Oligodendrocytes in Development, Myelin Generation and Beyond
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The Creation of Neuroscience
The Creation of Neuroscience The Society for Neuroscience and the Quest for Disciplinary Unity 1969-1995 Introduction rom the molecular biology of a single neuron to the breathtakingly complex circuitry of the entire human nervous system, our understanding of the brain and how it works has undergone radical F changes over the past century. These advances have brought us tantalizingly closer to genu- inely mechanistic and scientifically rigorous explanations of how the brain’s roughly 100 billion neurons, interacting through trillions of synaptic connections, function both as single units and as larger ensem- bles. The professional field of neuroscience, in keeping pace with these important scientific develop- ments, has dramatically reshaped the organization of biological sciences across the globe over the last 50 years. Much like physics during its dominant era in the 1950s and 1960s, neuroscience has become the leading scientific discipline with regard to funding, numbers of scientists, and numbers of trainees. Furthermore, neuroscience as fact, explanation, and myth has just as dramatically redrawn our cultural landscape and redefined how Western popular culture understands who we are as individuals. In the 1950s, especially in the United States, Freud and his successors stood at the center of all cultural expla- nations for psychological suffering. In the new millennium, we perceive such suffering as erupting no longer from a repressed unconscious but, instead, from a pathophysiology rooted in and caused by brain abnormalities and dysfunctions. Indeed, the normal as well as the pathological have become thoroughly neurobiological in the last several decades. In the process, entirely new vistas have opened up in fields ranging from neuroeconomics and neurophilosophy to consumer products, as exemplified by an entire line of soft drinks advertised as offering “neuro” benefits. -
Mixing Old and Young: Enhancing Rejuvenation and Accelerating Aging
Mixing old and young: enhancing rejuvenation and accelerating aging Ashley Lau, … , James L. Kirkland, Stefan G. Tullius J Clin Invest. 2019;129(1):4-11. https://doi.org/10.1172/JCI123946. Review Donor age and recipient age are factors that influence transplantation outcomes. Aside from age-associated differences in intrinsic graft function and alloimmune responses, the ability of young and old cells to exert either rejuvenating or aging effects extrinsically may also apply to the transplantation of hematopoietic stem cells or solid organ transplants. While the potential for rejuvenation mediated by the transfer of youthful cells is currently being explored for therapeutic applications, aspects that relate to accelerating aging are no less clinically significant. Those effects may be particularly relevant in transplantation with an age discrepancy between donor and recipient. Here, we review recent advances in understanding the mechanisms by which young and old cells modify their environments to promote rejuvenation- or aging-associated phenotypes. We discuss their relevance to clinical transplantation and highlight potential opportunities for therapeutic intervention. Find the latest version: https://jci.me/123946/pdf REVIEW The Journal of Clinical Investigation Mixing old and young: enhancing rejuvenation and accelerating aging Ashley Lau,1 Brian K. Kennedy,2,3,4,5 James L. Kirkland,6 and Stefan G. Tullius1 1Division of Transplant Surgery, Department of Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA. 2Departments of Biochemistry and Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. 3Singapore Institute for Clinical Sciences, Singapore. 4Agency for Science, Technology and Research (A*STAR), Singapore. -
Induction of Motor Neurons by Sonic Hedgehog Is Independent of Floor Plate Differentiation Yasuto Tanabe, Henk Roelink and Thomas M
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Induction of motor neurons by Sonic hedgehog is independent of floor plate differentiation Yasuto Tanabe, Henk Roelink and Thomas M. Jessell Howard Hughes Medical Institute, Deptartment of Biochemistry and Molecular Biophysics, Center for Neurobiology and Behavior, Columbia University, 701 West 168th Street, New York, New York 10032, USA. Background: The differentiation of floor plate cells and transfected with Shh induced both floor plate cells and motor neurons in the vertebrate neural tube appears to be motor neurons when grown in contact with neural plate induced by signals from the notochord. The secreted pro- explants, whereas only motor neurons were induced when tein encoded by the Sonic hedgehog (Shh) gene is expressed the explants were grown at a distance from Shh-trans- by axial midline cells and can induce floor plate cells in fected COS cells. Direct transfection of neural plate cells vivo and in vitro. Motor neurons can also be induced in with an Shh-expression construct induced both floor plate vitro by cells that synthesize Sonic hedgehog protein cells and motor neurons, with motor neuron differentia- (Shh). It remains unclear, however, if the motor-neuron- tion occurring prior to, or coincidentally with, floor plate inducing activity of Shh depends on the synthesis of a dis- differentiation. The induction of motor neurons appears, tinct signaling molecule by floor plate cells. To resolve therefore, not to depend on floor plate differentiation. this issue, we have developed an in vitro assay which Conclusions: The induction of motor neurons by uncouples the notochord-mediated induction of motor Shh does not depend on distinct floor-plate-derived neurons from floor plate differentiation, and have used signaling molecules. -
REVIEW Organ Fabrication Using Pigs As an in Vivo Bioreactor
REVIEW Organ Fabrication Using Pigs as An in Vivo Bioreactor Eiji Kobayashi,1 Shugo Tohyama1,2 and Keiichi Fukuda2 1Department of Organ Fabrication, Keio University School of Medicine, Tokyo, Japan 2Department of Cardiology, Keio University School of Medicine, Tokyo, Japan (Received for publication on May 23, 2019) (Revised for publication on July 15, 2019) (Accepted for publication on July 17, 2019) (Published online in advance on August 6, 2019) We present the most recent research results on the creation of pigs that can accept human cells. Pigs in which grafted human cells can flourish are essential for studies of the production of human organs in the pig and for verification of the efficacy of cells and tissues of human origin for use in regenerative therapy. First, against the background of a worldwide shortage of donor organs, the need for future medical technology to produce human organs for transplantation is discussed. We then describe proof- of-concept studies in small animals used to produce human organs. An overview of the history of studies examining the induction of immune tolerance by techniques involving fertilized animal eggs and the injection of human cells into fetuses or neonatal animals is also presented. Finally, current and future prospects for producing pigs that can accept human cells and tissues for experimental purposes are discussed. (DOI: 10.2302/kjm.2019-0006-OA; Keio J Med 69 (2) : 30–36, June 2020) Keywords: organ fabrication, donor shortage, in vivo bioreactor, pig, stem cell Introduction nor and has saved -
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. -
Build a Neuron
Build a Neuron Objectives: 1. To understand what a neuron is and what it does 2. To understand the anatomy of a neuron in relation to function This activity is great for ALL ages-even college students!! Materials: pipe cleaners (2 full size, 1 cut into 3 for each student) pony beads (6/student Introduction: Little kids: ask them where their brain is (I point to my head and torso areas till they shake their head yes) Talk about legos being the building blocks for a tower and relate that to neurons being the building blocks for your brain and that neurons send messages to other parts of your brain and to and from all your body parts. Give examples: touch from body to brain, movement from brain to body. Neurons are the building blocks of the brain that send and receive messages. Neurons come in all different shapes. Experiment: 1. First build soma by twisting a pipe cleaner into a circle 2. Then put a 2nd pipe cleaner through the circle and bend it over and twist the two strands together to make it look like a lollipop (axon) 3. take 3 shorter pipe cleaners attach to cell body to make dendrites 4. add 6 beads on the axon making sure there is space between beads for the electricity to “jump” between them to send the signal super fast. (myelin sheath) 5. Twist the end of the axon to make it look like 2 feet for the axon terminal. 6. Make a brain by having all of the neurons “talk” to each other (have each student hold their neuron because they’ll just throw them on a table for you to do it.) messages come in through the dendrites and if its a strong enough electrical change, then the cell body sends the Build a Neuron message down it’s axon where a neurotransmitter is released. -
Chapter 8 Nervous System
Chapter 8 Nervous System I. Functions A. Sensory Input – stimuli interpreted as touch, taste, temperature, smell, sound, blood pressure, and body position. B. Integration – CNS processes sensory input and initiates responses categorizing into immediate response, memory, or ignore C. Homeostasis – maintains through sensory input and integration by stimulating or inhibiting other systems D. Mental Activity – consciousness, memory, thinking E. Control of Muscles & Glands – controls skeletal muscle and helps control/regulate smooth muscle, cardiac muscle, and glands II. Divisions of the Nervous system – 2 anatomical/main divisions A. CNS (Central Nervous System) – consists of the brain and spinal cord B. PNS (Peripheral Nervous System) – consists of ganglia and nerves outside the brain and spinal cord – has 2 subdivisions 1. Sensory Division (Afferent) – conducts action potentials from PNS toward the CNS (by way of the sensory neurons) for evaluation 2. Motor Division (Efferent) – conducts action potentials from CNS toward the PNS (by way of the motor neurons) creating a response from an effector organ – has 2 subdivisions a. Somatic Motor System – controls skeletal muscle only b. Autonomic System – controls/effects smooth muscle, cardiac muscle, and glands – 2 branches • Sympathetic – accelerator “fight or flight” • Parasympathetic – brake “resting and digesting” * 4 Types of Effector Organs: skeletal muscle, smooth muscle, cardiac muscle, and glands. III. Cells of the Nervous System A. Neurons – receive stimuli and transmit action potentials -
Sonic Hedgehog Induces the Lateral Floor Plate
Development 129, 4785-4796 (2002) 4785 Printed in Great Britain © The Company of Biologists Limited 2002 DEV2912 Dual origin of the floor plate in the avian embryo Jean-Baptiste Charrier, Françoise Lapointe, Nicole M. Le Douarin and Marie-Aimée Teillet* Institut d’Embryologie Cellulaire et Moléculaire, CNRS and Collège de France, UMR 7128, 49bis Avenue de la Belle Gabrielle, 94736 Nogent-sur-Marne Cedex, France *Author for correspondence (e-mail: [email protected]) Accepted 30 July 2002 SUMMARY Molecular analysis carried out on quail-chick chimeras, in development, one can experimentally obtain a complete which quail Hensen’s node was substituted for its chick floor plate in the neural epithelium by the inductive action counterpart at the five- to six-somite stage (ss), showed that of either a notochord or a MFP. The competence of the the floor plate of the avian neural tube is composed of neuroepithelium to respond to notochord or MFP signals is distinct areas: (1) a median one (medial floor plate or MFP) restricted to a short time window, as only the posterior-most derived from Hensen’s node and characterised by the same region of the neural plate of embryos younger than 15 ss is gene expression pattern as the node cells (i.e. expression of able to differentiate a complete floor plate comprising MFP HNF3β and Shh to the exclusion of genes early expressed and LFP. Moreover, MFP differentiation requires between in the neural ectoderm such as CSox1); and (2) lateral 4 and 5 days of exposure to the inducing tissues. -
Pre-Oligodendrocytes from Adult Human CNS
The Journal of Neuroscience, April 1992, 12(4): 1538-l 547 Pre-Oligodendrocytes from Adult Human CNS Regina C. Armstrong,lJ Henry H. Dorn, l,b Conrad V. Kufta,* Emily Friedman,3 and Monique E. Dubois-Dalcq’ ‘Laboratory of Viral and Molecular Pathogenesis, and %urgical Neurology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892 and 3Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania 19104-3246 CNS remyelination and functional recovery often occur after Rapid and efficient neurotransmission is dependent upon the experimental demyelination in adult rodents. This has been electrical insulating capacity of the myelin sheath around axons attributed to the ability of mature oligodendrocytes and/or (reviewed in Ritchie, 1984a,b). Nerve conduction is impaired their precursor cells to divide and regenerate in response after loss of the myelin sheath and results in severe neurological to signals in demyelinating lesions. To determine whether dysfunction in human demyelinating diseases such as multiple oligodendrocyte precursor cells exist in the adult human sclerosis (MS). Remyelination can occur in the CNS of MS CNS, we have cultured white matter from patients under- patients but appears to be limited (Perier and Gregoire, 1965; going partial temporal lobe resection for intractable epilep- Prineas et al., 1984). Studies of acute MS cases have revealed sy. These cultures contained a population of process-bear- that recent demyelinating lesions can exhibit remyelination that ing cells that expressed antigens recognized by the 04 appears to correlate with the generation of new oligodendrocytes monoclonal antibody, but these cells did not express galac- (Prineas et al., 1984; Raine et al., 1988). -
Nernst Potentials and Membrane Potential Changes
UNDERSTANDING MEMBRANE POTENTIAL CHANGES IN TERMS OF NERNST POTENTIALS: For seeing how a change in conductance to ions affects the membrane potential, follow these steps: 1. Make a graph with membrane potential on the vertical axis (-100 to +55) and time on the horizontal axis. 2. Draw dashed lines indicating the standard Nernst potential (equilibrium potential) for each ion: Na+ = +55 mV, K+ = -90mV, Cl- = -65 mV. 3. Draw lines below the horizontal axis showing the increased conductance to individual ions. 4. Start plotting the membrane potential on the left. Most graphs will start at resting potential (-70 mV) 5. When current injection (Stim) is present, move the membrane potential upward to Firing threshold. 6. For the time during which membrane conductance to a particular ion increases, move the membrane potential toward the Nernst potential for that ion. 7. During the time when conductance to a particular ion decreases, move the membrane potential away from the Nernst potential of that ion, toward a position which averages the conductances of the other ions. 8. When conductances return to their original value, membrane potential will go to its starting value. +55mV ACTION POTENTIAL SYNAPTIC POTENTIALS 0mV Membrane potential Firing threshold Firing threshold -65mV -90mV Time Time Na+ K+ Conductances Stim CHANGES IN MEMBRANE POTENTIAL ALLOW NEURONS TO COMMUNICATE The membrane potential of a neuron can be measured with an intracellular electrode. This 1 provides a measurement of the voltage difference between the inside of the cell and the outside. When there is no external input, the membrane potential will usually remain at a value called the resting potential. -
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. -
Induction of Floor Plate Differentiation by Contact-Dependent
Development 117, 205-218 (1993) 205 Printed in Great Britain © The Company of Biologists Limited 1993 Induction of floor plate differentiation by contact-dependent, homeogenetic signals Marysia Placzek1, Thomas M. Jessell2 and Jane Dodd1,* 1Department of Physiology and Cellular Biophysics, 2Department of Biochemistry and Molecular Biophysics and Howard Hughes Medical Institute, and 1,2Center for Neurobiology and Behavior, Columbia University, New York, New York 10032, USA *Author for correspondence SUMMARY The floor plate is located at the ventral midline of the derive from medial floor plate cells. The response of neural tube and has been implicated in neural cell pat- neural plate cells to inductive signals declines with terning and axon guidance. To address the cellular embryonic age, suggesting that the mediolateral extent mechanisms involved in floor plate differentiation, we of the floor plate is limited by a loss of competence of have used an assay that monitors the expression of floor- neural cells. The rostral boundary of the floor plate at plate-specific antigens in neural plate explants cultured the midbrain-forebrain junction appears to result from in the presence of inducing tissues. Contact-mediated the lack of inducing activity in prechordal mesoderm signals from both the notochord and the floor plate act and the inability of rostral neural plate cells to respond directly on neural plate cells to induce floor plate differ- to inductive signals. entiation. Floor plate induction is initiated medially by a signal from the notochord, but appears to be propa- gated to more lateral cells by homeogenetic signals that Key words: floor plate, notochord, neural plate, induction.