Universität zu Köln

Volmering, Elisa, Niehusmann, Pitt, Peeva, Viktoriya, Grote, Alexander, Zsurka, Gabor ORCID: 0000-0002-6379-849X, Altmueller, Janine, Nuernberg, Peter, Becker, Albert J., Schoch, Susanne, Elger, Christian E. and Kunz, Wolfram S. ORCID: 0000-0003-1113-3493 (2016). Neuropathological signs of inflammation correlate with mitochondrial DNA deletions in mesial temporal lobe epilepsy. Acta Neuropathol., 132 (2). S. 277 - 289. NEW YORK: SPRINGER. ISSN 1432-0533

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Abstract

Accumulation of mitochondrial DNA (mtDNA) deletions has been proposed to be responsible for the presence of respiratory-deficient neurons in several CNS diseases. Deletions are thought to originate from double-strand breaks due to attack of reactive oxygen species (ROS) of putative inflammatory origin. In epileptogenesis, emerging evidence points to chronic inflammation as an important feature. Here we aimed to analyze the potential association of inflammation and mtDNA deletions in the hippocampal tissue of patients with mesial temporal lobe epilepsy (mTLE) and hippocampal sclerosis (HS). Hippocampal and parahippocampal tissue samples from 74 patients with drug-refractory mTLE served for mtDNA analysis by multiplex PCR as well as long-range PCR, single-molecule PCR and ultra-deep sequencing of mtDNA in selected samples. Patients were sub-classified according to neuropathological findings. Semi-quantitative assessment of neuronal cell loss was performed in the hippocampal regions CA1-CA4. Inflammatory infiltrates were quantified by cell counts in the CA1, CA3 and CA4 regions from well preserved hippocampal samples (n = 33). Samples with HS showed a significantly increased frequency of a 7436-bp mtDNA deletion (p < 0.0001) and a higher proportion of somatic G > T transversions compared to mTLE patients with different histopathology. Interestingly, the number of T-lymphocytes in the hippocampal CA1, CA3 and CA4 regions was, similar to the 7436-bp mtDNA deletion, significantly increased in samples with HS compared to other subgroups. Our findings show a coincidence of HS, increased somatic G > T transversions, the presence of a specific mtDNA deletion, and increased inflammatory infiltrates. These results support the hypothesis that chronic inflammation leads to mitochondrial dysfunction by ROS-mediated mtDNA mutagenesis which promotes epileptogenesis and neuronal cell loss in patients with mTLE and HS.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Volmering, Elisa UNSPECIFIED UNSPECIFIED UNSPECIFIED Niehusmann, Pitt UNSPECIFIED UNSPECIFIED UNSPECIFIED Peeva, Viktoriya UNSPECIFIED UNSPECIFIED UNSPECIFIED Grote, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Zsurka, Gabor UNSPECIFIED orcid.org/0000-0002-6379-849X UNSPECIFIED Altmueller, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuernberg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Becker, Albert J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schoch, Susanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Elger, Christian E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kunz, Wolfram S. UNSPECIFIED orcid.org/0000-0003-1113-3493 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-268604
DOI:	10.1007/s00401-016-1561-1
Journal or Publication Title:	Acta Neuropathol.
Volume:	132
Number:	2
Page Range:	S. 277 - 289
Date:	2016
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1432-0533
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HIPPOCAMPAL SCLEROSIS; OXIDATIVE STRESS; MUTATIONS; DYSFUNCTION; OXIDASE; DAMAGE; REPLICATION; INVOLVEMENT; DEFICIENCY; DISORDERS Multiple languages Clinical Neurology; Neurosciences; Pathology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/26860