Universität zu Köln

Kobow, Katja, Kaspi, Antony ORCID: 0000-0001-6576-5862, Harikrishnan, K. N., Kiese, Katharina, Ziemann, Mark ORCID: 0000-0002-7688-6974, Khurana, Ishant ORCID: 0000-0001-9050-2749, Fritzsche, Ina, Hauke, Jan, Hahnen, Eric, Coras, Roland, Muehlebner, Angelika, El-Osta, Assam ORCID: 0000-0001-7968-7375 and Bluemcke, Ingmar (2013). Deep sequencing reveals increased DNA methylation in chronic rat epilepsy. Acta Neuropathol., 126 (5). S. 741 - 757. NEW YORK: SPRINGER. ISSN 1432-0533

Full text not available from this repository.

Abstract

Epilepsy is a frequent neurological disorder, although onset and progression of seizures remain 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 remarkably diverse pattern of gene expression implicating epigenetic changes to contribute to disease progression. Here we mapped for the first time global DNA methylation patterns in chronic epileptic rats and controls. Using methyl-CpG capture associated with massive parallel sequencing (Methyl-Seq) we report the genomic methylation signature of the chronic epileptic state. We observed a predominant increase, rather than loss of DNA methylation in chronic rat epilepsy. Aberrant methylation patterns were inversely correlated with gene expression changes using mRNA sequencing from same animals and tissue specimens. Administration of a ketogenic, high-fat, low-carbohydrate diet attenuated seizure progression and ameliorated DNA methylation mediated changes in gene expression. This is the first report of unsupervised clustering of an epigenetic mark being used in epilepsy research to separate epileptic from non-epileptic animals as well as from animals receiving anti-convulsive dietary treatment. We further discuss the potential impact of epigenetic changes as a pathogenic mechanism of epileptogenesis.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kobow, Katja UNSPECIFIED UNSPECIFIED UNSPECIFIED Kaspi, Antony UNSPECIFIED orcid.org/0000-0001-6576-5862 UNSPECIFIED Harikrishnan, K. N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kiese, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Ziemann, Mark UNSPECIFIED orcid.org/0000-0002-7688-6974 UNSPECIFIED Khurana, Ishant UNSPECIFIED orcid.org/0000-0001-9050-2749 UNSPECIFIED Fritzsche, Ina UNSPECIFIED UNSPECIFIED UNSPECIFIED Hauke, Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED Hahnen, Eric UNSPECIFIED UNSPECIFIED UNSPECIFIED Coras, Roland UNSPECIFIED UNSPECIFIED UNSPECIFIED Muehlebner, Angelika UNSPECIFIED UNSPECIFIED UNSPECIFIED El-Osta, Assam UNSPECIFIED orcid.org/0000-0001-7968-7375 UNSPECIFIED Bluemcke, Ingmar UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-473232
DOI:	10.1007/s00401-013-1168-8
Journal or Publication Title:	Acta Neuropathol.
Volume:	126
Number:	5
Page Range:	S. 741 - 757
Date:	2013
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1432-0533
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TEMPORAL-LOBE EPILEPSY; DIFFERENTIAL EXPRESSION ANALYSIS; GENE-EXPRESSION; KETOGENIC DIET; HISTONE MODIFICATIONS; CHROMATIN; PROMOTER; SEIZURES; EPILEPTOGENESIS; INTERLEUKIN-10 Multiple languages Clinical Neurology; Neurosciences; Pathology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47323