预防性氯马斯汀治疗可改善甲型流感病毒诱发的小鼠认知功能障碍。

IF 3.7 Q2 IMMUNOLOGY
J.D. Tingling , S.A. Krauklis , P.L. Haak , R. Carr , A.Y. Louie , R.W. Johnson , A.J. Steelman
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引用次数: 0

摘要

众所周知,甲型流感病毒(IAV)引起的呼吸道感染会导致全身炎症、神经炎症和认知障碍。我们以前曾发现,IAV 的实验性感染会影响少突胶质细胞的稳态,这与参与髓鞘维护的基因表达以及脂质体的改变有关。在这项研究中,我们试图确定具有促进髓鞘特性的抗组胺药物氯马斯汀是否能逆转IAV对少突胶质细胞(OL)特异基因的影响,以及减轻感染诱导的认知障碍。根据氯马斯汀治疗、感染和性别将雌雄C57BL/6J小鼠随机分为实验组。在接种生理盐水或IAV前七天开始使用载体或氯马斯汀(10mg/kg/d)治疗,并持续整个实验过程。在整个感染过程中测量体重。空间学习和记忆通过莫里斯水迷宫进行评估。生病行为通过测量钻洞反应进行评估。免疫细胞反应通过流式细胞术、RT-qPCR、抗原回忆试验和ELISA测定,病毒载量通过RT-qPCR评估。海马神经炎症基因(Tnf、Cdkn1a)和髓鞘基因(Plp1、Mag、Ugt8a)的水平通过 RT-qPCR 进行测定。感染 IAV 的小鼠会出现体重减轻、认知灵活性受损、穴居行为减少、肺部免疫细胞浸润改变、循环中抗病毒 IgM 和 IgG 水平升高以及对 IAV 表位的 T 细胞反应增加等症状。感染增加了海马中与神经炎症相关的基因水平,降低了与髓鞘化相关的基因水平。氯马斯汀治疗可使雄性患者更早地恢复体重下降,并提高男女患者的IgM水平,但既不会影响Tnf或Cdkn1a的表达水平,也不会挽救少突胶质细胞基因的变化。不过,治疗减轻了感染引起的神经认知障碍。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Prophylactic clemastine treatment improves influenza A virus-induced cognitive dysfunction in mice.
Respiratory infection by influenza A virus (IAV) is known to cause systemic inflammation, neuroinflammation, and cognitive impairment. We previously found that experimental infection with IAV affected oligodendrocyte homeostasis, which was associated with altered expression of genes involved in myelin maintenance as well as the lipidome. In this study, we sought to determine if clemastine, an antihistamine with myelin promoting properties, could reverse the effects of IAV on oligodendrocyte (OL) specific genes, as well as mitigate infection-induced cognitive impairment. Male and female C57BL/6J mice were randomized into experimental groups based on clemastine treatment, infection, and sex. Treatment with vehicle or clemastine (10mg/kg/d) commenced seven days prior to inoculation with either saline or IAV and continued throughout the experiment. Body weight was measured throughout the infection. Spatial learning and memory were assessed by Morris water maze. Sickness behavior was assessed by measuring burrowing response. Immune cell responses were determined by flow cytometry, RT-qPCR, antigen recall assays and ELISA, and viral load assessed by RT-qPCR. Hippocampal levels of neuroinflammatory (Tnf, Cdkn1a) and myelin (Plp1, Mag, Ugt8a) genes were determined by RT-qPCR. Mice infected with IAV developed weight loss, impaired cognitive flexibility, reduced burrowing behavior, altered lung immune cell infiltration, increased circulating anti-viral IgM and IgG levels and increased T cell responses to IAV epitopes. Infection increased hippocampal levels of genes associated with neuroinflammation and decreased levels of genes involved in myelination. Clemastine treatment resulted in earlier recovery of weight loss in males and increased IgM levels for both sexes, but neither affected expression levels of Tnf or Cdkn1a, nor rescued changes to oligodendrocyte genes. However, treatment mitigated infection-induced neurocognitive impairment.
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来源期刊
Brain, behavior, & immunity - health
Brain, behavior, & immunity - health Biological Psychiatry, Behavioral Neuroscience
CiteScore
8.50
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0.00%
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审稿时长
97 days
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