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This open-access study evaluated whether sciatic nerve stimulation (SNS) mitigates stress-induced depressive-like behaviors and memory deficits in C57BL/6 mice using the water immersion restraint stress paradigm. Behavioral assays examined anxiety, depression-like behavior, locomotion, and memory, while hippocampal astrocytic dysfunction and cellular senescence were measured by GFAP and SA-β-gal staining and senescence markers p16 and p21. SNS improved cognitive function and reduced depression-like behavior, restoring GFAP and lowering senescence burden. Vitamin C reduced senescence and depressive behavior but did not rescue memory deficits or GFAP expression, suggesting SNS effects extend beyond anti-senescence.",{"@graph":69,"@context":126},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/sciatic-nerve-stimulation-mitigates-depression-like-behaviors-and-memory-deficits-in-stressed-mice/458873/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/sciatic-nerve-stimulation-mitigates-depression-like-behaviors-and-memory-deficits-in-stressed-mice/458873.png","ImageObject",300,407,{"name":92,"@type":93},"pop 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biological effects did SNS have in the hippocampus?",{"text":121,"@type":113},"SNS restored hippocampal GFAP expression and reduced senescence indicators, including SA-β-gal-positive cell accumulation and the expression of p16 and p21.",{"name":123,"@type":110,"acceptedAnswer":124},"Why did vitamin C not replicate SNS benefits on memory and astrocytic markers?",{"text":125,"@type":113},"Vitamin C alleviated stress-induced hippocampal senescence and depressive behavior, but it failed to reverse memory deficits or restore GFAP expression, indicating SNS benefits extend beyond anti-senescent actions.","https://schema.org",{"og:url":83,"og:type":128,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":130,"canonical":83},"index,follow",{"doc_id":132,"site_id":62},458873,1791070534,{"code":4,"msg":5,"data":135},{"doc_id":132,"user_id":136,"nickname":92,"user_avatar":137,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":138,"file_id":139,"file_url":140,"file_type":141,"file_size":142,"view_count":34,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":44,"language":143,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":144,"faqs":145,"seo_title":146,"seo_description":67,"update_tm":147,"read_time":148,"preview_page_count":4},962090760408,"https://ap-avatar.wpscdn.com/davatar_085a072bc5b1113ac321206ff7593b45","The Kaohsiung Journal of Medical Sciences  \nORIGINAL ARTICLE  OPEN ACCESS   \nSciatic Nerve Stimulation Mitigates Depression-Like Behaviors and Memory Deficits in Stressed Mice  \nChih-Hao Tien1 | Pei-Wen Chen2 | Ya-Hsin Hsiao3,4 | Chia-En Wong1,5 | Ming-Tse Wu4 | Ying-Fei Chen2 | Kuo-Chang Huang6 | Po-Hsuan Lee1  | Kun-Chia Chang7,8  | Heng-Juei Hsu9 | Jung-Shun Lee1,2,4,5   \n1Division of Neurosurgery, Department of Surgery, National Cheng Kung University Hospital, Tainan, Taiwan | 2Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, Taiwan | 3Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan | 4Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan | 5Center of Transformative Bioelectronic Medicine, National Cheng Kung University, Tainan, Taiwan | 6Department of Neurosurgery, Chiayi Christian Hospital, Chiayi, Taiwan | 7Department of General Psychiatry, Jianan Psychiatric Center, Ministry of Health and Welfare, Tainan, Taiwan | 8Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan | 9Department of  \nNeurosurgery, Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation), Tainan, Taiwan Correspondence: Jung-Shun Lee ([nslee1218@gmail.com](nslee1218@gmail.com))  \nReceived: 18 February 2025 | Revised: 15 July 2025 | Accepted: 28 July 2025  \nFunding: This study is supported by National Cheng Kung University Hospital, Tainan, Taiwan,(No: NCKUH-11302022) .  \nKeywords: depression | memory deficit | sciatic nerve stimulation | stress  \nABSTRACT  \nStress 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-induced 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-related behavioral deficits. Behavioral tests assessed locomotion, anxiety, depression-like behavior, and memory. Astrocytic disruption and cellular senescence in the hippocampus were assessed using glial fibrillary acidic protein (GFAP) immunostaining and senescence-associated β-galactosidase (SA-β-gal) staining. SNS at 20 Hz significantly improved cognitive function and reduced depression-like behavior in WIRS-treated mice. It also restored hippocampal GFAP expression and decreased both SA-β-gal-positive 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-mediated effects, we administered the anti-senescence agent vitamin C to WIRS mice. While vitamin C alleviated stress-induced 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-senescent 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-related depression and cognitive decline. Future studies should explore its clinical translation and broader therapeutic potential.  \n\n| Abbreviations: CA, cornu ammonis; DBS, deep brain stimulation; DG, dentate gyrus; ECT, electroconvulsive therapy; FST, forced swimming test; GFAP, glial fibrillary acidic protein; OLRT, object location recognition test; PBST, phosphate-buffered saline containing 0.3% Triton X-100; PSD, post-SNS day; rTMS, repetitive transcranial magnetic stimulation; SA-β-gal, senescence-associated β-galactosidase; SD, standard deviations; S","cbCaipqveHDEbHH0","https://ap.wps.com/l/cbCaipqveHDEbHH0","pdf",1321765,"English","# Abstract\n## Introduction\n## Materials and Methods\n## Results\n## Discussion\n## Conclusion","[{\"question\":\"What is the main goal of this study on sciatic nerve stimulation (SNS)?\",\"answer\":\"The study investigates whether SNS can reduce stress-induced depression-like behaviors and memory deficits by targeting hippocampal astrocytic dysfunction and cellular senescence.\"},{\"question\":\"How were depression-like behavior and memory assessed in stressed mice?\",\"answer\":\"C57BL/6 mice underwent the water immersion restraint stress paradigm, and behavioral tests measured locomotion, anxiety, depression-like behavior, and memory.\"},{\"question\":\"What biological effects did SNS have in the hippocampus?\",\"answer\":\"SNS restored hippocampal GFAP expression and reduced senescence indicators, including SA-β-gal-positive cell accumulation and the expression of p16 and p21.\"},{\"question\":\"Why did vitamin C not replicate SNS benefits on memory and astrocytic markers?\",\"answer\":\"Vitamin C alleviated stress-induced hippocampal senescence and depressive behavior, but it failed to reverse memory deficits or restore GFAP expression, indicating SNS benefits extend beyond anti-senescent actions.\"}]","Sciatic Nerve Stimulation Mitigates Depression-Like Behaviors and Memory Deficits in Stressed Mice | PDF",1790754667,23]