Shedding light on the toxicity of SARS-CoV-2-derived peptide in non-target COVID-19 organisms: A study involving inbred and outbred mice.

Despite advances in research on the vaccine and therapeutic strategies of COVID-19, little attention has been paid to the possible (eco)toxicological impacts of the dispersion of SARS-CoV-2 particles in natural environments. Thus, in this study, we aimed to evaluate the behavioral and biochemical consequences of the short exposure of outbred and inbred mice (male Swiss and C57Bl/6 J mice, respectively) to PSPD-2002 (peptide fragments of the Spike protein of SARS-CoV-2) synthesized in the laboratory. Our data demonstrated that after 24 h of intraperitoneal administration of PSPD-2002 (at 580 µg/kg) the animals did not present alterations in their locomotor, anxiolytic-like, or anxiety-like behavior (in the open field test), nor antidepressant-like or depressive behavior in the forced swimming test. However, the C57Bl/6 J mice exposed to PSPD-2002 showed memory deficit in the novel object recognition task, which was associated with higher production of thiobarbituric acid reactive substances, as well as the increased suppression of acetylcholinesterase brain activity, compared to Swiss mice also exposed to peptide fragments. In Swiss mice the reduction in the activity of superoxide dismutase and catalase in the brain was not associated with increased oxidative stress biomarkers (hydrogen peroxide), suggesting that other antioxidant mechanisms may have been activated by exposure to PSPD-2002 to maintain the animals' brain redox homeostasis. Finally, the results of all biomarkers evaluated were applied into the "Integrated Biomarker Response Index" (IBRv2) and the principal component analysis (PCA), and greater sensitivity of C57Bl/6 J mice to PSPD-2002 was revealed. Therefore, our study provides pioneering evidence of mammalian exposure-induced toxicity (non-target SARS-CoV-2 infection) to PSPD-2002, as well as "sheds light" on the influence of genetic profile on susceptibility/resistance to the effects of viral peptide fragments.

Effect of Sensory Deprivation of Nasal Respiratory on Behavior of C57BL/6J Mice.

Nasal breathing is a dynamic cortical organizer involved in various behaviors and states, such as locomotion, exploration, memory, emotion, introspection. However, the effect of sensory deprivation of nasal respiratory breath (NRD) on behavior remain poorly understood. Herein, general locomotor activity, emotion, learning and memory, social interaction, and mechanical pain were evaluated using a zinc sulfate nasal irrigation induced nasal respiratory sensory deprivation animal model (ZnSO4-induced mouse model). In the open field test, the elevated O-maze test, and forced swim test, NRD mice exhibited depressive and anxiety-like behaviors. In memory-associated tests, NRD mice showed cognitive impairments in the hippocampal-dependent memory (Y maze, object recognition task, and contextual fear conditioning (CFC)) and amygdala-dependent memory (the tone-cued fear conditioning test (TFC)). Surprisingly, NRD mice did not display deficits in the acquisition of conditional fear in both CFC and TFC tests. Still, they showed significant memory retrieval impairment in TFC and enhanced memory retrieval in CFC. At the same time, in the social novelty test using a three-chamber setting, NRD mice showed impaired social and social novelty behavior. Lastly, in the von Frey filaments test, we found that the pain sensitivity of NRD mice was reduced. In conclusion, this NRD mouse model showed a variety of behavioral phenotypic changes, which could offer an important insight into the behavioral impacts of patients with anosmia or those with an impaired olfactory bulb (OB) (e.g., in COVID-19, Alzheimer's disease, Parkinson's disease, etc.).