Pro-inflammatory activation of primary microglia and macrophages increases 18 kDa translocator protein expression in rodents but not humans
Open accessAbstract
The 18kDa Translocator Protein (TSPO) is the most commonly used tissue-specific marker of inflammation in positron emission tomography (PET) studies. It is expressed in myeloid cells such as microglia and macrophages, and in rodent myeloid cells expression increases with cellular activation. We assessed the effect of myeloid cell activation on TSPO gene expression in both primary human and rodent microglia and macrophages in vitro, and also measured TSPO radioligand binding with 3 H-PBR28 in primary human macrophages. As observed previously, we found that TSPO expression increases (∼9-fold) in rodent-derived macrophages and microglia upon pro-inflammatory stimulation. However, TSPO expression does not increase with classical pro-inflammatory activation in primary human microglia (fold change 0.85 [95% CI 0.58–1.12], p = 0.47). In contrast, pro-inflammatory activation of human monocyte-derived macrophages is associated with a reduction of both TSPO gene expression (fold change 0.60 [95% CI 0.45–0.74], p = 0.02) and TSPO binding site abundance (fold change 0.61 [95% CI 0.49–0.73], p < 0.0001). These findings have important implications for understanding the biology of TSPO in activated macrophages and microglia in humans. They are also clinically relevant for the interpretation of PET studies using TSPO targeting radioligands, as they suggest changes in TSPO expression may reflect microglial and macrophage density rather than activation phenotype.
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In vitro, TSPO gene and protein expression and TSPO radioligand binding increases in rodent microglia and macrophages with inflammatory stimulation.
“Recently, we have shown in vitro that, although TSPO gene and protein expression and TSPO radioligand binding increases in rodent microglia and macrophages with inflammatory stimulation, relative TSPO gene expression in human microglia and TSPO ligand binding in human monocyte-derived macrophages are reduced with pro-inflammatory activation (Owen et al., 2017).”
From A quantitative neuropathological assessment of translocator protein expression in multiple sclerosis (2019) · cites this paper as Owen et al., 2017
The Results section reports approximately ninefold increases in TSPO gene expression in stimulated rodent microglia and macrophages. The Introduction and Discussion also report increased TSPO protein expression in activated rodent myeloid cells. But the paper describes radioligand-binding measurements in human macrophages, not an increase in binding in rodent cells. (LLM, conf=0.88)
Experimental — accuracy not yet measuredRelative TSPO gene expression in human microglia and TSPO ligand binding in human monocyte-derived macrophages are reduced with pro-inflammatory activation.
“Recently, we have shown in vitro that, although TSPO gene and protein expression and TSPO radioligand binding increases in rodent microglia and macrophages with inflammatory stimulation, relative TSPO gene expression in human microglia and TSPO ligand binding in human monocyte-derived macrophages are reduced with pro-inflammatory activation (Owen et al., 2017).”
From A quantitative neuropathological assessment of translocator protein expression in multiple sclerosis (2019) · cites this paper as Owen et al., 2017
The Discussion reports an approximately 40% reduction in TSPO radioligand binding in human macrophages after pro-inflammatory activation. The Results section on primary human microglia reports no significant reduction in TSPO gene expression: the adult estimate was 0.85-fold with a confidence interval spanning no change, and the foetal estimate was 1.63-fold. Page numbers are not provided in our copy. (LLM, conf=0.90)
Experimental — accuracy not yet measuredIn humans, TSPO is not upregulated in either pro-inflammatory macrophages or primary microglia.
“However, in humans, TSPO is not upregulated in either pro-inflammatory macrophages (Narayan et al., 2017) or primary microglia (Owen et al., 2017).”
From A quantitative neuropathological assessment of translocator protein expression in multiple sclerosis (2019) · cites this paper as Owen et al., 2017
The TSPO expression signal does not distinguish between microglial phenotypes in human tissue.
“This new observation thus confirms in vitro data suggesting that the TSPO expression signal does not distinguish between microglial phenotypes in human tissue (Owen et al., 2017).”
From A quantitative neuropathological assessment of translocator protein expression in multiple sclerosis (2019) · cites this paper as Owen et al., 2017
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“Likewise, data showing a robust increase in CNS (11)C-PBR28 PET signal following systemic LPS administration to both humans and nonhuman primates may need to be reassessed.(57,58) In these experiments, the increased TSPO PET signal was interpreted as evidence of microglial activation.”
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Papadopoulos, V., & Miller, W. L. (2012) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2012.05.002 · Cited by 249 · cited 1× · see citing works
“Its functions in steroidogenic cells likely are related to de novo steroid synthesis, which it appears able to modulate, although it may not be a necessary part of the steroidogenic machinery.(39,40) However, rodent microglia(26) and human microglia (data not shown) lack CYP11A1, the enzyme necessary to synthesize ste…”
BackgroundPositron emission tomography and functional characterization of a complete PBR/TSPO knockout
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MethodSelf-citationMicroglia express GABA(B) receptors to modulate interleukin release
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“Microglia also express receptors for neurotransmitters including g-aminobutyric acid (GABA) and glutamate, providing another pathway for microglial phenotypic regulation.(1,50,51) Caution should therefore be used when extrapolating these findings in vivo and further work will therefore examine directly how TSPO expres…”
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“TSPO expression has been reported to increase in activated rodent myeloid cells, with very similar fold increases in both gene and protein expression.(13,15,21,26) Our rodent data are consistent with the literature and showed an approximately 10-fold increase in TSPO gene expression following activation, in both macro…”
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“Likewise, data showing a robust increase in CNS (11)C-PBR28 PET signal following systemic LPS administration to both humans and nonhuman primates may need to be reassessed.(57,58) In these experiments, the increased TSPO PET signal was interpreted as evidence of microglial activation.”
BackgroundThe 18 kDa Translocator Protein, Microglia and Neuroinflammation
Liu, G., Middleton, R. J., Hatty, C. R., Kam, W. W.-Y., Chan, R. H. Y., Pham, T. Q., Harrison‐Brown, M., Dodson, E., Veale, K., & Banati, R. B. (2014) · Brain Pathology · doi:10.1111/bpa.12196 · Cited by 212 · cited 1× · see citing works
“Increases in the PET signal suggesting increased TSPO density generally have been interpreted in terms of increases in TSPO expression in microglia with activation.(42,48) However, under the assumptions Figure 3.”
BackgroundP2Y12 expression and function in alternatively activated human microglia
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“For example, adherence of circulating leucocytes to the vascular endothelium and recruitment of peripheral monocytes into the parenchyma are both rapid processes that would increase the TSPO PET signal in the CNS.(59,60) Endothelial cells also express both TSPO and Toll-like receptor 4 (TLR4, an LPS receptor).”
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“While the precise function of TSPO is unknown, preliminary studies suggest TSPO may alter myeloid phenotype by modulating the increases in reactive oxygen species (ROS) production and bioenergetics shifts that accompany myeloid cellular activation.(15,25) In vitro, both mRNA and protein expression of TSPO increase sub…”
BackgroundResultTranslational evaluation of translocator protein as a marker of neuroinflammation in schizophrenia
Notter, T., Coughlin, J. M., Gschwind, T., Weber-Stadlbauer, U., Wang, Y.-C., Kassiou, M., Vernon, A., Benke, D., Pomper, M., Sawa, A., et al. (2018) · Molecular Psychiatry · doi:10.1038/mp.2016.248 · Cited by 195 · see citing works
Imaging Microglial Activation with TSPO PET: Lighting Up Neurologic Diseases?
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“For this reason, TSPO is the most commonly used marker of inflammation in positron emission tomography (PET) studies in clinical populations.(10) Furthermore, preclinical experiments show that TSPO ligands provide protection in animal models of neuroinflammation and degeneration.”
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A TSPO ligand is protective in a mouse model of multiple sclerosis
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Ligand for Translocator Protein Reverses Pathology in a Mouse Model of Alzheimer's Disease
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“For example, adherence of circulating leucocytes to the vascular endothelium and recruitment of peripheral monocytes into the parenchyma are both rapid processes that would increase the TSPO PET signal in the CNS.(59,60) Endothelial cells also express both TSPO and Toll-like receptor 4 (TLR4, an LPS receptor).”
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“Microglia also express receptors for neurotransmitters including g-aminobutyric acid (GABA) and glutamate, providing another pathway for microglial phenotypic regulation.(1,50,51) Caution should therefore be used when extrapolating these findings in vivo and further work will therefore examine directly how TSPO expres…”
BackgroundTranslocator Protein 18 kDa Negatively Regulates Inflammation in Microglia
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“TSPO expression has been reported to increase in activated rodent myeloid cells, with very similar fold increases in both gene and protein expression.(13,15,21,26) Our rodent data are consistent with the literature and showed an approximately 10-fold increase in TSPO gene expression following activation, in both macro…”
BackgroundResultTranslocator Protein 18 kDa (TSPO): An Old Protein with New Functions?
Li, F., Liu, J., Liu, N., Kuhn, L. A., Garavito, R. M., & Ferguson-Miller, S. M. (2016) · Biochemistry · doi:10.1021/acs.biochem.6b00142 · Cited by 112 · cited 3× · see citing works
“TSPO is a highly conserved protein, richly expressed in steroidogenic and myeloid cells.(5) Its functions in steroidogenic cells likely are related to de novo steroid synthesis, which it appears able to modulate, although it may not be a necessary part of the steroidogenic machinery.”
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“For quantification of TSPO binding signal, very large cell numbers are required and therefore peripheral blood monocytes were isolated from blood cones of healthy donors purchased from the National Blood Service (Colindale, Edgware, London UK) using density gradient centrifugation, and centrifugal elutriation performe…”
MethodBrain microglia express steroid-converting enzymes in the mouse
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“TSPO expression has been reported to increase in activated rodent myeloid cells, with very similar fold increases in both gene and protein expression.(13,15,21,26) Our rodent data are consistent with the literature and showed an approximately 10-fold increase in TSPO gene expression following activation, in both macro…”
BackgroundResultThalamic inflammation after brain trauma is associated with thalamo-cortical white matter damage
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“Furthermore, recent studies in conditions characterised by microglial activation but without peripheral monocyte recruitment (such as alcohol withdrawal and schizophrenia) have not demonstrated the expected increase in TSPO PET signal.(55,56) These unexpected findings merit reconsideration in light of the data we pres…”
BackgroundSelf-citationTranslocator protein (18 kDa) is involved in the regulation of reactive gliosis
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Imaging neuroinflammation in multiple sclerosis using TSPO-PET
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“Increases in the PET signal suggesting increased TSPO density generally have been interpreted in terms of increases in TSPO expression in microglia with activation.(42,48) However, under the assumptions Figure 3.”
BackgroundDendritic Cell Differentiation Signals Induce Anti-Inflammatory Properties in Human Adult Microglia
Lambert, C., Desbarats, J., Arbour, N., Hall, J. A., Olivier, A., Bar-Or, A., & Antel, J. P. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.12.8288 · Cited by 50 · cited 1× · see citing works
“Cells were isolated as previously described.(29) Briefly, brain tissue (gestational age 14–20 weeks) was minced and treated with DNase/trypsin.”
MethodSelf-citationDistinct migratory and cytokine responses of human microglia and macrophages to ATP
Lambert, C., Ase, A. R., Séguéla, P., & Antel, J. P. (2010) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2010.02.010 · Cited by 43 · cited 1× · see citing works
“The surgical brain tissue was processed as described previously.(3,27) Briefly, tissue was obtained in pieces <1 mm(3) and treated with DNase (Roche, Nutley, NJ) and trypsin (Invitrogen, Carlsbad, CA) for 30min at 37 C.”
MethodSelf-citationSmith, A. M., Graham, E. S., Feng, S. X., Oldfield, R. L., Bergin, P. M., Mee, E. W., Faull, R. L. M., Curtis, M. A., & Dragunow, M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0080463 · Cited by 38 · cited 1× · see citing works
“factor b1 (TGFb1) inhibits IFNg-induced microglial HLA expression.(36) Production of nitric oxide, an important molecule in the inflammatory response, requires greater stimulation in human compared with rodent microglia, and even so human cells produce much lower levels of it.”
BackgroundThe peripheral benzodiazepine receptor ligand PK 11195 inhibits arthritis in the MRL-lpr mouse model
Waterfield, J. D., McGeer, E. G., & McGeer, P. L. (1999) · Lara D. Veeken · doi:10.1093/rheumatology/38.11.1068 · Cited by 37 · see citing works
Translocator protein 18 kDa (TSPO) expression in multiple sclerosis patients
Harberts, E., Datta, D., Chen, S., Wohler, J. E., Oh, U., & Jacobson, S. (2013) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-012-9397-5 · Cited by 36 · see citing works
Mitochondrial ligand inhibits store‐operated calcium influx and COX‐2 production in human microglia
Hong, S. H., Choi, H. B., Kim, S. U., & McLarnon, J. G. (2006) · Journal of Neuroscience Research · doi:10.1002/jnr.20829 · Cited by 33 · see citing works
Ligands of the peripheral benzodiazepine receptor have therapeutic effects in pneumopathies in vivo
Bribes, E., Bourrié, B., & Casellas, P. (2003) · Immunology Letters · doi:10.1016/s0165-2478(03)00083-x · Cited by 27 · see citing works
Diazepam inhibits HIV-1 Tat-induced migration of human microglia
Lokensgard, J. R. (2001) · Journal of NeuroVirology · doi:10.1080/135502801753170345 · Cited by 27 · see citing works
Bazzichi, L. M., Betti, L., Giannaccini, G., Rossi, A., & Lucacchini, A. (2003) · Clinical Biochemistry · doi:10.1016/s0009-9120(02)00408-3 · Cited by 22 · see citing works
Differential transcriptional response profiles in human myeloid cell populations
Healy, L. M., Perron, G., Won, S., Rao, V. T. S., Guiot, M., Moore, C. S., Bar‐Or, A., & Antel, J. P. (2016) · Clinical Immunology · doi:10.1016/j.clim.2016.04.006 · Cited by 21 · cited 1× · see citing works
“Furthermore, many of the markers with differential expression profiles in human microglia relative to human macrophages are not expressed by rodent myeloid cells.(37,38) Our findings add to these differences and suggest that extrapolating TSPO biology from rodent to human myeloid cells should be done with extreme caut…”
BackgroundSelf-citationBranley, H. M., du Bois, R. M., Wells, A. U., & Jones, H. A. (2007) · Nuclear Medicine and Biology · doi:10.1016/j.nucmedbio.2007.03.005 · Cited by 12 · see citing works
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The Bidirectional Relationship of Depression and Inflammation: Double Trouble
Beurel, E., Toups, M., & Nemeroff, C. B. (2020) · Neuron · doi:10.1016/j.neuron.2020.06.002 · Cited by 2,136 · see citing works
“It is, however, important to note that the expression of TSPO initially thought to represent microglia activation, has been recently proposed to also measure local myeloid cell proliferation, or monocytes infiltration (Owen et al., 2017).”
BackgroundEnache, D., Pariante, C. M., & Mondelli, V. (2019) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2019.06.015 · Cited by 615 · see citing works
Brain glial activation in fibromyalgia – A multi-site positron emission tomography investigation
Albrecht, D. S., Forsberg, A., Sandström, A., Bergan, C., Kadetoff, D., Protsenko, E., Lampa, J., Lee, Y. C., Höglund, C. O., Catana, C., et al. (2019) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2018.09.018 · Cited by 310 · see citing works
“immune challenges induce TSPO upregulation in anti-inflammatory M2-like macrophages, and TSPO reduction in inflammatory M1-like macrophages (Narayan et al., 2017; Owen et al., 2017).”
Neuroinflammation in frontotemporal dementia
Bright, F., Werry, E. L., Dobson-Stone, C., Piguet, O., Ittner, L. M., Halliday, G. M., Hodges, J. R., Kiernan, M. C., Loy, C. T., Kassiou, M., et al. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0231-z · Cited by 280 · see citing works
Werry, E. L., Bright, F., Piguet, O., Ittner, L. M., Halliday, G. M., Hodges, J. R., Kiernan, M. C., Loy, C. T., Kril, J. J., & Kassiou, M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20133161 · Cited by 282 · see citing works
Neuroinflammation in psychiatric disorders: PET imaging and promising new targets
Meyer, J. H., Červenka, S., Kim, M.-J., Kreisl, W. C., Henter, I. D., & Innis, R. B. (2020) · The Lancet Psychiatry · doi:10.1016/s2215-0366(20)30255-8 · Cited by 274 · see citing works
PET Imaging of Neuroinflammation in Neurological Disorders
Kreisl, W., Kim, M.-J., Coughlin, J. M., Henter, I., Owen, D. R., & Innis, R. (2020) · Lancet Neurology · doi:10.1016/s1474-4422(20)30346-x · Cited by 180 · see citing works
Self-citationNutma, E., Fancy, N. N., Weinert, M., Tsartsalis, S., Marzin, M. C., Muirhead, R. C. J., Falk, I. N., Breur, M., de Bruin, J., Hollaus, D., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-40937-z · Cited by 192 · see citing works
“We have shown, however, that classical pro-in fl ammatory stimulation of human microglia and macrophages in vitro with the TLR4 ligand lipopolysaccharide (LPS) does not induce expression of TSPO 19 .”
Self-citationCellular sources of TSPO expression in healthy and diseased brain
Nutma, E., Ceyzériat, K., Amor, S., Tsartsalis, S., Millet, P., Owen, D. R., Papadopoulos, V., & Tournier, B. B. (2021) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-020-05166-2 · Cited by 192 · see citing works
“In this context, several reports using mouse primary glial cell cultures demonstrate that TSPO is more likely to be modified in activated (by pro-inflammatory stimuli) forms of microglia and astrocytes [139, 162, 163].”
BackgroundSelf-citationThe role of glial cells in multiple sclerosis disease progression
Healy, L. M., Stratton, J. A., Kuhlmann, T., & Antel, J. (2022) · Nature Reviews Neurology · doi:10.1038/s41582-022-00624-x · Cited by 152 · see citing works
Self-citationReconceptualization of translocator protein as a biomarker of neuroinflammation in psychiatry
Notter, T., Coughlin, J. M., Sawa, A., & Meyer, U. (2017) · Molecular Psychiatry · doi:10.1038/mp.2017.232 · Cited by 142 · see citing works
Microglial Pruning of Synapses in the Prefrontal Cortex During Adolescence
Mallya, A. P., Wang, H., Lee, H. N. R., & Deutch, A. Y. (2018) · Cerebral Cortex · doi:10.1093/cercor/bhy061 · Cited by 138 · see citing works
Kamma, E., Lasisi, W. O., Libner, C. D., Ng, H. S., & Plemel, J. R. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02408-y · Cited by 144 · see citing works
A quantitative neuropathological assessment of translocator protein expression in multiple sclerosis
Nutma, E., Stephenson, J. A., Gorter, R. P., de Bruin, J., Boucherie, D. M., Donat, C. K., Breur, M., van der Valk, P., Matthews, P. M., Owen, D. R., et al. (2019) · Brain · doi:10.1093/brain/awz287 · Cited by 138 · see citing works
“However, in humans, TSPO is not upregulated in either pro-inflammatory macrophages (Narayan et al. , 2017) or primary microglia (Owen et al. , 2017) .”
Self-citationChronic inflammation in multiple sclerosis - seeing what was always there
Matthews, P. M. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0240-y · Cited by 128 · see citing works
Self-citationLi, H., Sagar, A. P., & Kéri, S. (2017) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.12.011 · Cited by 134 · see citing works
“TSPO is also expressed by astroglia and endothelial cells, and in humans increased TSPO binding may indicate microglia and macrophage density rather than activation (Owen et al., 2017; Varrone and Lammertsma, 2015; Veronese et al., 2017).”
The Translocator Protein (TSPO) in Mitochondrial Bioenergetics and Immune Processes
Betlazar, C., Middleton, R. J., Banati, R. B., & Liu, G. J. (2020) · Cells · doi:10.3390/cells9020512 · Cited by 131 · see citing works
“In human primary monocyte-derived macrophages, stimulated with LPS/IFN-γ, decreased TSPO gene expression and radioligand binding has also been reported in another study [95].”
BackgroundPET Imaging of Microglial Activation—Beyond Targeting TSPO
Janssen, B., Vugts, D. J., Windhorst, A. D., & Mach, R. H. (2018) · Molecules · doi:10.3390/molecules23030607 · Cited by 127 · see citing works
“In addition, while radiotracers are often evaluated in rodent models of excitotoxin-induced neuroinflammation or models of human disease, these are not necessarily representative of human disease, as was recently also reported for TSPO [11].”
BackgroundInfluentialPlavén‐Sigray, P., Matheson, G. J., Collste, K., Ashok, A. H., Coughlin, J. M., Howes, O. D., Mizrahi, R., Pomper, M. G., Rusjan, P., Veronese, M., et al. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2018.02.1171 · Cited by 125 · see citing works
Neuronal activity increases translocator protein (TSPO) levels
Notter, T., Schalbetter, S. M., Clifton, N. E., Mattei, D., Richetto, J., Thomas, K., Meyer, U., & Hall, J. (2021) · Molecular Psychiatry · doi:10.1038/s41380-020-0745-1 · Cited by 118 · see citing works
In vivo molecular imaging of neuroinflammation in Alzheimer's disease
Chaney, A. M., Williams, S. R., & Boutin, H. (2018) · Journal of Neurochemistry · doi:10.1111/jnc.14615 · Cited by 116 · see citing works
“…of neurosteroids, playing a role in cholesterol transport across the mitochondrial membrane (Brown and Papadopoulos 2001) but is also linked to neuronal survival and neuroinflammation, and has been associated with the pathology of many neurological disorders including AD (Papadopoulos et al. 2006).”
BackgroundGuilarte, T. R., Rodichkin, A. N., McGlothan, J. L., de la Rocha, A. A., & Azzam, D. J. (2021) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.108048 · Cited by 113 · see citing works
Pannell, M., Economopoulos, V., Wilson, T. C., Kersemans, V., Isenegger, P. G., Larkin, J. R., Smart, S., Gilchrist, S., Gouverneur, V., & Sibson, N. R. (2020) · Glia · doi:10.1002/glia.23716 · Cited by 109 · see citing works
“Two recent studies attempted to address this question, but with conflicting results, and in both cases only the microglial/macrophage populations were assessed (Beckers et al., 2018; Owen et al., 2017).”
BackgroundResultSifting through the surfeit of neuroinflammation tracers
Cumming, P., Burgher, B., Patkar, O., Breakspear, M., Vasdev, N., Thomas, P., Liu, G.-J., & Banati, R. (2018) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x17748786 · Cited by 111 · see citing works
Translocator protein (TSPO): the new story of the old protein in neuroinflammation
Lee, Y. H., Park, Y., Nam, H., Lee, J., & Yu, S. (2020) · BMB Reports · doi:10.5483/bmbrep.2020.53.1.273 · Cited by 107 · see citing works
“org BMB Reports findings may imply aspects of brain homeostasis that are different between humans and rodents (52, 57, 61).”
BackgroundBhatt, S., Hillmer, A. T., Girgenti, M. J., Rusowicz, A., Kapinos, M., Nabulsi, N., Huang, Y. H., Matuskey, D., Angarita, G. A., Esterlis, I., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15930-5 · Cited by 106 · see citing works
Li, H., Sagar, A. P., & Kéri, S. (2018) · Journal of Affective Disorders · doi:10.1016/j.jad.2018.08.021 · Cited by 101 · see citing works
Microglial activation correlates in vivo with both tau and amyloid in Alzheimer’s disease
Dani, M., Wood, M., Mizoguchi, R., Fan, Z., Walker, Z., Morgan, R., Hinz, R., Biju, M., Kuruvilla, T., Brooks, D. J., et al. (2018) · Brain · doi:10.1093/brain/awy188 · Cited by 270 · see citing works
“Moreover, a blocking study showed tracer binding throughout the brain, indicates that there is no region in the brain that is truly devoid of binding that can be used as a reference for non-specific binding (Owen et al., 2014).”
BackgroundNeuroinflammation, Pain and Depression: An Overview of the Main Findings
Campos, A. C. P., Antunes, G. F., Matsumoto, M., Pagano, R. L., & Martinez, R. C. R. (2020) · Frontiers in Psychology · doi:10.3389/fpsyg.2020.01825 · Cited by 102 · see citing works
Böttcher, C., Fernández‐Zapata, C., Snijders, G. J. L., Schlickeiser, S., Sneeboer, M. A. M., Kunkel, D., de Witte, L. D., & Priller, J. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-00992-2 · Cited by 91 · see citing works
Nutma, E., Gebro, E., Marzin, M. C., van der Valk, P., Matthews, P. M., Owen, D. R., & Amor, S. (2021) · Glia · doi:10.1002/glia.24052 · Cited by 91 · see citing works
“…reflect activated pathogenic microglia, the early assumption that TSPO expression increases in human microglia as they become activated was inferred from animal studies using rodents (Bae et al., 2014; GottfriedBlackmore et al., 2008; Karlstetter et al., 2014; Owen et al., 2017; Wang et al., 2014).”
BackgroundInfluentialSelf-citationNettis, M. A., & Pariante, C. M. (2020) · International review of neurobiology · doi:10.1016/bs.irn.2019.12.004 · Cited by 81 · see citing works
In Vivo TSPO Signal and Neuroinflammation in Alzheimer’s Disease
Tournier, B. B., Tsartsalis, S., Ceyzériat, K., Garibotto, V., & Millet, P. (2020) · Cells · doi:10.3390/cells9091941 · Cited by 79 · see citing works
“In human adult microglia primary cell cultures, the addition of pro-inflammatory molecules did not result in changes in TSPO expression but induced a decrease in protein amounts [123].”
BackgroundNeuroinflammatory basis of depression: learning from experimental models
Afridi, R., & Suk, K. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.691067 · Cited by 82 · see citing works
Positron emission tomography in multiple sclerosis - straight to the target
Bodini, B., Tonietto, M., Airas, L., & Stankoff, B. (2021) · Nature Reviews Neurology · doi:10.1038/s41582-021-00537-1 · Cited by 74 · see citing works
Schroyen, G., Blommaert, J., Weehaeghe, D. V., Sleurs, C., Vandenbulcke, M., Dedoncker, N., Hatse, S., Goris, A., Koole, M., Smeets, A., et al. (2021) · Cancers · doi:10.3390/cancers13164198 · Cited by 70 · see citing works
“Additionally, TSPO-signal can be driven by other factors than microglia activation, such as expression on astrocytes/endothelial cells (~25%), recruitment of monocytes into the parenchyma, and changes in BBB permeability [72,73].”
BackgroundTSPO imaging in animal models of brain diseases
Camp, N. V., Lavisse, S., Roost, P., Gubinelli, F., Hillmer, A. T., & Boutin, H. (2021) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-021-05379-z · Cited by 71 · see citing works
“In vitro studies demonstrated that LPS slightly decreased TSPO gene expression in human microglia and [(3)H]PBR28 binding sites in human macrophages [36].”
BackgroundMicroglia mediated neuroinflammation in autism spectrum disorder
Liao, X., Yang, J., Wang, H., & Li, Y. (2020) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2020.07.013 · Cited by 74 · see citing works
Airas, L., Nylund, M., & Rissanen, E. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.00181 · Cited by 67 · see citing works
“How these in vitro experiments relate to MS immunopathology in MS brain in situ remains to be seen, but the findings do suggest that changes in TSPO expression in PET imaging studies of MS may reflect microglial and macrophage density rather than activation phenotype (36).”
BackgroundDimitrova‐Shumkovska, J., Krstanoski, L., & Veenman, L. (2020) · Cells · doi:10.3390/cells9040870 · Cited by 70 · see citing works
“Considering in vivo studies, TSPO expression mainly assayed by PET tracers’ uptake showed differences in the expression patterns in animal versus human microglia [48].”
BackgroundThe Role of Translocator Protein TSPO in Hallmarks of Glioblastoma
Ammer, L.-M., Vollmann‐Zwerenz, A., Ruf, V., Wetzel, C. H., Riemenschneider, M. J., Albert, N. L., Beckhove, P., & Hau, P. (2020) · Cancers · doi:10.3390/cancers12102973 · Cited by 68 · see citing works
“demonstrated that stimulation with IFNγ and LPS caused an increased TSPO expression in rodent-derived microglia, but decreased TSPO expression in primary human microglia [91].”
BackgroundA loss of mature microglial markers without immune activation in schizophrenia
Snijders, G. J. L., van Zuiden, W., Sneeboer, M. A. M., van Berlekom, A. B., van der Geest, A. T., Schnieder, T. P., MacIntyre, D. J., Hol, E. M., Kahn, R. S., & de Witte, L. D. (2021) · Glia · doi:10.1002/glia.23962 · Cited by 66 · see citing works
Postmortem Studies of Neuroinflammation in Autism Spectrum Disorder: a Systematic Review
Liao, X., Liu, Y., Fu, X. B., & Li, Y. (2020) · Molecular Neurobiology · doi:10.1007/s12035-020-01976-5 · Cited by 67 · see citing works
Conen, S., Gregory, C. J., Hinz, R., Smallman, R. P., Zuelli, F. M. D. G. C., Deakin, J. F. W., & Talbot, P. S. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-0829-y · Cited by 67 · see citing works
Neuroinflammation PET imaging of the translocator protein (TSPO) in Alzheimer's disease: An update
Gouilly, D., Saint‐Aubert, L., Ribeiro, M. J., Salabert, A., Tauber, C., Péran, P., Arlicot, N., Pariente, J., & Payoux, P. (2022) · European Journal of Neuroscience · doi:10.1111/ejn.15613 · Cited by 66 · see citing works
“…have shown that pro-inflammatory stimulation elicits a nine-fold increase in tspo mRNA levels in rodentderived macrophages and microglia, but unchanged tspo mRNA levels in human microglia and a decrease in tspo mRNA levels and binding site abundance in human macrophages (Owen et al., 2017).”
BackgroundAstrocytic TSPO upregulation appears before microglial TSPO in Alzheimer’s disease
Tournier, B. B., Tsartsalis, S., Ceyzériat, K., Fraser, B. H., Grégoire, M.-C., Kövari, E., & Millet, P. (2020) · Journal of Alzheimer’s Disease · doi:10.3233/jad-200136 · Cited by 65 · see citing works
“In culture, the presence of proinflammatory factors in the medium increased or had no effect on the expression of TSPO according to whether the microglia is of murine or human origin, respectively [79].”
BackgroundSnijders, G. J. L., Sneeboer, M. A. M., Fernández-Andreu, A., Udine, E., (NBB-Psy), P. D. P. O. T. N. B. B., Boks, M. P., Ormel, P. R., van Berlekom, A. B., van Mierlo, H. C., Böttcher, C., et al. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-00896-z · Cited by 65 · see citing works
Milenkovic, V. M., Slim, D., Bader, S. M., Koch, V. B., Heinl, E.-S., Alvarez-Carbonell, D., Nothdurfter, C., Rupprecht, R., & Wetzel, C. H. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20133359 · Cited by 62 · see citing works
“However, cytochrome P450scc is reported to be nearly absent in human microglia [29], preventing substantial de novo synthesis of pregnenolone from cholesterol in these cells.”
BackgroundPalada, V., Ahmed, A. S., Finn, A., Berg, S., Svensson, C. I., & Kosek, E. (2018) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2018.09.010 · Cited by 64 · see citing works
Scheepstra, K. W. F., Mizee, M. R., van Scheppingen, J., Adelia, A., Wever, D. D., Mason, M. R. J., Dubbelaar, M. L., Hsiao, C., Eggen, B. J. L., Hamann, J., et al. (2023) · Biological Psychiatry · doi:10.1016/j.biopsych.2023.04.020 · Cited by 58 · see citing works
Borchert, T., Beitar, L., Langer, L., Polyák, A., Wester, H., Roß, T. L., Hilfiker‐Kleiner, D., Bengel, F. M., & Thackeray, J. T. (2019) · Journal of Nuclear Cardiology · doi:10.1007/s12350-019-01929-z · Cited by 57 · see citing works
Immunotherapy for depression: Recent insights and future targets
Bai, Y., Cai, Y., Chang, D., Li, D., Huo, X., & Zhu, T. (2024) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2024.108624 · Cited by 54 · see citing works
Microglia in multiple sclerosis - pathogenesis and imaging
Airas, L., & Yong, V. W. (2022) · Current Opinion in Neurology · doi:10.1097/wco.0000000000001045 · Cited by 52 · see citing works
“humans [52], which has led to a notion that in addition toupregulation of the TSPOmolecule under proinflammatory conditions in microglia, the redistribution of these cells inMS brain contributes to the increasedTSPO-radioligandsignaldueto increased density of the cells [53].”
BackgroundNguyen, D. L., Wimberley, C., Truillet, C., Jégo, B., Caillé, F., Pottier, G., Boisgard, R., Buvat, I., & Bouilleret, V. (2018) · Epilepsia · doi:10.1111/epi.14083 · Cited by 51 · see citing works
“However, TSPO has been proven to be expressed in different cell types such as astrocytes and endothelial cells and the similarities and differences in TSPO expression mechanisms between humans and rodents has to be well recognized and handled.(18) The rodent model should be chosen in association with human data and as…”
BackgroundVignal, N., Cisternino, S., Rizzo-Padoin, N., San, C., Hontonnou, F., Gelé, T., Declèves, X., Sarda‐Mantel, L., & Hosten, B. (2018) · Molecules · doi:10.3390/molecules23061375 · Cited by 51 · see citing works
“The translocator protein of 18 kDa (TSPO) is the most advance target for the non-invasive and translational study of inflammatory processes using positron emission tomography (PET) imaging [1].”
BackgroundPlavén‐Sigray, P., Matheson, G. J., Coughlin, J. M., Hafizi, S., Laurikainen, H., Ottoy, J., Picker, L. D., Rusjan, P., Hietala, J. A., Howes, O. D., et al. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2020.05.028 · Cited by 50 · see citing works
“While TSPO has been shown to be sensitive in systemic inflammation paradigms (22,23), TSPO is not specific to microglia (24,25), and in vitro data have shown a lack of correspondence between TSPO and proinflammatory activation (26,27), although conflicting data exist (28,29).”
BackgroundNettis, M. A., Veronese, M., Nikkheslat, N., Mariani, N., Lombardo, G., Sforzini, L., Enache, D., Harrison, N. A., Turkheimer, F., Mondelli, V., et al. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-0768-z · Cited by 50 · see citing works
Insights into disseminated MS brain pathology with multimodal diffusion tensor and PET imaging
Bezukladova, S., Tuisku, J., Matilainen, M., Vuorimaa, A., Nylund, M., Smith, S., Sucksdorff, M., Mohammadian, M., Saunavaara, V., Laaksonen, S., et al. (2020) · Neurology Neuroimmunology & Neuroinflammation · doi:10.1212/nxi.0000000000000691 · Cited by 49 · see citing works
Spinal microglia-neuron interactions in chronic pain
Ho, I. H. T., Chan, M. T. V., Wu, W. K. K., & Liu, X. (2020) · Journal of Leukocyte Biology · doi:10.1002/jlb.3mr0520-695r · Cited by 49 · see citing works
Interferon β-Mediated Protective Functions of Microglia in Central Nervous System Autoimmunity
Scheu, S., Ali, S., Mann‐Nüttel, R., Richter, L., Arolt, V., Dannlowski, U., Kuhlmann, T., Klotz, L., & Alferink, J. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20010190 · Cited by 48 · see citing works
“However, increased TSPO expression in PET imaging studies of MS patients has also been linked to density but not activation of these cells [97].”
BackgroundIn Vivo Imaging of Microglia With Multiphoton Microscopy
Hierro‐Bujalance, C., Bacskai, B. J., & Garcı́a-Alloza, M. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00218 · Cited by 49 · see citing works
Microglia in Health and Diseases: Integrative Hubs of the Central Nervous System (CNS)
Sierra, A., Miron, V. E., Paolicelli, R. C., & Ransohoff, R. M. (2024) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a041366 · Cited by 47 · see citing works
miR-124-3p is a chronic regulator of gene expression after brain injury
Vuokila, N., Łukasiuk, K., Bot, A. M., van Vliet, E. A., Aronica, E., Pitkänen, A., & Puhakka, N. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2911-z · Cited by 45 · see citing works
Microglia immunometabolism: From metabolic disorders to single cell metabolism
Paolicelli, R. C., & Angiari, S. (2019) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2019.03.012 · Cited by 44 · see citing works
Microglial activation in schizophrenia: Is translocator 18 kDa protein (TSPO) the right marker?
Sneeboer, M. A. M., van der Doef, T. F., Litjens, M., Psy, N. B. B., Melief, J., Hol, E. M., Kahn, R. S., & de Witte, L. D. (2019) · Schizophrenia Research · doi:10.1016/j.schres.2019.10.045 · Cited by 45 · see citing works
Tau follows principal axes of functional and structural brain organization in Alzheimer’s disease
Ottoy, J., Kang, M. S., Tan, J. X. M., Boone, L., de Wael, R. V., Park, B., Bezgin, G., Lussier, F. Z., Pascoal, T. A., Rahmouni, N., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-49300-2 · Cited by 49 · see citing works
“Finally, the TSPO-PET uptake is not a direct measure of the in fl ammatory response and may re fl ect binding density and/or metabolic activity rather than an activation phenotype of (micro-)glia 98,99 .”
MerTK is a mediator of alpha-synuclein fibril uptake by human microglia
Dorion, M., Yaqubi, M., Senkevich, K. A., Kieran, N. W., MacDonald, A., Chen, C. X. ‐., Luo, W., Wallis, A., Shlaifer, I., Hall, J. A., et al. (2023) · Brain · doi:10.1093/brain/awad298 · Cited by 43 · see citing works
“16-20 Since human and murine microglia are inherently different in their genome, transcriptome and aspects of their function, 21-24 it is unclear whether the same receptors and mechanisms participate in the uptake of α -syn by human microglia.”
BackgroundSelf-citationEnomoto, S., & Kato, T. A. (2020) · Neurochemistry International · doi:10.1016/j.neuint.2020.104921 · Cited by 41 · see citing works
Translation Imaging in Parkinson’s Disease: Focus on Neuroinflammation
Belloli, S., Morari, M., Murtaj, V., Valtorta, S., Moresco, R., & Gilardi, M. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.00152 · Cited by 38 · see citing works
The Role of Inflammation in the Pathophysiology of Depression and Suicidal Behavior
Serafini, G., Costanza, A., Aguglia, A., Amerio, A., Trabucco, A., Escelsior, A., Sher, L., & Amore, M. (2022) · Medical Clinics of North America · doi:10.1016/j.mcna.2022.09.001 · Cited by 47 · see citing works
Microglial contribution to the pathology of neurodevelopmental disorders in humans
Matulevičiūtė, R., Akinluyi, E. T., Muntslag, T. A. O., Dewing, J. M., Long, K. R., Vernon, A. C., Tremblay, M., & Menassa, D. A. (2023) · Acta Neuropathologica · doi:10.1007/s00401-023-02629-2 · Cited by 41 · see citing works
“Compared to mouse microglia, human microglia are more complex morphologically and display reduced proliferation rates, as well as specific differences in genes regulating critical endogenous processes like inflammation and the cell cycle [144, 174].”
BackgroundPost-mortem validation of in vivo TSPO PET as a microglial biomarker
Wijesinghe, S. S., Rowe, J. B., Mason, H. D., Allinson, K. S. J., Thomas, R., Vontobel, D. S., Fryer, T. D., Hong, Y. T., Bacioglu, M., Spillantini, M. G., et al. (2025) · Brain · doi:10.1093/brain/awaf078 · Cited by 37 · see citing works
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Cytokine Signalling at the Microglial Penta-Partite Synapse
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“[43] reported that TSPO expression did not increase with classical pro-inflammatory activation in primary human microglia, unlike in rodent microglia.”
BackgroundMeta-analysis of molecular imaging of translocator protein in major depression
Eggerstorfer, B., Kim, J.-H., Cumming, P., Lanzenberger, R., & Gryglewski, G. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.981442 · Cited by 35 · see citing works
“Although inferences related to inflammatory states and TSPO should consider that TSPO expression is not unique to microglia and that elevated TSPO binding in humans could also be attributable to local proliferation of myeloid cells or increased recruitment of monocytes (Narayan et al., 2017; Owen et al., 2017), TSPO r…”
BackgroundLin, Y. C., Cheung, G., Porter, E. M., & Papadopoulos, V. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102110 · Cited by 34 · see citing works
“(2022) 298(7) 102110 human microglia (54, 55).”
Cervenka, S., Frick, A., Bodén, R., & Lubberink, M. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-01990-2 · Cited by 32 · see citing works
“TSPO is not specific to microglia [25, 26], and in vitro studies have shown conflicting results regarding the specificity of TSPO for pro-inflammatory cells [27, 28].”
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De novo Neurosteroidogenesis in Human Microglia: Involvement of the 18 kDa Translocator Protein
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Neurosteroidogenic enzymes: CYP11A1 in the central nervous system
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(Micro)Glia as Effectors of Cortical Volume Loss in Schizophrenia
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Molecular Imaging of Neuroinflammation in HIV
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“A recent study noted a decrease in TSPO expression in pro-inflammatory activated microglia (Owen et al. 2017).”
BackgroundTranslocator protein localises to CD11b+ macrophages in atherosclerosis
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Cyclooxygenases as Potential PET Imaging Biomarkers to Explore Neuroinflammation in Dementia
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“In addition, TPSO’s expression was shown to vary between rodents and human, where under pro-inflammatory conditions (treatment with lipopolysaccharide), TSPO gene expression increased in primary microglial cells from postnatal day 0–5 C57BL/6 mice contrary to adult microglia isolated from the temporal lobe of patients…”
BackgroundNieuwland, J. M., Nutma, E., Philippens, I. H. C. H. M., Böszörményi, K. P., Remarque, E. J., Bakker, J., Meijer, L., Woerdman, N., Fagrouch, Z. C., Verstrepen, B. E., et al. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02857-z · Cited by 27 · see citing works
“Recent studies imply that the increase in TSPO PET signal is due to an increase in glial cell density and not activation status [26, 27, 53].”
BackgroundEiff, B., Bullmore, E. T., Clatworthy, M. R., Fryer, T. D., Pariante, C. M., Mondelli, V., Maccioni, L., Hadjikhani, N. K., Loggia, M. L., Moskowitz, M. A., et al. (2024) · Brain · doi:10.1093/brain/awae343 · Cited by 26 · see citing works
“23 24-29 PET studies using radiotracers specific to TSPO have revealed evidence of neuroimmune activation across numerous neurological and psychiatric disorders.”
Katsumi, Y., Racine, A. M., Torrado-Carvajal, Á., Loggia, M. L., Hooker, J. M., Greve, D. N., Hightower, B. G., Catana, C., Cavallari, M., Arnold, S. E., et al. (2020) · NeuroImage Clinical · doi:10.1016/j.nicl.2020.102346 · Cited by 26 · see citing works
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Inflammation, Obsessive-Compulsive Disorder, and Related Disorders
Meyer, J. H. (2021) · Current topics in behavioral neurosciences · doi:10.1007/7854_2020_210 · Cited by 24 · see citing works
Liao, X., Chen, M., & Li, Y. (2023) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2023.101064 · Cited by 25 · see citing works
The mitochondrial translocator protein (TSPO): a key multifunctional molecule in the nervous system
Chemali, L. E., Akwa, Y., & Massaad-Massade, L. (2022) · Biochemical Journal · doi:10.1042/bcj20220050 · Cited by 23 · see citing works
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“The interpretation of TSPO PET signal as a true marker of microglial activation and therefore neuroinflammation has been a matter of debate in molecular imaging studies (40, 41).”
BackgroundSelf-citationComparison of [11C]-PBR28 Binding Between Persons Living With HIV and HIV-Uninfected Individuals
Boerwinkle, A. H., Strain, J. F., Burdo, T. H., Doyle, J., Christensen, J. J., Su, Y., Wisch, J. K., Cooley, S., Vaida, F., Smith, M. D., et al. (2020) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/qai.0000000000002435 · Cited by 22 · see citing works
Microglia-mediated neuroimmune suppression in PTSD is associated with anhedonia
Bonomi, R. E., Hillmer, A. T., Woodcock, E. A., Bhatt, S., Rusowicz, A., Angarita, G. A., Carson, R. E., Davis, M. T., Esterlis, I., Nabulsi, N., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2406005121 · Cited by 21 · see citing works
“Additionally, these regions are implicated in neuroimmune ( 39 ), neuroendocrine ( 40 ), and transcriptomic ( 41 ) neural circuits involved in the pathophysiology of PTSD. Based on our previous finding of lower TSPO levels ( 13 ), we hypothesized a lower magnitude neuroimmune system response, i.e.,…”
Perspective: Solving the Heterogeneity Conundrum of TSPO PET Imaging in Psychosis
Picker, L. D., & Morrens, M. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.00362 · Cited by 22 · see citing works
“However, findings derived from the study of macrophages or rodent microglia cannot be reliably extrapolated to the behavior of human microglial cells in vivo (59, 60).”
Background
- Authors
- Owen, D. R., Narayan, N., Wells, L., Healy, L., Smyth, E., Rabiner, E. A., Galloway, D., Williams, J. B., Lehr, J., Mandhair, H., Peferoen, L. A., Taylor, P. C., Amor, S., Antel, J. P., Matthews, P. M., & Moore, C. S.
- Affiliations
- Hammersmith Hospital (GB)
- University of Oxford (GB)
- Montreal Neurological Institute and Hospital (CA)
- King's College London (GB)
- Memorial University of Newfoundland (CA)
- Vrije Universiteit Amsterdam (NL)
- Queen Mary University of London (GB)
- Corresponding author
- Owen, David R
- ORCID
- Venue
- Journal of Cerebral Blood Flow & Metabolism
- Publisher
- SAGE Publications
- Published
- 2017-05-22
- Volume
- 37
- Issue
- 8
- Pages
- 2679-2690
- ISSN
- 0271-678X (ISSN-L)
- 1559-7016
- PMC
- PMC5536262
- OpenAlex
- W2619298813
- Cited by
- 194
- References
- 61
- Citations by year
- 2026: 10 · 2025: 12 · 2024: 22 · 2023: 25 · 2022: 26 · 2021: 24 · 2020: 35 · 2019: 18 · 2018: 17 · 2017: 5
- FWCI
- 10.22
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of Cerebral Blood Flow & Metabolism (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Portal (King's College London) (publishedVersion, other-oa)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Pure Amsterdam UMC (submittedVersion, cc-by)
- Spiral (Imperial College London) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- National Institute for Health and Care Research (NF-SI-0514-10022)
- Multiple Sclerosis Society
- Canadian Institutes of Health Research
- Medical Research Council (MR/N008219/1, MR/N026934/1)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pharmacological Receptor Mechanisms and Effects
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Keywords
- TSPO, microglia, macrophages, pro-inflammatory activation, myeloid cell activation, monocyte-derived macrophages
- MeSH terms
- Acetamides, Adult, Animals, Brain, Cells, Cultured, Humans, Interferon-gamma, Lipopolysaccharides, Macrophages, Mice, Inbred C57BL, Middle Aged, Protein Binding, Pyridines, Species Specificity, Gene Expression, Granulocyte-Macrophage Colony-Stimulating Factor, Microglia, Receptors, GABA, Myeloid Cells, Young Adult
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