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Identifying radiation exposure biomarkers from mouse blood transcriptome

ABSTRACT: Here, we present a whole-genome survey of the murine transcriptomic response to physiologically-relevant radiation doses, 2 and 8 Gy.

ORGANISM(S): Mus musculus

PROVIDER: GSE33172 | GEO | 2012/06/01

SECONDARY ACCESSION(S): PRJNA149219

REPOSITORIES: GEO

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Identifying radiation exposure biomarkers from mouse blood transcriptome

Project description:Here, we present a whole-genome survey of the murine transcriptomic response to physiologically-relevant radiation doses, 2 and 8 Gy. There are 18 distinct biological samples here. Mice were exposed to ionizing radiation (Cesium-138 source) and whole blood was collected by cardiac puncture 6 hours post treatment. Doses were 0 (7 samples), 2 (5 samples), and 8 (6 samples) gy.

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Project description:To further development of our gene expression approach to biodosimetry, we have employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential to distinguish radiation dose across an exposure range relevant for medical decision-making in a radiological emergency. Human peripheral blood from healthy donors was irradiated ex vivo, and a 74-gene consensus signature was identified that distinguished between four radiation doses (0.5, 2, 5 and 8 Gy) and control samples. The same set of genes separated samples by exposure level at both six and 24 hours after treatment, with overlap evident only at the highest two doses (5 and 8 Gy). Expression of five genes (CDKN1A, FDXR, SESN1, BBC3 and PHPT1) from this signature was quantified in the same RNA samples by real-time PCR, confirming low variability between donors as well as the predicted radiation response pattern. Experiment Overall Design: Radiation induced gene expression in human blood was measured at 6 and 24 hours after exposure to doses of 0, 0.5, 2, 5 and 8 Gy g-rays. Five independent experiments were performed at each time (6 or 24 hours) using different donors for each experiment

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Project description:Cognitive impairments are an important side effect after radiation exposure. Yet, it comes more and more into scientific focus that ionising radiation can resemble pathologies of neurodegenerative diseases such as Alzheimer´s. Here, we used a multidisciplinary approach to elucidate the effect of chronic low-dose irradiation exposure (1 mGy/day and 20 mGy/day) over 300 days (cumulative dose of 0.3 Gy and 6.0 Gy) on the murine ApoE-/- hippocampus as an Alzheimer´s model. By using mass spectrometry to quantify global expression levels of unmodified proteins, phospho-proteins and N-linked sialylated glycoproteins, we found nearly exclusive changes on the phospho-proteome at both doses. These proteins regulate signalling of synaptic plasticity and calcium-dependent signalling. We used synaptic plasticity-targeted transcriptomics, immunoblotting and ELISA to validate our findings and could identify that memory-related CREB signalling is reduced at both doses whereas Rac1-Cofilin signalling is only altered at 1 mGy/day. Interestingly, we noted a reduction in the number of activated microglia in the molecular layer of the hippocampus only at 1 mGy/day paralleled with reduced levels of TNFα mRNA and lipid peroxidation at this dose. Adult neurogenesis (Ki67, GFAP and NeuN as markers) and cell death (activated caspase-3) were not changed / initiated at both doses. Our analysis showed that several molecular targets induced by chronic low-dose radiation overlap with molecular targets of Alzheimer´s pathology. We suggest that chronic low-dose ionising radiation can be a potential confounder in Alzheimer´s disease.

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