{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T07:30:27Z","timestamp":1793345427381,"version":"4.5.0"},"reference-count":32,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82572460"],"award-info":[{"award-number":["82572460"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Repeated sevoflurane exposure has been associated with postoperative cognitive dysfunction, particularly in the aged population, yet the underlying mechanisms remain unclear. This study aimed to investigate whether PTEN nuclear translocation mediates sevoflurane\u2010induced hippocampal synaptic and cognitive deficits in aged female mice, and whether activation of ER\u03b1 can mitigate these effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Aged female mice were exposed to repeated sevoflurane, followed by assessment of PTEN subcellular localization using Western blot and immunofluorescence. Synaptic integrity was evaluated by PSD95 and SYP expression and dendritic spine density in the hippocampal CA1 region. Cognitive performance was assessed with the Morris water maze and Y\u2010maze tests. PTEN nuclear translocation was inhibited using AAV\u2010PTEN\u2010K13R, while Er\u03b1 activation was achieved using PPT, and its effects were further evaluated in the presence of AAV\u2010shAagab, a regulator of PTEN nuclear translocation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Repeated sevoflurane exposure significantly increased nuclear PTEN and decreased cytoplasmic PTEN, reduced PSD95 and synaptophysin expression, decreased dendritic spine density, and impaired spatial learning and working memory. Inhibition of PTEN nuclear translocation via AAV\n                      <jats:sub>PTEN\u2010K13R<\/jats:sub>\n                      restored synaptic protein levels, spine density, and cognitive performance. Er\u03b1 activation with PPT suppressed PTEN nuclear translocation, preserved synaptic structure, and improved cognitive function, whereas AAV\n                      <jats:sub>shAagab<\/jats:sub>\n                      largely abolished these protective effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study demonstrates that PTEN nuclear translocation mediates sevoflurane\u2010induced synaptic and cognitive deficits in aged female mice, and that Er\u03b1 activation mitigates these effects by modulating PTEN localization. These findings suggest that Er\u03b1\u2010mediated regulation of PTEN may represent a potential therapeutic pathway for mitigating anesthesia\u2010related cognitive dysfunction in the elderly.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.70959","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T11:45:52Z","timestamp":1780055152000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>ER\u03b1<\/scp>\n                    Agonist Protects Aged Female Mice From Sevoflurane Neurotoxicity via\n                    <scp>PTEN<\/scp>\n                    Nuclear Translocation"],"prefix":"10.1002","volume":"32","author":[{"given":"Xudong","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine University of Electronic Science and Technology of China  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Endoscopy Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine University of Electronic Science and Technology of China  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingqing","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Tianjin Medical University General Hospital, Tianjin Institute of Anesthesiology  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiquan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine University of Electronic Science and Technology of China  Chengdu Sichuan 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