Neural Cell News Volume 13.18 | May 15 2019

TOP STORY

Adult-Born Hippocampal Neurons Bidirectionally Modulate Entorhinal Inputs into the Dentate Gyrus

Scientists found that the actions of adult-born granule cells (abGCs) in the dentate gyrus depended on the origin of incoming afferents. In response to lateral entorhinal cortex inputs, abGCs exerted monosynaptic inhibition of mature granule cells through group II metabotropic glutamate receptors. [Science] Abstract | Editorial

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Pervasive H3K27 Acetylation Leads to ERV Expression and a Therapeutic Vulnerability in H3K27M Gliomas

High-grade gliomas defined by histone 3 K27M driver mutations exhibit global loss of H3K27 trimethylation and reciprocal gain of H3K27 acetylation (H3K27ac), respectively shaping repressive and active chromatin landscapes. Investigators generated tumor-derived isogenic models bearing this mutation and showed that it led to pervasive H3K27ac deposition across the genome. [Cancer Cell] Abstract | Graphical Abstract

TUBG1 Missense Variants Underlying Cortical Malformations Disrupt Neuronal Locomotion and Microtubule Dynamics but Not Neurogenesis

Researchers showed that TUBG1 mutants affected neuronal positioning, disrupting the locomotion of new-born neurons but without affecting progenitors’ proliferation. They further demonstrated that pathogenic TUBG1 variants were linked to reduced microtubule dynamics but without major structural nor functional centrosome defects in subject-derived fibroblasts. [Nat Commun] Full Article

Targeted Removal of Epigenetic Barriers during Transcriptional Reprogramming

The authors showed that the targeting of dCas9-VP64 to the promoter of the master transcription factor Sox1 resulted in strong transcript and protein up-regulation in neural progenitor cells. This gene activation restored lost neuronal differentiation potential, which substantiated the role of Sox1 as a master transcription factor. [Nat Commun] Full Article

Chromatin Remodeler Ep400 Ensures Oligodendrocyte Survival and Is Required for Myelination in the Vertebrate Central Nervous System

Mechanistically, Ep400 interacted with transcription factor Sox10, bound to regulatory regions of the Myrf gene and was required to induce this central transcriptional regulator of the myelination program. In addition to reduced and aberrant myelin formation, oligodendrocytes exhibited increased DNA damage and apoptosis so that numbers never reached wildtype levels during the short lifespan of Ep400-deficient mice. [Nucleic Acids Res] Abstract

Sphingosine-1-Phosphate Receptor 1 Activation in Astrocytes Contributes to Neuropathic Pain

Scientists provide evidence that sphingosine-1-phosphate (S1P) generated in the dorsal horn of the spinal cord in response to nerve injury drives neuropathic pain by selectively activating the S1P receptor subtype 1 in astrocytes. [Proc Natl Acad Sci USA] Abstract

oHSV Therapy Increases Trametinib Access to Brain Tumors and Sensitizes Them In Vivo

Infected glioma cells co-cultured with microglia or macrophages treated with or without trametinib were used to test trametinib effect on macrophages/microglia. ELISA, western blotting, and flow cytometry were utilized to evaluate the effect of the combination therapy. [Neuro Oncol] Abstract

Membrane Voltage Is a Direct Feedback Signal That Influences Correlated Ion Channel Expression in Neurons

Investigators isolated an identifiable neuron in crustaceans and then either kept this neuron silent or used a long-term voltage clamp protocol to artificially maintain activity. They found that physiological voltage activity-independent of all known forms of synaptic and neuromodulatory feedback-maintained most channel mRNA relationships, while metabotropic influences may play a relatively smaller role. [Curr Biol] Full Article | Press Release

Modeling Motor Neuron Resilience in ALS Using Stem Cells

Researchers demonstrated that in vitro-generated neurons are bona fide oculomotor neurons based on their cellular properties and similarity to their in vivo counterpart in rodent and man. They also showed that in vitro-generated oculomotor neurons displayed a robust activation of survival-promoting Akt signaling and were more resilient to the ALS-like toxicity of kainic acid than spinal motor neurons. [Stem Cell Reports] Full Article | Press Release

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Excitation-Inhibition Balance as a Framework for Investigating Mechanisms in Neuropsychiatric Disorders

The authors clarify the concept of excitatory-inhibitory balance, and update the original hypothesis in light of the field’s increasingly sophisticated understanding of neuronal circuits. They discuss how specific developmental mechanisms, which reduce inhibition, affect cortical and hippocampal functions. [Mol Psychiatry] Abstract

Visit our reviews page to see a complete list of reviews in the neural cell research field.

Novocure Announces 13 Presentations and a Symposium on Tumor Treating Fields

Novocure announced 13 presentations and a symposium on tumor treating fields. Of the presentations, six are oral presentations and seven are posters. [Press release from Novocure (Business Wire, Inc.) discussing research presented at the 70^th Annual Meeting of the German Society of Neurosurgery (DGNC), Würzburg] Press Release

Abbott Partners with NIH on BRAIN Initiative to Advance Research for Neurological Disorders

Abbott announced that it has partnered with the National Institutes of Health (NIH) on the BRAIN (Brain Research through Advancing Innovative Neurotechnologies) initiative to accelerate advancements in neuroscience research. [Abbott] Press Release

Jefferson and Wills Eye Launch World’s First Center Focused on Connections between the Eye and the Brain

Thomas Jefferson University, in partnership with Wills Eye Hospital and thanks to the generosity of several prescient philanthropists, has launched the world’s first center focused on the visual signatures of neurological diseases. [Wills Eye Hospital] Press Release

Principia Biopharma Announces First Patient Dosed in Sanofi’s Phase IIb Trial of SAR442168 in Multiple Sclerosis, Triggering $30 Million Milestone

Principia Biopharma Inc. announced that the first patient has been dosed in its partner Sanofi’s Phase IIb clinical trial of SAR442168 in patients with relapsing multiple sclerosis, triggering a $30 million milestone payment to Principia. [Principia Biopharma Inc.] Press Release

Alzheimer’s Clinical Trials Consortium Selects Elenbecestat and BAN2401 for Upcoming Clinical Studies on Prevention of Alzheimer’s Disease

The Alzheimer’s Clinical Trials Consortium (ACTC) and Eisai Co., Ltd. announced that the investigational oral beta amyloid cleaving enzyme inhibitor elenbecestat and the investigational anti-amyloid beta protofibril antibody BAN2401, which are currently being evaluated as treatments for early Alzheimer’s disease (AD), have been selected by the ACTC as treatments to be evaluated in upcoming clinical studies targeting primary prevention and secondary prevention of AD. [Eisai Co., Ltd.] Press Release

Ben-Gurion University Introduces Novel Combination Therapy for Treating Neurological Disorders

BGN Technologies introduced a novel drug combination therapy, based on two FDA approved drugs, for protecting the blood-brain-barrier, and therefore preventing the development of various neurological diseases that are affected by brain vasculature pathologies. [BGN Technologies Ltd.] Press Release

Sunovion and Psychogenics Announce That SEP-363856 Has Received FDA Breakthrough Therapy Designation for the Treatment of People with Schizophrenia

Sunovion Pharmaceuticals Inc. and PsychoGenics Inc. announced that the FDA has granted Breakthrough Therapy Designation for SEP-363856, a novel agent for the treatment of people with schizophrenia. With this Breakthrough Therapy Designation SEP-363856 is eligible for intensive guidance from the FDA on the drug development program and priority review. [Sunovion Pharmaceuticals Inc.] Press Release

Biogen’s SPINRAZA^® (Nusinersen) Receives Positive Recommendation from NICE for Funding in the United Kingdom for the Treatment of Infants, Children and Adults with Spinal Muscular Atrophy

Biogen Inc. announced that The National Institute for Health and Care Excellence (NICE) in the United Kingdom has recommended funding for SPINRAZA on the National Health Service. The positive recommendation is for the treatment of infants, children and adults with 5q spinal muscular atrophy, including pre-symptomatic and symptomatic SMA Types 1, 2 and 3. [Biogen Inc.] Press Release

Lixte Biotechnology’s LB-100 to Be Evaluated by the National Cancer Institute in a Clinical Study of LB-100’s Ability to Enter Recurrent Glioblastoma Multiforme Brain Tumors

Lixte Biotechnology Holdings, Inc. announced the opening of a pharmacologic study of the ability of its lead clinical compound, LB-100, to enter the brain and penetrate recurrent glioblastoma multiforme tumors in patients in which surgical removal of their cancers is indicated. [Lixte Biotechnology Holdings, Inc.] Press Release

NeuroVive’s IND for Clinical Development of NeuroSTAT Approved by FDA

NeuroVive Pharmaceutical AB announced that the FDA has approved NeuroVive’s Investigational New Drug (IND) application, enabling clinical studies in the US with the company’s drug candidate NeuroSTAT in development for treatment of moderate to severe traumatic brain injury. [NeuroVive Pharmaceutical AB] Press Release

McLean Receives $13.5 Million NIMH Grant for Translational Stress Research

The National Institute of Mental Health (NIMH) has awarded a $13.5 million grant to a team of McLean Hospital investigators to support their research into stress chemicals and circuits in the brain. Through the center, researchers will examine “stress peptides,” which are brain chemicals that regulate the body’s responses to stress. [McLean Hospital (American Association for the Advancement of Science)] Press Release

Muscular Dystrophy Association Awards 26 Grants Totaling More than $7.5 Million for Neuromuscular Disease Research

This round of grant funding reinforces the Muscular Dystrophy Association’s (MDA’s) unwavering commitment to the progress of neuromuscular disease research and builds on the more than $1 billion MDA has already invested in research to uncover new treatments and cures for neuromuscular diseases since its inception. [The Muscular Dystrophy Association] Press Release

Auris Medical Announces Closing of Two US Patent Acquisitions Related to the Use of Betahistine for the Treatment of Depression and ADHD

Auris Medical Holding Ltd. announced the successful closing of the purchase of two US patents related to the use of betahistine for the treatment of depression and attention-deficit/hyperactivity disorder (ADHD). [Auris Medical Holding Ltd.] Press Release

Medicare Issues Proposed Local Coverage Determination That Provides Coverage of Optune^® for Newly Diagnosed Glioblastoma

Novocure announced the Medicare durable medical equipment Medicare Administrative Contractors have issued a proposed local coverage determination that provides coverage of tumor treating fields, or Optune, for newly diagnosed glioblastoma. [Novocure] Press Release

Singapore Passes ‘Fake News’ Law Following Researcher Outcry

Singapore’s parliament has passed a law that bans the spreading of “a false statement of fact” that harms the public interest. Researchers and human-rights groups opposed the regulation, and warn that it will stifle academic debate. [Nature News] Editorial

New EU Research Funding Head Stresses ‘Superdisciplinarity’

Nanomedicine pioneer Mauro Ferrari will be the next president of the European Research Council, the funding organization announced. He will come to the job in Brussels with limited European policy experience, after almost 40 years in the United States, where he worked at the University of California; the National Cancer Institute in Bethesda; and the Houston Methodist Research Institute in Texas. [ScienceInsider] Editorial

NEW Gordon Research Conference: Amyotrophic Lateral Sclerosis (ALS) & Related Motor Neuron Diseases
July 21-26, 2019
West Dover, Vermont, United States

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Positions – Neuroscience (Weill Cornell Medical College)

NEW Lecturer – Neuroscience (University College London)

Postdoctoral Fellow – Ion Channel & Neuroscience Research (Johns Hopkins University)

Postdoctoral Fellow/Research Assistant Positions – Glioma Research (NIH National Cancer Institute Laboratory of Pathology)

Postdoctoral Positions – Astrocyte Research (Washington University in St.Louis)

Postdoctoral Research Scientist – Systems Neuroscience (University of Oxford)

Postdoctoral Position – Retinal Stem Cell Biology (Johns Hopkins University)

Postdoctoral Fellow – Alcohol & Adult Neurogenesis (The University of Texas at Austin)

Postdoctoral Researcher – Neurobiology (University of Rochester)

Staff Scientist – Molecular & Behavioral Neuroscience (Fred Hutchinson Cancer Research Center)

Postdoctoral Research Associate – Neurological Diseases (University of Utah)

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