The anticonvulsant and neuroprotective roles of sgk1.1

Zusammenfassung

Epilepsy is a neurological disease that affects more than 50 million people around the world. It is characterized by recurrent seizures, the most extreme form of synchronous brain activity. In the nervous system, Kv7 channels are responsible for the M-current, which is important to regulate neuronal excitability. Our laboratory has previously described a new modulator of Kv7.2/3 channels, the neuronal isoform of SGK1 kinase, SGK1.1, which up-regulates channel activity and counteracts hyperexcitability. Using a kainic acid-induced model of temporal lobe epilepsy with transgenic mice expressing a constitutively active form of SGK1.1, we have demonstrated that this kinase is a potent anticonvulsant factor, shortening seizure severity and duration independently of age, sex and genetic background. Furthermore, we show that SGK1.1 drastically reduces seizure-induced neuronal death and associated gliosis through M current-dependent and -independent mechanisms. In addition, our results demonstrate that constitutively active SGK1.1 is able to up-regulate Kv7 channels harboring epilepsy-causing mutations. Altogether, our results establish SGK1.1 as a new potential therapeutic target for epilepsy treatment.