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Hladik, D. ; Dalke, C. ; von Toerne, C. ; Hauck, S.M. ; Azimzadeh, O.* ; Philipp, J. ; Ung, M.-C. ; Schlattl, H. ; Rößler, U.* ; Graw, J. ; Atkinson, M.J. ; Tapio, S.

Creb signaling mediates dose-dependent radiation response in the murine hippocampus two years after total body exposure.

J. Proteome Res. 19, 337-345 (2020)
Postprint DOI PMC
Open Access Green
The impact of low-dose ionizing radiation (IR) on the human brain has recently attracted attention due to the increased use of IR for diagnostic purposes. The aim of this study was to investigate low-dose radiation response in the hippocampus. Female B6C3F1 mice were exposed to total body irradiation with 0 (control), 0.063, 0.125, or 0.5 Gy. Quantitative label-free proteomic analysis of the hippocampus was performed after 24 months. CREB signaling and CREB-associated pathways were affected at all doses. The lower doses (0.063 and 0.125 Gy) induced the CREB pathway, whereas the exposure to 0.5 Gy deactivated CREB. Similarly, the lowest dose (0.063 Gy) was anti-inflammatory, reducing the number of activated microglia. In contrast, induction of activated microglia and reactive astroglia was found at 0.5 Gy, suggesting increased inflammation and astrogliosis, respectively. The apoptotic markers BAX and cleaved CASP-3 and oxidative stress markers were increased only at the highest dose. Since the activated CREB pathway plays a central role in learning and memory, these data suggest neuroprotection at the lowest dose (0.063 Gy) but neurodegeneration at 0.5 Gy. The response to 0.5 Gy resembles alterations found in healthy aging and thus may represent radiation-induced accelerated aging of the brain.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Ionizing Radiation ; Label-free Proteomics ; Hippocampus ; Creb Signaling ; Brain ; Aging; Ionizing-radiation; Oxidative Stress; Synaptic Plasticity; Ct Scans; Brain; Transcription; Proteome; Defects; Risk; Neurodegeneration
ISSN (print) / ISBN 1535-3893
e-ISSN 1535-3907
Journal Journal of Proteome Research
Quellenangaben Volume: 19, Issue: 1, Pages: 337-345 Article Number: , Supplement: ,
Publisher American Chemical Society (ACS)
Publishing Place 1155 16th St, Nw, Washington, Dc 20036 Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Radiation Biology (ISB)
Institute of Developmental Genetics (IDG)
CF Metabolomics & Proteomics (CF-MPC)
Institute of Radiation Medicine (IRM)