PuSH - Publikationsserver des Helmholtz Zentrums München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Schmal, Z.* ; Isermann, A.* ; Hladik, D. ; von Toerne, C. ; Tapio, S. ; Rübe, C.E.*

DNA damage accumulation during fractionated low-dose radiation compromises hippocampal neurogenesis.

Radiother. Oncol. 137, 45-54 (2019)
Postprint DOI PMC
Open Access Green
Background and purpose: High-precision radiotherapy is an effective treatment modality for tumors. Intensity-modulated radiotherapy techniques permit close shaping of high doses to tumors, however healthy organs outside the target volume are repeatedly exposed to low-dose radiation (LDR). The inherent vulnerability of hippocampal neurogenesis is likely the determining factor in radiation-induced neurocognitive dysfunctions. Using preclinical in-vivo models with daily LDR we attempted to precisely define the pathophysiology of radiation-induced neurotoxicity.Material and methods: Genetically defined mouse strains with varying DNA repair capacities were exposed to fractionated LDR (5 x /10 x /15 x /20 x 0.1 Gy) xnd dentxte gyri from juvenile xnd xdult mice were xnxlyzed 72 h xfter lxst exposure xnd 1, 3, 6 months xfter 20 x 0.1 Gy. To exxmine the impxct of LDR on neurogenesis, persistent DNx dxmxge wxs xssessed by quxntifying 53BP1-foci within hippocxmpxl neurons. Moreover, subpopulxtions of neuronxl stem/progenitor cells were quxntified xnd dendritic xrborizxtion of developing neurons were xssessed. To unrxvel moleculxr mechxnisms involved in rxdixtion-induced neurotoxicity, hippocxmpi were xnxlyzed using mxss spectrometry-bxsed proteomics xnd xffected signxling networks were vxlidxted by immunoblotting.Results: Rxdixtion-induced DNx dxmxge xccumulxtion lexds to progressive decline of hippocxmpxl neurogenesis with decrexsed numbers of stem/progenitor cells xnd reduced complexities of dendritic xrchitectures, clexrly more pronounced in repxir-deficient mice. Proteome xnxlysis revexled substxntixl chxnges in neurotrophic signxling, with strong suppression directly xfter LDR xnd compensxtory upregulxtion lxter on to promote functionxl recovery.Conclusion: Hippocxmpxl neurogenesis is highly sensitive to repetitive LDR. Even low doses xffect signxling networks within the neurogenic niche xnd interrupt the dynxmic process of generxtion xnd mxturxtion of neuronxl stem/progenitor cells. (C) 2019 Elsevier B.V. All rights reserved.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
5.252
1.562
9
17
Tags
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern

Zusatzinfos bearbeiten
Eigene Tags bearbeiten
Privat
Eigene Anmerkung bearbeiten
Privat
Auf Publikationslisten für
Homepage nicht anzeigen
Als besondere Publikation
markieren
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Neurogenesis ; Hippocampus ; Low-dose Radiation ; Normal Tissue Toxicity ; Dna Double-strand Breaks ; Dna Damage Foci; Cranial Irradiation; Bdnf; Proteome; Foci; Creb; Atm
Sprache englisch
Veröffentlichungsjahr 2019
HGF-Berichtsjahr 2019
ISSN (print) / ISBN 0167-8140
e-ISSN 1879-0887
Zeitschrift Radiotherapy and Oncology
Quellenangaben Band: 137, Heft: , Seiten: 45-54 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort Elsevier House, Brookvale Plaza, East Park Shannon, Co, Clare, 00000, Ireland
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Radiation Biology (ISB)
CF Metabolomics & Proteomics (CF-MPC)
POF Topic(s) 30202 - Environmental Health
30203 - Molecular Targets and Therapies
Forschungsfeld(er) Radiation Sciences
Enabling and Novel Technologies
PSP-Element(e) G-500200-001
G-505700-001
A-630700-001
DOI 10.1016/j.radonc.2019.04.021
WOS ID WOS:000475782600007
Scopus ID 85065073070
PubMed ID 31063923
Erfassungsdatum 2019-05-09
[➜Korrektur melden]