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The latter causes early onset drug\u2010resistant seizures and enduring cognitive and behavioral deficits. In this pathological context, the implication of astrocytes remains insufficiently explored.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Using a heterozygous\n                      <jats:italic>Scn1a<\/jats:italic>\n                      knockout (\n                      <jats:italic>Scn1a<\/jats:italic>\n                      <jats:sup>+<\/jats:sup>\n                      \/\n                      <jats:sup>\u2212<\/jats:sup>\n                      ) mouse model that recapitulates the DS\u2010human phenotype, we examined astrocyte remodeling at landmark disease stages, as defined by video\u2010electroencephalography and behavioral readouts.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      From initial disease aggravation (postnatal day [PN] 20\u201335) to long\u2010term stabilization (up to PN90),\n                      <jats:italic>Scn1a<\/jats:italic>\n                      <jats:sup>+<\/jats:sup>\n                      \/\n                      <jats:sup>\u2212<\/jats:sup>\n                      mice showed increased hippocampal and cortical glial fibrillary acidic protein (GFAP) transcript and protein levels compared to age\u2010matched control littermates and to an earlier presymptomatic (&lt;PN20) time point. During the aggravation phase in\n                      <jats:italic>Scn1a<\/jats:italic>\n                      <jats:sup>+<\/jats:sup>\n                      \/\n                      <jats:sup>\u2212<\/jats:sup>\n                      mice, astrocyte branching, revealed by GFAP histological analysis and by intracellular delivery of Alexa Fluor 488 in hippocampal slices, was increased but not sustained long\u2010term. Importantly, these disease\u2010stage\u2010dependent astrocyte modifications were not associated with macroscopic hippocampal sclerosis or cortical atrophy. To further study astrocyte remodeling, we used biocytin diffusion following single\u2010astrocyte loading to reveal an expanded astrocyte\u2013astrocyte network in\n                      <jats:italic>Scn1a<\/jats:italic>\n                      <jats:sup>+<\/jats:sup>\n                      \/\n                      <jats:sup>\u2212<\/jats:sup>\n                      mice long\u2010term, along with increased connexin (Cx30 and Cx43) protein levels. An ethidium bromide uptake assay indicated impaired astrocytic hemichannel function in\n                      <jats:italic>Scn1a<\/jats:italic>\n                      <jats:sup>+<\/jats:sup>\n                      \/\n                      <jats:sup>\u2212<\/jats:sup>\n                      mice. Regionally, these long\u2010term cellular and network astrocyte modifications coincided with augmented posttetanic synaptic potentiation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>In DS, astrocytes undergo long\u2010term remodeling independent of tissue damage. We discuss the association between astrocyte network changes and seizures, as well as synaptic and cognitive deficits.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi.70185","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T17:24:26Z","timestamp":1773768266000},"page":"3226-3242","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Long\u2010lasting remodeling of astrocytes in an\n                    <i>Scna1<\/i>\n                    <sup>\n                      <i>+\/\u2212<\/i>\n                    <\/sup>\n                    mouse model of Dravet syndrome"],"prefix":"10.1002","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-8744-8138","authenticated-orcid":false,"given":"Ath\u00e9na\u00efs","family":"Genin","sequence":"first","affiliation":[{"name":"Institute of Functional Genomics, University of Montpellier, CNRS, Inserm  Montpellier 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