Genetic Targets of Epileptogenesis and Pharmacoresistance in Brain Glial Cells (Epiglia)
Temporal lobe epilepsy (TLE) consists of several subgroups of which Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis (MTLE-HS) is the most severe one. There is also a high association between TLE and febrile seizures. To identify the different TLE subgroups may open new possibilities to tailor pharmacological treatment. Recent findings suggest that modified glial function may play an important role in the hyperexcitability of neuronal tissue promoting epileptogenesis and disease progression, specifically in TLE.
This project tests the hypothesis that astrocytes play a critical role in generation, spreading, and maintenance of seizures in different TLE subgroups. To do this we aim to focus on genetic studies on glia targets, functional studies in living human epileptic tissue and MTLE-HS mouse models including febrile seizures, studies on knockout animals, and other functional and molecular biological studies.
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Picture: Association analysis in patients with temporal lobe epilepsy (TLE) with history of Febrile Seizures (FS) versus TLE patients without FS. Haploview analysis in KCNJ10/KCNJ9. SNPs with significant association with TLE-FS. KCNJ10 and KCNJ9 are encoded in opposite directions. LD plot for KCNJ10, KCNJ9 and the intermediate region in TLE-FS. Haplotype block containing both genes KCNJ10 and KCNJ9 and the intermediate region. Associated SNPs are marked with *. (from Oslo group)
PROJECT LEADER:
Professor Erik Taubøll, Department of Neurology, Oslo University Hospital (Rikshospitalet), Norway
PRINCIPAL INVESTIGATORS:
Professor Reetta Kälviäinen, Kuopio Epilepsy Center, Kuopio University Hospital, University of Eastern Finland
Professor Christian Steinhäuser, Institute of Cellular Neurosciences, University of Bonn, Germany
ASSOCIATED PARTNERS:
Dr Pierre N.E. de Graan, Rudolf Magnus Institute for Neuroscience, University Medical Center Utrecht, Netherlands
