Role of Hippocampal Glutamatergic Synaptic Alterations in Sevoflurane‐Induced Cognitive Dysfunction in Aged Mice

ABSTRACT Aims Perioperative neurocognitive disorders (PND), including postoperative delirium (POD) and postoperative cognitive dysfunction (POCD), are common following anesthesia and surgery in older patients and significantly increase morbidity and mortality. However, the underlying mechanism of PND is unclear. Our study aims to analyze the differentially expressed genes (DEGs) in excitatory neurons and investigate the role of hippocampal glutamatergic synaptic alterations in sevoflurane‐induced cognitive dysfunction in aged mice. Methods We performed single‐nucleus RNA sequencing (snRNA‐seq) technology to examine the alterations of excitatory neurons in hippocampus induced by sevoflurane in aged mice. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of DEGs were performed in excitatory neurons. At last, immunofluorescence staining was used to validate sevoflurane‐induced alternation of glutamatergic synapses in the hippocampus of aged mice. Results This study demonstrates that DEGs in excitatory neurons are associated with reduction of glutamatergic synapses and cognitive dysfunction. After immunofluorescence staining validation, we also confirmed that sevoflurane anesthesia decreased the density of glutamatergic synapses in the hippocampus of aged mice. Conclusions Our findings demonstrated a key role of hippocampal glutamatergic synaptic alterations in sevoflurane‐induced cognitive dysfunction in aged mice.