Sodium nitrite (SN), widely used as a food preservative in processed meat products, is a common dietary additive to which humans are chronically exposed. Beyond its dietary origin, SN is also directly applied as a corrosion inhibitor in coastal infrastructure and industrial wastewater treatment, resulting in its discharge into marine environments. Despite its widespread use, the potential impact of SN exposure on neurodevelopment remains poorly understood. In the current study, we aimed to investigate the neurodevelopmental effects of SN exposure both in vitro and in vivo, spanning from embryonic development to adulthood. First, we found that exposure to SN in primary cultured neurons led to a significant reduction in cell proliferation, increased apoptotic cell death, and marked inhibition of neurite outgrowth. In the developing embryonic mouse brain, SN exposure disrupted radial migration of cortical neurons. Subsequent analysis of adult mice revealed impaired cortical lamination, suggesting a lasting structural consequence of early exposure. Furthermore, synaptic analysis in adult mice demonstrated a significant reduction in cortical synaptic density, indicating compromised neural connectivity. In behavioral assessments, SN-exposed mice exhibited deficits in social behavior and sensory-related responses. In conclusion, our findings suggest that SN exposure adversely affects multiple stages of neurodevelopment, raising concerns about the neurodevelopmental risks.

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