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https://www.readbyqxmd.com/read/28318835/improvement-in-mismatch-negativity-generation-during-d-serine-treatment-in-schizophrenia-correlation-with-symptoms
#1
Joshua T Kantrowitz, Michael L Epstein, Migyung Lee, Nayla Lehrfeld, Karen A Nolan, Constance Shope, Eva Petkova, Gail Silipo, Daniel C Javitt
BACKGROUND: Deficits in N-methyl-d-aspartate-type (NMDAR) function contribute to symptoms and cognitive dysfunction in schizophrenia. The efficacy of NMDAR agonists in the treatment of persistent symptoms of schizophrenia has been variable, potentially reflecting limitations in functional target engagement. We recently demonstrated significant improvement in auditory mismatch negativity (MMN) with once-weekly treatment with d-serine, a naturally occurring NMDAR glycine-site agonist. This study investigates effects of continuous (daily) NMDAR agonists in schizophrenia/schizoaffective disorder...
March 17, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28269783/modulating-the-balance-of-synaptic-and-extrasynaptic-nmda-receptors-shows-positive-effects-against-amyloid-%C3%AE-induced-neurotoxicity
#2
Yan Huang, Wei Shen, Jie Su, Bin Cheng, Dong Li, Gang Liu, Wen-Xia Zhou, Yong-Xiang Zhang
Alzheimer's disease (AD) patients suffer a disturbance in the balance between synaptic (GluN2A, mediating the protective pathway) and extrasynaptic NMDA receptors (NMDARs) (GluN2B, mediating the excitotoxic pathway), and, therefore, restoring the balance of GluN2A and GluN2B should be beneficial for AD. In this study, the GluN2B-selective antagonist, ifenprodil, and the non-selective NMDAR agonist, NMDA, had little effect on amyloid-β (Aβ)-induced long-term potentiation deficits. Enhancing the activity of GluN2A had a protective effect against Aβ, and specific activation of GluN2A and inhibition of GluN2B showed a better protective effect...
March 2, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28262924/2-methoxyestradiol-impacts-on-amino-acids-mediated-metabolic-reprogramming-in-osteosarcoma-cells-by-interaction-with-nmda-receptor
#3
Magdalena Gorska-Ponikowska, Ugo Perricone, Alicja Kuban-Jankowska, Giosue Lo Bosco, Giampaolo Barone
Deregulation of serine and glycine metabolism, have been identified to function as metabolic regulators in supporting tumor cell growth. The role of serine and glycine in regulation of cancer cell proliferation is complicated, dependent on concentrations of amino acids and tissue-specific. D-serine and glycine are coagonists of N-methyl-D-aspartate receptor subunit GRIN1. Importantly, NMDA receptors are widely expressed in cancer cells and play an important role in regulation of cell death, proliferation and metabolism of numerous malignancies...
March 6, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28245819/effects-of-sarcosine-and-n-n-dimethylglycine-on-nmda-receptor-mediated-excitatory-field-potentials
#4
Mei-Yi Lee, Yi-Ruu Lin, Yi-Shu Tu, Yufeng Jane Tseng, Ming-Huan Chan, Hwei-Hsien Chen
BACKGROUND: Sarcosine, a glycine transporter type 1 inhibitor and an N-methyl-D-aspartate (NMDA) receptor co-agonist at the glycine binding site, potentiates NMDA receptor function. Structurally similar to sarcosine, N,N-dimethylglycine (DMG) is also N-methyl glycine-derivative amino acid and commonly used as a dietary supplement. The present study compared the effects of sarcosine and DMG on NMDA receptor-mediated excitatory field potentials (EFPs) in mouse medial prefrontal cortex brain slices using a multi-electrode array system...
February 28, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28236852/the-promising-anticancer-drug-3-bromopyruvate-is-metabolized-through-glutathione-conjugation-which-affects-chemoresistance-and-clinical-practice-an-evidence-based-view
#5
Salah Mohamed El Sayed, Hussam Baghdadi, Mohammed Zolaly, Hamdi H Almaramhy, Mongi Ayat, Jagadish G Donki
3-Bromopyruvate (3BP) is a promising effective anticancer drug against many different tumors in children and adults. 3BP exhibited strong anticancer effects in both preclinical and human studies e.g. energy depletion, oxidative stress, anti-angiogenesis, anti-metastatic effects, targeting cancer stem cells and antagonizing the Warburg effect. There is no report about 3BP metabolism to guide researchers and oncologists to improve clinical practice and prevent drug resistance. In this article, we provide evidences that 3BP is metabolized through glutathione (GSH) conjugation as a novel report where 3BP was confirmed to be attached to GSH followed by permanent loss of pharmacological effects in a picture similar to cisplatin...
March 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28220045/paternal-cocaine-taking-elicits-epigenetic-remodeling-and-memory-deficits-in-male-progeny
#6
M E Wimmer, L A Briand, B Fant, L A Guercio, A C Arreola, H D Schmidt, S Sidoli, Y Han, B A Garcia, R C Pierce
Paternal environmental perturbations including exposure to drugs of abuse can produce profound effects on the physiology and behavior of offspring via epigenetic modifications. Here we show that adult drug-naive male offspring of cocaine-exposed sires have memory formation deficits and associated reductions in NMDA receptor-mediated hippocampal synaptic plasticity. Reduced levels of the endogenous NMDA receptor co-agonist d-serine were accompanied by increased expression of the d-serine degrading enzyme d-amino acid oxidase (Dao1) in the hippocampus of cocaine-sired male progeny...
February 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28209394/ensifer-shofinae-sp-nov-a-novel-rhizobial-species-isolated-from-root-nodules-of-soybean-glycine-max
#7
Wen Hao Chen, Sheng Hui Yang, Zhao Hu Li, Xiao Xia Zhang, Xin Hua Sui, En Tao Wang, Wen Xin Chen, Wen Feng Chen
Two bacterial strains isolated from root nodules of soybean were characterized phylogenetically as members of a distinct group in the genus Ensifer based on 16S rRNA gene comparisons. They were also verified as a separated group by the concatenated sequence analyses of recA, atpD and glnII (with similarities ≤93.9% to the type strains for defined species), and by the average nucleotide identities (ANI) between the whole genome sequence of the representative strain CCBAU 251167(T) and those of the closely related strains in Ensifer glycinis and Ensifer fredii (90...
February 2, 2017: Systematic and Applied Microbiology
https://www.readbyqxmd.com/read/28202572/differential-regulation-of-nmda-receptors-by-d-serine-and-glycine-in-mammalian-spinal-locomotor-networks
#8
David Acton, Gareth Brian Miles
Activation of N-methyl-D-aspartate receptors (NMDARs) requires the binding of a co-agonist, either D-serine or glycine, in addition to glutamate. Changes in occupancy of the co-agonist binding site are proposed to modulate neural networks including those controlling swimming in frog tadpoles. Here, we characterize regulation of the NMDAR co-agonist binding site in mammalian spinal locomotor networks. Blockade of NMDARs by D(-)-2-amino-5-phosphonopentanoic acid (D-APV) or 5,7-dichlorokynurenic acid reduced the frequency and amplitude of pharmacologically induced locomotor-related activity recorded from the ventral roots of spinal-cord preparations from neonatal mice...
February 15, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28193731/selective-transport-of-neurotransmitters-and-modulators-by-distinct-volume-regulated-lrrc8-anion-channels
#9
Darius Lutter, Florian Ullrich, Jennifer C Lueck, Stefan Kempa, Thomas J Jentsch
In response to swelling, mammalian cells release chloride and organic osmolytes through VRAC volume-regulated anion channels. VRACs are heteromers of LRRC8A and other LRRC8 isoforms (B-E) which are co-expressed in HEK293 and most other cells. The spectrum of VRAC substrates and its dependence on particular LRRC8 isoforms remains largely unknown. We show that besides the osmolytes taurine and myo-inositol, LRRC8 channels transport the neurotransmitters glutamate, aspartate and GABA and the co-activator D-serine...
February 13, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28177792/utilization-of-carbon-sources-by-clinical-isolates-of-aeromonas
#10
Karoline C Prediger, Monica Surek, Cibelle B Dallagassa, Flávia E A Assis, Mario S Piantavini, Emanuel M Souza, Fábio O Pedrosa, Sônia M S S Farah, Dayane Alberton, Cyntia M T Fadel-Picheth
Bacteria in the genus Aeromonas are primarily aquatic organisms; however, some species can cause diseases in humans, ranging from wound infections to septicemia, of which diarrhea is the most common condition. The ability to use a variety of carbon substrates is advantageous for pathogenic bacteria. Therefore, we used Biolog GN2 microplates to analyze the ability of 103 clinical, predominantly diarrheal, isolates of Aeromonas to use various carbon sources, and we verified whether, among the substrates metabolized by these strains, there were some endogenous to the human intestine...
December 22, 2016: Canadian Journal of Microbiology
https://www.readbyqxmd.com/read/28089597/magnesium-and-calcium-ions-differentially-affect-human-serine-racemase-activity-and-modulate-its-quaternary-equilibrium-toward-a-tetrameric-form
#11
Stefano Bruno, Marilena Margiotta, Francesco Marchesani, Gianluca Paredi, Valentina Orlandi, Serena Faggiano, Luca Ronda, Barbara Campanini, Andrea Mozzarelli
Serine racemase is the pyridoxal 5'-phosphate dependent enzyme that catalyzes both production and catabolism of d-serine, a co-agonist of the NMDA glutamate receptors. Mg(2+), or, alternatively, Ca(2+), activate human serine racemase by binding both at a specific site and - as ATP-metal complexes - at a distinct ATP binding site. We show that Mg(2+) and Ca(2+) bind at the metal binding site with a 4.5-fold difference in affinity, producing a similar thermal stabilization and partially shifting the dimer-tetramer equilibrium in favour of the latter...
April 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28063222/astrocytic-ip3-rs-contribution-to-ca-2-signalling-and-hippocampal-ltp
#12
Mark William Sherwood, Misa Arizono, Chihiro Hisatsune, Hiroko Bannai, Etsuko Ebisui, John Lawrence Sherwood, Aude Panatier, Stéphane Henri Richard Oliet, Katsuhiko Mikoshiba
Astrocytes regulate hippocampal synaptic plasticity by the Ca(2+) dependent release of the N-methyl d-aspartate receptor (NMDAR) co-agonist d-serine. Previous evidence indicated that d-serine release would be regulated by the intracellular Ca(2+) release channel IP3 receptor (IP3 R), however, genetic deletion of IP3 R2, the putative astrocytic IP3 R subtype, had no impact on synaptic plasticity or transmission. Although IP3 R2 is widely believed to be the only functional IP3 R in astrocytes, three IP3 R subtypes (1, 2, and 3) have been identified in vertebrates...
January 7, 2017: Glia
https://www.readbyqxmd.com/read/28051338/activity-dependent-sulfhydration-signal-controls-nmdar-dependent-synaptic-plasticity-via-increasing-d-serine-availability
#13
Yuan-Long Li, Pei-Fei Wu, Jian-Guo Chen, Sheng Wang, Qian-Qian Han, Dan Li, Wen Wang, Xin-Lei Guan, Di Li, Li-Hong Long, Jian-Geng Huang, Fang Wang
AIMS: Reactive sulfur species (RSS) including hydrogen sulfide (H2S) and its oxydates have been raised as novel redox signaling molecules. The present study aimed at examining whether endogenous sulfhydration signal are required for long-term potentiation (LTP), a cellular model for memory. RESULTS: Here, we found that increased synaptic activity triggered sulfide generationand protein sulfhydration. Activity-triggered sulfide production was essential for N-methyl-D-aspartate subtype glutamate receptors (NMDARs)-dependent LTP via maintaining the availability of D-serine, a primary co-agonist for synaptic NMDARs...
January 4, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28043791/the-alteration-of-serine-transporter-activity-in-a-cell-line-model-of-amyotrophic-lateral-sclerosis-als
#14
Na-Young Lee, Yunha Kim, Hoon Ryu, Young-Sook Kang
The alteration of d-serine levels is associated with the pathogenesis of sporadic ALS and mutant SOD1 (G93A) animal model of ALS. However, the exact mechanism of d-serine transport is not known in ALS. To better understand the distribution of d-serine in ALS, we determined the activity and the expression of serine transporter in a motor neuronal cell line model of ALS (NSC-34/hSOD1(G93A) cells). The uptake of [(3)H]d-serine was significantly lower in NSC-34/hSOD1(G93A) cells than in control NSC-34 and NSC-34/hSOD1(wt) cells...
January 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28032990/iterative-focused-screening-with-biological-fingerprints-identifies-selective-asc-1-inhibitors-distinct-from-traditional-high-throughput-screening
#15
Peter S Kutchukian, Lee Warren, Brian C Magliaro, Adam Amoss, Jason A Cassaday, Gregory O'Donnell, Brian Squadroni, Paul Zuck, Danette Pascarella, J Chris Culberson, Andrew J Cooke, Danielle Hurzy, Kelly-Ann Sondra Schlegel, Fiona Thomson, Eric N Johnson, Victor N Uebele, Jeffrey D Hermes, Sophie Parmentier-Batteur, Michael Finley
N-methyl-d-aspartate receptors (NMDARs) mediate glutamatergic signaling that is critical to cognitive processes in the central nervous system, and NMDAR hypofunction is thought to contribute to cognitive impairment observed in both schizophrenia and Alzheimer's disease. One approach to enhance the function of NMDAR is to increase the concentration of an NMDAR coagonist, such as glycine or d-serine, in the synaptic cleft. Inhibition of alanine-serine-cysteine transporter-1 (Asc-1), the primary transporter of d-serine, is attractive because the transporter is localized to neurons in brain regions critical to cognitive function, including the hippocampus and cortical layers III and IV, and is colocalized with d-serine and NMDARs...
January 6, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28025800/intrathecal-delivery-of-ssaav9-dao-extends-survival-in-sod1-g93a-als-mice
#16
Wan Wang, Weisong Duan, Ying Wang, Di Wen, Yakun Liu, Zhongyao Li, Haojie Hu, Hongying Cui, Can Cui, Huiqian Lin, Chunyan Li
Amyotrophic lateral sclerosis (ALS) is an adult-onset, irreversible neurodegenerative disease that leads to progressive paralysis and inevitable death 3-5 years after diagnosis. The mechanisms underlying this process remain unknown, but new evidence indicates that accumulating levels of D-serine result from the downregulation of D-amino acid oxidase (DAO) and that this is a novel mechanism that leads to motoneuronal death in ALS via N-methyl-D-aspartate receptor-mediated cell toxicity. Here, we explored a new therapeutic approach to ALS by overexpressing DAO in the lumbar region of the mouse spinal cord using a single stranded adeno-associated virus serotype 9 (ssAAV9) vector...
December 26, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27995572/intramuscular-delivery-of-scaav9-higf1-prolongs-survival-in-the-hsod1-g93a-als-mouse-model-via-upregulation-of-d-amino-acid-oxidase
#17
HuiQian Lin, HaoJie Hu, WeiSong Duan, YaLing Liu, GuoJun Tan, ZhongYao Li, YaKun Liu, BinBin Deng, XueQin Song, Wan Wang, Di Wen, Ying Wang, ChunYan Li
Self-complementary adeno-associated viral vector 9 (scAAV9) has been confirmed to be an efficient AAV serotype for gene transfer to the central nervous system (CNS). Neurotrophic factors have been considered to be therapeutic targets for amyotrophic lateral sclerosis (ALS). In the present study, we intramuscularly injected scAAV9 encoding human insulin-like growth factor 1 (hIGF1) into an hSOD1(G93A) ALS mouse model. We observed that scAAV9-hIGF1 significantly reduced the loss of motor neurons of the anterior horn in the lumbar spinal cord and delayed muscle atrophy in ALS mice...
December 19, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27986591/spinal-d-serine-increases-pkc-dependent-glun1-phosphorylation-contributing-to-the-sigma-1-receptor-induced-development-of-mechanical-allodynia-in-a-mouse-model-of-neuropathic-pain
#18
Sheu-Ran Choi, Ji-Young Moon, Dae-Hyun Roh, Seo-Yeon Yoon, Soon-Gu Kwon, Hoon-Seong Choi, Suk-Yun Kang, Ho-Jae Han, Alvin J Beitz, Jang-Hern Lee
We have recently demonstrated that spinal sigma-1 receptor (Sig-1R) activation facilitates nociception via an increase in phosphorylation of the NMDA receptor GluN1 subunit (pGluN1). The present study was designed to examine whether the Sig-1R-induced facilitative effect on NMDA-induced nociception is mediated by D-serine, and whether D-serine modulates spinal pGluN1 expression and the development of neuropathic pain following chronic constriction injury (CCI) of the sciatic nerve. Intrathecal administration of the D-serine degrading enzyme, DAAO attenuated the facilitation of NMDA-induced nociception induced by the Sig-1R agonist, PRE084...
December 13, 2016: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/27984198/effects-of-pregabalin-on-spinal-d-serine-content-and-nmda-receptor-mediated-synaptic-transmission-in-mice-with-neuropathic-pain
#19
Eiko Kato, Rie Matsuzawa, Shunsaku Kobayashi, Teruyuki Fukushima, Masao Maekawa, Yuuichi Hori
Pregabalin (PGB) is a chemical derivative of the inhibitory neurotransmitter γ-aminobutyric acid, and is successfully used for the treatment of neuropathic pain. Substantial evidence suggests that D-serine, an endogenous co-agonist at the strychnine-insensitive glycine site of the NMDA receptor, counteracts the antinociceptive actions of PGB at the level of the spinal cord. In the present study, we examined the impact of PGB treatment on spinal D-serine content and NMDA receptor-mediated synaptic transmission in the superficial dorsal horn of peripheral nerve-ligated neuropathic mice...
October 28, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27934764/gliogenic-ltp-spreads-widely-in-nociceptive-pathways
#20
M T Kronschläger, R Drdla-Schutting, M Gassner, S D Honsek, H L Teuchmann, J Sandkühler
Learning and memory formation involve long-term potentiation (LTP) of synaptic strength. A fundamental feature of LTP induction in the brain is the need for coincident pre- and postsynaptic activity. This restricts LTP expression to activated synapses only (homosynaptic LTP) and leads to its input specificity. In the spinal cord, we discovered a fundamentally different form of LTP that is induced by glial cell activation and mediated by diffusible, extracellular messengers, including d-serine and tumor necrosis factor (TNF), and that travel long distances via the cerebrospinal fluid, thereby affecting susceptible synapses at remote sites...
December 2, 2016: Science
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