{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T01:58:25Z","timestamp":1781143105816,"version":"3.54.1"},"reference-count":46,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T00:00:00Z","timestamp":1761350400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T00:00:00Z","timestamp":1761350400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["1136322N"],"award-info":[{"award-number":["1136322N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["1140619N"],"award-info":[{"award-number":["1140619N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["11K0122N"],"award-info":[{"award-number":["11K0122N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["1282125N"],"award-info":[{"award-number":["1282125N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["1S84218N"],"award-info":[{"award-number":["1S84218N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Temporal lobe epilepsy (TLE) is characterized by recurrent, focal seizures, and up to one third of patients are not adequately treated by the current standard of care. This emphasizes the need for continued research into disease mechanisms and potential novel treatment strategies. In TLE, astrocytes transition to a reactive phenotype and we here investigate how modulation of their activity affects spontaneous seizures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used Gq\u2010coupled Designer Receptors Exclusively Activated by Designer Drugs (Gq\u2010DREADD) to target reactive astrocytes in the intrahippocampal kainic acid (IHKA) mouse model for TLE. Through immunohistochemistry, we first verified the astrocyte\u2010specific expression of Gq\u2010DREADDs and we quantified astrocytic c\u2010Fos expression upon Gq\u2010DREADD activation. Spontaneous inhibitory post\u2010synaptic currents (sIPSCs) were measured from dentate gyrus granule cells of live hippocampal slices before and after Gq\u2010DREADD activation. Hippocampal field potentials were monitored in\u00a0vivo to quantify seizure burden. Finally, metabolic profiling of the hippocampal tissue examined associated effects of Gq\u2010DREADD activation in epileptic mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Gq\u2010DREADD activation increased c\u2010Fos expression in astrocytes but not in the neurons of the epileptic hippocampus and rapidly increased sIPSC in hippocampal slices from epileptic mice. We found a significant reduction in the number of spontaneous hippocampal paroxysmal discharges (HPDs) and overall seizure burden 1\u2009day after Gq\u2010DREADD modulation of reactive astrocytes. The metabolomics analysis at this time point showed 78 metabolites that were significantly altered in epileptic mice, 11 of which were also altered upon Gq\u2010DREADD modulation of reactive astrocytes, belonging to several metabolic pathways that have been implicated in epilepsy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>Our findings provide converging evidence for a modulatory role of reactive astrocytes in TLE. Gq\u2010DREADD activation of hippocampal astrocytes suppressed HPDs and induced metabolic shifts, offering insight into astrocyte\u2010driven mechanisms and potential therapeutic targets.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.18684","type":"journal-article","created":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T14:50:55Z","timestamp":1761403855000},"page":"934-949","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Chemogenetic astrocyte modulation reduces spontaneous hippocampal discharges and metabolite changes in an epilepsy mouse model"],"prefix":"10.1111","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7186-7777","authenticated-orcid":false,"given":"Liam","family":"Nestor","sequence":"first","affiliation":[{"name":"Research Group Experimental Pharmacology (EFAR), Center for Neurosciences (C4N) Vrije Universiteit Brussel (VUB)  Brussels 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Neurosciences (C4N) Vrije Universiteit Brussel (VUB)  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5821-1842","authenticated-orcid":false,"given":"Evelien","family":"Hendrix","sequence":"additional","affiliation":[{"name":"Research Group Experimental Pharmacology (EFAR), Center for Neurosciences (C4N) Vrije Universiteit Brussel (VUB)  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5599-5055","authenticated-orcid":false,"given":"An","family":"Buckinx","sequence":"additional","affiliation":[{"name":"Research Group Experimental Pharmacology (EFAR), Center for Neurosciences (C4N) Vrije Universiteit Brussel (VUB)  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2232-4869","authenticated-orcid":false,"given":"Sofie","family":"Bournons","sequence":"additional","affiliation":[{"name":"Research 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