Regional and cellular distribution of the translocator protein 18 kDa (TSPO) in the normal brain

Betlazar C1,2, Harrison Brown M1,2, Middleton RJ1, Banati R1,2 and Liu GJ1,2

  1. Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia.
  2. Faculty of Medicine and Health, Brain and Mind Centre, University of Sydney, 94 Mallett Street, Camperdown, NSW 2050, Australia.

The 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 the specificity of TSPO antibodies, this study uses immunohistochemistry to systematically investigate the distribution and abundance of TSPO in the normal mouse brain. High magnification fluorescence microscopy reveals punctate TSPO immunostaining in vascular endothelial cells throughout the brain. Constitutive TSPO expression is also observed in neurogenic niches, the olfactory nerve layer and glomeruli of the olfactory bulb, and in cerebellar Purkinje cells. In contrast, there is no clearly discernible TSPO immunostaining in resting microglia and astrocytes of the normal brain. We conclude from these systematic observations the presence of a parenchymal-vascular expression of TSPO in the normal brain that is expected to give rise to a low baseline signal in molecular imaging studies using TSPO ligands. Mapping TSPO expression across the normal mouse brain is expected to expand future exploration into TSPO function in specific brain cell subtypes, and inform the interpretation of the growing number of studies utilising TSPO as an imaging biomarker of brain pathologies.