Gene profiling in temporal lobe epilepsy tissue and dysplastic lesions

Epilepsies are among the most frequent CNS disorders, affecting approximately 1% of the population in the world. In pharmacoresistant patients with focal epilepsies, surgical removal of the epileptogenic focus allows access to human tissue for neuropathologic and molecular biologic analyses. Ammon's horn sclerosis (AHS) of the hippocampal formation in temporal lobe epilepsy (TLE), highly differentiated glioneuronal malformations, and tumors such as gangliogliomas constitute frequent neuropathologic findings in biopsy specimens. The multifactorial pathogenesis of the epilepsies includes molecular mechanisms of compromised neurodevelopment, neuronal plasticity, and aberrant cellular excitability, as well as neuronal cell degeneration in affected CNS areas. The complex pathology of focal epilepsies (including those with glioneuronal lesions) renders them a particular challenge - and opportunity - for functional genomics investigations. A comprehensive analysis of transcriptional commands, as well as tissue- and cell-specific expression profiles, may provide insights into underlying mechanisms, despite the large number of expressed genes in normal and diseased brain tissue and the possibilities of dynamic epigenetic modifications. The recent development in microarray and gene-expression profiling technologies allows transcriptional studies of large numbers of genes, by using minute amounts of tissue (or even single cells). In combination, laser-microdissection approaches and powerful mRNA amplification strategies [e.g., quantitative reverse transcription-polymerase chain reaction (RT-PCR) technologies] facilitate large-scale expression analysis in well-defined tissue specimens or cellular subpopulations. The integration and interpretation of large amounts of array data, from different epilepsy models and disease states, are ongoing challenges. These data may provide an important basis from which to gain new insights in the pathogenesis of epilepsies.