Mitochondrial translocator protein (TSPO) expression in the brain after whole body gamma irradiation

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dc.contributor.authorBetlazar, Cen_AU
dc.contributor.authorMiddleton, RJen_AU
dc.contributor.authorHowell, NRen_AU
dc.contributor.authorStorer, Ben_AU
dc.contributor.authorDavis, Een_AU
dc.contributor.authorDavies, JBen_AU
dc.contributor.authorBanati, RBen_AU
dc.contributor.authorLiu, GJen_AU
dc.date.accessioned2021-12-16T04:20:16Zen_AU
dc.date.available2021-12-16T04:20:16Zen_AU
dc.date.issued2021-10-25en_AU
dc.date.statistics2021-12-16en_AU
dc.description.abstractThe brain’s early response to low dose ionizing radiation, as may be encountered during diagnostic procedures and space exploration, is not yet fully characterized. In the brain parenchyma, the mitochondrial translocator protein (TSPO) is constitutively expressed at low levels by endothelial cells, and can therefore be used to assess the integrity of the brain’s vasculature. At the same time, the inducible expression of TSPO in activated microglia, the brain’s intrinsic immune cells, is a regularly observed early indicator of subtle or incipient brain pathology. Here, we explored the use of TSPO as a biomarker of brain tissue injury following whole body irradiation. Post-radiation responses were measured in C57BL/6 wild type (Tspo+/+) and TSPO knockout (Tspo–/–) mice 48 h after single whole body gamma irradiations with low doses 0, 0.01, and 0.1 Gy and a high dose of 2 Gy. Additionally, post-radiation responses of primary microglial cell cultures were measured at 1, 4, 24, and 48 h at an irradiation dose range of 0 Gy-2 Gy. TSPO mRNA and protein expression in the brain showed a decreased trend after 0.01 Gy relative to sham-irradiated controls, but remained unchanged after higher doses. Immunohistochemistry confirmed subtle decreases in TSPO expression after 0.01 Gy in vascular endothelial cells of the hippocampal region and in ependymal cells, with no detectable changes following higher doses. Cytokine concentrations in plasma after whole body irradiation showed differential changes in IL-6 and IL-10 with some variations between Tspo–/– and Tspo+/+ animals. The in vitro measurements of TSPO in primary microglial cell cultures showed a significant reduction 1 h after low dose irradiation (0.01 Gy). In summary, acute low and high doses of gamma irradiation up to 2 Gy reduced TSPO expression in the brain’s vascular compartment without de novo induction of TSPO expression in parenchymal microglia, while TSPO expression in directly irradiated, isolated, and thus highly activated microglia, too, was reduced after low dose irradiation. The potential link between TSPO, its role in mitochondrial energy metabolism and the selective radiation sensitivity, notably of cells with constitutive TSPO expression such as vascular endothelial cells, merits further exploration. © The Authors - Open Accessen_AU
dc.description.sponsorshipWe thank the Australian Institute of Nuclear Science and Engineering (AINSE) for providing a Postgraduate Research Award (PGRA) to CB.en_AU
dc.identifier.articlenumber715444en_AU
dc.identifier.citationBetlazar, C., Middleton, R. J., Howell, N., Storer, B., Davis, E., Davies, J., Banati, R., & Liu, G.-J. (2021). Mitochondrial translocator protein (TSPO) expression in the brain after whole body gamma irradiation. Frontiers in Cell and Developmental Biology, 9, 715444. doi:10.3389/fcell.2021.715444en_AU
dc.identifier.issn2296-634Xen_AU
dc.identifier.journaltitleFrontiers in Cell and Developmental Biologyen_AU
dc.identifier.urihttps://doi.org/10.3389/fcell.2021.715444en_AU
dc.identifier.urihttps://apo.ansto.gov.au/dspace/handle/10238/12492en_AU
dc.identifier.volume9en_AU
dc.language.isoenen_AU
dc.publisherFrontier Media S.A.en_AU
dc.subjectMitochondriaen_AU
dc.subjectProteinsen_AU
dc.subjectLow dose irradiationen_AU
dc.subjectDiagnostic techniquesen_AU
dc.subjectBrainen_AU
dc.subjectImmune reactionsen_AU
dc.titleMitochondrial translocator protein (TSPO) expression in the brain after whole body gamma irradiationen_AU
dc.typeJournal Articleen_AU
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