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https://www.readbyqxmd.com/read/28539872/the-role-of-app-in-structural-spine-plasticity
#1
REVIEW
Elena Montagna, Mario M Dorostkar, Jochen Herms
Amyloid precursor protein (APP) is a transmembrane protein highly expressed in neurons. The full-length protein has cell-adhesion and receptor-like properties, which play roles in synapse formation and stability. Furthermore, APP can be cleaved by several proteases into numerous fragments, many of which affect synaptic function and stability. This review article focuses on the mechanisms of APP in structural spine plasticity, which encompasses the morphological alterations at excitatory synapses. These occur as changes in the number and morphology of dendritic spines, which correspond to the postsynaptic compartment of excitatory synapses...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28536503/epigenetic-activation-of-asct2-in-the-hippocampus-contributes-to-depression-like-behavior-by-regulating-d-serine-in-mice
#2
Jiesi Wang, Ke Zhang, Xiaojuan Chen, Xiaoqian Liu, Huajing Teng, Mei Zhao, Zhongsheng Sun
The roles of D-serine in depression are raised concerned recently as an intrinsic co-agonist for the NMDA receptor. However, the mechanisms underlying its regulation are not fully elucidated. ASCT2 is a Na(+)-dependent D-serine transporter. We found that decreased D-serine and increased hippocampal ASCT2 levels correlated with chronic social defeat stress (CSDS) in mice. Lentivirus-mediated shRNA-mediated knockdown of ASCT2 and the administration of exogenous D-serine in the hippocampus alleviated CSDS-induced social avoidance and immobility...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28536477/reduced-mismatch-negativity-is-associated-with-increased-plasma-level-of-glutamate-in-first-episode-psychosis
#3
Tatsuya Nagai, Kenji Kirihara, Mariko Tada, Daisuke Koshiyama, Shinsuke Koike, Motomu Suga, Tsuyoshi Araki, Kenji Hashimoto, Kiyoto Kasai
Reduced amplitude of mismatch negativity (MMN) is one of the more promising biological markers of schizophrenia. This finding holds true in both early and chronic phases of the disorder, and is compatible with the glutamatergic dysfunction hypothesis. To further establish MMN as a biomarker of aberrant glutamatergic neurotransmission, an exploration for an association with blood levels of glutamatergic amino acids is an important next step. Despite a large body of work investigating MMN in schizophrenia, no previous studies have undertaken this endeavor...
May 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28533113/a-novel-serine-racemase-inhibitor-suppresses-neuronal-over-activation-in-vivo
#4
Hisashi Mori, Ryogo Wada, Satoyuki Takahara, Yoshikazu Horino, Hironori Izumi, Tetsuya Ishimoto, Tomoyuki Yoshida, Mineyuki Mizuguchi, Takayuki Obita, Hiroaki Gouda, Shuichi Hirono, Naoki Toyooka
Serine racemase (SRR) is an enzyme that produces d-serine from l-serine. d-Serine acts as an endogenous coagonist of NMDA-type glutamate receptors (NMDARs), which regulate many physiological functions. Over-activation of NMDARs induces excitotoxicity, which is observed in many neurodegenerative disorders and epilepsy states. In our previous works on the generation of SRR gene knockout (Srr-KO) mice and its protective effects against NMDA- and Aβ peptide-induced neurodegeneration, we hypothesized that the regulation of NMDARs' over-activation by inhibition of SRR activity is one such therapeutic strategy to combat these disease states...
May 11, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28531844/development-of-an-uplc-ms-ms-method-for-simultaneous-quantitation-of-11-d-amino-acids-in-different-regions-of-rat-brain-application-to-a-study-on-the-associations-of-d-amino-acid-concentration-changes-and-alzheimer-s-disease
#5
Zhe Li, Yuping Xing, Xingjie Guo, Yan Cui
There are significant differences in d-amino acid concentrations between healthy people and Alzheimer's disease patients. In order to investigate the potential correlation between d-amino acids and Alzheimer's disease, a simple and sensitive ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method has been developed. The method was applied to simultaneous determination of 11 d-amino acids in different regions of rat brain. Rat brain homogenates were firstly pretreated with protein precipitation procedure and then derivatized with (S)-N-(4-nitrophenoxycarbonyl) phenylalanine methoxyethyl ester [(S)-NIFE]...
May 11, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28521121/untangling-a-cholinergic-pathway-from-wakefulness-to-memory
#6
Steffen Gais, Monika Schönauer
Acetylcholine is a major modulator of learning and memory, and its availability varies across the sleep-wake cycle. In this issue of Neuron, Papouin et al. (2017) describe a D-serine-dependent pathway involving astroglia by which the transmitter tunes the hippocampus toward memory encoding during wakefulness.
May 17, 2017: Neuron
https://www.readbyqxmd.com/read/28509930/elucidation-of-inhibitor-binding-pockets-of-d-amino-acid-oxidase-using-docking-simulation-and-n-sulfanylethylanilide-based-labeling-technology
#7
Taiki Kohiki, Yusuke Kato, Yusuke Nishikawa, Kazuko Yorita, Ikuko Sagawa, Masaya Denda, Tsubasa Inokuma, Akira Shigenaga, Kiyoshi Fukui, Akira Otaka
Because of the relevance of d-serine (d-Ser) to schizophrenia, inhibitors of d-amino acid oxidase (DAO), which catalyzes degradation of d-Ser in the presence of flavin adenine dinucleotide (FAD), are expected to be anti-schizophrenia therapeutics. In this study, binding pockets of DAO to its inhibitor 4-bromo-3-nitrobenzoic acid were searched by combining in silico docking simulation and labeling experiments employing an N-sulfanylethylanilide-based labeling technology that we have developed. The results clearly demonstrated that there are two binding pockets: one is shared with d-Ser and FAD, and the other is an unexpected cleft between the subunits of a DAO dimer...
May 16, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28487371/a-clostridium-difficile-alanine-racemase-affects-spore-germination-and-accommodates-serine-as-a-substrate
#8
Ritu Shrestha, Steve W Lockless, Joseph A Sorg
Clostridium difficile has become one of the most common bacterial pathogens in hospital-acquired infections in the United States. Although C. difficile is strictly anaerobic, it survives in aerobic environments and transmits between hosts via spores. C. difficile spore germination is triggered in response to certain bile acids and glycine. Although glycine is the most effective co-germinant, other amino acids can substitute with varying efficiencies. Of these, L-alanine is an effective co-germinant and is also a germinant for most bacterial spores...
May 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28479102/septal-cholinergic-neuromodulation-tunes-the-astrocyte-dependent-gating-of-hippocampal-nmda-receptors-to-wakefulness
#9
Thomas Papouin, Jaclyn M Dunphy, Michaela Tolman, Kelly T Dineley, Philip G Haydon
The activation of the N-methyl D-aspartate receptor (NMDAR) is controlled by a glutamate-binding site and a distinct, independently regulated, co-agonist-binding site. In most brain regions, the NMDAR co-agonist is the astrocyte-derived gliotransmitter D-serine. We found that D-serine levels oscillate in mouse hippocampus as a function of wakefulness, in vitro and in vivo. This causes a full saturation of the NMDAR co-agonist site in the dark (active) phase that dissipates to sub-saturating levels during the light (sleep) phase, and influences learning performance throughout the day...
May 17, 2017: Neuron
https://www.readbyqxmd.com/read/28472616/stereochemistry-and-concentration-dependent-effects-of-phosphatidylserine-enrichment-on-platelet-function
#10
Audrey F Meyer, Sarah M Gruba, Donghyuk Kim, Ben M Meyer, Secil Koseoglu, Joseph J Dalluge, Christy L Haynes
Platelets are small (1-2μm in diameter), circulating anuclear cell fragments with important roles in hemostasis and thrombosis that provide an excellent platform for studying the role of membrane components in cellular communication. Platelets use several forms of communication including exocytosis of three distinct granule populations, formation of bioactive lipid mediators, and shape change (allowing for adhesion). This work explores the role of stereochemistry and concentration of exogenous phosphatidylserine (PS) on platelet exocytosis and adhesion...
May 1, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28466270/synaptic-nmda-receptor-activation-induces-ubiquitination-and-degradation-of-step61
#11
Jian Xu, Pradeep Kurup, Angus C Nairn, Paul J Lombroso
NMDA receptor signaling is critical for the development of synaptic plasticity, learning, and memory, and dysregulation of NMDAR signaling is implicated in a number of neurological disorders including schizophrenia (SZ). Previous work has demonstrated that the STriatal-Enriched protein tyrosine Phosphatase 61 kDa (STEP61) is elevated in human SZ postmortem cortical samples and after administration of psychotomimetics to cultures or mice. Here, we report that activation of synaptic NMDAR by bicuculline or D-serine results in the ubiquitination and proteasomal degradation of STEP61, and increased surface localization of GluN1/GluN2B receptors...
May 2, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28435276/clinical-and-biochemical-study-of-d-serine-metabolism-among-schizophrenia-patients
#12
Hamdy N El-Tallawy, Tahia H Saleem, Abdallah Maa El-Ebidi, Mohammed H Hassan, Romany H Gabra, Wafaa Ma Farghaly, Nagwa Abo El-Maali, Hoda S Sherkawy
BACKGROUND: Schizophrenia is a typical N-methyl-d-aspartate receptor (NMDA-R) hypofunction disorder. Decreased d-serine (d-Ser) levels in the periphery occur in schizophrenia and may reflect decreased availability of d-Ser to activate NMDA-R in the brain. OBJECTIVE: The objective of this study was to investigate the role of d-Ser metabolism in the pathogenesis of schizophrenia via biochemical assays and correlates, the serum level of d-Ser, d-serine racemase (SR) (responsible for its formation from l-serine [l-Ser]) and d-amino acid oxidase (DAAO) (responsible for its catabolism), among different clinical types of schizophrenia patients...
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/28428746/expression-of-d-amino-acid-oxidase-dao-daao-and-d-amino-acid-oxidase-activator-daoa-g72-during-development-and-aging-in-the-human-post-mortem-brain
#13
Vinita Jagannath, Zoya Marinova, Camelia-Maria Monoranu, Susanne Walitza, Edna Grünblatt
In the brain, D-amino acid oxidase (DAO/DAAO) mainly oxidizes D-serine, a co-agonist of the N-methyl-D-aspartate (NMDA) receptors. Thus, DAO can regulate the function of NMDA receptors via D-serine breakdown. Furthermore, DAO activator (DAOA)/G72 has been reported as both DAOA and repressor. The co-expression of DAO and DAOA genes and proteins in the human brain is not yet elucidated. The aim of this study was to understand the regional and age span distribution of DAO and DAOA (mRNA and protein) in a concomitant manner...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28393748/gut-microbiota-of-mice-putatively-modifies-amino-acid-metabolism-in-the-host-brain
#14
Takahiro Kawase, Mao Nagasawa, Hiromi Ikeda, Shinobu Yasuo, Yasuhiro Koga, Mitsuhiro Furuse
Recently, it has been found that the gut microbiota influences functions of the host brain by affecting monoamine metabolism. The present study focused on the relationship between the gut microbiota and the brain amino acids. Specific pathogen-free (SPF) and germ-free (GF) mice were used as experimental models. Plasma and brain regions were sampled from mice at 7 and 16 weeks of age, and analysed for free d- and l-amino acids, which are believed to affect many physiological functions. At 7 weeks of age, plasma concentrations of d-aspartic acid (d-Asp), l-alanine (l-Ala), l-glutamine (l-Gln) and taurine were higher in SPF mice than in GF mice, but no differences were found at 16 weeks of age...
April 10, 2017: British Journal of Nutrition
https://www.readbyqxmd.com/read/28388932/the-efficacy-of-sodium-benzoate-as-an-adjunctive-treatment-in-early-psychosis-cadence-bz-study-protocol-for-a-randomized-controlled-trial
#15
Alex Ryan, Andrea Baker, Frances Dark, Sharon Foley, Anne Gordon, Sean Hatherill, Stephen Stathis, Sukanta Saha, George Bruxner, Martin Beckman, Drew Richardson, Michael Berk, Olivia Dean, John McGrath, Cadence Working Group, James Scott
BACKGROUND: Psychotic disorders affect up to 3% of the population and are often chronic and disabling. Innovation in the pharmacological treatment of psychosis has remained stagnant in recent decades. In order to improve outcomes for those with psychotic disorders, we present a protocol for the trial of a common food preservative, sodium benzoate, as an adjunctive treatment in early psychosis. METHODS: Persons experiencing early psychosis (n = 160) will be recruited through hospitals and community mental health services in Queensland, Australia...
April 7, 2017: Trials
https://www.readbyqxmd.com/read/28387240/the-low-binding-affinity-of-d-serine-at-the-ionotropic-glutamate-receptor-glud2-can-be-attributed-to-the-hinge-region
#16
Daniel Tapken, Thomas Bielefeldt Steffensen, Rasmus Leth, Lise Baadsgaard Kristensen, Alexander Gerbola, Michael Gajhede, Flemming Steen Jørgensen, Lars Olsen, Jette Sandholm Kastrup
Ionotropic glutamate receptors (iGluRs) are responsible for most of the fast excitatory communication between neurons in our brain. The GluD2 receptor is a puzzling member of the iGluR family: It is involved in synaptic plasticity, plays a role in human diseases, e.g. ataxia, binds glycine and D-serine with low affinity, yet no ligand has been discovered so far that can activate its ion channel. In this study, we show that the hinge region connecting the two subdomains of the GluD2 ligand-binding domain is responsible for the low affinity of D-serine, by analysing GluD2 mutants with electrophysiology, isothermal titration calorimetry and molecular dynamics calculations...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28375181/dietary-metabolites-and-chronic-kidney-disease
#17
REVIEW
Sho Hasegawa, Tzu-Ming Jao, Reiko Inagi
Dietary contents and their metabolites are closely related to chronic kidney disease (CKD) progression. Advanced glycated end products (AGEs) are a type of uremic toxin produced by glycation. AGE accumulation is not only the result of elevated glucose levels or reduced renal clearance capacity, but it also promotes CKD progression. Indoxyl sulfate, another uremic toxin derived from amino acid metabolism, accumulates as CKD progresses and induces tubulointerstitial fibrosis and glomerular sclerosis. Specific types of amino acids (d-serine) or fatty acids (palmitate) are reported to be closely associated with CKD progression...
April 4, 2017: Nutrients
https://www.readbyqxmd.com/read/28318835/improvement-in-mismatch-negativity-generation-during-d-serine-treatment-in-schizophrenia-correlation-with-symptoms
#18
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
#19
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
#20
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
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