The Morphological and Molecular Nature of Synaptic Vesicle Priming at Presynaptic Active Zones Scientists employed hippocampal organotypic slice cultures from mice lacking key presynaptic proteins, cryofixation, and three-dimensional electron tomography to study the mechanism of synaptic vesicle docking in the same experimental setting, with high precision, and in a near-native state. [Neuron] Abstract | Press Release Stochastic Nanoroughness Modulates Neuron-Astrocyte Interactions and Function via Mechanosensing Cation Channels The authors theorize a role for topography in neuronal development and demonstrate that survival and function of hippocampal neurons and differentiation of telencephalic neural stem cells is modulated by nanoroughness. [Proc Natl Acad Sci USA] Abstract Stretch-Activated Ion Channel Piezo1 Directs Lineage Choice in Human Neural Stem Cells Investigators found that the mechanically gated ion channel Piezo1 is expressed by brain-derived human neural stem/progenitor cells and is responsible for a mechanically induced ionic current. [Proc Natl Acad Sci USA] Abstract The Nuclear Receptor NR2E1/TLX Controls Senescence The nuclear receptor NR2E1 controls the self-renewal of neural stem cells (NSCs) and has been implied as an oncogene which initiates brain tumors including glioblastomas. Scientists confirmed that NR2E1 regulates CBX7 and restrains senescence in NSCs. [Oncogene] Abstract Sorting Nexin 27 Regulates Aβ Production through Modulating γ-Secretase Activity Scientists report a function of SNX27 in regulating β-amyloid (Aβ) generation by modulating γ-secretase activity. Genetic deletion of Snx27 promoted Aβ production and neuronal loss, whereas overexpression of SNX27 using an adeno-associated viral vector reduced hippocampal Aβ levels in a transgenic Alzheimer’s disease mouse model. [Cell Rep] Full Article | Graphical Abstract | Press Release Expression Quantitative Trait Loci and Receptor Pharmacology Implicate Arg1 and the GABA-A Receptor as Therapeutic Targets in Neuroblastoma Researchers combined genetics with gene-expression analysis in the peripheral sympathetic nervous system to implicate arginase 1 and GABA signaling in tumor formation in vivo. In human neuroblastoma cells, either blockade of ARG1 or benzodiazepine-mediated activation of GABA-A receptors induced apoptosis and inhibited mitogenic signaling through AKT and MAPK. [Cell Rep] Full Article | Graphical Abstract Engineering Toxin-Resistant Therapeutic Stem Cells to Treat Brain Tumors Scientists created toxin-resistant stem cells by modifying endogenous elongation factor-2, and engineered them to secrete pseudomonas exotoxin-cytotoxins targeting IL13Rα2 and EGFR expressed by many glioblastomas. [Stem Cells] Abstract | Press Release Huntingtin Promotes mTORC1 Signaling in the Pathogenesis of Huntington’s Disease Investigators found that huntingtin (Htt) promotes signaling by mTORC1 (mechanistic target of rapamycin [mTOR] complex 1) and that this signaling is potentiated by poly-Q-expanded Htt. Knocking out Htt in mouse embryonic stem cells or human embryonic kidney cells attenuated amino acid-induced mTORC1 activity, whereas overexpressing wild-type or poly-Q-expanded Htt in striatal neuronal cells increased basal mTOR activity. [Sci Signal] Abstract | Press Release A Smoothened Receptor Agonist Is Neuroprotective and Promotes Regeneration after Ischemic Brain Injury Investigators report the neuroprotective properties of a small-molecule agonist of the sonic hedgehog co-receptor Smoothened, purmorphamine (PUR), in the middle cerebral artery occlusion model of ischemic stroke. PUR increased the number of newly generated neurons in the peri-infarct and infarct area and promoted neovascularization in the ischemic zone. [Cell Death Dis] Full Article | Press Release Lab-on-a-Brain: Implantable Micro-Optical Fluidic Devices for Neural Cell Analysis In Vivo Scientists report a novel experimental platform, where the intact brain of a living mouse can be studied with the aid of a surgically implanted micro-optical fluidic device; acting as an interface between neurons and the outer world. [Sci Rep] Full Article | Press Release miR-21 Improves the Neurological Outcome after Traumatic Brain Injury in Rats Researchers found that upregulation of microRNA (miR)-21 level in brain conferred a better neurological outcome after traumatic brain injury (TBI) by improving long-term neurological function, alleviating brain edema and decreasing lesion volume. They evaluated the impact of miR-21 on apoptosis and angiogenesis in brain after TBI. [Sci Rep] Full Article |