PuSH - Publication Server of Helmholtz Zentrum München

Kempf, S.J. ; Janik, D. ; Barjaktarovic, Z. ; Braga-Tanaka III, I.* ; Tanaka, S.* ; Neff, F. ; Saran, A.* ; Larsen, M.R.* ; Tapio, S.

Chronic low-dose-rate ionising radiation affects the hippocampal phosphoproteome in the ApoE-/- Alzheimer's mouse model.

Oncotarget 7, 71817-71832 (2016)
Publ. Version/Full Text Research data DOI PMC
Creative Commons Lizenzvertrag
Accruing data indicate that radiation-induced consequences resemble pathologies of neurodegenerative diseases such as Alzheimer´s. The aim of this study was to elucidate the effect on hippocampus of chronic low-dose-rate radiation exposure (1 mGy/day or 20 mGy/day) given over 300 days with cumulative doses of 0.3 Gy and 6.0 Gy, respectively. ApoE deficient mutant C57Bl/6 mouse was used as an Alzheimer´s model. Using mass spectrometry, a marked alteration in the phosphoproteome was found at both dose rates. The radiation-induced changes in the phosphoproteome were associated with the control of synaptic plasticity, calcium-dependent signalling and brain metabolism. An inhibition of CREB signalling was found at both dose rates whereas Rac1-Cofilin signalling was found activated only at the lower dose rate. Similarly, the reduction in the number of activated microglia in the molecular layer of hippocampus that paralleled with reduced levels of TNFα expression and lipid peroxidation was significant only at the lower dose rate. Adult neurogenesis, investigated by Ki67, GFAP and NeuN staining, and cell death (activated caspase-3) were not influenced at any dose or dose rate. This study shows that several molecular targets induced by chronic low-dose-rate radiation overlap with those of Alzheimer´s pathology. It may suggest that ionising radiation functions as a contributing risk factor to this neurodegenerative disease.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Dendritic Spine ; Hippocampus ; Phosphoproteomics ; Synapse ; Synaptic Plasticity; Long-term Potentiation; Dentate Gyrus; X-irradiation; Phosphorylated Peptides; Synaptic Plasticity; Cranial Irradiation; Adult Neurogenesis; Disease; Mice; Brain
ISSN (print) / ISBN 1949-2553
e-ISSN 1949-2553
Journal OncoTarget
Quellenangaben Volume: 7, Issue: 44, Pages: 71817-71832 Article Number: , Supplement: ,
Publisher Impact Journals LLC
Publishing Place Albany
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Radiation Biology (ISB)
Institute of Pathology (PATH)