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A Pacwa, E Gorowska-Wojtowicz, A Ptak, P Pawlicki, A Milon, M Sekula, K Lesniak, B Bilinska, A Hejmej, M Kotula-Balak
Estrogen-related receptors (ERRs) α, β and γ appear to be novel molecules implicated in estrogen signaling. We blocked and activated ERRs in mouse (C57BL/6) adrenals and adrenocortical cells (H295R) using pharmacological agents XCT 790 (ERRα antagonist) and DY131 (ERRβ/γ agonist), respectively. Mice were injected with XCT 790 or DY131 (5 μg/kg bw) while cells were exposed to XCT 790 or DY131 (0.5 μg/L). Irrespectively of the agent used, changes in adrenocortical cell morphology along with changes in lutropin, cholesterol levels and estrogen production were found...
May 16, 2018: Acta Histochemica
Sung Won Kim, Corinde E Wiers, Ryan Tyler, Ehsan Shokri-Kojori, Yeon Joo Jang, Amna Zehra, Clara Freeman, Veronica Ramirez, Elsa Lindgren, Gregg Miller, Elizabeth A Cabrera, Tyler Stodden, Min Guo, Şükrü B Demiral, Nancy Diazgranados, Luke Park, Jeih-San Liow, Victor Pike, Cheryl Morse, Leandro F Vendruscolo, Robert B Innis, George F Koob, Dardo Tomasi, Gene-Jack Wang, Nora D Volkow
Neuroinflammation appears to contribute to neurotoxicity observed with heavy alcohol consumption. To assess whether chronic alcohol results in neuroinflammation we used PET and [11 C]PBR28, a ligand that binds to the 18-kDa translocator protein (TSPO), to compare participants with an alcohol use disorder (AUD: n = 19) with healthy controls (HC: n = 17), and alcohol-dependent (n = 9) with -nondependent rats (n = 10). Because TSPO is implicated in cholesterol's transport for steroidogenesis, we investigated whether plasma cholesterol levels influenced [11 C]PBR28 binding...
May 3, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Sultana Rasheed, Khurram Bashir, Jong-Myong Kim, Marina Ando, Maho Tanaka, Motoaki Seki
The Arabidopsis histone deacetylase 6 (HDA6) mutant exhibits increased tolerance to drought stress by negatively regulating the expression of ALDH2B7 and PDC1. Therefore, it was logical to determine if transgenic Arabidopsis plants expressing PDC1 or ALDH2B7 using a suitable promoter would also exhibit tolerance to drought stress. An analysis of published microarray data indicated the up-regulation of the TSPO gene, which encodes an outer membrane tryptophan-rich sensory protein (TSPO), by drought stress. RT-qPCR, as well as GUS analysis of the promoter, confirmed the up-regulation of TSPO by drought stress in Arabidopsis roots and shoots...
May 18, 2018: Scientific Reports
Gui-Lin Jin, Sai-Di He, Shao-Mei Lin, Li-Mian Hong, Wan-Qing Chen, Ying Xu, Jian Yang, Su-Ping Li, Chang-Xi Yu
Despite decades of studies, the currently available drugs largely fail to control neuropathic pain. Koumine-an alkaloidal constituent derived from the medicinal plant Gelsemium elegans Benth.-has been shown to possess analgesic and anti-inflammatory properties; however, the underlying mechanisms remain unclear. In this study, we aimed to investigate the analgesic and anti-inflammatory effects and the possible underlying mechanisms of koumine. The analgesic and anti-inflammatory effects of koumine were explored by using chronic constriction injury of the sciatic nerve (CCI) neuropathic pain model in vivo and LPS-induced injury in microglia BV2 cells in vitro ...
2018: Neural Plasticity
Vimal Selvaraj, Douglas M Stocco
No abstract text is available yet for this article.
May 10, 2018: Endocrinology
Jinjiang Fan, Barry Zirkin, Vassilios Papadopoulos
No abstract text is available yet for this article.
May 10, 2018: Endocrinology
Soumen Paul, Evan Gallagher, Jeih-San Liow, Sanche Mabins, Katharine Henry, Sami S Zoghbi, Roger N Gunn, William C Kreisl, Erica M Richards, Paolo Zanotti-Fregonara, Cheryl L Morse, Jinsoo Hong, Aneta Kowalski, Victor W Pike, Robert B Innis, Masahiro Fujita
Translocator protein 18 kDa (TSPO) has been widely imaged as a marker of neuroinflammation using several radioligands, including [11 C]PBR28. In order to study the effects of age, sex, and obesity on TSPO binding and to determine whether this binding can be accurately assessed using fewer radio high-performance liquid chromatography (radioHPLC) measurements of arterial blood samples, we created a database of 48 healthy subjects who had undergone [11 C]PBR28 scans (23 high-affinity binders (HABs) and 25 mixed-affinity binders (MABs), 20 F/28 M, age: 40...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
Sina Hafizi, Tania Da Silva, Jeffrey H Meyer, Michael Kiang, Sylvain Houle, Gary Remington, Ivana Prce, Alan A Wilson, Pablo M Rusjan, Napapon Sailasuta, Romina Mizrahi
Altered neuroimmune response and oxidative stress have both been implicated in the pathophysiology of schizophrenia. While preclinical studies have proposed several pathways regarding potential interactions between oxidative stress and neuroimmune imbalance in the development of psychosis, the molecular mechanisms underlying this interaction are not yet understood. To date, no study has investigated this link in vivo in the human brain. We conducted the first in vivo study linking translocator protein 18  kDa (TSPO) expression and glutathione (a major brain antioxidant and a marker for redox status) in the medial prefrontal cortex (mPFC) of a relatively large sample of participants (N = 48) including 27 antipsychotic-naïve individuals at clinical high risk for psychosis and 21 matched healthy volunteers using high-resolution PET with TSPO radioligand, [18 F]FEPPA, and 3T proton magnetic resonance spectroscopy (1 H MRS)...
April 13, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Xin Sun, Shuyuan Guo, Wei Wang, Zhengyu Cao, Juhua Dan, Jiali Cheng, Wei Cao, Fang Tian, Wenwu Cao, Ye Tian
Sonodynamic therapy (SDT) with exogenous protoporphyrin IX (PpIX) or endogenous PpIX derived from 5-aminolevulinic acid (ALA) has been carried out to produce apoptotic effects on macrophages, indicating a potential treatment methodology for atherosclerosis. Our previous studies have found that mitochondria damage by reactive oxygen species (ROS) plays a major role in the SDT-induced apoptosis. This study aimed at investigating the potential involvement of the mitochondrial 18 kDa translocator protein (TSPO) and ROS in the pro-apoptotic effects of SDT on THP-1 macrophages...
2018: PloS One
Leah H Rubin, Ned Sacktor, Jason Creighton, Yong Du, Christopher J Endres, Martin G Pomper, Jennifer M Coughlin
OBJECTIVE: Despite viral suppression, HIV-associated cognitive impairment persists and may be partially due to persistent immune signaling by cells of the myeloid-lineage. Here we aimed to understand the contribution of activated microglia located in vulnerable brain regions (e.g., frontal, subcortical) of HIV-infected, virally suppressed (HIV+VS) individuals in relation to cognitive and motor function. DESIGN: 21 HIV+VS individuals underwent positron emission tomography (PET) with [C]DPA-713 to image the translocator protein 18 KDa (TSPO), a marker of microglial activation, and completed a comprehensive neuropsychological test battery...
May 9, 2018: AIDS
Marcus Unterrainer, Daniel F Fleischmann, Simon Lindner, Matthias Brendel, Rainer Rupprecht, Joerg C Tonn, Claus Belka, Peter Bartenstein, Maximilian Niyazi, Nathalie L Albert
PET targeting the translocator protein (TSPO) represents an interesting approach for glioma visualization, as TSPO is highly expressed in tumor cells. We present a 32-year-old man with recurrent glioblastoma after multimodal treatment. PET with the novel TSPO ligand F-GE-180 was performed after reirradiation. Here, the previously reirradiated tumor showed a remaining circular TSPO expression. Moreover, cerebrospinal fluid dissemination was detected by a high focal uptake at the right lateral and at the fourth ventricle, whereas only a faint contrast enhancement was present in MRI...
April 30, 2018: Clinical Nuclear Medicine
Simone L Verweij, Lotte C A Stiekema, Ronak Delewi, Kang H Zheng, Sophie J Bernelot Moens, Jeffrey Kroon, Charlotte I Stroes, Miranda Versloot, Jan J Piek, Hein J Verberne, Erik S G Stroes
PURPOSE: An acute coronary syndrome (ACS) is characterized by a multi-level inflammatory response, comprising activation of bone marrow and spleen accompanied by augmented release of leukocytes into the circulation. The duration of this response after an ACS remains unclear. Here, we assessed the effect of an ACS on the multi-level inflammatory response in patients both acutely and after 3 months. METHODS: We performed 18 F-DPA-714 PET/CT acutely and 3 months post-ACS in eight patients and eight matched healthy controls...
May 4, 2018: European Journal of Nuclear Medicine and Molecular Imaging
Cristina Lois, Ivan Gonzalez, David Izquierdo-Garcia, Nicole R Zurcher, Paul Wilkens, Marco L Loggia, Jacob M Hooker, Herminia Diana Rosas
Huntington's disease is a devastating neurodegenerative genetic disorder that causes progressive motor dysfunction, emotional disturbances, and cognitive impairment. Unfortunately, there is no treatment to cure or slow down the progression of the disease. Neuroinflammation is one hallmark of Huntington's disease and modulation of neuroinflammation has been suggested as a potential target for therapeutic intervention. The relationship between neuroinflammation markers and the disease pathology is still poorly understood...
May 2, 2018: ACS Chemical Neuroscience
Vimal Selvaraj, Douglas M Stocco, Barbara J Clark
How rapid induction of steroid hormone biosynthesis occurs in response to trophic hormone stimulation of steroidogenic cells has been a subject of intensive investigation for approximately six decades. A key observation made very early was that acute regulation of steroid biosynthesis required swift and timely synthesis of a new protein whose role appeared to be involved in the delivery of the substrate for all steroid hormones, cholesterol, from the outer to the inner mitochondrial membrane where the process of steroidogenesis begins...
April 27, 2018: Biology of Reproduction
Chengbo Tan, Songji Zhao, Kei Higashikawa, Zifeng Wang, Masahito Kawabori, Takeo Abumiya, Naoki Nakayama, Ken Kazumata, Naoyuki Ukon, Hironobu Yasui, Nagara Tamaki, Yuji Kuge, Hideo Shichinohe, Kiyohiro Houkin
BACKGROUND: The potential application of bone marrow stromal cell (BMSC) therapy in stroke has been anticipated due to its immunomodulatory effects. Recently, positron emission tomography (PET) with [18 F]DPA-714, a translocator protein (TSPO) ligand, has become available for use as a neural inflammatory indicator. We aimed to evaluate the effects of BMSC administration after transient middle cerebral artery occlusion (MCAO) using [18 F]DPA-714 PET. The BMSCs or vehicle were administered intravenously to rat MCAO models at 3 h after the insult...
May 2, 2018: EJNMMI Research
Catherine A Foss, Donika Plyku, Alvaro A Ordonez, Julian Sanchez-Bautista, Hailey B Rosenthal, I L Minn, Martin A Lodge, Martin G Pomper, George Sgouros, Sanjay K Jain
Whole body PET/CT imaging was performed using 124 I-iodo-DPA-713, a radioligand for the 18-kDa translocator protein (TSPO), to determine biodistribution and radiation dosimetry. METHODS: Healthy subjects ages 18-65 years underwent whole body PET/CT imaging at either 4, 24 and 48 hours or 24, 48 and 72 hours after intravenous injection with 124 I-iodo-DPA-713. Time-activity curves were generated and used to calculate organ time-integrated activity coefficients for each subject. The resulting time-integrated activity coefficients provided input data for calculation of organ absorbed doses and effective dose for each subject using OLINDA...
April 26, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Monica Gomes Lima, Jonathan Cueto-Escobedo, Juan Francisco Rodríguez-Landa, Caio Maximino
FGIN-1-27 is an agonist at the translocator protein 18 kDa (TSPO), a cholesterol transporter that is associated with neurosteroidogenesis. This protein has been identified as a peripheral binding site for benzodiazepines; in anamniotes, however, a second TSPO isoform that is absent in amniotes has been implicated in erythropoiesis. Functional conservation of the central benzodiazepine-binding site located in the GABAA receptors has been demonstrated in anamniotes and amniotes alike; however, it was not previously demonstrated for TSPO...
April 23, 2018: Pharmacology, Biochemistry, and Behavior
Duc-Loc Nguyen, Catriona Wimberley, Charles Truillet, Benoit Jego, Fabien Caillé, Géraldine Pottier, Raphaël Boisgard, Irène Buvat, Viviane Bouilleret
OBJECTIVE: Mesiotemporal lobe epilepsy is the most common type of drug-resistant partial epilepsy, with a specific history that often begins with status epilepticus due to various neurological insults followed by a silent period. During this period, before the first seizure occurs, a specific lesion develops, described as unilateral hippocampal sclerosis (HS). It is still challenging to determine which drugs, administered at which time point, will be most effective during the formation of this epileptic process...
April 19, 2018: Epilepsia
Lorena Pantaleão, Gustavo Henrique Oliveira da Rocha, Chris Reutelingsperger, Manoela Tiago, Silvya Stucchi Maria-Engler, Egle Solito, Sandra P Farsky
BACKGROUND: Annexin A1 (ANXA1) and Translocator Protein-18KDa (TSPO) down-regulate neuroinflammation. We investigated the role of recombinant ANXA1 (rANXA) on TSPO functions on Toll Like Receptor (TLR) activated microglia. METHODS: BV-2 cells (murine microglia), were stimulated by E. coli Lipopolysaccharide (LPS) and treated with rANXA1 in order to measure TSPO expression and inflammatory parameters. Anti-sense ANXA1 and TLR4 and TSPO shRNA, as well as pharmacological treatments, were employed to assess the mechanisms involved...
April 9, 2018: Experimental Cell Research
Lorraine Hamelin, Julien Lagarde, Guillaume Dorothée, Marie Claude Potier, Fabian Corlier, Bertrand Kuhnast, Fabien Caillé, Bruno Dubois, Ludovic Fillon, Marie Chupin, Michel Bottlaender, Marie Sarazin
Although brain neuroinflammation may play an instrumental role in the pathophysiology of Alzheimer's disease, its actual impact on disease progression remains controversial, being reported as either detrimental or protective. This work aimed at investigating the temporal relationship between microglial activation and clinical progression of Alzheimer's disease. First, in a large cohort of patients with Alzheimer's disease we analysed the predictive value of microglial activation assessed by 18F-DPA-714 PET imaging on functional, cognitive and MRI biomarkers outcomes after a 2-year follow-up...
March 28, 2018: Brain: a Journal of Neurology
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