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https://www.readbyqxmd.com/read/28086916/microglial-activation-in-parkinson-s-disease-using-18-f-feppa
#1
Christine Ghadery, Yuko Koshimori, Sarah Coakeley, Madeleine Harris, Pablo Rusjan, Jinhee Kim, Sylvain Houle, Antonio P Strafella
BACKGROUND: Neuroinflammatory processes including activated microglia have been reported to play an important role in Parkinson's disease (PD). Increased expression of translocator protein (TSPO) has been observed after brain injury and inflammation in neurodegenerative diseases. Positron emission tomography (PET) radioligand targeting TSPO allows for the quantification of neuroinflammation in vivo. METHODS: Based on the genotype of the rs6791 polymorphism in the TSPO gene, we included 25 mixed-affinity binders (MABs) (14 PD patients and 11 age-matched healthy controls (HC)) and 27 high-affinity binders (HABs) (16 PD patients and 11 age-matched HC) to assess regional differences in the second-generation radioligand [(18)F]-FEPPA between PD patients and HC...
January 11, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28072413/decreased-hippocampal-translocator-protein-18%C3%A2-kda-expression-in-alcohol-dependence-a-11-c-pbr28-pet-study
#2
N J Kalk, Q Guo, D Owen, R Cherian, D Erritzoe, A Gilmour, A S Ribeiro, J McGonigle, A Waldman, P Matthews, J Cavanagh, I McInnes, K Dar, R Gunn, E A Rabiner, A R Lingford-Hughes
Repeated withdrawal from alcohol is clinically associated with progressive cognitive impairment. Microglial activation occurring during pre-clinical models of alcohol withdrawal is associated with learning deficits. We investigated whether there was microglial activation in recently detoxified alcohol-dependent patients (ADP), using [(11)C]PBR28 positron emission tomography (PET), selective for the 18kDa translocator protein (TSPO) highly expressed in activated microglia and astrocytes. We investigated the relationship between microglial activation and cognitive performance...
January 10, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28068403/normalisation-against-circadian-and-age-related-disturbances-enables-robust-detection-of-gene-expression-changes-in-liver-of-aged-mice
#3
Sara S Fonseca Costa, Daniel Wegmann, Jürgen A Ripperger
The expression of some genes is affected by age. To detect such age-related changes, their expression levels are related to constant marker genes. However, transcriptional noise increasing with advancing age renders difficult the identification of real age-related changes because it may affect the marker genes as well. Here, we report a selection procedure for genes appropriate to normalise the mouse liver transcriptome under various conditions including age. These genes were chosen from an initial set of 16 candidate genes defined based on a RNA-sequencing experiment and published literature...
2017: PloS One
https://www.readbyqxmd.com/read/28041963/4-chlorodiazepam-modulates-the-development-of-primary-hippocampal-neurons-in-a-sex-dependent-manner
#4
B D Arbo, C Vieira-Marques, I Ruiz-Palmero, A Ortiz-Rodriguez, M A Arevalo, L M Garcia-Segura, M F Ribeiro
The translocator protein 18kDa (TSPO) is located in the outer mitochondrial membrane and is involved in the cholesterol transport into the mitochondria and in the regulation of steroidogenesis and other mitochondrial functions. It is known that steroid hormones, such as estradiol, testosterone and dihydrotestosterone are neuroprotective and regulate neuritogenesis in the CNS by different mechanisms. However, the developmental effects of TSPO ligands in the CNS are not known. Therefore, the aim of this study was to identify the developmental effects of 4'-chlorodiazepam (4'-CD), a TSPO ligand, in primary cultures of male and female mouse hippocampal neurons...
December 29, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/28025995/prediction-of-key-genes-and-mirnas-responsible-for-loss-of-muscle-force-in-patients-during-an-acute-exacerbation-of-chronic-obstructive-pulmonary-disease
#5
Yanhong Duan, Min Zhou, Jian Xiao, Chaomin Wu, Lei Zhou, Feng Zhou, Chunling Du, Yuanlin Song
The present study aimed to identify genes and microRNAs (miRNAs or miRs) that were abnormally expressed in the vastus lateralis muscle of patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The gene expression profile of GSE10828 was downloaded from the Gene Expression Omnibus database, and this dataset was comprised of 4 samples from patients with AECOPD and 5 samples from patients with stable COPD. Differentially expressed genes (DEGs) were screened using the Limma package in R...
November 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28006025/itraq-based-quantitative-proteomics-identifies-potential-regulatory-proteins-involved-in-chicken-eggshell-brownness
#6
Guangqi Li, Congjiao Sun, Guiqin Wu, Fengying Shi, Aiqiao Liu, Ning Yang
Brown eggs are popular in many countries and consumers regard eggshell brownness as an important indicator of egg quality. However, the potential regulatory proteins and detailed molecular mechanisms regulating eggshell brownness have yet to be clearly defined. In the present study, we performed quantitative proteomics analysis with iTRAQ technology in the shell gland epithelium of hens laying dark and light brown eggs to investigate the candidate proteins and molecular mechanisms underlying variation in chicken eggshell brownness...
2016: PloS One
https://www.readbyqxmd.com/read/28004979/epigenetic-silencing-of-the-human-18%C3%A2-kda-translocator-protein-in-a-t-cell-leukemia-cell-line
#7
Ryan J Middleton, Winnie Wai-Ying Kam, Guo-Jun Liu, Richard B Banati
The mitochondrial membrane 18 kDa translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor, is constitutively expressed in most organs, most abundantly in hormonal tissue and cells of mononuclear phagocyte lineage, while in the brain, TSPO expression is induced in the wake of injury, inflammation, and neurodegeneration. Increased TSPO expression is also prominent in several cancerous tissues where it appears to correlate with the degree of malignancy. Currently, TSPO is thus actively investigated as a generic biomarker for disease activity and a therapeutic target for a wide range of diseases...
December 22, 2016: DNA and Cell Biology
https://www.readbyqxmd.com/read/27990801/tryptophan-rich-sensory-protein-translocator-protein-tspo-from-cyanobacterium-fremyella-diplosiphon-binds-a-broad-range-of-functionally-relevant-tetrapyrroles
#8
Andrea W U Busch, Zachary WareJoncas, Beronda L Montgomery
Tryptophan-rich sensory protein/translocator protein (TSPO) is a membrane protein involved in stress adaptation in the cyanobacterium Fremyella diplosiphon. Characterized mammalian and proteobacterial TSPO homologues bind tetrapyrroles and cholesterol ligands. We investigated the ligand binding properties of TSPO from F. diplosiphon (FdTSPO1), which was functionally characterized in prior genetic studies. Two additional TSPO proteins (FdTSPO2 and FdTSPO3) are present in F. diplosiphon; they are similar in size to reported bacterial TSPOs and smaller than FdTSPO1...
December 19, 2016: Biochemistry
https://www.readbyqxmd.com/read/27986860/quantification-of-ono-2952-occupancy-of-translocator-protein-18kda-in-conscious-monkey-brain-using-positron-emission-tomography
#9
Katsukuni Mitsui, Noriko Morimoto, Tomohiro Niwa, Yoshiyuki Yamaura, Hiroyuki Ohba, Hideo Tsukada, Seishi Katsumata
We have previously shown that ONO-2952, a novel translocator protein 18kDa (TSPO) antagonist, inhibits stress-induced neurosteroids accumulation and noradrenaline release in the rat brain and alleviates the subsequent symptomatic responses with a brain TSPO occupancy of 50% or more. In this study, we measured ONO-2952 brain TSPO occupancy in conscious rhesus monkeys using positron emission tomography (PET) with (11)C-PBR28 as ligand for translational research to clinical application. PET scans were performed following single and repeated oral administration of ONO-2952 at several dose levels for each animal with sequential arterial blood sampling...
December 16, 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27983605/effect-of-the-crac-peptide-vlnyyvw-on-mptp-opening-in-rat-brain-and-liver-mitochondria
#10
Tamara Azarashvili, Olga Krestinina, Yulia Baburina, Irina Odinokova, Vladimir Akatov, Igor Beletsky, John Lemasters, Vassilios Papadopoulos
The translocator protein (TSPO; 18 kDa) is a high-affinity cholesterol-binding protein located in the outer membrane of mitochondria. A domain in the C-terminus of TSPO was characterized as the cholesterol recognition/interaction amino acid consensus (CRAC). The ability of the CRAC domain to bind to cholesterol led us to hypothesize that this peptide may participate in the regulation of mitochondrial membrane permeability. Herein, we report the effect of the synthetic CRAC peptide, VLNYYVW, on mitochondrial permeability transition pore (mPTP) opening...
December 13, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27967259/vinpocetine-inhibited-the-cpg-oligodeoxynucleotide-induced-immune-response-in-plasmacytoid-dendritic-cells
#11
Xungang Feng, Yuzhong Wang, Yanlei Hao, Qun Ma, Jun Dai, Zhibo Liang, Yantao Liu, Xiangyuan Li, Yan Song, Chuanping Si
Plasmacytoid dendritic cells (pDCs) exert dual roles in immune responses through inducing inflammation and maintaining immune tolerance. A switch of pDC phenotype from pro-inflammation to tolerance has therapeutic promise in the treatment of autoimmune diseases. Vinpocetine, a vasoactive vinca alkaloid extracted from the periwinkle plant, has recently emerged as an immunomodulatory agent. In this study, we evaluated the effect of vinpocetine on phenotype of pDCs isolated from C57BL/6 mice and explored its possible mechanism...
December 14, 2016: Immunological Investigations
https://www.readbyqxmd.com/read/27939322/two-populations-of-tspo-binding-sites-in-oral-cancer-scc-15-cells
#12
Avishai Gavish, Ella Krayzler, Rafael Nagler
Oral cancer mortality and morbidity rates remain high. The main inducer of oral cancer is cigarette smoke (CS). Translocator protein 18kDa (TSPO) was shown to play a role in carcinogenesis. We characterized TSPO binding sites in human oral cancer cell line SCC-15 and examined effect of CS on TSPO binding. We exposed SCC-15 human squamous cells to cigarette smoke. [(3)H]PK 11195 binding results were assessed in cells confluent for one day. To characterize the number of population sites, a custom written Matlab program compared Pearson linear correlation coefficients between all points in the Scatchard plot...
January 1, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/27936510/systematic-evaluation-of-cs-rosetta-for-membrane-protein-structure-prediction-with-sparse-noe-restraints
#13
Katrin Reichel, Olivier Fisette, Tatjana Braun, Olivier F Lange, Gerhard Hummer, Lars V Schäfer
We critically test and validate the CS-Rosetta methodology for de novo structure prediction of α-helical membrane proteins (MPs) from NMR data, such as chemical shifts and NOE distance restraints. By systematically reducing the number and type of NOE restraints, we focus on determining the regime in which MP structures can be reliably predicted and pinpoint the boundaries of the approach. Five MPs of known structure were used as test systems, phototaxis sensory rhodopsin II (pSRII), a subdomain of pSRII, disul_de binding protein B (DsbB), microsomal prostaglandin E2 synthase-1 (mPGES-1), and translocator protein (TSPO)...
December 9, 2016: Proteins
https://www.readbyqxmd.com/read/27930666/development-of-pet-imaging-to-visualize-activated-macrophages-accumulated-in-the-transplanted-ipsc-derived-cardiac-myocytes-of-allogeneic-origin-for-detecting-the-immune-rejection-of-allogeneic-cell-transplants-in-mice
#14
Noriyuki Kashiyama, Shigeru Miyagawa, Satsuki Fukushima, Takuji Kawamura, Ai Kawamura, Shohei Yoshida, Akima Harada, Tadashi Watabe, Yasukazu Kanai, Koichi Toda, Jun Hatazawa, Yoshiki Sawa
Allogeneic transplantation (Tx) of induced pluripotent stem cells (iPSCs) is a promising tissue regeneration therapy. However, this inevitably induces macrophage-mediated immune response against the graft, limiting its therapeutic efficacy. Monitoring the magnitude of the immune response using imaging tools would be useful for prolonging graft survival and increasing the therapy longevity. Minimally invasive quantitative detection of activated macrophages by medical imaging technologies such as positron emission tomography (PET) imaging targets translocator protein (TSPO), which is highly expressed on mitochondrial membrane, especially in activated macrophage...
2016: PloS One
https://www.readbyqxmd.com/read/27923881/the-ligands-of-translocator-protein-inhibit-human-th1-responses-and-the-rejection-of-murine-skin-allografts
#15
Yannan Zhang, Sifei Yu, Xiaomin Li, Binyan Yang, Changyou Wu
The translocator protein (TSPO) ligands impacted inflammatory and immune responses. However, the exact effects of TSPO ligands on Th1 responses in vitro and in vivo are still unclear. In the current study, we found that TSPO ligands, FGIN1-27 and Ro5-4864, suppressed the cytokine production in a dose- dependent manner by purified human CD4(+) T cells from PBMCs after stimulation. TSPO ligands inhibited the production of IFN-γ by memory CD4(+) T cells and the differentiation of naïve CD4(+) T cells into Th1 cells via  suppressing the activity of the corresponding transcription factors as indicated by reduced expression of T-bet and downregulation of STAT1, STAT4 and STAT5 phosphorylation...
December 6, 2016: Clinical Science (1979-)
https://www.readbyqxmd.com/read/27907096/global-deletion-of-tspo-does-not-affect-the-viability-and-gene-expression-profile
#16
Huaishan Wang, Kangle Zhai, Yingchao Xue, Jia Yang, Qi Yang, Yi Fu, Yu Hu, Fang Liu, Weiqing Wang, Lianxian Cui, Hui Chen, Jianmin Zhang, Wei He
Translocator Protein (18kDa, TSPO) is a mitochondrial outer membrane transmembrane protein. Its expression is elevated during inflammation and injury. However, the function of TSPO in vivo is still controversial. Here, we constructed a TSPO global knockout (KO) mouse with a Cre-LoxP system that abolished TSPO protein expression in all tissues and showed normal phenotypes in the physiological condition. The birth rates of TSPO heterozygote (Het) x Het or KO x KO breeding were consistent with Mendel's Law, suggesting a normal viability of TSPO KO mice at birth...
2016: PloS One
https://www.readbyqxmd.com/read/27903933/translocator-positron-emission-tomography-and-magnetic-resonance-spectroscopic-imaging-of-brain-glial-cell-activation-in-multiple-sclerosis
#17
Gourab Datta, Ines R Violante, Gregory Scott, Karl Zimmerman, Andre Santos-Ribeiro, Eugenii A Rabiner, Roger N Gunn, Omar Malik, Olga Ciccarelli, Richard Nicholas, Paul M Matthews
BACKGROUND: Multiple sclerosis (MS) is characterised by a diffuse inflammatory response mediated by microglia and astrocytes. Brain translocator protein (TSPO) positron-emission tomography (PET) and [myo-inositol] magnetic resonance spectroscopy (MRS) were used together to assess this. OBJECTIVE: To explore the in vivo relationships between MRS and PET [(11)C]PBR28 in MS over a range of brain inflammatory burden. METHODS: A total of 23 patients were studied...
November 30, 2016: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/27893897/imaging-of-glial-cell-activation-and-white-matter-integrity-in-brains-of-active-and-recently-retired-national-football-league-players
#18
Jennifer M Coughlin, Yuchuan Wang, Il Minn, Nicholas Bienko, Emily B Ambinder, Xin Xu, Matthew E Peters, John W Dougherty, Melin Vranesic, Soo Min Koo, Hye-Hyun Ahn, Merton Lee, Chris Cottrell, Haris I Sair, Akira Sawa, Cynthia A Munro, Christopher J Nowinski, Robert F Dannals, Constantine G Lyketsos, Michael Kassiou, Gwenn Smith, Brian Caffo, Susumu Mori, Tomas R Guilarte, Martin G Pomper
Importance: Microglia, the resident immune cells of the central nervous system, play an important role in the brain's response to injury and neurodegenerative processes. It has been proposed that prolonged microglial activation occurs after single and repeated traumatic brain injury, possibly through sports-related concussive and subconcussive injuries. Limited in vivo brain imaging studies months to years after individuals experience a single moderate to severe traumatic brain injury suggest widespread persistent microglial activation, but there has been little study of persistent glial cell activity in brains of athletes with sports-related traumatic brain injury...
January 1, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/27886206/the-antidepressant-like-activity-of-ac-5216-a-ligand-for-18kda-translocator-protein-tspo-in-an-animal-model-of-diabetes-mellitus
#19
Zhi-Kun Qiu, Jia-Li He, Xu Liu, Guan-Hua Zhang, Jia Zeng, Hong Nie, Yong-Gang Shen, Ji-Sheng Chen
Diabetes mellitus is a chronic disease that is associated with depression. Also, depression is common in adults with type 2 diabetes mellitus (T2DM). Translocator protein (18kDa) (TSPO) and allopregnanolone play an important role in the depression treatment. However, few studies have evaluated TSPO and allopregnanolone in the treatment of depression in T2DM. AC-5216, a ligand for TSPO, produces anxiolytic- and antidepressant-like effects in animal models. The present study aimed to explore antidepressant-like effects of AC-5216 on diabetic rats...
November 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27884611/microglial-positron-emission-tomography-pet-imaging-in-epilepsy-applications-opportunities-and-pitfalls
#20
Gregory Scott, Mohammad Mahmud, David R Owen, Michael R Johnson
Neuroinflammation is increasingly implicated in epileptogenesis and epilepsy. Microglia are an important mediator of central nervous system inflammation, and the development of positron emission tomography (PET) radioligands which bind the Translocator Protein (TSPO), an outer mitochondrial membrane protein expressed by microglia, has enabled in vivo measurement of neuroinflammation. Here, we outline the principles and potential pitfalls of TSPO PET imaging in relation to epilepsy, and opportunities for using TSPO imaging as a biomarker for future anti-inflammatory based therapeutics in epilepsy...
November 13, 2016: Seizure: the Journal of the British Epilepsy Association
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