ArticleCell & bioscience2021
Neuregulin 1/ErbB4 signaling contributes to the anti-epileptic effects of the ketogenic diet.
Article in Cell & bioscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- From clinical practice to mechanistic insights in ketogenic diets for epilepsy.The Lancet. Neurology · 2026Review
- Bone-targeted celastrol nanocarrier suppresses osteoclastogenesis in postmenopausal osteoporosis.NPJ science of food · 2025Article
- Targeted activation of ErbB4 receptor ameliorates neuronal deficits and neuroinflammation in a food-borne polystyrene microplastic exposed mouse model.Journal of neuroinflammation · 2025Article
- A Ketogenic Diet Affects Gut Microbiota by Regulating Gut Microbiota and Promoting Hippocampal TRHR Expression to Combat Seizures.Journal of molecular neuroscience : MN · 2024Article
- The influence of the NRG1/ERBB4 signaling pathway on pulmonary artery endothelial cells.Pulmonary circulation · 2024Article
- Effects of Kv1.3 knockout on pyramidal neuron excitability and synaptic plasticity in piriform cortex of mice.Acta pharmacologica Sinica · 2024Article
- Agrin-Lrp4 pathway in hippocampal astrocytes restrains development of temporal lobe epilepsy through adenosine signaling.Cell & bioscience · 2024Article
- ADCY3: the pivotal gene in classical ketogenic diet for the treatment of epilepsy.Frontiers in cellular neuroscience · 2024Article
- NLRP3 Inflammasome Activation Enhances ADK Expression to Accelerate Epilepsy in Mice.Neurochemical research · 2022Article
- Review
- On the nutritional and therapeutic effects of ketone body D-β-hydroxybutyrate.Applied microbiology and biotechnology · 2021Review
- The ketogenic diet increases Neuregulin 1 expression via elevating histone acetylation and its anti-seizure effect requires ErbB4 kinase activity.Cell & bioscience · 2021Article
- Minireview of Epilepsy Detection Techniques Based on Electroencephalogram Signals.Frontiers in systems neuroscience · 2021Review
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Authors and funding
18 authors at 6 institutions in 1 country.
Funding
Abstract
backgroundThe ketogenic diet (KD) has been recognized as a potentially effective therapy to treat neuropsychiatric diseases, including epilepsy. Previous studies have indicated that KD treatment elevates γ-Amino butyric acid (GABA) levels in both human and murine brains, which presumably contributes to the KD's anti-seizure effects. However, this has not been systematically investigated at the synaptic level, and the underlying molecular mechanisms remain to be elucidated.
methodsKainic acid (KA)-induced acute and chronic seizure models were utilized to examine the effects of KD treatment on seizure threshold and epileptogenesis. Synaptic activities in the hippocampus were recorded with the technique of electrophysiology. The effects of the KD on Neuregulin 1 (Nrg1) expression were assessed via RNA sequencing, real-time PCR and Western blotting. The obligatory role of Nrg1 in KD's effects on seizures was evaluated through disruption of Nrg1 signaling in mice by genetically deleting its receptor-ErbB4.
resultsWe found that KD treatment suppressed seizures in both acute and chronic seizure models and enhanced presynaptic GABA release probability in the hippocampus. By screening molecular targets linked to GABAergic activity with transcriptome analysis, we identified that KD treatment dramatically increased the Nrg1 gene expression in the hippocampus. Disruption of Nrg1 signaling by genetically deleting its receptor-ErbB4 abolished KD's effects on GABAergic activity and seizures.
conclusionOur findings suggest a critical role of Nrg1/ErbB4 signaling in mediating KD's effects on GABAergic activity and seizures, shedding light on developing new therapeutic interventions to seizure control.
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