Environmental exposures and familial background alter the induction of neuropathology and inflammation after SARS-CoV-2 infection.
Publication/Presentation Date
12-2-2024
Abstract
Basal ganglia disease has been reported as a post-infection sequela of several viruses, with documentation of this phenomenon from the H1N1 Spanish flu to the recent COVID-19 (SARS-CoV-2) pandemic. SARS-CoV-2 infection leads to multisystem deficits, including those affecting the nervous system. Here, we investigated whether a SARS-CoV-2 infection alone increases the susceptibility to develop parkinsonian phenotypes in C57BL/6J mice expressing the human ACE2 receptor, or in addition to two well-known toxin exposures, MPTP and paraquat. Additionally, we examined mice carrying a G2019S mutation in the LRRK2 gene. We also examined if vaccination with either an mRNA- or protein-based vaccine can alter any observed neuropathology. We find that the infection with the WA-1/2020 (alpha) or omicron B1.1.529 strains in ACE2 and G2019S LRRK2 mice both synergize with a subtoxic exposure to the mitochondrial toxin MPTP to induce neurodegeneration and neuroinflammation in the substantia nigra. This synergy appears toxin-dependent since we do not observe this following exposure to the direct redox-inducing compound paraquat. This synergistic neurodegeneration and neuroinflammation is rescued in WT mice that were vaccinated using either mRNA- and protein- based vaccines directed against the Spike protein of the SARS-CoV-2 virus. However, in the G2019S LRRK2 mutant mice, we find that only the protein-based vaccine but not the mRNA- based vaccine resulted in a rescue of the SARS-CoV-2 mediated neuropathology. Taken together, our results highlight the role of both environmental exposures and familial background on the development of parkinsonian pathology secondary to viral infection and the benefit of vaccines in reducing these risks.
ISSN
2692-8205
Published In/Presented At
Chatterjee, D., Kurup, D., & Smeyne, R. J. (2024). Environmental exposures and familial background alter the induction of neuropathology and inflammation after SARS-CoV-2 infection. bioRxiv : the preprint server for biology, 2024.12.02.626375. https://doi.org/10.1101/2024.12.02.626375
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
39677638
Department(s)
Administration and Leadership
Document Type
Article