Sex-Specific Microglial Activation and SARS-CoV-2 Receptor Expression Induced by Chronic Unpredictable Stress

The coronavirus disease 2019 (COVID-19) pandemic has generated a lot of stress and anxiety among not only infected patients but also the general population across the globe, which disturbs cerebral immune homeostasis and potentially exacerbates the SARS-CoV-2 virus-induced neuroinflammation, especia...

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Autores principales:	Ling Yan, Mohan Jayaram, Keerthana Chithanathan, Alexander Zharkovsky, Li Tian
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	chronic unpredictable mild stress neuroinflammation glial cells COVID-19 SARS-CoV-2 neuropsychiatric disorders Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/e284ee987e3d4837b65950a904607958
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spelling	oai:doaj.org-article:e284ee987e3d4837b65950a9046079582021-11-30T18:55:45ZSex-Specific Microglial Activation and SARS-CoV-2 Receptor Expression Induced by Chronic Unpredictable Stress1662-510210.3389/fncel.2021.750373https://doaj.org/article/e284ee987e3d4837b65950a9046079582021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fncel.2021.750373/fullhttps://doaj.org/toc/1662-5102The coronavirus disease 2019 (COVID-19) pandemic has generated a lot of stress and anxiety among not only infected patients but also the general population across the globe, which disturbs cerebral immune homeostasis and potentially exacerbates the SARS-CoV-2 virus-induced neuroinflammation, especially among people susceptible to neuropsychiatric disorders. Here, we used a chronic unpredictable mild stress (CUMS) mouse model to study its effects on glia-mediated neuroinflammation and expression of SARS-CoV2 viral receptors. We observed that female mice showed depressive-like behavior after CUMS, whereas male mice showed enhanced anxiety and social withdrawal. Interestingly, CUMS led to increased amounts of total and MHCII+ microglia in the hippocampi of female mice but not male mice. mRNA levels of SARS-CoV-2 viral receptors angiotensin-converting enzyme 2 (Ace2) and basigin (Bsg) were also upregulated in the prefrontal cortices of stressed female mice but not male mice. Similarly, sex-specific changes in SARS-CoV-2 viral receptors FURIN and neuropilin-1 (NRP1) were also observed in monocytes of human caregivers enduring chronic stress. Our findings provided evidence on detrimental effects of chronic stress on the brain and behavior and implied potential sex-dependent susceptibility to SARS-CoV-2 infection after chronic stress.Ling YanMohan JayaramKeerthana ChithanathanAlexander ZharkovskyLi TianFrontiers Media S.A.articlechronic unpredictable mild stressneuroinflammationglial cellsCOVID-19SARS-CoV-2neuropsychiatric disordersNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Cellular Neuroscience, Vol 15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	chronic unpredictable mild stress neuroinflammation glial cells COVID-19 SARS-CoV-2 neuropsychiatric disorders Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	chronic unpredictable mild stress neuroinflammation glial cells COVID-19 SARS-CoV-2 neuropsychiatric disorders Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Ling Yan Mohan Jayaram Keerthana Chithanathan Alexander Zharkovsky Li Tian Sex-Specific Microglial Activation and SARS-CoV-2 Receptor Expression Induced by Chronic Unpredictable Stress
description	The coronavirus disease 2019 (COVID-19) pandemic has generated a lot of stress and anxiety among not only infected patients but also the general population across the globe, which disturbs cerebral immune homeostasis and potentially exacerbates the SARS-CoV-2 virus-induced neuroinflammation, especially among people susceptible to neuropsychiatric disorders. Here, we used a chronic unpredictable mild stress (CUMS) mouse model to study its effects on glia-mediated neuroinflammation and expression of SARS-CoV2 viral receptors. We observed that female mice showed depressive-like behavior after CUMS, whereas male mice showed enhanced anxiety and social withdrawal. Interestingly, CUMS led to increased amounts of total and MHCII+ microglia in the hippocampi of female mice but not male mice. mRNA levels of SARS-CoV-2 viral receptors angiotensin-converting enzyme 2 (Ace2) and basigin (Bsg) were also upregulated in the prefrontal cortices of stressed female mice but not male mice. Similarly, sex-specific changes in SARS-CoV-2 viral receptors FURIN and neuropilin-1 (NRP1) were also observed in monocytes of human caregivers enduring chronic stress. Our findings provided evidence on detrimental effects of chronic stress on the brain and behavior and implied potential sex-dependent susceptibility to SARS-CoV-2 infection after chronic stress.
format	article
author	Ling Yan Mohan Jayaram Keerthana Chithanathan Alexander Zharkovsky Li Tian
author_facet	Ling Yan Mohan Jayaram Keerthana Chithanathan Alexander Zharkovsky Li Tian
author_sort	Ling Yan
title	Sex-Specific Microglial Activation and SARS-CoV-2 Receptor Expression Induced by Chronic Unpredictable Stress
title_short	Sex-Specific Microglial Activation and SARS-CoV-2 Receptor Expression Induced by Chronic Unpredictable Stress
title_full	Sex-Specific Microglial Activation and SARS-CoV-2 Receptor Expression Induced by Chronic Unpredictable Stress
title_fullStr	Sex-Specific Microglial Activation and SARS-CoV-2 Receptor Expression Induced by Chronic Unpredictable Stress
title_full_unstemmed	Sex-Specific Microglial Activation and SARS-CoV-2 Receptor Expression Induced by Chronic Unpredictable Stress
title_sort	sex-specific microglial activation and sars-cov-2 receptor expression induced by chronic unpredictable stress
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/e284ee987e3d4837b65950a904607958
work_keys_str_mv	AT lingyan sexspecificmicroglialactivationandsarscov2receptorexpressioninducedbychronicunpredictablestress AT mohanjayaram sexspecificmicroglialactivationandsarscov2receptorexpressioninducedbychronicunpredictablestress AT keerthanachithanathan sexspecificmicroglialactivationandsarscov2receptorexpressioninducedbychronicunpredictablestress AT alexanderzharkovsky sexspecificmicroglialactivationandsarscov2receptorexpressioninducedbychronicunpredictablestress AT litian sexspecificmicroglialactivationandsarscov2receptorexpressioninducedbychronicunpredictablestress
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Sex-Specific Microglial Activation and SARS-CoV-2 Receptor Expression Induced by Chronic Unpredictable Stress

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