Intense proteolysis of cytoskeletal proteins occurs in brain within minutes transient ischemia, possibly because the activation calcium-sensitive proteases (calpains). This proteolytic event precedes overt signs neuronal degeneration, is most pronounced regions selective vulnerability, and could have significant consequences for integrity cellular function. The present studies demonstrate that (i) early phase enhanced a direct response to hypoxia rather than other actions (ii) it possible...

Pharmacological activation of the GABA B receptor with arbaclofen in a mouse model fragile X syndrome corrects neuronal defects associated disease.

This study investigated whether positive modulators of AMPA-type glutamate receptors influence neurotrophin expression by forebrain neurons. Treatments with the ampakine CX614 markedly and reversibly increased brain-derived neurotrophic factor (BDNF) mRNA protein levels in cultured rat entorhinal/hippocampal slices. Acute effects were dose dependent over range which drug synchronous neuronal discharges; threshold concentrations for acute responses had large on content when applied 3 d....

Protein synthesis in neurons is essential for the consolidation of memory and stabilization activity-dependent forms synaptic plasticity such as long-term potentiation (LTP). Activity-dependent translation dendritically localized mRNAs has been proposed to be a critical source new proteins necessary change. mRNA activity-regulated cytoskeletal protein, Arc, transcribed during LTP learning, disruption its gives rise deficits both. We have found that selective Arc synaptoneurosomal preparation...

The expression of Rbm3, a glycine-rich RNA-binding protein, is enhanced under conditions mild hypothermia, and Rbm3 has been postulated to facilitate protein synthesis at colder temperatures. To investigate this possibility, was overexpressed as c-Myc fusion in mouse neuroblastoma N2a cells. Cells expressing showed 3-fold increase both 37°C 32°C compared with control Although polysome profiles cells the were similar, several differences noted, suggesting that might enhance association 40S...

Changes in the morphology of dendritic spines are correlated with synaptic plasticity and may relate mechanistically to its expression stabilization. Recent work has shown that spine length can be altered by manipulations affect intracellular calcium, is abnormal genetic conditions affecting protein synthesis neurons. We have investigated how ligands group 1 metabotropic glutamate receptors (mGluRs) shape; stimulation these leads both calcium release from stores synthesis. Thirty-minute...

Fragile X syndrome (FXS) is a common inherited form of mental retardation that caused, in the vast majority cases, by transcriptional silencing single gene, fmr1 . The encoded protein, FMRP, regulates mRNA translation neuronal dendrites, and it thought changes translation-dependent forms synaptic plasticity lead to many symptoms FXS. However, little known about potentially extensive protein content accompany loss FMRP. Here, we describe development high-throughput quantitative proteomic...

Excitatory synaptic activity can evoke transient and substantial elevations of postsynaptic calcium. Downstream effects elevated calcium include the activation calcium-dependent protease calpain. We have developed a reagent that identifies dendritic spines in which calpain has been activated. A fusion protein was expressed contained enhanced yellow cyan fluorescent (EYFP ECFP, respectively) linked by peptide included μ-calpain cleavage site from α-spectrin. PDZ-binding fused to ECFP anchored...

Fragile X syndrome results from the transcriptional silencing of a gene, Fmr1 , that codes for an mRNA-binding protein (fragile mental retardation protein, FMRP) present in neuronal dendrites. FMRP can act as translational suppressor, and its own translation dendrites is regulated by group I metabotropic glutamate receptors (mGluRs). Multiple lines evidence suggest mGluR-induced exaggerated because lack inhibition normally provided FMRP. We characterized role regulation mRNA granules, which...

SLICES of hippocampus were incubated with Arg–Gly–Asp (RGD) peptides known to block members the Sntegrin class matrix receptors. Though caused no detectable difference in amount long–term potentiation (LTP) expressed CA1 field 1–2 min after induction high frequency stimulation, they did produce a reversible, dose dependent decay LTP over period 40 min. This effect was not obtained various non-RGD control peptides. These results suggest that stabilization requires adhesive interactions via...

Aberrant elevations in intracellular calcium levels, promoted by the excitatory amino acid glutamate, may be a final common mediator of neuronal damage that occurs hypoxic-ischemic and seizure disorders. Glutamate altered homeostasis have also been proposed to play roles more chronic neurodegenerative disorders, including Alzheimer's disease. Any extrinsic factors augment levels during such disorders significantly exacerbate resulting damage. Glucocorticoids (GCs), adrenal steroid hormones...

The brain-derived neurotrophic factor (BDNF) plays an important role in neuronal development, and the formation plasticity of synaptic connections. These effects BDNF are at least partially due to ability neurotrophin increase protein synthesis both globally locally. However, only a few proteins have been shown be up-regulated synapse by BDNF. Using multidimensional identification technology (MudPIT) relative quantification spectra counting, we found that several hundred synaptoneurosome...

Significance Fragile X syndrome (FXS) is a frequent mental disorder characterized by intellectual disability and other symptoms including autism. The disease gene-encoded protein FMRP regulates activity-dependent translation of large number mRNAs in neurons. We used quantitative mass spectrometry to systematically compare expression neocortical synaptic fractions between Fmr1 (fragile retardation 1) knockout (KO) wild-type mice during adolescence adulthood. discovered an upregulation...

Fragile X syndrome is produced by a defect in single X-linked gene, called Fmr1, and characterized abnormal dendritic spine morphologies with spines that are longer thinner neocortex than those from age-matched controls. Studies using Fmr1 knockout mice indicate abnormalities especially pronounced the first month of life, suggesting altered developmental plasticity underlies some behavioral phenotypes associated syndrome. To address this issue, we used intracellular recordings neocortical...

Abstract A diverse set of mRNA‐binding proteins (BPs) regulate local translation in neurons. However, little is known about the role(s) played by a family cold‐inducible, glycine‐rich mRNA‐BPs. Unlike neuronal mRNA‐BPs characterized thus far, these are induced hypothermia and comprised one RNA recognition motif an adjacent arginine‐ domain. We studied expression function RNA‐binding protein 3 (RBM3), member this family, RBM3 was expressed multiple brain regions, with highest levels...

MicroRNAs (miRNAs) play critical roles in diverse cellular events through their effects on translation. Emerging data suggest that modulation of miRNA biogenesis at post-transcriptional steps by RNA-binding proteins is a key point regulatory control over the expression some miRNAs and processes they influence. However, extent conditions under which pathway amenable to regulation posttranscriptional are poorly understood. Here we show RBM3, cold-inducible, developmentally regulated protein...

In many cell types, translation can be regulated by a redistribution of initiation factors to actin-based cytoskeletal compartments that contain bound mRNAs. This process is evoked extracellular signals and determinants organization, such as integrins. the present experiments, we provide evidence similar mechanisms regulate local in dendrites during synaptic plasticity. Treatment various neuronal preparations with brain-derived neurotrophic factor (BDNF) resulted critical eukaryotic 4E...

Abstract Cultured hippocampal slices retain many in vivo features with regard to circuitry, synaptic plasticity, and pathological responsiveness, while remaining accessible a variety of experimental manipulations. The present study used ligand binding, immunostaining, situ hybridization assays determine the stability AMPA‐ NMDA‐type glutamate receptors other proteins slice cultures obtained from 11 day postnatal rats maintained culture for at least 4 weeks. Binding receptor ligands [ 3...

Cold-inducible RNA-binding protein (RBM3) is suggested to be involved in the regulation of skeletal muscle mass. Cell death pathways are implicated loss mass and therefore role RBM3 apoptosis C 2 12 myoblasts was investigated this study. overexpression induced by either cold shock (32°C exposure for 6 h) or transient transfection with a myc-tagged expression vector. H O (1,000 μM) staurosporine (StSp, 5 μM), it shown that were associated attenuation morphological changes an increase cell...