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B6SJLF1\/J adult mice were pretreated with intranasal dantrolene nanoparticles (dantrolene: 5\u2009mg\/kg), daily, Monday to Friday, 5 days per week, for 4 weeks. Afterwards, mice were treated with a single intraperitoneal injection of LPS (5\u2009mg\/kg). Behavioral tests for depression and anxiety were performed 24\u2009h after the one-time LPS injection. Biomarkers for pyroptosis-related inflammation cytokine levels (IL-1\u03b2 and IL-18) in the blood and brain were measured using enzyme-linked immunosorbent assay (ELISA) and immunoblotting, respectively. Changes in primary protein (NLRP3: NLR family pyrin domain containing 3, Caspase-1, N-GSDMD: N-terminal protein gasdermin D) and synapse protein-related (PSD-95 and synaptin-1) activation of inflammatory pyroptosis in mouse brains were measured using immunoblotting. Results indicated that intranasal dantrolene nanoparticle treatment robustly inhibited LPS-induced increases in depressive and anxiety behavior, LPS-induced pathological elevation of IL-1\u03b2 and IL-18 levels in the blood and brain, and LPS-induced activation of pyroptosis. Furthermore, intranasal dantrolene nanoparticles significantly inhibited decreased PSD-95 and synaptin-1 levels. Intranasal dantrolene nanoparticles have demonstrated neuroprotective effects against inflammation-mediated depression and anxiety behaviors and should be studied further as a future effective drug treatment of major depressive or anxiety disorders.<\/jats:p>","DOI":"10.1038\/s41398-026-03816-x","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T08:07:48Z","timestamp":1770106068000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Intranasal dantrolene nanoparticles inhibit lipopolysaccharide-induced depression and anxiety behavior in mice"],"prefix":"10.1038","volume":"16","author":[{"given":"Jia","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piplu","family":"Bhuiyan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacob","family":"Gruttner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren","family":"St. Louis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yutong","family":"Yi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ge","family":"Liang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3077-6574","authenticated-orcid":false,"given":"Huafeng","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,2,3]]},"reference":[{"key":"3816_CR1","doi-asserted-by":"crossref","first-page":"e42","DOI":"10.1016\/S0140-6736(18)32408-5","volume":"393","author":"H Herrman","year":"2019","unstructured":"Herrman H, Kieling C, McGorry P, Horton R, Sargent J, Patel V. 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Antioxid Redox Signal. 2015;22:1111\u201329.","journal-title":"Antioxid Redox Signal"}],"container-title":["Translational Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41398-026-03816-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-026-03816-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-026-03816-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T14:04:09Z","timestamp":1771596249000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41398-026-03816-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,3]]},"references-count":104,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["3816"],"URL":"https:\/\/doi.org\/10.1038\/s41398-026-03816-x","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-6254774\/v1","asserted-by":"object"}]},"ISSN":["2158-3188"],"issn-type":[{"value":"2158-3188","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,3]]},"assertion":[{"value":"18 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 December 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 January 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 February 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Drs. Huafeng Wei and Ge Liang are listed as inventors of patents entitled \u201cIntranasal Administration of Dantrolene for Treatment of Alzheimer\u2019s Disease\u201d in multiple countries by The Trustees of the University of Pennsylvania. Dr. Huafeng Wei is listed as the inventor of the USA patents application repurposing intranasal dantrolene nanoparticles to treat neurodegenerative diseases and psychiatric disorders.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"All methods were performed in accordance with the relevant guidelines and regulations. This study was reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) at the University of Pennsylvania, under approval number 805897. Informed consent was obtained from all participants prior to their inclusion in the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}],"article-number":"104"}}