Microgliosis and neuronal proteinopathy in brain persist beyond viral clearance in SARS-CoV-2 hamster model
Summary: Background: Neurological symptoms such as cognitive decline and depression contribute substantially to post-COVID-19 syndrome, defined as lasting symptoms several weeks after initial SARS-CoV-2 infection. The pathogenesis is still elusive, which hampers appropriate treatment. Neuroinflamma...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-05-01
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| Series: | EBioMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396422001839 |
| _version_ | 1818017239693000704 |
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| author | Christopher Käufer Cara S. Schreiber Anna-Sophia Hartke Ivo Denden Stephanie Stanelle-Bertram Sebastian Beck Nancy Mounogou Kouassi Georg Beythien Kathrin Becker Tom Schreiner Berfin Schaumburg Andreas Beineke Wolfgang Baumgärtner Gülsah Gabriel Franziska Richter |
| author_facet | Christopher Käufer Cara S. Schreiber Anna-Sophia Hartke Ivo Denden Stephanie Stanelle-Bertram Sebastian Beck Nancy Mounogou Kouassi Georg Beythien Kathrin Becker Tom Schreiner Berfin Schaumburg Andreas Beineke Wolfgang Baumgärtner Gülsah Gabriel Franziska Richter |
| author_sort | Christopher Käufer |
| collection | DOAJ |
| description | Summary: Background: Neurological symptoms such as cognitive decline and depression contribute substantially to post-COVID-19 syndrome, defined as lasting symptoms several weeks after initial SARS-CoV-2 infection. The pathogenesis is still elusive, which hampers appropriate treatment. Neuroinflammatory responses and neurodegenerative processes may occur in absence of overt neuroinvasion. Methods: Here we determined whether intranasal SARS-CoV-2 infection in male and female syrian golden hamsters results in persistent brain pathology. Brains 3 (symptomatic) or 14 days (viral clearance) post infection versus mock (n = 10 each) were immunohistochemically analyzed for viral protein, neuroinflammatory response and accumulation of tau, hyperphosphorylated tau and alpha-synuclein protein. Findings: Viral protein in the nasal cavity led to pronounced microglia activation in the olfactory bulb beyond viral clearance. Cortical but not hippocampal neurons accumulated hyperphosphorylated tau and alpha-synuclein, in the absence of overt inflammation and neurodegeneration. Importantly, not all brain regions were affected, which is in line with selective vulnerability. Interpretation: Thus, despite the absence of virus in brain, neurons develop signatures of proteinopathies that may contribute to progressive neuronal dysfunction. Further in depth analysis of this important mechanism is required. Funding: Federal Ministry of Health (BMG; ZMV I 1-2520COR501), Federal Ministry of Education and Research (BMBF 01KI1723G), Ministry of Science and Culture of Lower Saxony in Germany (14 - 76103-184 CORONA-15/20), German Research Foundation (DFG; 398066876/GRK 2485/1), Luxemburgish National Research Fund (FNR, Project Reference: 15686728, EU SC1-PHE-CORONAVIRUS-2020 MANCO, no > 101003651). |
| first_indexed | 2024-04-14T07:23:34Z |
| format | Article |
| id | doaj.art-7fa0aba7ec2946cc8e68ddea03a9558e |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-04-14T07:23:34Z |
| publishDate | 2022-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-7fa0aba7ec2946cc8e68ddea03a9558e2022-12-22T02:06:04ZengElsevierEBioMedicine2352-39642022-05-0179103999Microgliosis and neuronal proteinopathy in brain persist beyond viral clearance in SARS-CoV-2 hamster modelChristopher Käufer0Cara S. Schreiber1Anna-Sophia Hartke2Ivo Denden3Stephanie Stanelle-Bertram4Sebastian Beck5Nancy Mounogou Kouassi6Georg Beythien7Kathrin Becker8Tom Schreiner9Berfin Schaumburg10Andreas Beineke11Wolfgang Baumgärtner12Gülsah Gabriel13Franziska Richter14Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, 30559 Hannover, GermanyDepartment of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, 30559 Hannover, Germany; Center for Systems Neuroscience, Hannover, GermanyDepartment of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, 30559 Hannover, Germany; Center for Systems Neuroscience, Hannover, GermanyDepartment of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, 30559 Hannover, GermanyLeibniz Institute for Experimental Virology, Hamburg, GermanyLeibniz Institute for Experimental Virology, Hamburg, GermanyLeibniz Institute for Experimental Virology, Hamburg, GermanyDepartment of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, GermanyDepartment of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, GermanyDepartment of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, GermanyLeibniz Institute for Experimental Virology, Hamburg, GermanyDepartment of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany; Center for Systems Neuroscience, Hannover, GermanyDepartment of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany; Center for Systems Neuroscience, Hannover, GermanyLeibniz Institute for Experimental Virology, Hamburg, Germany; Institute for Virology, University for Veterinary Medicine Hannover, 30559 Hannover, GermanyDepartment of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, 30559 Hannover, Germany; Center for Systems Neuroscience, Hannover, Germany; Corresponding Author: Franziska Richter DVM, Ph.D., Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, Foundation, Bünteweg 17, 30559 Hannover, GermanySummary: Background: Neurological symptoms such as cognitive decline and depression contribute substantially to post-COVID-19 syndrome, defined as lasting symptoms several weeks after initial SARS-CoV-2 infection. The pathogenesis is still elusive, which hampers appropriate treatment. Neuroinflammatory responses and neurodegenerative processes may occur in absence of overt neuroinvasion. Methods: Here we determined whether intranasal SARS-CoV-2 infection in male and female syrian golden hamsters results in persistent brain pathology. Brains 3 (symptomatic) or 14 days (viral clearance) post infection versus mock (n = 10 each) were immunohistochemically analyzed for viral protein, neuroinflammatory response and accumulation of tau, hyperphosphorylated tau and alpha-synuclein protein. Findings: Viral protein in the nasal cavity led to pronounced microglia activation in the olfactory bulb beyond viral clearance. Cortical but not hippocampal neurons accumulated hyperphosphorylated tau and alpha-synuclein, in the absence of overt inflammation and neurodegeneration. Importantly, not all brain regions were affected, which is in line with selective vulnerability. Interpretation: Thus, despite the absence of virus in brain, neurons develop signatures of proteinopathies that may contribute to progressive neuronal dysfunction. Further in depth analysis of this important mechanism is required. Funding: Federal Ministry of Health (BMG; ZMV I 1-2520COR501), Federal Ministry of Education and Research (BMBF 01KI1723G), Ministry of Science and Culture of Lower Saxony in Germany (14 - 76103-184 CORONA-15/20), German Research Foundation (DFG; 398066876/GRK 2485/1), Luxemburgish National Research Fund (FNR, Project Reference: 15686728, EU SC1-PHE-CORONAVIRUS-2020 MANCO, no > 101003651).http://www.sciencedirect.com/science/article/pii/S2352396422001839Alpha-synucleinTauNeuroinfectionNeurodegenerative diseaseAnimal model |
| spellingShingle | Christopher Käufer Cara S. Schreiber Anna-Sophia Hartke Ivo Denden Stephanie Stanelle-Bertram Sebastian Beck Nancy Mounogou Kouassi Georg Beythien Kathrin Becker Tom Schreiner Berfin Schaumburg Andreas Beineke Wolfgang Baumgärtner Gülsah Gabriel Franziska Richter Microgliosis and neuronal proteinopathy in brain persist beyond viral clearance in SARS-CoV-2 hamster model EBioMedicine Alpha-synuclein Tau Neuroinfection Neurodegenerative disease Animal model |
| title | Microgliosis and neuronal proteinopathy in brain persist beyond viral clearance in SARS-CoV-2 hamster model |
| title_full | Microgliosis and neuronal proteinopathy in brain persist beyond viral clearance in SARS-CoV-2 hamster model |
| title_fullStr | Microgliosis and neuronal proteinopathy in brain persist beyond viral clearance in SARS-CoV-2 hamster model |
| title_full_unstemmed | Microgliosis and neuronal proteinopathy in brain persist beyond viral clearance in SARS-CoV-2 hamster model |
| title_short | Microgliosis and neuronal proteinopathy in brain persist beyond viral clearance in SARS-CoV-2 hamster model |
| title_sort | microgliosis and neuronal proteinopathy in brain persist beyond viral clearance in sars cov 2 hamster model |
| topic | Alpha-synuclein Tau Neuroinfection Neurodegenerative disease Animal model |
| url | http://www.sciencedirect.com/science/article/pii/S2352396422001839 |
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