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https://www.readbyqxmd.com/read/28219319/biomarkers-in-alzheimer-s-disease-recent-update
#1
Sushil Sharma, Walter Lipincott
Alzheimer disease (AD) is an age-related neurodegenerative disorder, characterized by loss of memory and cognitive function. It is the common cause of dementia in elderly and is a global health concern as the population of people aged 85 and older, is growing alarmingly. Although pharmacotherapy for the treatment of AD has improved, lot of work remains to treat this devastating disease. AD pathology begins even before the onset of clinical symptoms. Because therapies could be more effective if implemented early in the disease progression, it is highly prudent to discover reliable biomarkers, to detect its exact pathophysiology during pre-symptomatic stage...
February 20, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28194003/lower-levels-of-the-glial-cell-marker-tspo-in-drug-naive-first-episode-psychosis-patients-as-measured-using-pet-and-11-c-pbr28
#2
K Collste, P Plavén-Sigray, H Fatouros-Bergman, P Victorsson, M Schain, A Forsberg, N Amini, S Aeinehband, S Erhardt, C Halldin, L Flyckt, L Farde, S Cervenka
Several lines of evidence are indicative of a role for immune activation in the pathophysiology of schizophrenia. Nevertheless, studies using positron emission tomography (PET) and radioligands for the translocator protein (TSPO), a marker for glial activation, have yielded inconsistent results. Whereas early studies using a radioligand with low signal-to-noise in small samples showed increases in patients, more recent studies with improved methodology have shown no differences or trend-level decreases. Importantly, all patients investigated thus far have been on antipsychotic medication, and as these compounds may dampen immune cell activity, this factor limits the conclusions that can be drawn...
February 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28156095/optimized-translocator-protein-ligand-for-optical-molecular-imaging-and-screening
#3
Jun Li, Jarrod A Smith, Eric S Dawson, Allie Fu, Michael L Nickels, Michael L Schulte, H Charles Manning
Translocator protein (TSPO) is a validated target for molecular imaging of a variety of human diseases and disorders. Given its involvement in cholesterol metabolism, TSPO expression is commonly elevated in solid tumors, including glioma, colorectal cancer, and breast cancer. TSPO ligands capable of detection by optical imaging are useful molecular tracers for a variety of purposes that range from quantitative biology to drug discovery. Leveraging our prior optimization of the pyrazolopyrimidine TSPO ligand scaffold for cancer imaging, we report herein a new generation of TSPO tracers with superior binding affinity and suitability for optical imaging and screening...
February 13, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28137769/combined-pet-imaging-of-the-inflammatory-tumor-microenvironment-identifies-margins-of-unique-radiotracer-uptake
#4
Bastian Zinnhardt, Hayet Pigeon, Benoit Thézé, Thomas Viel, Lydia Wachsmuth, Inga B Fricke, Sonja Schelhaas, Lisa Honold, Katrin Schwegmann, Stefan Wagner, Andreas Faust, Cornelius Faber, Michael T Kuhlmann, Sven Hermann, Michael Schäfers, Alexandra Winkeler, Andreas H Jacobs
The tumor microenvironment is highly heterogeneous. For gliomas, the tumor-associated inflammatory response is pivotal to support growth and invasion. Factors of glioma growth, inflammation, and invasion, such as the translocator protein (TSPO) and matrix metalloproteinases (MMP), may serve as specific imaging biomarkers of the glioma microenvironment. In this study, non-invasive imaging by positron emission tomography (PET) with [(18)F]DPA-714 (TSPO) and [(18)F]BR-351 (MMP) was used for assessment of localization and quantification of the expression of TSPO and MMP...
January 30, 2017: Cancer Research
https://www.readbyqxmd.com/read/28129443/anxiolytic-effects-of-hippocampal-neurosteroids-in-normal-and-neuropathic-rats-with-spared-nerve-injury
#5
Meng Zhang, Jia Liu, Meng-Meng Zhou, Honghai Wu, Yanning Hou, Yun-Feng Li, Yuxin Yin, Lemin Zheng, Jie Cai, Fei-Fei Liao, Feng-Yu Liu, Ming Yi, You Wan
Neurosteroids are synthesized in the nervous system from cholesterol or steroidal precursors imported from peripheral sources. These compounds are important allosteric modulators of GABAA receptors, which play a vital role in modulating hippocampal functions. Chronic pain is accompanied by increased neurosteroid production in the spinal cord and thalamus. We hypothesize that hippocampal neurosteroids participate in pain or pain-associated emotions, which we tested with high-performance liquid chromatography/tandem mass spectrometry and pharmacological behavioral tests...
January 27, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28128020/positron-emission-tomography-of-cerebral-angiogenesis-and-tspo-expression-in-a-mouse-model-of-chronic-hypoxia
#6
Iwao Kanno, Chie Seki, Hiroyuki Takuwa, Zhao-Hui Jin, Didier Boturyn, Pascal Dumy, Takako Furukawa, Tsuneo Saga, Hiroshi Ito, Kazuto Masamoto
The present study aimed to examine whether positron emission tomography (PET) could evaluate cerebral angiogenesis. Mice were housed in a hypoxic chamber with 8-9% oxygen for 4, 7, and 14 days, and the angiogenic responses were evaluated with a radiotracer, (64)Cu-cyclam-RAFT-c(-RGDfK-)4, which targeted αVβ3 integrin and was imaged with PET. The PET imaging results showed little uptake during all of the hypoxic periods. Immunofluorescence staining of the β3 integrin, CD61, revealed weak expression, while the microvessel density assessed by CD31 staining increased with the hypoxic duration...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28108322/effect-of-zbd-2-on-chronic-pain-depressive-like-behaviors-and-recovery-of-motor-function-following-spinal-cord-injury-in-mice
#7
Xiao-Ming Li, Jia Meng, Lin Tao Li, Ting Guo, Liu-Kun Yang, Qi-Xin Shi, Xu-Bo Li, Yong Chen, Qi Yang, Jian-Ning Zhao
In addition to debilitating sensory and motor deficits, patients with spinal cord injury (SCI) may experience chronic hyperpathic pain (SCI-pain). Recent studies have revealed that translocator protein (TSPO) is involved in repairing neural cells as well as reducing anxiety and depression. However, the role of TSPO in SCI-pain and pain-induced depression remains unknown. The present study aimed to determine the effects of a new TSPO ligand, ZBD-2, on SCI-pain and consequent pain-induced depressive-like behaviors in mice...
March 30, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28103888/photoreceptor-protection-via-blockade-of-bet-epigenetic-readers-in-a-murine-model-of-inherited-retinal-degeneration
#8
Lei Zhao, Jun Li, Yingmei Fu, Mengxue Zhang, Bowen Wang, Jonathan Ouellette, Pawan K Shahi, Bikash R Pattnaik, Jyoti J Watters, Wai T Wong, Lian-Wang Guo
BACKGROUND: The bromodomain and extraterminal domain (BET) family proteins (BET2, BET3, and BET4) "read" (bind) histone acetylation marks via two distinct bromodomains (Brom1 and Brom2) facilitating transcriptional activation. These epigenetic "readers" play crucial roles in pathogenic processes such as inflammation. The role of BETs in influencing the degenerative process in the retina is however unknown. METHODS: We employed the rd10 mouse model (Pde6b (rd10) mutation) of retinitis pigmentosa (RP) to examine the involvement of BET proteins in retinal neurodegeneration...
January 19, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28103132/functional-gains-in-energy-and-cell-metabolism-after-tspo-gene-insertion
#9
Guo-Jun Liu, Ryan J Middleton, Winnie Wai-Ying Kam, David Y Chin, Claire R Hatty, Ronald H Y Chan, Richard B Banati
Recent loss-of-function studies in tissue-specific as well as global Tspo (Translocator Protein 18 kDa) knockout mice have not confirmed its long assumed indispensability for the translocation of cholesterol across the mitochondrial inter-membrane space, a rate-limiting step in steroid biosynthesis. Instead, recent studies in global Tspo knockout mice indicate that TSPO may play a more fundamental role in cellular bioenergetics, which may include the indirect down-stream regulation of transport or metabolic functions...
January 19, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28093569/translational-evaluation-of-translocator-protein-as-a-marker-of-neuroinflammation-in-schizophrenia
#10
T Notter, J M Coughlin, T Gschwind, U Weber-Stadlbauer, Y Wang, M Kassiou, A C Vernon, D Benke, M G Pomper, A Sawa, U Meyer
Positron emission tomography (PET) imaging with radiotracers that target translocator protein 18 kDa (TSPO) has become a popular approach to assess putative neuroinflammatory processes and associated microglia activation in psychotic illnesses. It remains unclear, however, whether TSPO imaging can accurately capture low-grade inflammatory processes such as those present in schizophrenia and related disorders. Therefore, we evaluated the validity of TSPO as a disease-relevant marker of inflammation using a translational approach, which combined neurodevelopmental and neurodegenerative mouse models with PET imaging in patients with recent-onset schizophrenia and matched controls...
January 17, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28086916/microglial-activation-in-parkinson-s-disease-using-18-f-feppa
#11
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
#12
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
#13
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
#14
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...
February 3, 2017: 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
#15
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
#16
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
#17
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...
February 2017: 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
#18
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
#19
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
#20
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
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