Thesis – Athénaïs GENIN

Astrocyte remodeling in a murine model of Dravet syndrome

Jury

• Aude PANATIER, Research Director, Neurocentre Magendie, Bordeaux – Reviewer
• Gilles HUBERFELD, Hospital Practitioner, Adolphe de Rothschild Foundation Hospital, Paris – Reviewer
• Elena AVIGNONE, Associate Professor, Neurocentre Magendie, Bordeaux – Examiner
• François RASSENDREN, Research Director, IGF, University of Montpellier – Examiner
• Etienne AUDINAT, Research Director, IGF, University of Montpellier – Thesis supervisor
• Noémie CRESTO, Postdoctoral Researcher, IGF, University of Montpellier – Co-supervisor

Summary

Dravet syndrome is a developmental and epileptic encephalopathy caused by loss-of-function variants in SCN1A. Although neuronal dysfunction is well documented, the contribution of astrocytes remains unclear. Using Scn1a+/− mice, we identified astrocyte remodeling during disease progression. Mice exhibited increased GFAP expression in the hippocampus and cortex, with transient morphological changes in CA1 astrocytes during the worsening stage. In contrast, functional alterations persisted, including increased astrocytic coupling, elevated connexin 30 and 43 expression, and reduced hemichannel activity. These changes were associated with enhanced post-tetanic potentiation at Schaffer collateral–CA1 synapses and occurred in the absence of major tissue damage.Our findings reveal long-lasting astrocytic remodeling in Dravet syndrome that may contribute to network hyperexcitability and associated cognitive and behavioral deficits.