Activation of the extracellular signal-regulated kinase pathway contributes to the behavioral deficit of fragile x-syndrome.


:Fragile X syndrome (FXS) is a developmental disorder caused by the loss of Fragile X Mental Retardation 1 (FMR1) gene function because of a CGG repeat expansion (> 200 repeats) in the gene. The molecular mechanism(s) linking loss of FMR1 function to the molecular pathology and cognitive/behavioral disability remain unclear. Given the critical role of extracellular signal-regulated kinase (ERK) in synaptic plasticity and neurodevelopment, a number of recent studies have investigated ERK phosphorylation under basal conditions or upon mGluR-induction using neuronal and peripheral tissues from Fmr1 knockout mice and peripheral tissues from FXS patients. However, these reports have presented conflicting results. The current study is the first to focus on the levels of ERK phosphorylation in brain tissue from human FXS patients. In both human brain tissue and brain tissue from Fmr1 knockout mice there was significantly increased phosphorylation of MEK1/2 and ERK. Indeed, treating Fmr1 knockout mice with the MEK1/2 inhibitor SL327 abrogated audiogenic seizure activity, a feature of the Fmr1 knockout mice that replicates the symptom in patients with FXS. These findings suggest that activation of the ERK pathway results in some cardinal cognitive and clinical features in FXS patients and likely have profound translational implications.


J Neurochem


Wang X,Snape M,Klann E,Stone JG,Singh A,Petersen RB,Castellani RJ,Casadesus G,Smith MA,Zhu X




Has Abstract


2012-05-01 00:00:00












  • Estrogen-related receptor gamma regulates dopaminergic neuronal phenotype by activating GSK3β/NFAT signaling in SH-SY5Y cells.

    abstract::The orphan nuclear receptor estrogen-related receptor gamma (ERRγ) is highly expressed in the nervous system during embryogenesis and in adult brains, but its physiological role in neuronal development remains unknown. In this study, we evaluated the relevance of ERRγ in regulating dopaminergic (DAergic) phenotype and...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Lim J,Choi HS,Choi HJ

    更新日期:2015-05-01 00:00:00

  • RhoE stimulates neurite-like outgrowth in PC12 cells through inhibition of the RhoA/ROCK-I signalling.

    abstract::Neurite formation involves coordinated changes between the actin cytoskeleton and the microtubule network. Rho GTPases are clearly implicated in several aspects of neuronal development and function. Indeed, RhoA is a negative regulator of neurite outgrowth and its effector Rho-kinase mediates the Rho-driven neurite re...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Talens-Visconti R,Peris B,Guerri C,Guasch RM

    更新日期:2010-02-01 00:00:00

  • Threshold effects in synaptosomal and nonsynaptic mitochondria from hippocampal CA1 and paramedian neocortex brain regions.

    abstract::After a brief period of global ischemia, the hippocampal CA1 region is more susceptible to irreversible damage than the paramedian neocortex. To test whether primary differences in bioenergetic parameters may be present between these regions, respiration rates and respiratory control activities were measured. In synap...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Davey GP,Canevari L,Clark JB

    更新日期:1997-12-01 00:00:00

  • Region-specific targets of p42/p44MAPK signaling in rat brain.

    abstract::In vitro studies indicate that p42/p44MAPK phosphorylate both nuclear and cytoplasmic proteins. However, the functional targets of p42/p44MAPK activation in vivo remain unclear. To address this question, we localized activated p42/p44MAPK in hippocampus and cortex and determined their signaling effects after electroco...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Bhat RV,Engber TM,Finn JP,Koury EJ,Contreras PC,Miller MS,Dionne CA,Walton KM

    更新日期:1998-02-01 00:00:00

  • Analysis of the proenkephalin second messenger-inducible enhancer in rat striatal cultures.

    abstract::We have previously shown that in cell extracts from rat striatum, cyclic AMP response element (CRE) binding protein (CREB), rather than AP-1 proteins, preferentially interacts with the CRE-2 element of the proenkephalin second messenger-inducible enhancer, even under conditions in which AP-1 proteins are highly induce...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Konradi C,Cole RL,Green D,Senatus P,Leveque JC,Pollack AE,Grossbard SJ,Hyman SE

    更新日期:1995-09-01 00:00:00

  • Induction of pro-apoptotic calsenilin/DREAM/KChIP3 in Alzheimer's disease and cultured neurons after amyloid-beta exposure.

    abstract::Calsenilin/DREAM/KChIP3 was identified as a calcium-binding protein that interacts with presenilins, serves as a transcription repressor, and binds to the A-type potassium channel. In this study, we hypothesized that calsenilin might be involved in the neurodegeneration of Alzheimer's disease and examined calsenilin e...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Jo DG,Lee JY,Hong YM,Song S,Mook-Jung I,Koh JY,Jung YK

    更新日期:2004-02-01 00:00:00

  • A simple radioenzymatic method to measure picogram amounts of DOPA in brain and biological fluids.

    abstract::A simple radioenzymatic method for the determination of DOPA is described. The method is based on the conversion of DOPA to 3-O-[methyl-3H]DOPA by catechol-O-methyltransferase in the presence of S-adenosyl-[methyl-3H]methionine and purification of the labelled product by Sephadex G10 and Dowex 50 W x 4 ion exchange re...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Argiolas A,Gessa GL

    更新日期:1981-01-01 00:00:00

  • Glutamate inhibition of the adrenergic-stimulated production of melatonin in rat pineal gland in vitro.

    abstract::The effect of L-glutamate on the adrenergic-stimulated release of melatonin in the rat pineal gland was examined using an in vitro perfusion system. L-Glutamate by itself had no effect on melatonin secretion whereas L-glutamate administered prior to (-)-isoproterenol (beta-adrenergic agonist) and L-phenylephrine (alph...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Kus L,Handa RJ,McNulty JA

    更新日期:1994-06-01 00:00:00

  • Two possibly distinct prostaglandin E1 receptors in N1E-115 clone: one mediating inositol trisphosphate formation, cyclic GMP formation, and intracellular calcium mobilization and the other mediating cyclic AMP formation.

    abstract::Prostaglandin E1 (PGE1)-mediated transmembrane signal control systems were investigated in intact murine neuroblastoma cells (clone N1E-115). PGE1 increased intracellular levels of total inositol phosphates (IP), cyclic GMP, cyclic AMP, and calcium ([Ca2+]i). PGE1 transiently increased inositol 1,4,5-trisphosphate for...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Kanba S,Sasakawa N,Nakaki T,Kanba KS,Yagi G,Kato R,Richelson E

    更新日期:1991-12-01 00:00:00

  • Correlated changes in NMDA receptor phosphorylation, functional activity, and sedation by chronic ethanol consumption.

    abstract::Alcohol abuse leads to tolerance, dependence, and memory impairments that involve excitatory glutamatergic NMDA synaptic transmission. The NMDA receptor (NMDAR) is known to undergo activity-dependent adaptive functional changes. Since we observed that acute ethanol inhibition of the NMDAR was regulated by protein tyro...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Wu PH,Coultrap S,Browning MD,Proctor WR

    更新日期:2010-12-01 00:00:00

  • An aminopeptidase from mouse brain cytosol that cleaves N-terminal acidic amino acid residues.

    abstract::An aminopeptidase with specificity directed toward peptides with acidic N-terminal amino acid residues has been isolated from mouse brain cytosol. Purification by ion-exchange chromatography and gel filtration resulted in an enzyme that hydrolyzed aspartyl-phenylalanine methyl ester at a rate of 13.2 mumols/min/mg pro...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Kelly JA,Neidle EL,Neidle A

    更新日期:1983-06-01 00:00:00

  • Peroxidative stress selectively down-regulates the neuronal stress response activated under conditions of endoplasmic reticulum dysfunction.

    abstract::Oxidative stress has been implicated in mechanisms leading to neuronal cell injury in various pathological states of the brain. Here, we investigated the effect of peroxide exposure on the expression of genes coding for cytoplasmic and endoplasmic reticulum (ER) stress proteins. Primary neuronal cell cultures were exp...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Paschen W,Mengesdorf T,Althausen S,Hotop S

    更新日期:2001-03-01 00:00:00

  • Glucose transport and utilization are altered in the brain of rats deficient in n-3 polyunsaturated fatty acids.

    abstract::Long-chain polyunsaturated (n-3) fatty acids have been reported to influence the efficiency of membrane receptors, transporters and enzymes. Because the brain is particularly rich in docosahexaenoic acid (DHA, 22:6 n-3), the present study addresses the question of whether the 22:6 n-3 fatty acid deficiency induces dis...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Ximenes da Silva A,Lavialle F,Gendrot G,Guesnet P,Alessandri JM,Lavialle M

    更新日期:2002-06-01 00:00:00

  • Feedback control of mesolimbic somatodendritic dopamine release in rat brain.

    abstract::The objective of this study was to examine the role of dopamine (DA) receptors in the nucleus accumbens (ACB) in controlling feedback regulation of mesolimbic somatodendritic DA release in the ventral tegmental area (VTA) of Wistar rats using ipsilateral dual-probe in vivo microdialysis. Perfusion of the ACB for 60 mi...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Rahman S,McBride WJ

    更新日期:2000-02-01 00:00:00

  • Determination of serotonin turnover in the rat brain using 6-fluorotryptophan.

    abstract::After intraperitoneal injection of rats with 6-fluorotryptophan (6-FT), brain 5-hydroxytryptamine (5-HT) levels decreased exponentially over 1 h. Depletion was dose-dependent and maximum depletion was observed at 200 mg/kg. 6-FT (200 mg/kg) did not significantly alter the content of 5-hydroxyindoleacetic acid. Turnove...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Miwa S,Fujiwara M,Lee K,Fujiwara M

    更新日期:1987-05-01 00:00:00

  • Low-dose bafilomycin attenuates neuronal cell death associated with autophagy-lysosome pathway dysfunction.

    abstract::We have shown previously that the plecomacrolide antibiotics bafilomycin A1 and B1 significantly attenuate cerebellar granule neuron death resulting from agents that disrupt lysosome function. To further characterize bafilomycin-mediated cytoprotection, we examined its ability to attenuate the death of naïve and diffe...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Pivtoraiko VN,Harrington AJ,Mader BJ,Luker AM,Caldwell GA,Caldwell KA,Roth KA,Shacka JJ

    更新日期:2010-08-01 00:00:00

  • Reevaluation of the role of gangliosides as receptors for tetanus toxin.

    abstract::Binding of tetanus toxin to rat brain membranes was of lower affinity and capacity when binding was determined in 150 mM NaCl, 50 mM Tris-HCl (pH 7.4) than in 25 mM Tris-acetate (pH 6.0). Binding under both conditions was reduced by treating the membranes with neuraminidase. Pronase treatment, however, reduced toxin b...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Critchley DR,Habig WH,Fishman PH

    更新日期:1986-07-01 00:00:00

  • The requirement of Ras and Rap1 for the activation of ERKs by cAMP, PACAP, and KCl in cerebellar granule cells.

    abstract::In cerebellar granule cells, the mitogen-activated protein kinase (MAPK) or extracellular signal-regulated kinase (ERK) cascade mediates multiple functions, including proliferation, differentiation, and survival. In these cells, ERKs are activated by diverse stimuli, including cyclic adenosine monophosphate (cAMP), pi...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Obara Y,Horgan AM,Stork PJ

    更新日期:2007-04-01 00:00:00

  • 3-Nitropropionic acid toxicity in the striatum.

    abstract::We examined the effects of chronic systemic administration of the mitochondrial toxin 3-nitropropionic acid (3-NP) in doses ranging from 12 to 16 mg/kg/day for 30 days on striatal cytoarchitecture in rats. Administration of 3-NP at a dose of 16 mg/kg/day resulted in large lesions with a central necrotic core that was ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Wüllner U,Young AB,Penney JB,Beal MF

    更新日期:1994-11-01 00:00:00

  • Sequential treatment of SH-SY5Y cells with retinoic acid and brain-derived neurotrophic factor gives rise to fully differentiated, neurotrophic factor-dependent, human neuron-like cells.

    abstract::A rapid and simple procedure is presented to obtain nearly pure populations of human neuron-like cells from the SH-SY5Y neuroblastoma cell line. Sequential exposure of SH-SY5Y cells to retinoic acid and brain-derived neurotrophic factor in serum-free medium yields homogeneous populations of cells with neuronal morphol...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Encinas M,Iglesias M,Liu Y,Wang H,Muhaisen A,Ceña V,Gallego C,Comella JX

    更新日期:2000-09-01 00:00:00

  • Cholinergic muscarinic receptors in human fetal brain: ontogeny of [3H]quinuclidinyl benzilate binding sites in corpus striatum, brainstem, and cerebellum.

    abstract::The ontogeny of muscarinic receptors was studied in human fetal striatum, brainstem, and cerebellum to investigate general principles of synaptogenesis as well as the physiological balance between various chemical synapses during development in a given region of the brain. [3H]Quinuclidinyl benzilate ([3H]QNB) binding...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Ravikumar BV,Sastry PS

    更新日期:1985-12-01 00:00:00

  • Competitive inhibition of N-acetylated-alpha-linked acidic dipeptidase activity by N-acetyl-L-aspartyl-beta-linked L-glutamate.

    abstract::The endogenous neuropeptide N-acetyl-L-aspartyl-L-glutamate (NAAG) fulfills several criteria required to be accepted as a neurotransmitter. NAAG inactivation may proceed through enzymatic hydrolysis into N-acetyl-L-aspartate and glutamate by an N-acetylated-alpha-linked acidic dipeptidase (NAALADase). Therefore, some ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Serval V,Barbeito L,Pittaluga A,Cheramy A,Lavielle S,Glowinski J

    更新日期:1990-07-01 00:00:00

  • Sialylation enhances the secretion of neurotoxic amyloid-beta peptides.

    abstract::Alzheimer's disease (AD) is characterized by amyloid-beta peptide (Abeta) deposition in the brain. Abeta is produced by sequential cleavage of amyloid precursor protein (APP) by beta-secretase (BACE1: beta-site APP-cleaving enzyme 1) and gamma-secretase. Previously, we demonstrated that BACE1 also cleaves beta-galacto...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Nakagawa K,Kitazume S,Oka R,Maruyama K,Saido TC,Sato Y,Endo T,Hashimoto Y

    更新日期:2006-02-01 00:00:00

  • Purinergic modulation of hippocampal acetylcholine release involves alpha-dendrotoxin-sensitive potassium channels.

    abstract::Modulation of acetylcholine (ACh) release from superfused hippocampal slices was examined when the release of ACh was stimulated by exposure of slices to elevated K+ concentration. Evoked release was not sensitive to inhibition by 0.1 microM tetrodotoxin, but it could be inhibited in a dose-dependent manner by a musca...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Benishin CG

    更新日期:1990-12-01 00:00:00

  • Swiprosin1/EFhd2 is involved in the monoaminergic and locomotor responses of psychostimulant drugs.

    abstract::Psychostimulants are widely abused drugs that may cause addiction in vulnerable individuals. While the reward circuitry of the brain is involved in addiction establishment, various pathways in the brain may provide protection at the molecular level that limits the acute and chronic effects of drugs. These targets may ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Kogias G,Zheng F,Kalinichenko LS,Kornhuber J,Alzheimer C,Mielenz D,Müller CP

    更新日期:2020-08-01 00:00:00

  • D-Aspartate as a putative cell-cell signaling molecule in the Aplysia californica central nervous system.

    abstract::The content, synthesis and transport of D-aspartate (D-Asp) in the CNS of Aplysia californica is investigated using capillary electrophoresis (CE) with both laser-induced fluorescence and radionuclide detection. Millimolar concentrations of D-Asp are found in various regions of the CNS. In the cerebral ganglion, three...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Miao H,Rubakhin SS,Scanlan CR,Wang L,Sweedler JV

    更新日期:2006-04-01 00:00:00

  • Dopamine and adult neurogenesis.

    abstract::Dopamine is an important neurotransmitter implicated in the regulation of mood, motivation and movement. We have reviewed here recent data suggesting that dopamine, in addition to being a neurotransmitter, also plays a role in the regulation of endogenous neurogenesis in the adult mammalian brain. In addition, we appr...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章,评审


    authors: Borta A,Höglinger GU

    更新日期:2007-02-01 00:00:00

  • Metallothionein-III prevents glutamate and nitric oxide neurotoxicity in primary cultures of cerebellar neurons.

    abstract::Metallothionein (MT)-III, a member of the MT family of metal-binding proteins, is mainly expressed in the CNS and is abundant in glutamatergic neurons. Results in genetically altered mice indicate that MT-III may play neuroprotective roles in the brain, but the mechanisms through which this protein functions have not ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Montoliu C,Monfort P,Carrasco J,Palacios O,Capdevila M,Hidalgo J,Felipo V

    更新日期:2000-07-01 00:00:00

  • Role of neuronal signal input in the down-regulation of central noradrenergic receptor function by antidepressant drugs.

    abstract::Rats with unilateral lesions of the locus coeruleus were used to study the role of norepinephrine (NE) signal input in the down-regulation by antidepressants of the noradrenergic cyclic AMP-generating system in the cortex. Chronic administration of both desipramine (blockade of NE reuptake) and iprindole (no blockade ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Janowsky A,Steranka LR,Gillespie DD,Sulser F

    更新日期:1982-07-01 00:00:00

  • Characterization of binding sites for the angiotensin II antagonist 125I-[Sarc1,Ile8]-angiotensin II on murine neuroblastoma N1E-115 cells.

    abstract::The murine neuroblastoma N1E-115 cell line contains binding sites for the angiotensin II (Ang II) receptor antagonist 125I-[Sarc1,Ile8]-Ang II (125I-SARILE). Binding of 125I-SARILE to N1E-115 membranes was rapid, reversible, and specific for Ang II-related peptides. The rank order potency of 125I-SARILE binding was th...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Fluharty SJ,Reagan LP

    更新日期:1989-05-01 00:00:00