Unravelling the Role of System xc- in Epileptogenesis
Faculty of Medicine & Pharmacy, Center for Neurosciences, Department FASC
Vrije Universiteit Brussel

Abstract: Epilepsy is a common neurodegenerative disorder which affects about 65 million people worldwide. Approximately, 30% of patients are drug refractory and this data sheds light on the urgent need for innovative antiepileptic therapies to prevent the progression of the disease. In order to find new antiepileptic strategies, two main objectives should be achieved: the identification of new pharmacological targets and the validation of these targets on reliable animal models that mimic the process of epileptogenesis. It is well understood that oxidative stress and excessive glutamatergic activity play a key role in the induction of the neuronal pathology that leads to a variety of neurological diseases, such as epilepsy. The system xc-, a plasma membrane antiporter that imports cystine inside the cell, later to be used for glutathione synthesis, and exports, in turn, glutamate in the extracellular environment, seems to be the conjunction between the attempt of cells to produce antioxidant molecules and increased levels of glutamate, leading potentially to excitotoxicity. Since system xc- is one of the main source of extracellular glutamate in rodent hippocampus and it has been demonstrated that xCT-/- mice are less susceptible to chemoconvulsant drugs, this antiporter became the subject of our interest. The aim of this work is to provide a further investigation on the involvement of system xc- in the generation of seizures and in altering the epileptogenetic process. Therefore we will investigate the hippocampal xCT expression during the various phases of epileptogenesis and we will study the anticonvulsant effects of a knockdown of xCT using Vivo-Morpholino injections. Moreover, we will investigate the seizure susceptibility of both mice overexpressing xCT and xCT-/- mice in the amigdala kindling model and in a post-status epilepticus model. Lastly, since epilepsy is a multifactorial disease, we will investigate the involvement of system xc- in mechanisms of depression.
Original languageEnglish
Title of host publicationCenter for Neurosciences PhD Day, Brussels, Belgium, march 13, 2014
Publication statusPublished - 2014
EventPhD day Center for Neurosciences - Faculty of Medicine, Vrije Universiteit Brussel., Brussels, Belgium
Duration: 13 Mar 201413 Mar 2014


SeminarPhD day Center for Neurosciences

    Research areas

  • epilepsy, system xc-, epileptogenesis, glia

ID: 2497359