Presentation Details
| AChemS Undergrad Finalist: Spatial Gene Expression Profiling Reveals Acute and Persistent Olfactory Bulb Neuroimmune Responses to SARS-CoV-2 Infection Yaejin Kim1, Jiaying Liu1, Anthony Weidner1, Garret Roth1, Lark Coffey2, Hongwei Liu2, Qizhi Gong1. 1Department of Cell Biology and Human Anatomy, UC Davis School of Medicine, Davis, CA, USA.2Department of Pathology, Microbiology & Immunology, UC Davis School of Veterinary Medicine, Davis, CA, USA |
Abstract
Olfactory loss is a common clinical symptom of COVID-19, caused by SARS-CoV-2 infection. The olfactory mucosa is constantly exposed to the external environment and has direct access to the olfactory bulb (OB) of the brain. This unique anatomical arrangement may facilitate neuroimmune interactions that could contribute to neuropathogenesis in the central nervous system. Although the olfactory mucosal response to SARS-CoV-2 infection has been characterized, it remains unclear whether this mediates inflammatory responses within the OB and whether these result in long-term neuropathological changes. To address these questions, we performed spatial gene expression analysis to characterize acute (2 days post-infection [DPI]) and long-term (3 months post-infection [MPI]) changes in the mouse OB following SARS-CoV-2 infection. Xenium datasets were generated using the mouse Brain gene panel with an additional 99 custom gene targets. OB sections from mock- and SARS-CoV-2-infected wild-type and 5xFAD animals were analyzed and compared, with a total of 55,612 cells analyzed. At 2 DPI, we observed significant upregulation of antiviral gene expression in the olfactory nerve layer and the glomerular layer of the infected OB, while these signals were comparable to controls at 3 MPI. Consistent with olfactory mucosa dysfunction during acute infection, immediate early genes, Fos and Arc, in the glomerular and granule cell layers of the OB were significantly decreased at 2DPI. SARS-CoV-2 infection also resulted in differential expression of neuroplasticity genes (Cpne6, Calb2) in 5xFAD compared to wild-type mice at 3MPI. Our spatial gene expression data indicate that the inflammatory signals enter the OB via the olfactory pathway and may contribute to long-term neurodegeneration in the OB.
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