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Although lipid disturbances are implicated in epileptogenesis, how astrocyte\u2010associated lipid responses relate to\u00a0hippocampal remodeling remains poorly understood. Here, human TLE and kainic acid (KA)\u2010treated mouse transcriptomic datasets identified ATP\u2010binding cassette transporter A1 (ABCA1)\/Abca1 as a nominal astrocyte\u2010associated candidate, while KA\u2010 and pilocarpine\u2010induced status epilepticus\u00a0(SE)\u00a0elicited astrocyte\u2010associated ABCA1\/apolipoprotein E (APOE) responses. Ectopic granule cells and immature neurons accumulated in the hilus and were spatially associated with ABCA1\u2010positive cells, including astrocytic profiles; perilipin 2 (PLIN2)\u2010positive puncta were nearby.\u00a0Pretreatment with the retinoid X receptor (RXR) agonist bexarotene increased hippocampal ABCA1 expression, delayed severe KA\u2010induced behavioral seizure onset, and was associated with fewer chronic spontaneous seizures and reduced ectopic neuronal accumulation. Post\u2010SE bexarotene administration was associated with lower\u00a0seizure frequency, ectopic neuronal accumulation, and astrocytic marker\u2010positive cell densities. Multi\u2010omic profiling identified bexarotene\u2010associated metabolic and lipidomic changes; transmission electron microscopy (TEM) showed a smaller mean hilar neuronal lipid\u2010droplet area per image, and protein analyses identified early changes in p38 and extracellular signal\u2010regulated kinase 1\/2 (Erk1\/2) phosphorylation. Together, these findings\u00a0warrant further investigation of astrocyte\u2010associated lipid pathways as potential therapeutic targets in epilepsy\u2010associated hippocampal remodeling.<\/jats:p>","DOI":"10.1002\/advs.78329","type":"journal-article","created":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T14:25:03Z","timestamp":1792333503000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Astrocyte\u2010Associated ABCA1\/APOE Responses Accompany Hippocampal Lipid Remodeling and Ectopic Neuronal Accumulation During Epileptogenesis"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1013-1197","authenticated-orcid":false,"given":"Lu","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Neurology Beijing Tiantan Hospital Capital Medical University  Beijing China"},{"name":"China National Clinical Research Center For Neurological Diseases Beijing Tiantan Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5403-6097","authenticated-orcid":false,"given":"Xiao\u2010Rui","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Neurology Beijing Tiantan Hospital Capital Medical University  Beijing China"},{"name":"China National Clinical Research Center For Neurological Diseases Beijing Tiantan Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2010Yi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology Beijing Tiantan Hospital Capital Medical University  Beijing China"},{"name":"National\u2010Local Joint Engineering Research Center For Drug Research and Development (R&amp;D) of Neurodegenerative Diseases Dalian Medical University  Dalian 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Research Center For Neurological Diseases Beijing Tiantan Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun\u2010Min","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology Beijing Tiantan Hospital Capital Medical University  Beijing China"},{"name":"China National Clinical Research Center For Neurological Diseases Beijing Tiantan Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An\u2010Chen","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Neurology Beijing Tiantan Hospital Capital Medical University  Beijing China"},{"name":"China National Clinical Research Center For Neurological Diseases Beijing Tiantan Hospital Capital Medical University  Beijing 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