Etiology matters - Genomic DNA Methylation Patterns in Three Rat Models of Acquired Epilepsy

被引:78
作者
Debski, Konrad J. [1 ]
Pitkanen, Asla [2 ]
Puhakka, Noora [2 ]
Bot, Anna M. [1 ]
Khurana, Ishant [3 ]
Harikrishnan, K. N. [3 ]
Ziemann, Mark [3 ]
Kaspi, Antony [3 ]
El-Osta, Assam [3 ]
Lukasiuk, Katarzyna [1 ]
Kobow, Katja [4 ]
机构
[1] Polish Acad Sci, M Nencki Inst Expt Biol, Dept Mol & Cellular Neurobiol, Lab Epileptogenesis, Warsaw, Poland
[2] Univ Eastern Finland, Epilepsy Res Lab, AI Virtanen Inst Mol Sci, POB 1627, FIN-70211 Kuopio, Finland
[3] Alfred Med Res & Educ Precinct, Baker IDI Heart & Diabet Inst, Epigenet Human Hlth & Dis, Melbourne, Vic, Australia
[4] Univ Hosp Erlangen, Dept Neuropathol, Schwabachanlage 6, D-91054 Erlangen, Germany
基金
芬兰科学院;
关键词
TRAUMATIC BRAIN-INJURY; DIFFERENTIAL EXPRESSION ANALYSIS; EPIGENETIC MECHANISMS; PROMOTER METHYLATION; STATUS EPILEPTICUS; MESSENGER-RNA; GENE LISTS; EPILEPTOGENESIS; ISSUES; MEMORY;
D O I
10.1038/srep25668
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
This study tested the hypothesis that acquired epileptogenesis is accompanied by DNA methylation changes independent of etiology. We investigated DNA methylation and gene expression in the hippocampal CA3/dentate gyrus fields at 3 months following epileptogenic injury in three experimental models of epilepsy: focal amygdala stimulation, systemic pilocarpine injection, or lateral fluid-percussion induced traumatic brain injury (TBI) in rats. In the models studies, DNA methylation and gene expression profiles distinguished controls from injured animals. We observed consistent increased methylation in gene bodies and hypomethylation at non-genic regions. We did not find a common methylation signature in all three different models and few regions common to any two models. Our data provide evidence that genome-wide alteration of DNA methylation signatures is a general pathomechanism associated with epileptogenesis and epilepsy in experimental animal models, but the broad pathophysiological differences between models (i.e. pilocarpine, amygdala stimulation, and post-TBI) are reflected in distinct etiology-dependent DNA methylation patterns.
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页数:14
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