Universität zu Köln

Neuhaus, Johannes F. G., Baris, Olivier R., Hess, Simon, Moser, Natasha, Schroeder, Hannsjoerg, Chinta, Shankar J., Andersen, Julie K., Kloppenburg, Peter and Wiesner, Rudolf J. (2014). Catecholamine metabolism drives generation of mitochondrial DNA deletions in dopaminergic neurons. Brain, 137. S. 354 - 366. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2156

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Abstract

Accumulation of mitochondrial DNA deletions is observed especially in dopaminergic neurons of the substantia nigra during ageing and even more in Parkinson's disease. The resulting mitochondrial dysfunction is suspected to play an important role in neurodegeneration. However, the molecular mechanisms involved in the preferential generation of mitochondrial DNA deletions in dopaminergic neurons are still unknown. To study this phenomenon, we developed novel polymerase chain reaction strategies to detect distinct mitochondrial DNA deletions and monitor their accumulation patterns. Applying these approaches in in vitro and in vivo models, we show that catecholamine metabolism drives the generation and accumulation of these mitochondrial DNA mutations. As in humans, age-related accumulation of mitochondrial DNA deletions is most prominent in dopaminergic areas of mouse brain and even higher in the catecholaminergic adrenal medulla. Dopamine treatment of terminally differentiated neuroblastoma cells, as well as stimulation of dopamine turnover in mice over-expressing monoamine oxidase B both induce multiple mitochondrial DNA deletions. Our results thus identify catecholamine metabolism as the driving force behind mitochondrial DNA deletions, probably being an important factor in the ageing-associated degeneration of dopaminergic neurons.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Neuhaus, Johannes F. G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Baris, Olivier R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hess, Simon UNSPECIFIED UNSPECIFIED UNSPECIFIED Moser, Natasha UNSPECIFIED UNSPECIFIED UNSPECIFIED Schroeder, Hannsjoerg UNSPECIFIED UNSPECIFIED UNSPECIFIED Chinta, Shankar J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Andersen, Julie K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kloppenburg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Wiesner, Rudolf J. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-447480
DOI:	10.1093/brain/awt291
Journal or Publication Title:	Brain
Volume:	137
Page Range:	S. 354 - 366
Date:	2014
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1460-2156
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SUBSTANTIA-NIGRA; PARKINSONS-DISEASE; CLONAL EXPANSION; SKELETAL-MUSCLE; SH-SY5Y CELLS; HUMAN BRAIN; DAMAGE; MTDNA; NEUROMELANIN; CALCIUM Multiple languages Clinical Neurology; Neurosciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/44748