Candice Quin

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

Publisher: Springer Science and Business Media LLC

Date: 19-11-2014

DOI: 10.1038/NCOMMS6452

Abstract: The 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- Tspo tm1GuWu(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 GuwiyangWurra TSPO 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 GuwiyangWurra TSPO 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.

McMaster University

Location: Canada

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University Of Aberdeen

Location: United Kingdom of Great Britain and Northern Ireland

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The University Of British Columbia Okanagan

Location: Canada

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