SARS-CoV-2的S1蛋白穿過小鼠的血腦屏障
作者:
小柯機器人發布時間:2020/12/18 21:37:21
美國西雅圖大學William A. Banks小組發現,SARS-CoV-2的S1蛋白可穿過小鼠的血腦屏障。該項研究成果於2020年12月16日在線發表在《自然—神經科學》雜誌上。
研究人員發現,靜脈注射放射性碘突刺蛋白S1亞基(I-S1)可以輕易越過雄性小鼠的血腦屏障,被大腦區域吸收並進入實質性腦部空間。I-S1也被肺、脾、腎和肝吸收。鼻內給藥的I-S1也進入大腦,儘管其水平比靜脈內給藥後低約十倍。APOE的基因型和性別不會影響全腦I-S1的攝取,但對嗅球、肝臟、脾臟和腎臟的攝取具有不同的影響。脂多糖誘導的炎症減少了海馬和嗅球中I-S1的攝取。
機理研究表明,I-S1通過吸附性胞吞作用穿越血腦屏障,鼠類血管緊張素轉化酶2參與腦和肺的攝取,但不參與腎臟、肝臟或脾臟的攝取。
據悉,目前尚不清楚SARS-CoV-2是否可以進入大腦。SARS-CoV-2通過其刺突蛋白的S1亞基與細胞結合。
附:英文原文
Title: The S1 protein of SARS-CoV-2 crosses the blood–brain barrier in mice
Author: Elizabeth M. Rhea, Aric F. Logsdon, Kim M. Hansen, Lindsey M. Williams, May J. Reed, Kristen K. Baumann, Sarah J. Holden, Jacob Raber, William A. Banks, Michelle A. Erickson
Issue&Volume: 2020-12-16
Abstract: It is unclear whether severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019, can enter the brain. Severe acute respiratory syndrome coronavirus 2 binds to cells via the S1 subunit of its spike protein. We show that intravenously injected radioiodinated S1 (I-S1) readily crossed the blood–brain barrier in male mice, was taken up by brain regions and entered the parenchymal brain space. I-S1 was also taken up by the lung, spleen, kidney and liver. Intranasally administered I-S1 also entered the brain, although at levels roughly ten times lower than after intravenous administration. APOE genotype and sex did not affect whole-brain I-S1 uptake but had variable effects on uptake by the olfactory bulb, liver, spleen and kidney. I-S1 uptake in the hippocampus and olfactory bulb was reduced by lipopolysaccharide-induced inflammation. Mechanistic studies indicated that I-S1 crosses the blood–brain barrier by adsorptive transcytosis and that murine angiotensin-converting enzyme 2 is involved in brain and lung uptake, but not in kidney, liver or spleen uptake.
DOI: 10.1038/s41593-020-00771-8
Source: https://www.nature.com/articles/s41593-020-00771-8