DOCSLIB.ORG

The Roles of Lysosomal Exocytosis in Regulated Myelination

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Roles of Lysosomal Exocytosis in Regulated Myelination Shen YT, Yuan Y, Su WF, Gu Y, Chen G. J Neurol Neuromed (2016) 1(5): 4-8 Neuromedicine www.jneurology.com www.jneurology.com Journal of Neurology & Neuromedicine Mini Review Open Access The Roles of Lysosomal Exocytosis in Regulated Myelination Yun-Tian Shen1, Ying Yuan1,2, Wen-Feng Su1, Yun Gu1, Gang Chen1 1Jiangsu Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China 2Affiliated Hospital of Nantong University, Nantong, China ABSTRACT Article Info Article Notes The myelin sheath wraps axons is an intricate process required for Received: June 02, 2016 rapid conduction of nerve impulses, which is formed by two kinds of glial Accepted: July 21, 2016 cells, oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system. Myelin biogenesis is a complex and finely *Correspondence: regulated process and accumulating evidence suggests that myelin protein Dr. Gang Chen Jiangsu Key Laboratory of Neuroregeneration Co-innovation synthesis, storage and transportation are key elements of myelination, Center of Neuroregeneration, Nantong University, Nantong, however the mechanisms of regulating myelin protein trafficking are still not China. 226001, Tel: 86-513-85051805, very clear. Recently, the evidences of lysosomal exocytosis in oligodendrocytes Email: [email protected] and Schwann cells are involved in regulated myelination have emerged. In this paper, we briefly summarize how the major myelin-resident protein, as © 2016 Chen G. This article is distributed under the terms of the proteolipid protein in the central nervous system and P0 in the peripheral Creative Commons Attribution 4.0 International License nervous system, transport from lysosome to cell surface to form myelin sheath and focus on the possible mechanisms involved in these processes. Advances in our understanding of glia, as well as new tools engineering, will further improve the knowing of myelin biogenesis. Introduction Myelin is a specialized membrane structure generated by oligodendrocytes and Schwann cells, which offers electrical insulation around the axon and involves in mutual communication with neurons and the outside environment1. Myelin biogenesis is a complex and process and accumulating evidence suggests that myelin protein synthesis, storage and transportation are key elementsfinely of regulated myelination 1. However, the mechanisms of regulatingLysosomes myelin are protein acidic traffickingorganelles still and remain generally poorly considered understood. to be responsible for the degradation of endocytic and autophagic substrates. Interestingly, some cells used their lysosomes as secretory compartment. Compared to conventional lysosomes, this kind of lysosomes serve dual functions – for degradation of proteins and for storage of newly synthesized secretory proteins, were named as secretory lysosomes2. as a process that a lysosome responds to extracellular stimuli, docks at the interior of the cell surfaceLysosomal and fuses exocytosis with the is definedplasma membrane to their contents2,3. In nervous system Ca2+-dependent lysosomal exocytosis is already proved as a new pathway for gliotransmitter secreted from astrocytes4-6 meanwhile the lysosome exocytic process was also found in microglia7,8, oligodendrocyte9 and Schwann cells10,11. Recently, the roles of lysosomal exocytosis in myelin formation Page 4 of 4 Shen YT, Yuan Y, Su WF, Gu Y, Chen G. J Neurol Neuromed (2016) 1(5): 4-8 Journal of Neurology & Neuromedicine were investigated. It was discovered that some neuronal surface transport in oligodendrocytes, indicating rab3A signals can induce proteolipid protein (PLP), the major myelin-resident protein in CNS (about 50% of the transport vesicles30. Our recent study demonstrated that total protein component) and myelin protein P0, the mayanother regulate small the GTPase membrane Rab27b trafficking is primarily of PLP-containing expressed in major myelin protein in PNS (about 50% of the total lysosomes of mature oligodendrocytes and co-localized protein component), release from late endosomes/ with PLP31. Downregulation of Rab27b in cultured lysosomes membrane stores to plasma membrane during myelination9,11 strongly reduces lysosomal exocytosis and inhibits abnormalities are very common phenomenon in many PLPmature transport oligodendrocytes from lysosome by specific to plasmasiRNA transfectionmembrane. lysosomal storage. Consistent diseases with(LSDs), these a group findings, of inherited myelin Furthermore, downregulation of Rab27b also affects the and acquired diseases that are characterized by an formation of myelin-like membranes in vitro analysis using accumulation of undigested material inside the lysosome demonstration that Rab27b is implicated in myelin protein 12, including Niemann-Pick disease, Gaucher oligodendrocyte–neuron co-culture system. This is the first disease,as a result metachromatic of one or more leukodystrophy, specific lysosomal multiple sulfataseenzymes exocytosis and contributes to myelin formation31. Above deficiencies 12-15. all,PLP these trafficking results in strongly oligodendrocytes suggest that via lysosomal regulates exocytosislysosomal in oligodendrocytes contributes to myelin protein PLP deficiencyOwing toand the globoid critical cell cellular leukodystrophy role of lysosomes in the myelination, mounting studies focus on the mechanisms CNS. underlying exocytosis of lysosome in nervous system has trafficking and plays an important role in myelination in Roles of Lysosomal Exocytosis in Regulated advances in this respect. Myelination in PNS emerged. In this paper, we briefly introduce the recent Roles of Lysosomal Exocytosis in Regulated Compared to the CNS, peripheral nerves have a Myelination in CNS remarkable capacity to regenerate and remyelination allowing for functional recovery in affected body regions32. As an integral membrane protein, proteolipid protein This regenerative ability to a great degree is dependent on (PLP) is the most prominently component of myelin- and supported by Schwann cells, the myelin-forming glial 16,17. PLP is major expressed in cells of the PNS33,34. Schwann cells myelinating are regulated oligodendrocytes and it is synthesized in the rough ER by extrinsic signals from the axon, and the extracellular thenspecific transported proteins into CNS the Golgi and plasma membrane matrix35. Peripheral nerve injury can induce Schwann cells via vesicles, followed to form the myelin sheath with transition from axon myelination to an immature Schwann neuronal signals or internalized and stored into late cell - like stage, proliferate, supports neuronal survival endosomal/lysosome without neuronal signals. The which is followed by remyelination of newly-regenerated process of PLP transportation is carefully regulated by axons36,37 intracellular and extracellular signal. PLP localized in late endosomal/lysosome is particularly evident during . Therefore to find out the potential mechanisms of 18 active myelinogenesis in the brain . The mechanisms of roleregulate of lysosomal myelin proteins exocytosis trafficking in the in PNS Schwann has been cells studied during recently.this process It isis believedone of matters that in of thecardinal process significance. of Wallerian The lysosome membrane stores to plasma membrane, thereby degeneration lysosomal exocytosis is involved in Schwann regulation of the trafficking of PLP from late endosomal/ promoting the formation and maintenance of myelin cell demyelination, dedifferentiation, proliferation 19-21 are still not very clear . Feldmann et al. found that and remyelination38. Our previous results showed that the vesicle-soluble N-ethylmaleimide-sensitive factor lysosomal exocytosis in Schwann cells also contribute attachment protein receptors (v-SNAREs) protein VAMP7 to myelination in PNS. We found that Rab27a, another small GTPase of Rab27 family, is required for secretory to plasma membrane and is involved in myelin formation9. mediates trafficking of PLP from late endosomal/lysosome Stx3 and SNAP23 serve as putative target SNAREs in the PNS11. The mechanism was dissected by several evidences. VAMP7-dependent pathway9 First,lysosome myelin trafficking protein inP0 Schwann was stored cells in and Schwann myelination cell late in mocha mice, with a defect in lysosomal exocytosis caused endosomes/lysosomes. Second, Rab27a is also distributed by VAMP7 missorting, exhibit .normal However, levels AP3-δ of myelination mutant in late endosomes/lysosomes and co-localized with P0 which may due to the functional redundancy9. On the in Schwann cells. Third, the potent and selective calcium other hand, some members of the Rab family have been ionophore ionomycin, which acts as a motile Ca2+ carrier indicated to regulate membrane transport process in the and enhances Ca2+ late endosomes - lysosomes system, including Rab322,23, Rab724,25, Rab926,27, Rab2723, Rab2628 and Rab1429. For downregulated Schwann influx, cells,induced which lysosomal were transfectedexocytosis example, overexpression of rab3A and PLP promoted PLP within Schwann Rab27a cells shRNA was plasmid. significantly Finally, decreased after sciatic in Rab27a nerve Page 5 of 5 Shen YT, Yuan Y, Su WF, Gu Y, Chen G. J Neurol Neuromed (2016) 1(5): 4-8 Journal of Neurology & Neuromedicine injury, the remyelination of the injured axon was obviously time and place, involved multiple transport pathways. 11. In addition, our Due to a lot of lysosomal diseases have a severe phenotype unpublished data
Load more

Recommended publications
  • Spring 2013 Lecture 23
    CHM333 LECTURES 23: 3/25/13 SPRING 2013 Professor Christine Hrycyna LIPIDS III EFFECT OF CHOLESTEROL ON MEMBRANES: - Bulky rigid molecule - Moderates fluidity of membranes – both increases and decreases o Cholesterol in membranes DECREASES fluidity because it is rigid o Prevents crystallization (making solid) of fatty acyl side chains by fitting between them. Disrupts close packing of fatty acyl chains. Therefore, INCREASED fluidity BIOLOGICAL MEMBRANES CONTAIN PROTEINS AS WELL AS LIPIDS: - Proteins are 20-80% of cell membrane - Rest is lipid or carbohydrate; supramolecular assembly of lipid, protein and carbohydrate - Proteins are also distributed asymmetrically - TWO classes of Membrane Proteins: o Integral Membrane Proteins o Peripheral Membrane Proteins 178 CHM333 LECTURES 23: 3/25/13 SPRING 2013 Professor Christine Hrycyna - INTEGRAL MEMBRANE PROTEINS o Located WITHIN the lipid bilayer o Usually span the bilayer one or more times – called transmembrane (TM) proteins o Hydrophobic amino acids interact with fatty acid chains in the hydrophobic core of the membrane o Can be removed from the membrane with detergents like SDS – need to disrupt the hydrophobic interactions § Membrane Disruption Animation: o http://www.youtube.com/watch?v=AHT37pvcjc0 o Function: § Transporters – moving molecules into or out of cells or cell membranes § Receptors – transmitting signals from outside of the cell to the inside - β Barrel Integral Membrane Proteins § Barrel-shaped membrane protein that is made up of antiparallel β-strands with hydrophilic (interior) and hydrophobic (facing lipid tails). § So far found only in outer membranes of Gram-negative bacteria, cell wall of Gram-positive bacteria, and outer membranes of mitochondria and chloroplasts. 179 CHM333 LECTURES 23: 3/25/13 SPRING 2013 Professor Christine Hrycyna - α-Helical Membrane Proteins - Can cross the membrane once or many times and have multiple transmembrane segments.
    [Show full text]
  • Oligodendrocytes in Development, Myelin Generation and Beyond
    cells Review Oligodendrocytes in Development, Myelin Generation and Beyond Sarah Kuhn y, Laura Gritti y, Daniel Crooks and Yvonne Dombrowski * Wellcome-Wolfson Institute for Experimental Medicine, Queen’s University Belfast, Belfast BT9 7BL, UK; [email protected] (S.K.); [email protected] (L.G.); [email protected] (D.C.) * Correspondence: [email protected]; Tel.: +0044-28-9097-6127 These authors contributed equally. y Received: 15 October 2019; Accepted: 7 November 2019; Published: 12 November 2019 Abstract: Oligodendrocytes are the myelinating cells of the central nervous system (CNS) that are generated from oligodendrocyte progenitor cells (OPC). OPC are distributed throughout the CNS and represent a pool of migratory and proliferative adult progenitor cells that can differentiate into oligodendrocytes. The central function of oligodendrocytes is to generate myelin, which is an extended membrane from the cell that wraps tightly around axons. Due to this energy consuming process and the associated high metabolic turnover oligodendrocytes are vulnerable to cytotoxic and excitotoxic factors. Oligodendrocyte pathology is therefore evident in a range of disorders including multiple sclerosis, schizophrenia and Alzheimer’s disease. Deceased oligodendrocytes can be replenished from the adult OPC pool and lost myelin can be regenerated during remyelination, which can prevent axonal degeneration and can restore function. Cell population studies have recently identified novel immunomodulatory functions of oligodendrocytes, the implications of which, e.g., for diseases with primary oligodendrocyte pathology, are not yet clear. Here, we review the journey of oligodendrocytes from the embryonic stage to their role in homeostasis and their fate in disease. We will also discuss the most common models used to study oligodendrocytes and describe newly discovered functions of oligodendrocytes.
    [Show full text]
  • Glial Cell Development and Function in Zebrafish
    Downloaded from http://cshperspectives.cshlp.org/ on September 26, 2021 - Published by Cold Spring Harbor Laboratory Press Glial Cell Development and Function in Zebrafish David A. Lyons1 and William S. Talbot2 1Centre for Neuroregeneration, University of Edinburgh, Edinburgh EH16 4SB, United Kingdom 2Department of Developmental Biology, Stanford University, Stanford, California 94305 Correspondence: [email protected] The zebrafish is a premier vertebrate model system that offers many experimental advantages for in vivo imaging and genetic studies. This review provides an overview of glial cell types in the central and peripheral nervous system of zebrafish. We highlight some recent work that exploited the strengths of the zebrafish system to increase the understanding of the role of Gpr126 in Schwann cell myelination and illuminate the mechanisms controlling oligoden- drocyte development and myelination. We also summarize similarities and differences between zebrafish radial glia and mammalian astrocytes and consider the possibility that their distinct characteristics may represent extremes in a continuum of cell identity. Finally, we focus on the emergence of zebrafish as a model for elucidating the development and function of microglia. These recent studies have highlighted the power of the zebrafish system for analyzing important aspects of glial development and function. ollowing the pioneering work of George Ho and Kane 1990; Hatta et al. 1991; Grunwald FStreisinger in the early 1980s, the zebrafish and Eisen 2002), attracting many researchers
    [Show full text]
  • Clinical Neurophysiology Board Review Q&A
    Clinical Neurophysiology Board Review Board Clinical Neurophysiology Clinical Neurophysiology Board Review Q&A Clinical Puneet K. Gupta, MD, MSE • Pradeep N. Modur, MD, MS • Srikanth Muppidi, MD his high-yield, illustrated clinical neurophysiology board review is a comprehen- Neurophysiology sive resource for assessing and refining the knowledge tested on multiple board Texaminations. Written by authors who are collectively board certified in all of the areas covered, the book is a valuable study tool for candidates preparing for certifica- tion or recertification in clinical neurophysiology, neuromuscular medicine, epilepsy, Board Review sleep medicine, and neurology. Using structured question formats typically encountered on boards, this comprehensive review allows users to assess their knowledge in a wide range of topics, provides rationales for correct answers, and explains why the other choices are incorrect. A unique “Pearls” section at the end of the book allows for quick review of the most important concepts prior to exam day. Clinical Neurophysiology Board Review Q&A contains 801 questions with answers and detailed explanations. The book is divided into eight chapters covering anatomy Q and physiology, electronics and instrumentation, nerve conduction studies and EMG, & EEG, evoked potentials and intraoperative monitoring, sleep studies, ethics and safety, and advanced topics including QEEG, MEG, TES, autonomic testing, and more. A Liberal use of image-based questions illustrating the full spectrum of neurophysiologic & tests and findings build interpretive skills. Questions are randomized and include Q A both case-related questions in series and stand-alone items to familiarize candidates Gu with the question types and formats they will find on the exam.
    [Show full text]
  • Calmodulin Complexation in Neurons and Brain Degeneration in Alzheimer’S Disease
    International Journal of Molecular Sciences Review The Relevance of Amyloid β-Calmodulin Complexation in Neurons and Brain Degeneration in Alzheimer’s Disease Joana Poejo 1 , Jairo Salazar 1,2, Ana M. Mata 1,3 and Carlos Gutierrez-Merino 1,3,* 1 Instituto de Biomarcadores de Patologías Moleculares, Universidad de Extremadura, 06006 Badajoz, Spain; [email protected] (J.P.); [email protected] (J.S.); [email protected] (A.M.M.) 2 Departamento de Química, Universidad Nacional Autónoma de Nicaragua-León, León 21000, Nicaragua 3 Departamento de Bioquímica y Biología Molecular y Genética, Facultad de Ciencias, Universidad de Extremadura, 06006 Badajoz, Spain * Correspondence: [email protected] Abstract: Intraneuronal amyloid β (Aβ) oligomer accumulation precedes the appearance of amyloid plaques or neurofibrillary tangles and is neurotoxic. In Alzheimer’s disease (AD)-affected brains, intraneuronal Aβ oligomers can derive from Aβ peptide production within the neuron and, also, from vicinal neurons or reactive glial cells. Calcium homeostasis dysregulation and neuronal ex- citability alterations are widely accepted to play a key role in Aβ neurotoxicity in AD. However, the identification of primary Aβ-target proteins, in which functional impairment initiating cytosolic calcium homeostasis dysregulation and the critical point of no return are still pending issues. The micromolar concentration of calmodulin (CaM) in neurons and its high affinity for neurotoxic Aβ peptides (dissociation constant ≈ 1 nM) highlight a novel function of CaM, i.e., the buffering of free Aβ concentrations in the low nanomolar range. In turn, the concentration of Aβ-CaM complexes within neurons will increase as a function of time after the induction of Aβ production, and free Aβ Citation: Poejo, J.; Salazar, J.; Mata, will rise sharply when accumulated Aβ exceeds all available CaM.
    [Show full text]
  • NF-Jb Signalling Requirement for Brain Myelin Formation Is Shown by Genotype/MRI Phenotype Correlations in Patients with Xq28 Duplications
    European Journal of Human Genetics (2013) 21, 195–199 & 2013 Macmillan Publishers Limited All rights reserved 1018-4813/13 www.nature.com/ejhg ARTICLE NF-jB signalling requirement for brain myelin formation is shown by genotype/MRI phenotype correlations in patients with Xq28 duplications Orianne Philippe1, Marle`ne Rio1, Vale´rie Malan1, Hilde Van Esch2, Genevie`ve Baujat1, Nadia Bahi-Buisson3, Vassili Valayannopoulos4, Roseline Gesny1, Jean-Paul Bonnefont1, Arnold Munnich1,GuyFroyen5, Jeanne Amiel1, Nathalie Boddaert1,3 and Laurence Colleaux*,1 One of the key signals regulating peripheral myelin formation by Schwann cell is the activation of the transcription factor NF-jB. Yet, whether NF-jB exerts similar functions in central myelin formation by oligodendrocytes remains largely unknown. We previously reported white matter abnormalities with unusual discordance between T2 and FLAIR sequences in a patient with intellectual disability and defective NF-jB signalling. These observations prompted us to hypothesise that NF-jB signalling may have a role in the axon myelination process of central neurons. We report here on five male patients with Xq28 duplications encompassing MECP2, three of which presented white matter anomalies on brain MRI. Array-CGH and FISH analyses demonstrated that brain abnormalities correlate with additional copies of the IKBKG, a gene encoding a key regulator of NF-jB activation. Quantitative RT-PCR experiments and jB-responsive reporter gene assays provide evidence that IKBKG overexpression causes impaired NF-jB signalling in skin fibroblasts derived from patients with white matter anomalies. These data further support the role of NF-jB signalling in astroglial cells for normal myelin formation of the central nervous system.
    [Show full text]
  • Integrating Brain-Based Psychoeducation Into Clinical Practice Raissa Miller Boise State University
    Boise State University ScholarWorks Counselor Education Faculty Publications and Department of Counselor Education Presentations 4-1-2016 Neuroeducation: Integrating Brain-Based Psychoeducation into Clinical Practice Raissa Miller Boise State University This document was originally published in Journal of Mental Health Counseling by the American Mental Health Counselors Association. Copyright restrictions may apply. doi: 10.17744/mehc.38.2.02 Volume 38/Number 2/April 2016/Pages 103-1 IS/doi: 10. l7744/mehc.38.2.02 PRACTICE Neuroeducation: Integrating Brain- Based Psychoeducation into Clinical Practice Raissa M iller Boise State University Understanding and integrating neuroscience research into clinical practice represents a rapidly growing area in mental health. An expanding body of neuroscience literature increasingly informs clinical practice by validating theory, guiding clinical assessment and conceptualiza­ tion, directing effective interventions, and facilitating cross-disciplinary communication. Little attention, however, has been given to the use of neuroeducation with clients. In this article, the author provides mental health counselors with a definition of neuroeducation and a rationale for incorporating neuroeducation into clinical practice. The author identifies common neuro­ education topics and offers activity suggestions to illustrate their use in counseling. Finally, the author offers best practices for implementing neuroeducation, including attention to counselor competence, client readiness, and neuroscience of learning
    [Show full text]
  • The Membrane
    The Membrane Natalie Gugala1*, Stephana J Cherak1 and Raymond J Turner1 1Department of Biological Sciences, University of Calgary, Canada *Corresponding author: RJ Turner, Department of Biological Sciences, University of Calgary, Alberta, Canada, Tel: 1-403-220-4308; Fax: 1-403-289-9311; Email: [email protected] Published Date: February 10, 2016 ABSTRACT and continues to be studied. The biological membrane is comprised of numerous amphiphilic The characterization of the cell membrane has significantly extended over the past century lipids, sterols, proteins, carbohydrates, ions and water molecules that result in two asymmetric polar leaflets, in which the interior is hydrophobic due to the hydrocarbon tails of the lipids. generated a dynamic heterogonous image of the membrane that includes lateral domains and The extension of the Fluid Mosaic Model, first proposed by Singer and Nicolson in 1972, has clusters perpetrated by lipid-lipid, protein-lipid and protein-protein interactions. Proteins found within the membrane, which are generally characterized as either intrinsic or extrinsic, have an array of biological functions vital for cell activity. The primary role of the membrane, among many, is to provide a barrier that conveys both separation and protection, thus maintaining the integrity of the cell. However, depending on the permeability of the membrane several ions are able to move down their concentration gradients. In turn this generates a membrane potential difference between the cytosol, which is found to have an excess negative charge, and surrounding extracellular fluid. Across a biological cell membrane, several potentials can be found. These include the Nernst or equilibrium potential, in which there is no overall flow of a Basicparticular Biochemistry ion and | www.austinpublishinggroup.com/ebooks the Donnan potential, created by an unequal distribution of ions.
    [Show full text]
  • Original Article Schistosoma Japonicum-Derived Peptide SJMHE1 Promotes Peripheral Nerve Repair Through a Macrophage-Dependent Mechanism
    Am J Transl Res 2021;13(3):1290-1306 www.ajtr.org /ISSN:1943-8141/AJTR0118598 Original Article Schistosoma japonicum-derived peptide SJMHE1 promotes peripheral nerve repair through a macrophage-dependent mechanism Yongbin Ma1,2, Chuan Wei1, Xin Qi1, Yanan Pu1, Liyang Dong3, Lei Xu1, Sha Zhou1, Jifeng Zhu1, Xiaojun Chen1, Xuefeng Wang4, Chuan Su1 1State Key Lab of Reproductive Medicine, Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology and Immunology, Center for Global Health, Nanjing Medical University, Nanjing 211166, Jiangsu, P. R. China; 2Department of Neurology Laboratory, Jintan Hospital, Jiangsu University, Jintan, Changzhou 213200, Jiangsu, P. R. China; 3Department of Nuclear Medicine and Institute of Oncology, The Affiliated Hospital of Jiangsu University, Zhenjiang 212000, Jiangsu, P. R. China; 4Department of Central Laboratory, The Affiliated Hospital of Jiangsu University, Zhenjiang 212000, Jiangsu, P. R. China Received July 21, 2020; Accepted December 11, 2020; Epub March 15, 2021; Published March 30, 2021 Abstract: Peripheral nerve injury, a disease that affects 1 million people worldwide every year, occurs when periph- eral nerves are destroyed by injury, systemic illness, infection, or an inherited disorder. Indeed, repair of damaged peripheral nerves is predominantly mediated by type 2 immune responses. Given that helminth parasites induce type 2 immune responses in hosts, we wondered whether helminths or helminth-derived molecules might have the potential to improve peripheral nerve repair. Here, we demonstrated that schistosome-derived SJMHE1 promoted peripheral myelin growth and functional regeneration via a macrophage-dependent mechanism and simultaneously increased the induction of M2 macrophages. Our findings highlight the therapeutic potential of schistosome-derived SJMHE1 for improving peripheral nerve repair.
    [Show full text]
  • UC Riverside UC Riverside Electronic Theses and Dissertations
    UC Riverside UC Riverside Electronic Theses and Dissertations Title Remote-Activated Electrical Stimulation via Piezoelectric Scaffold System for Functional Peripheral and Central Nerve Regeneration Permalink https://escholarship.org/uc/item/7hb5g2x7 Author Low, Karen Gail Publication Date 2017 License https://creativecommons.org/licenses/by/4.0/ 4.0 Peer reviewed|Thesis/dissertation eScholarship.org Powered by the California Digital Library University of California UNIVERSITY OF CALIFORNIA RIVERSIDE Remote-Activated Electrical Stimulation via Piezoelectric Scaffold System for Functional Nerve Regeneration A Dissertation submitted in partial satisfaction of the requirements of for the degree of Doctor of Philosophy in Bioengineering by Karen Gail Low December 2017 Dissertation Committee: Dr. Jin Nam, Chairperson Dr. Hyle B. Park Dr. Nosang V. Myung Copyright by Karen Gail Low 2017 The Dissertation of Karen Gail Low is approved: _____________________________________________ _____________________________________________ _____________________________________________ Committee Chairperson University of California, Riverside ACKNOWLEDGEMENTS First and foremost, I would like to express my deepest appreciation to my PhD advisor and mentor, Dr. Jin Nam. I came from a background with no research experience, therefore his guidance, motivation, and ambition for me to succeed helped developed me into the researcher I am today. And most of all, I am forever grateful for his patience with all my blood, sweat and tears that went into this 5 years. He once said, “it takes pressure to make a diamond.” His words of wisdom will continue to guide me through my career. I would also like to thank my collaborator, Dr. Nosang V. Myung. He gave me the opportunity to explore a field that was completely outside of my comfort zone of biology.
    [Show full text]
  • Supplementation with Complex Milk Lipids During Brain Development Promotes Neuroplasticity Without Altering Myelination Or Vascular Density
    food & nutrition æ research ORIGINAL ARTICLE Supplementation with complex milk lipids during brain development promotes neuroplasticity without altering myelination or vascular density Rosamond B. Guillermo1,2, Panzao Yang1,2, Mark H. Vickers1, Paul McJarrow3 and Jian Guan1,2* 1Liggins Institute, The University of Auckland, Auckland, New Zealand; 2Centre for Brain Research, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand; 3Fonterra Research and Development Centre, Palmerston North, New Zealand Abstract Background: Supplementation with complex milk lipids (CML) during postnatal brain development has been shown to improve spatial reference learning in rats. Objective: The current study examined histo-biological changes in the brain following CML supplementation and their relationship to the observed improvements in memory. Design: The study used the brain tissues from the rats (male Wistar, 80 days of age) after supplementing with either CML or vehicle during postnatal day 10Á80. Immunohistochemical staining of synaptophysin, glutamate receptor-1, myelin basic protein, isolectin B-4, and glial fibrillary acidic protein was performed. The average area and the density of the staining and the numbers of astrocytes and capillaries were assessed and analysed. Results: Compared with control rats, CML supplementation increased the average area of synaptophysin staining and the number of GFAP astrocytes in the CA3 sub-region of the hippocampus (pB0.01), but not in the CA4 sub-region. The supplementation also led to an increase in dopamine output in the striatum that was related to nigral dopamine expression (pB0.05), but did not alter glutamate receptors, myelination or vascular density. Conclusion: CML supplementation may enhance neuroplasticity in the CA3 sub-regions of the hippocampus.
    [Show full text]
  • Presynaptic Gabaergic Inhibition Regulated by BDNF Contributes to Neuropathic Pain Induction
    ARTICLE Received 29 Apr 2014 | Accepted 22 Sep 2014 | Published 30 Oct 2014 DOI: 10.1038/ncomms6331 OPEN Presynaptic GABAergic inhibition regulated by BDNF contributes to neuropathic pain induction Jeremy Tsung-chieh Chen1, Da Guo1, Dario Campanelli1,2, Flavia Frattini1, Florian Mayer1, Luming Zhou3, Rohini Kuner4, Paul A. Heppenstall5, Marlies Knipper2 & Jing Hu1 The gate control theory proposes the importance of both pre- and post-synaptic inhibition in processing pain signal in the spinal cord. However, although postsynaptic disinhibition caused by brain-derived neurotrophic factor (BDNF) has been proved as a crucial mechanism underlying neuropathic pain, the function of presynaptic inhibition in acute and neuropathic pain remains elusive. Here we show that a transient shift in the reversal potential (EGABA) together with a decline in the conductance of presynaptic GABAA receptor result in a reduction of presynaptic inhibition after nerve injury. BDNF mimics, whereas blockade of BDNF signalling reverses, the alteration in GABAA receptor function and the neuropathic pain syndrome. Finally, genetic disruption of presynaptic inhibition leads to spontaneous development of behavioural hypersensitivity, which cannot be further sensitized by nerve lesions or BDNF. Our results reveal a novel effect of BDNF on presynaptic GABAergic inhibition after nerve injury and may represent new strategy for treating neuropathic pain. 1 Centre for Integrative Neuroscience, Otfried-Mueller-Strasse 25, 72076 Tu¨bingen, Germany. 2 Hearing Research Centre, Elfriede Aulhornstrasse 5, 72076 Tu¨bingen, Germany. 3 Laboratory for NeuroRegeneration and Repair, Center for Neurology, Hertie Institute for Clinical Brain Research, 72076 Tu¨bingen, Germany. 4 Pharmacology Institute, University of Heidelberg, Im Neuenheimer Feld 584, 69120 Heidelberg, Germany.
    [Show full text]