Neural Cell News Volume 13.27 | Jul 17 2019

TOP STORY

GPD1 Specifically Marks Dormant Glioma Stem Cells with a Distinct Metabolic Profile

Through a ribosome-profiling analysis of mouse neural stem cells (NSCs) and brain tumor stem cells (BTSCs), scientists found glycerol-3-phosphate dehydrogenase 1 (GPD1) expression specifically in BTSCs and not in NSCs. GPD1 expression was present in the dormant BTSC population, which was enriched at tumor borders and drove tumor relapse after chemotherapy. [Cell Stem Cell] Abstract | Press Release | Graphical Abstract

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Elevated Levels of Secreted-Frizzled-Related-Protein 1 Contribute to Alzheimer’s Disease Pathogenesis

Secreted-frizzled-related protein 1 (SFRP1) overexpression in an Alzheimer’s disease-like mouse model anticipated the appearance of amyloid plaques and dystrophic neurites, whereas its genetic inactivation or the infusion of α-SFRP1-neutralizing antibodies favors non-amyloidogenic amyloid precurson protein processing. [Nat Neurosci] Abstract | Editorial

Reward Signaling in a Recurrent Circuit of Dopaminergic Neurons and Peptidergic Kenyon Cells

Using optogenetic activation of Kenyon cells the authors provide evidence that recurrent signaling exists between Kenyon cells and dopaminergic neurons of the primary protocerebral anterior cluster. Optogenetic activation of Kenyon cells paired with odor stimulation was sufficient to induce appetitive memory. [Nat Commun] Full Article

Choroid Plexus-Derived miR-204 Regulates the Number of Quiescent Neural Stem Cells in the Adult Brain

miR-204 regulated a spectrum of transcripts involved in cell cycle regulation, neuronal migration, and differentiation in quiescent neural stem cells (qNSCs). Importantly, inhibition of miR-204 function reduced the number of qNSCs in the subependymal zone by inducing pre-mature activation and differentiation of NSCs without changing their neurogenic potential. [EMBO J] Abstract | Graphical Abstract

ID1 Is Critical for Tumorigenesis and Regulates Chemoresistance in Glioblastoma

Inhibitor of DNA-binding-1 (ID1)-positive cells were enriched by chemotherapy and drove tumor recurrence in glioblastoma. Addition of the neuroleptic drug pimozide to inhibit ID1 expression enhanced the cytotoxic effects of temozolomide therapy on glioma cells and significantly prolonged time to tumor recurrence. [Cancer Res] Abstract

Conversion of Astrocytes and Fibroblasts into Functional Noradrenergic Neurons

Researchers showed that seven transcription factors were able to convert astrocytes and fibroblasts into induced noradrenergic (iNA) neurons. These iNA neurons expressed the genes required for the biosynthesis, release, and re-uptake of noradrenaline. Moreover, iNA neurons fired action potentials, received synaptic inputs, and controlled the beating rate of co-cultured ventricular myocytes. [Cell Rep] Full Article | Graphical Abstract

Deficiency in BDNF/TrkB Neurotrophic Activity Stimulates δ-Secretase by Upregulating C/EBPβ in Alzheimer’s Disease

Investigators showed that deprivation of BDNF/TrkB increased inflammatory cytokines and activated the JAK2/STAT3 pathway, resulting in the upregulation of transcription factor C/EBPβ. This, in turn, resulted in increased expression of δ-secretase, leading to both APP and Tau fragmentation by δ-secretase and neuronal loss, which could be blocked by expression of STAT3 Y705F, knockdown of C/EBPβ, or the δ-secretase enzymatic-dead C189S mutant. [Cell Rep] Full Article | Graphical Abstract

miRNA-210 Induces Microglial Activation and Regulates Microglia-Mediated Neuroinflammation in Neonatal Hypoxic-Ischemic Encephalopathy

Scientists demonstrated that miR-210 induced microglial M1 activation partly by targeting SIRT1, thereby reducing the deacetylation of the NF-κB subunit p65 and increasing NF-κB signaling activity. [Cell Mol Immunol] Abstract

Mesenchymal Transition and Increased Therapy Resistance of Glioblastoma Cells Is Related to Astrocyte Reactivity

The authors investigated how mesenchymal (MES) transition of glioblastoma multiforme (GBM) cells relates to inflammatory responses of normal astroglia. They found that the MES signature showed strong resemblance to gene programs induced in reactive astrocytes. Likewise, astrocyte reactivity gene signatures were enriched in therapy-resistant MES-like glioma-initiating cell clones. [J Pathol] Abstract

Knockdown ATG4C Inhibits Gliomas Progression and Promotes Temozolomide Chemosensitivity by Suppressing Autophagic Flux

Knockdown autophagy related 4C cysteine peptidase (ATG4C) suppressed glioma cell proliferation by inducing cell cycle arrest at G1 phase. ATG4C depletion suppressed autophagy and triggered apoptosis through ROS accumulation. Depletion of ATG4C suppressed temozolomide (TMZ)-activated autophagy and promoted sensitivity of glioma cells to TMZ. [J Exp Clin Cancer Res] Full Article

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Born This Way: Hippocampal Neurogenesis across the Lifespan

The authors discuss the complex process and associated functional relevance of hippocampal neurogenesis during the embryonic/postnatal period and in adulthood. They consider the implications of hippocampal neurogenesis during the developmentally critical periods of adolescence and older age. [Aging Cell] Full Article

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Ivy Brain Tumor Center and Karyopharm Therapeutics Collaborate to Develop Tissue-Based Clinical Trial for Brain Cancer

The Ivy Brain Tumor Center at the Barrow Neurological Institute has announced a partnership with Karyopharm Therapeutics to accelerate the treatment of brain cancer. The Ivy Brain Tumor Center will employ Karyopharm’s first-in-class oral Selective Inhibitor of Nuclear Export compound, selinexor, in combination with other new-in-class drugs, as a dual-drug experimental therapy for adult glioblastoma. [Ivy Brain Tumor Center] Press Release

Amgen, Novartis and Banner Alzheimer’s Institute Discontinue Clinical Research Program with BACE Inhibitor CNP520 for Alzheimer’s Prevention

Amgen, Novartis and Banner Alzheimer’s Institute announced the collective decision to discontinue investigation of the BACE1 inhibitor CNP520 in two pivotal Phase II/III studies in the Alzheimer’s Prevention Initiative Generation Program. An assessment of unblinded data during a regular pre-planned review identified worsening in some measures of cognitive function. [Amgen Inc.] Press Release

Neurotrope Concludes Data Collection in Confirmatory Phase II Clinical Trial of Moderately Severe to Severe Alzheimer’s Disease

Neurotrope Inc. announced that the company has concluded data collection in its confirmatory Phase II double blind, placebo controlled clinical trial of bryostatin-1 in the treatment of moderately severe to severe Alzheimer’s disease. [Neurotrope Inc.] Press Release

Mallinckrodt Halts Phase IIB Trial Investigating the Use of Acthar^® Gel (Repository Corticotropin Injection) in Amyotrophic Lateral Sclerosis (ALS)

Mallinckrodt plc announced that it is permanently discontinuing its Phase IIB study designed to assess the efficacy and safety of Acthar^® Gel as an investigational treatment for ALS. Mallinckrodt made the decision to halt the trial after careful consideration of a recent recommendation by the study’s independent Data and Safety Monitoring Board. [Mallinckrodt plc] Press Release

EIP Pharma Initiates New Study with Neflamapimod for the Treatment of Cognitive Deficits in Patients with Dementia with Lewy Bodies

EIP Pharma, Inc. announced the initiation of a new Phase II proof-of-concept study evaluating neflamapimod as a treatment for the cognitive dysfunction associated with dementia with Lewy bodies (DLB). This Phase II proof-of-concept study is a double-blind, placebo-controlled, 16-week treatment study of neflamapimod in Stage 1 DLB. [EIP Pharma, Inc.] Press Release

Pitt Receives $6 Million for Vision Restoration Research

The University of Pittsburgh received a $6 million grant from the Richard King Mellon Foundation to support the development of a cortical vision research program in the Pitt School of Medicine Department of Ophthalmology. The program will aim to understand how the eye and the brain work together to help us see the world, and use that knowledge to develop new ways to restore vision using various technologies such as brain computer interfaces and novel genetic technologies. [University of Pittsburgh School of Medicine] Press Release

BU Researcher Receives NIH Grant to Study Down Syndrome

Funds from the $453,750 grant will be used to develop human stem cell-derived cultures to study a developmental abnormality in the formation and/or maintenance of white matter in the brain of people with Down syndrome. [Boston University School of Medicine (American Association for the Advancement of Science)] Press Release

Scientists Explore Blood Flow Bump that Happens when Our Neurons Are Significantly Activated

Dr. Philip O’Herron has received a two-year, $420,000 Exploratory/Developmental Research Grant from the National Institutes of Health that is enabling him to learn more about this natural, common response, including how neural activity drives blood flow increases, how important the increases are for the health and proper functioning of neurons and whether there really is overkill. [Augusta University] Press Release

Key Patent Grants Expand Exosome IP Portfolio

ReNeuron Group plc announced that it has expanded its intellectual property (IP) estate via the grant of a number of key patents covering its exosome technology platform. New patents have recently issued covering ReNeuron’s neural stem cell-derived exosomes and their methods of production. [ReNeuron Group plc] Press Release

The Plan to Mine the World’s Research Papers

Carl Malamud is on a crusade to liberate information locked up behind paywalls — and his campaigns have scored many victories. Now, the 60-year-old American technologist is turning his sights on a new objective: freeing paywalled scientific literature. And he thinks he has a legal way to do it. [Nature News] Editorial

Virologists Escorted Out of Lab in Canada

Canada’s national police force is investigating “possible policy breaches” after researchers were escorted from a lab at Canada’s National Microbiology Laboratory in Winnipeg, CBC News reported. Prominent virologist Xiangguo Qiu, her colleague and husband Keding Cheng, and an unknown number of her students from China were removed from the lab. [The Scientist] Editorial

NEW CSH: Neurobiology of Drosophila
October 1-5, 2019
Cold Spring Harbor, New York, United States

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

Early Stage Researchers – Multiple Sclerosis Research (National University of Ireland Galway)

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

Postdoctoral Fellowship – Bioinformatics & Neurogenesis (Lund University)

Postdoctoral Fellowship – Reprogramming Glioblastoma (Lund University)

Research Associate – Cellular & Molecular Neuroscience (University of Cambridge)

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

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

Tenure Track Faculty Positions – Neuropharmacology or Neurodegeneration (The University of Tennessee Health Science Center)

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

Postdoctoral Research Fellow – Molecular Neuroscience (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Nanoparticle-Based Therapeutic Delivery to the Brain (Johns Hopkins School of Medicine)

Postdoctoral Researcher – Brain Cancer Research (University of Alabama at Birmingham)

Postdoctoral Position – Neuropsychiatric Disorders (Stanford University)

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

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