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The spatial and cell-type distribution of SARS-CoV-2 receptor ACE2 in human and mouse brain

Rongrong Chen, Keer Wang, Jie Yu, Derek Howard, Leon French, Zhong Chen, Chengping Wen, View ORCID ProfileZhenghao Xu
doi: https://doi.org/10.1101/2020.04.07.030650
Rongrong Chen
1Institute of TCM Clinical Basic Medicine, School of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
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Keer Wang
1Institute of TCM Clinical Basic Medicine, School of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
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Jie Yu
1Institute of TCM Clinical Basic Medicine, School of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
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Derek Howard
2Krembil Centre for Neuroinformatics, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
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Leon French
2Krembil Centre for Neuroinformatics, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
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Zhong Chen
3Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
4Key Laboratory of Medical Neurobiology of National Health Commission and Chinese Academy of Medical Sciences, Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China
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Chengping Wen
1Institute of TCM Clinical Basic Medicine, School of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
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  • For correspondence: wengcp@163.com xuzhenghao@zcmu.edu.cn
Zhenghao Xu
1Institute of TCM Clinical Basic Medicine, School of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
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  • ORCID record for Zhenghao Xu
  • For correspondence: wengcp@163.com xuzhenghao@zcmu.edu.cn
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Abstract

By engaging angiotensin-converting enzyme 2 (ACE2 or Ace2), the novel pathogenic SARS-coronavirus 2 (SARS-CoV-2) may invade host cells in many organs, including the brain. However, the distribution of ACE2 in the brain is still obscure. Here we investigated the ACE2 expression in the brain by analyzing data from publicly available brain transcriptome databases. According to our spatial distribution analysis, ACE2 was relatively highly expressed in some brain locations, such as the choroid plexus and paraventricular nuclei of the thalamus. According to cell-type distribution analysis, nuclear expression of ACE2 was found in many neurons (both excitatory and inhibitory neurons) and some non-neuron cells (mainly astrocytes, oligodendrocytes, and endothelial cells) in human middle temporal gyrus and posterior cingulate cortex. A few ACE2-expressing nuclei were found in a hippocampal dataset, and none were detected in the prefrontal cortex. Except for the additional high expression of Ace2 in the olfactory bulb areas for spatial distribution as well as in the pericytes and endothelial cells for cell-type distribution, the distribution of Ace2 in mouse brain was similar to that in the human brain. Thus, our results reveal an outline of ACE2/Ace2 distribution in the human and mouse brain, which indicates the brain infection of SARS-CoV-2 may be capable of inducing central nervous system symptoms in coronavirus disease 2019 (COVID-19) patients. Potential species differences should be considered when using mouse models to study the neurological effects of SARS-CoV-2 infection.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • With the help of Derek Howard and Leon French, we further analyzed a new database (Mouse brain atlas database (http://mousebrain.org). We revised Figure 6. All Supplementary Figures were moved to the supplementary file. Thank you very much.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted June 15, 2020.
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The spatial and cell-type distribution of SARS-CoV-2 receptor ACE2 in human and mouse brain
Rongrong Chen, Keer Wang, Jie Yu, Derek Howard, Leon French, Zhong Chen, Chengping Wen, Zhenghao Xu
bioRxiv 2020.04.07.030650; doi: https://doi.org/10.1101/2020.04.07.030650
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The spatial and cell-type distribution of SARS-CoV-2 receptor ACE2 in human and mouse brain
Rongrong Chen, Keer Wang, Jie Yu, Derek Howard, Leon French, Zhong Chen, Chengping Wen, Zhenghao Xu
bioRxiv 2020.04.07.030650; doi: https://doi.org/10.1101/2020.04.07.030650

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