Neural Cell News Volume 13.43 | Nov 6 2019

TOP STORY

Trans-Synaptic Signaling through the Glutamate Receptor Delta-1 Mediates Inhibitory Synapse Formation in Cortical Pyramidal Neurons

Researchers showed that the glutamate receptor delta-1 (GluD1), a member of ionotropic glutamate receptors, was a postsynaptic organizer of inhibitory synapses in cortical pyramidal neurons. GluD1 was selectively required for the formation of inhibitory synapses and regulates GABAergic synaptic transmission accordingly. [Neuron] Full Article

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Cortical Astrocytes Develop in a Plastic Manner at Both Clonal and Cellular Levels

Investigators performed multiclonal lineage tracing using combinatorial genetic markers together with a new large volume color imaging approach to study astrocyte development in the mouse cortex. They showed that cortical astrocyte clones intermix with their neighbors and displayed extensive variability in terms of spatial organization, number and subtypes of cells generated. [Nat Commun] Full Article

Neuronal Network Dysfunction in a Model for Kleefstra Syndrome Mediated by Enhanced NMDAR Signaling

To study the impact of decreased EHMT1 function in human cells, the authors generated excitatory cortical neurons from induced pluripotent stem cells derived from Kleefstra syndrome patients. Neuronal networks of patient-derived cells exhibited network bursting with a reduced rate, longer duration, and increased temporal irregularity compared to control networks. [Nat Commun] Full Article

Spatiotemporally Dependent Vascularization Is Differently Utilized among Neural Progenitor Subtypes during Neocortical Development

Dividing basal progenitors and oligodendrocyte precursors preferentially contacted honeycomb vessels, but dividing apical progenitors were localized in avascular regions without Flt1-positive endothelial cells but directly contacted with sprouting neovascular tip cells. Therefore, not all blood vessels were associated equally with neural progenitors. [Cell Rep] Full Article | Graphical Abstract

Function of hTim8a in Complex IV Assembly in Neuronal Cells Provides Insight into Pathomechanism Underlying Mohr-Tranebjærg Syndrome

Investigators showed that hTim8a was required for the assembly of Complex IV in neurons, which was mediated through a transient interaction with Complex IV assembly factors, in particular the copper chaperone COX17. Complex IV assembly defects resulting from loss of hTim8a led to oxidative stress and changes to key apoptotic regulators, including cytochrome c and Bax, which primes cells for death. [eLife] Full Article

A CD133-AKT-Wnt Signaling Axis Drives Glioblastoma Brain Tumor-Initiating Cells

Using several patient-derived CD133^high and CD133^low glioblastomas, scientists describe intrinsic differences in determinants of stemness, which they owed to a CD133-AKT-Wnt signaling axis in which CD133 functioned as a putative cell surface receptor for AKT-dependent Wnt activation. [Oncogene] Abstract

Ablation of RIP3 Protects From Dopaminergic Neurodegeneration in Experimental Parkinson’s Disease

RIP3 deficiency in cultured cells and in mouse brain abrogated all phenotypes. Curiously, astrogliosis was increased in the striatum of MPTP-injected Wt mice and further exacerbated in RIP3ko mice. This was accompanied by absence of microgliosis and reposition of glial cell line-derived neurotrophic factor levels in the striata of MPTP-injected RIP3ko mice when compared to MPTP-injected Wt mice, which in turn showed a massive GDNF decrease. [Cell Death Dis] Full Article

Deletion of the Na/HCO₃ Transporter NBCn1 Protects Hippocampal Neurons from NMDA-Induced Seizures and Neurotoxicity in Mice

In knockouts, the nitric oxide synthase activity, caspase-3 expression/activity and the number of TUNEL-positive cells were significantly low. Immunochemical analysis revealed decreased expression levels of the NMDA receptor subunit GluN1 and the postsynaptic density protein PSD-95 in knockouts. [Sci Rep] Full Article

Inhibiting the LPS-Induced Enhancement of mEPSC Frequency in Superficial Dorsal Horn Neurons May Serve as an Electrophysiological Model for Alleviating Pain

Researchers measured spontaneous synaptic activity of miniature excitatory postsynaptic currents (mEPSCs) in rat spinal cord superficial dorsal horn (SDH) neurons. Lipopolysaccharide (LPS) and ATP increased the frequency, but not amplitude, of mEPSCs in SDH neurons. [Sci Rep] Full Article

Dopaminergic Neuron Injury in Parkinson’s Disease Is Mitigated by Interfering lncRNA SNHG14 Expression to Regulate the miR-133b/α-Synuclein Pathway

In MN9D cells, the rotenone treatment enhanced the binding between transcriptional factor SP-1 and SNHG14 promoter, thus promoting SNHG14 expression. Interference of SNHG14 ameliorated the DA neuron injury induced by rotenone. Investigators found an interaction between SNHG14 and miR-133b. [Aging (Albany NY)] Full Article

Single-Cell RNA-Seq Reveals Profound Alterations in Mechanosensitive Dorsal Root Ganglion Neurons with Vitamin E Deficiency

In stark contrast to expected changes in proprioceptive neurons, Ttpa^-/- dorsal root ganglia (DRGN) showed marked up-regulation of voltage-gated Ca²⁺ and K⁺ channels in mechanosensitive, tyrosine-hydroxylase positive DRGNs. The ensuing significant conductance changed resulted in reduced excitability in mechanosensitive Ttpa^-/- DRGNs. [iScience] Abstract | Full Article | Graphical Abstract

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Rapid Cortical Plasticity Supports Long-Term Memory Formation

The authors propose that cortical hubs can support rapid learning through synchronous activation of sensorimotor representational cortices. Candidate neurobiological mechanisms include unmasking of latent synaptic connections and rapid synaptic remodeling driven by disinhibitory processes. [Trends Cogn Sci] Abstract

Accumulators, Neurons, and Response Time

A brief survey of the history of the proposition precedes a review of multiple conundrums and paradoxes concerning the accuracy, precision, and transparency of that linking proposition. Correctly establishing how abstract models of decision-making are instantiated by particular neural circuits would represent a remarkable accomplishment in mapping mind to brain. [Trends Neurosci] Abstract

Astroglia-Derived ATP Modulates CNS Neuronal Circuits

Whereas the fast (co)transmitter function of ATP in the peripheral nervous system has been convincingly documented, in the central nervous system (CNS) ATP appears to be primarily a slow transmitter/modulator. Data discussed in the present review suggest that the slow modulatory effects of ATP arise as a result of its vesicular/nonvesicular release from astrocytes. [Trends Neurosci] Abstract

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ACADIA Pharmaceuticals Initiates Phase III Pivotal Study of Trofinetide in Rett Syndrome, a Rare Neurodevelopmental Congenital CNS Disorder

ACADIA Pharmaceuticals Inc. announced that it has initiated the Phase III LAVENDER placebo-controlled study to evaluate the efficacy and safety of trofinetide for girls and young women with Rett syndrome. [ACADIA Pharmaceuticals Inc.] Press Release

VBL Therapeutics Announces New IND for an Investigator-Sponsored Phase II Trial of VB-111 in Recurrent Glioblastoma

VBL Therapeutics announced that an investigational new drug (IND) application has received clearance from the FDA. The IND is for a Phase II randomized, controlled, clinical trial of VB-111 in recurrent glioblastoma patients undergoing a second surgery. [VBL Therapeutics] Press Release

Pinteon Therapeutics Launches Phase I Trial of Novel Tau Antibody That Targets a Potent Driver of Neurodegenerative Disease

Pinteon Therapeutics announced the launch of a Phase I trial of PNT001, a novel tau antibody that uniquely targets a toxic epitope known to drive neurodegenerative disease. The company’s lead asset, PNT001, targets a highly neurotoxic conformation of tau, known as cis-pT231 tau, that promotes the abnormal aggregation of tau proteins in neurons. [Pinteon Therapeutics] Press Release

Alzheimer’s Experts Greet China’s Surprise Approval of a Drug for Brain Disease with Hope and Caution

A Chinese biotech startup has startled neuroscientists and drug developers with a new plant-based compound it claims improves cognitive function in Alzheimer’s patients by altering their gut microbiomes. The news has elicited both hope and skepticism from researchers not connected to the company. [ScienceInsider] Editorial

More, Unfortunately, on the Chinese Alzheimer’s Drug Approval

In a follow up to the surprise decision by the Chinese regulators to allow a new Alzheimer’s drug on the market, article author Derek Lowe finds that the compound did not appear to reach statistical significance versus placebo. Not in the trial shown. Why, you wonder, was it progressed to Phase III in the first place? [ScienceInsider] Editorial

Report Sketches Vision for UK Research After Brexit

An eagerly awaited external report, commissioned by the government, lays out research priorities and options if those relationships with Europe are severed. It calls for increased spending on R&D nationwide, a new research fellowship program, and larger chunks of money for universities to quickly target research opportunities. [ScienceInsider] Editorial

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