{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T22:18:25Z","timestamp":1792189105247,"version":"4.4.0"},"reference-count":84,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["PNRR\u2010MR1\u20102022\u201012376430"],"award-info":[{"award-number":["PNRR\u2010MR1\u20102022\u201012376430"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Objective<\/jats:title>\n                    <jats:p>\n                      Lafora disease (LD) is a rare progressive disorder caused by mutations in the\n                      <jats:italic>EPM2A<\/jats:italic>\n                      or\n                      <jats:italic>EPM2B<\/jats:italic>\n                      genes, characterized by the accumulation of Lafora bodies, drug\u2010resistant epilepsy, and cognitive decline. To investigate the early molecular mechanisms of LD, we studied electrophysiological changes in the dentate gyrus (DG) of the\n                      <jats:italic>Epm2a<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>R240X<\/jats:italic>\n                      <\/jats:sup>\n                      knock\u2010in mouse model at various ages.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Electrophysiological recordings measured neuronal membrane properties, epileptic\u2010like activity, epileptic thresholds, and synaptic plasticity in\n                      <jats:italic>Epm2a<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>R240X<\/jats:italic>\n                      <\/jats:sup>\n                      mice at 1, 3, and 12\u2009months. We also employed Periodic Acid\u2013Schiff (PAS) diastase staining, immunofluorescence, and Western blotting to detect Lafora bodies, amyloid beta deposition, and the expression of glutamate receptor subunits.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Epileptic\u2010like activity began at 1\u2009month and intensified with age. Aberrant long\u2010term potentiation (LTP) appeared at 3\u2009months and worsened by 12\u2009months. Notably, cannabidiol treatment reduced excitability and restored LTP in older mice, suggesting its potential therapeutic value.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>The reversibility of synaptopathy, even at advanced stages, reinforces the importance of early detection of hyperexcitability and the development of effective therapeutic approaches.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.70024","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T07:06:16Z","timestamp":1766041576000},"page":"1449-1468","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Neuronal hyperexcitability: A key to unraveling hippocampal synaptic dysfunction in Lafora disease"],"prefix":"10.1111","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4862-4221","authenticated-orcid":false,"given":"Cinzia","family":"Costa","sequence":"first","affiliation":[{"name":"Section of Neurophysiopathology S.M. della Misericordia Hospital, Section of Neurology and Laboratory of Experimental Neurology, Department of Medicine and Surgery University of Perugia  Perugia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Bellingacci","sequence":"additional","affiliation":[{"name":"Section of Physiology and Biochemistry, Department of Medicine and Surgery University of Perugia  Perugia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacopo","family":"Canonichesi","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Neurology, Department of Medicine and Surgery University of Perugia  Perugia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Imperatore","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Neurology, Department of Medicine and Surgery University of Perugia  Perugia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6731-2343","authenticated-orcid":false,"given":"Anna Aurora","family":"Taddei","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Neurology, Department of Medicine and Surgery University of Perugia  Perugia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1807-7538","authenticated-orcid":false,"given":"Luis","family":"Zafra\u2010Puerta","sequence":"additional","affiliation":[{"name":"Laboratory of Neurology Instituto de Investigaci\u00f3n Sanitaria\u2010Fundaci\u00f3n Jim\u00e9nez D\u00edaz, Universidad Aut\u00f3noma de Madrid (IIS\u2010FJD, UAM)  Madrid Spain"},{"name":"PhD Program in Neuroscience Universidad Auton\u00f2ma de Madrid\u2010Cajal Institute  Madrid Spain"},{"name":"Fondazione Malattie Rare Mauro Baschirotto BIRD Onlus  Longare Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nerea","family":"Iglesias\u2010Cabeza","sequence":"additional","affiliation":[{"name":"Laboratory of Neurology Instituto de Investigaci\u00f3n Sanitaria\u2010Fundaci\u00f3n Jim\u00e9nez D\u00edaz, Universidad Aut\u00f3noma de Madrid (IIS\u2010FJD, UAM)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Prontera","sequence":"additional","affiliation":[{"name":"Medical Genetics and Rare Diseases Unit, Maternal\u2010Infantile Department S.M. 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