SGK1. 1 reduces kainic acid-induced seizure severity and leads to rapid termination of seizures
N Armas-Capote, LE Maglio, L Pérez-Atencio… - Cerebral …, 2020 - academic.oup.com
Cerebral Cortex, 2020•academic.oup.com
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 …
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 …
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.
Oxford University Press
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