ArticleProceedings of the National Academy of Sciences of the United States of America2014
Neurosteroids promote phosphorylation and membrane insertion of extrasynaptic GABAA receptors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 120 citations in OpenAlex.
- SAGE-217, A Novel GABAClinical pharmacokinetics · 2020Trial
- Beyond lactation: Central oxytocin in maternal mental health and disease.Neuroscience and biobehavioral reviews · 2026Review
- Transcription of GABATranslational psychiatry · 2025Article
- Membrane progesterone and oestrogen receptors modulate GABAergic transmission in the prefrontal cortex of prepubertal male, but not female, mice.Experimental physiology · 2025Article
- Neuroactive steroids activate membrane progesterone receptors to induce sex specific effects on protein kinase activity.iScience · 2025Article
- Proteostasis regulation of GABABiomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Review
- New directions in neurosteroid therapeutics in neuropsychiatry.Neuroscience and biobehavioral reviews · 2025Review
- Synthesis and Evaluation of a Novel Zuranolone Analog with High GABAMolecules (Basel, Switzerland) · 2025Article
- GABAiScience · 2025Article
- Clinical Utility of Zuranolone for Postpartum Depression: A Narrative Review.Neuropsychiatric disease and treatment · 2025Review
- Neurosteroids: a lifelong impact on brain health.Frontiers in behavioral neuroscience · 2025Review
- Parvalbumin interneuron mGluNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Forskolin reverses the O-GlcNAcylation dependent decrease in GABAScientific reports · 2024Article
- Forskolin reverses the O-GlcNAcylation dependent decrease in GABAAR current amplitude at hippocampal synapses possibly at a neurosteroid site on GABAARs.Research square · 2024Article
- Parvalbumin interneuron mGlubioRxiv : the preprint server for biology · 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
- The Role of Extrasynaptic GABA Receptors in Postpartum Depression.Molecular neurobiology · 2024Review
- Cyclin D1-Cdk4 regulates neuronal activity through phosphorylation of GABAA receptors.Cellular and molecular life sciences : CMLS · 2023Article
- Neurosteroid influence on affective tone.Neuroscience and biobehavioral reviews · 2023Review
- Inhibitory and excitatory synaptic neuroadaptations in the diazepam tolerant brain.Neurobiology of disease · 2023Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Neurosteroids are synthesized within the brain and act as endogenous anxiolytic, anticonvulsant, hypnotic, and sedative agents, actions that are principally mediated via their ability to potentiate phasic and tonic inhibitory neurotransmission mediated by γ-aminobutyric acid type A receptors (GABAARs). Although neurosteroids are accepted allosteric modulators of GABAARs, here we reveal they exert sustained effects on GABAergic inhibition by selectively enhancing the trafficking of GABAARs that mediate tonic inhibition. We demonstrate that neurosteroids potentiate the protein kinase C-dependent phosphorylation of S443 within α4 subunits, a component of GABAAR subtypes that mediate tonic inhibition in many brain regions. This process enhances insertion of α4 subunit-containing GABAAR subtypes into the membrane, resulting in a selective and sustained elevation in the efficacy of tonic inhibition. Therefore, the ability of neurosteroids to modulate the phosphorylation and membrane insertion of α4 subunit-containing GABAARs may underlie the profound effects these endogenous signaling molecules have on neuronal excitability and behavior.
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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.