INVOLVEMENT OF SYNAPSIN GENES IN EPILEPSY: GENETIC AND FUNCTIONAL ANALYSIS IN HUMAN AND MOUSE

Epilepsy affects more than 1% of the world’s population and age-specific incidence studies showed a distribution with the highest peak in childhood and adolescence. Seizures are the clinical manifestation of underlying abnormalities in the activity of cortical networks. Many epilepsies have a genetic component and considerable progress has been made in recent years in the investigation of familial epilepsies. It is very likely that a number of epilepsy-associated genes are to be uncovered in the human genome. In addition to the genes coding for ion channels , a number of genes involved in the structural maturation of neuronal connectivity and in synaptic transmission are likely to be involved. Very recently, it was found that a form of familial epilepsy with the onset within the first two decades of life was characterized by a non-sense mutation in the gene encoding for synapsin I. This discovery represents the first form of genetic epilepsy with a defect in a synaptic vesicle protein. The aim of this project is: (1) to identify mutations in the genes of synapsin I and synapsin II in patients affected by idiopathic or familial epilepsy; (2) to use an animal model of mice lacking synapsins to better elucidate, at cellular and circuit level, the molecular mechanisms that lead to epileptic seizures and (3) to identify antiepileptic drugs effective on this form of epilepsy in order to develop more powerful therapeutic strategies.