Vitamin K2 prevents postoperative cognitive impairments, anxiety-like behavior, and motor dysfunction induced by nanoplastics in young adult mice.

Nanoplastics (NPs) pollution poses serious health risks and worsens various diseases. However, its role in postoperative complications, particularly perioperative neurocognitive disorders (PNDs), remains unclear. While PNDs are common in the elderly and rare in young adults, lifelong and cumulative exposure to NPs may increase the susceptibility of young individuals to PNDs. Herein, surgery alone caused no neurobehavioral impairments in young adult male and female mice and exposed to NPs alone exhibited anxiety-like behavior. However, young adult male and female mice exposed to NPs for 30 days, with surgery on day 31, exhibited postoperative cognitive impairment and anxiety-like behavior associated with PNDs, along with motor dysfunction. Vitamin K2 (VK2) pretreatment mitigated the behavioral impairments induced by nanoplastics and surgery (NS) exposure. RNA sequencing and bioinformatics analysis of male mice revealed that NS activated inflammatory and cell death pathways in the hippocampus (HIP), with upregulation of key genes such as Selp, Timp1, and Emp3. In the medial prefrontal cortex (mPFC), NS exposure upregulated pathways associated with neuronal apoptosis, reactive oxygen species (ROS) processes, and cell death, accompanied by dysregulated expression of genes such as Tert, Adam8, Esr2, and Emp3. VK2 pretreatment rescued these molecular alterations by normalizing the expression of key genes. Additionally, VK2 reduced levels of IL-1β, TNF-α, IL-6, ROS and MDA, while attenuating brain cell apoptosis and microglial activation in the HIP and mPFC of male mice. This study demonstrates that NS exposure increases the susceptibility of young adults to PNDs and highlights VK2 as a promising preventive strategy. Moreover, it elucidates critical molecular pathways and genes, providing a solid foundation for future research.