The age and genomic integrity of neurons after cortical stroke in humans

Hagen B Huttner; Olaf Bergmann; Mehran Salehpour; Attila Rácz; Jemal Tatarishvili; Emma Lindgren; Tamás Csonka; László Csiba; Tibor Hortobágyi; Gábor Méhes; Elisabet Englund; Beata Werne Solnestam; Sofia Zdunek; Christian Scharenberg; Lena Ström; Patrik Ståhl; Benjamin Sigurgeirsson; Andreas Dahl; Stefan Schwab; Göran Possnert; Samuel Bernard; Zaal Kokaia; Olle Lindvall; Joakim Lundeberg; Jonas Frisén

doi:10.1038/nn.3706

The age and genomic integrity of neurons after cortical stroke in humans

Nat Neurosci. 2014 Jun;17(6):801-3. doi: 10.1038/nn.3706. Epub 2014 Apr 20.

Authors

Hagen B Huttner¹, Olaf Bergmann², Mehran Salehpour³, Attila Rácz⁴, Jemal Tatarishvili⁵, Emma Lindgren⁶, Tamás Csonka⁷, László Csiba⁸, Tibor Hortobágyi⁷, Gábor Méhes⁷, Elisabet Englund⁹, Beata Werne Solnestam¹⁰, Sofia Zdunek⁶, Christian Scharenberg¹¹, Lena Ström⁶, Patrik Ståhl⁶, Benjamin Sigurgeirsson¹⁰, Andreas Dahl¹², Stefan Schwab⁴, Göran Possnert³, Samuel Bernard¹³, Zaal Kokaia⁵, Olle Lindvall⁵, Joakim Lundeberg¹⁰, Jonas Frisén⁶

Affiliations

¹ 1] Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden. [2] Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany. [3].
² 1] Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden. [2].
³ Department of Physics and Astronomy, Ion Physics, Uppsala University, Sweden.
⁴ Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany.
⁵ Lund Stem Cell Center, University Hospital, Lund, Sweden.
⁶ Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden.
⁷ Department of Neuropathology, Institute of Pathology, University of Debrecen, Medical and Health Science Centre, Debrecen, Hungary.
⁸ Department of Neurology, University of Debrecen, Medical and Health Science Centre, Debrecen, Hungary.
⁹ Department of Pathology, University Hospital, Lund, Sweden.
¹⁰ Department of Gene Technology, Royal Institute of Technology, SciLifeLab, Stockholm, Sweden.
¹¹ 1] Center for Hematology and Regenerative Medicine, Karolinska University Hospital, Huddinge, Sweden. [2] Department of Medicine, Skaraborgs Sjukhus Skövde, Sweden.
¹² Deep Sequencing Group, SFB655, Biotechnology Center, TU-Dresden, Dresden, Germany.
¹³ Department of Mathematics, Institut Camille Jordan, Université de Lyon, Villeurbanne cedex, France.

PMID: 24747576
DOI: 10.1038/nn.3706

Abstract

It has been unclear whether ischemic stroke induces neurogenesis or neuronal DNA rearrangements in the human neocortex. Using immunohistochemistry; transcriptome, genome and ploidy analyses; and determination of nuclear bomb test-derived (14)C concentration in neuronal DNA, we found neither to be the case. A large proportion of cortical neurons displayed DNA fragmentation and DNA repair a short time after stroke, whereas neurons at chronic stages after stroke showed DNA integrity, demonstrating the relevance of an intact genome for survival.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Cellular Senescence / physiology*
DNA Fragmentation*
DNA Repair / physiology*
Female
Humans
Male
Middle Aged
Neocortex / pathology*
Neocortex / physiology
Neurons / pathology*
Neurons / physiology
Stroke / genetics*
Stroke / pathology*

Associated data

GEO/GSE56267
SRA/SRP040676