Neurobehavioral and neurochemical alterations in female mice following pregestational exposure to SARS-CoV-2 lysate protein

The rapid introduction of new environmental contaminants, including viral agents like SARS-CoV-2, has raised concerns about their indirect effects on non-target terrestrial organisms, especially through contaminated water sources. In this study, we investigated the potential neurotoxic effects of pre-mating and gestational exposure to SARS-CoV-2 lysate protein. Female C57Bl/6 J mice were exposed to a concentration of 20 μg/L for 30 days via drinking water. No significant effects were observed on gestational duration, litter size, or offspring biomass, suggesting no direct impact on reproductive performance. However, exposed females exhibited marked neurobehavioral alterations, including increased anxiety-like behavior in the open field test and altered maternal care dynamics, characterized by hyper-responsiveness and increased nest attendance duration. These behavioral changes were strongly correlated with neurochemical imbalances, including elevated dopamine levels in the olfactory bulb, brain, and hypothalamic-pituitary region. Additionally, cholinesterase activity was significantly altered, with increased acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity in the olfactory bulb and brain, but decreased AChE activity in the hypothalamus-pituitary region, suggesting disrupted cholinergic signaling. Furthermore, oxidative and nitrosative stress markers (ROS and NO) were significantly elevated in mammary and ovarian tissues, indicating a persistent inflammatory response even after exposure cessation. These findings highlight long-term neurochemical and behavioral disruptions following environmentally relevant exposure to SARS-CoV-2 lysate protein, which could compromise neurophysiological homeostasis, stress regulation, and maternal investment in non-target mammals. In natural environments, such alterations may reduce individual fitness and population resilience, emphasizing the need to further investigate the ecotoxicological consequences of viral pollutants on terrestrial organisms.