{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:18Z","timestamp":1787028558915,"version":"build-2736575974"},"reference-count":135,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T00:00:00Z","timestamp":1741132800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008431","name":"Spanish \u201cConsejer\u00eda de Educaci\u00f3n de Castilla y Le\u00f3n\u201d","doi-asserted-by":"publisher","award":["SA072G24"],"award-info":[{"award-number":["SA072G24"]}],"id":[{"id":"10.13039\/501100008431","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Salamanca Research Projects 2023\u20132024","award":["SA072G24"],"award-info":[{"award-number":["SA072G24"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Epilepsy is a multifaceted neurological disorder characterized by recurrent seizures and associated with molecular and immune alterations in key brain regions. The GASH\/Sal (Genetic Audiogenic Seizure Hamster, Salamanca), a genetic model for audiogenic epilepsy, provides a powerful tool to study seizure mechanisms and resistance in predisposed individuals. This study investigates the proteomic and immune responses triggered by audiogenic kindling in the inferior colliculus, comparing non-responder animals exhibiting reduced seizure severity following repeated stimulation versus GASH\/Sal na\u00efve hamsters. To assess auditory pathway functionality, Auditory Brainstem Responses (ABRs) were recorded, revealing reduced neuronal activity in the auditory nerve of non-responders, while central auditory processing remained unaffected. Cytokine profiling demonstrated increased levels of proinflammatory markers, including IL-1 alpha (Interleukin-1 alpha), IL-10 (Interleukin-10), and TGF-beta (Transforming Growth Factor beta), alongside decreased IGF-1 (Insulin-like Growth Factor 1) levels, highlighting systemic inflammation and its interplay with neuroprotection. Building on these findings, a proteomic analysis identified 159 differentially expressed proteins (DEPs). Additionally, bioinformatic approaches, including Gene Set Enrichment Analysis (GSEA) and Weighted Gene Co-expression Network Analysis (WGCNA), revealed disrupted pathways related to metabolic and inflammatory epileptic processes and a module potentially linked to a rise in the threshold of seizures, respectively. Differentially expressed genes, identified through bioinformatic and statistical analyses, were validated by RT-qPCR. This confirmed the upregulation of six genes (Gpc1\u2014Glypican-1; Sdc3\u2014Syndecan-3; Vgf\u2014Nerve Growth Factor Inducible; Cpne5\u2014Copine 5; Agap2\u2014Arf-GAP with GTPase domain, ANK repeat, and PH domain-containing protein 2; and Dpp8\u2014Dipeptidyl Peptidase 8) and the downregulation of two (Ralb\u2014RAS-like proto-oncogene B\u2014and S100b\u2014S100 calcium-binding protein B), aligning with reduced seizure severity. This study may uncover key proteomic and immune mechanisms underlying seizure susceptibility, providing possible novel therapeutic targets for refractory epilepsy.<\/jats:p>","DOI":"10.3390\/ijms26052331","type":"journal-article","created":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T11:20:57Z","timestamp":1741173657000},"page":"2331","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Changes in the Proteomic Profile After Audiogenic Kindling in the Inferior Colliculus of the GASH\/Sal Model of Epilepsy"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5323-4287","authenticated-orcid":false,"given":"Laura","family":"Zeballos","sequence":"first","affiliation":[{"name":"Instituto de Neurociencias de Castilla y Le\u00f3n (INCYL), Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Departamento de Biolog\u00eda Celular y Patolog\u00eda, Facultad de Medicina, Universidad de Salamanca, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5863-2084","authenticated-orcid":false,"given":"Carlos","family":"Garc\u00eda-Peral","sequence":"additional","affiliation":[{"name":"Instituto de Neurociencias de Castilla y Le\u00f3n (INCYL), Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Departamento de Biolog\u00eda Celular y Patolog\u00eda, Facultad de Medicina, Universidad de Salamanca, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9080-2108","authenticated-orcid":false,"given":"Mart\u00edn M.","family":"Ledesma","sequence":"additional","affiliation":[{"name":"Unidad de Conocimiento Traslacional, Hospital de Alta Complejidad del Bicentenario Esteban Echeverr\u00eda, Monte Grande B1842, Argentina"},{"name":"Hospital de Alta Complejidad en Red El Cruce Dr. N. 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Kirchner SAMIC, Florencio Varela B1888, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jer\u00f3nimo","family":"Auzmendi","sequence":"additional","affiliation":[{"name":"Instituto de Fisiopatolog\u00eda y Bioqu\u00edmica Cl\u00ednica (INFIBIOC), Facultad de Farmacia y Bioqu\u00edmica, Universidad de Buenos Aires, Buenos Aires C1417, Argentina"},{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y Tecnol\u00f3gicas (CONICET), Godoy Cruz M2290, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Lazarowski","sequence":"additional","affiliation":[{"name":"Instituto de Fisiopatolog\u00eda y Bioqu\u00edmica Cl\u00ednica (INFIBIOC), Facultad de Farmacia y Bioqu\u00edmica, Universidad de Buenos Aires, Buenos Aires C1417, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1450-7246","authenticated-orcid":false,"given":"Dolores E.","family":"L\u00f3pez","sequence":"additional","affiliation":[{"name":"Instituto de Neurociencias de Castilla y Le\u00f3n (INCYL), Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Departamento de Biolog\u00eda Celular y Patolog\u00eda, Facultad de Medicina, Universidad de Salamanca, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,5]]},"reference":[{"key":"ref_1","first-page":"735","article-title":"Kindling model of epilepsy","volume":"16","author":"Kulkarni","year":"1994","journal-title":"Methods Find. 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