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Cited by 124Neuroinflammation and Neurodegeneration MechanismsPharmacological Receptor Mechanisms and EffectsBarrier Structure and Function Studies

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

Open access
Betlazar, Calina, Harrison-Brown, Meredith, Middleton, Ryan, Banati, Richard, Liu, Guo-Jun·2018·International Journal of Molecular Sciences
DOI 10.3390/ijms19092707PMC PMC6163555
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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.

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  • TSPO is expressed in almost all CNS cells, including astrocytes, neurons and endothelial cells.

    “Although increased TSPO expression has historically been mostly associated with microglial activation, TSPO is now known to be expressed in almost all CNS cells including astrocytes, neurons and endothelial cells [21–27], all of which may also be involved in, or be affected by neuroinflammation [28].”

    From Pharmacological modulation of TSPO in microglia/macrophages and neurons in a chronic neurodegenerative model of prion disease (2023) · cites this paper as [25]

    Results §2.2 identifies vascular endothelial cells as a major source of TSPO in the normal mouse brain, but reports no discernible staining in astrocytes or mature NeuN+ neurons across the brain. It does find expression in particular neuronal populations, including Purkinje cells; that does not support the claim that TSPO is expressed in almost all CNS cells. Page numbers were not supplied in our copy. (LLM, conf=0.88)

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  • TSPO is expressed in glial and endothelial cells.

    “along with the established presence in the glial and endothelial cells [26, 45]”

    From Pharmacological modulation of TSPO in microglia/macrophages and neurons in a chronic neurodegenerative model of prion disease (2023) · cites this paper as [45]

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2 of the 61 references couldn’t be matched to a known paper.

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  1. [12]Mirzaei N. Tang S.P. Ashworth S. Coello C. Plisson C. Passchier J. Selvaraj V. Tyacke R.J. Nutt D.J. Sastre M. In vivo imaging of microglial activation by positron emission tomography with [(11)c]pbr28 in the 5xfad model of alzheimer’s disease Glia 2016 64 993 1006 26959396
  2. [60]Paxinos G. Franklin K.B.J. The Mouse Brain in Stereotaxic Coordinates Elsevier Academic Press Cambridge, MA, USA 2004

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Authors
Betlazar, C., Harrison-Brown, M., Middleton, R., Banati, R., & Liu, G.-J.
Affiliations
  • The University of Sydney (AU)
  • Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia
  • Australian Nuclear Science and Technology Organisation (AU)
Corresponding author
  • Betlazar, Calina
  • Banati, Richard
  • Liu, Guo-Jun
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2018-09-11
Volume
19
Issue
9
Pages
2707
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms19092707
PMC
PMC6163555
OpenAlex
W2889952876
Cited by
124
References
61
Citations by year
2026: 1 · 2025: 7 · 2024: 10 · 2023: 13 · 2022: 10 · 2021: 49 · 2020: 21 · 2019: 13
FWCI
9.33
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • The Australian Nuclear Science and Technology Organisation Institutional Repository (The Australian Nuclear Science and Technology Organisation) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Australian Nuclear Science and Technology Organisation
  • Australian Institute of Nuclear Science and Engineering
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pharmacological Receptor Mechanisms and Effects
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Keywords
translocator protein (TSPO), normal brain, regional distribution, vascular endothelial cells, microglia, neuroinflammation imaging, olfactory bulb, choroid plexus, ependyma, neurogenesis, Purkinje cells
MeSH terms
Animals, Brain, Brain Chemistry, Immunohistochemistry, Mice, Inbred C57BL, Microscopy, Fluorescence, Receptors, GABA, Mice, Knockout, Positron-Emission Tomography

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