Volume 7.14 | Apr 10

Neural Cell News 7.14 April 10, 2013
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An Inhibitor of Mutant IDH1 Delays Growth and Promotes Differentiation of Glioma Cells
Scientists examined the role of mutant isocitrate dehydrogenase 1 (IDH1) in fully transformed cells with endogenous IDH1 mutations. A selective R132H-IDH1 inhibitor identified through a high-throughput screen blocked, in a dose-dependent manner, the ability of the mutant enzyme (mIDH1) to produce R-2-hydroxyglutarate (R-2HG). Under conditions of near complete R-2HG inhibition, the mIDH1 inhibitor induced demethylation of histone H3K9me3 and expression of genes associated with gliogenic differentiation. [Science] Abstract | Press Release

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Reactive Glia in the Injured Brain Acquire Stem Cell Properties in Response to Sonic Hedgehog Glia
As a result of brain injury, astrocytes become activated and start to proliferate in the vicinity of the injury site. Recently, researchers demonstrated that these reactive astrocytes, or glia, can form self-renewing and multipotent neurospheres in vitro. In this study they demonstrated that it is only invasive injury, such as stab wounding or cerebral ischemia, and not noninvasive injury conditions, such as chronic amyloidosis or induced neuronal death, that can elicit this increase in plasticity. [Cell Stem Cell]
Abstract | Graphical Abstract

Ablation of the mTORC2 Component Rictor in Brain or Purkinje Cells Affects Size and Neuron Morphology
Investigators describe two mouse lines that are devoid of the mTORC2 component rictor in the entire central nervous system or in Purkinje cells. In both lines neurons were smaller and their morphology and function were strongly affected. [J Cell Biol] Abstract

MAP1B Regulates Microtubule Dynamics by Sequestering EB1/3 in the Cytosol of Developing Neuronal Cells
Scientists showed that MAP1B interacts directly with EB1 and EB3, two core ‘microtubule plus-end tracking proteins’, and sequesters them in the cytosol of developing neuronal cells. [EMBO J] Abstract

Multipotent Stem Cells Isolated from the Adult Mouse Retina Are Capable of Producing Functional Photoreceptor Cells
Scientists have successfully cultured Nestin+Sox2+Pax6+ multipotent retinal stem cells from the adult mouse retina, which are capable of producing functional photoreceptor cells that restore the light response of photoreceptor-deficient rd1 mutant mice following transplantation. [Cell Res] Abstract

Mitotic Spindle Orientation Predicts Outer Radial Glial Cell Generation in Human Neocortex
Investigators showed that human ventricular radial glial cells produce outer radial glial cells and seed formation of the outer subventricular zone via horizontal divisions, which occur more frequently in humans than in rodents. [Nat Commun] Abstract

Tax-Interacting Protein 1 Coordinates the Spatiotemporal Activation of Rho GTPases and Regulates the Infiltrative Growth of Human Glioblastoma
Researchers have identified ARHGEF7, a guanine nucleotide exchange factor for Rho GTPases, as one novel tax-interacting protein (TIP-1)-interacting protein in human glioblastoma cells. They found that the presence of TIP-1 protein is essential to the intracellular redistribution of ARHGEF7 and rhotekin, one Rho effector and the spatiotemporally coordinated activation of Rho GTPases in migrating glioblastoma cells. [Oncogene] Abstract

Inhibition of 12/15-Lipoxygenase by Baicalein Induces Microglia PPARβ/δ: A Potential Therapeutic Role for CNS Autoimmune Disease
Researchers showed that inhibition of 12/15-lipoxygenase by baicalein (BA) significantly attenuated clinical severity of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. Inhibited migration of autoimmune T cells into the central nervous system (CNS) by BA treatment could be attributed to reduced activation of microglia, which was indicated by suppressed phagocytosis, and decreased production of proinflammatory cytokines and chemokines in the CNS. [Cell Death Dis] Full Article

A DR6/p75NTR Complex Is Responsible for β-Amyloid-Induced Cortical Neuron Death
Investigators demonstrated that death receptor 6 (DR6) binds to p75 neurotrophin receptor (p75NTR) and is a component of the p75NTR signaling complex responsible for Aβ (β-amyloid)-induced cortical neuron death. Cortical neurons isolated from either DR6 or p75NTR null mice are resistant to Aβ-induced neurotoxicity. [Cell Death Dis] Full Article

A Hydroxylated Metabolite of Flame-Retardant PBDE-47 Decreases the Survival, Proliferation and Neuronal Differentiation of Primary Cultured Adult Neural Stem Cells and Interferes with Signaling of ERK5 MAP Kinase and Neurotrophin 3
Researchers examined the toxicity of polybrominated diphenyl ethers (PBDEs) for primary adult neural stem/progenitor cells (aNSCs) isolated from the subventricular zone of adult mice. They discovered that 6-OH-PBDE-47, but not its parent compound PBDE-47, is cytotoxic for aNCSs using MTS metabolism and cell number as a measure of cytotoxicity. [Toxicol Sci] Abstract

U-Shape Suppressive Effect of Phenol Red on the Epileptiform Burst Activity via Activation of Estrogen Receptors in Primary Hippocampal Culture
By using patch clamp technique, scientists demonstrated that hippocampal pyramidal neurons cultured in neurobasal medium containing no phenol red had large depolarization-associated epileptiform bursting activities, which were rarely seen in neurons cultured in phenol red-containing medium. [PLoS One]
Full Article

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Cell-Based Therapeutics: The Next Pillar of Medicine

Two decades ago, the pharmaceutical industry – long dominated by small-molecule drugs – was revolutionized by the the advent of biologics. Today, biomedicine sits on the cusp of a new revolution: the use of microbial and human cells as versatile therapeutic engines. Researchers discuss the promise of this “third pillar” of therapeutics in the context of current scientific, regulatory, economic, and perceptual challenges. [Sci Transl Med] Abstract | Press Release

Visit our reviews page to see a complete list of reviews in the neuroscience field.

Researchers to Develop Next Generation Immunotherapy for Children with Deadly Solid Tumors
Researchers at the Children’s Hospital of Philadelphia, the University of Pennsylvania, and the Primary Children’s Medical Center of Salt Lake City received a $550,000 collaborative grant to test next generation T-cell immunotherapy strategies in children with neuroblastoma. [Solving Kids’ Cancer] Press Release

Neuralstem Receives Notice of Allowance of Patent Covering Use of Stem Cells to Treat Amyotrophic Lateral Sclerosis
Neuralstem, Inc. announced that it received a notice of allowance for patent application 12/404,841. This patent covers methods for treating amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease) with expanded spinal cord stem cells, including NSI-566. Neuralstem completed a Phase I safety trial of its NSI-566 stem cells in ALS earlier this year, for which it has also been granted an Orphan Drug Designation. [Neuralstem, Inc.] Press Release

UCSF Neurologist Wins Top International Prize for Multiple Sclerosis Research
The Multiple Sclerosis International Federation has named UC San Francisco neurologist Stephen L. Hauser, MD, the winner of its 2013 Charcot award, the top international prize for multiple sclerosis research. [University of California San Francisco]
Press Release

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As White House Embraces BRAIN Initiative, Questions Linger
For neuroscientist Rafael Yuste, sitting in an ornate White House chamber listening to President Barack Obama heap praise – and some $100 million – on a brain-mapping initiative that he helped hatch was a “luminous” experience. For all the lofty rhetoric, however, the White House didn’t provide many details about how the BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative will accomplish its mission. [White House, United States] Press Release

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European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

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NEW Cold Spring Harbor: Ion Channels & Synaptic Transmission
May 5-25, 2013
Cold Spring Harbor, United States

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Postdoctoral Position – Neurobiology (Weizmann Institute of Science)

Postdoctoral Fellow – Neural Stem Cells and Neurogenesis (UT Southwestern Medical Center)

Postdoctoral Position – Adult Neurogenesis and Neural Survival Signaling (University of Kentucky)

Postdoctoral Fellow – Regulation of Gliomagenesis (UT Southwestern Medical Center at Dallas)

PhD Opportunity (University of East Anglia)

Director – Centre of Developmental Neurobiology (King’s College London)

Doctoral Studentship – Neural Cell Physiology (CNR-ISMN)

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