Positron emission tomography and functional characterization of a complete PBR/TSPO knockout

Simple item page
dc.contributor.authorBanati, RBen_AU
dc.contributor.authorMiddleton, RJen_AU
dc.contributor.authorChan, RHYen_AU
dc.contributor.authorHatty, CRen_AU
dc.contributor.authorWai-Ying Kam, Wen_AU
dc.contributor.authorQuin, Cen_AU
dc.contributor.authorGraeber, MBen_AU
dc.contributor.authorParmar, Aen_AU
dc.contributor.authorZahra, Den_AU
dc.contributor.authorCallaghan, PDen_AU
dc.contributor.authorFok, Sen_AU
dc.contributor.authorHowell, NRen_AU
dc.contributor.authorGrégoire, MCen_AU
dc.contributor.authorSzabo, Aen_AU
dc.contributor.authorPham, TQen_AU
dc.contributor.authorDavis, Een_AU
dc.contributor.authorLiu, GJen_AU
dc.date.accessioned2018-09-14T00:54:11Zen_AU
dc.date.available2018-09-14T00:54:11Zen_AU
dc.date.issued2014-11-19en_AU
dc.date.statistics2018-07-26en_AU
dc.description.abstractThe evolutionarily conserved peripheral benzodiazepine receptor (PBR), or 18-kDa translocator protein (TSPO), is thought to be essential for cholesterol transport and steroidogenesis, and thus life. TSPO has been proposed as a biomarker of neuroinflammation and a new drug target in neurological diseases ranging from Alzheimer’s disease to anxiety. Here we show that global C57BL/6-Tspotm1GuWu(GuwiyangWurra)-knockout mice are viable with normal growth, lifespan, cholesterol transport, blood pregnenolone concentration, protoporphyrin IX metabolism, fertility and behaviour. However, while the activation of microglia after neuronal injury appears to be unimpaired, microglia from GuwiyangWurraTSPO knockouts produce significantly less ATP, suggesting reduced metabolic activity. Using the isoquinoline PK11195, the ligand originally used for the pharmacological and structural characterization of the PBR/TSPO, and the imidazopyridines CLINDE and PBR111, we demonstrate the utility of GuwiyangWurraTSPO knockouts to provide robust data on drug specificity and selectivity, both in vitro and in vivo, as well as the mechanism of action of putative TSPO-targeting drugs. Copyright © 2014, Springer Natureen_AU
dc.identifier.articlenumber5452en_AU
dc.identifier.citationBanati, R. B., Middleton, R. J., Chan, R., Hatty, C. R., Wai-Ying Kam, W., Quin, C., Graeber, M. B., Parmar, A., Zahra, D., Callaghan, P., Fok, S., Howell, N.,Grégoire , M., Szabo, A., Pham, T., Davis, E., & Liu, G. J. (2014). Positron emission tomography and functional characterization of a complete PBR/TSPO knockout. Nature Communications, 5, 5452. doi:10.1038/ncomms6452en_AU
dc.identifier.govdoc9107en_AU
dc.identifier.issn2041-1723en_AU
dc.identifier.journaltitleNature Communicationsen_AU
dc.identifier.urihttps://doi.org/10.1038/ncomms6452en_AU
dc.identifier.urihttp://apo.ansto.gov.au/dspace/handle/10238/8979en_AU
dc.identifier.volume5en_AU
dc.language.isoenen_AU
dc.publisherSpringer Natureen_AU
dc.subjectPositron computed tomographyen_AU
dc.subjectProteinsen_AU
dc.subjectTranslocationen_AU
dc.subjectNeurologyen_AU
dc.subjectDrugsen_AU
dc.subjectTransgenic miceen_AU
dc.titlePositron emission tomography and functional characterization of a complete PBR/TSPO knockouten_AU
dc.typeJournal Articleen_AU
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
ncomms6452.pdf
Size:
2.64 MB
Format:
Adobe Portable Document Format
Description:
Download
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Journal Articles