A suitable model to investigate acute neurological consequences of coronavirus infection

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 fth 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-in ammatory 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 anxietylike 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.

Neuropsychiatric sequelae in an experimental model of post-COVID syndrome in mice

“…Previous findings from our research group demonstrated that synaptosomes from MHV-3 infected mice have increased glutamate release and intracellular calcium levels (Pimenta et al, 2023). In the current model, MHV-A59-infected female mice also had significant glutamate release and increased intracellular Ca 2+ levels in the hippocampus at 30-dpi.…”

“…Neuromuscular dysfunction is also an important symptom related to COVID-19 (Rossi et al, 2023). At 16 dpi, both female MHV-A59-infected mice displayed a significant decrease in the forelimb and for all limbs grip force compared with mock controls (Fig.…”

“…The inflammatory score in mice lungs and brain was blinded-determined by a pathologist (C.M.Q.-J.) (Pimenta et al 2023). Lung inflammatory score encompasses (1) airway (0 to 4 points), (2) vascular (0 to 4 points), (3) parenchyma damage (0 to 5 points), and (4) general neutrophil infiltration (0 to 5 points).…”

“…Meningeal inflammation was assessed using a point scale (0 to 4), with 0 representing no inflammation and 1 to 4 corresponding to 1 to 4 layers affected by inflammation. The final score was the sum of the cerebral cortex and hippocampus scores plus the meningitis score, totaling 12 points (Pimenta et al, 2023).…”

“…Grip-force in the forelimbs and all limbs was measured using Grip Strength Meter (Insight Equipamentos, Ribeirão Preto, SP) as previously described (Rossi et al, 2023). Mice were allowed to grasp the smooth pull bar with forelimbs and all limbs by holding their tails.…”