{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T11:07:47Z","timestamp":1779361667504,"version":"3.51.4"},"reference-count":49,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T00:00:00Z","timestamp":1741046400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T00:00:00Z","timestamp":1741046400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003359","name":"Generalitat Valenciana","doi-asserted-by":"publisher","award":["CIPROM2022\/42"],"award-info":[{"award-number":["CIPROM2022\/42"]}],"id":[{"id":"10.13039\/501100003359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003359","name":"Generalitat Valenciana","doi-asserted-by":"publisher","award":["Prometeo CIPROM2022\/42"],"award-info":[{"award-number":["Prometeo CIPROM2022\/42"]}],"id":[{"id":"10.13039\/501100003359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006280","name":"Ministerio de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["PID2020\u2010112972RB\u2010I00"],"award-info":[{"award-number":["PID2020\u2010112972RB\u2010I00"]}],"id":[{"id":"10.13039\/501100006280","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006280","name":"Ministerio de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["PID2023\u20101481023OB\u2010I00"],"award-info":[{"award-number":["PID2023\u20101481023OB\u2010I00"]}],"id":[{"id":"10.13039\/501100006280","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008666","name":"Fundaci\u00f3 la Marat\u00f3 de TV3","doi-asserted-by":"publisher","award":["202032"],"award-info":[{"award-number":["202032"]}],"id":[{"id":"10.13039\/100008666","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01NS097197"],"award-info":[{"award-number":["P01NS097197"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Lafora disease (LD; OMIM#254780) is a rare form of progressive myoclonus epilepsy characterised by the accumulation of insoluble deposits of glycogen in the brain and peripheral tissues. In mouse models of LD, we have identified neuroinflammation as a secondary hallmark of the disease, characterised by increased levels of reactive astrocytes and activated microglia. Our previous work demonstrated that the TNF and IL\u20106 inflammatory signalling pathways are the primary drivers of this neuroinflammatory phenotype. In this work, we aimed to investigate whether TNF and IL\u20106 pathway activation contributes to alterations in the glutamatergic and GABAergic signalling pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed immunofluorescence and western blot analyses on the hippocampus of a mouse model of LD to evaluate potential changes in proteins associated with glutamatergic and GABAergic signalling pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our findings reveal dysregulation in the expression of subunits of excitatory glutamatergic receptors (phospho\u2010GluN2B and GluK2), as well as an increase in the levels of the GABA transporter GAT1. In addition, we detected activated forms of the Src and Lyn protein kinases in the hippocampus. More importantly, these alterations predominantly occur in nonneuronal cells, such as reactive astrocytes and microglia, underscoring the critical involvement of glial cells in the pathophysiology of LD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The observed upregulation of glutamatergic receptor subunits likely amplifies excitatory glutamatergic signalling, whereas the increased expression of GAT1 may reduce the inhibitory GABAergic tone. These changes contribute to the characteristic hyperexcitability of LD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nan.70009","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T17:53:51Z","timestamp":1741715631000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Glial Alterations in the Glutamatergic and GABAergic Signalling Pathways in a Mouse Model of Lafora Disease, a Severe Form of Progressive Myoclonus Epilepsy"],"prefix":"10.1111","volume":"51","author":[{"given":"Rosa","family":"Viana","sequence":"first","affiliation":[{"name":"Instituto de Biomedicina de Valencia Consejo Superior de Investigaciones Cient\u00edficas  Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa","family":"Rubio","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Valencia Consejo Superior de Investigaciones Cient\u00edficas  Valencia Spain"},{"name":"Faculty of Health Science Universidad Europea de Valencia  Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00c1ngela","family":"Campos\u2010Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Valencia Consejo Superior de Investigaciones Cient\u00edficas  Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2399-4103","authenticated-orcid":false,"given":"Pascual","family":"Sanz","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Valencia Consejo Superior de Investigaciones Cient\u00edficas  Valencia Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER) Instituto de Salud Carlos III  Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,3,4]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02863929"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells7080087"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-021-01989-w"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/2470"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1238"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm339"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2023.105998"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24076020"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-014-8747-0"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.11.1251"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr590"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23899"},{"key":"e_1_2_11_14_1","article-title":"Enhanced Sensitivity of Laforin\u2010 and Malin\u2010Deficient Mice to the Convulsant Agent Pentylenetetrazole","volume":"8","author":"Garcia\u2010Cabrero A. M.","year":"2014","journal-title":"Frontiers in Neuroscience"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23956"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-019-01842-z"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2022.105964"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2020.09.015"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-016-0708-2"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2018.12.001"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.741280"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-023-01700-8"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1860-14.2014"},{"issue":"1","key":"e_1_2_11_24_1","first-page":"S35","article-title":"In the Fast Lane: Receptor Trafficking During Status Epilepticus","volume":"8","author":"Naylor D. E.","year":"2023","journal-title":"Epilepsia Open"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24032540"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2021.108615"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004647\u2010199703000\u201000006"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2016.05.012"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.24537"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2007.07.007"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26723"},{"issue":"3","key":"e_1_2_11_32_1","first-page":"783","article-title":"The Role of Glutamate Receptors in Epilepsy","volume":"11","author":"Chen T. S.","year":"2023","journal-title":"Biomedicine"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2022.892497"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.618193"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871527319666200910153827"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22147258"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2012.12.015"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21114096"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2016.03.008"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2019.112959"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcae104"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/neup.12560"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-031-00793-4_10"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.16081"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e3182a4b266"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhy196"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1042\/ebc20220208"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-022-02956-7"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2016.06.041"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes15020171"}],"container-title":["Neuropathology and Applied Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nan.70009","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/nan.70009","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nan.70009","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T10:45:20Z","timestamp":1779360320000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nan.70009"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,4]]},"references-count":49,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1111\/nan.70009"],"URL":"https:\/\/doi.org\/10.1111\/nan.70009","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/NAN.70009\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/NAN.70009\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/NAN.70009\/v1\/review2","asserted-by":"object"}]},"ISSN":["0305-1846","1365-2990"],"issn-type":[{"value":"0305-1846","type":"print"},{"value":"1365-2990","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,4]]},"assertion":[{"value":"2024-10-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70009"}}