{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T15:39:13Z","timestamp":1767800353533,"version":"3.49.0"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:00Z","timestamp":1756166400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004844","name":"National Cheng Kung University Hospital","doi-asserted-by":"publisher","award":["NCKUH\u201011302022"],"award-info":[{"award-number":["NCKUH\u201011302022"]}],"id":[{"id":"10.13039\/501100004844","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Kaohsiung J of Med Scie"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Stress causes depression and cognitive decline. With limitations in pharmacotherapy, sciatic nerve stimulation (SNS) offers a promising nondrug alternative. This study aimed to explore the therapeutic efficacy of SNS in mitigating stress\u2010induced depressive behaviors and memory deficits by focusing on astrocytic dysfunction and cellular senescence in the hippocampus. C57BL\/6 mice were subjected to the water immersion restraint stress (WIRS) paradigm to induce stress\u2010related behavioral deficits. Behavioral tests assessed locomotion, anxiety, depression\u2010like behavior, and memory. Astrocytic disruption and cellular senescence in the hippocampus were assessed using glial fibrillary acidic protein (GFAP) immunostaining and senescence\u2010associated \u03b2\u2010galactosidase (SA\u2010\u03b2\u2010gal) staining. SNS at 20\u2009Hz significantly improved cognitive function and reduced depression\u2010like behavior in WIRS\u2010treated mice. It also restored hippocampal GFAP expression and decreased both SA\u2010\u03b2\u2010gal\u2010positive cell accumulation and the expression of senescence markers p16 and p21, suggesting an attenuation of cellular senescence. To further explore the link between cellular senescence and SNS\u2010mediated effects, we administered the anti\u2010senescence agent vitamin C to WIRS mice. While vitamin C alleviated stress\u2010induced hippocampal senescence and depressive behavior, it failed to reverse memory deficits or restore GFAP expression, indicating that the benefits of SNS extend beyond its anti\u2010senescent actions. In summary, SNS effectively counteracts the neurobehavioral consequences of chronic stress by targeting astrocytic dysfunction and cellular senescence. These findings support SNS as a promising, nonpharmacological strategy for treating stress\u2010related depression and cognitive decline. Future studies should explore its clinical translation and broader therapeutic potential.<\/jats:p>","DOI":"10.1002\/kjm2.70091","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T07:17:59Z","timestamp":1756192679000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sciatic Nerve Stimulation Mitigates Depression\u2010Like Behaviors and Memory Deficits in Stressed Mice"],"prefix":"10.1002","volume":"42","author":[{"given":"Chih\u2010Hao","family":"Tien","sequence":"first","affiliation":[{"name":"Division of Neurosurgery, Department of Surgery National Cheng Kung University Hospital  Tainan Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pei\u2010Wen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Anatomy, College of Medicine National Cheng Kung University  Tainan 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