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

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 under...

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Detalles Bibliográficos
Autores principales: Erickson, Michelle A., Logsdon, Aric F., Rhea, Elizabeth M., Hansen, Kim M., Holden, Sarah J, Banks, William A, Smith, Jessica L., German, Cody, Farr, Susan A., Morley, John E., Weaver, Riley R, Hirsch, Alec J., Kovac, Andrej, Kontsekova, Eva, Baumann, Kristen K., Omer, Mohamed A., Raber, Jacob
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Published by Elsevier Inc. 2023
Materias:
Full-length Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9867649/
https://www.ncbi.nlm.nih.gov/pubmed/36682515
http://dx.doi.org/10.1016/j.bbi.2023.01.010
Descripción
Sumario: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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