PXD003969

PXD003969 is an original dataset announced via ProteomeXchange.

Title	Chronic low-dose ionising radiation rates affect the hippocampal phospho-proteome of synaptogenesis in an ApoE-/--Alzheimer mouse model over 300 days of exposure
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.
HostingRepository	PRIDE
AnnounceDate	2017-07-25
AnnouncementXML	Submission_2017-07-25_06:02:32.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Stefan J. Kempf
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; phosphorylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2016-04-14 03:34:04	ID requested
⏵ 1	2017-07-25 06:02:33	announced

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]

curator keyword: Biomedical

submitter keyword: Synaptic plasticity, hippocampus, dendritic spine, CREB, synapse, proteomics, phospho-proteomics

Martin R. Larsen
contact affiliation	Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark
contact email	mrl@bmb.sdu.dk
lab head
Stefan J. Kempf
contact affiliation	University of Southern Denmark
contact email	stefank@bmb.sdu.dk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD003969
     1. Label: PRIDE project
     2. Name: Chronic low-dose ionising radiation rates affect the hippocampal phospho-proteome of synaptogenesis in an ApoE-/--Alzheimer mouse model over 300 days of exposure