{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:47:37Z","timestamp":1787168857695,"version":"build-2736575974"},"reference-count":68,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T00:00:00Z","timestamp":1729036800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82201338"],"award-info":[{"award-number":["82201338"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U23A20421"],"award-info":[{"award-number":["U23A20421"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Postoperative neurocognitive disorders (pNCD) are a common neurological complication, especially in elderly following anesthesia and surgery. Yet, the underlying mechanisms of pNCD remain elusive. This study aimed to investigate the molecular mechanisms that compromise synaptic metaplasticity in pNCD development with a focus on the involvement of Nogo\u201066 receptor 1 (NgR1) in the pathogenesis of pNCD in aged mice. Aged mice subjected to anesthesia and laparotomy surgery exhibited anxiety\u2010like behavior and contextual fear memory impairment. Moreover, the procedure significantly increased NogoA and NgR1 expressions, particularly in the hippocampal CA1 and CA3 regions. This increase led to the depolymerization of F\u2010actin, attributed to the activation of the RhoA\u2010GTPase, resulting in a reduction of dendritic spines and changes in their morphology. Additionally, these changes hindered the efficient postsynaptic delivery of the subunit GluA1 and GluA2 of AMPA receptors (AMPARs), consequently diminishing excitatory neurotransmission in the hippocampus. Importantly, administering the competitive NgR1 antagonist peptide NEP1\u201040 (Nogo\u2010A extracellular peptide residues 1\u201340 amino acids of Nogo\u201066) and Fasudil (a Rho\u2010kinase inhibitor) effectively mitigated synaptic impairments and reversed neurocognitive deficits in aged mice following anesthesia and surgery. Our work indicates that high hippocampal Nogo66\u2010NgR1 signaling disrupts postsynaptic AMPA receptor surface delivery due to F\u2010actin depolymerization in the pathophysiology of pNCD.<\/jats:p>","DOI":"10.1111\/acel.14366","type":"journal-article","created":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T09:05:20Z","timestamp":1729069520000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Hippocampal Nogo66\u2010\n                    <scp>NgR1<\/scp>\n                    signaling activation restricts postsynaptic assembly in aged mice with postoperative neurocognitive disorders"],"prefix":"10.1111","volume":"24","author":[{"given":"Min","family":"Jia","sequence":"first","affiliation":[{"name":"Department of Anaesthesiology, Pain and Perioperative Medicine The First Affiliated Hospital of Zhengzhou University  Zhengzhou 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Anaesthetics, Pain Medicine &amp; Intensive Care, Department of Surgery &amp; Cancer, Faculty of Medicine Imperial College London, Chelsea &amp; Westminster Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mu\u2010huo","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology The Second Affiliated Hospital, Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6785-9627","authenticated-orcid":false,"given":"Jian\u2010jun","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, Pain and Perioperative Medicine The First Affiliated Hospital of Zhengzhou University  Zhengzhou 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