DOCSLIB.ORG

Olfactory Ensheathing Cell Phenotype After Implantation Into the Lesioned

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Olfactory Ensheathing Cell Phenotype After Implantation Into the Lesioned Olfactory Ensheathing Cell Phenotype after Implantation into the Lesioned Spinal Cord Emma Woodhall BSc. Hons. Submitted in fulfilment ofthe requirements for the degree of Doctor ofPhilosophy University of Tasmania April 2004 STATEMENT This thesis contains no material which has been accepted for a degree or diploma by the University of Tasmania or any other institution, except by way of background information duly acknowledged in the text. To the best of my knowledge and belief this thesis contains no material previously published or written by another person except where due acknowledgment is made. Emma Woodhall STATEMENT OF AUTHORITY OF ACCESS This thesis may be made available for loan and limited copying in accordance with the Copyright Act 1968. EmmaWoodhall Acknowlegements ACKNOWLEGEMENTS Many thanks to my supervisors Dr Inn Chuah and Dr Adrian West (for all their help and support), Julie Harris, Dr Adele Holloway, Dr Lisa Foa and Dr Niels Anderson (for all the encouragement), Dr Derek Choi-Lundberg (for help with the surgery), each of my office mates Lee-Lee, Liz, Meredith, and Adele W (for entertainment, conversation and lots of mocha coffee), Gerry Nash (for expert technical assistance with the electron microscope), to the animal house staff (without whom this project would not have been possible), Roger (just for being himself), Adele V (for loads of excellent tech tips), Jill Aschman (for being the chief distraction), all of the MBUites (your wonderful), the Anatomy and Physiology crew, the Biochemistry Department and Pete (for being such a sweetie). Thankyou all for making my time at UTAS most enjoyable!!. Abstract ABSTRACT Although olfactory ensheathing cells (OECs) are used to promote repair in the injured spinal cord, little is known of their phenotype in this environment. This study examined the effect of the injured spinal cord on OEC morphology and gene expression. For in situ experiments OECs were encapsulated in porous polymer tubes and implanted into the lesioned rat spinal cord. Adult male hooded Wistar rats (300-350g) were anaesthetised with isoflurane maintained at 2.5% with 100% 02 (0.5L/min). Lesions were made to the corticospinal tract at the level ofT7-T8 and OEC-filled capsules were inserted under the dura above the lesion. After one week animals were sacrificed and the capsules retrieved. Procedures were performed in accordance with NHMRC guidelines approved by the University of Tasmania Animal Ethics Committee. Morphological characteristics were examined using scanning electron microscopy (SEM) for which implanted and un-implanted capsules were cut into halves so as the inner surfaces could be viewed. Implanted capsules were filled with rounded OECs and extracellular matrix (ECM)-like matter. Although no cells with the morphology of cultured OECs were observed these may have been obscured by the abundant ECM. In the un-implanted capsules cells with morphology typical of cultured OECs were predominant and although some rounded cells were detected. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) was used to analyse expression of Neuregulin-1 (Nrg-1) and Nogo in cultured OECs and encapsulated OECs both in culture and after implantation. Neuregulins are known mitogens and survival factors for central nervous system (CNS) cells whilst Nogo is an axonal growth regulator. For comparison transcripts were also examined in a number of other glial cell types. Similar to astrocytes (ASTs) and fibroblasts (FBs), OECs expressed various Nrg-1 subtypes Abstract including neu Differentiation Factor (NDF), Glial Growth Factor (GGF) and Sensory and Motomeuron-derived Factor (SMDF) along with other splice variants including those containing the epidermal growth factor (EGF), a-EGF, P-EGF and secreted domains. After implantation, OECs increased expression of NDF and secreted Neuregulin and decreased expression of the other variants. Olfactory ensheathing cells, oligodendrocytes (OLGs) Schwann cells (SCs) and ASTs all expressed Nogo-A, -B and -ABC. OECs and OLGs were also immunopositive for Nogo-A protein. Unlike OLGs, OECs, SCs and ASTs expressed mRNA for the Nogo-66 receptor (NgR) although the protein could not be detected by immunocytochemistry in OECs. Implantation of OECs resulted in an increase in Nogo-A and -B and a decrease in Nogo-ABC and the NgR. Taken together these results show that OEC phenotype in the lesion environment is different from their characteristic profile in culture. Table of contents TABLE OF CONTENTS LIST OF TABLES------------------------------------------------------------------------------ 4 LIST OF FIGURES----------------------------------------------------------------------------- 5 C::IIA:PTEll ONE--------------------------------------------------------------------------------6 Introduction-------------------------------------------------------------------------------------- 6 1.1. Injury in the C::entral Nervous System--------------------------------------------------- 6 1.2. Inhibitors ofNeurite llegeneration in the C::entral Nervous System----------------- 7 1.2.1. The G lial Scar------------------------------------------------------------------------- 7 1. 2. 2. Nogo------------------------------------------------------ ------------------------------ 8 1.2.2.1. The Nogo-66 lleceptor --------------------------------------------------------16 1.2.2.2. OMgp and MAG Signaling via the Ngll------------------------------------16 1.2.2.3. Mechanisms of Ngll Function------------------------------------------------18 1.2.2.4. The p75NTR as a C::o-receptor for the Ngll-----------------------------------18 1.2.3. Myelin-Associated Glycoprotein--------------------------------------------------19 1.2.4. llho Signaling by Myelin-Associated Inhibitors ofNeurite llegeneration---22 1.3. Use of Olfactory Ensheathing C::ells in :Promoting llepair in the Injured C::NS -- 23 1.3.1. Origin of Olfactory Ensheathing C::ells--------------------------------------------23 1.3 .2. :Phenotypic :Properties and :Plasticity----------------------------------------------24 1.3 .3. llegulation of OEC:: :Proliferation, Differentiation and Survival In Vitro -----25 1. 3 .4. 0 EC::s :Promote Axonal Growth----------------------------------------------------2 7 1.3. 5. OEC:: Transplant-Mediated llemyelination ---------------------------------------3 0 1.3.6. The Effect of the Injured Spinal C::ord on OEC::s---------------------------------33 1.4. :Properties of OEC::s that :Promote C::entral Nervous Tissue llepair ---------------- 35 1.4.1. Integration Within the IIost Environment----------------------------------------35 1.4.2. N eurotrophic Factors----------------------------------------------------------------3 6 1.4.2.1. N eurotrophin Family-----------------------------------------------------------3 6 1.4.2.2. N eurotrophin-llelated Factors ------------------------------------------------3 8 1.4.2.3. N euregulins ---------------------------------------------------------------------3 9 1.4 .2.4. Other Growth Factors ----------------------------------------------------------4 2 1.4.3. C::ell Adhesion Molecules and Guidance C::ues-----------------------------------44 1.5. Summary---------------------------------------------------------------------------------- 46 C::IIA:PTEll TWO ----------------------------------------------------------------------------- 48 General Materials and Methods------------------------------------------------------------- 48 2.1. C::ell C::ultures------------------------------------------------------------------------------ 48 2.1.1. OEC:: C::ulture -------------------------------------------------------------------------48 2.1.2. Astrocyte and Oligodendrocyte C::ulture ------------------------------------------51 2.1.2.1. Mixed C::ulture ------------------------------------------------------------------51 2.1.2.2. :Purification of Astrocytes -----------------------------------------------------52 2.1.2.3. :Purification of 0 ligodendrocytes---------------------------------------------5 2 2.1.3. Fibroblast C::ulture -------------------------------------------------------------------5 6 2.2. Immunohistochemistry and C::ell :Purity----------------------------------------------- 56 2.2.1. Immunostaining :Procedure---------------------------------------------------------56 2.2.2. C::ell C::ounts ---------------------------------------------------------------------------57 2.3. llat Brain Tissue :Procurement --------------------------------------------------------- 57 2.4. Total llNA Isolation and Quantitation ------------------------------------------------ 58 2.4.1. llNA Isolation------------------------------------------------------------------------5 8 Table of contents 2 2.4.1.1. Monolayered Cells -------------------------------------------------------------58 2.4.1.2. Encapsulated Cells -------------------------------------------------------------59 2.4.1.3. Rat Brain Tissue----------------------------------------------------------------60 2 .4 .2. DNase-1 Treatment------------------------------------------------------------------60 2.4.3. RNA Quantitation and Purity------------------------------------------------------61 2.5. Media and Solutions--------------------------------------------------------------------- 61 2. 5 .1. Ce 11 Culture --------------------------------------------------------------------------61 2 .5 .2. So 1utions ------------------------------------------------------------------------------64 2.5.2.1. RNA Extraction and RT-PCR ------------------------------------------------64
Load more

Recommended publications
  • The GDNF Family: a Role in Cancer? Graeme C
    Volume 20 Number 1 January 2018 pp. 99–117 99 www.neoplasia.com The GDNF Family: A Role in Cancer? Graeme C. Fielder*, 1, 2, Teresa Wen-Shan Yang*, 1, Mahalakshmi Razdan†, Yan Li†, Jun Lu†, Jo K. Perry‡, Peter E. Lobie§ and Dong-Xu Liu† *University of Auckland, Auckland, New Zealand; †The Centre for Biomedical and Chemical Sciences, School of Science, Faculty of Health and Environmental Sciences, Auckland University of Technology, Auckland, New Zealand; ‡Liggins Institute, University of Auckland, Auckland, New Zealand; §Cancer Science Institute of Singapore and Department of Pharmacology, National University of Singapore, Singapore; Tsinghua Berkeley Shenzhen Institute, Tsinghua University, Shenzhen, Guangdong, P. R. China Abstract The glial cell line–derived neurotrophic factor (GDNF) family of ligands (GFLs) comprising of GDNF, neurturin, artemin, and persephin plays an important role in the development and maintenance of the central and peripheral nervous system, renal morphogenesis, and spermatogenesis. Here we review our current understanding of GFL biology, and supported by recent progress in the area, we examine their emerging role in endocrine-related and other non–hormone-dependent solid neoplasms. The ability of GFLs to elicit actions that resemble those perturbed in an oncogenic phenotype, alongside mounting evidence of GFL involvement in tumor progression, presents novel opportunities for therapeutic intervention. Neoplasia (2018) 20, 99–117 Introduction GFL Signaling The glial cell line–derived neurotrophic factor (GDNF) family of Each member of the GDNF family is expressed as a pre-pro-precursor ligands (GFLs) is comprised of four structurally related factors: protein, which is proteolytically cleaved at a putative furin-like GDNF,neurturin(NRTN),artemin(ARTN),andpersephin cleavage site (RAAR) by yet unidentified enzymes to generate an (PSPN) [1–3].
    [Show full text]
  • GDNF Family Ligands and DRG Sensory Neurons 4337
    Development 127, 4335-4344 (2000) 4335 Printed in Great Britain © The Company of Biologists Limited 2000 DEV1547 Positive and negative interactions of GDNF, NTN and ART in developing sensory neuron subpopulations, and their collaboration with neurotrophins Christel Baudet1, Åsa Mikaels1, Heiner Westphal2, Jens Johansen3, Teit E. Johansen3 and Patrik Ernfors1,* 1Laboratory of Molecular Neurobiology, Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm, Sweden 2Laboratory of Mammalian Genes and Development, National Institute of Health, Bethesda, MD 20892, USA 3NsGene A/S, DK-2570 Ballerup, Denmark *Author for correspondence (e-mail: [email protected]) Accepted 25 July; published on WWW 26 September 2000 SUMMARY Glial cell line-derived neurotrophic factor (GDNF), family receptors are medium sized, whereas small-caliber neurturin (NTN) and neublastin/artemin (ART) are distant nociceptive cells preferentially express a single receptor. In members of the transforming growth factor β family, contrast to brain-derived neurotrophic factor (BDNF)- and have been shown to elicit neurotrophic effects upon dependent neurons, embryonic nerve growth factor (NGF)- several classes of peripheral and central neurons. Limited dependent nociceptive neurons switch dependency to information from in vitro and expression studies has GDNF, NTN and ART postnatally. Neurons that survive in also substantiated a role for GDNF family ligands in the presence of neurotrophin 3 (NT3) or neurotrophin 4 mammalian somatosensory neuron development. Here, we (NT4), including proprioceptive afferents, Merkel end show that although dorsal root ganglion (DRG) sensory organs and D-hair afferents, are also supported by GDNF neurons express GDNF family receptors embryonically, family ligands neonatally, although at postnatal stages they they do not survive in response to their ligands.
    [Show full text]
  • Current and Future Role of Tyrosine Kinases Inhibition in Thyroid Cancer: from Biology to Therapy
    International Journal of Molecular Sciences Review Current and Future Role of Tyrosine Kinases Inhibition in Thyroid Cancer: From Biology to Therapy 1, 1, 1,2,3, 3,4 María San Román Gil y, Javier Pozas y, Javier Molina-Cerrillo * , Joaquín Gómez , Héctor Pian 3,5, Miguel Pozas 1, Alfredo Carrato 1,2,3 , Enrique Grande 6 and Teresa Alonso-Gordoa 1,2,3 1 Medical Oncology Department, Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain; [email protected] (M.S.R.G.); [email protected] (J.P.); [email protected] (M.P.); [email protected] (A.C.); [email protected] (T.A.-G.) 2 The Ramon y Cajal Health Research Institute (IRYCIS), CIBERONC, 28034 Madrid, Spain 3 Medicine School, Alcalá University, 28805 Madrid, Spain; [email protected] (J.G.); [email protected] (H.P.) 4 General Surgery Department, Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain 5 Pathology Department, Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain 6 Medical Oncology Department, MD Anderson Cancer Center, 28033 Madrid, Spain; [email protected] * Correspondence: [email protected] These authors have contributed equally to this work. y Received: 30 June 2020; Accepted: 10 July 2020; Published: 13 July 2020 Abstract: Thyroid cancer represents a heterogenous disease whose incidence has increased in the last decades. Although three main different subtypes have been described, molecular characterization is progressively being included in the diagnostic and therapeutic algorithm of these patients. In fact, thyroid cancer is a landmark in the oncological approach to solid tumors as it harbors key genetic alterations driving tumor progression that have been demonstrated to be potential actionable targets.
    [Show full text]
  • Regulation of GDNF Expression in Sertoli Cells
    157 3 REPRODUCTIONREVIEW Regulation of GDNF expression in Sertoli cells Parag A Parekh1, Thomas X Garcia2,3 and Marie-Claude Hofmann1 1Department of Endocrine Neoplasia, UT MD Anderson Cancer Center, Houston, Texas, USA, 2Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA, 3Department of Biological and Environmental Sciences, University of Houston-Clear Lake, Houston, Texas, USA Correspondence should be addressed to M-C Hofmann; Email: [email protected] Abstract Sertoli cells regulate male germ cell proliferation and differentiation and are a critical component of the spermatogonial stem cell (SSC) niche, where homeostasis is maintained by the interplay of several signaling pathways and growth factors. These factors are secreted by Sertoli cells located within the seminiferous epithelium, and by interstitial cells residing between the seminiferous tubules. Sertoli cells and peritubular myoid cells produce glial cell line-derived neurotrophic factor (GDNF), which binds to the RET/GFRA1 receptor complex at the surface of undifferentiated spermatogonia. GDNF is known for its ability to drive SSC self- renewal and proliferation of their direct cell progeny. Even though the effects of GDNF are well studied, our understanding of the regulation its expression is still limited. The purpose of this review is to discuss how GDNF expression in Sertoli cells is modulated within the niche, and how these mechanisms impact germ cell homeostasis. Reproduction (2019) 157 R95–R107 Introduction reserve stem cells (A0), coexisting with a population of renewing spermatogonia that they called A1–A4 Proper regulation of stem cell fate is critical to maintain (Clermont & Leblond 1953, Clermont & Bustos-Obregon adequate cell numbers in health and diseases.
    [Show full text]
  • Neuronal Types and Their Specification Dynamics in the Autonomic Nervous System
    From the Department of Medical Biochemistry and Biophysics Karolinska Institutet, Stockholm, Sweden NEURONAL TYPES AND THEIR SPECIFICATION DYNAMICS IN THE AUTONOMIC NERVOUS SYSTEM Alessandro Furlan Stockholm 2016 All previously published papers were reproduced with permission from the publisher. Published by Karolinska Institutet. Printed by E-Print AB © Alessandro Furlan, 2016 ISBN 978-91-7676-419-0 On the cover: abstract illustration of sympathetic neurons extending their axons Credits: Gioele La Manno NEURONAL TYPES AND THEIR SPECIFICATION DYNAMICS IN THE AUTONOMIC NERVOUS SYSTEM THESIS FOR DOCTORAL DEGREE (Ph.D.) By Alessandro Furlan Principal Supervisor: Opponent: Prof. Patrik Ernfors Prof. Hermann Rohrer Karolinska Institutet Max Planck Institute for Brain Research Department of Medical Biochemistry and Research Group Developmental Neurobiology Biophysics Division of Molecular Neurobiology Examination Board: Prof. Jonas Muhr Co-supervisor(s): Karolinska Institutet Prof. Ola Hermansson Department of Cell and Molecular Biology Karolinska Institutet Department of Neuroscience Prof. Tomas Hökfelt Karolinska Institutet Assistant Prof. Francois Lallemend Department of Neuroscience Karolinska Institutet Division of Chemical Neurotransmission Department of Neuroscience Prof. Ted Ebedal Uppsala University Department of Neuroscience Division of Developmental Neuroscience To my parents ABSTRACT The autonomic nervous system is formed by a sympathetic and a parasympathetic division that have complementary roles in the maintenance of body homeostasis. Autonomic neurons, also known as visceral motor neurons, are tonically active and innervate virtually every organ in our body. For instance, cardiac outflow, thermoregulation and even the focusing of our eyes are just some of the plethora of physiological functions under the control of this system. Consequently, perturbation of autonomic nervous system activity can lead to a broad spectrum of disorders collectively known as dysautonomia and other diseases such as hypertension.
    [Show full text]
  • Multiple Endocrine Neoplasia Type 2: an Overview Jessica Moline, MS1, and Charis Eng, MD, Phd1,2,3,4
    GENETEST REVIEW Genetics in Medicine Multiple endocrine neoplasia type 2: An overview Jessica Moline, MS1, and Charis Eng, MD, PhD1,2,3,4 TABLE OF CONTENTS Clinical Description of MEN 2 .......................................................................755 Surveillance...................................................................................................760 Multiple endocrine neoplasia type 2A (OMIM# 171400) ....................756 Medullary thyroid carcinoma ................................................................760 Familial medullary thyroid carcinoma (OMIM# 155240).....................756 Pheochromocytoma ................................................................................760 Multiple endocrine neoplasia type 2B (OMIM# 162300) ....................756 Parathyroid adenoma or hyperplasia ...................................................761 Diagnosis and testing......................................................................................756 Hypoparathyroidism................................................................................761 Clinical diagnosis: MEN 2A........................................................................756 Agents/circumstances to avoid .................................................................761 Clinical diagnosis: FMTC ............................................................................756 Testing of relatives at risk...........................................................................761 Clinical diagnosis: MEN 2B ........................................................................756
    [Show full text]
  • Artemin-Stimulated Progression of Human Non–Small Cell Lung Carcinoma Is Mediated by BCL2
    Published OnlineFirst June 8, 2010; DOI: 10.1158/1535-7163.MCT-09-1077 Research Article Molecular Cancer Therapeutics Artemin-Stimulated Progression of Human Non–Small Cell Lung Carcinoma Is Mediated by BCL2 Jian-Zhong Tang1, Xiang-Jun Kong3, Jian Kang1, Graeme C. Fielder1, Michael Steiner1, Jo K. Perry1, Zheng-Sheng Wu4, Zhinan Yin5, Tao Zhu3, Dong-Xu Liu1, and Peter E. Lobie1,2 Abstract We herein show that Artemin (ARTN), one of the glial cell line–derived neurotrophic factor family of li- gands, promotes progression of human non–small cell lung carcinoma (NSCLC). Oncomine data indicate that expression of components of the ARTN signaling pathway (ARTN, GFRA3, and RET) is increased in neoplas- tic compared with normal lung tissues; increased expression of ARTN in NSCLC also predicted metastasis to lymph nodes and a higher grade in certain NSCLC subtypes. Forced expression of ARTN stimulated survival, anchorage-independent, and three-dimensional Matrigel growth of NSCLC cell lines. ARTN increased BCL2 expression by transcriptional upregulation, and inhibition of BCL2 abrogated the oncogenic properties of ARTN in NSCLC cells. Forced expression of ARTN also enhanced migration and invasion of NSCLC cells. Forced expression of ARTN in H1299 cells additionally resulted in larger xenograft tumors, which were high- ly proliferative, invasive, and metastatic. Concordantly, either small interfering RNA–mediated depletion or functional inhibition of endogenous ARTN with antibodies reduced oncogenicity and invasiveness of NSCLC cells. ARTN therefore mediates progression of NSCLC and may be a potential therapeutic target for NSCLC. Mol Cancer Ther; 9(6); 1697–708. ©2010 AACR. Introduction Therefore, identification and subsequent targeting of novel oncogenic pathways may provide an advantage to Lung carcinoma is currently responsible for the highest the current regimens used to treat lung carcinoma and cancer-related mortality worldwide, with overall 5-year consequently improve prognosis.
    [Show full text]
  • Expression and Regulation of GFR 3, a Glial Cell Line-Derived Neurotrophic
    Proc. Natl. Acad. Sci. USA Vol. 95, pp. 1295–1300, February 1998 Neurobiology Expression and regulation of GFRa3, a glial cell line-derived neurotrophic factor family receptor PHILIPPE NAVEILHAN*, CHRISTEL BAUDET*, ÅSA MIKAELS*, LIYA SHEN†,HEINER WESTPHAL†, AND PATRIK ERNFORS*‡ *Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, S17177 Stockholm, Sweden, and †Laboratory of Mammalian Genes and Development, National Institutes of Health, Bethesda, MD 20892 Communicated by Tomas Hokfelt, Karolinska Institute, Stockholm, Sweden, November 26, 1997 (received for review September 22, 1997) ABSTRACT We report the identification of an additional The switch from NT3 dependency is paralleled by the down- member of the glial cell line-derived neurotrophic factor regulation of the NT3 receptor, trkC (25). (GDNF) family receptor, termed GFRa3, that is homologous Recently, a family of neurotrophic factors has been discov- to the previously identified GDNF and neurturin ligand ered, including the structurally related ligands glial cell line- binding receptors GFRa1 and GFRa2. GFRa3 is 32% and 37% derived neurotrophic factor (GDNF) and neurturin (NTN) identical to GFRa1 and GFRa2, respectively. RNase protec- (26, 27). They are distant members to the transforming growth tion assays show that whereas gfra1 and gfra2 are abundant factor b family. GDNF is a potent survival factor for several in both developing and adult brain, gfra3 is exclusively populations of central neurons in culture and in vivo. GDNF expressed during development. All receptors are widely protects lesioned adult substantia nigra dopaminergic neurons present in both the developing and adult peripheral nervous from death (26, 28–30) and rescues developing and lesioned system and in peripheral organs.
    [Show full text]
  • Plasma Membrane Localization of the GFL Receptor Components: a Nexus for Receptor Crosstalk
    Cell and Tissue Research (2020) 382:57–64 https://doi.org/10.1007/s00441-020-03235-4 AT-A-GLANCE ARTICLE Plasma membrane localization of the GFL receptor components: a nexus for receptor crosstalk Christopher R. Donnelly1 & Brian A. Pierchala2 Received: 19 March 2020 /Accepted: 4 June 2020 / Published online: 7 August 2020 # The Author(s) 2020 Abstract The glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) comprise a group of four homologous and potent growth factors that includes GDNF, neurturin (NRTN), artemin (ARTN), and persephin (PSPN). The survival, growth, and mitotic activities of the GFLs are conveyed by a single receptor tyrosine kinase, Ret. The GFLs do not bind directly to Ret in order to activate it, and instead bind with high affinity to glycerophosphatidylinositol (GPI)-anchored coreceptors called the GDNF family receptor-αs(GFRαs). Several mechanisms have recently been identified that influence the trafficking of Ret and GFRαs in and out of the plasma membrane, thereby affecting their availability for ligand binding, as well as their levels by targeting to degradative pathways. This review describes these mechanisms and their powerful effects on GFL signaling and function. We also describe the recent discovery that p75 and Ret form a signaling complex, also regulated by plasma membrane shuttling, that either enhances GFL survival signals or p75 pro-apoptotic signals, dependent on the cellular context. Keywords Ret . GFRα . Plasma membrane . Intracellular trafficking . GDNF . GFLs . TGF-β regulation Introduction receptors, as well as other classes of receptors, and the cellular context of these interactions ultimately determines the fate of In the past, illustrations detailing neurotrophic factor signaling neurons during neural development (e.g., survival, death, dif- pathways often indicated relatively simplistic interactions be- ferentiation, axon growth).
    [Show full text]
  • R&D Systems Products for Neuroscience Research
    R&D Systems Tools for Cell Biology Research™ R&D Systems Products for Neuroscience Research ON THE COVER This illustration was featured in the Cytokine Bulletin (2010, Issue 1). TLR2 IL-6 IL-6 R MOG IL-21 R TGF-β R STAT3 Dendritic TGF-β Cell STAT3 Batf, RORγt IL-23 Batf RORγt Th17 Cell IL-23 R IL-17 JunB Batf RORγt IL-17 NO Myelin TNF-α Axon MMPs Macrophages Neuron Oligodendrocyte Prolonged production of IL-17 by Th17 cells is dependent on the transcription factor Batf. Recent studies suggest that prolonged production of IL-17 by Th17 cells is dependent on the synergistic actions of the RORt and Batf-JunB transcription factors. These fi ndings may have implications for Th17-related autoimmune disorders such as multiple sclerosis. Following induction of autoimmune conditions in mice using myelin oligodendrocyte glycoprotein (MOG) immunization, diff erentiated Th17 cells secrete proinfl ammatory cytokines, and activated macrophages destroy myelin and damage oligodendrocytes. It remains to be determined whether the induction of Batf expression is dependent on STAT3 in Th17 cells, and whether an interaction between Batf and Irf4 or Ahr is required to promote the respective induction of IL-21 and IL-22. Schraml, B.U. et al. (2009) Nature 460:405. To request the most recent issue of the Cytokine Bulletin and other R&D Systems literature please visit www.RnDSystems.com/go/Request R&D Systems Tools for Cell Biology Research™ R&D Systems Cytokine Bulletin Cytokine BULLETIN 2011 | Issue 2 Adipose Tissue INSIDE s)NFLAMMATION s$ECREASEDADIPOGENESIS
    [Show full text]
  • Gdnf Family Receptors in Peripheral Target Innervation and Hormone Production
    GDNF FAMILY RECEPTORS IN PERIPHERAL TARGET INNERVATION AND HORMONE PRODUCTION Päivi Lindfors Neuroscience Center and Department of Biological and Environmental Sciences and Helsinki Graduate School in Biotechnology and Molecular Biology, Faculty of Biosciences, University of Helsinki Academic dissertation To be presented for public criticism, with the permission of the Faculty of Biosciences, University of Helsinki, in auditorium 1041 at Viikki Biocenter, on 1 September, 2006, at 12 noon. Helsinki 2006 1 Supervised by: Docent Matti Airaksinen Neuroscience Center University of Helsinki Finland Reviewed by: Docent Kirsi Sainio Institute of Biomedicine University of Helsinki Finland and Docent Juha Partanen Institute of Biotechnology University of Helsinki Finland Opponent: Professor Klaus Unsicker Institute for Anatomy and Cell Biology University of Heidelberg Germany ISBN 952-10-3309-6 (print) ISBN 952-10-3310-X (ethesis, pdf) Yliopistopaino, Helsinki 2006 2 To Mika 3 TABLE OF CONTENTS SELECTED ABBREVIATIONS ..................................................................................6 LIST OF ORIGINAL PUBLICATIONS.......................................................................7 ABSTRACT...................................................................................................................8 REVIEW OF THE LITERATURE ...............................................................................9 Introduction....................................................................................................................9
    [Show full text]
  • Neurotrophic Factors and Receptors in the Immature and Adult Spinal Cord After Mechanical Injury Or Kainic Acid
    The Journal of Neuroscience, May 15, 2001, 21(10):3457–3475 Neurotrophic Factors and Receptors in the Immature and Adult Spinal Cord after Mechanical Injury or Kainic Acid Johan Widenfalk, Karin Lundstro¨ mer, Marie Jubran, Stefan Brene´ , and Lars Olson Department of Neuroscience, Karolinska Institute, S-171 77 Stockholm, Sweden Delivery of neurotrophic factors to the injured spinal cord has mRNA increased in astrocytes of degenerating white matter. been shown to stimulate neuronal survival and regeneration. The relatively limited upregulation of neurotrophic factors in the This indicates that a lack of sufficient trophic support is one spinal cord contrasted with the response of affected nerve factor contributing to the absence of spontaneous regeneration roots, in which marked increases of NGF and GDNF mRNA in the mammalian spinal cord. Regulation of the expression of levels were observed in Schwann cells. The difference between neurotrophic factors and receptors after spinal cord injury has the ability of the PNS and CNS to provide trophic support not been studied in detail. We investigated levels of mRNA- correlates with their different abilities to regenerate. Kainic acid encoding neurotrophins, glial cell line-derived neurotrophic fac- delivery led to only weak upregulations of BDNF and CNTF tor (GDNF) family members and related receptors, ciliary neu- mRNA. Compared with several brain regions, the overall re- rotrophic factor (CNTF), and c-fos in normal and injured spinal sponse of the spinal cord tissue to kainic acid was weak. The cord. Injuries in adult rats included weight-drop, transection, relative sparseness of upregulations of endogenous neurotro- and excitotoxic kainic acid delivery; in newborn rats, partial phic factors after injury strengthens the hypothesis that lack of transection was performed.
    [Show full text]