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https://www.readbyqxmd.com/read/28733954/assessment-of-simplified-ratio-based-approaches-for-quantification-of-pet-11-c-pbr28-data
#1
Granville J Matheson, Pontus Plavén-Sigray, Anton Forsberg, Andrea Varrone, Lars Farde, Simon Cervenka
PURPOSE: Kinetic modelling with metabolite-corrected arterial plasma is considered the gold standard for quantification of [(11)C]PBR28 binding to the translocator protein (TSPO), since there is no brain region devoid of TSPO that can serve as reference. The high variability in binding observed using this method has motivated the use of simplified ratio-based approaches such as standardised uptake value ratios (SUVRs) and distribution volume (VT) ratios (DVRs); however, the reliability of these measures and their relationship to VT have not been sufficiently evaluated...
December 2017: EJNMMI Research
https://www.readbyqxmd.com/read/28705919/time-courses-of-cortical-glucose-metabolism-and-microglial-activity-across-the-life-span-of-wild-type-mice-a-pet-study
#2
Matthias Brendel, Carola Focke, Tanja Blume, Finn Peters, Maximilian Deussing, Federico Probst, Anna Jaworska, Felix Overhoff, Nathalie Albert, Simon Lindner, Barbara von Ungern-Sternberg, Peter Bartenstein, Christian Haass, Gernot Kleinberger, Jochen Herms, Axel Rominger
Contrary to findings in human brain, [(18)F]-FDG PET shows cerebral hypermetabolism of aged wild-type (WT) mice relative to younger animals, supposedly due to microglial activation. Therefore, we used dual tracer µPET to examine directly the link between neuroinflammation and hypermetabolism in aged mice. Methods: WT mice (5-20 months) were investigated in a cross-sectional design using [(18)F]-FDG (N = 43) and TSPO ([(18)F]-GE180; N = 58) µPET, with volume-of-interest and voxel-wise analyses. Biochemical analysis of plasma cytokine levels and immunohistochemical confirmation of microglial activity were also performed...
July 13, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28701948/microglial-activation-in-traumatic-brain-injury
#3
REVIEW
Cornelius K Donat, Gregory Scott, Steve M Gentleman, Magdalena Sastre
Microglia have a variety of functions in the brain, including synaptic pruning, CNS repair and mediating the immune response against peripheral infection. Microglia rapidly become activated in response to CNS damage. Depending on the nature of the stimulus, microglia can take a number of activation states, which correspond to altered microglia morphology, gene expression and function. It has been reported that early microglia activation following traumatic brain injury (TBI) may contribute to the restoration of homeostasis in the brain...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28698896/the-role-of-tspo-pet-in-assessing-neuroinflammation
#4
Ania A Crawshaw, Neil P Robertson
No abstract text is available yet for this article.
July 11, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28698403/identifying-mitotane-induced-mitochondria-associated-membranes-dysfunctions-metabolomic-and-lipidomic-approaches
#5
Ségolène Hescot, Larbi Amazit, Marie Lhomme, Simon Travers, Anais DuBow, Stéphanie Battini, Geoffrey Boulate, Izzie Jacques Namer, Anne Lombès, Anatol Kontush, Alessio Imperiale, Eric Baudin, Marc Lombès
Mitotane (o,p'DDD), the most effective drug in adrenocortical carcinoma, concentrates into the mitochondria and impacts mitochondrial functions. To address the molecular mechanisms of mitotane action and to identify its potential target, metabolomic and lipidomic approaches as well as imaging analyses were employed in human adrenocortical H295R cells allowing identification of Mitochondria-Associated Membranes dysfunction as a critical impact of mitotane. Study of intracellular energetic metabolites by NMR spectroscopy showed that mitotane significantly decreased aspartate while concomitantly increased glutamate content in a time- and concentration-dependent manner...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28695372/increased-expression-of-translocator-protein-tspo-marks-pro-inflammatory-microglia-but-does-not-predict-neurodegeneration
#6
Lien Beckers, Dieter Ory, Ivana Geric, Lieven Declercq, Michel Koole, Michael Kassiou, Guy Bormans, Myriam Baes
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...
July 10, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28675779/neurosteroidogenesis-and-progesterone-anti-inflammatory-neuroprotective-effects
#7
REVIEW
Alejandro F De Nicola, Laura I Garay, Maria Meyer, Rachida Guennoun, Regine Sitruk-Ware, Michael Schumacher, Maria Claudia Gonzalez Deniselle
Progesterone shows anti-inflammatory and promyelinating effects in mice with autoimmune experimental encephalomyelitis (EAE), a commonly used model for multiple sclerosis (MS). Since neurosteroids have been implicated as protective factors for MS and EAE, we analyzed the expression of neurosteroidogenic enzymes in the compromised spinal cord of EAE mice. EAE was induced in female C57Bl6 mice and killed on day 16 after induction. Progesterone was given by pellet implantation 1 week before EAE induction. Untreated EAE mice showed decreased mRNAs for the steroidogenic acute regulatory protein (Star), voltage-dependent anion channel (VDAC), cholesterol side-chain cleavage (P450scc), 5α-reductase, 3α-hydroxysteroid dehydrogenase (3α-HSOR) and aromatase, whereas changes of 3β-hydroxysteroid dehydrogenase (3β-HSD) were not significant...
July 4, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28667781/translocator-protein-18-kda-an-update-on-its-function-in-steroidogenesis
#8
REVIEW
Vassilios Papadopoulos, Jinjiang Fan, Barry Zirkin
Translocator protein (18 kDa), TSPO, is a ubiquitous mitochondrial protein. Studies of its responses to drug and endogenous ligands have shown TSPO to be involved either directly or indirectly in numerous biological functions, including mitochondrial cholesterol transport and steroid hormone biosynthesis, porphyrin transport and heme synthesis, apoptosis, cell proliferation, and anion transport. Localized to the outer mitochondrial membrane of steroidogenic cells, TSPO has been shown to associate with cytosolic and mitochondrial proteins as part of a large multiprotein complex involved in mitochondrial cholesterol transport, the rate-limiting step in steroidogenesis...
July 1, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28655607/overexpression-of-the-18%C3%A2-kda-translocator-protein-tspo-in-the-hippocampal-dentate-gyrus-produced-anxiolytic-and-antidepressant-like-behavioural-effects
#9
Lei Li, Wei Wang, Li-Ming Zhang, Xiang-Yun Jiang, Shuzheng Sun, Li-Jun Sun, Ying Guo, Jie Gong, Youzhi Zhang, Henglin Wang, Yunfeng Li
The 18 kDa translocator protein (TSPO) is a five transmembrane domain protein that plays a crucial role in neurosteroid (e.g., allopregnanolone) synthesis by promoting the transport of cholesterol to the inner mitochondrial membrane. This protein is predominantly expressed in steroid-synthesizing tissues, including the central and peripheral nervous system, affecting stress-related disorders such as anxiety and depression. Recent studies have focused on the hippocampal dentate gyrus, which is very important for involvement of anxiety and depression...
June 24, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28645478/a-tspo-ligand-prevents-mitochondrial-sterol-accumulation-and-dysfunction-during-myocardial-ischemia-reperfusion-in-hypercholesterolemic-rats
#10
Julien Musman, Stéphanie Paradis, Mathieu Panel, Sandrine Pons, Caroline Barau, Claudio Caccia, Valerio Leoni, Bijan Ghaleh, Didier Morin
A major cause of cell death during myocardial ischemia-reperfusion is mitochondrial dysfunction. We previously showed that the reperfusion of an ischemic myocardium was associated with an accumulation of cholesterol into mitochondria and a concomitant strong generation of auto-oxidized oxysterols. The inhibition of mitochondrial accumulation of cholesterol abolished the formation of oxysterols and prevented mitochondrial injury at reperfusion. The aim of this study was to investigate the impact of hypercholesterolemia on sterol and oxysterol accumulation in rat cardiac cytosols and mitochondria and to analyse the effect of the translocator protein ligand 4'-chlorodiazepam on this accumulation and mitochondrial function...
June 20, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28640253/a-role-for-tspo-in-mitochondrial-ca-2-homeostasis-and-redox-stress-signaling
#11
Jemma Gatliff, Daniel A East, Aarti Singh, Maria Soledad Alvarez, Michele Frison, Ivana Matic, Caterina Ferraina, Natalie Sampson, Federico Turkheimer, Michelangelo Campanella
The 18 kDa translocator protein TSPO localizes on the outer mitochondrial membrane (OMM). Systematically overexpressed at sites of neuroinflammation it is adopted as a biomarker of brain conditions. TSPO inhibits the autophagic removal of mitochondria by limiting PARK2-mediated mitochondrial ubiquitination via a peri-organelle accumulation of reactive oxygen species (ROS). Here we describe that TSPO deregulates mitochondrial Ca(2+) signaling leading to a parallel increase in the cytosolic Ca(2+) pools that activate the Ca(2+)-dependent NADPH oxidase (NOX) thereby increasing ROS...
June 22, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28636705/inflammation-in-the-neurocircuitry-of-obsessive-compulsive-disorder
#12
Sophia Attwells, Elaine Setiawan, Alan A Wilson, Pablo M Rusjan, Romina Mizrahi, Laura Miler, Cynthia Xu, Margaret Anne Richter, Alan Kahn, Stephen J Kish, Sylvain Houle, Lakshmi Ravindran, Jeffrey H Meyer
Importance: For a small percentage of obsessive-compulsive disorder (OCD) cases exhibiting additional neuropsychiatric symptoms, it was proposed that neuroinflammation occurs in the basal ganglia as an autoimmune response to infections. However, it is possible that elevated neuroinflammation, inducible by a diverse range of mechanisms, is important throughout the cortico-striato-thalamo-cortical circuit of OCD. Identifying brain inflammation is possible with the recent advance in positron emission tomography (PET) radioligands that bind to the translocator protein (TSPO)...
June 21, 2017: JAMA Psychiatry
https://www.readbyqxmd.com/read/28609670/differential-effects-of-the-18-kda-translocator-protein-tspo-ligand-etifoxine-on-steroidogenesis-in-rat-brain-plasma-and-steroidogenic-glands-pharmacodynamic-studies
#13
Philippe Liere, Antoine Pianos, Jean-Paul Oudinet, Michael Schumacher, Yvette Akwa
Etifoxine is indicated in humans for treating anxiety. In rodents, besides its anxiolytic-like properties, it has recently shown neuroprotective and neuroregenerative activities. It acts by enhancing GABAA receptor function and by stimulating acute steroid biosynthesis via the activation of the 18-kDa translocator protein. However, the regulatory action of etifoxine on steroid production is not well characterized. In this work, we performed dose-response, acute and chronic time-course experiments on the effects of intraperitoneal injections of etifoxine on steroid levels in adult male rat brain and plasma analyzed by gas chromatography-mass spectrometry...
June 3, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28604733/imaging-microglial-activation-in-individuals-at-clinical-high-risk-for-psychosis-an-in-vivo-pet-study-with-18-f-feppa
#14
Sina Hafizi, Tania Da Silva, Cory Gerritsen, Michael Kiang, R Michael Bagby, Ivana Prce, Alan A Wilson, Sylvain Houle, Pablo M Rusjan, Romina Mizrahi
Several lines of evidence implicate microglial activation and abnormal immune response in the etiology of psychosis. Previous positron emission tomography (PET) neuroimaging studies of the translocator protein 18 kDa, TSPO, were limited by low affinity of the first-generation radioligand, low-resolution scanners, and small sample sizes. Moreover, there is a dearth of literature on microglial activation in individuals at clinical high risk (CHR) for psychosis. We used a novel second-generation TSPO radioligand, [(18)F]FEPPA, to examine whether microglial activation is elevated in the dorsolateral prefrontal cortex (DLPFC) and hippocampus of antipsychotic-naive CHR...
June 12, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28580888/kinetic-modelling-of-11-c-pbr28-for-18%C3%A2-kda-translocator-protein-pet-data-a-validation-study-of-vascular-modelling-in-the-brain-using-xbd173-and-tissue-analysis
#15
Mattia Veronese, Tiago Reis Marques, Peter S Bloomfield, Gaia Rizzo, Nisha Singh, Deborah Jones, Erjon Agushi, Dominic Mosses, Alessandra Bertoldo, Oliver Howes, Federico Roncaroli, Federico E Turkheimer
The 18 kDa translocator protein (TSPO) is a marker of microglia activation in the central nervous system and represents the main target of radiotracers for the in vivo quantification of neuroinflammation with positron emission tomography (PET). TSPO PET is methodologically challenging given the heterogeneous distribution of TSPO in blood and brain. Our previous studies with the TSPO tracers [(11)C]PBR28 and [(11)C]PK11195 demonstrated that a model accounting for TSPO binding to the endothelium improves the quantification of PET data...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28572290/the-variability-of-translocator-protein-signal-in-brain-and-blood-of-genotyped-healthy-humans-using-in-vivo-123-i-clinde-spect-imaging-a-test-retest-study
#16
Ling Feng, Per Jensen, Gerda Thomsen, Agnete Dyssegaard, Claus Svarer, Lars V Knudsen, Kirsten Møller, Carsten Thomsen, Jens D Mikkelsen, Denis Guilloteau, Gitte M Knudsen, Lars H Pinborg
(123)I-CLINDE is a radiotracer developed for SPECT and targets the 18-kDa translocator protein (TSPO). TSPO is upregulated in glial cells and used as a measure of neuroinflammation in a variety of central nervous system diseases. The aim of this study was to examine the test-retest variability of (123)I-CLINDE binding in healthy subjects. Methods: SPECT scans were acquired over 90 min in 16 healthy controls (9 women, 8 mixed-affinity binders [MABs] and 8 high-affinity binders [HABs] twice with an interval of 35 ± 15 d)...
June 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28559417/the-ftd-like-syndrome-causing-trem2-t66m-mutation-impairs-microglia-function-brain-perfusion-and-glucose-metabolism
#17
Gernot Kleinberger, Matthias Brendel, Eva Mracsko, Benedikt Wefers, Linda Groeneweg, Xianyuan Xiang, Carola Focke, Maximilian Deußing, Marc Suárez-Calvet, Fargol Mazaheri, Samira Parhizkar, Nadine Pettkus, Wolfgang Wurst, Regina Feederle, Peter Bartenstein, Thomas Mueggler, Thomas Arzberger, Irene Knuesel, Axel Rominger, Christian Haass
Genetic variants in the triggering receptor expressed on myeloid cells 2 (TREM2) increase the risk for several neurodegenerative diseases including Alzheimer's disease and frontotemporal dementia (FTD). Homozygous TREM2 missense mutations, such as p.T66M, lead to the FTD-like syndrome, but how they cause pathology is unknown. Using CRISPR/Cas9 genome editing, we generated a knock-in mouse model for the disease-associated Trem2 p.T66M mutation. Consistent with a loss-of-function mutation, we observe an intracellular accumulation of immature mutant Trem2 and reduced generation of soluble Trem2 similar to patients with the homozygous p...
July 3, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28545084/feasibility-study-of-tspo-quantification-with-18f-feppa-using-population-based-input-function
#18
Rostom Mabrouk, Antonio P Strafella, Dunja Knezevic, Christine Ghadery, Romina Mizrahi, Avideh Gharehgazlou, Yuko Koshimori, Sylvain Houle, Pablo Rusjan
PURPOSE: The input function (IF) is a core element in the quantification of Translocator protein 18 kDa with positron emission tomography (PET), as no suitable reference region with negligible binding has been identified. Arterial blood sampling is indeed needed to create the IF (ASIF). In the present manuscript we study individualization of a population based input function (PBIF) with a single arterial manual sample to estimate total distribution volume (VT) for [18F]FEPPA and to replicate previously published clinical studies in which the ASIF was used...
2017: PloS One
https://www.readbyqxmd.com/read/28540077/role-of-molecular-imaging-with-positron-emission-tomographic-in-aortic-aneurysms
#19
REVIEW
Parmanand Singh, Zaid Almarzooq, Brian Salata, Richard B Devereux
Aortic aneurysms (AA) are often asymptomatic before the occurrence of acute, potentially fatal complications including dissection and/or rupture. Beyond aortic size, the ability to assess aortic wall characteristics and processes contributing to aneurysm development may allow improved selection of patients who may benefit from prophylactic surgical intervention. Current risk stratification for aneurysms relies upon routine noninvasive imaging of aortic size without assessing the underlying pathophysiologic processes, including features such as inflammation, which may be associated with aneurysm development and progression...
April 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28533150/molecular-imaging-of-neuroinflammation-in-alzheimer-s-disease-and-mild-cognitive-impairment
#20
REVIEW
Dunja Knezevic, Romina Mizrahi
Neuroinflammatory changes have been demonstrated to be an important feature of Alzheimer's disease (AD); however, the exact role of neuroinflammation and its progression during disease is still not well understood. One of the main drivers of the neuroinflammatory process are microglial cells. Positron Emission Tomography allows for the quantification of microglial activation by labelling the Translocator Protein 18kDa (TSPO), which becomes overexpressed upon activation of microglial cells. Several radioligands have been designed to target TSPO and have been studied in-vivo in AD populations...
May 19, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
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