Floriana;Maione, Francesco
背景和目的阿尔茨海默病（AD）是一种常见的神经退行性疾病，其特征是神经炎症状态，迄今为止，尚无治愈方法，其治疗代表了巨大的未满足的临床需求。多项研究已报道 Th17 细胞参与 AD 相关神经炎症的发病机制。然而，细胞因子 IL-17 的作用尚未得到很好的解决。在此，我们研究了静脉注射IL-17中和抗体（IL-17Ab）的作用。或鼻内（IN）途径对淀粉样蛋白-β（Aβ）诱导的小鼠神经炎症和记忆障碍的影响。实验方法将A beta(1-42)注射到成年CD1小鼠的脑室中。这些小鼠通过静脉注射接受 IL-17Ab。在 A beta(1-42) 注射前 1 小时或在 A beta(1-42) 注射后 5 和 12 天进行。服用 A beta(1-42) 7 天和 14 天后，我们评估了嗅觉、空间和工作记忆，并对全脑和特定脑区进行了生化分析。主要结果 静脉注射 IL-17Ab 预处理可显着减少 A beta(1-42) 诱导的神经变性，改善记忆功能，并在 7 和 14 天时以剂量依赖性方式阻止促炎介质的增加。同样，注射 A beta(1-42) 后双重注射 IL-17Ab 可减少神经变性、记忆力下降以及促炎介质和细胞因子的水平。结论和意义 这些发现表明 IL-17Ab 减少了 Aβ 诱导的神经炎症和行为症状。 IL-17Ab IN 给药在减少 A beta(1-42) 神经变性方面的功效表明了 AD 患者未来可能的治疗方法。链接文章 本文是痴呆症和阿尔茨海默病治疗学主题部分的一部分：精准医学的新方向。要查看本节中的其他文章，请访问 http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.18/issuetoc
Background and purpose Alzheimer's disease (AD) is a common neurodegenerative disease characterized by a neuroinflammatory state, and to date, there is no cure and its treatment represents a large unmet clinical need. The involvement of Th17 cells in the pathogenesis of AD-related neuroinflammation has been reported in several studies. However, the role of the cytokine, IL-17 has not been well addressed. Herein, we investigate the effects of IL-17 neutralizing antibody (IL-17Ab) injected by i.c.v. or intranasal (IN) routes on amyloid-beta (A beta)-induced neuroinflammation and memory impairment in mice. Experimental approach A beta(1-42) was injected into cerebral ventricles of adult CD1 mice. These mice received IL-17Ab via i.c.v. either at 1 h prior to A beta(1-42) injection or IN 5 and 12 days after A beta(1-42) injection. After 7 and 14 days of A beta(1-42) administration, we evaluated olfactory, spatial and working memory and performed biochemical analyses on whole brain and specific brain areas. Key results Pretreatment with IL-17Ab, given, i.c.v., markedly reduced A beta(1-42)-induced neurodegeneration, improved memory function, and prevented the increase of pro-inflammatory mediators in a dose-dependent manner at 7 and 14 days. Similarly, the double IN administration of IL-17Ab after A beta(1-42) injection reduced neurodegeneration, memory decline, and the levels of proinflammatory mediators and cytokines. Conclusion and implications These findings suggest that the IL-17Ab reduced neuroinflammation and behavioural symptoms induced by A beta. The efficacy of IL-17Ab IN administration in reducing A beta(1-42) neurodegeneration points to a possible future therapeutic approach in patients with AD. Linked Articles This article is part of a themed section on Therapeutics for Dementia and Alzheimer's Disease: New Directions for Precision Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.18/issuetoc