Caveolin-1 mediates blood-brain barrier permeability, neuroinflammation, and cognitive impairment in SARS-CoV-2 infection.
J Neuroimmunol
; 388: 578309, 2024 03 15.
Article
en En
| MEDLINE
| ID: mdl-38335781
ABSTRACT
Blood-brain barrier (BBB) permeability can cause neuroinflammation and cognitive impairment. Caveolin-1 (Cav-1) critically regulates BBB permeability, but its influence on the BBB and consequent neurological outcomes in respiratory viral infections is unknown. We used Cav-1-deficient mice with genetically encoded fluorescent endothelial tight junctions to determine how Cav-1 influences BBB permeability, neuroinflammation, and cognitive impairment following respiratory infection with mouse adapted (MA10) SARS-CoV-2 as a model for COVID-19. We found that SARS-CoV-2 infection increased brain endothelial Cav-1 and increased transcellular BBB permeability to albumin, decreased paracellular BBB Claudin-5 tight junctions, and caused T lymphocyte infiltration in the hippocampus, a region important for learning and memory. Concordantly, we observed learning and memory deficits in SARS-CoV-2 infected mice. Importantly, genetic deficiency in Cav-1 attenuated transcellular BBB permeability and paracellular BBB tight junction losses, T lymphocyte infiltration, and gliosis induced by SARS-CoV-2 infection. Moreover, Cav-1 KO mice were protected from the learning and memory deficits caused by SARS-CoV-2 infection. These results establish the contribution of Cav-1 to BBB permeability and behavioral dysfunction induced by SARS-CoV-2 neuroinflammation.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Disfunción Cognitiva
/
COVID-19
Límite:
Animals
Idioma:
En
Revista:
J Neuroimmunol
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos