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https://www.readbyqxmd.com/read/28326936/a-role-for-the-locus-coeruleus-in-the-analgesic-efficacy-of-n-acetylaspartylglutamate-peptidase-gcpii-inhibitors-zj43-and-2-pmpa
#1
Takahiro Nonaka, Toshihiko Yamada, Tatsuhiro Ishimura, Daiying Zuo, John R Moffett, Joseph H Neale, Tatsuo Yamamoto
N-acetylaspartylglutamate (NAAG) is the third most prevalent and widely distributed neurotransmitter in the mammalian nervous system. NAAG activates a group II metabotropic glutamate receptor (mGluR3) and is inactivated by an extracellular enzyme, glutamate carboxypeptidase II (GCPII) in vivo. Inhibitors of this enzyme are analgesic in animal models of inflammatory, neuropathic and bone cancer pain. NAAG and GCPII are present in the locus coeruleus, a center for the descending noradrenergic inhibitory pain system...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28285415/naag-peptidase-inhibitors-act-via-mglur3-animal-models-of-memory-alzheimer-s-and-ethanol-intoxication
#2
Rafal T Olszewski, Karolina J Janczura, Tomasz Bzdega, Elise K Der, Faustino Venzor, Brennen O'Rourke, Timothy J Hark, Kirsten E Craddock, Shankar Balasubramanian, Charbel Moussa, Joseph H Neale
Glutamate carboxypeptidase II (GCPII) inactivates the peptide neurotransmitter N-acetylaspartylglutamate (NAAG) following synaptic release. Inhibitors of GCPII increase extracellular NAAG levels and are efficacious in animal models of clinical disorders via NAAG activation of a group II metabotropic glutamate receptor. mGluR2 and mGluR3 knock-out (ko) mice were used to test the hypothesis that mGluR3 mediates the activity of GCPII inhibitors ZJ43 and 2-PMPA in animal models of memory and memory loss. Short- (1...
March 11, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28251297/glutamate-carboxypeptidase-ii-gcpii-inhibitor-2-pmpa-reduces-rewarding-effects-of-the-synthetic-cathinone-mdpv-in-rats-a-role-for-n-acetylaspartylglutamate-naag
#3
Callum Hicks, Ryan A Gregg, Sunil U Nayak, Lee Anne Cannella, Giana J Schena, Christopher S Tallarida, Allen B Reitz, Garry R Smith, Scott M Rawls
RATIONALE: Metabotropic glutamate 2 and 3 (mGluR2/3) receptors are implicated in drug addiction as they limit excessive glutamate release during relapse. N-acetylaspartylglutamate (NAAG) is an endogenous mGluR2/3 agonist that is inactivated by the glutamate carboxypeptidase II (GCPII) enzyme. GCPII inhibitors, and NAAG itself, attenuate cocaine-seeking behaviors. However, their effects on the synthetic cathinone 3,4-methylenedioxypyrovalerone (MDPV) have not been examined. OBJECTIVES: We determined whether withdrawal following repeated MDPV administration alters GCPII expression in corticolimbic regions...
March 1, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28182070/analysis-of-lipid-profile-in-cancer-patients-smokers-and-nonsmokers
#4
A Vikramsimha Reddy, Lakshmi Keerthana Killampalli, A Ravi Prakash, Sushma Naag, G Sreenath, Sunil Kumar Biraggari
BACKGROUND: Lipids play an important role in maintaining the cell membrane integrity. Lipid profile is a panel of blood tests that serve as an initial medical screening for abnormalities in lipids and approximate risk for cancer, cardiovascular diseases, pancreatitis, etc., The present study evaluates the alterations in lipid profile in cancer patients, smokers, and nonsmokers and aims to achieve a correlation between them. MATERIALS AND METHODS: The study is an in vitro type of cross-sectional study with 25 oral cancer patients, 25 chronic smokers (habit persisting for 15 years or more), and 15 nonsmokers as control group...
November 2016: Dental Research Journal
https://www.readbyqxmd.com/read/28072448/identification-of-altered-brain-metabolites-associated-with-tnap-activity-in-a-mouse-model-of-hypophosphatasia-using-untargeted-nmr-based-metabolomics-analysis
#5
Thomas Cruz, Marie Gleizes, Stéphane Balayssac, Etienne Mornet, Grégory Marsal, José Luis Millán, Myriam Malet-Martino, Lionel G Nowak, Véronique Gilard, Caroline Fonta
Tissue non-specific alkaline phosphatase (TNAP) is a key player of bone mineralization and TNAP gene (ALPL) mutations in human are responsible for hypophosphatasia (HPP), a rare heritable disease affecting the mineralization of bones and teeth. Moreover, TNAP is also expressed by brain cells and the severe forms of HPP are associated with neurological disorders, including epilepsy and brain morphological anomalies. However, TNAP's role in the nervous system remains poorly understood. To investigate its neuronal functions, we aimed to identify without any a priori the metabolites regulated by TNAP in the nervous tissue...
March 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28025130/high-and-ultra-high-resolution-metabolite-mapping-of-the-human-brain-using-1-h-fid-mrsi-at-9-4t
#6
Sahar Nassirpour, Paul Chang, Anke Henning
Magnetic resonance spectroscopic imaging (MRSI) is a promising technique for mapping the spatial distribution of multiple metabolites in the human brain. These metabolite maps can be used as a diagnostic tool to gain insight into several biochemical processes and diseases in the brain. In comparison to lower field strengths, MRSI at ultra-high field strengths benefits from a higher signal to noise ratio (SNR) as well as higher chemical shift dispersion, and hence spectral resolution. This study combines the benefits of an ultra-high field magnet with the advantages of an ultra-short TE and TR single-slice FID-MRSI sequence (such as negligible J-evolution and loss of SNR due to T2 relaxation effects) and presents the first metabolite maps acquired at 9...
December 23, 2016: NeuroImage
https://www.readbyqxmd.com/read/27917121/neurochemical-and-neuroanatomical-plasticity-following-memory-training-and-yoga-interventions-in-older-adults-with-mild-cognitive-impairment
#7
Hongyu Yang, Amber M Leaver, Prabha Siddarth, Pattharee Paholpak, Linda Ercoli, Natalie M St Cyr, Harris A Eyre, Katherine L Narr, Dharma S Khalsa, Helen Lavretsky
Behavioral interventions are becoming increasingly popular approaches to ameliorate age-related cognitive decline, but their underlying neurobiological mechanisms and clinical efficiency have not been fully elucidated. The present study explored brain plasticity associated with two behavioral interventions, memory enhancement training (MET) and a mind-body practice (yogic meditation), in healthy seniors with mild cognitive impairment (MCI) using structural magnetic resonance imaging (s-MRI) and proton magnetic resonance spectroscopy ((1)H-MRS)...
2016: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/27696530/stimulation-induced-transient-changes-in-neuronal-activity-blood-flow-and-n-acetylaspartate-content-in-rat-prefrontal-cortex-a-chemogenetic-fmrs-bold-study
#8
Morris H Baslow, Christopher K Cain, Robert Sears, Donald A Wilson, Alvin Bachman, Scott Gerum, David N Guilfoyle
Brain activation studies in humans have shown the dynamic nature of neuronal N-acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) based on changes in their MRS signals in response to stimulation. These studies demonstrated that upon visual stimulation there was a focal increase in cerebral blood flow (CBF) and a decrease in NAA or in the total of NAA and NAAG signals in the visual cortex, and that these changes were reversed upon cessation of stimulation. In the present study we have developed an animal model in order to explore the relationships between brain stimulation, neuronal activity, CBF and NAA...
December 2016: NMR in Biomedicine
https://www.readbyqxmd.com/read/27589333/radiolabeled-enzyme-inhibitors-and-binding-agents-targeting-psma-effective-theranostic-tools-for-imaging-and-therapy-of-prostate-cancer
#9
REVIEW
Maroor Raghavan Ambikalmajan Pillai, Raviteja Nanabala, Ajith Joy, Arun Sasikumar, Furn F Russ Knapp
Because of the broad incidence, morbidity and mortality associated with prostate-derived cancer, the development of more effective new technologies continues to be an important goal for the accurate detection and treatment of localized prostate cancer, lymphatic involvement and metastases. Prostate-specific membrane antigen (PSMA; Glycoprotein II) is expressed in high levels on prostate-derived cells and is an important target for visualization and treatment of prostate cancer. Radiolabeled peptide targeting technologies have rapidly evolved over the last decade and have focused on the successful development of radiolabeled small molecules that act as inhibitors to the binding of the N-acetyl-l-aspartyl-l-glutamate (NAAG) substrate to the PSMA molecule...
November 2016: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/27498291/impaired-brain-metabolism-and-neurocognitive-function-in-childhood-leukemia-survivors-despite-complete-hormone-supplementation-in-adulthood
#10
Cecilia Follin, Eva Marie Erfurth, Aki Johansson, Jimmy Lätt, Pia C Sundgren, Kai Österberg, Gabriella Spulber, Peter Mannfolk, Isabella M Björkman-Burtscher
Cranial radiotherapy is a known risk factor for neurocognitive impairment in survivors of childhood acute lymphoblastic leukemia (ALL). Understanding the nature of cognitive dysfunction during adulthood in ALL survivors is important as it has an impact on major life situations. Thirty-eight (21 women) ALL survivors were investigated 34 years after diagnosis. Median-age was 38 (27-46) years. All were treated with a CRT dose of 24Gy and 11 years (3-13) of complete hormone supplementation. Comparisons were made to 29 matched controls...
November 2016: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/27430729/in-silico-approaches-to-identify-the-potential-inhibitors-of-glutamate-carboxypeptidase-ii-gcpii-for-neuroprotection
#11
Shaik Mohammad Naushad, M Janaki Ramaiah, Balraj Alex Stanley, S Prasanna Lakshmi, J Vishnu Priya, Tajamul Hussain, Salman A Alrokayan, Vijay Kumar Kutala
To develop a potential inhibitor for glutamate carboxypeptidase II (GCPII) effective against all the eight common genetic variants reported, PyMOL molecular visualization system was used to generate models of variants using the crystal structure of GCPII i.e. 2OOT as a template. High-throughput virtual screening of 29 compounds revealed differential efficacy across the eight genetic variants (pIC50: 4.70 to 10.22). Pharmacophore analysis and quantitative structure-activity relationship (QSAR) studies revealed a urea-based N-acetyl aspartyl glutamate (NAAG) analogue as more potent inhibitor, which was effective across all the genetic variants of GCPII as evidenced by glide scores (-4...
October 7, 2016: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/27405321/case-control-study-magnetic-resonance-spectroscopy-of-brain-in-hiv-infected-patients
#12
Devender Bairwa, Virendra Kumar, Surabhi Vyas, Bimal Kumar Das, Achal Kumar Srivastava, Ravinder M Pandey, Surendra K Sharma, Naranamangalam R Jagannathan, Sanjeev Sinha
BACKGROUND: In vivo proton magnetic resonance spectroscopy ((1)H-MRS) studies on brain in HIV infected patients have shown significant alteration in neuro-biochemicals. METHODS: In this study, we measured the neuro-biochemical metabolites from the left frontal white matter (FWM) and left basal ganglia (BG) caudate head nucleus in 71 subjects that include 30 healthy controls, 20 asymptomatic HIV and 21 HIV patients with CNS lesion. Proton MR spectra were acquired at 3 T MRI system and the concentration (institutional units) of tNAA (N-acetylaspartate, NAA + N-acetylaspartylglutamate, NAAG), tCr (Creatine, Cr + phosphocreatine, PCr), choline containing compounds (tCho), glutamate + glutamine (Glx) and lipid and macromolecules at 0...
July 12, 2016: BMC Neurology
https://www.readbyqxmd.com/read/27371836/-lipid-derivative-of-benzylidene-malononitrile-ag490-attenuates-airway-inflammation-of-mice-with-neutrophilic-asthma
#13
Min Zhang, Guangmin Nong, Min Jiang, Wenjie Zhan
Objective To observe the effect of lipid derivative of benzylidene malononitrile AG490 on the airway inflammation in a mouse model of neutrophilic asthma (NA). Methods Fifty-four specific pathogen-free (SPF) female C57BL/6 mice were randomly divided into 3 groups: NA group, AG490-treated NA (NAAG) group, and normal control (NC) group, 18 mice in each group. The NA group and the NAAG group were sensitized by airway instillation of ovalbumin (OVA) and lipopolysaccharide (LPS) on day 0, 6 and 13. The NAAG group was injected with AG490 (500 μg/mouse, i...
June 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/27125544/a-high-fat-diet%C3%A2-alters-metabolic-and-bioenergetic-function-in-the-brain-a-magnetic-resonance-spectroscopy-study
#14
Kayla Raider, Delin Ma, Janna L Harris, Isabella Fuentes, Robert S Rogers, Joshua L Wheatley, Paige C Geiger, Hung-Wen Yeh, In-Young Choi, William M Brooks, John A Stanford
Diet-induced obesity and associated metabolic effects can lead to neurological dysfunction and increase the risk of developing Alzheimer's disease (AD) and Parkinson's disease (PD). Despite these risks, the effects of a high-fat diet on the central nervous system are not well understood. To better understand the mechanisms underlying the effects of high fat consumption on brain regions affected by AD and PD, we used proton magnetic resonance spectroscopy ((1)H-MRS) to measure neurochemicals in the hippocampus and striatum of rats fed a high fat diet vs...
July 2016: Neurochemistry International
https://www.readbyqxmd.com/read/27089868/hermes-hadamard-encoding-and-reconstruction-of-mega-edited-spectroscopy
#15
Kimberly L Chan, Nicolaas A J Puts, Michael Schär, Peter B Barker, Richard A E Edden
PURPOSE: To investigate a novel Hadamard-encoded spectral editing scheme and evaluate its performance in simultaneously quantifying N-acetyl aspartate (NAA) and N-acetyl aspartyl glutamate (NAAG) at 3 Tesla. METHODS: Editing pulses applied according to a Hadamard encoding scheme allow the simultaneous acquisition of multiple metabolites. The method, called HERMES (Hadamard Encoding and Reconstruction of MEGA-Edited Spectroscopy), was optimized to detect NAA and NAAG simultaneously using density-matrix simulations and validated in phantoms at 3T...
July 2016: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/27087952/effectiveness-of-focal-vs-balloon-radiofrequency-ablation-devices-in-the-treatment-of-barrett-s-esophagus
#16
Jesica Brown, Benjamin Alsop, Neil Gupta, Daniel C Buckles, Mojtaba S Olyaee, Prashanth Vennalaganti, Vijay Naag Kanakadandi, Shreyas Saligram, Prateek Sharma
BACKGROUND AND AIMS: The safety and efficacy of radiofrequency ablation (RFA) in treatment of Barrett's esophagus (BE)-associated dysplasia has been well established. The effectiveness of focal and balloon RFA devices has not been compared. Therefore, the aim of our study was to assess the effectiveness of focal and balloon RFA devices in the treatment of BE by calculating absolute and percentage change in BE length with RFA therapy by comparing pre- and post-treatment BE length. PATIENTS AND METHODS: This is a retrospective cross-sectional study of patients who underwent at least one treatment with either focal and/or balloon RFA devices who were identified from two tertiary centers...
April 2016: United European Gastroenterology Journal
https://www.readbyqxmd.com/read/27076878/metabolomic-profiling-of-post-mortem-brain-reveals-changes-in-amino-acid-and-glucose-metabolism-in-mental-illness-compared-with-controls
#17
Rong Zhang, Tong Zhang, Ali Muhsen Ali, Mohammed Al Washih, Benjamin Pickard, David G Watson
Metabolomic profiling was carried out on 53 post-mortem brain samples from subjects diagnosed with schizophrenia, depression, bipolar disorder (SDB), diabetes, and controls. Chromatography on a ZICpHILIC column was used with detection by Orbitrap mass spectrometry. Data extraction was carried out with m/z Mine 2.14 with metabolite searching against an in-house database. There was no clear discrimination between the controls and the SDB samples on the basis of a principal components analysis (PCA) model of 755 identified or putatively identified metabolites...
2016: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/27068862/suppression-of-glutamate-carboxypeptidase-ii-ameliorates-neuronal-apoptosis-from-ischemic-brain-injury
#18
Weiqiao Zhang, Zhijie Zhang, Liping Wu, Yongming Qiu, Yingying Lin
BACKGROUND: Ischemia stroke is a destructive cerebrovascular disease and a major cause of death and lifelong neurological disability. N-Acetyl-l-aspartyl-l-glutamate (NAAG) is a neurotransmitter in the mammalian brain and involves a variety of physiological and pathological functions including ischemia brain injury. Full understanding of the functions of NAAG peptidase (GCPII) in the pathogenesis of ischemia brain injury is extremely valuable for effective therapies to ischemia stroke...
July 2016: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/27064916/-metabolism-of-n-acetyl-l-aspartate-its-diagnostic-and-prognostic-value
#19
REVIEW
Manuel A Martinez, Néstor V Florenzano, Esteban A Macchia
AIMS: To analyse the clinical involvement of the amino acid N-acetyl-L-aspartate (NAA) and the peptide N-acetyl-aspartyl-glutamate (NAAG) regarding their diagnostic and prognostic value by means of magnetic resonance spectroscopy. To conduct a review of the metabolism of NAA and NAAG, bearing in mind their chemical structure and physiology, in terms of the variations in their concentration and the correlation with the clinical features. DEVELOPMENT: The review is divided into two parts: in one it was found that the only site where NAA synthesis takes place is in the neuronal mitochondria, while the second part addresses magnetic resonance and, especially, spectroscopic techniques...
April 16, 2016: Revista de Neurologia
https://www.readbyqxmd.com/read/26990992/structural-plasticity-of-pam-recognition-by-engineered-variants-of-the-rna-guided-endonuclease-cas9
#20
Carolin Anders, Katja Bargsten, Martin Jinek
The RNA-guided endonuclease Cas9 from Streptococcus pyogenes (SpCas9) forms the core of a powerful genome editing technology. DNA cleavage by SpCas9 is dependent on the presence of a 5'-NGG-3' protospacer adjacent motif (PAM) in the target DNA, restricting the choice of targetable sequences. To address this limitation, artificial SpCas9 variants with altered PAM specificities have recently been developed. Here we report crystal structures of the VQR, EQR, and VRER SpCas9 variants bound to target DNAs containing their preferred PAM sequences...
March 17, 2016: Molecular Cell
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