SGK1.1 reduces Kainic acid-induced seizure severity and leads to rapid termination of seizures
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Abstract
Approaches to control epilepsy, one of the most important idiopathic brain disorders, are of great importance for public health. We have previously shown that in sympathetic neurons the neuronal isoform of the serum and glucocorticoid-regulated kinase (SGK1.1) increases the M-current, a well-known target for seizure control. The effect of SGK1.1 activation on kainate-induced seizures and neuronal excitability was studied in transgenic mice that express a permanently active form of the kinase, using electroencephalogram recordings and electrophysiological measurements in hippocampal brain slices. Our results demonstrate that SGK1.1 activation leads to reduced seizure severity and lower mortality rates following status epilepticus, in an M-current–dependent manner. EEG is characterized by reduced number, shorter duration, and early termination of kainate-induced seizures in the hippocampus and cortex. Hippocampal neurons show decreased excitability associated to increased M-current, without altering basal synaptic transmission or other neuronal properties. Altogether, our results reveal a novel and selective anticonvulsant pathway that promptly terminates seizures, suggesting that SGK1.1 activation can be a potent factor to secure the brain against permanent neuronal damage associated to epilepsy.
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SGK1 mitigates Nedd4-2-mediated internalization of Kv7.2/3 channels, thereby regulating M-current and neuronal excitability, through phosphorylation of Nedd4-2.
“SGK1 mitigates the Nedd4–2-mediated internalization of Kv7.2/3 channels, thereby regulating M-current and neuronal excitability, through the phosphorylation of Nedd4–2”
From Serum/glucocorticoid regulated kinase 1 (SGK1) in neurological disorders: pain or gain (2024) · cites this paper as Armas-Capote et al., 2020
The Introduction says SGK1.1 activation upregulates M-current via Nedd4-2 phosphorylation and reduces hippocampal neuronal excitability. The section on CA1 pyramidal neurons also reports increased Nedd4-2 phosphorylation and describes increased Kv7.2/7.3 surface expression through a Nedd4-2-related mechanism. It does not establish the more specific claim that SGK1 reduces Nedd4-2-mediated channel internalization. (LLM, conf=0.84)
Experimental — accuracy not yet measuredActivation of SGK1 reduces severity and mortality of seizures following status epilepticus in an M-current-dependent manner.
“Activation of SGK1 reduces the severity and mortality of seizures following the status epilepticus in an M-current-dependent manner”
From Serum/glucocorticoid regulated kinase 1 (SGK1) in neurological disorders: pain or gain (2024) · cites this paper as Armas-Capote et al., 2020
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- Authors
- Armas-Capote, N., Maglio, L. E., Pérez-Atencio, L., Martin-Batista, E., Reboreda, A., Barios, J. A., Hernandez, G., Alvarez de la Rosa, D., Lamas, J. A., Barrio, L. C., & Giraldez, T.
- Affiliations
- Universidad de La Laguna (ES)
- Instituto Ramón y Cajal de Investigación Sanitaria (ES)
- Departamento de Ciencias Medicas Basicas-Fisiologia and Instituto de Tecnologías Biomedicas (ITB), Universidad de La Laguna, Tenerife, 38071 Spain
- Universidade de Vigo (ES)
- Universitat de Miguel Hernández d'Elx (ES)
- ORCID
- Venue
- Cerebral Cortex
- Publisher
- Oxford University Press (OUP)
- Published
- 2019-12-09
- Volume
- 30
- Issue
- 5
- Pages
- 3184-3197
- ISSN
- 1047-3211 (ISSN-L)
- 1460-2199
- OpenAlex
- W2996169145
- Cited by
- 12
- References
- 57
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 1 · 2022: 2 · 2021: 3
- FWCI
- 1.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Cerebral Cortex (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- Funders
- Ministerio de Economia y Competitividad
- Ministerio de Ciencia
- Innovacion y Universidades (BFU2015-66490-R, RTI2018-098768-B-I00, BFU2015-71078-P, BFU2014-58999-P, BFU2015-70067-REDC)
- FPI predoctoral (BES-2016-077337)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- serum and glucocorticoid-regulated kinase, kainic acid-induced seizures, status epilepticus, M-current, neuronal excitability, hippocampal neurons, epilepsy, seizure termination, transgenic mice
- MeSH terms
- Serum-Glucocorticoid Regulated Kinases, Animals, Electroencephalography, Hippocampus, Kainic Acid, Mice, Transgenic, Neurons, Seizures, Status Epilepticus, Protein Serine-Threonine Kinases, Alternative Splicing, Immediate-Early Proteins, Excitatory Amino Acid Agonists, Protein Isoforms, Mice, KCNQ2 Potassium Channel, KCNQ3 Potassium Channel
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