Chronic low-dose-rate ionising radiation affects the hippocampal phosphoproteome in the ApoE

Stefan J. Kempf, Dirk Janik, Zarko Barjaktarovic, Ignacia Braga-Tanaka, Satoshi Tanaka, Frauke Neff, Anna Saran, Martin R. Larsen, Soile Tapio

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Abstract

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, calciumdependent 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 TNFa 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.
Original languageEnglish
Pages (from-to)71817 - 71832
Number of pages16
JournalOncotarget
Volume7
Issue number44
DOIs
Publication statusPublished - 2016
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Kempf, S. J., Janik, D., Barjaktarovic, Z., Braga-Tanaka, I., Tanaka, S., Neff, F., Saran, A., Larsen, M. R., & Tapio, S. (2016). Chronic low-dose-rate ionising radiation affects the hippocampal phosphoproteome in the ApoE. Oncotarget, 7(44), 71817 - 71832. https://doi.org/10.18632/oncotarget.12376