tetano
Editor, Senior Moderator
EBioMedicine
. 2022 Apr 16;79:103999.
doi: 10.1016/j.ebiom.2022.103999. Online ahead of print.
Microgliosis and neuronal proteinopathy in brain persist beyond viral clearance in SARS-CoV-2 hamster model
Christopher Käufer[SUP] 1 [/SUP], Cara S Schreiber[SUP] 2 [/SUP], Anna-Sophia Hartke[SUP] 2 [/SUP], Ivo Denden[SUP] 1 [/SUP], Stephanie Stanelle-Bertram[SUP] 3 [/SUP], Sebastian Beck[SUP] 3 [/SUP], Nancy Mounogou Kouassi[SUP] 3 [/SUP], Georg Beythien[SUP] 4 [/SUP], Kathrin Becker[SUP] 4 [/SUP], Tom Schreiner[SUP] 4 [/SUP], Berfin Schaumburg[SUP] 3 [/SUP], Andreas Beineke[SUP] 5 [/SUP], Wolfgang Baumgärtner[SUP] 5 [/SUP], Gülsah Gabriel[SUP] 6 [/SUP], Franziska Richter[SUP] 7 [/SUP]
Affiliations
Abstract
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).
Keywords: Alpha-synuclein; Animal model; Neurodegenerative disease; Neuroinfection; Tau.
. 2022 Apr 16;79:103999.
doi: 10.1016/j.ebiom.2022.103999. Online ahead of print.
Microgliosis and neuronal proteinopathy in brain persist beyond viral clearance in SARS-CoV-2 hamster model
Christopher Käufer[SUP] 1 [/SUP], Cara S Schreiber[SUP] 2 [/SUP], Anna-Sophia Hartke[SUP] 2 [/SUP], Ivo Denden[SUP] 1 [/SUP], Stephanie Stanelle-Bertram[SUP] 3 [/SUP], Sebastian Beck[SUP] 3 [/SUP], Nancy Mounogou Kouassi[SUP] 3 [/SUP], Georg Beythien[SUP] 4 [/SUP], Kathrin Becker[SUP] 4 [/SUP], Tom Schreiner[SUP] 4 [/SUP], Berfin Schaumburg[SUP] 3 [/SUP], Andreas Beineke[SUP] 5 [/SUP], Wolfgang Baumgärtner[SUP] 5 [/SUP], Gülsah Gabriel[SUP] 6 [/SUP], Franziska Richter[SUP] 7 [/SUP]
Affiliations
- PMID: 35439679
- DOI: 10.1016/j.ebiom.2022.103999
Abstract
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).
Keywords: Alpha-synuclein; Animal model; Neurodegenerative disease; Neuroinfection; Tau.