Neural Cell News Volume 13.32 | Aug 21 2019

TOP STORY

Niche Stiffness Underlies the Aging of Central Nervous System Progenitor Cells

The authors showed that the oligodendrocyte progenitor cell (OPC) microenvironment stiffened with age, and that this mechanical change was sufficient to cause age-related loss of function of OPCs. Using biological and synthetic scaffolds to mimic the stiffness of young brains, they found that isolated aged OPCs cultured on these scaffolds were molecularly and functionally rejuvenated. [Nature] Abstract | Press Release

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Specialized Cutaneous Schwann Cells Initiate Pain Sensation

Investigators discovered a specialized cutaneous glial cell type with extensive processes forming a mesh-like network in the subepidermal border of the skin that conveyed noxious thermal and mechanical sensitivity. They demonstrated a direct excitatory functional connection to sensory neurons and provided evidence of a previously unknown organ that had an essential physiological role in sensing noxious stimuli. [Science] Abstract | Press Release | Editorial

CRISPR Interference-Based Platform for Multimodal Genetic Screens in Human iPSC-Derived Neurons

Scientists describe a CRISPR interference-based platform for genetic screens in human neurons derived from induced pluripotent stem cells (iPSCs). They demonstrated robust and durable knockdown of endogenous genes in such neurons and present results from three complementary genetic screens. [Neuron] Abstract | Press Release | Graphical Abstract

Driving Neuronal Differentiation through Reversal of an ERK1/2-miR-124-SOX9 Axis Abrogates Glioblastoma Aggressiveness

Constitutive extracellular signal-regulated kinase 1/2 (ERK1/2) activation globally regulated miRNA expression in murine and human glioblastomas (GBMs), while neuronal differentiation of GBM tumorspheres following the inhibition of ERK1/2 activation required the functional expression of miR-124 and the depletion of its target gene SOX9. Overexpression of miR124 depleted SOX9 in vivo and promoted a stem-like-to-neuronal transition, with reduced tumorigenicity and increased radiation sensitivity. [Cell Rep] Full Article | Graphical Abstract

Complement C3 Is Activated in Human AD Brain and Is Required for Neurodegeneration in Mouse Models of Amyloidosis and Tauopathy

Researchers found that glial cells showed increased expression of classical complement components and the central component C3 in mouse models of amyloidosis (PS2APP) and more extensively tauopathy (TauP301S). Blocking complement function by deleting C3 rescued plaque-associated synapse loss in PS2APP mice and ameliorated neuron loss and brain atrophy in TauP301S mice, improving neurophysiological and behavioral measurements. [Cell Rep] Full Article | Graphical Abstract

An miR-340-5p-Macrophage Feedback Loop Modulates the Progression and Tumor Microenvironment of Glioblastoma Multiforme

Scientists showed that downregulation of miR-340-5p in glioblastoma multiforme (GBM) was correlated with tumor size, recurrence, and poor survival. They found that miR-340-5p levels were correlated with the density of tumor-associated macrophages (TAMs) and M2-polarized TAMs in GBM. [Oncogene] Abstract

UPF1 Regulates the Malignant Biological Behaviors of Glioblastoma Cells via Enhancing the Stability of Linc-00313

UPF1 and Linc-00313 were both upregulated in glioma tissues and cells. Knockdown of UPF1 or Linc-00313 significantly inhibited malignant biological behaviors of glioma cells by regulating miR-342-3p and miR-485-5p, which were downregulated and functioned as tumor suppressors in glioma. [Cell Death Dis] Full Article

Dystrophin Deficiency Leads to Dysfunctional Glutamate Clearance in iPSC Derived Astrocytes

Investigators generated cortical neuronal and astrocytic progeny from induced pluripotent stem cells (PSC) from six Duchenne muscular dystrophy (DMD) subjects carrying different mutations and several unaffected PSC lines. DMD astrocytes displayed cytoskeletal abnormalities, defects in Ca⁺² homeostasis and nitric oxide signaling. [Transl Psychiatry] Full Article

Buffering of Cytosolic Calcium Plays a Neuroprotective Role by Preserving the Autophagy-Lysosome Pathway during MPP⁺-Induced Neuronal Death

The authors report that in 1-methyl-4-phenylpyridinium (MPP⁺)-induced culture models of Parkinson’s disease, the buffering of cytosolic Ca²⁺ by calbindin-D28 overexpression or treatment with a chemical Ca²⁺ chelator reversed impaired autophagic flux, protecting cells against MPP⁺-mediated neurotoxicity. [Cell Death Discov] Full Article

Donepezil Modulates Amyloid Precursor Protein Endocytosis and Reduction by Up-Regulation of SNX33 Expression in Primary Cortical Neurons

Donepezil induced an increase in sorting nexin protein 33 (SNX33) expression in primary cortical neurons. The secretion of soluble amyloid precursor protein (APP)α in culture media increased, whereas the expression of full-length APP in the cell lysate remained unchanged. [Sci Rep] Full Article

Early Functional Alterations in Membrane Properties and Neuronal Degeneration Are Hallmarks of Progressive Hearing Loss in Nod Mice

Researchers demonstrated that hair cell loss was preceded by, or in parallel with altered primary auditory neuron functions, and latent neurite retraction at the hair cell-auditory neuron synapse. The results were observed first in afferent inner hair cell synapse of type I neurites, followed by type II neuronal cell-body degeneration. [Sci Rep] Full Article

Mouse Induced Pluripotent Stem Cells-Derived Alzheimer’s Disease Cerebral Organoid Culture and Neural Differentiation Disorders

Alzheimer’s disease (AD) cerebral organoids were generated by overexpressing familial AD mutations in mouse induced pluripotent stem cells, so that the early pathogenesis of AD could be investigated well with protein and cellular phenotype analyses. [Neurosci Lett] Abstract

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Dissecting and Rebuilding the Glioblastoma Microenvironment with Engineered Materials

Researchers summarize key features of the glioblastoma (GBM) microenvironment and discuss different strategies for the engineering of GBM tumor microenvironment models, including 2D and 3D models featuring chemical and mechanical gradients, interfaces and fluid flow. [Nat Rev Mater] Abstract

Convergence of Human Cellular Models and Genetics to Study Neural Stem Cell Signaling to Enhance Central Nervous System Regeneration and Repair

The authors focus on the recent lessons from lower organism central nervous system regeneration genetics and how such findings are starting to illuminate our understanding of neural stem cell signaling pathways in humans. [Semin Cell Dev Biol] Abstract

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

Nascent Biotech Has Entered into an Agreement to Perform Phase I Clinical Study for Brain Cancer

Nascent Biotech, Inc. announced they have entered into a contractual agreement in Orange County, CA to conduct Phase I human clinical trials on Nascent antibody, Pritumumab, for the treatment of brain cancer. [Nascent Biotech, Inc. (GlobeNewswire, Inc.)] Press Release

Moleculin Announces CTRC Approval of WP1066 Pediatric Brain Tumor Trial

Moleculin Biotech, Inc. announced approval by the Emory University Clinical Trial Review Committee (CTRC) to move forward with an Investigator Initiated clinical trial of Moleculin’s immune-stimulating/transcriptional-modulator, WP1066, for the treatment of pediatric brain tumors. [Moleculin Biotech, Inc.] Press Release

$4.96 Million CIRM Grant Awarded to Sanford Burnham Prebys to Help the Tiniest Patients

The California Institute for Regenerative Medicine (CIRM) has awarded a $4.96 million grant to Sanford Burnham Prebys Professor Evan Y. Snyder, M.D., Ph.D. The funding will allow Snyder to complete pre-investigational new drug-enabling studies, a step toward securing FDA approval of a human trial for neural stem cells as a potential treatment for newborns who experience oxygen and blood-flow deprivation during birth. [Sanford Burnham Prebys] Press Release

Alzheimer’s Foundation of America Awards $100,000 Grant to NYU Winthrop Hospital for Research Project to Develop New Alzheimer’s Treatments

The Alzheimer’s Foundation of America announced a $100,000 grant to NYU Winthrop Hospital for a research project aimed at uncovering the underlying causes of Alzheimer’s disease and developing new treatments. The cutting-edge research will re-engineer human cells, collected through a single voluntary blood test, to behave like brain neurons, allowing researchers to achieve what they believe is the closest approximation to brain behavior possible. [The Alzheimer’s Foundation of America] Press Release

Italian Blindness Researchers Planning Monkey Studies Threatened after Health Ministry Releases Names

Marco Tamietto was aware that animal rights activists might target him after his team won ethical approval for an experiment in monkeys on blindness. But he hadn’t anticipated the threats of violence. [ScienceInsider] Editorial

Brazil’s Budget Cuts Threaten More Than 80,000 Science Scholarships

Brazil’s main science-funding agency will have to suspend more than 80,000 scholarships to postdoctoral researchers and graduate and undergraduate students starting in September unless it receives additional cash from the government. [Nature News] Editorial

NEW 7^th Cambridge Neuroscience Symposium: Artificial and Biological Cognition
September 12-13, 2019
Cambridge, United Kingdom

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

NEW Postdoctoral Research Associate – Neural Stem Cell Research (St. Jude Children’s Research Hospital)

Scientific Communications Coordinator (STEMCELL Technologies Inc.)

PhD Position – Neuroproteomics and Brain Organoids (University of Southern Denmark)

Associate Research Scientist – Brain Research (Mortimer B. Zuckerman Mind Brain Behavior Institute)

Postdoctoral Associate – Cerebral Organoids (Weill Cornell Medicine)

Tenure-Track Assistant Professor – Cognitive Neuroscience (Lawrence University of Wisconsin)

Postdoctoral Fellowship – Neurogenesis & Neural Cell Aging (Lund University)

Postdoctoral Fellowship – Bioinformatics & Neurogenesis (Lund University)

Postdoctoral Fellowship – Reprogramming Glioblastoma (Lund University)

Postdoctoral Scientist – Glioma Organoids (Rutgers Cancer Institute of New Jersey)

Research Lab Specialist – Tumor Microenvironment & Cell Behavior (University of Southern California)

Postdoctoral Researcher – Retinal Stem Cell Biology (NIH National Eye Institute)

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