A suitable model to investigate acute neurological consequences of coronavirus infection

Abstract

Abstract Objective and design: The present study aimed to investigate the neurochemical and behavioral effects of the acute consequences after coronavirus infection through a murine model. Material: Wild type C57 BL/6 mice were infected intranasally (i.n) with the murine coronavirus 3 (MHV-3). Methods: Mice were submitted to behavioral tests. Euthanasia was performed on the fifth day after infection (5 dpi), and the brain tissue was subjected to plaque assays for viral titration, synaptosome, ELISA, histopathological and immunohistochemical analysis. Results: Increased viral titers associated with mild histological changes, including signs of neuronal degeneration, were observed in the cerebral cortex of infected mice. Importantly, MHV-3 infection induced an increase in cortical levels of glutamate and calcium, as well as increased levels of pro-inflammatory cytokines (IL-6, IFN-γ) and reduced levels of neuroprotective mediators (BDNF and CX3CL1) in the mice brain, which is suggestive of excitotoxicity. Finally, behavioral analysis showed impaired motor, anhedonic and anxiety-like behaviors in animals infected with MHV-3. Conclusions: Overall, the data presented emulate many aspects of the acute neurological outcomes seen in patients with COVID-19. Therefore, this model may provide a preclinical platform to study acute neurological sequelae induced by coronavirus infection and test possible therapies.