Blood-brain barrier penetration of non-replicating SARS-CoV-2 and S1 variants of concern induce neuroinflammation which is accentuated in a mouse model of Alzheimer's disease

Michelle A. Erickson; Aric F. Logsdon; Elizabeth M. Rhea; Kim M. Hansen; Sarah J. Holden; William A. Banks; Jessica L. Smith; Cody German; Susan A. Farr; John E. Morley; Riley R. Weaver; Alec J. Hirsch; Andrej Kovac; Eva Kontsekova; Kristen K. Baumann; Mohamed A. Omer; Jacob Raber

doi:10.1016/j.bbi.2023.01.010

Blood-brain barrier penetration of non-replicating SARS-CoV-2 and S1 variants of concern induce neuroinflammation which is accentuated in a mouse model of Alzheimer's disease

Michelle A. Erickson, Aric F. Logsdon, Elizabeth M. Rhea, Kim M. Hansen, Sarah J. Holden, William A. Banks, Jessica L. Smith, Cody German, Susan A. Farr, John E. Morley, Riley R. Weaver, Alec J. Hirsch, Andrej Kovac, Eva Kontsekova, Kristen K. Baumann, Mohamed A. Omer, Jacob Raber

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

COVID-19 and especially Long COVID are associated with severe CNS symptoms and may place persons at risk to develop long-term cognitive impairments. Here, we show that two non-infective models of SARS-CoV-2 can cross the blood–brain barrier (BBB) and induce neuroinflammation, a major mechanism underpinning CNS and cognitive impairments, even in the absence of productive infection. The viral models cross the BBB by the mechanism of adsorptive transcytosis with the sugar N-acetylglucosamine being key. The delta and omicron variants cross the BB B faster than the other variants of concern, with peripheral tissue uptake rates also differing for the variants. Neuroinflammation induced by icv injection of S1 protein was greatly enhanced in young and especially in aged SAMP8 mice, a model of Alzheimer's disease, whereas sex and obesity had little effect.

Original language	English (US)
Pages (from-to)	251-268
Number of pages	18
Journal	Brain, Behavior, and Immunity
Volume	109
DOIs	https://doi.org/10.1016/j.bbi.2023.01.010
State	Published - Mar 2023

Keywords

Aging
Alzheimer's disease
Blood–brain barrier
COVID-19
Glycoprotein
Microglia
Neuroinflammation
Obesity
SARS-CoV-2
Virus

ASJC Scopus subject areas

Immunology
Endocrine and Autonomic Systems
Behavioral Neuroscience

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10.1016/j.bbi.2023.01.010

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Erickson, M. A., Logsdon, A. F., Rhea, E. M., Hansen, K. M., Holden, S. J., Banks, W. A., Smith, J. L., German, C., Farr, S. A., Morley, J. E., Weaver, R. R., Hirsch, A. J., Kovac, A., Kontsekova, E., Baumann, K. K., Omer, M. A., & Raber, J. (2023). Blood-brain barrier penetration of non-replicating SARS-CoV-2 and S1 variants of concern induce neuroinflammation which is accentuated in a mouse model of Alzheimer's disease. Brain, Behavior, and Immunity, 109, 251-268. https://doi.org/10.1016/j.bbi.2023.01.010

Blood-brain barrier penetration of non-replicating SARS-CoV-2 and S1 variants of concern induce neuroinflammation which is accentuated in a mouse model of Alzheimer's disease. / Erickson, Michelle A.; Logsdon, Aric F.; Rhea, Elizabeth M. et al.
In: Brain, Behavior, and Immunity, Vol. 109, 03.2023, p. 251-268.

Research output: Contribution to journal › Article › peer-review

Erickson, MA, Logsdon, AF, Rhea, EM, Hansen, KM, Holden, SJ, Banks, WA, Smith, JL, German, C, Farr, SA, Morley, JE, Weaver, RR, Hirsch, AJ, Kovac, A, Kontsekova, E, Baumann, KK, Omer, MA & Raber, J 2023, 'Blood-brain barrier penetration of non-replicating SARS-CoV-2 and S1 variants of concern induce neuroinflammation which is accentuated in a mouse model of Alzheimer's disease', Brain, Behavior, and Immunity, vol. 109, pp. 251-268. https://doi.org/10.1016/j.bbi.2023.01.010

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abstract = "COVID-19 and especially Long COVID are associated with severe CNS symptoms and may place persons at risk to develop long-term cognitive impairments. Here, we show that two non-infective models of SARS-CoV-2 can cross the blood–brain barrier (BBB) and induce neuroinflammation, a major mechanism underpinning CNS and cognitive impairments, even in the absence of productive infection. The viral models cross the BBB by the mechanism of adsorptive transcytosis with the sugar N-acetylglucosamine being key. The delta and omicron variants cross the BB B faster than the other variants of concern, with peripheral tissue uptake rates also differing for the variants. Neuroinflammation induced by icv injection of S1 protein was greatly enhanced in young and especially in aged SAMP8 mice, a model of Alzheimer's disease, whereas sex and obesity had little effect.",

keywords = "Aging, Alzheimer's disease, Blood–brain barrier, COVID-19, Glycoprotein, Microglia, Neuroinflammation, Obesity, SARS-CoV-2, Virus",

author = "Erickson, {Michelle A.} and Logsdon, {Aric F.} and Rhea, {Elizabeth M.} and Hansen, {Kim M.} and Holden, {Sarah J.} and Banks, {William A.} and Smith, {Jessica L.} and Cody German and Farr, {Susan A.} and Morley, {John E.} and Weaver, {Riley R.} and Hirsch, {Alec J.} and Andrej Kovac and Eva Kontsekova and Baumann, {Kristen K.} and Omer, {Mohamed A.} and Jacob Raber",

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doi = "10.1016/j.bbi.2023.01.010",

language = "English (US)",

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AU - Rhea, Elizabeth M.

AU - Hansen, Kim M.

AU - Holden, Sarah J.

AU - Banks, William A.

AU - Smith, Jessica L.

AU - German, Cody

AU - Farr, Susan A.

AU - Morley, John E.

AU - Weaver, Riley R.

AU - Hirsch, Alec J.

AU - Kovac, Andrej

AU - Kontsekova, Eva

AU - Baumann, Kristen K.

AU - Omer, Mohamed A.

AU - Raber, Jacob

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N2 - COVID-19 and especially Long COVID are associated with severe CNS symptoms and may place persons at risk to develop long-term cognitive impairments. Here, we show that two non-infective models of SARS-CoV-2 can cross the blood–brain barrier (BBB) and induce neuroinflammation, a major mechanism underpinning CNS and cognitive impairments, even in the absence of productive infection. The viral models cross the BBB by the mechanism of adsorptive transcytosis with the sugar N-acetylglucosamine being key. The delta and omicron variants cross the BB B faster than the other variants of concern, with peripheral tissue uptake rates also differing for the variants. Neuroinflammation induced by icv injection of S1 protein was greatly enhanced in young and especially in aged SAMP8 mice, a model of Alzheimer's disease, whereas sex and obesity had little effect.

AB - COVID-19 and especially Long COVID are associated with severe CNS symptoms and may place persons at risk to develop long-term cognitive impairments. Here, we show that two non-infective models of SARS-CoV-2 can cross the blood–brain barrier (BBB) and induce neuroinflammation, a major mechanism underpinning CNS and cognitive impairments, even in the absence of productive infection. The viral models cross the BBB by the mechanism of adsorptive transcytosis with the sugar N-acetylglucosamine being key. The delta and omicron variants cross the BB B faster than the other variants of concern, with peripheral tissue uptake rates also differing for the variants. Neuroinflammation induced by icv injection of S1 protein was greatly enhanced in young and especially in aged SAMP8 mice, a model of Alzheimer's disease, whereas sex and obesity had little effect.

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Blood-brain barrier penetration of non-replicating SARS-CoV-2 and S1 variants of concern induce neuroinflammation which is accentuated in a mouse model of Alzheimer's disease

Abstract

Keywords

ASJC Scopus subject areas

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