Neural Cell News Volume 13.14 | Apr 17 2019

TOP STORY

Single-Cell Transcriptomics Uncovers Glial Progenitor Diversity and Cell Fate Determinants during Development and Gliomagenesis

By applying lineage-targeted single-cell transcriptomics, scientists uncovered an unanticipated diversity of glial progenitor pools with unique molecular identities in the developing brain. Their analysis identified distinct transitional intermediate states and their divergent developmental trajectories in astroglial and oligodendroglial lineages. [Cell Stem Cell] Abstract | Press Release | Graphical Abstract

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Aberrant Oligodendroglial-Vascular Interactions Disrupt the Blood-Brain Barrier, Triggering CNS Inflammation

Perivascular oligodendrocyte precursor cells could themselves disrupt the blood-brain barrier, interfering with astrocyte endfeet and endothelial tight junction integrity, resulting in altered vascular permeability and an associated CNS inflammation. [Nat Neurosci] Abstract

Binding of α-Synuclein Oligomers to Cx32 Facilitates Protein Uptake and Transfer in Neurons and Oligodendrocytes

In vitro, researchers demonstrated a clear correlation between connexin-32 (Cx32) expression and alpha-synuclein oligomeric assemblies (oα-syn) uptake. Pharmacological and genetic strategies targeting Cx32 successfully blocked oα-syn uptake. In cellular and transgenic mice modeling Parkinson’s disease and multiple system atrophy, they observed significant upregulation of Cx32 which correlated with α-syn accumulation. [Acta Neuropathol] Full Article

FUS Pathology in ALS Is Linked to Alterations in Multiple ALS-Associated Proteins and Rescued by Drugs Stimulating Autophagy

Scientists used a combination of ALS patient autopsy tissue and induced pluripotent stem cell-derived neurons to study the effects of FUS mutations on RNA-binding protein (RBP) homeostasis. They showed that FUS’ tendency to aggregate was normally buffered by interacting RBPs, but this buffering was lost when FUS mislocalized to the cytoplasm due to ALS mutations. [Acta Neuropathol] Full Article

Glutamate-Releasing SWELL1 Channel in Astrocytes Modulates Synaptic Transmission and Promotes Brain Damage in Stroke

The authors report non-vesicular release of glutamate through the glutamate-permeable volume-regulated anion channel (VRAC). Both cell swelling and receptor stimulation activated astrocytic VRAC, which requires its only obligatory subunit, Swell1. Astrocyte-specific Swell1 knockout mice exhibited impaired glutamatergic transmission due to the decreases in presynaptic release probability and ambient glutamate level. [Neuron] Abstract | Graphical Abstract

TET3 Prevents Terminal Differentiation of Adult NSCs by a Non-Catalytic Action at Snrpn

Investigators showed that a non-catalytic action of ten-eleven-translocation (TET)3 was essentially required for the maintenance of the neural stem cell (NSC) pool in the adult subventricular zone niche by preventing premature differentiation of NSCs into non-neurogenic astrocytes. [Nat Commun] Full Article

Stem Cell-Associated Heterogeneity in Glioblastoma Results from Intrinsic Tumor Plasticity Shaped by the Microenvironment

Scientists report that cells expressing cancer stem cell-associated cell membrane markers in glioblastoma do not represent a clonal entity defined by distinct functional properties and transcriptomic profiles, but rather a plastic state that most cancer cells can adopt. [Nat Commun] Full Article

Familial Alzheimer’s Disease Patient-Derived Neurons Reveal Distinct Mutation-Specific Effects on Amyloid Beta

Using five control induced pluripotent stem cell (iPSC) lines and seven iPSC lines generated from familial Alzheimer’s disease patients, researchers investigated the effects of mutations on the amyloid-β secretome in human neurons generated in 2D and 3D. They also analyzed matched CSF, post-mortem brain tissue, and iPSCs from the same participant with the amyloid precursor protein V717I mutation. [Mol Psychiatry] Abstract

Mitigation of Cocaine-Mediated Mitochondrial Damage, Defective Mitophagy and Microglial Activation by Superoxide Dismutase Mimetics

Exposure of microglia to cocaine resulted in increased expression of DNM1L and OPTN with a concomitant decrease in the rate of mitochondrial oxygen consumption as well as impaired mitochondrial functioning. Additionally, in the presence of cocaine, microglia also exhibited upregulated expression of autophagosome markers, BECN1, MAP1LC3B-II, and SQSTM1. [Autophagy] Abstract

Somatic Autophagy of Axonal Mitochondria in Ischemic Neurons

Axonal mitochondria elimination was not abolished in Atg7^fl/fl;nes-Cre neurons, suggesting the absence of direct mitophagy in axons. Instead, axonal mitochondria were enwrapped by autophagosomes in soma and axon-derived mitochondria prioritized for elimination by autophagy. [J Cell Biol] Abstract

Overlapping Activities of Two Neuronal Splicing Factors Switch the GABA Effect from Excitatory to Inhibitory by Regulating REST

Investigators showed that SRRM3 limited the Srrm4 mutation-associated defects to the ear and that, in cortical neurons, overlapping SRRM3-SRRM4 activity regulated the development of interneuronal inhibition. In vitro, SRRM3 and SRRM4 regulated the same splicing events, but a mutation in mouse Srrm3 caused tremors and mild defects in neuronal alternative splicing, demonstrating unique SRRM3 roles in vivo. [Cell Rep] Full Article | Graphical Abstract

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Immunoneuropsychiatry — Novel Perspectives on Brain Disorders

The authors highlight outstanding findings that have transformed the understanding of neuropsychiatric diseases and to suggest new diagnostic and therapeutic criteria for the emerging field of immunoneuropsychiatry. [Nat Rev Neurol] Abstract

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Presentation of New Masitinib Preclinical Data in ALS

AB Science SA presented new preclinical data for masitinib in amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease. Findings have revealed for the first time a mechanism of neurogenic inflammation in an animal model ALS that can be effectively targeted by masitinib. [Press release from AB Science SA discussing research presented at the 2019 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, Orlando] Press Release

SB623 Demonstrated Statistically Significant Improvement in Motor Function among Patients with Chronic Motor Deficit from Traumatic Brain Injury (TBI)

The SanBio Group announced that SB623 met its primary endpoint, with patients treated with SB623 achieving an average 8.7 point improvement from baseline in the FMMS, versus 2.4 in the control group, at 24 weeks, in a Phase II trial of patients with chronic motor deficit from TBI. [Press release from SanBio Co, Ltd. discussing research presented at the American Association of Neurological Surgeons (AANS) Annual Scientific Meeting, San Diego] Press Release

Cortexyme Announces Phase II/III Clinical Trial Based on Transformational Understanding of Alzheimer’s Disease Now Open for Enrollment

Cortexyme, Inc. announced the launch of the GAIN Trial, an international Phase II/III clinical study of the company’s lead investigational medicine, COR388, in subjects with mild to moderate Alzheimer’s disease. A first wave of US trial sites are now screening patients for participation, and additional trial centers in the US and Europe are expected to be open for enrollment in the coming months. [Cortexyme, Inc.] Press Release

MediciNova Announces Plans to Move Forward with a Phase III Trial of MN-166 (Ibudilast) in ALS

MediciNova, Inc. announced that the FDA has completed its review of the protocol and determined that MediciNova may proceed with a Phase IIb/III clinical trial of MN-166 in amyotrophic lateral sclerosis (ALS). If this potentially pivotal trial is successful, the Phase IIb/III efficacy and safety data is intended to support a New Drug Application for MN-166 in ALS. [MediciNova, Inc.] Press Release

Cassava Sciences Completes Patient Enrollment for a Phase IIa Study in Patients with Alzheimer’s Disease

Cassava Sciences, Inc. announced the completion of patient enrollment in a clinical study evaluating the safety of its investigational drug, PTI-125, in patients with Alzheimer’s disease. Cassava Sciences is conducting this Phase IIa study with scientific and financial support from the National Institutes of Health. [Cassava Sciences, Inc. (GlobeNewswire, Inc.)] Press Release

Qrons Announces Filing of PCT Patent – Techniques for Promoting Neuronal Recovery

Qrons Inc. announced that its PCT (Patent Cooperation Treaty) patent application, “Techniques for Promoting Neuronal Recovery”, relating to the treatment of traumatic injury to the central nervous system, such as TBI was filed on April 7, 2019 (Application No. PCT/IB2019/052850). [Qrons Inc.] Press Release

Report: Prominent Neuroscientist Worked for Months after University Found he Violated Sexual Relationship Policies

The student newspaper at Columbia University published a three-part series documenting how strict procedural protections for tenured professors have compromised the university’s ability to eject from campus tenured faculty, including prominent neuroscientist Thomas Jessell, who have been found guilty by the university of sexual harassment, misconduct, or assault-or who have lost or settled lawsuits alleging the same. [ScienceInsider] Editorial

Indian Scientists Launch Preprint Repository to Boost Research Quality

Researchers in India will soon have their own preprint repository where they can post manuscripts from any discipline. The founders of IndiaRxiv hope it will improve the quality of science in the country. [Nature News] Editorial

NEW Forum of Neurosciences
June 10-12, 2019
Brussels, Belgium

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NEW Postdoctoral Research Scientist – Systems Neuroscience (University of Oxford)

NEW Postdoctoral Researcher – Neurobiological Mechanisms (Columbia University)

Senior Scientist – Neuroscience (STEMCELL Technologies Inc.)

Senior Scientist – Tau Biology in Neuroscience Discovery (AbbVie Deutschland GmbH)

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

Postdoctoral Position – Developmental Neurobiology (University of Liège)

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

Postdoctoral Research Fellow – Neuroscience (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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