Glioblastoma Stem Cells Generate Vascular Pericytes to Support Vessel Function and Tumor Growth Scientists showed that glioma stem cells (GSCs) give rise to pericytes to support vessel function and tumor growth. In vivo cell lineage tracing with constitutive and lineage-specific fluorescent reporters demonstrated that GSCs generate the majority of vascular pericytes. Selective elimination of GSC-derived pericytes disrupts the neovasculature and potently inhibits tumor growth. [Cell] Abstract | Graphical Abstract Degeneration and Impaired Regeneration of Gray Matter Oligodendrocytes in Amyotrophic Lateral Sclerosis In the spinal cord of amyotrophic lateral sclerosis (ALS) mice, oligodendrocytes downregulate transporters that transfer glycolytic substrates to neurons and oligodendrocyte progenitors exhibit enhanced proliferation and differentiation, although the cause of these changes in oligodendroglia is unknown. Scientists found extensive degeneration of gray matter oligodendrocytes in the spinal cord of SOD1 ALS mice prior to disease onset. Although new oligodendrocytes were formed, they failed to mature, resulting in progressive demyelination. [Nat Neurosci] Abstract | Press Release FIP200 Is Required for Maintenance and Differentiation of Postnatal Neural Stem Cells Investigators report that ablation of FIP200, a gene essential for autophagy induction in mammalian cells, results in a progressive loss of neural stem cells and impairment in neuronal differentiation specifically in the postnatal brain, but not the embryonic brain, in mice. [Nat Neurosci] Abstract OPA1 Loss of Function Affects In Vitro Neuronal Maturation Researchers showed that in rodent cortical primary neurons, downregulation of the OPA1 protein leads to fragmented mitochondria that become less abundant along the dendrites. Furthermore, this inhibition results in reduced expression of mitochondrial respiratory complexes as well as mitochondrial DNA, decreased mitochondrial membrane potential, and diminished reactive oxygen species levels. [Brain] Abstract Tumorigenic Potential of miR-18A* in Glioma Initiating Cells Requires NOTCH-1 Signaling Using human glioma initiating cells researchers found that miR-18a* expression promotes clonal proliferation in vitro and tumorigenicity in vivo. Mechanistically, ERK-dependent induction of miR-18a* directly represses expression of DLL3, an autocrine inhibitor of NOTCH, thus enhancing the level of activated NOTCH-1. [Stem Cells] Abstract Schwann Cell LRP1 Regulates Remak Bundle Ultrastructure and Axonal Interactions to Prevent Neuropathic Pain Trophic support and myelination of axons by Schwann cells in the PNS are essential for normal nerve function. Investigators showed that deletion of the LDL receptor-related protein-1 (LRP1) gene in Schwann cells induces abnormalities in axon myelination and in ensheathment of axons by nonmyelinating Schwann cells in Remak bundles. [J Neurosci] Abstract Ophiobolin A Induces Paraptosis-Like Cell Death in Human Glioblastoma Cells by Decreasing BKCa Channel Activity Researchers investigated ophiobolin A (OP-A), a fungal metabolite from Bipolaris species, for its promising anticancer activity against human glioblastoma multiforme (GBM) cells exhibiting varying degrees of resistance to proapoptotic stimuli. They found that OP-A induced marked changes in the dynamic organization of the F-actin cytoskeleton, and inhibited the proliferation and migration of GBM cells, likely by inhibiting big conductance Ca2+-activated K+ channel (BKCa) channel activity. [Cell Death Dis] Full Article Lewy Body-Like α-Synuclein Aggregates Resist Degradation and Impair Macroautophagy Activation of macroautophagy is suggested to facilitate degradation of certain proteinaceous inclusions, but it is unclear if this pathway is capable of degrading α-synuclein (α-syn) aggregates. Scientists examined this issue by utilizing cellular models in which intracellular Lewy body-like α-syn inclusions accumulate after internalization of pre-formed α-syn fibrils into α-syn-expressing HEK293 cells or cultured primary neurons. They demonstrated that α-syn inclusions cannot be effectively degraded, even though they co-localize with essential components of both the autophagic and proteasomal protein degradation pathways. [J Biol Chem] Abstract Phosphatidylinositol 4-Phosphate 5-Kinase α Negatively Regulates Nerve Growth Factor-Induced Neurite Outgrowth in PC12 Cells Scientists addressed whether type I phosphatidylinositol (PI) 4-phosphate 5-kinase (PIP5K)α, an isoform of PIP5K, could have a role in neurite outgrowth induced by nerve growth factor (NGF). For this purpose, they knocked down PIP5Kα in PC12 rat pheochromocytoma cells by stable expression of PIP5Kα microRNA that significantly reduced PIP5Kα expression and PI 4,5-bisphosphate level. Interestingly, NGF-induced neurite outgrowth was more prominent in PIP5Kα-knockdown cells than in control cells. [Exp Mol Med] Full Article Three-Dimensional Graphene Foam As a Biocompatible and Conductive Scaffold for Neural Stem Cells The authors report the first utilization of graphene foam, a 3D porous structure, as a novel scaffold for neural stem cells (NSCs) in vitro. It was found that three-dimensional graphene foams can not only support NSC growth, but also keep cell at an active proliferation state with upregulation of Ki67 expression than that of two-dimensional graphene films. [Sci Rep] Full Article |