Neural Cell News Volume 11.11 | Mar 22 2017

TOP STORY

Ancient Evolutionary Origin of Vertebrate Enteric Neurons from Trunk-Derived Neural Crest

Investigators examined development of the enteric nervous system in the basal jawless vertebrate, the sea lamprey (Petromyzon marinus), to gain insight into its evolutionary origin. They found no evidence for the existence of a vagally derived enteric neural crest population in the lamprey. Rather, labeling with the lipophilic dye DiI showed that late-migrating cells, originating from the trunk neural tube and associated with nerve fibers, differentiate into neurons within the gut wall and typhlosole. [Nature] Abstract | Press Release

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Volumetric Two-Photon Imaging of Neurons Using Stereoscopy (vTwINS)

Scientists introduce vTwINSs, a volumetric calcium imaging method that uses an elongated, V-shaped point spread function to image a 3D brain volume. Single neurons project to spatially displaced ‘image pairs’ in the resulting 2D image, and the separation distance between projections is proportional to depth in the volume. [Nat Methods] Abstract

Developmental Alterations in Huntington’s Disease Neural Cells and Pharmacological Rescue in Cells and Mice

Researchers observed a strong correlation between Huntington’s disease (HD)-related histone marks, gene expression and unique peak profiles associated with dysregulated genes, suggesting a coordinated epigenetic program. Treatment with isoxazole-9, which targets key dysregulated pathways, led to amelioration of expanded polyglutamine repeat-associated phenotypes in neural cells and of cognitive impairment and synaptic pathology in HD model R6/2 mice. [Nat Neurosci] Abstract

Cerebellar Granule Cells Acquire a Widespread Predictive Feedback Signal during Motor Learning

The authors showed, using two-photon microscopy to track neural activity over multiple days of cerebellum-dependent eyeblink conditioning in mice, that granule cell populations acquire a dense representation of the anticipatory eyelid movement. Granule cells responded to neutral visual and somatosensory stimuli as well as periorbital airpuffs used for training. [Nat Neurosci] Abstract

Disrupting the CD47-SIRPα Anti-Phagocytic Axis by a Humanized Anti-CD47 Antibody Is an Efficacious Treatment for Malignant Pediatric Brain Tumors

Investigators demonstrated the effect of a humanized anti-CD47 antibody, Hu5F9-G4, on five aggressive and etiologically distinct pediatric brain tumors: group three medulloblastoma, atypical teratoid rhabdoid tumor, primitive neuroectodermal tumor, pediatric glioblastoma, and diffuse intrinsic pontine glioma. Hu5F9-G4 demonstrated therapeutic efficacy in vitro and in vivo in patient-derived orthotopic xenograft models. [Sci Transl Med] Abstract | Press Release

Basolateral to Central Amygdala Neural Circuits for Appetitive Behaviors

Scientists identified several genetically distinct populations of central amygdala (CeA) neurons that mediate appetitive behaviors and dissect the basolateral amygdala (BLA)-to-CeA circuit for appetitive behaviors. Protein phosphatase 1 regulatory subunit 1B⁺ BLA pyramidal neurons to dopamine receptor 1⁺ CeA neurons define a pathway for promoting appetitive behaviors, while R-spondin 2⁺ BLA pyramidal neurons to dopamine receptor 2⁺ CeA neurons define a pathway for suppressing appetitive behaviors. [Neuron] Abstract | Press Release | Video Abstract

Endogenous Opioids Regulate Moment-to-Moment Neuronal Communication and Excitability

Researchers found endogenous opioids are released by synaptic stimulation to act via two distinct mechanisms within the main intercalated cells cluster. Endogenously released opioids inhibit glutamate release through the δ-opioid receptor (DOR), an effect potentiated by a DOR-positive allosteric modulator. [Nat Commun] Full Article

Systemic Deregulation of Autophagy upon Loss of ALS- and FTD-linked C9orf72

Using a 3110043O21Rik/C9orf72 knockout mouse model, as well as cellular analysis, the authors have found that loss of C9orf72 causes alterations in the signaling states of central autophagy regulators. In particular, C9orf72 depletion lead to reduced activity of MTOR, a negative regulator of macroautophagy/autophagy, and concomitantly increased TFEB levels and nuclear translocation. [Autophagy] Abstract

β-Arrestin2 Couples Metabotropic Glutamate Receptor 5 to Neuronal Protein Synthesis and Is a Potential Target to Treat Fragile X

Investigators provide evidence that β-arrestin2 mediates metabotropic glutamate receptor 5 (mGlu₅)-stimulated protein synthesis in the hippocampus and showed that genetic reduction of β-arrestin2 corrects aberrant synaptic plasticity and cognition in the Fmr1^−/y mouse model of fragile X. Importantly, reducing β-arrestin2 did not induce psychotomimetic activity associated with full mGlu₅ inhibitors and did not affect G_q signaling. [Cell Rep] Full Article | Graphical Abstract

Sphingosine-1-Phosphate Induces Ca²⁺ Signaling and CXCL1 Release via TRPC6 Channel in Astrocytes

Scientists investigated the involvement of transient receptor potential canonical (TRPC) channels in sphingosine-1-phosphate (S1P)-induced cellular responses. In Ca²⁺ imaging experiments, S1P at 1 μM elicited a transient increase in intracellular Ca²⁺ in astrocytes, followed by sustained elevation. The sustained Ca²⁺ response was markedly suppressed by S1P₂ receptor antagonist JTE013, S1P₃ receptor antagonist CAY10444, or non-selective TRPC channel inhibitor Pyr2. [Glia] Abstract

BDE-99 Impairs Differentiation of Human and Mouse NPCs into the Oligodendroglial Lineage by Species-Specific Modes of Action

Researchers tested whether disturbance of neural progenitor cell (NPC) differentiation into the oligodendrocyte lineage (O4⁺ cells) by BDE-99 involved disruption of thyroid hormone (TH) action in human and mouse (h,m)NPCs. They quantified differentiation of NPCs into O4⁺ cells and measured their maturation via expression of myelin-associated genes in presence and absence of TH and/or BDE-99. [Sci Rep] Full Article

Partial Reprogramming of Pluripotent Stem Cell-Derived Cardiomyocytes into Neurons

Investigators demonstrated that partial direct reprogramming of mesoderm-derived cardiomyocytes into neurons is feasible, generating cells exhibiting structural and electrophysiological properties of both cardiomyocytes and neurons. Human and mouse pluripotent stem cell-derived CMs were transduced with the neurogenic transcription factors Brn2, Ascl1, Myt1l and NeuroD. [Sci Rep] Full Article

Ontogeny and Homeostasis of CNS Myeloid Cells

Myeloid cells in the central nervous system (CNS) represent a heterogeneous class of innate immune cells that contribute to the maintenance of tissue homeostasis differentially during development and adulthood. [Nat Immunol] Abstract

Restoring Brain Function after Stroke — Bridging the Gap Between Animals and Humans

Stroke is the leading cause of complex adult disability in the world. Recovery from stroke is often incomplete, which leaves many people dependent on others for their care. The improvement of long-term outcomes should, therefore, be a clinical and research priority. [Nat Rev Neurol] Abstract

Insights Into Molecular Therapy of Glioma: Current Challenges and Next Generation Blueprint

The author captures the latest trends associated with the molecular mechanisms involved in glial tumorigenesis as well as the limitations of surgery, radiation and chemotherapy. They also critically discuss the next generation molecular therapeutic strategies and their mechanisms for the successful treatment of glioma. [Acta Pharmacol Sin] Full Article

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EnGeneIC Doses First Patient in U.S. Phase I Clinical Study of Targeted EDV^™ Nanocells in Recurrent Glioblastoma Multiforme

EnGeneIC Limited announced that it has begun dosing patients in a USA-based open-label Phase I clinical trial evaluating its proprietary EDV^™ nanocells to treat recurrent glioblastoma multiforme (GBM) in adults. [EnGeneIC Limited] Press Release

InVivo Therapeutics Announces Enrollment of New Patient into the INSPIRE Study at New Jersey’s Cooper Neurological Institute

InVivo Therapeutics Holdings Corp. announced that a new patient has been enrolled into The INSPIRE Study: InVivo Study of Probable Benefit of the Neuro-Spinal Scaffold^™ for Safety and Neurologic Recovery in Subjects with Complete Thoracic AIS A Spinal Cord Injury at the Cooper Neurological Institute, which is part of Cooper University Hospital, a network providing care to Southern New Jersey and the Delaware Valley. [InVivo Therapeutics Holdings Corp.] Press Release

InVivo Therapeutics Announces Submission to the FDA of Its Nonclinical Studies Module for the Neuro-Spinal Scaffold^™

InVivo Therapeutics Holdings Corp. announced that it has submitted its first module containing nonclinical studies to the U.S. Food and Drug Administration (FDA) as part of its Humanitarian Device Exemption modular submission and review process for the Neuro-Spinal Scaffold. [InVivo Therapeutics Holdings Corp.] Press Release

Lin BioScience Licenses Novel Therapeutic Program for Brain Cancer from the University of Sydney

Lin BioScience announced an exclusive licensing agreement with the University of Sydney for a microtubule-targeting agent to treat brain cancers. The therapeutic candidate, LBS-002, is a small molecule that disrupts the division of cancer cells by preventing the formation of microtubules. [Lin Bioscience Inc. (PR Newswire Association LLC.)] Press Release

Noted Sanford Burnham Prebys Scientist Joins Forces with Rady Children’s Institute for Genomic Medicine to Help Fight Childhood Brain Cancer

Rady Children’s Institute for Genomic Medicine (RCIGM) announced that Robert Wechsler-Reya, PhD, has been named program director for the Joseph Clayes III Research Center for Neuro-Oncology and Genomics at RCIGM. [Rady Children’s Hospital San Diego] Press Release

South Korea’s Scientists Seek Change amid Political Chaos

When South Korea’s Constitutional Court removed scandal-ridden President Park Geun-hye from office on 10^th March, citizens rejoiced in the streets — and many scientists breathed a sigh of relief. Her downfall has inspired a public appetite for broad governmental reforms, including changes in how the country supports scientific research. Many in the research community hope to end South Korea’s decades-long focus on applied research and shift more resources to basic science. [Nature News] Editorial

Ethical Guidelines on Lab-Grown Embryos Beg for Revamping, Scientists Say

Researchers in the U.K. and U.S. recently succeeded for the first time in growing embryos in the lab for nearly two weeks before terminating them, showing that the so-called 14-day rule is no longer a scientific limitation — although it remains a cultural one. Now, a group of Harvard University scientists has published a paper arguing that it is time to reconsider the 14-day rule because of advances in synthetic biology. [Scientific American] Editorial

NEW American Society of Gene & Cell Therapy (ASGCT)
May 10-13, 2017
Washington, D.C., United States

NEW Metabolism in Time and Space: Emerging Links to Cellular and Developmental Programs
May 11-13, 2017
Heidelberg, Germany

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NEW Assistant/Associate Professor – Canada Research Chair in Mental Health (University of Alberta)

NEW Senior Scientist – Cognitive Neurophysiology (Forschungszentrum Jülich – FZJ – Helmholtz Association)

Postdoctoral Fellow – Stem Cell Dynamics in the Adult Hippocampus (The Francis Crick Institute)

Postdoctoral Research Associate – Developmental Neuroscience (University of Nebraska Medical Center)

PhD Student and Postdoctoral Positions – Molecular and Cellular Biology/Systems Biology/Neurobiology (University of Fribourg)

Scientist – Retina and CNS Degenerative Disease (University Health Network)

Assistant Professor – Neuroscience (Pennsylvania State University)

Postdoctoral Fellow – Translational Neuroscience and Neuroregeneration (Houston Methodist Research Institute)

Research Scientist – Neurobiology of the Visual System (National Eye Institute – National Institutes of Health)

Postdoctoral Researcher – Stem Cell Differentiation (University of Oklahoma)

Postdoctoral Positions – Stem Cell Technology/Neuroscience/Drug Discovery (University of California Davis)

Neuroscientist – Precision Neurotherapeutics (University of California Davis)

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

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