SARS-CoV-2的S1蛋白穿过小鼠的血脑屏障
2020-12-22   阅读:401   来源:自然

美国西雅图大学William A. Banks小组发现,SARS-CoV-2的S1蛋白可穿过小鼠的血脑屏障。该项研究成果于2020年12月16日在线发表在《自然—神经科学》杂志上。

研究人员发现,静脉注射放射性碘突刺蛋白S1亚基(I-S1)可以轻易越过雄性小鼠的血脑屏障,被大脑区域吸收并进入实质性脑部空间。I-S1也被肺、脾、肾和肝吸收。鼻内给药的I-S1也进入大脑,尽管其水平比静脉内给药后低约十倍。APOE的基因型和性别不会影响全脑I-S1的摄取,但对嗅球、肝脏、脾脏和肾脏的摄取具有不同的影响。脂多糖诱导的炎症减少了海马和嗅球中I-S1的摄取。

机理研究表明,I-S1通过吸附性胞吞作用穿越血脑屏障,鼠类血管紧张素转化酶2参与脑和肺的摄取,但不参与肾脏、肝脏或脾脏的摄取。

据悉,目前尚不清楚SARS-CoV-2是否可以进入大脑。SARS-CoV-2通过其刺突蛋白的S1亚基与细胞结合。

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

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