ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Development and persistence of limbic epileptogenesis are impaired in mice lacking progesterone receptors.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 62 citations in OpenAlex.
- Rapid hippocampal kindling of mice as a model of sudden unexpected death in temporal lobe epilepsy.Experimental neurology · 2026Article
- Kindling Models of Epileptogenesis for Developing Disease-Modifying Drugs for Epilepsy.Current protocols · 2024Article
- Neurosteroids as Novel Anticonvulsants for Refractory Status Epilepticus and Medical Countermeasures for Nerve Agents: A 15-Year Journey to Bring Ganaxolone from Bench to Clinic.The Journal of pharmacology and experimental therapeutics · 2024Review
- Preclinical and clinical pharmacology of brexanolone (allopregnanolone) for postpartum depression: a landmark journey from concept to clinic in neurosteroid replacement therapy.Psychopharmacology · 2023Review
- Neurosteroid replacement therapy for catamenial epilepsy, postpartum depression and neuroendocrine disorders in women.Journal of neuroendocrinology · 2022Review
- Does Stress Trigger Seizures? Evidence from Experimental Models.Current topics in behavioral neurosciences · 2022Article
- Convulsive behaviors of spontaneous recurrent seizures in a mouse model of extended hippocampal kindling.Frontiers in behavioral neuroscience · 2022Article
- Progesterone modulates neuronal excitability bidirectionally.Neuroscience letters · 2021Review
- Electrographic Features of Spontaneous Recurrent Seizures in a Mouse Model of Extended Hippocampal Kindling.Cerebral cortex communications · 2021Article
- Isobolographic Analysis of Antiseizure Activity of the GABA Type A Receptor-Modulating Synthetic Neurosteroids Brexanolone and Ganaxolone with Tiagabine and Midazolam.The Journal of pharmacology and experimental therapeutics · 2020Article
- Glial source of nitric oxide in epileptogenesis: A target for disease modification in epilepsy.Journal of neuroscience research · 2019Review
- Plasma concentrations of steroid precursors, steroids, neuroactive steroids, and neurosteroids in healthy neonatal foals from birth to 7 days of age.Journal of veterinary internal medicine · 2019Article
- Progesterone receptor activation regulates seizure susceptibility.Annals of clinical and translational neurology · 2019Article
- Zinc reduces antiseizure activity of neurosteroids by selective blockade of extrasynaptic GABA-A receptor-mediated tonic inhibition in the hippocampus.Neuropharmacology · 2019Article
- Interactions of Aromatase and Seladin-1: A Neurosteroidogenic and Gender Perspective.Translational neuroscience · 2019Article
- 3The Journal of pharmacology and experimental therapeutics · 2018Article
- A novel therapeutic approach for treatment of catamenial epilepsy.Neurobiology of disease · 2018Article
- Catamenial-like seizure exacerbation in mice with targeted ablation of extrasynaptic δGABA-a receptors in the brain.Journal of neuroscience research · 2017Article
- Novel therapeutic approaches for disease-modification of epileptogenesis for curing epilepsy.Biochimica et biophysica acta. Molecular basis of disease · 2017Review
- Prospects of modeling poststroke epileptogenesis.Journal of neuroscience research · 2017Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Progesterone plays a key role in ovarian cycle-related synaptic plasticity and neuronal excitability. Progesterone receptors (PRs), which mediate the cellular actions of progesterone, are expressed in the hippocampus and other limbic regions, but their functional significance remains unknown. Here, we report a novel role of PRs as crucial mediators in the development of epileptogenesis, which is the process whereby a normal brain becomes progressively epileptic because of precipitating factors. The PR knock-out (PR(-/-)) mouse, which lacks both the PR-A and PR-B isoforms, exhibited an increased resistance to epileptogenesis in the hippocampus and amygdala kindling models. Lack of PRs markedly impaired the persistence of seizure expression at 4 weeks after kindling development. We further show that selective inhibition of PRs in the brain by antisense oligos or pharmacological blockade of PRs by RU-486 [11β-[p-(dimethylamino)phenyl]-17β-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one] resulted in a significant decrease in epileptogenesis in wild-type (PR(+/+)) mice. The delayed epileptogenesis in PR knock-out mice was not substantially affected by inhibition of neurosteroid synthesis. Mice lacking PRs show supersensitivity to the antiseizure responses of progesterone. Collectively, these results suggest that PRs in the hippocampus are linked to signaling pathways that control susceptibility to epileptogenesis and possibly persistence of an epileptic-like state. The PR pathway may represent a unique target for preventing or retarding epileptogenesis in females.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.