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本帖最后由 顾汉现 于 2021-8-14 19:51 编辑
Nature:最新研究揭示新冠病毒损害神经系统的病理基础
严重新冠的患者大脑存在明显的炎症及神经通路受损。脑脉络丛的屏障细胞感知并诱导大脑出现外周炎症反应,外周T细胞浸润到实质。与认知、精神分裂症和抑郁症相关的基因在新冠患者的大脑中更频繁地被激活。与新冠病毒 COVID-19有关的小胶质细胞和星形胶质细胞亚群具有与阿尔茨海默病、帕金森病等人类神经退行性疾病相似的病理细胞特征。上层兴奋性神经元的突触信号更容易受COVID-19影响。COVID-19相关细胞扰动与慢性脑部疾病中的扰动重叠。
本文为新冠病毒感染损伤、损害大脑的基础医学研究论文。
科研圈
2021/06/28
论文
论文标题:Dysregulation of brain and choroid plexus cell types in severe COVID-19
作者:Andrew C. Yang, Fabian Kern, Patricia M. Losada, Maayan R. Agam, Christina A. Maat, Georges P. Schmartz, Tobias Fehlmann, Julian A. Stein, Nicholas Schaum, Davis P. Lee, Kruti Calcuttawala, Ryan T. Vest, Daniela Berdnik, Nannan Lu, Oliver Hahn, David Gate, M. Windy McNerney, Divya Channappa, Inma Cobos, Nicole Ludwig, Walter J. Schulz-Schaeffer, Andreas Keller, Tony Wyss-Coray
期刊:Nature
发表时间:2021/06/21
数字识别码:10.1038/s41586-021-03710-0
摘要:Though SARS-CoV-2 primarily targets the respiratory system, patients and survivors can suffer neurological symptoms1–3. Yet, an unbiased understanding of the cellular and molecular processes affected in the brains of COVID-19 patients is still missing. Here, we profile 65,309 single-nucleus transcriptomes from 30 frontal cortex and choroid plexus samples across 14 control (including 1 terminal influenza) and 8 COVID-19 patients. While a systematic analysis yields no molecular traces of SARS-CoV-2 in the brain, we observe broad cellular perturbations which predict that choroid plexus barrier cells sense and relay peripheral inflammation into the brain and show that peripheral T cells infiltrate the parenchyma. We discover COVID-19 disease-associated microglia and astrocyte subpopulations that share features with pathological cell states reported in human neurodegenerative disease4–6. Synaptic signaling of upper-layer excitatory neurons—evolutionarily expanded in humans7 and linked to cognitive function8—are preferentially affected in COVID-19. Across cell types, COVID-19 perturbations overlap with those in chronic brain disorders and reside in genetic variants associated with cognition, schizophrenia, and depression. Our findings and public dataset provide a molecular framework to understand COVID-19 related neurological disease observed now and which may emerge later.
所属学科:
医学
免疫学
(领研网导读 郭怿暄)本研究对8名COVID-19患者和14名对照组个体的30份额叶皮质和脉络丛样品进行单核转录组测序。发现广泛的细胞扰动,脉络丛的屏障细胞感知并诱导大脑出现外周炎症反应,外周T细胞浸润到实质。与COVID-19有关的小胶质细胞和星形胶质细胞亚群具有与人类神经退行性疾病相似的病理细胞特征。上层兴奋性神经元的突触信号更容易受COVID-19影响。COVID-19相关细胞扰动与慢性脑部疾病中的扰动重叠。该发现为理解COVID-19相关神经性疾病提供分子框架。
新冠患者特别是重症患者会出现多种神经或精神疾病的症状,且可能在新冠痊愈后持续存在。为理解其中的机制,美国斯坦福大学医学院(Stanford School of Medicine)和德国萨尔大学(Saarland University)合作团队通过分子生物学的方法,对 8 名重症新冠死亡患者和 14 名其他原因死亡患者的新鲜冷冻脑组织的特定细胞类型进行单细胞转录组测序和综合评估,分析了 65309 个单细胞转录组中的数千个基因。结果表明,死于新冠的患者大脑存在明显的炎症及神经通路受损,与死于阿尔茨海默病、帕金森病等神经退行性疾病的患者的大脑情况非常相似,且与认知、精神分裂症和抑郁症相关的基因在新冠患者的大脑中更频繁地被激活。但该研究没有在大脑中发现新冠病毒的分子痕迹,表明病毒在身体其他部位的感染就可能足以引起神经系统症状。该研究已公开原始测序数据,为进一步剖析新冠病毒对大脑影响的分子机制提供资源。相关论文 6 月 21 日发表于《自然》(Nature)。(Stanford School of Medicine,Nature)
https://www.nature.com/articles/s41586-021-03710-0
https://www.linkresearcher.com/t ... 0-b88e-222c07419f8a
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