Increased Reelin Promoter Methylation Is Associated With Granule Cell Dispersion in Human Temporal Lobe Epilepsy
| Autor: | Ina Jeske, Michael Buchfelder, Hermann Stefan, Jan Hauke, Elisabeth Pauli, Michelle Hildebrandt, Eric Hahnen, Rolf Buslei, Ingmar Blümcke, Burkhard S. Kasper, Katja Kobow, Daniel Weigel |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Adult
Male Pathology medicine.medical_specialty Cell Adhesion Molecules Neuronal Hippocampus Cell Count Nerve Tissue Proteins Hippocampal formation Pathology and Forensic Medicine Cellular and Molecular Neuroscience S100 Calcium Binding Protein G medicine Humans Reelin Epigenetics Promoter Regions Genetic Neurons Analysis of Variance Extracellular Matrix Proteins Chi-Square Distribution biology Tumor Suppressor Proteins Dentate gyrus Serine Endopeptidases Nuclear Proteins Tumor Protein p73 General Medicine Methylation DNA Methylation Middle Aged Granule cell Granule cell dispersion DNA-Binding Proteins Reelin Protein medicine.anatomical_structure Epilepsy Temporal Lobe Gene Expression Regulation nervous system Neurology Calbindin 2 biology.protein Female Neurology (clinical) |
| Zdroj: | Journal of Neuropathology & Experimental Neurology. 68:356-364 |
| ISSN: | 1554-6578 0022-3069 |
| Popis: | Mesial temporal sclerosis (MTS) is the most common lesion in chronic, intractable temporal lobe epilepsies (TLE) and characterized by segmental neuronal cell loss in major hippocampal segments. Another histopathological hallmark includes granule cell dispersion (GCD), an architectural disturbance of the dentate gyrus encountered in approximately 50% of patients with mesial temporal sclerosis. Reelin, which plays a key role during hippocampal development and maintenance of laminar organization, is synthesized and released by Cajal-Retzius cells of the dentate molecular layer, and previous studies have shown that Reelin transcript levels are downregulated in human temporal lobe epilepsies specimens. To investigate whether epigenetic silencing by Reelin promoter methylation may be an underlying pathogenetic mechanism of GCD, DNA was harvested from 3 microdissected hippocampal subregions (i.e. molecular and granule cell layers of the dentate gyrus and presubiculum) from 8 MTS specimens with GCD, 5 TLE samples without GCD, and 3 autopsy controls. Promoter methylation was analyzed after bisulfite treatment, cloning, and direct sequencing; immunohistochemistry was performed to identify Cajal-Retzius cells. Reelin promoter methylation was found to be greater in TLE specimens than in controls; promoter methylation correlated with GCD among TLE specimens (p < 0.0002). No other clinical or histopathological parameter (i.e. sex, age, seizure duration, medication or extent, of MTS) correlated with promoter methylation. These data support a compromised Reelin-signaling pathway and identify promoter methylation as an epigenetic mechanism in the pathogenesis of TLE. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|