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Int. J. Mol. Sci. 2018, 19(9), 2707; https://doi.org/10.3390/ijms19092707

Cellular Sources and Regional Variations in the Expression of the Neuroinflammatory Marker Translocator Protein (TSPO) in the Normal Brain

1
Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia
2
Discipline of Medical Imaging & Radiation Sciences, Faculty of Medicine and Health, Brain and Mind Centre, University of Sydney, 94 Mallett Street, Camperdown, NSW 2050, Australia
*
Authors to whom correspondence should be addressed.
Received: 4 August 2018 / Revised: 9 September 2018 / Accepted: 9 September 2018 / Published: 11 September 2018
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Abstract

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 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. View Full-Text
Keywords: translocator protein; positron emission tomography; neuroinflammation; mitochondria; immunohistochemistry translocator protein; positron emission tomography; neuroinflammation; mitochondria; immunohistochemistry
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Betlazar, C.; Harrison-Brown, M.; Middleton, R.J.; Banati, R.; Liu, G.-J. Cellular Sources and Regional Variations in the Expression of the Neuroinflammatory Marker Translocator Protein (TSPO) in the Normal Brain. Int. J. Mol. Sci. 2018, 19, 2707.

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