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

NOELIA LINO; MARIANA CASALIA; JUAN CRUZ CASABONA; VERONICA CAVALIERE CANDEDO; MARIA ISABEL FARIAS; JOAQUIN GONZALEZ; VALERIA ROCA; MARCELO KAUFFMAN; FRANCISCO URBANO; GUSTAVO MURER; LORENA RELA; FERNANDO PITOSSI

Mar del Plata

Congreso; XXX Congreso Anual; 2015

Sociedad Argentina de Neurociencias

Epilepsy is one of the most common and disabling neurologic conditions, characterized by an enduring predisposition to generate epileptic seizures. Those seizures are paroxysmal alterations of neurologic function caused by the excessive, hypersynchronous discharge of neurons in the brain, that becomes apparent when there is a distortion of the normal balance between excitation and inhibition. For a better understanding of the pathophysiology of the disease, we developed a cellular model of epilepsy by differentiating iPSCs lines obtained from patients with an epileptic syndrome classified as a ?benign focal epilepsy of childhood? (BFEC) and healthy individuals. After validating those cell lines, the functionality of the corresponding neurons was characterized. A delay in the development of electrophysiological properties was observed, with patients´ neurons being more excitable than controls. These neurons not only exhibited a lower action potential threshold, but also a marked tendency towards an increase of voltage-dependent K+ (rapidly inactivating and non-inactivating) currents, after 12 weeks of differentiation. Our observations suggest that patients´ neurons present a developmental delay, explaining the occurrence of seizures in children and being in accordance with the progression of BFECs, which are resolved by the end of adolescence, when the inhibitory circuitry matures. Further analysis would be necessary to elucidate the exact mechanisms underlying BFECs.