Differences between RNA and DNA due to RNA editing in temporal lobe epilepsy

• Published in: Neurobiology of disease 2013-08, Vol.56, p.66-73
• Main Authors: Krestel, Heinz, Raffel, Simon, von Lehe, Marec, Jagella, Caroline, Moskau-Hartmann, Susanna, Becker, Albert, Elger, Christian E, Seeburg, Peter H, Nirkko, Arto
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Age; All-or-none RNA editing; Animals; Clinical parameter correlation; DNA - genetics; Electroencephalography; Epilepsy, Temporal Lobe - genetics; Estimated effect size; Female; GluA3; Hippocampus - drug effects; Hippocampus - metabolism; Humans; Kv1.1; Kv1.1 Potassium Channel - metabolism; Male; Mice; Mice, Inbred C57BL; Neurology; Pharmacotherapy-resistant epilepsy; Receptors, AMPA - genetics; RNA - genetics; RNA Editing - physiology; Young Adult
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1016/j.nbd.2013.04.006

Abstract To investigate whether alterations in RNA editing (an enzymatic base-specific change to the RNA sequence during primary transcript formation from DNA) of neurotransmitter receptor genes and of transmembrane ion channel genes play a role in human temporal lobe epilepsy (TLE), this exploratory study analyzed 14 known cerebral editing sites in RNA extracted from the brain tissue of 41 patients who underwent surgery for mesial TLE, 23 with hippocampal sclerosis (MTLE + HS). Because intraoperatively sampled RNA cannot be obtained from healthy controls and the best feasible control is identically sampled RNA from patients with a clinically shorter history of epilepsy, the primary aim of the study was to assess the correlation between epilepsy duration and RNA editing in the homogenous group of MTLE + HS. At the functionally relevant I/V site of the voltage-gated potassium channel Kv1.1, an inverse correlation of RNA editing was found with epilepsy duration (r = − 0.52, p = 0.01) but not with patient age at surgery, suggesting a specific association with either the epileptic process itself or its antiepileptic medication history. No significant correlations were found between RNA editing and clinical parameters at other sites within glutamate receptor or serotonin 2C receptor gene transcripts. An “all-or-none” (≥ 95% or ≤ 5%) editing pattern at most or all sites was discovered in 2 patients. As a secondary part of the study, RNA editing was also analyzed as in the previous literature where up to now, few single editing sites were compared with differently obtained RNA from inhomogenous patient groups and autopsies, and by measuring editing changes in our mouse model. The present screening study is first to identify an editing site correlating with a clinical parameter, and to also provide an estimate of the possible effect size at other sites, which is a prerequisite for power analysis needed in planning future studies.