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57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

German Society for Neuropathology and Neuroanatomy

12. - 15.09.2012, Erlangen

57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

The methylation hypothesis in epilepsy

Meeting Abstract

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  • presenting/speaker Katja Kobow - University Hospital Erlangen, Neuropathology, Erlangen, Germany
  • Ingmar Blümcke - University Hospital Erlangen, Neuropathology, Erlangen, Germany

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie. 57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN). Erlangen, 12.-15.09.2012. Düsseldorf: German Medical Science GMS Publishing House; 2012. Doc12dgnnOP10

DOI: 10.3205/12dgnn010, URN: urn:nbn:de:0183-12dgnn0101

Published: September 11, 2012

© 2012 Kobow et al.
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Outline

Text

Epilepsy is a frequent neurological disorder. Onset and progression of seizures remain, however, difficult to predict in affected patients, irrespective of their epileptogenic condition. Previous studies in animal models as well as human epileptic brain tissue revealed a plethora of abnormally expressed genes until a chronic disease stage, suggesting aberrant epigenetic chromatin modifications to play an important role. DNA methylation is a covalent chromatin modification, characterized by the biochemical addition of a methyl group (-CH3) to cytosine nucleotides via a DNA methyltransferase enzyme. 5'-methylcytosine (5-mC), frequently called the fifth base, has been implicated in genome stability, silencing of transposable elements and repression of gene expression. DNA methylation dynamics influence brain development (e.g., lineage commitment) and function (e.g., LTP and memory formation) and are altered in many neurological disorders including autism, bipolar disorders, schizophrenia, brain tumors and neurodegeneration. There is growing evidence for aberrant epigenetic chromatin modifications also in experimental and human TLE. Thus, we hypothesize that initial precipitating injuries as much as seizures by themselves are a potent inducer of epigenetic alterations and thereby aggravate the epileptogenic condition resulting in structural brain lesion, drug resistance, and cognitive dysfunction (Kobow and Blumcke, 2011). It is the dynamics of epigenetic mechanisms which provide a likely explanation for some features of complex diseases, like symptomatic epilepsies, including late onset, parent-of-origin effects, discordance of monozygotic twins, and fluctuation of symptoms (Petronis, 2001).