ArticleNeuropharmacology2019
Zinc reduces antiseizure activity of neurosteroids by selective blockade of extrasynaptic GABA-A receptor-mediated tonic inhibition in the hippocampus.
Article in Neuropharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- Review
- Metallothioneins in Neurodegenerative Diseases: Metal Homeostasis, Autoimmunity, and Therapeutic Potential.Molecular neurobiology · 2026Review
- Effects of GABAAR modulators CL218872 and MRK-016 on neural repair and synaptic plasticity in mice with Intracerebral hemorrhage.PloS one · 2026Article
- Decoding the structural and functional diversity of GABAFrontiers in pharmacology · 2025Review
- On the genesis and unique functions of zinc neuromodulation.Journal of neurophysiology · 2024Review
- Zinc, Copper, and Calcium: A Triangle in the Synapse for the Pathogenesis of Vascular-Type Senile Dementia.Biomolecules · 2024Review
- 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
- Unveiling the hidden connection: the blood-brain barrier's role in epilepsy.Frontiers in neurology · 2024Review
- Preclinical and clinical pharmacology of brexanolone (allopregnanolone) for postpartum depression: a landmark journey from concept to clinic in neurosteroid replacement therapy.Psychopharmacology · 2023Review
- Pathophysiological basis and promise of experimental therapies for Gulf War Illness, a chronic neuropsychiatric syndrome in veterans.Psychopharmacology · 2023Review
- COVID-19-induced neurological symptoms: focus on the role of metal ions.Inflammopharmacology · 2023Review
- Zinc Homeostasis: An Emerging Therapeutic Target for Neuroinflammation Related Diseases.Biomolecules · 2023Review
- Zinc Inhibits the GABAInternational journal of molecular sciences · 2023Article
- Crosstalk of copper and zinc in the pathogenesis of vascular dementia.Journal of clinical biochemistry and nutrition · 2022Article
- GABAkines - Advances in the discovery, development, and commercialization of positive allosteric modulators of GABAPharmacology & therapeutics · 2022Review
- Post-Traumatic Epilepsy and Comorbidities: Advanced Models, Molecular Mechanisms, Biomarkers, and Novel Therapeutic Interventions.Pharmacological reviews · 2022Review
- Neurosteroid replacement therapy for catamenial epilepsy, postpartum depression and neuroendocrine disorders in women.Journal of neuroendocrinology · 2022Review
- 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
- Mechanism-based novel antidotes for organophosphate neurotoxicity.Current opinion in toxicology · 2019Article
- Comparison of Serum Trace Nutrient Concentrations in Epileptics Compared to Healthy Dogs.Frontiers in veterinary science · 2019Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Zinc is an abundant trace metal in the hippocampus nerve terminals. Previous studies demonstrate the ability of zinc to selectively block neurosteroid-sensitive, extrasynaptic GABA-A receptors in the hippocampus (Carver et al, 2016). Here we report that zinc prevents the seizure protective effects of the synthetic neurosteroid ganaxolone (GX) in an experimental model of epilepsy. GABA-gated and tonic currents were recorded from dissociated dentate gyrus granule cells (DGGCs), CA1 pyramidal cells (CA1PCs), and hippocampal slices from adult mice. Antiseizure effects of GX and the reversal of these effects by zinc were evaluated in fully-kindled mice expressing generalized (stage 5) seizures. In electrophysiological studies, zinc blocked the GABA-evoked and GX-potentiated GABA-gated chloride currents in DGGCs and CA1PCs in a concentration-dependent fashion similar to the competitive GABA-A receptor antagonists bicuculline and gabazine. Zinc completely blocked GX potentiation of extrasynaptic tonic currents, but not synaptic phasic currents. In hippocampus kindling studies, systemic administration of GX produced a dose-dependent suppression of behavioral and electrographic seizures in fully-kindled mice with complete seizure protection at the 10 mg/kg dose. However, the antiseizure effects of GX were significantly prevented by intrahippocampal administration of zinc (ED
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