913440
doi
10.1007/s11307-017-1099-1
oai:zenodo.org:913440
user-inmind
user-eu
Ory, Dieter
Department of Pharmaceutical and Pharmacological Sciences, Laboratory for Radiopharmacy, KU Leuven - University of Leuven, Leuven, Belgium
Geric, Ivana
Department of Pharmaceutical and Pharmacological Sciences, Laboratory for Cell Metabolism, KU Leuven - University of Leuven, Campus Gasthuisberg O/N2, Herestraat 49, 3000, Leuven, Belgium
Declercq, Lieven
Department of Pharmaceutical and Pharmacological Sciences, Laboratory for Radiopharmacy, KU Leuven - University of Leuven, Leuven, Belgium
Koole, Michel
Department of Nuclear Medicine and Molecular Imaging, KU Leuven- University of Leuven, Leuven, Belgium
Kassiou, Michael
School of Chemistry, The University of Sydney, NSW 2006, Australia
Bormans, Guy
Department of Pharmaceutical and Pharmacological Sciences, Laboratory for Radiopharmacy, KU Leuven - University of Leuven, Leuven, Belgium
Baes, Myriam
Department of Pharmaceutical and Pharmacological Sciences, Laboratory for Cell Metabolism, KU Leuven - University of Leuven, Campus Gasthuisberg O/N2, Herestraat 49, 3000, Leuven, Belgium
Increased Expression of Translocator Protein (TSPO) Marks Pro-inflammatory Microglia but Does Not Predict Neurodegeneration.
Beckers, Lien
Department of Pharmaceutical and Pharmacological Sciences, Laboratory for Cell Metabolism, KU Leuven - University of Leuven, Campus Gasthuisberg O/N2, Herestraat 49, 3000, Leuven, Belgium
info:eu-repo/semantics/openAccess
Creative Commons Attribution 4.0 International
https://creativecommons.org/licenses/by/4.0/legalcode
Microglia
Mouse model
Neuroinflammation
PET tracer
Peroxisomes
TSPO
<p>ABSTRACT</p>
<p>PURPOSE: Activation of the innate immune system plays a significant role in pathologies of the central nervous system (CNS). In order to follow disease progression and evaluate effectiveness of potential treatments involved in neuroinflammation, it is important to track neuroinflammatory markers in vivo longitudinally. The translocator protein (TSPO) is used as a target to image neuroinflammation as its expression is upregulated in reactive glial cells during CNS pathologies. However, it remains unclear in which microglial phenotypes TSPO levels are upregulated, as microglia can display a plethora of activation states that can be protective or detrimental to the CNS.</p>
<p>PROCEDURES: We assessed the levels of TSPO transcripts in cultured microglia that were polarized into pro- and anti-inflammatory states in vitro and in the brain of mice in which an anti-inflammatory environment was induced in vivo. In addition, we used a mouse model of peroxisomal multifunctional protein-2 (MFP2) deficiency that exhibits widespread neuroinflammation despite no neuronal loss and monitored TSPO expression by immunohistochemistry and by imaging using the TSPO radiotracer [<sup>18</sup>F]DPA-714.</p>
<p>RESULTS: TSPO expression was selectively increased in so-called classically activated or M1 microglia but not in alternatively activated or M2 microglia in vitro. In agreement, TSPO transcript levels were not induced in an anti-inflammatory brain environment. We found that both transcript and protein levels of TSPO are significantly increased in the brain of Mfp2 <sup>-/-</sup> compared to those of the control mice and TSPO immunoreactivity colocalized predominantly with microglia in Mfp2 <sup>-/-</sup> brain. In vitro and ex vivo autoradiography in Mfp2 <sup>-/-</sup> mice using the TSPO radiotracer [<sup>18</sup>F]DPA-714 confirmed increased expression of TSPO. These data demonstrate that TSPO imaging reveals microgliosis in non-neurodegenerative brain pathologies.</p>
<p>CONCLUSIONS: We show that induced TSPO expression marks a pro-inflammatory brain environment that is not necessarily accompanied by neuronal loss.</p>
Zenodo
2017-07-10
info:eu-repo/semantics/article
913439
user-inmind
user-eu
award_title=Imaging of Neuroinflammation in Neurodegenerative Diseases; award_number=278850; award_identifiers_scheme=url; award_identifiers_identifier=https://cordis.europa.eu/projects/278850; funder_id=00k4n6c32; funder_name=European Commission;
1579541805.581756
580145
md5:1ce1a72ce0c8e10ad1936f08f7a1ccb3
https://zenodo.org/records/913440/files/Beckers_MolImagingBiol_2017-P13a-AAM.pdf
public
Molecular Imaging and Biology
20
1
94-102
2017-07-10