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PXD003969

PXD003969 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleChronic low-dose ionising radiation rates affect the hippocampal phospho-proteome of synaptogenesis in an ApoE-/--Alzheimer mouse model over 300 days of exposure
DescriptionCognitive 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.
HostingRepositoryPRIDE
AnnounceDate2017-07-25
AnnouncementXMLSubmission_2017-07-25_06:02:32.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterStefan J. Kempf
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListTMT6plex-126 reporter+balance reagent acylated residue; phosphorylated residue; deamidated residue; iodoacetamide derivatized residue
InstrumentQ Exactive HF; Orbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02016-04-14 03:34:04ID requested
12017-07-25 06:02:33announced
Publication List
Kempf SJ, Janik D, Barjaktarovic Z, Braga-Tanaka I, Tanaka S, Neff F, Saran A, Larsen MR, Tapio S, Chronic low-dose-rate ionising radiation affects the hippocampal phosphoproteome in the ApoE-/- Alzheimer's mouse model. Oncotarget, 7(44):71817-71832(2016) [pubmed]
Keyword List
curator keyword: Biomedical
submitter keyword: Synaptic plasticity, hippocampus, dendritic spine, CREB, synapse, proteomics, phospho-proteomics
Contact List
Martin R. Larsen
contact affiliationDepartment of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark
contact emailmrl@bmb.sdu.dk
lab head
Stefan J. Kempf
contact affiliationUniversity of Southern Denmark
contact emailstefank@bmb.sdu.dk
dataset submitter
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