Lysosomal Functions in Glia Associated with Neurodegeneration
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A Guide to Glutamate Receptors
A guide to glutamate receptors 1 Contents Glutamate receptors . 4 Ionotropic glutamate receptors . 4 - Structure ........................................................................................................... 4 - Function ............................................................................................................ 5 - AMPA receptors ................................................................................................. 6 - NMDA receptors ................................................................................................. 6 - Kainate receptors ............................................................................................... 6 Metabotropic glutamate receptors . 8 - Structure ........................................................................................................... 8 - Function ............................................................................................................ 9 - Group I: mGlu1 and mGlu5. .9 - Group II: mGlu2 and mGlu3 ................................................................................. 10 - Group III: mGlu4, mGlu6, mGlu7 and mGlu8 ............................................................ 10 Protocols and webinars . 11 - Protocols ......................................................................................................... 11 - Webinars ......................................................................................................... 12 References and further reading . 13 Excitatory synapse pathway -
Seq2pathway Vignette
seq2pathway Vignette Bin Wang, Xinan Holly Yang, Arjun Kinstlick May 19, 2021 Contents 1 Abstract 1 2 Package Installation 2 3 runseq2pathway 2 4 Two main functions 3 4.1 seq2gene . .3 4.1.1 seq2gene flowchart . .3 4.1.2 runseq2gene inputs/parameters . .5 4.1.3 runseq2gene outputs . .8 4.2 gene2pathway . 10 4.2.1 gene2pathway flowchart . 11 4.2.2 gene2pathway test inputs/parameters . 11 4.2.3 gene2pathway test outputs . 12 5 Examples 13 5.1 ChIP-seq data analysis . 13 5.1.1 Map ChIP-seq enriched peaks to genes using runseq2gene .................... 13 5.1.2 Discover enriched GO terms using gene2pathway_test with gene scores . 15 5.1.3 Discover enriched GO terms using Fisher's Exact test without gene scores . 17 5.1.4 Add description for genes . 20 5.2 RNA-seq data analysis . 20 6 R environment session 23 1 Abstract Seq2pathway is a novel computational tool to analyze functional gene-sets (including signaling pathways) using variable next-generation sequencing data[1]. Integral to this tool are the \seq2gene" and \gene2pathway" components in series that infer a quantitative pathway-level profile for each sample. The seq2gene function assigns phenotype-associated significance of genomic regions to gene-level scores, where the significance could be p-values of SNPs or point mutations, protein-binding affinity, or transcriptional expression level. The seq2gene function has the feasibility to assign non-exon regions to a range of neighboring genes besides the nearest one, thus facilitating the study of functional non-coding elements[2]. Then the gene2pathway summarizes gene-level measurements to pathway-level scores, comparing the quantity of significance for gene members within a pathway with those outside a pathway. -
Plp-Positive Progenitor Cells Give Rise to Bergmann Glia in the Cerebellum
Citation: Cell Death and Disease (2013) 4, e546; doi:10.1038/cddis.2013.74 OPEN & 2013 Macmillan Publishers Limited All rights reserved 2041-4889/13 www.nature.com/cddis Olig2/Plp-positive progenitor cells give rise to Bergmann glia in the cerebellum S-H Chung1, F Guo2, P Jiang1, DE Pleasure2,3 and W Deng*,1,3,4 NG2 (nerve/glial antigen2)-expressing cells represent the largest population of postnatal progenitors in the central nervous system and have been classified as oligodendroglial progenitor cells, but the fate and function of these cells remain incompletely characterized. Previous studies have focused on characterizing these progenitors in the postnatal and adult subventricular zone and on analyzing the cellular and physiological properties of these cells in white and gray matter regions in the forebrain. In the present study, we examine the types of neural progeny generated by NG2 progenitors in the cerebellum by employing genetic fate mapping techniques using inducible Cre–Lox systems in vivo with two different mouse lines, the Plp-Cre-ERT2/Rosa26-EYFP and Olig2-Cre-ERT2/Rosa26-EYFP double-transgenic mice. Our data indicate that Olig2/Plp-positive NG2 cells display multipotential properties, primarily give rise to oligodendroglia but, surprisingly, also generate Bergmann glia, which are specialized glial cells in the cerebellum. The NG2 þ cells also give rise to astrocytes, but not neurons. In addition, we show that glutamate signaling is involved in distinct NG2 þ cell-fate/differentiation pathways and plays a role in the normal development of Bergmann glia. We also show an increase of cerebellar oligodendroglial lineage cells in response to hypoxic–ischemic injury, but the ability of NG2 þ cells to give rise to Bergmann glia and astrocytes remains unchanged. -
Control of Synapse Number by Glia Erik M
R EPORTS RGCs (8). Similar results were obtained un- der both conditions. After 2 weeks in culture, Control of Synapse Number we used whole-cell patch-clamp recording to measure the significant enhancement of spon- by Glia taneous synaptic activity by astrocytes (Fig. 1, A and B) (9). In the absence of astroglia, Erik M. Ullian,* Stephanie K. Sapperstein, Karen S. Christopherson, little synaptic activity occurred even when Ben A. Barres RGCs were cultured with their tectal target cells (6). This difference in synaptic activity Although astrocytes constitute nearly half of the cells in our brain, their persisted even after a month in culture, indi- function is a long-standing neurobiological mystery. Here we show by quantal cating that it is not accounted for by a matu- analyses, FM1-43 imaging, immunostaining, and electron microscopy that few rational delay. To examine whether glia reg- synapses form in the absence of glial cells and that the few synapses that do ulate synaptic activity by enhancing postsyn- form are functionally immature. Astrocytes increase the number of mature, aptic responsiveness, we measured the re- functional synapses on central nervous system (CNS) neurons by sevenfold and sponse of RGCs to pulses of L-glutamate are required for synaptic maintenance in vitro. We also show that most syn- applied to the cell somas. Regardless of the apses are generated concurrently with the development of glia in vivo. These presence of glia, RGCs responded with in- data demonstrate a previously unknown function for glia in inducing and ward currents (Fig. 1C) that were blocked by stabilizing CNS synapses, show that CNS synapse number can be profoundly glutamate receptor antagonists (10). -
Neuregulin 1–Erbb2 Signaling Is Required for the Establishment of Radial Glia and Their Transformation Into Astrocytes in Cerebral Cortex
Neuregulin 1–erbB2 signaling is required for the establishment of radial glia and their transformation into astrocytes in cerebral cortex Ralf S. Schmid*, Barbara McGrath*, Bridget E. Berechid†, Becky Boyles*, Mark Marchionni‡, Nenad Sˇ estan†, and Eva S. Anton*§ *University of North Carolina Neuroscience Center and Department of Cell and Molecular Physiology, University of North Carolina School of Medicine, Chapel Hill, NC 27599; †Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06510; and ‡CeNes Pharamceuticals, Inc., Norwood, MA 02062 Communicated by Pasko Rakic, Yale University School of Medicine, New Haven, CT, January 27, 2003 (received for review December 12, 2002) Radial glial cells and astrocytes function to support the construction mine whether NRG-1-mediated signaling is involved in radial and maintenance, respectively, of the cerebral cortex. However, the glial cell development and differentiation in the cerebral cortex. mechanisms that determine how radial glial cells are established, We show that NRG-1 signaling, involving erbB2, may act in maintained, and transformed into astrocytes in the cerebral cortex are concert with Notch signaling to exert a critical influence in the not well understood. Here, we show that neuregulin-1 (NRG-1) exerts establishment, maintenance, and appropriate transformation of a critical role in the establishment of radial glial cells. Radial glial cell radial glial cells in cerebral cortex. generation is significantly impaired in NRG mutants, and this defect can be rescued by exogenous NRG-1. Down-regulation of expression Materials and Methods and activity of erbB2, a member of the NRG-1 receptor complex, leads Clonal Analysis to Study NRG’s Role in the Initial Establishment of to the transformation of radial glial cells into astrocytes. -
Area-Specific Synapse Structure in Branched Posterior Nucleus Axons Reveals a New Level of Complexity in Thalamocortical Networks
The Journal of Neuroscience, March 25, 2020 • 40(13):2663–2679 • 2663 Systems/Circuits Area-Specific Synapse Structure in Branched Posterior Nucleus Axons Reveals a New Level of Complexity in Thalamocortical Networks Javier Rodriguez-Moreno,1 Cesar Porrero,1 Astrid Rollenhagen,2 Mario Rubio-Teves,1 Diana Casas-Torremocha,1 X Lidia Alonso-Nanclares,3 Rachida Yakoubi,2 XAndrea Santuy,3 XAngel Merchan-Pe´rez,3,5,6 XJavier DeFelipe,3,4,5 Joachim H.R. Lu¨bke,2,7,8* and XFrancisco Clasca1* 1Department of Anatomy and Neuroscience, School of Medicine, Auto´noma de Madrid University, 28029 Madrid, Spain, 2Institute of Neuroscience and Medicine INM-10, Research Centre Ju¨lich GmbH, 52425 Ju¨lich, Germany, 3Laboratorio Cajal de Circuitos Corticales, Centro de Tecnología Biome´dica, Universidad Polite´cnica de Madrid, Pozuelo de Alarco´n, 28223 Madrid, Spain, 4Instituto Cajal, Consejo Superior de Investigaciones Científicas, Arce 37 28002, Madrid, Spain, 5CIBERNED, Centro de Investigacio´n Biome´dica en Red de Enfermedades Neurodegenerativas, 28031 Madrid, Spain, 6Departamento de Arquitectura y Tecnología de Sistemas Informa´ticos, Universidad Polite´cnica de Madrid. Boadilla del Monte, 28660 Madrid, Spain, 7Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty RWTH University Hospital Aachen, 52074 Aachen, Germany, and 8JARA-Translational Brain Medicine, 52425 Ju¨lich-Aachen, Germany Thalamocortical posterior nucleus (Po) axons innervating the vibrissal somatosensory (S1) and motor (MC) cortices are key links in the brain neuronal network that allows rodents to explore the environment whisking with their motile snout vibrissae. Here, using fine-scale high-end 3D electron microscopy, we demonstrate in adult male C57BL/6 wild-type mice marked differences between MC versus S1 Po synapses in (1) bouton and active zone size, (2) neurotransmitter vesicle pool size, (3) distribution of mitochondria around synapses, and (4) proportion of synapses established on dendritic spines and dendritic shafts. -
Anti-COPE Picoband Antibody Catalog # ABO13033
10320 Camino Santa Fe, Suite G San Diego, CA 92121 Tel: 858.875.1900 Fax: 858.622.0609 Anti-COPE Picoband Antibody Catalog # ABO13033 Specification Anti-COPE Picoband Antibody - Product Information Application IHC Primary Accession O14579 Host Rabbit Reactivity Human, Mouse, Rat Clonality Polyclonal Format Lyophilized Description Rabbit IgG polyclonal antibody for Coatomer subunit epsilon(COPE) detection. Tested with WB, IHC-P in Human;Mouse;Rat. Figure 4. IHC analysis of COPE using Reconstitution anti-COPE antibody (ABO13033). Add 0.2ml of distilled water will yield a concentration of 500ug/ml. Anti-COPE Picoband Antibody - Additional Information Gene ID 11316 Other Names Coatomer subunit epsilon, Epsilon-coat protein, Epsilon-COP, COPE Calculated MW 34482 MW KDa Application Details Immunohistochemistry(Paraffin-embedded Section), 0.5-1 µg/ml, Human, Mouse, Rat, By Heat<br> Western blot, 0.1-0.5 µg/ml, Human, Mouse, Rat, <br> <br> Subcellular Localization Cytoplasm . Golgi apparatus membrane ; Peripheral membrane protein ; Cytoplasmic side . Cytoplasmic vesicle, COPI-coated vesicle membrane ; Peripheral membrane protein ; Cytoplasmic side . The coatomer is cytoplasmic or polymerized on the cytoplasmic side of the Golgi, as well as on the vesicles/buds originating from it. Page 1/3 10320 Camino Santa Fe, Suite G San Diego, CA 92121 Tel: 858.875.1900 Fax: 858.622.0609 Contents Each vial contains 5mg BSA, 0.9mg NaCl, 0.2mg Na2HPO4, 0.05mg NaN3. Immunogen E. coli-derived human COPE recombinant protein (Position: E80-A308). Human COPE shares 89.5% amino acid (aa) sequence identity with mouse COPE. Purification Immunogen affinity purified. Cross Reactivity No cross reactivity with other proteins. -
The Interplay Between Neurons and Glia in Synapse Development And
Available online at www.sciencedirect.com ScienceDirect The interplay between neurons and glia in synapse development and plasticity Jeff A Stogsdill and Cagla Eroglu In the brain, the formation of complex neuronal networks and regulate distinct aspects of synaptic development and amenable to experience-dependent remodeling is complicated circuit connectivity. by the diversity of neurons and synapse types. The establishment of a functional brain depends not only on The intricate communication between neurons and glia neurons, but also non-neuronal glial cells. Glia are in and their cooperative roles in synapse formation are now continuous bi-directional communication with neurons to direct coming to light due in large part to advances in genetic the formation and refinement of synaptic connectivity. This and imaging tools. This article will examine the progress article reviews important findings, which uncovered cellular made in our understanding of the role of mammalian and molecular aspects of the neuron–glia cross-talk that perisynaptic glia (astrocytes and microglia) in synapse govern the formation and remodeling of synapses and circuits. development, maturation, and plasticity since the previ- In vivo evidence demonstrating the critical interplay between ous Current Opinion article [1]. An integration of past and neurons and glia will be the major focus. Additional attention new findings of glial control of synapse development and will be given to how aberrant communication between neurons plasticity is tabulated in Box 1. and glia may contribute to neural pathologies. Address Glia control the formation of synaptic circuits Department of Cell Biology, Duke University Medical Center, Durham, In the CNS, glial cells are in tight association with NC 27710, USA synapses in all brain regions [2]. -
PRESYNAPTIC Α2δ SUBUNITS ARE KEY ORGANIZERS of GLUTAMATERGIC SYNAPSES Clemens L
bioRxiv preprint doi: https://doi.org/10.1101/826016; this version posted October 31, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. PRESYNAPTIC α2δ SUBUNITS ARE KEY ORGANIZERS OF GLUTAMATERGIC SYNAPSES Clemens L. Schöpf1, Stefanie Geisler1, Ruslan I. Stanika1, Marta Campiglio1, Walter A. Kaufmann3, Benedikt Nimmervoll1, Bettina Schlick1, Ryuichi Shigemoto3, and Gerald J. Obermair1,2* From Division of Physiology, Medical University Innsbruck, A-6020 Innsbruck1, Division Physiology, Karl Landsteiner University of Health Sciences, A-3500 Krems2, and Institute of Science and Technology Austria, A-3400 Klosterneuburg3, Austria. Running head: Presynaptic α2δ subunits organize synapses Address correspondence to: *Gerald J. Obermair, Univ.-Prof. Dr., Phone: +43-2732-72090490, E-mail: [email protected], [email protected] In nerve cells the genes encoding for α2δ the auxiliary β and α2δ subunits. α2δ subunits, the subunits of voltage-gated calcium channels targets of the widely prescribed anti-epileptic and (VGCCs) have been linked to synaptic functions anti-allodynic drugs gabapentin and pregabalin, are and neurological disease. Here we show that α2δ membrane-anchored extracellular glycoproteins, subunits are essential for the formation and which modulate VGCC trafficking and calcium organization of glutamatergic synapses. Using a currents (Arikkath and Campbell, 2003; Dolphin, cellular α2δ subunit triple loss-of-function model, 2013; Geisler et al., 2015; Obermair et al., 2008; we demonstrate a failure in presynaptic Zamponi et al., 2015). -
Neural Control and Neuromodulationof Lower Urinary
Neural Control and Neuromodulation of Lower Urinary Tract Function William C. de Groat University of Pittsburgh Topics • Anatomy and functions of the lower urinary tract • Peripheral innervation (efferent and afferent nerves) • Central neural control of the lower urinary tract • Lower urinary tract dysfunction • Treatment of dysfunction (neuromodulation) • Research opportunities Anatomy and Functions of the Lower Urinary Tract Functions Two Types of Voiding 1. Urine storage - Reservoir: Bladder INVOLUNTARY (Reflex) (infant & fetus) Defect in 2. Urine release Maturation Maturation - Outlet: Urethra INVOLUNTARY THERAPY VOLUNTARY (Reflex) (adult) (adult) Bladder Parkinson’s, MS, stroke, brain tumors, spinal cord injury, Urethra aging, cystitis Lower Urinary Tract Innervation Two Types of Visceral Afferent Neurons: Bladder & Bowel Aδ-fibers responsible for normal bladder sensations C-fibers contribute to urgency, frequency and incontinence Afferent Sensitivity may be Influenced by Substances Released from the Urothelium Aδ fiber C fiber X CNS Urothelium The Bladder U rothelium Glycosaminoglycan Layer Uroplakin Plaques and Discoidal Vesicles r=_zo_"_"l_a_o_cc-lu---.dens } Umbrella Cell Stratum Intermediate Cell Stratum } Basal Cell Stratum Afferent Nerve fiber Urothelial-Afferent Interactions ( I ( I ( I ( ' ( I ( I ( I Urothelium ( I ( 0 I I I AChR ATP, NO, NKA, ACh, NGF ~erves ' Efferent ' nerves nerves Interaction of Sensory Pathways of Multiple Pelvic Organs Convergent Dichotomizing Branch Bladder point Colon Somatic and Visceral Afferent -
Electrical Synapses and Their Functional Interactions with Chemical Synapses
REVIEWS Electrical synapses and their functional interactions with chemical synapses Alberto E. Pereda Abstract | Brain function relies on the ability of neurons to communicate with each other. Interneuronal communication primarily takes place at synapses, where information from one neuron is rapidly conveyed to a second neuron. There are two main modalities of synaptic transmission: chemical and electrical. Far from functioning independently and serving unrelated functions, mounting evidence indicates that these two modalities of synaptic transmission closely interact, both during development and in the adult brain. Rather than conceiving synaptic transmission as either chemical or electrical, this article emphasizes the notion that synaptic transmission is both chemical and electrical, and that interactions between these two forms of interneuronal communication might be required for normal brain development and function. Communication between neurons is required for Electrical and chemical synapses are now known to brain function, and the quality of such communica- coexist in most organisms and brain structures, but details tion enables hardwired neural networks to act in a of the properties and distribution of these two modalities of dynamic fashion. Functional interactions between transmission are still emerging. Most research efforts neurons occur at anatomically identifiable cellular have focused on exploring the mechanisms of chemi- regions called synapses. Although the nature of synaptic cal transmission, and considerably less is known transmission has been an area of enormous controversy about those underlying electrical transmission. It was (BOX 1), two main modalities of synaptic transmission — thought that electrical synapses were more abundant namely, chemical and electrical — are now recognized. At in invertebrates and cold-blooded vertebrates than chemical synapses, information is transferred through in mammals. -
Myelin Biogenesis Is Associated with Pathological Ultrastructure That Is
bioRxiv preprint doi: https://doi.org/10.1101/2021.02.02.429485; this version posted February 4, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. 1 Myelin biogenesis is associated with pathological ultrastructure that 2 is resolved by microglia during development 3 4 5 Minou Djannatian1,2*, Ulrich Weikert3, Shima Safaiyan1,2, Christoph Wrede4, Cassandra 6 Deichsel1,2, Georg Kislinger1,2, Torben Ruhwedel3, Douglas S. Campbell5, Tjakko van Ham6, 7 Bettina Schmid2, Jan Hegermann4, Wiebke Möbius3, Martina Schifferer2,7, Mikael Simons1,2,7* 8 9 1Institute of Neuronal Cell Biology, Technical University Munich, 80802 Munich, Germany 10 2German Center for Neurodegenerative Diseases (DZNE), 81377 Munich, Germany 11 3Max-Planck Institute of Experimental Medicine, 37075 Göttingen, Germany 12 4Institute of Functional and Applied Anatomy, Research Core Unit Electron Microscopy, 13 Hannover Medical School, 30625, Hannover, Germany 14 5Department of Neuronal Remodeling, Graduate School of Pharmaceutical Sciences, Kyoto 15 University, Sakyo-ku, Kyoto 606-8501, Japan. 16 6Department of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, 3015 CN, 17 the Netherlands 18 7Munich Cluster of Systems Neurology (SyNergy), 81377 Munich, Germany 19 20 *Correspondence: [email protected] or [email protected] 21 Keywords 22 Myelination, degeneration, phagocytosis, microglia, oligodendrocytes, phosphatidylserine 23 24 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.02.02.429485; this version posted February 4, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.