Towards Unmasking the Pathophysiology of Epilepsy using a New Cellular Model based on Human iPSCs

NOELIA LINO; MARIANA CASALIA; JUAN CRUZ CASABONA; VERÓNICA CAVALIERE CANDEDO; ISABEL FARIAS; JOAQUÍN GONZÁLEZ; MARCELO KAUFFMAN; FRANCISCO URBANO; MARIO GUSTAVO MURER; LORENA RELA; FERNANDO PITOSSI

Mar del Plata

Congreso; XXX Reunion Anual; 2015

Sociedad Argentina de Investigacion en Neurociencias

Epilepsy is one of the most common and disabling neurologic conditions, characterized byan enduring predisposition to generate epileptic seizures. Those seizures are paroxysmalalterations of neurologic function caused by the excessive, hypersynchronous discharge ofneurons in the brain, that becomes apparent when there is a distortion of the normalbalance between excitation and inhibition. For a better understanding of thepathophysiology of the disease, we developed a cellular model of epilepsy bydifferentiating iPSCs lines obtained from patients with an epileptic syndrome classified as a?benign focal epilepsy of childhood? (BFEC) and healthy individuals. After validating thosecell lines, the functionality of the corresponding neurons was characterized. A delay in thedevelopment of electrophysiological properties was observed, with patients´ neuronsbeing more excitable than controls. These neurons not only exhibited a lower actionpotential threshold, but also a marked tendency towards an increase of voltage-dependentK+ (rapidly inactivating and non-inactivating) currents, after 12 weeks of differentiation.Our observations suggest that patients´ neurons present a developmental delay, explainingthe occurrence of seizures in children and being in accordance with the progression ofBFECs, which are resolved by the end of adolescence, when the inhibitory circuitrymatures. Further analysis would be necessary to elucidate the exact mechanismsunderlying BFECs.