NOD1 contributes to reduced postoperative memory performance induced by preoperative sleep deprivation and anesthesia/surgery in mice

Background Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) recognizes bacterial peptidoglycan fragments and regulates inflammatory responses. However, its role in perioperative memory performance remains unclear. This study investigated the involvement of NOD1 in the hippocampal CA1 region and gut-related alterations in postoperative memory performance.Methods Mice underwent preoperative acute sleep deprivation, anesthesia/surgery, or both. Behavioral testing, hippocampal transcriptomics, fecal metagenomic sequencing, western blotting and immunofluorescence were performed. Iba1 promoter-driven NOD1 knockdown in the hippocampal CA1 region and Lyz1-/- mice were used to investigate the involvement of NOD1 in the hippocampal CA1 region and intestinal lysozyme, respectively.Results No statistically significant synergistic or facilitating interaction between sleep deprivation and anesthesia/surgery was detected. Significant main effects were observed in the object location memory test (OLMT) and novel object recognition test (NORT), whereas the Y-maze showed only a post hoc difference between the SD + Sur and Con groups. The reduced postoperative memory performance was accompanied by increased NOD1 expression, an elevated p-p65/p65 ratio and Iba1-related changes in the hippocampal CA1 region, together with gut microbiota dysbiosis and increased ileal expression of lysozyme. Both Iba1 promoter-driven NOD1 knockdown and Lyz1 deficiency reduced NOD1 expression, p65 phosphorylation and Iba1-related changes. Iba1 promoter-driven NOD1 knockdown improved memory performance, whereas Lyz1 deficiency improved OLMT and Y-maze performance and showed a trend toward improved NORT performance.Conclusions Hippocampal CA1 NOD1, gut microbiota dysbiosis and ileal lysozyme may contribute to reduced postoperative memory performance associated with preoperative acute sleep deprivation and anesthesia/surgery.