Neural Cell News Volume 7.16 | Apr 24 2013

Medial Ganglionic Eminence-Like Cells Derived from Human Embryonic Stem Cells Correct Learning and Memory Deficits
The authors present a method for differentiating human embryonic stem cells to a nearly uniform population of NKX2.1⁺ medial ganglionic eminence (MGE)-like progenitor cells. Mice transplanted with MGE-like but not spinal progenitors showed improvements in learning and memory deficits. [Nat Biotechnol]
Abstract | Press Release

Peli1 Promotes Microglia-Mediated CNS Inflammation by Regulating Traf3 Degradation
Researchers showed that the E3 ubiquitin ligase Peli1 is abundantly expressed in microglia and promotes microglial activation during the course of experimental autoimmune encephalomyelitis induction. Peli1 mediates the induction of chemokines and proinflammatory cytokines in microglia and thereby promotes recruitment of T cells into the central nervous system (CNS). [Nat Med] Abstract

Subcellular Localization Determines the Stability and Axon Protective Capacity of Axon Survival Factor Nmnat2
Researchers investigated the mechanism of fast axonal transport of Nicotinamide mononucleotide adenlylyltransferase (Nmnat2) and its site of action for axon maintenance. Using dual-color live-cell imaging of axonal transport in superior cervical ganglion primary culture neurons, they found that Nmnat2 is bidirectionally trafficked in axons together with markers of the trans-Golgi network and synaptic vesicles. [PLoS Biol] Full Article

Autocrine Signaling Based Selection of Combinatorial Antibodies that Transdifferentiate Human Stem Cells
Researchers report the generation of antibody agonists from intracellular combinatorial libraries that transdifferentiate human stem cells. Unlike the natural granulocyte-colony stimulating factor that activates cells to differentiate along a predetermined pathway, the isolated agonist antibodies transdifferentiated human myeloid lineage CD34+ bone marrow cells into neural progenitors. [Proc Natl Acad Sci USA]
Abstract | Press Release

TFEB-Mediated Autophagy Rescues Midbrain Dopamine Neurons from α-Synuclein Toxicity
Using an adeno-associated virus model of Parkinson disease to overexpress α-synuclein in the substantia nigra, researchers showed that genetic transcription factor EB (TFEB) and Beclin-1 overexpression or pharmacological manipulations that enhance autophagy protect nigral neurons from α-synuclein toxicity, but inhibiting autophagy exacerbates α-synuclein toxicity. [Proc Natl Acad Sci USA] Abstract

The Therapeutic Activities of Engrafted Neural Stem/Precursor Cells are Not Dormant in the Chronically Injured Spinal Cord
Researchers performed temporal analysis of injured spinal cords and demonstrated their multiphasic cellular and molecular responses. In particular, chronically injured spinal cords were growth factor-enriched environments, whereas acutely injured spinal cords were enriched by neurotrophic and inflammatory factors. To determine how these environmental differences affect engrafted cells, neural stem/precursor cells transplanted into acutely, subacutely, and chronically injured spinal cords were selectively isolated by flow-cytometry, and their whole transcriptomes were compared by RNA-sequencing. [Stem Cells] Abstract

Doxycycline Restrains Glia and Confers Neuroprotection in a 6-OHDA Parkinson Model
Results suggest that doxycycline blocks 6-OHDA neurotoxicity in vivo by inhibiting microglial and astrocyte expression. This action of doxycycline in nigrostriatal dopaminergic neuron protection is consistent with a role of glial cells in Parkinson’s disease neurodegeneration. [Glia] Abstract

The LIM Homeobox Gene ceh-14 Is Required for Phasmid Function and Neurite Outgrowth
The authors previously showed that the LIM homeodomain factor CEH-14 is expressed in the AFD neurons where it is required for thermotaxis behavior in Caenorhabditis elegans. In this study, they showed that ceh-14 is expressed in the phasmid sensory neurons, PHA and PHB, a number of neurons in the tail, i.e., PHC, DVC, PVC, PVN, PVQ, PVT, PVW and PVR, as well as the touch neurons. [Dev Biol] Abstract

Morphological and Functional Differentiation in BE(2)-M17 Human Neuroblastoma Cells by Treatment with Trans-Retinoic Acid
The clonal human neuroblastoma BE(2)-M17 cell line is known to differentiate into a more prominent neuronal cell type by treatment with trans-retinoic acid. Researchers studied the effects of trans-retinoic acid treatment on (a) some differentiation marker proteins, (b) types of voltage-gated calcium (Ca2+) channels and (c) Ca2+-dependent neurotransmitter ([3H] glycine) release in cultured BE(2)-M17 cells. [BMC Neurosci]
Abstract | Full Article

Expression of the Protein Chaperone, Clusterin, in Spinal Cord Cells Constitutively and Following Cellular Stress, and Upregulation by Treatment with Hsp90 Inhibitor
To assess relevance to amyotrophic lateral sclerosis (ALS) and other motor neuron disorders, clusterin expression was evaluated using long-term dissociated cultures of murine spinal cord and SOD1^G93A transgenic mice, a model of familial ALS. Motor neurons and astrocytes constitutively expressed nuclear and cytoplasmic forms of clusterin, and secreted clusterin accumulated in culture media. [Cell Stress Chaperones] Abstract

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Research Associate  – Neuroscience (University College London)

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