Neural Cell News Volume 10.01 | Jan 13 2016

Neural Stem Cells Sustain Natural Killer Cells that Dictate Recovery from Brain Inflammation
Scientists report the unexpected finding that natural killer cells are retained in the brain subventricular zone during the chronic phase of multiple sclerosis in humans and its animal model in mice. [Nat Neurosci] Abstract

KIF1A Inhibition Immortalizes Brain Stem Cells but Blocks BDNF-Mediated Neuronal Migration
To understand the consequences of altered basal interkinetic nuclear migration (INM) and the roles of kinesin KIF1A in disease, the authors performed constitutive and conditional RNAi and expressed mutant KIF1A in E16 to P7 rat radial glial progenitors (RGPs) and neurons. RGPs inhibited in basal INM still showed normal cell cycle progression, although neurogenic divisions were severely reduced. [Nat Neurosci] Abstract

Age-Dependent Specific Changes in Area CA2 of the Hippocampus and Social Memory Deficit in a Mouse Model of the 22q11.2 Deletion Syndrome
Researchers report several age-dependent CA2 alterations: a decrease in the density of parvalbumin-expressing interneurons, a reduction in the amount of feedforward inhibition, and a change in CA2 pyramidal-neuron intrinsic properties. [Neuron] Abstract | Press Release 

Yap Is Required for Ependymal Integrity and Is Suppressed in LPA-Induced Hydrocephalus
Researchers identify Yap, the downstream effector of the evolutionarily conserved Hippo pathway, as a central regulator for generating developmentally controlled ependymal cells along the ventricular lining of the aqueduct. [Nat Commun] Full Article

Novel Role for Anti-Mullerian Hormone in the Regulation of GnRH Neuron Excitability and Hormone Secretion
Investigators demonstrated that a significant subset of GnRH neurons both in mice and humans express the anti-Müllerian hormone (AMH) receptor, and that AMH potently activates the GnRH neuron firing in mice. [Nat Commun] Abstract

Impairment of PARK14-Dependent Ca²⁺ Signaling Is a Novel Determinant of Parkinson’s Disease
Investigators demonstrate that genetic or molecular impairment of PLA2g6-dependent Ca²⁺ signaling is a trigger for autophagic dysfunction, progressive loss of dopaminergic neurons in substantia nigra pars compacta and age-dependent L-DOPA-sensitive motor dysfunction. [Nat Commun] Full Article | Press Release

The Rag-Ragulator Complex Regulates Lysosome Function and Phagocytic Flux in Microglia
Researchers showed that RagA and Lamtor4, two components of the Rag-Ragulator complex, are essential regulators of lysosomes in microglia. In zebrafish lacking RagA function, microglia exhibit an expanded lysosomal compartment, but they are unable to properly digest apoptotic neuronal debris. [Cell Rep]
Full Article | Graphical Abstract

Disrupted in Schizophrenia 1 (DISC1) L100P Mutants Have Impaired Activity-Dependent Plasticity In Vivo and In Vitro
The authors report that DISC1 L100P mutants are less able to reorganize cortical circuitry in response to stimulation in vivo. Molecular analysis reveals that the mutants have a reduced expression of PSD95 and pCREB in visual cortex and fail to adjust expression of such markers in response to altered stimulation. [Transl Psychiatry] Full Article

Prion Protein Localizes at the Ciliary Base during Neural and Cardiovascular Development, and Its Depletion Affects Alpha-Tubulin Post-Translational Modifications
Investigators report prion protein (PrP(C)) enrichment at the base of the primary cilium in stem and progenitor cells from the central nervous system and cardiovascular system of developing mouse embryos. PrP(C) depletion in a neuroepithelial cell line dramatically altered key cilium-dependent processes, such as Sonic hedgehog signaling and alpha-tubulin post-translational modifications. [Sci Rep] Full Article

Remote and Reversible Inhibition of Neurons and Circuits by Small Molecule Induced Potassium Channel Stabilization
Scientists applied a chemogenetic approach in brain research for the first time in order to control a potassium channel in a remote and reversible manner. They showed that shield1-mediated ectopic Kir2.1 stabilization induces neuronal silencing in vitro and in vivo in the mouse brain. [Sci Rep] Full Article

Targeting NF-κB in Glioblastoma: A Therapeutic Approach
Investigators have established a lentivirus-induced mouse model of malignant gliomas, which faithfully captures the pathophysiology and molecular signature of mesenchymal human glioblastoma multiforme. [Sci Adv] Abstract | Full Article

Merging DBS with Viral Vector or Stem Cell Implantation: “Hybrid” Stereotactic Surgery as an Evolution in the Surgical Treatment of Parkinson’s Disease
The reviewers discuss approaches used for central nervous system biologic delivery in Parkinson’s disease patients in previous trials and propose a new set of strategies based on novel molecular targets. [Mol Ther Methods Clin Dev] Full Article

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SanBio and Sunovion Begin Patient Recruitment for Phase IIb Trial to Test Regenerative Treatment for Chronic Stroke in North America
SanBio, Inc., announced that it has initiated patient recruitment for a Phase IIb clinical trial to further test the safety and efficacy of its proprietary cell therapy. Earlier clinical trial results suggested the therapy’s potential to improve motor function following an ischemic stroke. [SanBio, Inc. [BusinessWire]] Press Release

DelMar Pharmaceuticals to Collaborate with MD Anderson Cancer Center on Development of DelMar’s VAL-083 in Brain Cancer
DelMar Pharmaceuticals, Inc. announced that it has entered into a collaboration with the University of Texas MD Anderson Cancer Center to accelerate the clinical development of DelMar’s lead anti-cancer candidate, VAL-083, for the treatment of glioblastoma multiforme, the most common and deadly form of brain cancer. [DelMar Pharmaceuticals, Inc.] Press Release

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NEW Post-Doc Fellowship – Regulation/Function/Structure of the Synapse (National Institutes of Health)

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Postdoctoral Fellow – Pediatric Brain Cancer (Fred Hutchinson Cancer Research Center)

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