Neural Cell News Volume 6.45 | Nov 14 2012

Pathogenic SYNGAP1 Mutations Impair Cognitive Development by Disrupting Maturation of Dendritic Spine Synapses
In the SYNGAP1 mouse model of intellectual disability and autism spectrum disorder, researchers found that dendritic spine synapses develop prematurely during the early postnatal period. Premature spine maturation dramatically enhanced excitability in the developing hippocampus, which corresponded with the emergence of behavioral abnormalities. [Cell] Abstract | Press Release | Graphical Abstract

A Chemical Genetic Approach Reveals Distinct EphB Signaling Mechanisms during Brain Development
The authors engineered triple knock-in mice in which the kinase activity of three neuronally expressed EphBs can be rapidly, reversibly and specifically blocked. They found that the tyrosine kinase activity of EphBs was required for axon guidance in vivo. In contrast, EphB-mediated synaptogenesis occurred normally when the kinase activity of EphBs was inhibited, suggesting that EphBs mediate synapse development by an EphB tyrosine kinase-independent mechanism. [Nat Neurosci] Abstract

Neuroligin-1-Dependent Competition Regulates Cortical Synaptogenesis and Synapse Number
Scientists found that neuroligin-1 (NL1), which is located at excitatory postsynaptic densities, regulates activity-dependent synaptogenesis and mature synapse number on cortical layer 2/3 pyramidal neurons in vivo. However, synapse number was not sensitive to absolute NL1 levels but instead depended on transcellular differences in the relative amounts of NL1. [Nat Neurosci] Abstract

Bidirectional Influence of Sodium Channel Activation on NMDA Receptor-Dependent Cerebrocortical Neuron Structural Plasticity
Researchers demonstrated that brevetoxin-2 (PbTx-2) mimics activity-dependent neuronal structural plasticity in cerebrocortical neurons through an increase in intracellular sodium, up-regulation of N-methyl-d-aspartate (NMDA) receptor function, and engagement of downstream Ca²⁺-dependent signaling pathways. [Proc Natl Acad Sci USA] Abstract | Press Release

Differential Sulfation Remodelling of Heparan Sulfate by Extracellular 6-O-Sulfatases Regulates Fibroblast Growth Factor-Induced Boundary Formation by Glial Cells: Implications for Glial Cell Transplantation
Previously, it has been shown that rat Schwann cells (SCs), but not olfactory ensheathing cells, form a boundary with astrocytes, due to a SC-specific secreted factor. In this study, researchers identified highly sulfated heparan sulfates and fibroblast growth factors 1 and 9 as possible determinants of boundary formation induced by rat SCs. [J Neurosci] Abstract | Press Release

BMP4 Sufficiency to Induce Choroid Plexus Epithelial Fate from Embryonic Stem Cell-Derived Neuroepithelial Progenitors
During development, choroid plexus epithelial cells (CPECs) differentiate from preneurogenic neuroepithelial cells and require bone morphogenetic protein (BMP) signaling, but whether BMPs suffice for CPEC induction is unknown. In this report, researchers provide evidence for BMP4 sufficiency to induce CPEC fate from neural progenitors derived from mouse embryonic stem cells. [J Neurosci] Abstract | Press Release

In Vitro Localization of Human Neural Stem Cell Neurogenesis by Engineered FGF-2 Gradients
Researchers adapted a microfluidic approach for creating stable concentration gradients in 3D hydrogels to explore whether fibroblast growth factor 2 (FGF-2) gradients can establish defined regions of proliferation and neurogenesis in human neural stem cell (hNSC) cultures. Exponential but not linear FGF-2 gradients between 0-2 ng mL⁻¹ were able to preferentially boost the percentage of TuJ1⁺ neurons in the low concentration regions of the gradient and at levels significantly higher than in non-gradient controls. However, no gradient-dependent localization was observed for dividing hNSCs or hNSC-derived intermediate progenitors. [Integr Biol (Camb)] Abstract

Stem Cell Therapy: Social Recognition Recovery in a FASD Model
To better understand the cellular pathogenetic mechanisms of fetal alcohol spectrum disorder (FASD) and the therapeutic benefit of stem cell treatment, researchers exposed pregnant rats to ethanol followed by intravenous administration of neural stem cells complexed with atelocollagen to the new born rats and studied recovery of GABAergic interneuron numbers and synaptic protein density in the anterior cingulate cortex, hippocampus and amygdala. [Transl Psychiatry] Full Article

Maturation-Promoting Activity of SATB1 in MGE-Derived Cortical Interneurons
The authors provide evidence that the nuclear matrix and genome organizer protein SATB1 is induced by neuronal activity and functions downstream of Lhx6 to control the transition of tangentially migrating immature interneurons into the terminally differentiated Somatostatin-expressing subtype. [Cell Rep] Abstract

Amorfix Research and Development Programs Leading the Way for New Therapeutics For ALS
Amorfix Life Sciences Ltd. announced that anti-SOD1 antibodies developed by the company are being used by a leading academic scientist, Dr. Serge Przedborski at Columbia University, to investigate the pathogenesis and mechanisms of disease progression in ALS. [Amorfix Life Sciences, Ltd.] Press Release

Amarantus BioSciences Appoints Amgen Co-Founder Dr. Joseph Rubinfeld to Advisory Board
Amarantus BioSciences, Inc., a biotechnology company developing new treatments and diagnostics for Parkinson’s disease and Traumatic Brain Injury centered on its proprietary anti-apoptosis therapeutic protein MANF, announced that it has appointed Amgen Co-Founder Joseph Rubinfeld, PhD to its Corporate Advisory Board. [Amarantus BioSciences, Inc.] Press Release

Nuron Biotech Completes Enrollment of a Pivotal Phase III Study for Proprietary Recombinant Human Interferon Beta-1b (NU100) in Relapsing Remitting Multiple Sclerosis
Nuron Biotech Inc. announced the completion of enrollment in its randomized, double-blind, placebo-controlled, parallel-group, pivotal Phase III study to evaluate the safety and efficacy of NU100 for the treatment of relapsing remitting multiple sclerosis. [Nuron Biotech, Inc.] Press Release

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