SARS-CoV-2感染急性后神经精神和认知后遗症——来自K18-hACE C57BL/6 J小鼠的证据

IF 3.7 2区 医学 Q1 CLINICAL NEUROLOGY
Marco Maria Santi, Eleonora Genovese, Thor Mertz Schou, Matheus da Silva, Sophie Erhardt, Lilly Schwieler, Jacob Ahlberg Weidenfors, Giorgia Marino, Søren Riis Paludan, Samia Joca, Gregers Wegener, Line Reinert, Cecilie Bay-Richter
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引用次数: 0

摘要

背景:COVID-19幸存者经常报告精神和认知后遗症。这些后遗症的来源尚未确定,因为很难确定这些症状是由病毒引起的,还是与大流行相关的环境压力因素有关。在当前的研究中,我们使用SARS-CoV-2感染后急性后遗症(PASC)小鼠模型来评估后遗症的神经生物学性质,而不干扰SARS-CoV-2感染后环境对行为的影响。结果:SARS-CoV-2感染导致与认知相关的行为缺陷,但不会导致焦虑或抑郁样行为。认知缺陷受急性疾病严重程度的影响。细胞因子和趋化因子水平以及犬尿氨酸途径代谢物在感染小鼠的大脑中显著改变。细胞因子/趋化因子水平和犬尿氨酸途径代谢物均与急性疾病的严重程度相关。微生物组分类分析显示各组之间存在显著差异,表明特定的细菌种类可能与PASC的发展有关。结论:这些结果表明,SARS-CoV-2感染导致PASC认知缺陷,受急性疾病严重程度的影响。相比之下,PASC焦虑和抑郁样行为与病毒感染本身无关。这可能表明,PASC焦虑和抑郁与大流行相关的情境压力因素联系更紧密,而不是病毒感染本身。此外,我们的研究结果指出细胞因子,特别是犬尿氨酸途径的代谢物在PASC中的作用,表明它们作为生物标志物和药物治疗靶点的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Neuropsychiatric- and cognitive post-acute sequelae of SARS-CoV-2 infection - evidence from K18-hACE C57BL/6 J mice.

Background: Survivors of COVID-19 frequently report psychiatric and cognitive sequelae. The origin of such sequelae has not been determined, as it has been a challenge to resolve whether these symptoms have a viral origin or are related to the contextual stressors associated with the pandemic. In the current study, we used a mouse model of post-acute sequelae of SARS-CoV-2 infection (PASC) to evaluate the neurobiological nature of the sequelae without the interference of the contextual effects on behavior following SARS-CoV-2 infection.

Results: SARS-CoV-2 infection resulted in behavioral deficits related to cognition but not anxiety- or depression-like behavior. The cognitive deficits were affected by the severity of the acute disease. Cytokine and chemokine levels as well as kynurenine pathway metabolites were significantly altered in the brains of infected mice. Both cytokine/chemokine levels and kynurenine pathway metabolites correlated with the severity of the acute disease. Microbiome taxonomic profiling revealed significant differences between groups, suggesting that specific bacterial species may be associated with the development of PASC.

Conclusions: These results suggest that SARS-CoV-2 infection leads to cognitive deficits in PASC, influenced by the severity of the acute disease. In contrast, PASC anxiety- and depression-like behavior was not related to the viral infection itself. This could indicate that PASC anxiety and depression is more linked to contextual stressors related to the pandemic, rather than the viral infection per se. Additionally, our results points to a role of cytokines and in particular metabolites of the kynurenine pathway in PASC, suggesting their potential as biomarkers and targets for pharmacological treatment.

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来源期刊
CiteScore
8.40
自引率
2.10%
发文量
230
审稿时长
4-8 weeks
期刊介绍: The central focus of the journal is on research that advances understanding of existing and new neuropsychopharmacological agents including their mode of action and clinical application or provides insights into the biological basis of psychiatric disorders and thereby advances their pharmacological treatment. Such research may derive from the full spectrum of biological and psychological fields of inquiry encompassing classical and novel techniques in neuropsychopharmacology as well as strategies such as neuroimaging, genetics, psychoneuroendocrinology and neuropsychology.
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