{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:45:02Z","timestamp":1791409502100,"version":"4.3.3"},"reference-count":51,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T00:00:00Z","timestamp":1752105600000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012542","name":"Sichuan Provincial Science and Technology Support Program","doi-asserted-by":"publisher","award":["2024YFHZ0359"],"award-info":[{"award-number":["2024YFHZ0359"]}],"id":[{"id":"10.13039\/100012542","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":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Neuropsychiatric symptoms, such as anxiety and depression, are prevalent during the prodromal phase of Alzheimer's disease (AD). Social isolation (SI) has been implicated as a potential exacerbating factor for emotional disturbances in AD pathogenesis. Despite the well\u2010established role of oxytocin (OXT) in regulating social behavior and mental health, its function and mechanisms in alleviating AD\u2010related psychiatric symptoms remain poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>We utilized a 12\u2010week SI model to assess its effects on anxiety, depression\u2010like behaviors, and social cognition in early\u2010stage AD mice. Through immunofluorescence, enzyme\u2010linked immunosorbent assay, and 16S rDNA sequencing, we examined the changes in AD pathology and gut microbiota composition induced by SI, as well as the effects of OXT intervention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our findings revealed that SI markedly intensified anxiety\u2010like behaviors, depression\u2010like phenotypes, and social cognitive impairments in AD mice. Mechanistically, SI resulted in decreased OXT levels and upregulated OXT receptor expression while also exacerbating AD\u2010related pathological features, including increased A\u03b2 plaque deposition, aberrant microglial proliferation, and reduced PSD\u201095 expression in the prefrontal cortex. Furthermore, SI induced significant changes in gut microbiota composition. OXT intervention demonstrated therapeutic efficacy by mitigating behavioral deficits, alleviating AD\u2010related pathological damage, and restoring gut microbiota homeostasis in SI AD mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These results underscore OXT as a promising therapeutic avenue for AD, offering novel insights into treatment strategies and identifying potential therapeutic targets through the restoration of gut homeostasis and mitigation of pathological processes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.70511","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T07:10:37Z","timestamp":1752131437000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Oxytocin Intervention Mitigates Pathological and Behavioral Impairments in\n                    <scp>APP<\/scp>\n                    \/\n                    <scp>PS1<\/scp>\n                    Mice Subjected to Early Social Isolation"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4276-752X","authenticated-orcid":false,"given":"Junjun","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Sichuan Provincial People's Hospital, MOE Key Lab for Neuroinformation, School of Life Science and Technology University of Electronic Science and Technology of China  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Sichuan Provincial People's Hospital, MOE Key Lab for Neuroinformation, School of Life Science and Technology University of Electronic Science and Technology of China  Chengdu 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