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Its effects on neural remodeling in the hippocampal region, which is vital for cognitive function, remain poorly understood. This study employs single\u2010cell RNA sequencing (scRNA\u2010seq) and high\u2010throughput transcriptomic analysis to elucidate the molecular mechanisms by which propofol impairs hippocampal neural remodeling. Our findings indicate that propofol suppresses the (5\u2010Hydroxytryptamine Receptor 1A\/Glutamate Receptor 2\/Phosphoinositide 3\u2010Kinase Regulatory Subunit 1) HTR1A\/GRIA2\/PIK3R1 signaling pathway, contributing to cognitive dysfunction in mice. In\u00a0vitro experiments reveal that propofol treatment reduces the expression of HTR1A\/GRIA2\/PIK3R1\u2010related factors, decreases neuronal activity and synaptic plasticity, and increases apoptosis and inflammation. In\u00a0vivo experiments demonstrate significant impairments in spatial memory and learning abilities in mice treated with propofol. These results provide new insights into the long\u2010term effects of anesthetic drugs and offer a scientific basis for their judicious use in clinical practice. The study highlights potential strategies and targets for preventing and treating POCD, emphasizing the importance of understanding the molecular mechanisms underlying anesthetic\u2010induced cognitive dysfunction.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70070-fig-0007-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70070","type":"journal-article","created":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T06:59:04Z","timestamp":1745391544000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Molecular Mechanisms of 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