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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
#1
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...
January 9, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28063222/astrocytic-ip3-rs-contribution-to-ca-2-signalling-and-hippocampal-ltp
#2
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
#3
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
#4
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...
December 31, 2016: 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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/27913408/neurophysiological-mechanisms-of-cortical-plasticity-impairments-in-schizophrenia-and-modulation-by-the-nmda-receptor-agonist-d-serine
#11
Joshua T Kantrowitz, Michael L Epstein, Odeta Beggel, Stephanie Rohrig, Jonathan M Lehrfeld, Nadine Revheim, Nayla P Lehrfeld, Jacob Reep, Emily Parker, Gail Silipo, Merav Ahissar, Daniel C Javitt
Schizophrenia is associated with deficits in cortical plasticity that affect sensory brain regions and lead to impaired cognitive performance. Here we examined underlying neural mechanisms of auditory plasticity deficits using combined behavioural and neurophysiological assessment, along with neuropharmacological manipulation targeted at the N-methyl-D-aspartate type glutamate receptor (NMDAR). Cortical plasticity was assessed in a cohort of 40 schizophrenia/schizoaffective patients relative to 42 healthy control subjects using a fixed reference tone auditory plasticity task...
December 2016: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/27880078/serine-racemase-is-expressed-in-islets-and-contributes-to-the-regulation-of-glucose-homeostasis
#12
Amber D Lockridge, Daniel C Baumann, Brian Akhaphong, Alleah Abrenica, Robert F Miller, Emilyn U Alejandro
NMDA receptors (NMDARs) have recently been discovered as functional regulators of pancreatic β-cell insulin secretion. While these excitatory receptor channels have been extensively studied in the brain for their role in synaptic plasticity and development, little is known about how they work in β-cells. In neuronal cells, NMDAR activation requires the simultaneous binding of glutamate and a rate-limiting co-agonist, such as D-serine. D-serine levels and availability in most of the brain rely on endogenous synthesis by the enzyme serine racemase (Srr)...
November 2016: Islets
https://www.readbyqxmd.com/read/27853241/supplementation-with-d-serine-prevents-the-onset-of-cognitive-deficits-in-adult-offspring-after-maternal-immune-activation
#13
Yuko Fujita, Tamaki Ishima, Kenji Hashimoto
Prenatal maternal infection contributes to the etiology of schizophrenia, with D-serine, an endogenous co-agonist of the N-methyl-D-aspartate (NMDA) receptor, playing a role in the pathophysiology of this disease. We examined whether supplementation with D-serine during juvenile and adolescent stages could prevent the onset of cognitive deficits, prodromal and the core symptoms of schizophrenia in adult offspring after maternal immune activation (MIA). Juvenile offspring exposed prenatally to poly(I:C) showed reduced expression of NMDA receptor subunits in the hippocampus...
November 17, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27846159/laparoscopic-sleeve-gastrectomy-outcomes-of-750-patients-a-2-5-year-experience-at-a-bariatric-center-of-excellence
#14
Hasan Altun, Burcin Batman, Salim D Uymaz, Rahmi K Serin, Serpil Salman, Yelda Tayyareci, Ferah Ece, Tugce Hurkal, Didem Dal
Laparoscopic sleeve gastrectomy (LSG) is gaining popularity worldwide. This retrospective cohort study evaluated the outcomes of a large cohort of patients with obesity who underwent LSG in a Bariatric Center of Excellence. All consecutive patients who underwent LSG between July 2013 and April 2016 were identified retrospectively. Preoperative and postoperative variables and comorbidities were recorded. The study consisted of 750 patients. Their mean age was 37.4 years; 72% were women, and the mean body mass index was 42...
December 2016: Surgical Laparoscopy, Endoscopy & Percutaneous Techniques
https://www.readbyqxmd.com/read/27793449/antibacterial-profiling-of-abietane-type-diterpenoids
#15
Andreas Helfenstein, Mikko Vahermo, Dorota A Nawrot, Fatih Demirci, Gökalp İşcan, Sara Krogerus, Jari Yli-Kauhaluoma, Vânia M Moreira, Päivi Tammela
Abietic and dehydroabietic acid are interesting diterpenes with a highly diverse repertoire of associated bioactivities. They have, among others, shown antibacterial and antifungal activity, potentially valuable in the struggle against the increasing antimicrobial resistance and imminent antibiotic shortage. In this paper, we describe the synthesis of a set of 9 abietic and dehydroabietic acid derivatives containing amino acid side chains and their in vitro antimicrobial profiling against a panel of human pathogenic microbial strains...
January 1, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27773581/protein-rna-networks-regulated-by-normal-and-als-associated-mutant-hnrnpa2b1-in-the-nervous-system
#16
Fernando J Martinez, Gabriel A Pratt, Eric L Van Nostrand, Ranjan Batra, Stephanie C Huelga, Katannya Kapeli, Peter Freese, Seung J Chun, Karen Ling, Chelsea Gelboin-Burkhart, Layla Fijany, Harrison C Wang, Julia K Nussbacher, Sara M Broski, Hong Joo Kim, Rea Lardelli, Balaji Sundararaman, John P Donohue, Ashkan Javaherian, Jens Lykke-Andersen, Steven Finkbeiner, C Frank Bennett, Manuel Ares, Christopher B Burge, J Paul Taylor, Frank Rigo, Gene W Yeo
HnRNPA2B1 encodes an RNA binding protein associated with neurodegeneration. However, its function in the nervous system is unclear. Transcriptome-wide crosslinking and immunoprecipitation in mouse spinal cord discover UAGG motifs enriched within ∼2,500 hnRNP A2/B1 binding sites and an unexpected role for hnRNP A2/B1 in alternative polyadenylation. HnRNP A2/B1 loss results in alternative splicing (AS), including skipping of an exon in amyotrophic lateral sclerosis (ALS)-associated D-amino acid oxidase (DAO) that reduces D-serine metabolism...
November 23, 2016: Neuron
https://www.readbyqxmd.com/read/27756833/the-frontal-cortex-as-a-network-hub-controlling-mood-and-cognition-probing-its-neurochemical-substrates-for-improved-therapy-of-psychiatric-and-neurological-disorders
#17
Mark J Millan, Jean-Michel Rivet, Alain Gobert
The highly-interconnected and neurochemically-rich frontal cortex plays a crucial role in the regulation of mood and cognition, domains disrupted in depression and other central nervous system disorders, and it is an important site of action for their therapeutic control. For improving our understanding of the function and dysfunction of the frontal cortex, and for identifying improved treatments, quantification of extracellular pools of neuromodulators by microdialysis in freely-moving rodents has proven indispensable...
October 17, 2016: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/27742076/the-rise-and-fall-of-the-d-serine-mediated-gliotransmission-hypothesis
#18
REVIEW
Herman Wolosker, Darrick T Balu, Joseph T Coyle
d-Serine modulates N-methyl d-aspartate receptors (NMDARs) and regulates synaptic plasticity, neurodevelopment, and learning and memory. However, the primary site of d-serine synthesis and release remains controversial, with some arguing that it is a gliotransmitter and others defining it as a neuronal cotransmitter. Results from several laboratories using different strategies now show that the biosynthetic enzyme of d-serine, serine racemase (SR), is expressed almost entirely by neurons, with few astrocytes appearing to contain d-serine...
November 2016: Trends in Neurosciences
https://www.readbyqxmd.com/read/27730500/expanding-frontiers-in-weight-control-research-explored-by-young-investigators
#19
REVIEW
Yoshiro Ishimaru, Chisayo Kozuka, Kenichiro Nakajima, Tsutomu Sasaki
At the 93rd annual meeting of the Physiological Society of Japan, a symposium entitled "Expanding frontiers in weight-control research explored by young investigators" was organized. The latest research on weight control was presented by young up-and-coming investigators. The symposium consisted of the following presentations: Gastrointestinal brush cells, immunity, and energy homeostasis; Impact of a brown rice-derived bioactive product on feeding regulation and fuel metabolism; A novel G protein-coupled receptor-regulated neuronal signaling pathway triggers sustained orexigenic effects; and NMDA receptor co-agonist D-serine regulates food preference...
January 2017: Journal of Physiological Sciences: JPS
https://www.readbyqxmd.com/read/27717827/low-d-serine-levels-in-schizophrenia-a-systematic-review-and-meta-analysis
#20
Seo-Eun Cho, Kyoung-Sae Na, Seong-Jin Cho, Seung Gul Kang
An increasing amount of evidence indicates that d-serine, a potent and selective endogenous coagonist of the N-methyl-d-aspartate receptor (NMDAR), is efficacious in the treatment of schizophrenia. Although the therapeutic efficacy of d-serine supplementation is based on the d-serine deficit and NMDAR hypofunction hypothesis, it has not been confirmed whether d-serine levels are decreased in patients with schizophrenia compared to healthy controls. We searched the following electronic databases: Embase, Ovid Medline, and the Cochrane Library...
October 4, 2016: Neuroscience Letters
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