ArticleNature neuroscience2011
Neuregulin 1 represses limbic epileptogenesis through ErbB4 in parvalbumin-expressing interneurons.
Article in Nature neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 1 of them a synthesis that pooled it.
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Who cites it
77 citing papers in PubMed, 1 synthesis or guideline pooled it, 134 citations in OpenAlex.
- Pooled it
- Insight into Haploinsufficiency of the ERBB4 Gene: Expanding the Spectrum of Associated Phenotypes.Journal of autism and developmental disorders · 2026Article
- Structure, mechanism and clinical relevance of NRG1 fusions in cancer.Journal of biomedical science · 2026Review
- Dynamic regulation of mRNA acetylation at synapses by spatial memory in mouse hippocampus.eLife · 2026Article
- Junction-mediating and regulatory protein (JMY) is a promoting protein for radial migration of cortical neurons.Cell death discovery · 2026Article
- Vitamin D is involved in regulating limbic epileptogenesis.Brain communications · 2026Article
- Cytoprotective and Immunomodulatory Properties of Mesenchymal Stem Cell Secretome and Its Effect on Organotypic Hippocampal Cultures in Mouse Model of Temporal Lobe Epilepsy.International journal of molecular sciences · 2025Article
- Both GEF domains of the autism and developmental epileptic encephalopathy-associated Trio protein are required for proper tangential migration of GABAergic interneurons.Molecular psychiatry · 2025Article
- Psychosis of Epilepsy: An Update on Clinical Classification and Mechanism.Biomolecules · 2025Review
- Toxoplasma infection induces an aged neutrophil population in the CNS that is associated with neuronal protection.Journal of neuroinflammation · 2024Article
- Molecular Genetics of Acquired Temporal Lobe Epilepsy.Biomolecules · 2024Review
- Transmembrane protein modulates seizure in epilepsy: evidence from temporal lobe epilepsy patients and mouse models.Experimental animals · 2024Article
- Delineating mechanisms underlying parvalbumin neuron impairment in different neurological and neurodegenerative disorders: the emerging role of mitochondrial dysfunction.Biochemical Society transactions · 2024Review
- nNOS in Erbb4-positive neurons regulates GABAergic transmission in mouse hippocampus.Cell death & disease · 2024Article
- Impairments of GABAergic transmission in hippocampus mediate increased susceptibility of epilepsy in the early stage of Alzheimer's disease.Cell communication and signaling : CCS · 2024Article
- Effects of Anti-Seizure Medication on Neuregulin-1 Gene and Protein in Patients with First-Episode Focal Epilepsy.Neuropsychiatric disease and treatment · 2024Article
- Role of Exogenous Neuregulin-1 as a Therapeutic Agent in Focal Epilepsy [Letter].Neuropsychiatric disease and treatment · 2024Article
- Strategic pathway analysis for dual management of epilepsy and comorbid depression: a systems biology perspective.In silico pharmacology · 2024Article
- Tyrosine Kinase Receptor ErbB4 in Advillin-Positive Neurons Contributes to Inflammatory Pain Hypersensitivity in Mouse DRG.Aging and disease · 2023Article
- Prenatal dexamethasone exposure induces anxiety- and depressive-like behavior of male offspring rats through intrauterine programming of the activation of NRG1-ErbB4 signaling in hippocampal PV interneurons.Cell biology and toxicology · 2023Article
17 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epilepsy is a common and refractory neurological disorder, but the neuronal regulatory mechanisms of epileptogenesis remain largely unclear. Activity-dependent transcription of genes for neurotrophins such as brain-derived neurotrophic factor (BDNF) has been shown to promote epileptogenesis; however, little is known about factors that may act as intrinsic, homeostatic or counterbalancing mechanisms. Using rodent models, here we show that limbic seizure activity upregulated NRG1-ErbB4 signaling and that epileptogenesis was inhibited by infusing NRG1 intracerebrally but exacerbated by neutralizing endogenous NRG1 with soluble ErbB4 extracellular domain, by inhibiting ErbB4 activation or by deleting the Erbb4 gene. Furthermore, specific depletion of ErbB4 in parvalbumin-expressing interneurons abolished NRG1-mediated inhibition of epileptogenesis and promoted kindling progression, resulting in increased spontaneous seizures and exuberant mossy fiber sprouting. In contrast, depleting ErbB4 in CaMKIIα-positive pyramidal neurons had no effect. Thus, NRG1-induced activation of ErbB4 in parvalbumin-expressing inhibitory interneurons may serve as a critical endogenous negative-feedback mechanism to suppress limbic epileptogenesis.
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