ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2016
Ablation of Newly Generated Hippocampal Granule Cells Has Disease-Modifying Effects in Epilepsy.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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51 citing papers in PubMed, 76 citations in OpenAlex.
- Ras-MAPK somatic variants in mesial temporal lobe epilepsy.Current opinion in genetics & development · 2026Review
- Targeted interneuron ablation in an mTORopathy model: Testing a two-hit mechanism of epileptogenesis.Progress in neurobiology · 2026Article
- Cell-Intrinsic Regulation of Epilepsy-Associated Pathology by mTORC1 and mTORC2.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Ablation of Unilateral Hippocampal GABAergic Neurons: A Novel Mouse Model of Mesial Temporal Lobe Epilepsy With Hippocampal Sclerosis.CNS neuroscience & therapeutics · 2026Article
- Adult hippocampal neurogenesis: New avenues for treatment of brain disorders.Stem cell reports · 2025Review
- Inhibiting aberrant seizure-induced neurogenesis by temozolomide improves cognitive impairments associated with long-term amygdala kindling.Frontiers in neuroscience · 2025Article
- Article
- Increasing adult-born neurons protects mice from epilepsy.bioRxiv : the preprint server for biology · 2024Article
- Transient Seizure Clusters and Epileptiform Activity Following Widespread Bilateral Hippocampal Interneuron Ablation.eNeuro · 2024Article
- Adult-Born Granule Cells Contribute to Dentate Gyrus Circuit Reorganization after Traumatic Brain Injury.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Seizure-induced hilar ectopic granule cells in the adult dentate gyrus.Frontiers in neuroscience · 2023Review
- Hippocampal transplants of fetal GABAergic progenitors regulate adult neurogenesis in mice with temporal lobe epilepsy.Neurobiology of disease · 2022Article
- Spontaneous recurrent seizures in an intra-amygdala kainate microinjection model of temporal lobe epilepsy are differentially sensitive to antiseizure drugs.Experimental neurology · 2022Article
- What do Newborn Granule Cells Do, and When Do They Do It?Epilepsy currents · 2021Article
- The glucocorticoid receptor specific modulator CORT108297 reduces brain pathology following status epilepticus.Experimental neurology · 2021Article
- Glutamatergic Fate of Neural Progenitor Cells of Rats with Inherited Audiogenic Epilepsy.Brain sciences · 2020Article
- Adult Neurogenesis in Epileptogenesis: An Update for Preclinical Finding and Potential Clinical Translation.Current neuropharmacology · 2020Review
- Microglial P2Y12 Receptor Regulates Seizure-Induced Neurogenesis and Immature Neuronal Projections.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Article
- MicroRNA inhibition upregulates hippocampal A-type potassium current and reduces seizure frequency in a mouse model of epilepsy.Neurobiology of disease · 2019Article
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3 authors at 1 institution in 1 country.
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Abstract
Hippocampal granule cells generated in the weeks before and after an epileptogenic brain injury can integrate abnormally into the dentate gyrus, potentially mediating temporal lobe epileptogenesis. Previous studies have demonstrated that inhibiting granule cell production before an epileptogenic brain insult can mitigate epileptogenesis. Here, we extend upon these findings by ablating newly generated cells after the epileptogenic insult using a conditional, inducible diphtheria-toxin receptor expression strategy in mice. Diphtheria-toxin receptor expression was induced among granule cells born up to 5 weeks before pilocarpine-induced status epilepticus and these cells were then eliminated beginning 3 d after the epileptogenic injury. This treatment produced a 50% reduction in seizure frequency, but also a 20% increase in seizure duration, when the animals were examined 2 months later. These findings provide the first proof-of-concept data demonstrating that granule cell ablation therapy applied at a clinically relevant time point after injury can have disease-modifying effects in epilepsy. SIGNIFICANCE STATEMENT: These findings support the long-standing hypothesis that newly generated dentate granule cells are pro-epileptogenic and contribute to the occurrence of seizures. This work also provides the first evidence that ablation of newly generated granule cells can be an effective therapy when begun at a clinically relevant time point after an epileptogenic insult. The present study also demonstrates that granule cell ablation, while reducing seizure frequency, paradoxically increases seizure duration. This paradoxical effect may reflect a disruption of homeostatic mechanisms that normally act to reduce seizure duration, but only when seizures occur frequently.
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