{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T03:45:05Z","timestamp":1785296705460,"version":"3.55.0"},"reference-count":59,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T00:00:00Z","timestamp":1750377600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Education","award":["PRIN-2022: Prot. 2022PFFPBL"],"award-info":[{"award-number":["PRIN-2022: Prot. 2022PFFPBL"]}]},{"name":"Italian Ministry of Education","award":["2018\/R\/11"],"award-info":[{"award-number":["2018\/R\/11"]}]},{"name":"Nando and Elsa Peretti Foundation 2019","award":["PRIN-2022: Prot. 2022PFFPBL"],"award-info":[{"award-number":["PRIN-2022: Prot. 2022PFFPBL"]}]},{"name":"Nando and Elsa Peretti Foundation 2019","award":["2018\/R\/11"],"award-info":[{"award-number":["2018\/R\/11"]}]},{"name":"FISM-Fondazione Italiana Sclerosi Multipla","award":["PRIN-2022: Prot. 2022PFFPBL"],"award-info":[{"award-number":["PRIN-2022: Prot. 2022PFFPBL"]}]},{"name":"FISM-Fondazione Italiana Sclerosi Multipla","award":["2018\/R\/11"],"award-info":[{"award-number":["2018\/R\/11"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>It has been demonstrated that S100B actively participates in neuroinflammatory processes of different diseases of the central nervous system (CNS), such as experimental autoimmune encephalomyelitis (EAE), a recognized animal model for multiple sclerosis (MS). The inhibition of S100B activity using pentamidine and of S100B synthesis using arundic acid are able to determine an amelioration of the clinical and pathologic parameters of MS with milder and delayed symptoms. This study further goes in detail on the role of S100B, and in particular of astrocytic S100B, in these neuroinflammatory processes. To this aim, we used a model of S100B knockout (KO) mice. As expected, S100B protein levels were significantly reduced in the S100B KO mouse strain resulting in an amelioration of clinical and pathological parameters (clinical and morphological analyses). To dissect the potential mechanisms that could explain the role of S100B in the development of EAE, we sorted, cultured, and compared glial subpopulations (astrocytes, oligodendrocytes, and microglia) derived from S100B KO and wild type mice, through flow cytometric panels and ELISA. Glial cells were analyzed for proinflammatory molecules showing a significant reduction of TNF\u03b1 protein in mice where S100B was silenced. To dissect the role of S100B in MS, we cultured astrocytes and microglial cells magnetically sorted and enriched from the brains of EAE-affected animals, both from KO and wild type animals. Both genetic silencing of S100B and pharmacological inhibition with S100B-targeting compounds demonstrated a direct impact on specific subpopulations of astrocytes (mainly), oligodendrocytes, and microglia. The present results further individuate astrocytic S100B as a key factor and as a potential therapeutic target for EAE neuroinflammatory processes.<\/jats:p>","DOI":"10.3390\/ijms26135948","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T11:23:24Z","timestamp":1750418604000},"page":"5948","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Effect on Different Glial Cell Types of S100B Modulation in Multiple Sclerosis Experimental Models"],"prefix":"10.3390","volume":"26","author":[{"given":"Maria","family":"De Carluccio","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Universit\u00e0 Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6608-3388","authenticated-orcid":false,"given":"Gabriele","family":"Di Sante","sequence":"additional","affiliation":[{"name":"Department of Surgery and Medicine, Institute of Human, Clinical and Forensic Anatomy, P.le L Severi 1, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4615-7826","authenticated-orcid":false,"given":"Maria Elisabetta","family":"Clementi","sequence":"additional","affiliation":[{"name":"Istituto di Scienze e Tecnologie Chimiche \u201cGiulio Natta\u201d SCITEC-CNR, Largo F. Vito 1, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariangela","family":"Ruggirello","sequence":"additional","affiliation":[{"name":"Department of Surgery and Medicine, Institute of Human, Clinical and Forensic Anatomy, P.le L Severi 1, 06132 Perugia, Italy"},{"name":"Department of Translational Medicine and Surgery, Section of General Pathology, Universit\u00e0 Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1047-4210","authenticated-orcid":false,"given":"Anna Maria","family":"Stabile","sequence":"additional","affiliation":[{"name":"Department of Surgery and Medicine, Institute of Human, Clinical and Forensic Anatomy, P.le L Severi 1, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4740-2504","authenticated-orcid":false,"given":"Alessandra","family":"Pistilli","sequence":"additional","affiliation":[{"name":"Department of Surgery and Medicine, Institute of Human, Clinical and Forensic Anatomy, P.le L Severi 1, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Marini","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Translational Medicine, Universit\u00e0 of Rome \u201cTor Vergata\u201d, Via Montpellier 1, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2900-6399","authenticated-orcid":false,"given":"Vincenzo","family":"Romano Spica","sequence":"additional","affiliation":[{"name":"Department of Movement, Human and Health Sciences, Laboratory of Epidemiology and Biotechnologies, University of Rome \u201cForo Italico\u201d, Piazza Lauro De Bosis 6, 00135 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Rende","sequence":"additional","affiliation":[{"name":"Department of Surgery and Medicine, Institute of Human, Clinical and Forensic Anatomy, P.le L Severi 1, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7455-4290","authenticated-orcid":false,"given":"Francesco","family":"Ria","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine and Surgery, Section of General Pathology, Universit\u00e0 Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy"},{"name":"Department of Laboratory and Hematological Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Agostino Gemelli 1-8, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2546-0532","authenticated-orcid":false,"given":"Fabrizio","family":"Michetti","sequence":"additional","affiliation":[{"name":"Department of Movement, Human and Health Sciences, Laboratory of Epidemiology and Biotechnologies, University of Rome \u201cForo Italico\u201d, Piazza Lauro De Bosis 6, 00135 Rome, Italy"},{"name":"Department of Medicine, \u201cLibera Universit\u00e0 Mediterranea\u201d University, 70010 Casamassima, Italy"},{"name":"Genes, Via Venti Settembre 118, 00187 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ponath, G., Park, C., and Pitt, D. (2018). The Role of Astrocytes in Multiple Sclerosis. Front. 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