NR2B ANTAGONISM IN EPILEPTOGENESIS

The most common form of human epilepsy is temporal lobe epilepsy (TLE) that is characterized by recurrent seizures originating from the temporal lobe. Over the last decades, a new generation of antiepileptic drugs has emerged in medication of TLE however, the concept of satisfactory control of chronic seizures is still elusive for about 40% of patients for whom the disorder is refractory to currently available pharmacotherapies. For this reason new therapeutic strategies are desired, and one of the main research targets for TLE medication is epileptogenesis. Usually there is a latency period in epileptogenesis that lasts up to several months upon the process initiation, after which a clinical epilepsy with associated recurrent seizures gradually develops. This critical period of latency offers a time window during which an appropriate treatment would saffect the process of epileptogenesis. Our preliminary results suggests that a specialized subpopulation of N-metylo-D-aspartate receptor (NMDAR) containing NR2B subunit (NMDARNR2B) could comprise a very substantial component of the aberrant synaptic transmission during TLE development. Since synaptic transmission in developing connections promotes the formation of synapses, the inhibition of NMDARNR2B may contribute to the inhibition of epileptogenesis. Consequently, the aim of that project is to test thehypothesis that selective inhibition of the NMDARNR2B receptor during epileptogenesis could comprise an effective way of preventing the development of TLE and related chronic seizures.

TRANS-SYNAPTIC CADHERINS AND KAINATE RECEPTOR STABILIZATION AT MOSSY FIBER SYNAPSES IN PATHOPHYSIOLOGY OF TEMPORAL LOBE EPILEPSY

One of the very key features of the nervous system is the exquisite precision of synaptic connections. Adequate components of the synapse are specifically targeted to a given synaptic junction and mature synapses retain this specificity through the highly dynamic processes, which involve trans-synaptic adhesion complexes to control the correct placement of pre- and post-synaptic molecules. My ongoing study concentrates on the molecular mechanisms underlying synaptic segregation of kainate receptors in hippocampus in patophysiology of temporal lobe epilepsy. The goal of this project is to verify the hypothesis, that both trans-synaptic Cadherin-9 and N-cadherin complexes are involved in the recruitment of GluK2-containing kainate receptors to the athypical epiletiform mossy fiber synapses.