Reprogramming reactive glia into interneurons reduces chronic seizure activity in a mouse model of mesial temporal lobe epilepsy - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Cell Stem Cell Année : 2021

Reprogramming reactive glia into interneurons reduces chronic seizure activity in a mouse model of mesial temporal lobe epilepsy

Karl-Klaus Conzelmann
Antoine Depaulis

Résumé

Reprogramming brain-resident glial cells into clinically relevant induced neurons (iNs) is an emerging strategy toward replacing lost neurons and restoring lost brain functions. A fundamental question is now whether iNs can promote functional recovery in pathological contexts. We addressed this question in the context of therapy-resistant mesial temporal lobe epilepsy (MTLE), which is associated with hippocampal seizures and degeneration of hippocampal GABAergic interneurons. Using a MTLE mouse model, we show that retrovirus-driven expression of Ascl1 and Dlx2 in reactive hippocampal glia in situ, or in cortical astroglia grafted in the epileptic hippocampus, causes efficient reprogramming into iNs exhibiting hallmarks of interneurons. These induced interneurons functionally integrate into epileptic networks and establish GABAergic synapses onto dentate granule cells. MTLE mice with GABAergic iNs show a significant reduction in both the number and cumulative duration of spontaneous recurrent hippocampal seizures. Thus glia-to-neuron reprogramming is a potential disease-modifying strategy to reduce seizures in therapy-resistant epilepsy.
Fichier principal
Vignette du fichier
PIIS1934590921003787(1).pdf (9.53 Mo) Télécharger le fichier
Origine Publication financée par une institution

Dates et versions

hal-03435876 , version 1 (20-11-2021)

Licence

Identifiants

Citer

Célia Lentini, Marie D’orange, Nicolás Marichal, Marie-Madeleine Trottmann, Rory Vignoles, et al.. Reprogramming reactive glia into interneurons reduces chronic seizure activity in a mouse model of mesial temporal lobe epilepsy. Cell Stem Cell, 2021, 28 (12), pp.2104-2121.e10. ⟨10.1016/j.stem.2021.09.002⟩. ⟨hal-03435876⟩
86 Consultations
29 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More