Molecular profiling of temporal lobe epilepsy: comparison of data from human tissue samples and animal models

Abstract

The advent of gene chip technology and the era of functional genomics have initially been accompanied by huge anticipations to quickly unravel the molecular pathogenesis of multifactorial diseases. Expectations have, today, given way to some concerns about this non-hypothesis driven approach. However, the careful and controlled application of expression microarrays in concert with refined bioinformatic tools may provide novel insights in major disorders particularly of highly complex organs such as the central nervous system (CNS). Epilepsies are among the most frequent CNS disorders affecting approximately 1.5% of the population worldwide. In temporal lobe epilepsy (TLE), the seizure origin typically involves the hippocampal formation, a structure located in the mesial temporal lobe. Many TLE patients develop pharmacoresistance, i.e. seizures can no more be controlled by antiepileptic drugs. In order to achieve seizure control, surgical removal of the epileptogenic focus has been established as successful therapeutic strategy. Hippocampal biopsy tissue of pharmacoresistant TLE patients represents an excellent substrate to analyze molecular mechanisms related to structural and cellular reorganization in epilepsy. The complexity of alterations in TLE hippocampi suggests numerous genes and signaling cascades to be involved in the pathogenesis. By microarrays, genome wide expression profiles can be constituted from TLE tissues. However, hippocampi of pharmacoresistant TLE patients represent an advanced stage of the disease. Early stages of epilepsy development are not available for functional genome analysis in humans. Animal models of TLE appear particularly helpful to study molecular mechanisms of highly dynamic processes such as the development of hyperexcitability and pharmacoresistance. In this review, we summarize recent data of gene expression profiles in human and experimental TLE and discuss the relevance of novel tools for bioinformatic analysis and data mining.