Cellular sources and regional variations in the expression of the neuroinflammatory marker translocator protein (TSPO) in the normal brain

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dc.contributor.authorBetlazar, Cen_AU
dc.contributor.authorHarrison-Brown, Men_AU
dc.contributor.authorMiddleton, RJen_AU
dc.contributor.authorBanati, RBen_AU
dc.contributor.authorLiu, GJen_AU
dc.date.accessioned2022-08-29T02:10:49Zen_AU
dc.date.available2022-08-29T02:10:49Zen_AU
dc.date.issued2018-09-11en_AU
dc.date.statistics2022-08-04en_AU
dc.descriptionThis is an open access article distributed under the Creative Commons Attribution Licenseen_AU
dc.description.abstractThe inducible expression of the mitochondrial translocator protein 18 kDa (TSPO) by activated microglia is a prominent, regular feature of acute and chronic-progressive brain pathology. This expression is also the rationale for the continual development of new TSPO binding molecules for the diagnosis of “neuroinflammation” by molecular imaging. However, there is in the normal brain an ill-defined, low-level constitutive expression of TSPO. Taking advantage of healthy TSPO knockout mouse brain tissue to validate TSPO antibody specificity, this study uses immunohistochemistry to determine the regional distribution and cellular sources of TSPO in the normal mouse brain. Fluorescence microscopy revealed punctate TSPO immunostaining in vascular endothelial cells throughout the brain. In the olfactory nerve layers and glomeruli of the olfactory bulb, choroid plexus and ependymal layers, we confirm constitutive TSPO expression levels similar to peripheral organs, while some low TSPO expression is present in regions of known neurogenesis, as well as cerebellar Purkinje cells. The distributed-sparse expression of TSPO in endothelial mitochondria throughout the normal brain can be expected to give rise to a low baseline signal in TSPO molecular imaging studies. Finally, our study emphasises the need for valid and methodologically robust verification of the selectivity of TSPO ligands through the use of TSPO knockout tissues. © 2018 The Authorsen_AU
dc.description.sponsorshipThe authors would like to thank the Australian Institute of Nuclear Science and Engineering (AINSE) for providing financial assistance in the form of a Postgraduate Research Award (PGRA) to Calina Betlazar.en_AU
dc.identifier.articlenumber2707en_AU
dc.identifier.citationBetlazar, C., Harrison-Brown, M., Middleton, R. J., Banati, R., & Liu, G.-J. (2018). Cellular sources and regional variations in the expression of the neuroinflammatory marker translocator protein (TSPO) in the normal brain. International Journal of Molecular Sciences, 19(9), 2707. doi:10.3390/ijms19092707en_AU
dc.identifier.issn1422-0067en_AU
dc.identifier.issue9en_AU
dc.identifier.journaltitleInternational Journal of Molecular Sciencesen_AU
dc.identifier.urihttps://doi.org/10.3390/ijms19092707en_AU
dc.identifier.urihttps://apo.ansto.gov.au/dspace/handle/10238/13641en_AU
dc.identifier.volume19en_AU
dc.language.isoenen_AU
dc.publisherMultidisciplinary Digital Publishing Institute (MDPI)en_AU
dc.subjectAnimal cellsen_AU
dc.subjectInflammationen_AU
dc.subjectProteinsen_AU
dc.subjectBrainen_AU
dc.subjectMitochondriaen_AU
dc.subjectPositron computed tomographyen_AU
dc.titleCellular sources and regional variations in the expression of the neuroinflammatory marker translocator protein (TSPO) in the normal brainen_AU
dc.typeJournal Articleen_AU
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