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https://www.readbyqxmd.com/read/28071826/gat-1-mediated-gaba-uptake-in-rat-oligodendrocytes
#1
Giorgia Fattorini, Marcello Melone, María Victoria Sánchez-Gómez, Rogelio O Arellano, Silvia Bassi, Carlos Matute, Fiorenzo Conti
Stimulated by the results of a recent paper on the effects of tiagabine, a selective inhibitor of the main GABA transporter GAT-1, on oligodendrogenesis, we verified the possibility that GAT-1 may be expressed in oligodendrocytes using immunocytochemical methods and functional assays. Light microscopic analysis of the subcortical white matter of all animals revealed the presence of numerous GAT-1+ cells of different size (from 3 to 29 µm) and morphology. An electron microscope analysis revealed that, besides fibrous astrocytes and interstitial neurons, GAT-1 immunoreactivity was present in immature and mature oligodendrocytes...
January 10, 2017: Glia
https://www.readbyqxmd.com/read/28063222/astrocytic-ip3-rs-contribution-to-ca-2-signalling-and-hippocampal-ltp
#2
Mark William Sherwood, Misa Arizono, Chihiro Hisatsune, Hiroko Bannai, Etsuko Ebisui, John Lawrence Sherwood, Aude Panatier, Stéphane Henri Richard Oliet, Katsuhiko Mikoshiba
Astrocytes regulate hippocampal synaptic plasticity by the Ca(2+) dependent release of the N-methyl d-aspartate receptor (NMDAR) co-agonist d-serine. Previous evidence indicated that d-serine release would be regulated by the intracellular Ca(2+) release channel IP3 receptor (IP3 R), however, genetic deletion of IP3 R2, the putative astrocytic IP3 R subtype, had no impact on synaptic plasticity or transmission. Although IP3 R2 is widely believed to be the only functional IP3 R in astrocytes, three IP3 R subtypes (1, 2, and 3) have been identified in vertebrates...
January 7, 2017: Glia
https://www.readbyqxmd.com/read/28063215/hypoxia-independent-mechanisms-of-hif-1%C3%AE-expression-in-astrocytes-after-ischemic-preconditioning
#3
Yuri Hirayama, Schuichi Koizumi
We recently demonstrated that ischemic tolerance was dependent on astrocytes, for which HIF-1α had an essential role. The mild ischemia (preconditioning; PC) increased HIF-1α in a biphasic pattern, that is, a quick and transient increase in neurons, followed by a slow and sustained increase in astrocytes. However, mechanisms underlying such temporal difference in HIF-1α increase remain totally unknown. Here, we show that unlike a hypoxia-dependent mechanism in neurons, astrocytes increase HIF-1α via a novel hypoxia-independent but P2X7-dependent mechanism...
January 7, 2017: Glia
https://www.readbyqxmd.com/read/28063173/identification-of-highly-connected-hub-genes-in-the-protective-response-program-of-human-macrophages-and-microglia-activated-by-alpha-b-crystallin
#4
Inge R Holtman, Malika Bsibsi, Wouter H Gerritsen, Hendrikus W G M Boddeke, Bart J L Eggen, Paul van der Valk, Markus Kipp, Johannes M van Noort, Sandra Amor
The glial stress protein alpha B-crystallin (HSPB5) is an endogenous agonist for Toll-like receptor 2 in CD14(+) cells. Following systemic administration, HSPB5 acts as a potent inhibitor of neuroinflammation in animal models and reduces lesion development in multiple sclerosis patients. Here, we show that systemically administered HSPB5 rapidly crosses the blood-brain barrier, implicating microglia as additional targets for HSPB5 along with peripheral monocytes and macrophages. To compare key players in the HSPB5-induced protective response of human macrophages and microglia, we applied weighted gene co-expression network analysis on transcript expression data obtained 1 and 4 h after activation...
January 7, 2017: Glia
https://www.readbyqxmd.com/read/28063167/conditional-knockout-of-tog-results-in-cns-hypomyelination
#5
Michael J Maggipinto, Joshay Ford, Kristine H Le, Jessica W Tutolo, Miki Furusho, John W Wizeman, Rashmi Bansal, Elisa Barbarese
The tumor overexpressed gene (TOG) protein is present in RNA granules that transport myelin basic protein (MBP) mRNA in oligodendrocyte processes to the myelin compartment. Its role was investigated by conditionally knocking it out (KO) in myelinating glia in vivo. TOG KO mice have severe motor deficits that are already apparent at the time of weaning. This phenotype correlates with a paucity of myelin in several CNS regions, the most severe being in the spinal cord. In the TOG KO optic nerve <30% of axons are myelinated...
January 7, 2017: Glia
https://www.readbyqxmd.com/read/28032919/expression-of-the-human-isoform-of-glutamate-dehydrogenase-hgdh2-augments-tca-cycle-capacity-and-oxidative-metabolism-of-glutamate-during-glucose-deprivation-in-astrocytes
#6
Jakob D Nissen, Kasper Lykke, Jaroslaw Bryk, Malin H Stridh, Ioannis Zaganas, Dorte M Skytt, Arne Schousboe, Lasse K Bak, Wolfgang Enard, Svante Pääbo, Helle S Waagepetersen
A key enzyme in brain glutamate homeostasis is glutamate dehydrogenase (GDH) which links carbohydrate and amino acid metabolism mediating glutamate degradation to CO2 and expanding tricarboxylic acid (TCA) cycle capacity with intermediates, i.e. anaplerosis. Humans express two GDH isoforms, GDH1 and 2, whereas most other mammals express only GDH1. hGDH1 is widely expressed in human brain while hGDH2 is confined to astrocytes. The two isoforms display different enzymatic properties and the nature of these supports that hGDH2 expression in astrocytes potentially increases glutamate oxidation and supports the TCA cycle during energy-demanding processes such as high intensity glutamatergic signaling...
December 29, 2016: Glia
https://www.readbyqxmd.com/read/27896839/dopamine-elevates-and-lowers-astroglial-ca-2-through-distinct-pathways-depending-on-local-synaptic-circuitry
#7
Alistair Jennings, Olga Tyurikova, Lucie Bard, Kaiyu Zheng, Alexey Semyanov, Christian Henneberger, Dmitri A Rusakov
Whilst astrocytes in culture invariably respond to dopamine with cytosolic Ca(2+) rises, the dopamine sensitivity of astroglia in situ and its physiological roles remain unknown. To minimize effects of experimental manipulations on astroglial physiology, here we monitored Ca(2+) in cells connected via gap junctions to astrocytes loaded whole-cell with cytosolic indicators in area CA1 of acute hippocampal slices. Aiming at high sensitivity of [Ca(2+) ] measurements, we also employed life-time imaging of the Ca(2+) indicator Oregon Green BAPTA-1...
November 29, 2016: Glia
https://www.readbyqxmd.com/read/27888531/fate-of-microglia-during-hiv-1-infection-from-activation-to-senescence
#8
REVIEW
Natalie C Chen, Andrea T Partridge, Christian Sell, Claudio Torres, Julio Martín-García
Microglia support productive human immunodeficiency virus type 1 (HIV-1) infection and disturbed microglial function could contribute to the development of HIV-associated neurocognitive disorders (HAND). Better understanding of how HIV-1 infection and viral protein exposure modulate microglial function during the course of infection could lead to the identification of novel therapeutic targets for both the eradication of HIV-1 reservoir and treatment of neurocognitive deficits. This review first describes microglial origins and function in the normal central nervous system (CNS), and the changes that occur during aging...
November 26, 2016: Glia
https://www.readbyqxmd.com/read/27878997/corneal-epithelial-cells-function-as-surrogate-schwann-cells-for-their-sensory-nerves
#9
REVIEW
Mary Ann Stepp, Gauri Tadvalkar, Raymond Hakh, Sonali Pal-Ghosh
The eye is innervated by neurons derived from both the central nervous system and peripheral nervous system (PNS). While much is known about retinal neurobiology and phototransduction, less attention has been paid to the innervation of the eye by the PNS and the roles it plays in maintaining a functioning visual system. The ophthalmic branch of the trigeminal ganglion contains somas of neurons that innervate the cornea. These nerves provide sensory functions for the cornea and are referred to as intraepithelial corneal nerves (ICNs) consisting of subbasal nerves and their associated intraepithelial nerve terminals...
November 23, 2016: Glia
https://www.readbyqxmd.com/read/27862359/the-conversion-of-glutamate-by-glutamine-synthase-in-neocortical-astrocytes-from-juvenile-rat-is-important-to-limit-glutamate-spillover-and-peri-extrasynaptic-activation-of-nmda-receptors
#10
Yosra Trabelsi, Mohamed Amri, Hélène Becq, Florence Molinari, Laurent Aniksztejn
Glutamate transporters (EAATs) are important to maintain spatial and temporal specificity of synaptic transmission. Their efficiency to uptake and transport glutamate into the intracellular space depends on several parameters including the intracellular concentrations of Na(+) and glutamate, the elevations of which may slow down the cycling rate of EAATs. In astrocytes, glutamate is maintained at low concentration due to the presence of specific enzymes such as glutamine synthase (GS). GS inhibition results in cytosolic accumulation of glutamate suggesting that the conversion of glutamate by GS is important for EAATs operation...
February 2017: Glia
https://www.readbyqxmd.com/read/27862351/p2y12-receptor-is-expressed-on-human-microglia-under-physiological-conditions-throughout-development-and-is-sensitive-to-neuroinflammatory-diseases
#11
Alexander Mildner, Hao Huang, Josefine Radke, Werner Stenzel, Josef Priller
Microglia are resident immune cells in the central nervous system (CNS), which are essential for immune defence and critically contribute to neuronal functions during homeostasis. Until now, little is known about microglia biology in humans in part due to the lack of microglia-specific markers. We therefore investigated the expression of the purinergic receptor P2Y12 in human brain tissue. Compared to classical markers used to identify microglia such as Iba1, CD68 or MHCII, we found that P2Y12 is expressed on parenchymal microglia but is absent from perivascular or meningeal macrophages...
February 2017: Glia
https://www.readbyqxmd.com/read/27859601/the-protein-tyrosine-phosphatase-dep-1-promotes-migration-and-phagocytic-activity-of-microglial-cells-in-part-through-negative-regulation-of-fyn-tyrosine-kinase
#12
Nadine Schneble, Julia Müller, Stefanie Kliche, Reinhard Bauer, Reinhard Wetzker, Frank-D Böhmer, Zhao-Qi Wang, Jörg P Müller
Microglia cells are brain macrophages whose proper functioning is essential for maintenance and repair processes of the central nervous system (CNS). Migration and phagocytosis are critical aspects of microglial activity. By using genetically modified cell lines and knockout mice we demonstrate here that the receptor protein-tyrosine phosphatase (PTP) DEP-1 (also known as PTPRJ or CD148) acts as a positive regulator of both processes in vitro and in vivo. Notably, reduced microglial migration was detectable in brains of Ptprj(-/-) mice using a wounding assay...
February 2017: Glia
https://www.readbyqxmd.com/read/27859594/glutamate-transporter-associated-anion-channels-adjust-intracellular-chloride-concentrations-during-glial-maturation
#13
Verena Untiet, Peter Kovermann, Niklas J Gerkau, Thomas Gensch, Christine R Rose, Christoph Fahlke
Astrocytic volume regulation and neurotransmitter uptake are critically dependent on the intracellular anion concentration, but little is known about the mechanisms controlling internal anion homeostasis in these cells. Here we used fluorescence lifetime imaging microscopy (FLIM) with the chloride-sensitive dye MQAE to measure intracellular chloride concentrations in murine Bergmann glial cells in acute cerebellar slices. We found Bergmann glial [Cl(-) ]int to be controlled by two opposing transport processes: chloride is actively accumulated by the Na(+) -K(+) -2Cl(-) cotransporter NKCC1, and chloride efflux through anion channels associated with excitatory amino acid transporters (EAATs) reduces [Cl(-) ]int to values that vary upon changes in expression levels or activity of these channels...
February 2017: Glia
https://www.readbyqxmd.com/read/27807898/yap-functions-as-a-mechanotransducer-in-oligodendrocyte-morphogenesis-and-maturation
#14
Takeshi Shimizu, Yasuyuki Osanai, Kenji F Tanaka, Manabu Abe, Rie Natsume, Kenji Sakimura, Kazuhiro Ikenaka
Oligodendrocytes (OLs) are myelinating cells of the central nervous system. Recent studies have shown that mechanical factors influence various cell properties. Mechanical stimuli can be transduced into intracellular biochemical signals through mechanosensors and intracellular mechanotransducers, such as YAP. However, the molecular mechanisms underlying mechanical regulation of OLs by YAP remain unknown. We found that OL morphology and interactions between OLs and neuronal axons were affected by knocking down YAP...
February 2017: Glia
https://www.readbyqxmd.com/read/27807896/transient-cnp-expression-by-early-progenitors-causes-cre-lox-based-reporter-lines-to-map-profoundly-different-fates
#15
Reshmi Tognatta, Wenjing Sun, Sandra Goebbels, Klaus-Armin Nave, Akiko Nishiyama, Susanne Schoch, Leda Dimou, Dirk Dietrich
NG2 expressing oligodendroglial precursor cells are ubiquitous in the central nervous system and the only cell type cycling throughout life. Previous fate mapping studies have remained inconsistent regarding the question whether NG2 cells are capable of generating certain types of neurons. Here, we use CNP-Cre mice to map the fate of a sub-population of NG2 cells assumed to be close to differentiation. When crossing these mice with the ROSA26/YFP Cre-reporter line we discovered large numbers of reporter-expressing pyramidal neurons in the piriform and dorsal cortex...
February 2017: Glia
https://www.readbyqxmd.com/read/27796063/endogenous-gaba-controls-oligodendrocyte-lineage-cell-number-myelination-and-cns-internode-length
#16
Nicola B Hamilton, Laura E Clarke, I Lorena Arancibia-Carcamo, Eleni Kougioumtzidou, Moritz Matthey, Ragnhildur Káradóttir, Louise Whiteley, Linda H Bergersen, William D Richardson, David Attwell
Adjusting the thickness and internodal length of the myelin sheath is a mechanism for tuning the conduction velocity of axons to match computational needs. Interactions between oligodendrocyte precursor cells (OPCs) and developing axons regulate the formation of myelin around axons. We now show, using organotypic cerebral cortex slices from mice expressing eGFP in Sox10-positive oligodendrocytes, that endogenously released GABA, acting on GABAA receptors, greatly reduces the number of oligodendrocyte lineage cells...
February 2017: Glia
https://www.readbyqxmd.com/read/27785828/rapid-sodium-signaling-couples-glutamate-uptake-to-breakdown-of-atp-in-perivascular-astrocyte-endfeet
#17
Julia Langer, Niklas J Gerkau, Amin Derouiche, Christian Kleinhans, Behrouz Moshrefi-Ravasdjani, Michaela Fredrich, Karl W Kafitz, Gerald Seifert, Christian Steinhäuser, Christine R Rose
Perivascular endfeet of astrocytes are highly polarized compartments that ensheath blood vessels and contribute to the blood-brain barrier. They experience calcium transients with neuronal activity, a phenomenon involved in neurovascular coupling. Endfeet also mediate the uptake of glucose from the blood, a process stimulated in active brain regions. Here, we demonstrate in mouse hippocampal tissue slices that endfeet undergo sodium signaling upon stimulation of glutamatergic synaptic activity. Glutamate-induced endfeet sodium transients were diminished by TFB-TBOA, suggesting that they were generated by sodium-dependent glutamate uptake...
February 2017: Glia
https://www.readbyqxmd.com/read/27778404/progranulin-protects-against-exaggerated-axonal-injury-and-astrogliosis-following-traumatic-brain-injury
#18
Lutz Menzel, Lisa Kleber, Carina Friedrich, Regina Hummel, Larissa Dangel, Jennifer Winter, Katja Schmitz, Irmgard Tegeder, Michael K E Schäfer
In response to traumatic brain injury (TBI) microglia/macrophages and astrocytes release inflammatory mediators with dual effects on secondary brain damage progression. The neurotrophic and anti-inflammatory glycoprotein progranulin (PGRN) attenuates neuronal damage and microglia/macrophage activation in brain injury but mechanisms are still elusive. Here, we studied histopathology, neurology and gene expression of inflammatory markers in PGRN-deficient mice (Grn(-/-) ) 24 h and 5 days after experimental TBI...
February 2017: Glia
https://www.readbyqxmd.com/read/27778395/complement-c3-on-microglial-clusters-in-multiple-sclerosis-occur-in-chronic-but-not-acute-disease-implication-for-disease-pathogenesis
#19
Iliana Michailidou, Daphne M P Naessens, Simon Hametner, Willemijn Guldenaar, Evert-Jan Kooi, Jeroen J G Geurts, Frank Baas, Hans Lassmann, Valeria Ramaglia
Microglial clusters with C3d deposits are observed in the periplaque of multiple sclerosis (MS) brains and were proposed as early stage of lesion formation. As such they should appear in the brain of MS donors with acute disease but thus far this has not been shown. Using postmortem brain tissue from acute (n = 10) and chronic (n = 15) MS cases we investigated whether C3d+ microglial clusters are part of an acute attack against myelinated axons, which could have implications for disease pathogenesis...
February 2017: Glia
https://www.readbyqxmd.com/read/27778377/dynamics-of-pdgfr%C3%AE-expression-in-different-cell-types-after-brain-injury
#20
Jenni Kyyriäinen, Xavier Ekolle Ndode-Ekane, Asla Pitkänen
Platelet-derived growth factor receptor β (PDGFRβ) is upregulated after brain injury and its depletion results in the blood-brain barrier (BBB) damage. We investigated the time-window and localization of PDGFRβ expression in mice with intrahippocampal kainic acid-induced status epilepticus (SE) and in rats with lateral fluid-percussion-induced traumatic brain injury (TBI). Tissue immunohistochemistry was evaluated at several time-points after SE and TBI. The distribution of PDGFRβ was analyzed, and its cell type-specific expression was verified with double/triple-labeling of astrocytes (GFAP), NG2 cells, and endothelial cells (RECA-1)...
February 2017: Glia
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