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https://www.readbyqxmd.com/read/28822034/microrna-expression-target-genes-and-signaling-pathways-in-infants-with-a-ventricular-septal-defect
#1
Hui Chai, Zhaoyuan Yan, Ke Huang, Yuanqing Jiang, Lin Zhang
This study aimed to systematically investigate the relationship between miRNA expression and the occurrence of ventricular septal defect (VSD), and characterize the miRNA target genes and pathways that can lead to VSD. The miRNAs that were differentially expressed in blood samples from VSD and normal infants were screened and validated by implementing miRNA microarrays and qRT-PCR. The target genes regulated by differentially expressed miRNAs were predicted using three target gene databases. The functions and signaling pathways of the target genes were enriched using the GO database and KEGG database, respectively...
August 18, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28821679/upf1-governs-synaptic-plasticity-through-association-with-a-stau2-rna-granule
#2
Tyson E Graber, Erika Freemantle, Mina Anadolu, Sarah Hébert-Seropian, Robyn MacAdam, Unkyung Shin, Huy-Dung Hoang, Tommy Alain, Jean-Claude Lacaille, Wayne S Sossin
Neuronal mRNAs can be packaged in reversibly stalled polysome granules prior to their transport to distant synaptic locales. Stimulation of synaptic metabotropic glutamate receptors (mGluRs) reactivates translation of these particular mRNAs to produce plasticity-related protein; a phenomenon exhibited during mGluR-mediated long-term depression (mGluR-LTD). This form of plasticity is deregulated in Fragile X Syndrome, a monogenic form of autism in humans, and understanding the stalling and reactivation mechanism could reveal new approaches to therapies...
August 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28821676/brief-novel-visual-experience-fundamentally-changes-synaptic-plasticity-in-the-mouse-visual-cortex
#3
Shuo Li, Laijian Wang, Xiaoxiu Tie, Kazuhiro Sohya, Xian Lin, Alfredo Kirkwood, Bin Jiang
Long-term potentiation (LTP) has been known to be a mechanism by which experience modifies synaptic responses in the neocortex. Visual deprivation in the form of dark exposure or dark rearing from birth enhances NMDAR-dependent LTP in layer 2/3 of visual cortex, a process often termed metaplasticity, which may involve changes in NMDAR subunit composition and function. However, the effects of re-exposure to light after dark rearing from birth on LTP induction have not been explored. Here, we showed that the light exposure after dark rearing revealed a novel NMDAR independent form of LTP in the layer 2/3 pyramidal cells in visual cortex of mice of both sexes which is dependent on mGluR5 activation and is associated with intracellular Ca2+ rise, CaMKII activity, PKC activity and intact protein synthesis...
August 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28813782/urea-cycle-pathway-targeted-therapeutic-action-of-naringin-against-ammonium-chloride-induced-hyperammonemic-rats
#4
Arumugam Ramakrishnan, Natesan Vijayakumar
Ammonia is a well-known neurotoxin that causes liver disease and urea cycle disorder. Excessive ammonia content in the blood leads to hyperammonemic condition and affects both excitatory and inhibitory neurotransmission including brain edema and coma. Naringin, a plant bioflavonoid present in various citrus fruits and mainly extracted from the grape fruit. This study was designed to assess the protective effect of naringin on ammonium chloride (NH4Cl) induced hyperammonemic rats. Experimental hyperammonemia was induced by intraperitoneal injections (i...
August 12, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28800512/metabotropic-glutamate-receptors-as-emerging-research-targets-in-bipolar-disorder
#5
REVIEW
Caren J Blacker, Charles P Lewis, Mark A Frye, Marin Veldic
Glutamatergic dysregulation is implicated in the neuropathology of bipolar disorder (BD). There is increasing interest in investigating the role of metabotropic glutamate receptors (mGluRs) in BD and as a target for treatment intervention. Bipolar mGluR studies (published January 1992-April 2016) were identified via PubMed, Embase, Web of Science, and Scopus. Full-text screening, data extraction, and quality appraisal were conducted in duplicate, with strict inclusion and exclusion criteria. The initial literature search for mGluRs in BD, including non-bipolar mood disorders and primary psychotic disorders, identified 1544 articles...
July 31, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/28772121/cell-type-specific-translation-profiling-reveals-a-novel-strategy-for-treating-fragile-x-syndrome
#6
Sophie R Thomson, Sang S Seo, Stephanie A Barnes, Susana R Louros, Melania Muscas, Owen Dando, Caoimhe Kirby, David J A Wyllie, Giles E Hardingham, Peter C Kind, Emily K Osterweil
Excessive mRNA translation downstream of group I metabotropic glutamate receptors (mGlu1/5) is a core pathophysiology of fragile X syndrome (FX); however, the differentially translating mRNAs that contribute to altered neural function are not known. We used translating ribosome affinity purification (TRAP) and RNA-seq to identify mistranslating mRNAs in CA1 pyramidal neurons of the FX mouse model (Fmr1(-/y)) hippocampus, which exhibit exaggerated mGlu1/5-induced long-term synaptic depression (LTD). In these neurons, we find that the Chrm4 transcript encoding muscarinic acetylcholine receptor 4 (M4) is excessively translated, and synthesis of M4 downstream of mGlu5 activation is mimicked and occluded...
August 2, 2017: Neuron
https://www.readbyqxmd.com/read/28740338/localization-and-role-of-metabotropic-glutamate-receptors-subtype-5-in-the-gastrointestinal-tract
#7
REVIEW
Andrea Ferrigno, Clarissa Berardo, Laura G Di Pasqua, Veronica Siciliano, Plinio Richelmi, Mariapia Vairetti
Metabotropic glutamate receptor subtype 5 (mGluR5) is a Group I mGlu subfamily of receptors coupled to the inositol trisphosphate/diacylglycerol pathway. Like other mGluR subtypes, mGluR5s contain a phylogenetically conserved, extracellular orthosteric binding site and a more variable allosteric binding site, located on the heptahelical transmembrane domain. The mGluR5 receptor has proved to be a key pharmacological target in conditions affecting the central nervous system (CNS) but its presence outside the CNS underscores its potential role in pathologies affecting peripheral organs such as the gastrointestinal (GI) tract and accessory digestive organs such as the tongue, liver and pancreas...
July 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28694498/analysis-of-positive-and-negative-allosteric-modulation-in-metabotropic-glutamate-receptors-4-and-5-with-a-dual-ligand
#8
James A R Dalton, Jean-Philippe Pin, Jesús Giraldo
As class C GPCRs and regulators of synaptic activity, human metabotropic glutamate receptors (mGluRs) 4 and 5 are prime targets for allosteric modulation, with mGlu5 inhibition or mGlu4 stimulation potentially treating conditions like chronic pain and Parkinson's disease. As an allosteric modulator that can bind both receptors, 2-Methyl-6-(phenylethynyl)pyridine (MPEP) is able to negatively modulate mGlu5 or positively modulate mGlu4. At a structural level, how it elicits these responses and how mGluRs undergo activation is unclear...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28669525/mechanisms-of-skin-toxicity-associated-with-metabotropic-glutamate-receptor-5-negative-allosteric-modulators
#9
Falgun Shah, Antonia F Stepan, Alison O'Mahony, Sharlene Velichko, Alexandra E Folias, Christopher Houle, Christopher L Shaffer, John Marcek, Jessica Whritenour, Robert Stanton, Ellen L Berg
Cutaneous reactions represent one of the most common adverse drug effects observed in clinical trials leading to substantial compound attrition. Three negative allosteric modulators (NAMs) of metabotropic glutamate receptors (mGluRs), which represent an important target for neurological diseases, developed by Pfizer, were recently failed in preclinical development due to delayed type IV skin hypersensitivity observed in non-human primates (NHPs). Here we employed large-scale phenotypic profiling in standardized panels of human primary cell/co-culture systems to characterize the skin toxicity mechanism(s) of mGluR5 NAMs from two different series...
July 20, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28661401/pharmacological-evidence-for-a-metabotropic-glutamate-receptor-heterodimer-in-neuronal-cells
#10
David Moreno Delgado, Thor C Møller, Jeanne Ster, Jesús Giraldo, Damien Maurel, Xavier Rovira, Pauline Scholler, Jurriaan M Zwier, Julie Perroy, Thierry Durroux, Eric Trinquet, Laurent Prezeau, Philippe Rondard, Jean-Philippe Pin
Metabotropic glutamate receptors (mGluRs) are mandatory dimers playing important roles in regulating CNS function. Although assumed to form exclusive homodimers, 16 possible heterodimeric mGluRs have been proposed but their existence in native cells remains elusive. Here, we set up two assays to specifically identify the pharmacological properties of rat mGlu heterodimers composed of mGlu2 and 4 subunits. We used either a heterodimer-specific conformational LRET-based biosensor or a system that guarantees the cell surface targeting of the heterodimer only...
June 29, 2017: ELife
https://www.readbyqxmd.com/read/28645622/in-vivo-effects-of-knocking-down-metabotropic-glutamate-receptor-5-in-the-sod1-g93a-mouse-model-of-amyotrophic-lateral-sclerosis
#11
Tiziana Bonifacino, Luca Cattaneo, Elena Gallia, Aldamaria Puliti, Marcello Melone, Francesca Provenzano, Simone Bossi, Ilaria Musante, Cesare Usai, Fiorenzo Conti, Giambattista Bonanno, Marco Milanese
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder due to loss of upper and lower motor neurons (MNs). The mechanisms of neuronal death are largely unknown, thus prejudicing the successful pharmacological treatment. One major cause for MN degeneration in ALS is represented by glutamate(Glu)-mediated excitotoxicity. We have previously reported that activation of Group I metabotropic Glu receptors (mGluR1 and mGluR5) at glutamatergic spinal cord nerve terminals produces abnormal Glu release in the widely studied SOD1(G93A) mouse model of ALS...
September 1, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28607044/regulation-of-spinogenesis-in-mature-purkinje-cells-via-mglur-pkc-mediated-phosphorylation-of-camkii%C3%AE
#12
Takeyuki Sugawara, Chihiro Hisatsune, Hiroyuki Miyamoto, Naoko Ogawa, Katsuhiko Mikoshiba
Dendritic spines of Purkinje cells form excitatory synapses with parallel fiber terminals, which are the primary sites for cerebellar synaptic plasticity. Nevertheless, how density and morphology of these spines are properly maintained in mature Purkinje cells is not well understood. Here we show an activity-dependent mechanism that represses excessive spine development in mature Purkinje cells. We found that CaMKIIβ promotes spine formation and elongation in Purkinje cells through its F-actin bundling activity...
June 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28569048/astrocyte-mediated-synapse-remodeling-in-the-pathological-brain
#13
REVIEW
Sun Kwang Kim, Junichi Nabekura, Schuichi Koizumi
Astrocytes, a major type of glia, reciprocally influence synaptic transmission and connectivity, forming the "tripartite synapses". Astrocytic metabotropic glutamate receptor (mGluR)-mediated Ca(2+) waves and release of gliotransmitters or synaptogenic molecules mediate this neuron-glia interaction in the developing brain, but this signaling has been challenged for adult brain. However, cumulative evidence has suggested that mature astrocytes exhibit re-awakening of such immature phenotype in the pathological adult brain...
June 1, 2017: Glia
https://www.readbyqxmd.com/read/28560482/integrated-in-silico-fragment-based-drug-design-case-study-with-allosteric-modulators-on-metabotropic-glutamate-receptor-5
#14
Yuemin Bian, Zhiwei Feng, Peng Yang, Xiang-Qun Xie
GPCR allosteric modulators target at the allosteric binding pockets of G protein-coupled receptors (GPCRs) with indirect influence on the effects of an orthosteric ligand. Such modulators exhibit significant advantages compared to the corresponding orthosteric ligands, including better chemical tractability or physicochemical properties, improved selectivity, and reduced risk of oversensitization towards their receptors. Metabotropic glutamate receptor 5 (mGlu5), a member of class C GPCRs, is a promising therapeutic target for treating many central nervous system diseases...
May 30, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28555566/activation-of-the-same-mglur5-receptors-in-the-amygdala-causes-divergent-effects-on-specific-versus-indiscriminate-fear
#15
Mohammed Mostafizur Rahman, Sonal Kedia, Giselle Fernandes, Sumantra Chattarji
Although mGluR5-antagonists prevent fear and anxiety, little is known about how the same receptor in the amygdala gives rise to both. Combining in vitro and in vivo activation of mGluR5 in rats, we identify specific changes in intrinsic excitability and synaptic plasticity in basolateral amygdala neurons that give rise to temporally distinct and mutually exclusive effects on fear-related behaviors. The immediate impact of mGluR5 activation is to produce anxiety manifested as indiscriminate fear of both tone and context...
May 30, 2017: ELife
https://www.readbyqxmd.com/read/28554247/association-of-social-defeat-stress-induced-anhedonia-like-symptoms-with-mglur1-dependent-decrease-in-membrane-bound-ampa-glur1-in-the-mouse-ventral-midbrain
#16
Sayori Yashiro, Kenjiro Seki
Anhedonia is a core symptom of social defeat stress (SDS)-induced depression associated with the reward system. We previously reported that decreased membrane-bound AMPA-GluR1 in the reward system is associated with lipopolysaccharide-induced anhedonia-like symptoms. Since group I metabotropic glutamate receptor (mGluR) activation reduces the surface density of GluR1, we examined whether group I mGluR-dependent decrease in membrane-bound GluR1 in the reward system is involved in SDS-induced anhedonia-like symptoms...
June 29, 2017: Stress: the International Journal on the Biology of Stress
https://www.readbyqxmd.com/read/28518055/a-positive-feedback-loop-linking-enhanced-mglur-function-and-basal-calcium-in-spinocerebellar-ataxia-type-2
#17
Pratap Meera, Stefan Pulst, Thomas Otis
Metabotropic glutamate receptor 1 (mGluR1) function in Purkinje neurons (PNs) is essential for cerebellar development and for motor learning and altered mGluR1 signaling causes ataxia. Downstream of mGluR1, dysregulation of calcium homeostasis has been hypothesized as a key pathological event in genetic forms of ataxia but the underlying mechanisms remain unclear. We find in a spinocerebellar ataxia type 2 (SCA2) mouse model that calcium homeostasis in PNs is disturbed across a broad range of physiological conditions...
May 18, 2017: ELife
https://www.readbyqxmd.com/read/28503134/aquaporin-4-mediated-glutamate-induced-astrocyte-swelling-is-partially-mediated-through-metabotropic-glutamate-receptor-5-activation
#18
Zhongfang Shi, Wei Zhang, Yang Lu, Yi Lu, Lixin Xu, Qing Fang, Min Wu, Mei Jia, Yujiao Wang, Liping Dong, Xu Yan, Shaohua Yang, Fang Yuan
Astrocytes are one of the most abundant cell types in the mammalian central nervous system (CNS), and astrocyte swelling is the primary event associated with brain edema. Glutamate, the principal excitatory amino acid neurotransmitter in the CNS, is released at high levels after brain injury including cerebral ischemia. This leads to astrocyte swelling, which we previously demonstrated is related to metabotropic glutamate receptor (mGluR) activation. Aquaporin 4 (AQP4), the predominant water channel in the brain, is expressed in astrocyte endfeet and plays an important role in brain edema following ischemia...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28487223/obesogenic-diet-intake-during-pregnancy-programs-aberrant-synaptic-plasticity-and-addiction-like-behavior-to-a-palatable-food-in-offspring
#19
Alberto Camacho, Larisa Montalvo-Martinez, Robbi E Cardenas-Perez, Lizeth Fuentes-Mera, Lourdes Garza-Ocañas
Contextual food conditioned behaviors require plasticity of glutamatergic neurotransmission in the reward system, involving changes in the expression of including a-amino-3-hydroxy-5-methylisoxazole 4-propionate receptors (AMPA), N-methyl-d-aspartic acid (NMDA) and metabotropic glutamate 2,3 (mGlur 2,3). However, the role of changes in glutamatergic synaptic markers on energy-dense palatable food preference during development has not been described. Here, we determine the effect of nutritional programing during gestation on fat food choices using a conditioned place preference (CPP) test and an operant training response and its effect on glutamatergic markers in the nucleus accumbens (Nac) shell and prefrontal cortex (PFC)...
May 6, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28455524/mechanisms-underlying-cognitive-deficits-in-a-mouse-model-for-costello-syndrome-are-distinct-from-other-rasopathy-mouse-models
#20
Jadwiga Schreiber, Laura-Anne Grimbergen, Iris Overwater, Thijs van der Vaart, Jeffrey Stedehouder, Alberto J Schuhmacher, Carmen Guerra, Steven A Kushner, Dick Jaarsma, Ype Elgersma
RASopathies, characterized by germline mutations in genes encoding proteins of the RAS-ERK signaling pathway, show overlapping phenotypes, which manifest themselves with a varying severity of intellectual disability. However, it is unclear to what extent they share the same downstream pathophysiology that underlies the cognitive deficits. Costello syndrome (CS) is a rare RASopathy caused by activating mutations in the HRAS gene. Here we investigated the mechanisms underlying the cognitive deficits of HRas (G12V/G12V) mice...
April 28, 2017: Scientific Reports
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