Abstract:
:A great body of evidence points toward a functional interaction between metabotropic glutamate 5 receptors (mGluR5) and NMDA receptors (NMDAR) that enhances synaptic plasticity and cognition. However, the molecular mechanism underlying this interaction remains unclear. Here, we show that co-activation of mGluR5 and NMDAR in hippocampal slices synergistically leads to a robust phosphorylation of NR2B (Tyr1472), which is Src kinase dependent and is enabled by endogenous adenosine acting on A2A receptors. As it is well known, NR2B (Tyr1472) phosphorylation anchors NR2B-containing NMDARs to the surface of post-synaptic membranes, preventing their internalization. This is supported by our electrophysiological experiments showing that co-activation of mGluR5 and NMDARs robustly enhances NMDAR-dependent neuronal excitability recorded in CA1 hippocampal region, which temporally coincides with the robust increase in NR2B (Tyr1472) phosphorylation, depends on Src kinases and is also permitted by A2A receptors. Thus, we strongly suggest that NR2B (Tyr1472) phosphorylation constitutes, at least to some extent, the molecular mechanism underlying the mGluR5-mediated enhancement of NMDAR-dependent responses, which is modulated by A2A receptors. A better understanding of the molecular basis of mGluR5/NMDAR interaction would elucidate their role in synaptic plasticity processes as well as in pathological conditions. We propose the following molecular mechanism by which metabotropic Glutamate Receptor 5 (mGluR5) potentiate ionotropic Glutamate N-Methyl-D-Aspartate Receptor (NMDAR) responses in rat hippocampus. Co-activation of mGLUR5/NMDAR activates Src kinases, leading to NR2B(Tyr1472) phosphorylation, which anchors NR2B-containing NMDAR to the plasma membrane, thus inducing a robust increase in the NMDA-dependent excitability. Interestingly, adenosine A2A receptors license the mGluR5-induced NR2B(Tyr1472) phosphorylation.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Sarantis K,Tsiamaki E,Kouvaros S,Papatheodoropoulos C,Angelatou Fdoi
10.1111/jnc.13291subject
Has Abstractpub_date
2015-11-01 00:00:00pages
714-26issue
4eissn
0022-3042issn
1471-4159journal_volume
135pub_type
杂志文章abstract::There is growing evidence that activation of either protein kinases or protein phosphatases determines the type of plasticity observed after different patterns of hippocampal stimulation. Because activation of the extracellular signal-regulated kinase (ERK) has been shown to be necessary for long-term potentiation, we...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2000.0740192.x
更新日期:2000-01-01 00:00:00
abstract::Rat cerebellar granule cells differentiated in culture were fed [1-(3)H]sphingosine, allowing the metabolic radiolabelling of all cell sphingolipids and phosphatidylethanolamine. A detergent-insoluble sphingolipid-enriched membrane fraction, containing about 60% of cell sphingolipids, but only trace amounts of phospha...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2001.00515.x
更新日期:2001-09-01 00:00:00
abstract::Noradrenaline (NA) release and its modulation via presynaptic opioid receptors were studied in rabbit hippocampal slices, which were preincubated with [3H]NA, continuously superfused in the presence of 30 microM cocaine and stimulated electrically. The evoked release of [3H]NA was strongly reduced by the preferential ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1986.tb08499.x
更新日期:1986-06-01 00:00:00
abstract::The export of glutamine from astrocytes, and the uptake of glutamine by neurons, are integral steps in the glutamate-glutamine cycle, a major pathway for the replenishment of neuronal glutamate. We review here the functional and molecular identification of the transporters that mediate this transfer. The emerging pict...
journal_title:Journal of neurochemistry
pub_type: 杂志文章,评审
doi:10.1046/j.1471-4159.2001.00322.x
更新日期:2001-05-01 00:00:00
abstract::A specific and sensitive gas chromatographic-mass spectrometric assay for measurement of normetanephrine (NMN) in different rat brain regions is presented. The results show that hypothalamus contains the highest concentrations of the norepinephrine metabolite. An increase of NMN concentrations has been detected in ani...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1981.tb06334.x
更新日期:1981-12-01 00:00:00
abstract::Excitotoxicity, caused by exaggerated neuronal stimulation by Glutamate (Glu), is a major cause of neurodegeneration in brain ischemia. While we know that neurodegeneration is triggered by overstimulation of Glu-receptors (GluRs), the subsequent mechanisms that lead to cellular demise remain controversial. Surprisingl...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.14629
更新日期:2019-02-01 00:00:00
abstract::Glutamate receptor (GluR) δ1 is widely expressed in the developing forebrain, whereas GluRδ2 is selectively expressed in cerebellar Purkinje cells. Recently, we found that trans-synaptic interaction of postsynaptic GluRδ2 and pre-synaptic neurexins (NRXNs) through cerebellin precursor protein (Cbln) 1 mediates excitat...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2011.07631.x
更新日期:2012-06-01 00:00:00
abstract::Early malnutrition is a risk factor for depression and schizophrenia. Since the offspring of malnourished dams exhibit increased brain levels of serotonin (5-HT), a tryptophan-derived neurotransmitter involved in the pathophysiology of these mental disorders, it is believed that the deleterious effects of early malnut...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.13874
更新日期:2017-01-01 00:00:00
abstract::Marked accumulation of arachidonic acid (AA) and intracellular Ca2+ and Na+ overloads are seen during brain ischemia. In this study, we show that, in neurons, AA induces cytosolic Na+ ([Na+](cyt)) and Ca2+ ([Ca2+](cyt)) overload via a non-selective cation conductance (NSCC), resulting in mitochondrial [Na+](m) and [Ca...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2007.05022.x
更新日期:2008-03-01 00:00:00
abstract::Ethanol provides neuroprotection following ischemia/reperfusion. This study assessed ethanol's effect on hyperglycolysis and NADPH oxidase (NOX) activation. Adult, male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h. Three sets of experiments were conducted to determine ethanol's...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.12169
更新日期:2013-07-01 00:00:00
abstract::The ability of cholinergic vesicles to incorporate acetylcholine (ACh) was studied using highly purified synaptic vesicles from Torpedo electric organ. Depleted vesicles were capable of rapidly taking up exogenous ACh. Evidence that this represented true incorporation was that labelled ACh comigrated with vesicular AT...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1981.tb00479.x
更新日期:1981-08-01 00:00:00
abstract::Gabapentin is an anticonvulsant that successfully treats many neuropathic pain syndromes, although the mechanism of its antihyperalgesic action remains elusive. This study aims to help delineate gabapentin's antihyperalgesic mechanisms. We assessed the effectiveness of gabapentin at decreasing mechanical and cold hype...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2005.03263.x
更新日期:2005-08-01 00:00:00
abstract::Quinolinic acid (QA) has been shown to evoke neurotoxic events via NMDA receptor (NMDAR) overactivation and oxidative stress. NMDARs are particularly vulnerable to free radicals, which can modulate protein tyrosine kinase (PTK) and phosphotyrosine phosphatase (PTP) activities. The src family of tyrosine kinases are as...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2006.03814.x
更新日期:2006-06-01 00:00:00
abstract::[3H]Spiroperidol binding to homogenates of rat striatum is saturable and shows either monophasic or biphasic saturation isotherms under specified conditions. In poorly washed membrane fragment preparations, saturation isotherms of [3H]spiroperidol binding are monophasic, revealing an apparently homogeneous set of site...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1980.tb07865.x
更新日期:1980-11-01 00:00:00
abstract::The later phases of neuronal plasticity are invariably dependent on gene transcription. Induction of the transcription factor Zif268 (Egr-1) in neurones is closely associated with many forms of functional plasticity, yet the neuronal target genes modulated by Zif268 have not been characterized. After transfection of a...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2005.03400.x
更新日期:2005-11-01 00:00:00
abstract::Melanocortin-4 receptors (MC4 R) are unique among G-protein-coupled receptors (GPCRs) as they have endogenous ligands that can exhibit inverse agonistic properties in the case of elevated basal activity. It is known that the constitutive activity of GPCRs strongly affects the ligand-dependent physiological responses, ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.14933
更新日期:2020-05-01 00:00:00
abstract::Light stimulates dopamine release in the retina and has been shown to rapidly up-regulate rod opsin mRNA. In the present study, we tested the effect of dopamine on rod opsin mRNA expression and examined the hypothesis that dopamine can mediate a light-evoked increase in opsin gene expression. Northern blots showed tha...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2001.00109.x
更新日期:2001-02-01 00:00:00
abstract::[3H]Strychnine binding to rat pons + medulla membranes was used as a measure of glycine receptors or glycine receptor-coupled chloride channels in vitro. A series of compounds structurally related to 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP), which previously were shown to antagonize glycine responses in c...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1986.tb00667.x
更新日期:1986-09-01 00:00:00
abstract::Brain-derived neurotrophic factor (BDNF) which is primarily associated with neuronal survivability, differentiation and synaptic plasticity has been reported to mediate neurodegeneration in hypoxia through its p75 Neurotrophin receptors (p75NTR). The molecular events promoting BDNF-mediated pro-death signalling in hyp...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.14609
更新日期:2019-01-01 00:00:00
abstract::The roles of two subtypes of corticotrophin-releasing factor (CRF) receptor in corticostriatal synaptic plasticity under cocaine withdrawal condition were examined in this study. Neither the resting membrane potential and input resistance of striatal neurons nor the long-term potentiation (LTP) of corticostriatal slic...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2010.06981.x
更新日期:2010-11-01 00:00:00
abstract::Clinical and experimental data indicate that spinal cord injury (SCI) elicits pathological T-cell responses. Implicit in these data, but poorly understood, is that B lymphocytes (B cells) also contribute to the delayed pathophysiology of spinal trauma. Here, for the first time, we show that experimental spinal contusi...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2006.04147.x
更新日期:2006-11-01 00:00:00
abstract::Myelination, during both normal development and with respect to disorders of myelination, is commonly studied by morphological and/or biochemical techniques that assay as their end-points the extent of myelination. The rate of myelination is potentially a more useful parameter, but it is difficult and time-consuming t...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2001.00015.x
更新日期:2001-01-01 00:00:00
abstract::We examined the modulation of nitric oxide production in vivo by measuring levels of nitrite (NO2-) and nitrate (NO3-) in the dialysate of the cerebellum in conscious rats, by using an in vivo brain microdialysis technique. The levels of both NO2- and NO3- were decreased by the intraperitoneal injection of NG-nitro-L-...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1997.68031234.x
更新日期:1997-03-01 00:00:00
abstract::Incubation of [2-3H]glycerol-labeled phosphatidylinositol with a crude cytosol fraction of rat brain in the presence of EDTA yielded [3H]lysophosphatidylinositol predominantly without accumulation of labeled monoacylglycerol and diacylglycerol. The pH optimum of this phospholipase A activity was 8.0. The activity for ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1993.tb09829.x
更新日期:1993-11-01 00:00:00
abstract::Myristoylated alanine-rich C kinase substrate (MARCKS) and MARCKS-related protein (MRP) have been implicated in membrane-cytoskeletal events underlying cell adhesion, migration, secretion, and phagocytosis. In BV-2 microglial cells, lipopolysaccharide (LPS) elicited a dose-dependent increase in mRNA of both MRP (sixfo...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2001.00458.x
更新日期:2001-08-01 00:00:00
abstract::Synaptosomes and mitochondria were isolated from the brains of warm-adapted, hibernating, and cold-acclimated golden hamsters (Mesocricetus auratus). Lipid extracts of these subcellular fractions were prepared and assayed for plasmenylethanolamine (ethanolamine plasmalogen) and cholesterol levels. The ganglioside comp...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1983.tb08098.x
更新日期:1983-04-01 00:00:00
abstract::Sequence data from key fragments of the P2 protein established the order of cyanogen bromide (CNBr) peptides in the structure of the protein and the primary structure for approximately one-half of the molecule. Data were obtained from the three tryptic peptides of blocked NH2-terminal CNBr peptide (CN3), the large CNB...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1980.tb06276.x
更新日期:1980-08-01 00:00:00
abstract::Our results provide evidence that 6-hydroxydopamine induced, after auto-oxidation, toxic levels of hydrogen peroxide (H2O2) that caused bovine chromaffin cell toxicity and death. 6-Hydroxydopamine (6-OHDA) treatment markedly reduced, in a dose-response fashion, chromaffin cell viability. Cell death was accompanied by ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2003.01592.x
更新日期:2003-03-01 00:00:00
abstract::Catechol-O-methyltransferase (COMT) has both soluble (S-COMT) and membrane-bound (MB-COMT) isoforms. A specific COMT antibody was used in immunohistochemical and confocal co-localization studies to explore the distribution of COMT in general in normal mice and MB-COMT in particular, in an S-COMT deficient mouse line. ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2010.06723.x
更新日期:2010-06-01 00:00:00
abstract::Complex biological systems are best modeled as highly modular, fluid systems exhibiting a plasticity that allows them to adapt to a vast array of changing conditions. Here we highlight several novel network-based approaches to elucidate genetic networks underlying complex traits. These integrative genomic approaches c...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2006.03661.x
更新日期:2006-04-01 00:00:00