Changes in the Proteomic Profile After Audiogenic Kindling in the Inferior Colliculus of the GASH/Sal Model of Epilepsy

• Autores: Zeballos, Laura; García Peral, Carlos; Ledesma, Martín M.; Auzmendi, Jerónimo Andrés; Lazarowski, Alberto; López, Dolores E.
• Año de publicación: 2025
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: EPILEPSY; AUDIOGENIC SEIZURE; GASH SAL; INFLAMATION
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

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 naïve 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—Glypican-1; Sdc3—Syndecan-3; Vgf—Nerve Growth Factor Inducible; Cpne5—Copine 5; Agap2—Arf-GAP with GTPase domain, ANK repeat, and PH domain-containing protein 2; and Dpp8—Dipeptidyl Peptidase 8) and the downregulation of two (Ralb—RAS-like proto-oncogene B—and S100b—S100 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.
Fil: Zeballos, Laura. Universidad de Salamanca; España
Fil: García Peral, Carlos. Universidad de Salamanca; España
Fil: Ledesma, Martín M.. Gobierno de la Provincia de Buenos Aires. Hospital de Alta Complejidad del Bicentenario Esteban Echeverria; . Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; Argentina
Fil: Auzmendi, Jerónimo Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Fisiopatología y Bioquímica Clínica; Argentina
Fil: Lazarowski, Alberto. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Fisiopatología y Bioquímica Clínica; Argentina
Fil: López, Dolores E.. Universidad de Salamanca; España