Translocator Protein (TSPO) Expression in Platelets of Depressed Patients Decreases during Antidepressant Therapy

Sarubin, Nina; Baghai, Thomas C.; Lima-Ojeda, Juan M.; Melchner, D; Hallof-Buestrich, H; Wolf, Lisa; Hilbert, Sven; Milenkovic, Vladimir M.; Wetzel, Christian H.; Rupprecht, Rainer

doi:10.1055/s-0042-107795

Cited by 13 publications

(8 citation statements)

References 30 publications

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“…As this study did not demonstrate changes in TSPO expression in microglia in vivo after irradiation, this suggests that the reduction in TSPO seen after LDIR was primarily from cells which constitutively express TSPO rather than from inducible expression. This is consistent with previous studies which have demonstrated a downregulation in TSPO expression from baseline in several neurological and psychiatric disorders, including PTSD ( Gavish et al, 1996 ), depression ( Chelli et al, 2008 ; Sarubin et al, 2016 ), and reduced TSPO ligand binding in PET imaging of recent onset schizophrenia ( Notter et al, 2018a ), despite the induction of systemic cytokine immune responses. We previously speculated that the reduced levels of TSPO that have sometimes been demonstrated in molecular imaging studies under certain subtle disease states reflect changes in vascular endothelial cells, which we found to have widely distributed, albeit low-level, expression of TSPO across the brain ( Betlazar et al, 2018 ).…”

Section: Discussionsupporting

confidence: 93%

Mitochondrial Translocator Protein (TSPO) Expression in the Brain After Whole Body Gamma Irradiation

Betlazar

Middleton

Howell

et al. 2021

Front. Cell Dev. Biol.

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The brain’s early response to low dose ionizing radiation, as may be encountered during diagnostic procedures and space exploration, is not yet fully characterized. In the brain parenchyma, the mitochondrial translocator protein (TSPO) is constitutively expressed at low levels by endothelial cells, and can therefore be used to assess the integrity of the brain’s vasculature. At the same time, the inducible expression of TSPO in activated microglia, the brain’s intrinsic immune cells, is a regularly observed early indicator of subtle or incipient brain pathology. Here, we explored the use of TSPO as a biomarker of brain tissue injury following whole body irradiation. Post-radiation responses were measured in C57BL/6 wild type (Tspo+/+) and TSPO knockout (Tspo–/–) mice 48 h after single whole body gamma irradiations with low doses 0, 0.01, and 0.1 Gy and a high dose of 2 Gy. Additionally, post-radiation responses of primary microglial cell cultures were measured at 1, 4, 24, and 48 h at an irradiation dose range of 0 Gy-2 Gy. TSPO mRNA and protein expression in the brain showed a decreased trend after 0.01 Gy relative to sham-irradiated controls, but remained unchanged after higher doses. Immunohistochemistry confirmed subtle decreases in TSPO expression after 0.01 Gy in vascular endothelial cells of the hippocampal region and in ependymal cells, with no detectable changes following higher doses. Cytokine concentrations in plasma after whole body irradiation showed differential changes in IL-6 and IL-10 with some variations between Tspo–/– and Tspo+/+ animals. The in vitro measurements of TSPO in primary microglial cell cultures showed a significant reduction 1 h after low dose irradiation (0.01 Gy). In summary, acute low and high doses of gamma irradiation up to 2 Gy reduced TSPO expression in the brain’s vascular compartment without de novo induction of TSPO expression in parenchymal microglia, while TSPO expression in directly irradiated, isolated, and thus highly activated microglia, too, was reduced after low dose irradiation. The potential link between TSPO, its role in mitochondrial energy metabolism and the selective radiation sensitivity, notably of cells with constitutive TSPO expression such as vascular endothelial cells, merits further exploration.

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Section: Discussionsupporting

confidence: 93%

Mitochondrial Translocator Protein (TSPO) Expression in the Brain After Whole Body Gamma Irradiation

Betlazar

Middleton

Howell

et al. 2021

Front. Cell Dev. Biol.

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“…It plays an important role in neurosteroid synthesis and in systemic endocrine regulation, with implications in the pathophysiology of immune, inflammatory, neurodegenerative, neoplastic and psychiatric diseases 113 . Interestingly, Sarubin et al 114 investigated the effects of antidepressant treatment on TSPO expression levels in platelets obtained from 37 patients suffering from MDD, analysing TSPO levels in depressed patients before and after 6 weeks of antidepressant treatment. A significant change in TSPO levels over 6 weeks of treatment was observed within the complete sample of MDD patients.…”

Section: Treatmentmentioning

confidence: 99%

Gene expression studies in Depression development and treatment: an overview of the underlying molecular mechanisms and biological processes to identify biomarkers

et al. 2021

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A combination of different risk factors, such as genetic, environmental and psychological factors, together with immune system, stress response, brain neuroplasticity and the regulation of neurotransmitters, is thought to lead to the development of major depressive disorder (MDD). A growing number of studies have tried to investigate the underlying mechanisms of MDD by analysing the expression levels of genes involved in such biological processes. These studies have shown that MDD is not just a brain disorder, but also a body disorder, and this is mainly due to the interplay between the periphery and the Central Nervous System (CNS). To this purpose, most of the studies conducted so far have mainly dedicated to the analysis of the gene expression levels using postmortem brain tissue as well as peripheral blood samples of MDD patients. In this paper, we reviewed the current literature on candidate gene expression alterations and the few existing transcriptomics studies in MDD focusing on inflammation, neuroplasticity, neurotransmitters and stress-related genes. Moreover, we focused our attention on studies, which have investigated mRNA levels as biomarkers to predict therapy outcomes. This is important as many patients do not respond to antidepressant medication or could experience adverse side effects, leading to the interruption of treatment. Unfortunately, the right choice of antidepressant for each individual still remains largely a matter of taking an educated guess.

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“…Since the semiquantitative parameter SUV, which does not account for changes in peripheral metabolism of the radioligand [13], did not exhibit a decrease in uptake after blocking of TSPO, we investigated if we could use a pseudo-reference agent as in the brain where the cerebellum has been used [14]. We used both blood and cancellous bone, both of which contain TSPO [15,16] as pseudo-reference region as an estimate specific [ 11 C]PBR28 tissue uptake. We found that like V T , a decrease in SUVr 50-70 blood and SUVr 50-70 bone was observed after TSPO blocking with XBD-173 was noted with a decrease, indicating that both SUVr 50-70 blood and SUVr 50-70 bone could be used to quantify [ 11 C]PBR28 uptake.…”

Section: Discussionmentioning

confidence: 99%

Specificity of translocator protein-targeted positron emission tomography in inflammatory joint disease

et al. 2020

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Objective Expression of the translocator protein (TSPO) on inflammatory cells has facilitated imaging of synovitis with TSPO-targeted positron emission tomography (PET). We aimed to quantitatively assess the specificity of the second-generation TSPO PET radioligand, [11C]PBR28, and to generate simplified PET protocols in patients with inflammatory joint disease (IJD) in this pilot study. Methods Three IJD patients (two rheumatoid arthritis and one osteoarthritis) with knee involvement underwent dynamic [11C]PBR28-PET scans before and after administration of 90 mg of oral emapunil (XBD-173), a TSPO ligand the same day. Radial arterial blood sampling was performed throughout the scan, and total radioactivity and radioactive metabolites were obtained. A semi-automated method was used to generate regions of interest. Standardized uptake value (SUV) and SUV ratio corrected for activity in bone and blood between 50 and 70 min (SUVr50–70 bone, SUVr50–70 blood, respectively) and PET volume of distribution (VT) of the radioligand were calculated. Results A mean [11C]PBR28 radioactivity of 378 (range 362–389) MBq was administered. A significant decrease (p < 0.05) in VT, SUVr50–70 bone and SUVr50–70 blood observed after oral emapunil confirmed the TSPO specificity of [11C]PBR28. A decrease in SUV was not observed in the post-block scan. Conclusion [11C]PBR28 is TSPO-specific radioligand in IJD patients. Simplified PET protocols with static PET acquisition can be used in the management and evaluation of novel therapeutics that target TSPO overexpressing cells.

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Translocator Protein (TSPO) Expression in Platelets of Depressed Patients Decreases during Antidepressant Therapy

Cited by 13 publications

References 30 publications

Mitochondrial Translocator Protein (TSPO) Expression in the Brain After Whole Body Gamma Irradiation

Mitochondrial Translocator Protein (TSPO) Expression in the Brain After Whole Body Gamma Irradiation

Gene expression studies in Depression development and treatment: an overview of the underlying molecular mechanisms and biological processes to identify biomarkers

Specificity of translocator protein-targeted positron emission tomography in inflammatory joint disease

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