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. 2023 Nov;72(10-11):2073-2088.
doi: 10.1007/s00011-023-01798-w. Epub 2023 Oct 14.

A suitable model to investigate acute neurological consequences of coronavirus infection

Jordane Pimenta #  1 , Bruna Da Silva Oliveira #  1 , Anna Luiza Diniz Lima  2 , Caroline Amaral Machado  1 , Larisse De Souza Barbosa Lacerda  1 , Leonardo Rossi  1 , Celso Martins Queiroz-Junior  1 , Luiz Pedro De Souza-Costa  3 , Ana Claudia Santos Pereira Andrade  1 , Matheus Rodrigues Gonçalves  4 , Bárbara Mota  1 , Fernanda Martins Marim  5 , Renato Santana Aguiar  5 , Pedro Pires Goulart Guimarães  2 , Antônio Lúcio Teixeira  6 , Luciene Bruno Vieira  2 , Cristina Guatimosim  1 , Mauro Martins Teixeira  3 , Aline Silva De Miranda  7 , Vivian Vasconcelos Costa  8
Affiliations

A suitable model to investigate acute neurological consequences of coronavirus infection

Jordane Pimenta et al. Inflamm Res. 2023 Nov.

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 C57BL/6 mice were infected intranasally (i.n) with the murine coronavirus 3 (MHV-3).

Methods: Mice underwent 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, ELISA, histopathological, immunohistochemical and synaptosome analysis.

Results: Increased viral titers and 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, which is indicative of excitotoxicity, 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. Finally, behavioral analysis showed impaired motor, anhedonia-like and anxiety-like behaviors in animals infected with MHV-3.

Conclusions: In conclusion, 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.

Keywords: Acute neurological outcomes; Animal behavior; COVID-19; Glutamatergic levels; MHV; SARS-CoV-2.

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