RT Journal Article
SR Electronic
T1 A Quantum Dot Biomimetic for SARS-CoV-2 to Interrogate Dysregulation of the Neurovascular Unit Relevant to Brain Inflammation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.04.20.488933
DO 10.1101/2022.04.20.488933
A1 Wesley Chiang
A1 Angela Stout
A1 Francine Yanchik-Slade
A1 Herman Li
A1 Bradley Nilsson
A1 Harris Gelbard
A1 Todd Krauss
YR 2022
UL http://biorxiv.org/content/early/2022/04/22/2022.04.20.488933.abstract
AB Despite limited evidence for competent infection and viral replication of SARS-CoV-2 in the central nervous system (CNS), neurologic dysfunction is a common post-acute medical condition reported in “recovered” COVID-19 patients. To identify a potential noninfectious route for SARS-CoV-2-mediated neurological damage, we constructed colloidal nanocrystal quantum dots linked to micelles decorated with spike protein (COVID-QDs) as a biomimetic to interrogate how blood-brain barrier (BBB) dysregulation may subsequently induce neuroinflammation in the absence of infection. In transwell co-culture of endothelial bEnd.3 monolayers and primary neuroglia, we exposed only the bEnd.3 monolayers to COVID-QDs and examined by fluorescence microscopy whether such treatment led to (i) increased inflammation and leakage across the bEnd.3 monolayers, (ii) permeability of the COVID-QDs across the monolayers, and (iii) induction of neuroinflammation in neuroglial cultures. The results of our study provide evidence of neuroinflammatory hallmarks in cultured neurons and astrocytes without direct exposure to SARS-CoV-2-like nanoparticles. Additionally, we found that pre-treatment of our co-cultures with a small-molecule, broad-spectrum inhibitor of mixed lineage and leucine rich repeat kinases led to reversal of the observed dysregulation in endothelial monolayers and resulted in neuroglial protection. The results reported here may serve to guide future studies into the potential mechanisms by which SARS-CoV-2 mediates neurologic dysfunction.Competing Interest StatementHAG is the Chief Science Officer of Pioneura Corp, (Fairport, NY) which holds the exclusive license for URMC-099, but did not contribute either salary support or funding for this work.