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

S. J. Kempf, Dirk Janik, Zarko Barjaktarovic, I. Braga-Tanaka III, Satoshi Tanaka, Frauke Neff, Anna Saran, Martin Røssel Larsen, Soile Tapio

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Resumé

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.
OriginalsprogEngelsk
TidsskriftOncoTarget
Vol/bind7
Udgave nummer44
Sider (fra-til)71817-71832
ISSN1949-2553
DOI
StatusUdgivet - 2016

Citer dette

Kempf, S. J., Janik, D., Barjaktarovic, Z., Braga-Tanaka III, I., Tanaka, S., Neff, F., ... Tapio, S. (2016). Chronic low-dose-rate ionising radiation affects the hippocampal phosphoproteome in the ApoE-/- Alzheimer's mouse model. OncoTarget, 7(44), 71817-71832. https://doi.org/10.18632/oncotarget.12376
Kempf, S. J. ; Janik, Dirk ; Barjaktarovic, Zarko ; Braga-Tanaka III, I. ; Tanaka, Satoshi ; Neff, Frauke ; Saran, Anna ; Larsen, Martin Røssel ; Tapio, Soile. / Chronic low-dose-rate ionising radiation affects the hippocampal phosphoproteome in the ApoE-/- Alzheimer's mouse model. I: OncoTarget. 2016 ; Bind 7, Nr. 44. s. 71817-71832.
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title = "Chronic low-dose-rate ionising radiation affects the hippocampal phosphoproteome in the ApoE-/- Alzheimer's mouse model",
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.",
author = "Kempf, {S. J.} and Dirk Janik and Zarko Barjaktarovic and {Braga-Tanaka III}, I. and Satoshi Tanaka and Frauke Neff and Anna Saran and Larsen, {Martin R{\o}ssel} and Soile Tapio",
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Kempf, SJ, Janik, D, Barjaktarovic, Z, Braga-Tanaka III, I, Tanaka, S, Neff, F, Saran, A, Larsen, MR & Tapio, S 2016, 'Chronic low-dose-rate ionising radiation affects the hippocampal phosphoproteome in the ApoE-/- Alzheimer's mouse model', OncoTarget, bind 7, nr. 44, s. 71817-71832. https://doi.org/10.18632/oncotarget.12376

Chronic low-dose-rate ionising radiation affects the hippocampal phosphoproteome in the ApoE-/- Alzheimer's mouse model. / Kempf, S. J.; Janik, Dirk; Barjaktarovic, Zarko; Braga-Tanaka III, I.; Tanaka, Satoshi; Neff, Frauke; Saran, Anna; Larsen, Martin Røssel; Tapio, Soile.

I: OncoTarget, Bind 7, Nr. 44, 2016, s. 71817-71832.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Chronic low-dose-rate ionising radiation affects the hippocampal phosphoproteome in the ApoE-/- Alzheimer's mouse model

AU - Kempf, S. J.

AU - Janik, Dirk

AU - Barjaktarovic, Zarko

AU - Braga-Tanaka III, I.

AU - Tanaka, Satoshi

AU - Neff, Frauke

AU - Saran, Anna

AU - Larsen, Martin Røssel

AU - Tapio, Soile

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

U2 - 10.18632/oncotarget.12376

DO - 10.18632/oncotarget.12376

M3 - Journal article

C2 - 27708245

VL - 7

SP - 71817

EP - 71832

JO - OncoTarget

JF - OncoTarget

SN - 1949-2553

IS - 44

ER -