Neural Cell News Volume 10.16 | Apr 27 2016

Sequential Regulatory Loops as Key Gatekeepers for Neuronal Reprogramming in Human Cells
The authors recently elucidated an RNA program mediated by the polypyrimidine tract binding protein PTB to convert mouse embryonic fibroblasts into functional neurons. In human adult fibroblasts (HAFs), however, they unexpectedly found that invoking the documented PTB–REST–miR-124 loop generates only immature neurons. They now report that the functionality requires sequential inactivation of PTB and the PTB paralog nPTB in HAFs. [Nat Neurosci] Abstract

Dysregulation of miRNA-9 in a Subset of Schizophrenia Patient-Derived Neural Progenitor Cells
Researchers observed a strong correlation between microRNA (miR)-9 expression and miR-9 regulatory activity in neural progenitor cells (NPCs) as well as between miR-9 levels/activity, neural migration, and diagnosis. Overexpression of miR-9 was sufficient to ameliorate a previously reported neural migration deficit in schizophrenia NPCs, whereas knockdown partially phenocopied aberrant migration in control NPCs. [Cell Rep] Full Article | Graphical Abstract | Press Release

Alternative Splicing of Neuronal Differentiation Factor TRF2 Regulated by HNRNPH1/H2
Heterogeneous nuclear ribonucleoproteins H1 and H2 (HNRNPH) levels decline while telomere repeat-binding factor 2 (TRF2) protein isoform levels increase during neuronal differentiation. In addition, CRISPR/Cas9-mediated deletion of hnRNPH2 selectively accelerates the NGF-triggered differentiation of rat pheochromocytoma cells into neurons. [Cell Rep] Full Article | Graphical Abstract

p53 Isoforms Regulate Astrocyte-Mediated Neuroprotection and Neurodegeneration
The authors demonstrated that the p53 isoforms Δ133p53 and p53β are expressed in astrocytes and regulate their toxic and protective effects on neurons. Primary human astrocytes undergoing cellular senescence upon serial passaging in vitro showed diminished expression of Δ133p53 and increased p53β, which were attributed to the autophagic degradation and the SRSF3-mediated alternative RNA splicing, respectively. [Cell Death Differ] Abstract

Epigallocatechin Gallate (EGCG) Inhibits Adhesion and Migration of Neural Progenitor Cells In Vitro
Researchers characterized the neurodevelopmental effects of the green tea catechin EGCG, which is now commercialized as high-dose food supplement. They used the “Neurosphere Assay” to study the effects and unravel underlying molecular mechanisms of EGCG treatment on human and rat neural progenitor cells development in vitro. [Arch Toxicol] Abstract

A Biofidelic 3D Culture Model to Study the Development of Brain Cellular Systems
Researchers built a neurobiology platform that consists of fetal rat cerebral cortical cells grown within 3D silk scaffolds. Ivermectin (Ivm), a glycine receptor agonist, was used to modulate cell resting membrane potential according to methods described in a previous work that implicated Ivm in the arrangement and connectivity of cortical cell assemblies. [Sci Rep] Full Article

Optogenetic Control of Human Neurons in Organotypic Brain Cultures
Scientists report the application of optogenetic tools to human brain tissue providing a proof-of-concept for the use of optogenetics in neuromodulation of human cortical and hippocampal neurons as a possible tool to explore network mechanisms and develop future therapeutic strategies. [Sci Rep] Full Article

Protection of Cultured Dopamine Neurons from MPP⁺ Requires a Combination of Neurotrophic Factors
The authors examined the effect of combinations of neurotrophic factors after acute exposure to the toxin 1-methyl-4-phenylpyridinium (MPP⁺) using dissociated postnatal rat midbrain cultures isolated from substantia nigra and ventral tegmental area. [Eur J Neurosci] Abstract

Neural Stem Cells, the Subventricular Zone and Radiotherapy: Implications for Treating Glioblastoma
The authors discuss the connection between neural stem cells and development of glioblastoma, explore the behavior of tumors associated with the subventricular zone, summarize the discordant literature with respect to the effects of irradiation, and review other targeted therapies to this intriguing region. [J Neurooncol] Abstract

Mature Neurons Modulate Neurogenesis through Chemical Signals Acting on Neural Stem Cells
Although the association between organismal behavior and neurogenesis is well documented, much less is known about the cellular and molecular mechanisms by which neurons control stem cell activity. The authors discuss the existing data on this type of regulation from the three best characterized germinal niches in the adult nervous system: the subventricular zone, the hippocampal subgranular zone, and the carotid body. [Dev Growth Differ] Abstract

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Alzheimer’s Association Awards $4.3 Million to Accelerate the Launch of New Drug Treatment Arms in Landmark Prevention Trial
The Alzheimer’s Association announced a new $4.3 million research grant for a new phase of the Dominantly Inherited Alzheimer’s Network Trials Unit (DIAN-TU) known as DIAN-TU Next Generation. [The Alzheimer’s Association] Press Release

Albert Einstein College of Medicine Receives $3.6 Million NIH Grant to Investigate Potential Cause of Alzheimer’s Disease
Luciano D’Adamio, M.D., Ph.D., professor of microbiology & immunology at Albert Einstein College of Medicine, has received a five-year, $3.6-million grant from the National Institutes of Health to continue his research into how amyloid precursor protein is processed in the brain. [Albert Einstein College of Medicine] Press Release

$185 Million Gift Launches UCSF Weill Institute for Neurosciences
In the largest-ever gift to UC San Francisco, the Weill Family Foundation and Joan and Sanford I. “Sandy” Weill have donated $185 million to establish the UCSF Weill Institute for Neurosciences, in an ambitious effort to accelerate the development of new therapies for diseases affecting the brain and nervous system, including psychiatric disorders. [UC San Francisco] Press Release

Regenerating Brain Tissue Brings Hope for a New Treatment against Alzheimer’s and Parkinson’s
Mexican researchers developed a nanogel that enables the growth of new neurons. Working with animal models, they were able to cross the electroencephalic barrier, introduce a nanogel and achieve the growth of neurons within the gel, which shows that it is possible to promote regeneration of brain tissue. [Investigación y Desarrollo (AlphaGalileo)] Press Release

FDA Approves Investigational Device Exemption for RTOG Trial of Novocure’s Optune together with Bevacizumab for Patients with Bevacizumab-Refractory Recurrent Glioblastoma
RTOG Foundation announced that it will conduct a Phase II trial testing the Novocure™ Optune device together with bevacizumab for patients with bevacizumab-refractory recurrent glioblastoma. [RTOG Foundation] Press Release

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Scientist – Human Pluripotent Stem Cell Neural Differentiation (STEMCELL Technologies)

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Faculty Positions – Brain Research (IDG/McGovern Institute for Brain Research at Peking University)

Postdoctoral Fellow – Neuroscience (University of Maryland Baltimore)

Postdoctoral Position – Neuroscience (Washington University in St. Louis)

PhD Studentship – Neuroscience (The Roskamp Institute)

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Principal Investigator Positions – Neuroscience and Neurological Disorders (Institutes of Brain Science Fudan University)

Postdoctoral Fellowship – Stem Cells, Oligodendrogenesis and Remyelination (UC Davis)

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