Neural Cell News Volume 11.10 | Mar 15 2017

TOP STORY

Gpr124 Is Essential for Blood–Brain Barrier Integrity in Central Nervous System Disease

The endothelial G-protein-coupled receptor Gpr124 has been reported to be required for normal forebrain angiogenesis and blood–brain barrier (BBB) function in mouse embryos, but the role of this receptor in adult animals is unknown. Gpr124 conditional knockout in the endothelia of adult mice did not affect homeostatic BBB integrity, but resulted in BBB disruption and microvascular hemorrhage in mouse models of both ischemic stroke and glioblastoma, accompanied by reduced cerebrovascular canonical Wnt–β-catenin signaling. [Nat Med] Abstract

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PRC2 Facilitates the Regulatory Topology Required for Poised Enhancer Function during Pluripotent Stem Cell Differentiation

Using CRISPR/Cas9 technology to engineer precise genetic deletions, scientists demonstrated that poised enhancers are necessary for the induction of major anterior neural regulators. Interestingly, circularized chromosome conformation capture sequencing showed that poised enhancers already establish physical interactions with their target genes in embryonic stem cells in a polycomb repressive complex 2 (PRC2)-dependent manner. [Cell Stem Cell] Abstract | Graphical Abstract

Regulatory T Cells Promote Myelin Regeneration in the Central Nervous System

The authors report that regulatory T cells (T_reg) promote oligodendrocyte differentiation and (re)myelination. T_reg-deficient mice exhibited substantially impaired remyelination and oligodendrocyte differentiation, which was rescued by adoptive transfer of T_reg. In brain slice cultures, T_reg accelerated developmental myelination and remyelination, even in the absence of overt inflammation. [Nat Neurosci] Abstract

C1 Neurons Mediate a Stress-Induced Anti-Inflammatory Reflex in Mice

Investigators describe a powerful anti-inflammatory effect of restraint stress, mediated by C1 neurons: protection against renal ischemia-reperfusion injury. Restraint stress or optogenetic C1 neuron (C1) stimulation protected mice from ischemia-reperfusion injury. [Nat Neurosci] Abstract

Stage-Specific Functions of Semaphorin7A during Adult Hippocampal Neurogenesis Rely on Distinct Receptors

The authors showed that Semaphorin7A utilizes different cell surface receptors to control the proliferation and differentiation of neural progenitors in the adult hippocampal dentate gyrus, one of the select regions of the mature brain where neurogenesis occurs. [Nat Commun] Full Article

MTCL1 Plays an Essential Role in Maintaining Purkinje Neuron Axon Initial Segment

Researchers demonstrated that in vivo knockdown of microtubule cross‐linking factor 1 (MTCL1) in cerebellar Purkinje cells causes loss of axonal polarity coupled with AnkG mislocalization. MTCL1 lacking MT‐stabilizing activity failed to restore these defects, and stable MT bundles spanning the axon initial segment were disorganized in knockdown cells. [EMBO J] Abstract | Graphical Abstract

Phenotypic Screening Identifies Modulators of Amyloid Precursor Protein Processing in Human Stem Cell Models of Alzheimer’s Disease

Amyloid precursor protein (APP) processing and the accumulation of APP-derived amyloid β peptides are key processes in Alzheimer’s disease (AD). The authors designed a phenotypic small-molecule screen to identify modulators of APP processing in trisomy 21/Down syndrome neurons, a complex genetic model of AD. [Stem Cell Reports] Full Article

Modeling Anorexia Nervosa: Transcriptional Insights from Human iPSC-Derived Neurons

Scientists generated induced pluripotent stem cells (iPSCs) from adolescent females with anorexia nervosa (AN) and unaffected controls. These iPSCs were differentiated into neural cultures and subjected to extensive transcriptome analysis. Within a small cohort of patients who presented for treatment, they identified a novel gene that appears to contribute to AN pathophysiology, tachykinin 1 receptor. [Transl Psychiatry] Full Article

Hyaluronan Synthesis by Developing Cortical Neurons In Vitro

Investigators examined the expression of hyaluronan and hyaluronan synthases throughout cortical neuron development in vitro. Enriched cultures of cortical neurons were established from E16 rats. Neurons were collected at days in vitro 0, 1, 3, 7, 14, and 21 for qPCR or immunocytochemistry. [Sci Rep] Full Article

In Vitro Generation of Mature Midbrain-Type Dopamine Neurons by Adjusting Exogenous Nurr1 and Foxa2 Expressions to Their Physiologic Patterns

Researchers showed that the physiological levels and timing of Nurr1 and Foxa2 expression can be replicated in neural stem/precursor cells by choosing the right vectors and promoters. Controlled expression combined with a strategy for transgene expression maintenance induced generation of fully mature midbrain-type DA neurons. [Exp Mol Med] Full Article

Systemic Injection of AAV9-GDNF Provides Modest Functional Improvements in the SOD1^G93A ALS Rat but Has Adverse Side Effects

Systemic AAV9-glial cell line-derived neurotrophic factor (GDNF) was delivered via tail vein injections to young rats to determine whether this could be a safe and functional strategy to treat the SOD1^G93A rat model of ALS and, therefore, translated to a therapy for ALS patients. [Gene Ther] Full Article

Endoplasmic Reticulum Proteostasis in Glioblastoma – From Molecular Mechanisms to Therapeutic Perspectives

The authors provide an overview of the regulatory mechanisms underlying unfolded protein response signaling and how this pathway modulates cancer progression, particularly the aggressiveness and chemotherapeutic resistance exhibited by glioblastoma, a form of brain cancer. [Sci Signal] Abstract

Immune Microenvironment of Gliomas

High-grade gliomas are rapidly progressing tumors of the central nervous system with a very poor prognosis despite extensive resection combined with radiation and/or chemotherapy. Histopathological and flow cytometry analyses of human and rodent experimental gliomas revealed heterogeneity of a tumor and its niche, composed of reactive astrocytes, endothelial cells, and numerous immune cells. [Lab Invest] Abstract

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Inhibikase Awarded $433,000 from the Michael J. Fox Foundation to Advance Development of Kinase Inhibitor Treatment for Parkinson’s Disease

Inhibikase Therapeutics announced that the company has received a $433,000 research grant from the Michael J. Fox Foundation for Parkinson’s research to help fund pre-IND studies of the company’s novel c-Abl kinase inhibitors as a potential disease-modifying treatment for Parkinson’s disease. [Inhibikase Therapeutics] Press Release

Flowonix^® Medical Inc. and Cerebral Therapeutics Announce World-First Clinical Trial Delivering Medication Directly into the Brain for Patients with Refractory Epilepsy

Flowonix Medical Inc. and Colorado-based Cerebral Therapeutics, announced the first patients implanted with the Prometra^® II Programmable Infusion System in the Australian Direct Drug Administration for Refractory Epilepsy clinical trial at St. Vincent’s Hospital, Melbourne, Australia. The jointly developed therapy features a micro-infusion device that tightly controls drug delivery to a region of the brain for patients with medically refractory epilepsy. [Flowonix^® Medical Inc. (PR Newswire Association LLC.)] Press Release

Rosalind Franklin University Announces Construction of New Innovation and Research Park

Rosalind Franklin University of Medicine and Science announced plans for a new Innovation and Research Park, providing state-of-the-art research labs and incubator space for faculty and commercial biotech startups. The expansion will also include space for national and international life science firms. [Rosalind Franklin University of Medicine and Science] Press Release

ReadCoor Joins the Wyss Institute’s IARPA MICrONS Brain Mapping Consortium

ReadCoor, Inc. announced that it has joined the multi-disciplinary consortium led by the Wyss Institute for Biologically Inspired Engineering at Harvard University to map the brain’s neural circuitry with unprecedented resolution and precision. The consortium is made possible through a $21 million contract from the Intelligence Advanced Research Projects Activity (IARPA) under the MICrONS program to discover the brain’s learning rules and synaptic ‘circuit design,’ further enhancing neurally-derived machine learning algorithms. [ReadCoor (PR Newswire Association LLC.)] Press Release

‘Zombie’ Patent Fights over Mutant Mice Return

Like a zombie that keeps on kicking, legal battles over mutant mice used for Alzheimer’s research are haunting the field once again — four years after the last round of lawsuits. In the latest case, the University of South Florida in Tampa has sued the US National Institutes of Health for authorizing the distribution of a particular type of mouse used in the field. [Nature News] Editorial

U.K. Scientists Prepare for Impending Break with European Union

For months after the United Kingdom (U.K.) voted last June to leave the European Union (EU), many British scientists clung to hopes of a “soft Brexit,” which would not cut them off from EU funding and collaborators. But Prime Minister Theresa May, who is expected to trigger the two-year process of exiting the European Union, has signaled the break will be sharp. U.K. [ScienceInsider] Editorial

Canada’s New Genetic Privacy Law Is Causing Huge Headaches for Justin Trudeau

A vote in Canada’s Parliament to approve a genetic privacy bill is creating a self-inflicted political headache for Prime Minister Justin Trudeau’s Liberal government—and could result in a relatively rare and unusual court case. [ScienceInsider] Editorial

Physician with Drug-Industry Ties Is Trump’s FDA Pick

President Donald Trump has nominated Scott Gottlieb — a conservative pundit, physician and venture capitalist — to head the US Food and Drug Administration (FDA). [Nature News] Editorial

NEW Stem Cell Summit
April 26-28, 2017
Boston, United States

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May 4-6, 2017
Sao Paulo, Brazil

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

NEW 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)

Postdoctoral Research Associate – Alzheimer’s Disease (King’s College London)

Postdoctoral Studies – In Vitro Neural Systems (Karolinska Institute)

PhD Student – Developmental Neuroscience (Karolinska Institute)

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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