The ketogenic diet (KD) has been used as an effective therapy to treat epilepsy. Previous studies indicate an elevated level of GABA in the brain by KD treatment. However, the underlying mechanisms remain to be elucidated. Here we report that KD treatment suppresses seizures in both acute and chronic seizure models and enhances presynaptic GABA release probability in the hippocampus. By screening molecular targets that potentially linked to GABAergic activity with transcriptome analysis, we identify that KD treatment dramatically increased the Nrg1 gene expression in the hippocampus. Disruption of Nrg1 signaling by genetically deleting its receptor-ErbB4 or blocking ErbB4 kinase activity abolishes KDs effects on GABAergic activity and seizures. Mechanistically, KD treatment increases Nrg1 expression via up-regulating histone acetylation. Our findings suggest a critical role of Nrg1/ErbB4 signaling in mediating KDs effects on GABAergic activity and seizures, which sheds light on the development of new therapeutic interventions to seizure control. SOURCE: jin wang (Wj561120@126.com) -  Guangzhou Medical University

Pluto Bioinformatics

GSE156687: Nrg1/ErbB4 signaling contributes to the effects of the ketogenic diet on GABAergic activity and seizures