Search results for: GRIN1
#34952289 2021/12/21 To Up
N-Methyl-d-Aspartate receptor and inflammation in dorsolateral prefrontal cortex in schizophrenia.Lower N-methyl-d-aspartate receptor (NMDAR) GluN1 subunit levels and heightened neuroinflammation are found in the cortex in schizophrenia. Since neuroinflammation can lead to changes in NMDAR function, it is possible that these observations are linked in schizophrenia. We aimed to extend our previous studies by measuring molecular indices of NMDARs that define key functional properties of this receptor - particularly the ratio of GluN2A and GluN2B subunits - in dorsolateral prefrontal cortex (DLPFC) from schizophrenia and control cases (37/37). We sought to test whether changes in these measures are specific to the subset of schizophrenia cases with high levels of inflammation-related mRNAs, defined as a high inflammatory subgroup. Quantitative autoradiography was used to detect 'functional' NMDARs ([H]MK-801), GluN1-coupled-GluN2A subunits ([H]CGP-39653), and GluN1-coupled-GluN2B subunits ([H]Ifenprodil). Quantitative RT-PCR was used to measure NMDAR subunit transcripts (GRIN1, GRIN2A and GRIN2B). The ratios of GluN2A:GluN2B binding and GRIN2A:GRIN2B mRNAs were calculated as an index of putative NMDAR composition. We found: 1) GluN2A binding, and 2) the ratios of GluN2A:GluN2B binding and GRIN2A:GRIN2B mRNAs were lower in schizophrenia cases versus controls (pÂ <Â 0.05), and 3) lower GluN2A:GluN2B binding and GRIN2A:GRIN2B mRNA ratios were exaggerated in the high inflammation/schizophrenia subgroup compared to the low inflammation/control subgroup (pÂ <Â 0.05). No other NMDAR-related indices were significantly changed in the high inflammation/schizophrenia subgroup. This suggests that neuroinflammation may alter NMDAR stoichiometry rather than targeting total NMDAR levels overall, and future studies could aim to determine if anti-inflammatory treatment can alleviate this aspect of NMDAR-related pathology.
Tasnim Rahman, Tertia Purves-Tyson, Amy E Geddes, Xu-Feng Huang, Kelly A Newell, Cynthia Shannon Weickert
2459 related Products with: N-Methyl-d-Aspartate receptor and inflammation in dorsolateral prefrontal cortex in schizophrenia.100ug16 Arrays/Slide96 wells (1 kit)100ug124 Sample Kit100ug100 μg32-50 Sample Kit100ug16 Arrays/Slide
#34899420 2021/11/25 To Up
Cre-Activation in ErbB4-Positive Neurons of Floxed /NMDA Receptor Mice Is Not Associated With Major Behavioral Impairment.Extensive evidence suggests a dysfunction of the glutamate NMDA receptor (NMDAR) in schizophrenia, a severe psychiatric disorder with putative early neurodevelopmental origins, but clinical onset mainly during late adolescence. On the other hand, pharmacological models using NMDAR antagonists and the clinical manifestation of anti-NMDAR encephalitis indicate that NMDAR blockade/hypofunction can trigger psychosis also at adult stages, without any early developmental dysfunction. Previous genetic models of NMDAR hypofunction restricted to parvalbumin-positive interneurons indicate the necessity of an early postnatal impairment to trigger schizophrenia-like abnormalities, whereas the cellular substrates of NMDAR-mediated psychosis at adolescent/adult stages are unknown. Neuregulin 1 (NRG1) and its receptor ErbB4 represent schizophrenia-associated susceptibility factors that closely interact with NMDAR. To determine the neuronal populations implicated in "late" NMDAR-driven psychosis, we analyzed the effect of the inducible ablation of NMDARs in -expressing cells in mice during late adolescence using a pharmacogenetic approach. Interestingly, the tamoxifen-inducible NMDAR deletion during this late developmental stage did not induce behavioral alterations resembling depression, schizophrenia or anxiety. Our data indicate that post-adolescent NMDAR deletion, even in a wider cell population than parvalbumin-positive interneurons, is also not sufficient to generate behavioral abnormalities resembling psychiatric disorders. Other neuronal substrates that have to be revealed by future studies, may underlie post-adolescent NMDAR-driven psychosis.
Anne S Mallien, Natascha Pfeiffer, Miriam A Vogt, Sabine Chourbaji, Rolf Sprengel, Peter Gass, Dragos Inta
2019 related Products with: Cre-Activation in ErbB4-Positive Neurons of Floxed /NMDA Receptor Mice Is Not Associated With Major Behavioral Impairment.100 μg100ug Lyophilized100ug Lyophilized 100ul100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized
#34884460 2021/11/23 To Up
Paradigmatic De Novo Variants Recapitulate Pathophysiological Mechanisms Underlying GRIN1-Related Disorder Clinical Spectrum.GRIN-related disorders (GRD), the so-called grinpathies, is a group of rare encephalopathies caused by mutations affecting genes (mostly , and genes), which encode for the GluN subunit of the -methyl D-aspartate (NMDA) type ionotropic glutamate receptors. A growing number of functional studies indicate that GRIN-encoded GluN1 subunit disturbances can be dichotomically classified into gain- and loss-of-function, although intermediate complex scenarios are often present.
Ana Santos-GÃ³mez, Federico Miguez-Cabello, Natalia JuliÃ¡-Palacios, Deyanira GarcÃa-Navas, VÃctor Soto-Insuga, Juan J GarcÃa-PeÃ±as, Patricia Fuentes, Salvador IbÃ¡Ã±ez-MicÃ³, Laura Cuesta, RamÃ³n Cancho, Patricia Andreo-Lillo, Gema GutiÃ©rrez-Aguilar, Olga Alonso-Luengo, Ignacio MÃ¡laga, Antonio Hedrera-FernÃ¡ndez, Ãngels GarcÃa-Cazorla, David Soto, Mireia Olivella, Xavier Altafaj
1222 related Products with: Paradigmatic De Novo Variants Recapitulate Pathophysiological Mechanisms Underlying GRIN1-Related Disorder Clinical Spectrum.100ul5mg10mg10mg50mg96T5mg
#34840971 2021/11/19 To Up
Identification of Hub Gene GRIN1 Correlated with Histological Grade and Prognosis of Glioma by Weighted Gene Coexpression Network Analysis.The function of glutamate ionotropic receptor NMDA type subunit 1 (GRIN1) in neurodegenerative diseases has been widely reported; however, its role in the occurrence of glioma remains less explored. We obtained clinical data and transcriptome data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Hub gene's expression differential analysis and survival analysis were conducted by browsing the Gene Expression Profiling Interactive Analysis (GEPIA) database, Human Protein Atlas database, and LOGpc database. We conducted a variation analysis of datasets obtained from GEO and TCGA and performed a weighted gene coexpression network analysis (WGCNA) using the R programming language (3.6.3). Kaplan-Meier (KM) analysis was used to calculate the prognostic value of GRIN1. Finally, we conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Using STRING, we constructed a protein-protein interaction (PPI) network. Cytoscape software, a prerequisite of visualizing core genes, was installed, and CytoHubba detected the 10 most tumor-related core genes. We identified 185 differentially expressed genes (DEGs). GO and KEGG enrichment analyses illustrated that the identified DEGs are imperative in different biological functions and ascertained the potential pathways in which the DEGs may be enriched. The overall survival calculated by KM analysis showed that patients with lower expression of GRIN1 had worse prognoses than patients with higher expression of GRIN1 ( = 0.004). The GEPIA and LOGpc databases were used to verify the expression difference of GRIN1 among GBM, LGG, and normal brain tissues. Ultimately, immunohistochemical assay results showed that GRIN1 was detected in normal tissue and not in the tumor specimens. Our results highlight a potential target for glioma treatment and will further our understanding of the molecular mechanisms underlying the treatment of glioma.
Aoran Yang, Xinhuan Wang, Yaofeng Hu, Chao Shang, Yang Hong
1457 related Products with: Identification of Hub Gene GRIN1 Correlated with Histological Grade and Prognosis of Glioma by Weighted Gene Coexpression Network Analysis.500 gm50 ug1 plate50 ug50 ug50 ug300 units50 ug50 ug50 ug
#34830191 2021/11/15 To Up
The Effect of Oxidative Stress and Memantine-Incorporated Reactive Oxygen Species-Sensitive Nanoparticles on the Expression of -Methyl-d-aspartate Receptor Subunit 1 in Brain Cancer Cells for Alzheimer's Disease Application.The aim of this study is to fabricate reactive oxygen species (ROS)-sensitive nanoparticles composed of succinyl Î²-cyclodextrin (bCDsu), memantine and thioketal linkages for application in Alzheimer's disease, and to investigate the suppression of -methyl-d-aspartate (NMDA) receptor 1 (NMDAR1) in cells. Thioketal diamine was attached to the carboxyl group of bCDsu to produce thioketal-decorated bCDsu conjugates (bCDsu-thioketal conjugates) and memantine was conjugated with thioketal dicarboxylic acid (memantine-thioketal carboxylic acid conjugates). Memantine-thioketal carboxylic acid conjugates were attached to bCDsu-thioketal conjugates to produce bCDsu-thioketal-memantine (bCDsuMema) conjugates. SH-SY5Y neuroblastoma cells and U87MG cells were used for NMDAR1 protein expression and cellular oxidative stress. Nanoparticles of bCDsuMema conjugates were prepared by means of a dialysis procedure. Nanoparticles of bCDsuMema conjugates had small particle sizes less than 100 nm and their morphology was found to be spherical in transmission electron microscopy observations (TEM). Nanoparticles of bCDsuMema conjugates responded to HO and disintegrated or swelled in aqueous solution. Then, the nanoparticles rapidly released memantine according to the concentration of HO. In an in vivo animal imaging study, thioketal-decorated nanoparticles labelled with fluorescent dye such as chlorin e6 (Ce6) showed that the fluorescence intensity was stronger in the brain than in other organs, indicating that bCDsuMema nanoparticles can efficiently target the brain. When cells were exposed to HO, the viability of cells was time-dependently decreased. Memantine or bCDsuMema nanoparticles did not practically affect the viability of the cells. Furthermore, a western blot assay showed that the oxidative stress produced in cells using HO increased the expression of NMDAR1 protein in both SH-SY5Y and U87MG cells. Memantine or bCDsuMema nanoparticles efficiently suppressed the NMDAR1 protein, which is deeply associated with Alzheimer's disease. Fluorescence microscopy also showed that HO treatment induced green fluorescence intensity, which represents intracellular ROS levels. Furthermore, HO treatment increased the red fluorescence intensity, which represents the NMDAR1 protein, i.e., oxidative stress increases the expression of NMDAR1 protein level in both SH-SY5Y and U87MG cells. When memantine or bCDsuMema nanoparticles were treated in cells, the oxidative stress-mediated expression of NMDAR1 protein in cells was significantly decreased, indicating that bCDsuMema nanoparticles have the capacity to suppress NMDAR1 expression in brain cells, which has relevance in terms of applications in Alzheimer's disease.
Jung Sun Park, Taeyeon Kim, Dohoon Kim, Young-Il Jeong
1844 related Products with: The Effect of Oxidative Stress and Memantine-Incorporated Reactive Oxygen Species-Sensitive Nanoparticles on the Expression of -Methyl-d-aspartate Receptor Subunit 1 in Brain Cancer Cells for Alzheimer's Disease Application.100ul 100ul 100ul 100ul 100ul 100ul 100ul 100ul 100ul 100ul 100ul
#34726335 2021/11/02 To Up
N-methyl-d-aspartate (NMDA) receptor genetics: The power of paralog homology and protein dynamics in defining dominant genetic variants.Predicting genotype-to-phenotype correlations from genomic variants has been challenging, particularly for genes that have a complex balance of dominant and recessive inheritance for phenotypes. Variants in NMDA receptor components GRIN1, GRIN2A, and GRIN2B cause a myriad of dominant disease phenotypes, with the most common being epilepsy and autism spectrum disorder. Starting from the analysis of a variant of uncertain significance (VUS, GRIN2A G760S), we realized the need for tools to map dominant variants for the components of the NMDA receptor. Some variants within GRIN1, GRIN2A, and GRIN2B exert dominant epilepsy and developmental delay, yet other amino acid variants are conserved and predicted to alter protein function but do not have dominant phenotypes. Common variant annotation tools are not powered to determine pathogenic dominant outcomes. To address this gap, we integrated sequence and structural analyses for GRIN1, GRIN2A, and GRIN2B. Using this approach, we determined that paralog homology mapping and topology can segregate dominant variants, with an elevation of intermolecular contacts between the subunits. Furthermore, demonstrating the general utility of our methodology, we show that 25 VUS within ClinVar also reach a dominant variant annotation, including the GRIN2A G760S variant. Our work suggests paralog homology and protein topology as a powerful strategy within the receptor complex to resolve dominant genetic variants relative to variants that would fit a recessive inheritance, requiring two damaging variants. These strategies should be tested in additional dominant genetic disorders to determine the broader utility.
Jacob G Charron, Angel Hernandez, Stephanie M Bilinovich, Daniel L Vogt, Laura A Bedinger, Laurie H Seaver, Michael Williams, Seth Devries, Daniel B Campbell, Caleb P Bupp, Jeremy W Prokop
1056 related Products with: N-methyl-d-aspartate (NMDA) receptor genetics: The power of paralog homology and protein dynamics in defining dominant genetic variants.100ul200ul100 μg1 Set1 Set1 Set1 Set 100ul100ug1 Set1 Set
#34680965 2021/10/01 To Up
Alternative Splicing Mechanisms Underlying Opioid-Induced Hyperalgesia.Prolonged use of opioids can cause opioid-induced hyperalgesia (OIH). The impact of alternative splicing on OIH remains partially characterized. A study of the absolute and relative modes of action of alternative splicing further the understanding of the molecular mechanisms underlying OIH. Differential absolute and relative isoform profiles were detected in the trigeminal ganglia and nucleus accumbens of mice presenting OIH behaviors elicited by chronic morphine administration relative to control mice. Genes that participate in glutamatergic synapse (e.g., Grip1, Grin1, Wnk3), myelin protein processes (e.g., Mbp, Mpz), and axon guidance presented absolute and relative splicing associated with OIH. Splicing of genes in the gonadotropin-releasing hormone receptor pathway was detected in the nucleus accumbens while splicing in the vascular endothelial growth factor, endogenous cannabinoid signaling, circadian clock system, and metabotropic glutamate receptor pathways was detected in the trigeminal ganglia. A notable finding was the prevalence of alternatively spliced transcription factors and regulators (e.g., Ciart, Ablim2, Pbx1, Arntl2) in the trigeminal ganglia. Insights into the nociceptive and antinociceptive modulatory action of Hnrnpk were gained. The results from our study highlight the impact of alternative splicing and transcriptional regulators on OIH and expose the need for isoform-level research to advance the understanding of morphine-associated hyperalgesia.
Pan Zhang, Olivia C Perez, Bruce R Southey, Jonathan V Sweedler, Amynah A Pradhan, Sandra L Rodriguez-Zas10mg100ug10mg10mg5mg5mg50 ul100ug Lyophilized50mg10mg5mg100ug
#34635992 2021/10/11 To Up
How an increase in the copy number of HSV-1 during latency can cause Alzheimer's disease: the viral and cellular dynamics according to the microcompetition model.Numerous studies observed a link between the herpes smplex virus-1 (HSV-1) and Alzheimer's disease. However, the exact viral and cellular dynamics that lead from an HSV-1 infection to Alzheimer's disease are unknown. In this paper, we use the microcompetition model to formulate these dynamics by connecting seemingly unconnected observations reported in the literature. We concentrate on four pathologies characteristic of Alzheimer's disease. First, we explain how an increase in the copy number of HSV-1 during latency can decrease the expression of BECN1/Beclin1, the degradative trafficking protein, which, in turn, can cause a dysregulation of autophagy and Alzheimer's disease. Second, we show how an increase in the copy number of the latent HSV-1 can decrease the expression of many genes important for mitochondrial genome metabolism, respiratory chain, and homeostasis, which can lead to oxidative stress and neuronal damage, resulting in Alzheimer's disease. Third, we describe how an increase in this copy number can reduce the concentration of the NMDA receptor subunits NR1 and NR2b (Grin1 and Grin2b genes), and brain derived neurotrophic factor (BDNF), which can cause an impaired synaptic plasticity, AÎ² accumulation and eventually Alzheimer's disease. Finally, we show how an increase in the copy number of HSV-1 in neural stem/progenitor cells in the hippocampus during the latent phase can lead to an abnormal quantity and quality of neurogenesis, and the clinical presentation of Alzheimer's disease. Since the current understanding of the dynamics and homeostasis of the HSV-1 reservoir during latency is limited, the proposed model represents only a first step towards a complete understanding of the relationship between the copy number of HSV-1 during latency and Alzheimer's disease.
Hanan Polansky, Benjamin Goral
1153 related Products with: How an increase in the copy number of HSV-1 during latency can cause Alzheimer's disease: the viral and cellular dynamics according to the microcompetition model.100ul1
#34630033 2021/09/14 To Up
NMDARs Drive the Expression of Neuropsychiatric Disorder Risk Genes Within GABAergic Interneuron Subtypes in the Juvenile Brain.Medial ganglionic eminence (MGE)-derived parvalbumin (PV)+, somatostatin (SST)+and Neurogliaform (NGFC)-type cortical and hippocampal interneurons, have distinct molecular, anatomical, and physiological properties. However, the molecular mechanisms regulating their maturation remain poorly understood. Here, via single-cell transcriptomics, we show that the obligate NMDA-type glutamate receptor (NMDAR) subunit gene mediates transcriptional regulation of gene expression in specific subtypes of MGE-derived interneurons, leading to altered subtype abundances. Notably, MGE-specific early developmental Grin1 loss results in a broad downregulation of diverse transcriptional, synaptogenic and membrane excitability regulatory programs in the juvenile brain. These widespread gene expression abnormalities mirror aberrations that are typically associated with neurodevelopmental disorders. Our study hence provides a road map for the systematic examination of NMDAR signaling in interneuron subtypes, revealing potential MGE-specific genetic targets that could instruct future therapies of psychiatric disorders.
Vivek Mahadevan, Apratim Mitra, Yajun Zhang, Xiaoqing Yuan, Areg Peltekian, Ramesh Chittajallu, Caroline Esnault, Dragan Maric, Christopher Rhodes, Kenneth A Pelkey, Ryan Dale, Timothy J Petros, Chris J McBain
2800 related Products with: NMDARs Drive the Expression of Neuropsychiatric Disorder Risk Genes Within GABAergic Interneuron Subtypes in the Juvenile Brain.1 100ul1 ml
#34611970 2021/10/06 To Up
A homozygous GRIN1 null variant causes a more severe phenotype of early infantile epileptic encephalopathy.Pathogenic variants in glutamate receptor, ionotropic, NMDA-1 (GRIN1) cause an autosomal dominant or recessive neurodevelopmental disorder with global developmental delay, with or without seizures (AD or AR GRIN1-NDD). Here, we describe a novel homozygous canonical splice site variant in GRIN1 in a 12-month-old boy with early infantile epileptic encephalopathy and severe global developmental delay. This represents only the second family with a homozygous predicted-null variant in GRIN1 reported to date. We review the published literature on AR GRIN1-NDD and find that the phenotype in our patient is much more severe than those seen with homozygous missense variants. A similarly severe phenotype of intractable epilepsy and infantile death has only been reported in one other family with a homozygous nonsense variant in GRIN1. We, therefore, propose that biallelic predicted-null variants in GRIN1 can cause a markedly more severe clinical phenotype than AR GRIN1-NDD caused by missense variants.
Alexander J M Blakes, Joel English, Siddharth Banka, Helen Basu
2201 related Products with: A homozygous GRIN1 null variant causes a more severe phenotype of early infantile epileptic encephalopathy.0.2 mg250ul100ug100ug100ug1 mg0.1ml (1mg/ml)100ug2 mL100 μg 100ul0.1 mg
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