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Akihiro Ishii, Miki Furusho, Wendy Macklin, Rashmi Bansal
Multiple extracellular and intracellular signals regulate the functions of oligodendrocytes as they progress through the complex process of developmental myelination and then maintain a functionally intact myelin sheath throughout adult life, preserving the integrity of the axons. Recent studies suggest that Mek/ERK1/2-MAPK and PI3K/Akt/mTOR intracellular signaling pathways play important, often overlapping roles in the regulation of myelination. However, it remains poorly understood whether they function independently, sequentially, or converge using a common mechanism to facilitate oligodendrocyte differentiation, myelin growth, and maintenance...
February 13, 2019: Glia
Anirudh Patir, Barbara Shih, Barry W McColl, Tom C Freeman
Growing recognition of the pivotal role microglia play in neurodegenerative and neuroinflammatory disorders has accentuated the need to characterize their function in health and disease. Studies in mouse have applied transcriptome-wide profiling of microglia to reveal key features of microglial ontogeny, functional profile, and phenotypic diversity. While similar, human microglia exhibit clear differences to their mouse counterparts, underlining the need to develop a better understanding of the human microglial profile...
February 13, 2019: Glia
Coralie Brifault, HyoJun Kwon, Wendy M Campana, Steven L Gonias
Following injury to the peripheral nervous system (PNS), microglia in the spinal dorsal horn (SDH) become activated and contribute to the development of local neuro-inflammation, which may regulate neuropathic pain processing. The molecular mechanisms that control microglial activation and its effects on neuropathic pain remain incompletely understood. We deleted the gene encoding the plasma membrane receptor, LDL Receptor-related Protein-1 (LRP1), conditionally in microglia using two distinct promoter-Cre recombinase systems in mice...
February 11, 2019: Glia
Eric Tsai, Patrizia Casaccia
Oligodendrocytes differentiate from oligodendrocyte progenitor cells (OPCs) in response to distinct extracellular signals. This process requires changes in gene expression resulting from the interplay between transcription factors and epigenetic modulators. Extracellular signals include chemical and physical stimuli. This review focuses on the signaling mechanisms activated in oligodendrocyte progenitors in response to mechanical forces. Of particular interest is a better understanding on how these forces are transduced into the OPC nuclei and subsequently reshape their epigenetic landscape...
February 8, 2019: Glia
Martina Cantone, Melanie Küspert, Simone Reiprich, Xin Lai, Martin Eberhardt, Peter Göttle, Felix Beyer, Kasum Azim, Patrick Küry, Michael Wegner, Julio Vera
Oligodendrocytes (OLs) facilitate information processing in the vertebrate central nervous system via axonal ensheathment. The structure and dynamics of the regulatory network that mediates oligodendrogenesis are poorly understood. We employed bioinformatics and meta-analysis of high-throughput datasets to reconstruct a regulatory network underpinning OL differentiation. From this network, we identified families of feedforward loops comprising the transcription factors (TFs) Olig2, Sox10, and Tcf7l2 and their targets...
February 7, 2019: Glia
Werend Boesmans, Marlene M Hao, Candice Fung, Zhiling Li, Chris Van den Haute, Jan Tack, Vassilis Pachnis, Pieter Vanden Berghe
Coordination of gastrointestinal function relies on joint efforts of enteric neurons and glia, whose crosstalk is vital for the integration of their activity. To investigate the signaling mechanisms and to delineate the spatial aspects of enteric neuron-to-glia communication within enteric ganglia we developed a method to stimulate single enteric neurons while monitoring the activity of neighboring enteric glial cells. We combined cytosolic calcium uncaging of individual enteric neurons with calcium imaging of enteric glial cells expressing a genetically encoded calcium indicator and demonstrate that enteric neurons signal to enteric glial cells through pannexins using paracrine purinergic pathways...
February 7, 2019: Glia
Wenhui Huang, Qilin Guo, Xianshu Bai, Anja Scheller, Frank Kirchhoff
In the central nervous system, the type I transmembrane glycoprotein NG2 (nerve-glia antigen 2) is only expressed by pericytes and oligodendrocyte precursor cells (OPCs). Therefore, OPCs are also termed NG2 glia. Their fate during development has been investigated systematically in several genetically modified mouse models. Consensus exists that postnatal NG2 glia are restricted to the oligodendrocyte (OL) lineage, while, at least in the forebrain, embryonic NG2 glia could also generate astrocytes. In addition, experimental evidence for a neurogenic potential of NG2 glia in the early embryonic brain (before E16...
February 6, 2019: Glia
Chi Young Chang, Sae-Bom Jeon, Hee Jung Yoon, Bum-Kyu Choi, Sang Soo Kim, Masanobu Oshima, Eun Jung Park
Growing interest has been focused on the roles of microglia as sentinels and effector cells that guard diverse pathological milieu in the brain. Here, it has been reported that microglial TLR2 is a crucial molecule that confers innate and adaptive immunity against brain tumor. TLR2 is preferentially expressed on microglia, brain-resident immune cells, in the tumor-bearing cerebral hemisphere of mouse and rat intracranial tumor models. Microglial TLR2 rapidly responds to brain tumor and modulates the inflammation-associated immune responses including phagocytosis, which are markedly decreased in TLR2-deficient mice...
February 5, 2019: Glia
David C Spray, Rodolfo Iglesias, Nathanael Shraer, Sylvia O Suadicani, Vitali Belzer, Regina Hanstein, Menachem Hanani
Peripheral sensory ganglia contain the somata of neurons mediating mechanical, thermal, and painful sensations from somatic, visceral, and oro-facial organs. Each neuronal cell body is closely surrounded by satellite glial cells (SGCs) that have properties and functions similar to those of central astrocytes, including expression of gap junction proteins and functional dye coupling. As shown in other pain models, after systemic pain induction by intra-peritoneal injection of lipopolysaccharide, dye coupling among SGCs in intact trigeminal ganglion was enhanced...
February 4, 2019: Glia
Arshed Nazmi, Robert H Field, Eadaoin W Griffin, Orla Haugh, Edel Hennessy, Donal Cox, Renata Reis, Lucas Tortorelli, Carol L Murray, Ana Belen Lopez-Rodriguez, Lei Jin, Ed C Lavelle, Aisling Dunne, Colm Cunningham
Type I interferons (IFN-I) are the principal antiviral molecules of the innate immune system and can be made by most cell types, including central nervous system cells. IFN-I has been implicated in neuroinflammation during neurodegeneration, but its mechanism of induction and its consequences remain unclear. In the current study, we assessed expression of IFN-I in murine prion disease (ME7) and examined the contribution of the IFN-I receptor IFNAR1 to disease progression. The data indicate a robust IFNβ response, specifically in microglia, with evidence of IFN-dependent genes in both microglia and astrocytes...
January 25, 2019: Glia
Emma J van Bodegraven, Jessy V van Asperen, Pierre A J Robe, Elly M Hol
Gliomas are a heterogenous group of malignant primary brain tumors that arise from glia cells or their progenitors and rely on accurate diagnosis for prognosis and treatment strategies. Although recent developments in the molecular biology of glioma have improved diagnosis, classical histological methods and biomarkers are still being used. The glial fibrillary acidic protein (GFAP) is a classical marker of astrocytoma, both in clinical and experimental settings. GFAP is used to determine glial differentiation, which is associated with a less malignant tumor...
January 22, 2019: Glia
Naomi Tanga, Kazuya Kuboyama, Ayako Kishimoto, Hiroshi Kiyonari, Aki Shiraishi, Ryoko Suzuki, Toshio Watanabe, Akihiro Fujikawa, Masaharu Noda
Protein tyrosine phosphatase receptor type Z (PTPRZ) maintains oligodendrocyte precursor cells (OPCs) in an undifferentiated state. The inhibition of PTPase by its ligand pleiotrophin (PTN) promotes OPC differentiation; however, the substrate molecules of PTPRZ involved in the differentiation have not yet been elucidated in detail. We herein demonstrated that the tyrosine phosphorylation of AFAP1L2, paxillin, ERBB4, GIT1, p190RhoGAP, and NYAP2 was enhanced in OPC-like OL1 cells by a treatment with PTN. AFAP1L2, an adaptor protein involved in the PI3K-AKT pathway, exhibited the strongest response to PTN...
January 22, 2019: Glia
Inês Dinis Aires, Raquel Boia, Ana Catarina Rodrigues-Neves, Maria Helena Madeira, Carla Marques, António Francisco Ambrósio, Ana Raquel Santiago
Glaucoma is a retinal degenerative disease characterized by the loss of retinal ganglion cells and damage of the optic nerve. Recently, we demonstrated that antagonists of adenosine A2A receptor (A2A R) control retinal inflammation and afford protection to rat retinal cells in glaucoma models. However, the precise contribution of microglia to retinal injury was not addressed, as well as the effect of A2A R blockade directly in microglia. Here we show that blocking microglial A2A R prevents microglial cell response to elevated pressure and it is sufficient to protect retinal cells from elevated pressure-induced death...
January 22, 2019: Glia
Elena Montagna, Sophie Crux, Manja Luckner, Julia Herber, Alessio V Colombo, Petar Marinković, Sabina Tahirovic, Stefan F Lichtenthaler, Gerhard Wanner, Ulrike C Müller, Carmelo Sgobio, Jochen Herms
The investigation of amyloid precursor protein (APP) has been mainly confined to its neuronal functions, whereas very little is known about its physiological role in astrocytes. Astrocytes exhibit a particular morphology with slender extensions protruding from somata and primary branches. Along these fine extensions, spontaneous calcium transients occur in spatially restricted microdomains. Within these microdomains mitochondria are responsible for local energy supply and Ca2+ buffering. Using two-photon in vivo Ca2+ imaging, we report a significant decrease in the density of active microdomains, frequency of spontaneous Ca2+ transients and slower Ca2+ kinetics in mice lacking APP...
January 22, 2019: Glia
Li Zhang, Rougang Xie, Jiping Yang, Youyi Zhao, Chuchu Qi, Ganlan Bian, Mengmeng Wang, Junjia Shan, Chen Wang, Dong Wang, Ceng Luo, Yazhou Wang, Shengxi Wu
Chronic pain is one of the most prevalent chronic diseases in the world. The plastic changes of sensory neurons in dorsal root ganglia (DRG) have been extensively studied as the underlying periphery mechanism. Recent studies revealed that satellite cells, the major glial cells in DRG, also played important roles in the development/modulation of chronic pain. Whether DRG satellite glial cells generate new neurons as their counterparts in enteric nerve ganglia and carotid body do under pathological conditions remains poorly investigated...
January 16, 2019: Glia
Katja A Lüders, Stefan Nessler, Kathrin Kusch, Julia Patzig, Ramona B Jung, Wiebke Möbius, Klaus-Armin Nave, Hauke B Werner
Proteolipid protein (PLP) is the most abundant integral membrane protein in central nervous system (CNS) myelin. Expression of the Plp-gene in oligodendrocytes is not essential for the biosynthesis of myelin membranes but required to prevent axonal pathology. This raises the question whether the exceptionally high level of PLP in myelin is required later in life, or whether high-level PLP expression becomes dispensable once myelin has been assembled. Both models require a better understanding of the turnover of PLP in myelin in vivo...
January 14, 2019: Glia
Jan W Robering, Lisa Gebhardt, Katharina Wolf, Helen Kühn, Andreas E Kremer, Michael J M Fischer
Pruritus is a common and disabling symptom in patients with hepatobiliary disorders, particularly in those with cholestatic features. Serum levels of lysophosphatidic acid (LPA) and its forming enzyme autotaxin were increased in patients suffering from hepatic pruritus, correlated with itch severity and response to treatment. Here we show that in a culture of dorsal root ganglia LPA 18:1 surprisingly activated a large fraction of satellite glia cells, and responses to LPA 18:1 correlated inversely with responses to neuronal expressed transient receptor potential channels...
January 13, 2019: Glia
Syam Nair, Kristina S Sobotka, Pooja Joshi, Pierre Gressens, Bobbi Fleiss, Claire Thornton, Carina Mallard, Henrik Hagberg
Accumulating evidence suggests that changes in the metabolic signature of microglia underlie their response to inflammation. We sought to increase our knowledge of how pro-inflammatory stimuli induce metabolic changes. Primary microglia exposed to lipopolysaccharide (LPS)-expressed excessive fission leading to more fragmented mitochondria than tubular mitochondria. LPS-mediated Toll-like receptor 4 (TLR4) activation also resulted in metabolic reprogramming from oxidative phosphorylation to glycolysis. Blockade of mitochondrial fission by Mdivi-1, a putative mitochondrial division inhibitor led to the reversal of the metabolic shift...
January 13, 2019: Glia
Masaaki Kitada, Toru Murakami, Shohei Wakao, Gen Li, Mari Dezawa
Direct conversion is considered a promising approach to obtain tissue-specific cells for cell therapies; however, this strategy depends on exogenous gene expression that may cause undesired adverse effects such as tumorigenesis. By optimizing the Schwann cell induction system, which was originally developed for trans-differentiation of bone marrow mesenchymal stem cells into Schwann cells, we established a system to directly convert adult human skin fibroblasts into cells comparable to authentic human Schwann cells without gene introduction...
January 13, 2019: Glia
Katalin Bartus, Emily R Burnside, Jorge Galino, Nicholas D James, David L H Bennett, Elizabeth J Bradbury
We recently discovered a novel role for neuregulin-1 (Nrg1) signaling in mediating spontaneous regenerative processes and functional repair after spinal cord injury (SCI). We revealed that Nrg1 is the molecular signal responsible for spontaneous functional remyelination of dorsal column axons by peripheral nervous system (PNS)-like Schwann cells after SCI. Here, we investigate whether Nrg1/ErbB signaling controls the unusual transformation of centrally derived progenitor cells into these functional myelinating Schwann cells after SCI using a fate-mapping/lineage tracing approach...
January 13, 2019: Glia
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