Imaging neuroinflammation with TSPO: A new perspective on the cellular sources and subcellular localization

Guilarte, Tomás R.; Rodichkin, Alexander N.; McGlothan, Jennifer L.; Rocha, Arlet Maria Acanda de la; Azzam, Diana J.

doi:10.1016/j.pharmthera.2021.108048

Cited by 65 publications

(57 citation statements)

References 96 publications

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“…The TSPO signal is not specific to microglia, and the contribution from other cell types (particularly astrocytes and endothelial cells) is increasingly acknowledged 8 . The justification for quantifying TSPO as a marker of microglial activation is based on the assumption that when microglia become activated, they adopt a classical proinflammatory phenotype and TSPO expression is substantially increased 7,9,10 .…”

Section: Introductionmentioning

confidence: 99%

Translocator protein is a marker of activated microglia in rodent models but not human neurodegenerative diseases

Nutma

Fancy

Marzin

et al. 2022

Preprint

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Microglial activation plays central roles in neuro-inflammatory and neurodegenerative diseases. Positron emission tomography (PET) targeting 18kDa Translocator Protein (TSPO) is widely used for localising inflammation in vivo, but its quantitative interpretation remains uncertain. For the first time, we show that TSPO gene and protein expression increases in activated microglia in mouse brain disease models postmortem, but does not change in a non-human primate (Callithrix jacchus) disease model or in common neurodegenerative and neuroinflammatory human diseases. We describe genetic divergence in the TSPO gene promoter that may be responsible for this, which is consistent with the hypothesis that the increase in TSPO in activated myeloid cells is unique to a subset of species within the Muroidea superfamily of rodents. These data emphasise that TSPO expression in human myeloid cells is related to different phenomena than in mice, and that TSPO PET reflects density of inflammatory cells rather than their activation state.

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Section: Introductionmentioning

confidence: 99%

Translocator protein is a marker of activated microglia in rodent models but not human neurodegenerative diseases

Nutma

Fancy

Marzin

et al. 2022

Preprint

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“…The expression of Translocator Protein 18 kDa (TSPO), first described as the peripheral benzodiazepine receptor, was considered to be upregulated in the activated microglia [ 8 ]. This biomarker for brain neuroinflammation can be accessed by using TSPO positron emission tomography (PET) neuroimaging [ 9 ]. Compared with the radiotracer of 11 C-PK11195, 18 F-DPA-714 showed better imaging performance on affinity, bioavailability, and signal-to-noise ratio (SNR) [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

“…is biomarker for brain neuroinflammation can be accessed by using TSPO positron emission tomography (PET) neuroimaging [9]. Compared with the radiotracer of 11 C-PK11195, 18 F-DPA-714 showed better imaging performance on affinity, bioavailability, and signal-to-noise ratio (SNR) [10,11].…”

Section: Introductionmentioning

confidence: 99%

The Anti-Inflammatory Effect of Preventive Intervention with Ketogenic Diet Mediated by the Histone Acetylation of mGluR5 Promotor Region in Rat Parkinson’s Disease Model: A Dual-Tracer PET Study

Zhu

Tang

Cheng

et al. 2022

Parkinson's Disease

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Background and Objectives. The exact pathological mechanism of Parkinson’s disease (PD) remains elusive, and the existing therapies fail to reverse the disease progression. This study intended to explore the epigenetic anti-inflammatory mechanism of ketogenic diet (KD). Materials and Methods. The neuroprotective effect of ketosis state prior to the onset of PD (preventive KD, KDp) was compared with that receiving KD after the onset (therapeutic KD, KDt) in the lipopolysaccharide- (LPS-) induced rat PD model. A total of 100 rats were randomly assigned to the following 4 groups: sham, LPS, LPS + KDp, and LPS + KDt groups. Results. Significant dopamine deficient behaviors (rotational behavior and contralateral forelimb akinesia), upregulation of proinflammatory mediators (TNF-α, IL-1β, and IL-6), loss of dopaminergic neurons, reduction of mGluR5+ microglia cells, increase of TSPO+ microglia cells, reduction of H3K9 acetylation in the mGluR5 promoter region and mGluR5 mRNA expression, and decline in the phosphorylation levels of Akt/GSK-3β/CREB pathway were observed after the intervention of LPS ( P < 0.01 ). TSPO and DAT PET imaging revealed the increased uptake of 18F-DPA-714 in substantia nigra and decreased uptake of 18F-FP-CIT in substantia nigra and striatum in LPS-treated rats ( P < 0.001 ). These impairments were alleviated by the dietary intervention of KD, especially with the strategy of KDp ( P < 0.05 ). Conclusions. The anti-inflammatory effect of KD on PD was supposed to be related to the modulation of Akt/GSK-3β/CREB signaling pathway mediated by the histone acetylation of mGluR5 promotor region. The KD intervention should be initiated prior to the PD onset in high-risk population to achieve a more favorable outcome.

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“…The TSPO signal is not specific to microglia, and the contribution from other cell types (particularly astrocytes and endothelial cells) is increasingly acknowledged 8 . The justification for quantifying TSPO as a marker of microglial activation is based on the assumption that when microglia become activated, they adopt a classical pro-inflammatory phenotype and TSPO expression is substantially increased, 7, 9 10 .…”

Section: Introductionmentioning

confidence: 99%

Translocator protein is a marker of activated microglia in rodent models but not human neurodegenerative diseases

Nutma

Fancy

Weinert

et al. 2022

Preprint

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Microglial activation plays central roles in neuro-inflammatory and neurodegenerative diseases. Positron emission tomography (PET) targeting 18kDa Translocator Protein (TSPO) is widely used for localising inflammation in vivo, but its quantitative interpretation remains uncertain. We show that TSPO expression increases in activated microglia in mouse brain disease models but does not change in a non-human primate disease model or in common neurodegenerative and neuroinflammatory human diseases. We describe genetic divergence in the TSPO gene promoter, consistent with the hypothesis that the increase in TSPO expression in activated myeloid cells is unique to a subset of species within the Muroidea superfamily of rodents. We show that TSPO is mechanistically linked to classical pro-inflammatory myeloid cell function in rodents but not humans. These data emphasise that TSPO expression in human myeloid cells is related to different phenomena than in mice, and that TSPO PET reflects density of inflammatory cells rather than activation state.

show abstract

Imaging neuroinflammation with TSPO: A new perspective on the cellular sources and subcellular localization

Cited by 65 publications

References 96 publications

Translocator protein is a marker of activated microglia in rodent models but not human neurodegenerative diseases

Translocator protein is a marker of activated microglia in rodent models but not human neurodegenerative diseases

The Anti-Inflammatory Effect of Preventive Intervention with Ketogenic Diet Mediated by the Histone Acetylation of mGluR5 Promotor Region in Rat Parkinson’s Disease Model: A Dual-Tracer PET Study

Translocator protein is a marker of activated microglia in rodent models but not human neurodegenerative diseases

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