Nonrenewal of Neurons in the Cerebral Neocortex of Adult Macaque Monkeys

Total Page:16

File Type:pdf, Size:1020Kb

Nonrenewal of Neurons in the Cerebral Neocortex of Adult Macaque Monkeys The Journal of Neuroscience, February 1, 2003 • 23(3):937–942 • 937 Nonrenewal of Neurons in the Cerebral Neocortex of Adult Macaque Monkeys Daisuke Koketsu,1 Akichika Mikami,2 Yusei Miyamoto,1 and Tatsuhiro Hisatsune1 1Department of Integrated Biosciences, University of Tokyo, Kashiwa 277-8562, Japan, and 2Primate Research Institute, Kyoto University, Inuyama 484-8506, Japan The concept that, after developmental periods, neocortical neurons become numerically stable and are normally nonrenewable has been challengedbyareportofcontinuousneurogenesisintheassociationareasofthecerebralcortexintheadultMacaquemonkey.Therefore, we have reexamined this issue in two different Macaque species using the thymidine analog bromodeoxyuridine (BrdU) as an indicator of DNA replication during cell division. We found several BrdUϩ/NeuNϩ (neuronal nuclei) double-labeled cells, but cortical neurons, distinguished readily by their size and cytological and immunohistochemical properties, were not BrdU positive. We examined in detail the frontal cortex, where it is claimed that the largest daily addition of neurons has been made, but did not see migratory streams or any sign of addition of new neurons. Thus, we concluded that, in the normal condition, cortical neurons of adult primates, similar to other mammalian species, are neither supplemented nor renewable. Key words: adult neurogenesis; cerebral cortex; primates; DNA synthesis; glial markers; 3D immunohistochemistry Most neurons of the mammalian brain are generated from neu- Gould and colleagues assert, on the basis of labeling with the roepithelial cells near cerebral ventricles during well defined de- thymidine analog bromodeoxyuridine (BrdU), that streams of velopmental stages and then act as substrates of neural circuitry new neurons are generated continuously and added to the asso- throughout life (Rakic, 1985). However, recent findings of adult ciation neocortex of adult Macaque monkeys (Gould et al., neurogenesis in selected structures of the mammalian brain 1999b), where many form connections and survive for weeks present the possibility that this concept does not apply for all before dying (Gould et al., 2001). The daily addition of thousands brain regions, in particular, the neural circuits of the olfactory of new neurons to the principal sulcus alone (Gould et al., 1999b) bulb and dentate gyrus of the hippocampus, which may be in the absence of net growth indicated high turnover. To verify changing their basic circuitry with the arrival of newly born neu- this claim, Kornack and Rakic (2001a) have performed experi- rons (Rochefort et al., 2002; van Praag et al., 2002). In addition, ments using the BrdU method in adult Macaque monkeys. They the application of new staining methods in the adult Macaque found BrdU-labeled non-neuronal cells, but they did not detect monkeys uncovered some new neurons in the olfactory bulb newly born neurons in the neocortex, nor did they find the (Kornack and Rakic, 2001b) and dentate gyrus of the hippocam- stream of migrating neurons from the proliferative subventricu- pus (Gould et al., 1999a; Kornack and Rakic, 1999). lar zone to the principal sulcus of the prefrontal cortex (Kornack In terms of the cerebral neocortex, studies in various mam- and Rakic, 2001a). This discrepancy in basic findings required a malian species that range from mice and rats to ferrets and cats reexamination in other laboratories (Nowakowski and Hayes, have indicated that neurogenesis in this structure stops after well 2000). defined developmental periods (Hicks and D’Amato, 1968; Cavi- Therefore, we addressed the question of whether new neurons ness and Sidman, 1973; Luskin and Shatz, 1985; Jackson et al., are generated and continuously added in the neocortex of juve- 1989; Takahashi et al., 1996). Furthermore, no sign of neuronal nile and young adult Macaque monkeys using BrdU methods for renewal has been found in the cortex of adult rodents (Magavi et labeling DNA synthesis in the dividing brain cells (Nowakowski al., 2000). An extensive analysis of Macaque monkeys exposed to [ 3H]thymidine indicated that the neocortical neurons in pri- et al., 1989) that were used by previous investigators. We exam- mates are generated prenatally (Rakic, 1974) and not normally ined in detail the frontal cortex, where it has been previously renewed during adulthood (Rakic, 1985, 2002a). It was suggested claimed that the largest daily addition of neurons is made (Gould that a stable population of neurons in the cortex might be an et al., 1999b). We selected juvenile and young adult monkeys important mechanism for continuity of learning and preserving because they presumably have more neuronal plasticity and to memory over a lifetime (Rakic, 1985). Contrary to this theory, avoid the possibility of BrdU labeling during unscheduled DNA synthesis in the process of cell death (apoptosis) in aged animals (Yang et al., 2001). We also avoided high doses of BrdU to avoid Received Sept. 13, 2002; revised Nov. 4, 2002; accepted Nov. 20, 2002. This study is supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports its possible mutagenic and stimulation effect on DNA synthesis andCultureofJapan.WethankDr.JoseAntonioCampos-OrtegaandDr.YukioHirataforinformativediscussionand (Nowakowski and Hayes, 2001; Rakic, 2002b). To identify the technical advice. We also thank Dr. Shinichi Kohsaka for kindly providing an anti-Iba-1 antibody. phenotypes of BrdU-labeled cells in the neocortex, an immuno- Correspondence should be addressed to Tatsuhiro Hisatsune, Department of Integrated Biosciences, Graduate histochemical analysis was performed with neuronal markers School of Frontier Sciences, The University of Tokyo, Bioscience Building 402, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan. E-mail: [email protected]. NeuN, a transcriptional factor that is expressed in the nucleus Copyright © 2003 Society for Neuroscience 0270-6474/03/230937-06$15.00/0 and cytoplasm of neurons (Mullen et al., 1992), and doublecortin 938 • J. Neurosci., February 1, 2003 • 23(3):937–942 Kotetsu et al. • Stability of Cortical Neuron in Adult Primates tions were preserved in a cryoprotectant solution (30% ethylene glycol, 30% glycerol in 0.05 M phosphate buffer) at Ϫ20°C until they were processed. Immunohistochemistry. Sections were washed twice with Tris-buffered saline (TBS) for 10 min. Sections were then treated in 10 M citric acid buffer at 90°C for 5 min. The heated sections were left at room temper- ature for 30 min and washed with TBS for 10 min. The sections were incubated in 1 M HCl at 37°C for 30 min and neutralized by rinsing with 0.1 M borate buffer and washed twice with TBS. The sections were then Figure1. BrdUinjectionschedule.ThedayofBrdUinjectionisrepresentedbythefilledcircle, blocked with a blocking solution (5% normal donkey serum and 0.3% and the day of perfusion is represented by the arrowhead. M. fascicularis I received once-daily Triton X-100 in TBS) for 30 min at room temperature with gentle shak- BrdU injections for 3 consecutive days and one more injection after 7 d and then was perfused ing. The blocked sections were reacted with primary antibodies at 4°C. 1 d after the final injection. M. fascicularis II received five once-daily injections every other day The concentration of Triton X-100 in the blocking solution dissolving and then was perfused 14 d after the final injection. M. fuscata I and M. fuscata II received primary antibodies with 1 or 3 d reaction time was 0.3 or 0.1%, respec- once-dailyinjectionsfor5consecutivedays.Then,M.fuscataIandM.fuscataIIwereperfused25 tively. Monoclonal rat anti-BrdU antibody (Harlan, Leicestershine, UK) or26dafterthefinalinjection,respectively.Thenumberofdaysrepresentstheperiodbetween with a 1:200 dilution and monoclonal mouse anti-BrdU (Becton Dick- the first injection and perfusion. inson, Franklin Lake, NJ) at 1:33 were used. Some antibodies to identify cell types were also used. As antibodies to the neuronal marker, mono- clonal mouse anti-NeuN antibody (1:1000; Chemicon, Temecula, CA) (DCX) (Gleeson et al., 1999; Nacher et al., 2001) and also with and polyclonal goat anti-DCX antibody (1:100; Santa Cruz Biotechnol- markers of other non-neuronal cell types. GFAP and S-100␤ (as- ogy, Santa Cruz, CA) were used. The reaction time of NeuN was1dand troglial cell), O4 (oligodendrocyte), and Iba-1 (microglial cell) that of DCX was 3 d. As antibodies to the astroglial marker, polyclonal (Ito et al., 1998) were used. rabbit anti-GFAP antibody (1:10,000; Dako, Carpinteria, CA) and poly- clonal rabbit anti-S-100␤ antibody (1:5000; Swant, Bellinzona, Switzer- Materials and Methods land) were used. As the antibody to oligodendrocyte marker, monoclonal Animals. Two young adult female Macaca fascicularis (Cynomolgus mouse IgM anti-O4 antibody (1:10; Chemicon) was used. Then, as the monkey; 5 years of age) and two juvenile female M. fuscata (Japanese antibody to microglial marker, polyclonal rabbit IgG anti-Iba-1 antibody monkey; 2 years of age) were used. Monkeys were housed at the Primate (1:250; kind gift from S. Kohsaka, National Institute of Neuroscience, Research Institute of Kyoto University and were maintained in individ- Tokyo, Japan) was used. The reaction time of GFAP, O4, and Iba-1 was ␤ ual cages with up to 16 cages facing each other in a single room. Thus, the 1 d and that of S-100 and O4 was 3 d. After immunoreaction with these monkeys could see and interact with other monkeys. In addition, Japa- primary antibodies, sections were washed with TBS. The sections were nese monkeys were provided with a piece of wood that was hung in the then reacted with fluorochromo-conjugated secondary antibodies. As cage as a playing tool and a food pickup toy that was placed in front of the secondary antibodies, Alexa 488 (1:1000; Molecular Probes, Eugene, OR) cage every day for several hours. The size of the toy was 60 ϫ 60 cm with and rhodamine Red-X (1:200; Jackson ImmunoResearch, West Grove, 480 holes, half of which were covered with a piece of plate so that the PA) were used.
Recommended publications
  • Quiescent Satellite Glial Cells of the Adult Trigeminal Ganglion
    Cent. Eur. J. Med. • 9(3) • 2014 • 500-504 DOI: 10.2478/s11536-013-0285-z Central European Journal of Medicine Quiescent satellite glial cells of the adult trigeminal ganglion Research Article Mugurel C. Rusu*1,2,3, Valentina M. Mănoiu4, Nicolae Mirancea3, Gheorghe Nini5 1 „Carol Davila” University of Medicine and Pharmacy, 050511 Bucharest, Romania. 2 MEDCENTER - Center of Excellence in Laboratory Medicine and Pathology 013594 Bucharest, Romania 3 Institute of Biology of Bucharest – The Romanian Academy, , 060031 Bucharest, Romania 4 Faculty of Geography, University of Bucharest, 050107 Bucharest, Romania 5 Faculty of Medicine, Pharmacy and Dental Medicine, “Vasile Goldiş” Western University, 310045 Arad, Romania Received 18 August 2013; Accepted 27 November 2013 Abstract: Sensory ganglia comprise functional units built up by neurons and satellite glial cells (SGCs). In animal species there was proven the presence of neuronoglial progenitor cells in adult samples. Such neural crest-derived progenitors were found in immunohistochemistry (IHC). These fi ndings were not previously documented in transmission electron microscopy (TEM). It was thus aimed to assess in TEM if cells of the human adult trigeminal ganglion indeed have ultrastructural features to qualify for a progenitor, or quiescent phenotype. Trigeminal ganglia were obtained from fi fteen adult donor cadavers. In TEM, cells with heterochromatic nuclei, a pancytoplasmic content of free ribosomes, few perinuclear mitochondria, poor developed endoplasmic reticulum, lack of Golgi complexes and membrane traffi cking specializations, were found included in the neuronal envelopes built-up by SGCs. The ultrastructural pattern was strongly suggestive for these cells being quiescent progenitors. However, further experiments should correlate the morphologic and immune phenotypes of such cells.
    [Show full text]
  • Canine Dorsal Root Ganglia Satellite Glial Cells Represent an Exceptional Cell Population with Astrocytic and Oligodendrocytic P
    www.nature.com/scientificreports OPEN Canine dorsal root ganglia satellite glial cells represent an exceptional cell population with astrocytic and Received: 17 August 2017 Accepted: 6 October 2017 oligodendrocytic properties Published: xx xx xxxx W. Tongtako1,2, A. Lehmbecker1, Y. Wang1,2, K. Hahn1,2, W. Baumgärtner1,2 & I. Gerhauser 1 Dogs can be used as a translational animal model to close the gap between basic discoveries in rodents and clinical trials in humans. The present study compared the species-specifc properties of satellite glial cells (SGCs) of canine and murine dorsal root ganglia (DRG) in situ and in vitro using light microscopy, electron microscopy, and immunostainings. The in situ expression of CNPase, GFAP, and glutamine synthetase (GS) has also been investigated in simian SGCs. In situ, most canine SGCs (>80%) expressed the neural progenitor cell markers nestin and Sox2. CNPase and GFAP were found in most canine and simian but not murine SGCs. GS was detected in 94% of simian and 71% of murine SGCs, whereas only 44% of canine SGCs expressed GS. In vitro, most canine (>84%) and murine (>96%) SGCs expressed CNPase, whereas GFAP expression was diferentially afected by culture conditions and varied between 10% and 40%. However, GFAP expression was induced by bone morphogenetic protein 4 in SGCs of both species. Interestingly, canine SGCs also stimulated neurite formation of DRG neurons. These fndings indicate that SGCs represent an exceptional, intermediate glial cell population with phenotypical characteristics of oligodendrocytes and astrocytes and might possess intrinsic regenerative capabilities in vivo. Since the discovery of glial cells over a century ago, substantial progress has been made in understanding the origin, development, and function of the diferent types of glial cells in the central nervous system (CNS) and peripheral nervous system (PNS)1.
    [Show full text]
  • Nomina Histologica Veterinaria, First Edition
    NOMINA HISTOLOGICA VETERINARIA Submitted by the International Committee on Veterinary Histological Nomenclature (ICVHN) to the World Association of Veterinary Anatomists Published on the website of the World Association of Veterinary Anatomists www.wava-amav.org 2017 CONTENTS Introduction i Principles of term construction in N.H.V. iii Cytologia – Cytology 1 Textus epithelialis – Epithelial tissue 10 Textus connectivus – Connective tissue 13 Sanguis et Lympha – Blood and Lymph 17 Textus muscularis – Muscle tissue 19 Textus nervosus – Nerve tissue 20 Splanchnologia – Viscera 23 Systema digestorium – Digestive system 24 Systema respiratorium – Respiratory system 32 Systema urinarium – Urinary system 35 Organa genitalia masculina – Male genital system 38 Organa genitalia feminina – Female genital system 42 Systema endocrinum – Endocrine system 45 Systema cardiovasculare et lymphaticum [Angiologia] – Cardiovascular and lymphatic system 47 Systema nervosum – Nervous system 52 Receptores sensorii et Organa sensuum – Sensory receptors and Sense organs 58 Integumentum – Integument 64 INTRODUCTION The preparations leading to the publication of the present first edition of the Nomina Histologica Veterinaria has a long history spanning more than 50 years. Under the auspices of the World Association of Veterinary Anatomists (W.A.V.A.), the International Committee on Veterinary Anatomical Nomenclature (I.C.V.A.N.) appointed in Giessen, 1965, a Subcommittee on Histology and Embryology which started a working relation with the Subcommittee on Histology of the former International Anatomical Nomenclature Committee. In Mexico City, 1971, this Subcommittee presented a document entitled Nomina Histologica Veterinaria: A Working Draft as a basis for the continued work of the newly-appointed Subcommittee on Histological Nomenclature. This resulted in the editing of the Nomina Histologica Veterinaria: A Working Draft II (Toulouse, 1974), followed by preparations for publication of a Nomina Histologica Veterinaria.
    [Show full text]
  • Advances in Transcription Factors Related to Neuroglial Cell Reprogramming
    Translational Neuroscience 2020; 11: 17–27 Review Article Kuangpin Liu, Wei Ma, Chunyan Li, Junjun Li, Xingkui Zhang, Jie Liu, Wei Liu, Zheng Wu, Chenghao Zang, Yu Liang, Jianhui Guo, Liyan Li* Advances in transcription factors related to neuroglial cell reprogramming https://doi.org/10.1515/tnsci-2020-0004 glia. Neuroglial cells are intimate partners of neurons Received August 23, 2019; accepted January 7, 2020 throughout their life cycle [2]. In embryos, neuroglial cells form a cellular framework and regulate the survival Abstract: Neuroglial cells have a high level of plasticity, and differentiation of neurons. In addition, during and many types of these cells are present in the nervous neurogenesis and early development, neuroglial cells system. Neuroglial cells provide diverse therapeutic mediate the proliferation and differentiation of neurons targets for neurological diseases and injury repair. Cell by synthesizing and secreting various growth factors and reprogramming technology provides an efficient pathway extracellular matrix components [2]. The most prominent for cell transformation during neural regeneration, while function of neuroglial cells during development is transcription factor-mediated reprogramming can facilitate formation of myelin sheaths around axons, which provide the understanding of how neuroglial cells mature into necessary signals and maintain rapid conduction for functional neurons and promote neurological function nervous system function [3]. Additionally, neuroglial recovery. cells maintain homeostasis in nerve cells and participate in synaptic plasticity and cell repair [2]. Similar to Keywords: Neuroglial cell; Reprogramming; Transcription developmental processes in other types of animal cells, factor the development of neuroglial cells is influenced by interactions between cells; cell lineage and extracellular signaling can regulate the migration, proliferation and 1 Introduction differentiation of glial cells.
    [Show full text]
  • Neuron-Satellite Glial Cell Interactions in Sympathetic Nervous System Development
    NEURON-SATELLITE GLIAL CELL INTERACTIONS IN SYMPATHETIC NERVOUS SYSTEM DEVELOPMENT by Erica D. Boehm A dissertation submitted to the Johns Hopkins University in conformity with the requirements for the degree of Doctor of Philosophy Baltimore, Maryland July 2020 © 2020 Erica Boehm All rights reserved. ABSTRACT Glial cells play crucial roles in maintaining the stability and structure of the nervous system. Satellite glial cells are a loosely defined population of glial cells that ensheathe neuronal cell bodies, dendrites, and synapses of the peripheral nervous system (Elfvin and Forsman 1978; Pannese 1981). Satellite glial cells are closely juxtaposed to peripheral neurons with only 20nm of space between their membranes (Dixon 1969). This close association suggests a tight coupling between the cells to allow for possible exchange of important nutrients, yet very little is known about satellite glial cell function and development. How neurons and glial cells co-develop to create this tightly knit unit remains undefined, as well as the functional consequences of disrupting these contacts. Satellite glial cells are derived from the same population of cells that give rise to peripheral neurons, but do not begin differentiation and proliferation until neurogenesis has been completed (Hall and Landis 1992). A key signaling pathway involved in glial specification is the Delta/Notch signaling pathway (Tsarovina et al. 2008). However, recent studies also implicate Notch signaling in the maturation of glia through non- canonical Notch ligands such as Delta/Notch-like EGF-related Receptor (DNER) (Eiraku et al. 2005). Interestingly, it has been reported that levels of DNER in sympathetic neurons may be dependent on the target-derived growth factor, nerve growth factor (NGF), and this signal is prominent in sympathetic neurons at the time in which satellite glial cells are developing (Deppmann et al.
    [Show full text]
  • The Characterization of G-Protein Coupled Receptors in Isolated Rat Dorsal Root Ganglion Cells
    The Characterization of G-protein Coupled Receptors in Isolated Rat Dorsal Root Ganglion Cells YEUNG, Barry Ho Sing A Thesis Submitted in Partial Fulfillment of the Requirements for the Degree of Master of Philosophy in Pharmacology I The ChineseSeptembe Universitr y201 of1 Hon g Kong |1 I e SEP 2ot^ij WrwiiiTY 一"/M Thesis/Assessment Committee Professor John A. RUDD (Chair) Professor Helen WISE (Thesis Supervisor) Professor Wing Tai CHEUNG (Committee Member) Professor Daisy K.Y. SHUM (External Examiner) I Abstract Abstract of thesis entitled: The Characterization of G-protein Coupled Receptors in Isolated Rat Dorsal Root Ganglion Cells Submitted by Barry Ho Sing YEUNG For the degree of Master of Philosophy in Pharmacology At The Chinese University of Hong Kong in September 2011 Sensory stimuli are detected by primary sensory neurons whose cell bodies reside in the dorsal root ganglia (DRG) of the peripheral nervous system (PNS). In the DRG, glial cells, including satellite glial cells (SGCs) and Schwann cells, are closely associated with the primary sensory neurons. The primary functions of glial cells are to regulate the trafficking of extracellular ions and neurotransmitters for proper neuronal function and survival. In the early study of pain, DRG were examined and sensory neurons were presumed to be the sole players leading to the development of pain while the associated glial cells were thought not to be directly involved. Recently, however, glial cells have emerged as important contributors to the maintenance and amplification of pain by bidirectional neuron-glia interactions.' i In isolated DRG cell cultures, neurons and glial cells in a mixed cell population can be enriched and studied separately.
    [Show full text]
  • Diversity Among Satellite Glial Cells in Dorsal Root Ganglia of the Rat
    SatelliteBrazilian glial Journal cells of in Medical rat spinal and ganglion Biological Research (2008) 41: 1011-1017 1011 ISSN 0100-879X Short Communication Diversity among satellite glial cells in dorsal root ganglia of the rat R.S. Nascimento1,2, M.F. Santiago3, S.A. Marques1,2, S. Allodi1,2 and A.M.B. Martinez1,2 1Departamento de Histologia e Embriologia, 2Programa de Pós-Graduação em Ciências Morfológicas, Instituto de Ciências Biomédicas, 3Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil Correspondence to: A.M.B. Martinez, Departamento de Histologia e Embriologia, ICB, CCS, Bloco F, UFRJ, Av. Brig. Trompowsky, s/n, 21941-540 Rio de Janeiro, RJ, Brasil E-mail: [email protected] Peripheral glial cells consist of satellite, enteric glial, and Schwann cells. In dorsal root ganglia, besides pseudo-unipolar neurons, myelinated and nonmyelinated fibers, macrophages, and fibroblasts, satellite cells also constitute the resident components. Information on satellite cells is not abundant; however, they appear to provide mechanical and metabolic support for neurons by forming an envelope surrounding their cell bodies. Although there is a heterogeneous population of neurons in the dorsal root ganglia, satellite cells have been described to be a homogeneous group of perineuronal cells. Our objective was to characterize the ultrastructure, immunohistochemistry, and histochemistry of the satellite cells of the dorsal root ganglia of 17 adult 3-4-month-old Wistar rats of both genders. Ultrastructurally, the nuclei of some satellite cells are heterochromatic, whereas others are euchromatic, which may result from different amounts of nuclear activity.
    [Show full text]
  • Development of an in Vitro Model for Activation of Satellite Glial Cells in The
    Development of an in vitro Model for Activation of Satellite Glial Cells in the Sympathetic Nervous System Master’s Thesis Presented to The Faculty of the Graduate School of Arts and Sciences Brandeis University Graduate Program in Molecular and Cell Biology Susan Birren, Advisor In Partial Fulfillment Of the Requirements for the Degree Master of Science in Molecular and Cell Biology by Surbhi Sona February 2014 Acknowledgement I would like to thank my advisor Dr. Susan Birren for giving me this learning opportunity in her lab. I thank her for her constant guidance and support and for critiquing my work. I also thank her for her insightful questions and suggestions. I am extremely grateful to Dr. Joana Enes for mentoring my work and training me in the various techniques used in this research. I thank her for her patience and valuable guidance which made this a wonderful learning experience for me. I deeply thank her for providing me with some of the materials used in my experiments - She established the primary rat cultures used in this study. The various HEK cell constructs, used in the neurotrophin experiments, were also developed by her. I also thank all the members of the Birren lab for their support and valuable discussions on my work. ii Abstract Development of an in vitro Model for Activation of Satellite Glial Cells in the Sympathetic Nervous System A thesis presented to the Graduate Program in Molecular and Cell Biology Graduate School of Arts and Sciences Brandeis University Waltham, Massachusetts By Surbhi Sona Glial cells of the central nervous system are activated upon injury and modulate the course of several diseases.
    [Show full text]
  • Neuronal Processes and Glial Precursors Form a Scaffold for Wiring the Developing Mouse Cochlea ✉ N
    ARTICLE https://doi.org/10.1038/s41467-020-19521-2 OPEN Neuronal processes and glial precursors form a scaffold for wiring the developing mouse cochlea ✉ N. R. Druckenbrod1,2, E. B. Hale1, O. O. Olukoya 1, W. E. Shatzer1 & L. V. Goodrich 1 In the developing nervous system, axons navigate through complex terrains that change depending on when and where outgrowth begins. For instance, in the developing cochlea, spiral ganglion neurons extend their peripheral processes through a growing and hetero- fi 1234567890():,; geneous environment en route to their nal targets, the hair cells. Although the basic prin- ciples of axon guidance are well established, it remains unclear how axons adjust strategies over time and space. Here, we show that neurons with different positions in the spiral ganglion employ different guidance mechanisms, with evidence for both glia-guided growth and fasciculation along a neuronal scaffold. Processes from neurons in the rear of the ganglion are more directed and grow faster than those from neurons at the border of the ganglion. Further, processes at the wavefront grow more efficiently when in contact with glial precursors growing ahead of them. These findings suggest a tiered mechanism for reliable axon guidance. 1 Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA. 2Present address: Decibel Therapeutics, 1325 ✉ Boylston St #500, Boston, MA 02215, USA. email: [email protected] NATURE COMMUNICATIONS | (2020) 11:5866 | https://doi.org/10.1038/s41467-020-19521-2 | www.nature.com/naturecommunications 1 ARTICLE NATURE COMMUNICATIONS | https://doi.org/10.1038/s41467-020-19521-2 euroscientists have long puzzled how neurons make the Several observations suggest that glia might be involved in the connections needed for proper circuit function, with earliest stages of cochlear wiring.
    [Show full text]
  • Nomina Histologica Veterinaria
    NOMINA HISTOLOGICA VETERINARIA Submitted by the International Committee on Veterinary Histological Nomenclature (ICVHN) to the World Association of Veterinary Anatomists Published on the website of the World Association of Veterinary Anatomists www.wava-amav.org 2017 CONTENTS Introduction i Principles of term construction in N.H.V. iii Cytologia – Cytology 1 Textus epithelialis – Epithelial tissue 10 Textus connectivus – Connective tissue 13 Sanguis et Lympha – Blood and Lymph 17 Textus muscularis – Muscle tissue 19 Textus nervosus – Nerve tissue 20 Splanchnologia – Viscera 23 Systema digestorium – Digestive system 24 Systema respiratorium – Respiratory system 32 Systema urinarium – Urinary system 35 Organa genitalia masculina – Male genital system 38 Organa genitalia feminina – Female genital system 42 Systema endocrinum – Endocrine system 45 Systema cardiovasculare et lymphaticum [Angiologia] – Cardiovascular and lymphatic system 47 Systema nervosum – Nervous system 52 Receptores sensorii et Organa sensuum – Sensory receptors and Sense organs 58 Integumentum – Integument 64 INTRODUCTION The preparations leading to the publication of the present first edition of the Nomina Histologica Veterinaria has a long history spanning more than 50 years. Under the auspices of the World Association of Veterinary Anatomists (W.A.V.A.), the International Committee on Veterinary Anatomical Nomenclature (I.C.V.A.N.) appointed in Giessen, 1965, a Subcommittee on Histology and Embryology which started a working relation with the Subcommittee on Histology of the former International Anatomical Nomenclature Committee. In Mexico City, 1971, this Subcommittee presented a document entitled Nomina Histologica Veterinaria: A Working Draft as a basis for the continued work of the newly-appointed Subcommittee on Histological Nomenclature. This resulted in the editing of the Nomina Histologica Veterinaria: A Working Draft II (Toulouse, 1974), followed by preparations for publication of a Nomina Histologica Veterinaria.
    [Show full text]
  • Expression of Glial Fibrillary Acidic Protein (GFAP) in the Trigeminal Ganglion of Male Wistar Rats
    Original Research Expression of Glial Fibrillary Acidic Protein (GFAP) in the Trigeminal Ganglion of Male Wistar Rats P.K. Sankaran1,*, M.Kumaresan2, G. Karthikeyan3, Yuvaraj M.4 1,3Assistant Professor, 2,4Tutor, Dept. of Anatomy, Saveetha Medical College & Research Institute, Chennai *Corresponding Author: Email: [email protected] ABSTRACT Background Significance: The pseudounipolar neurons in the sensory ganglia are wrapped by small satellite cells which play a similar role like Schwann cells in the peripheral nervous system. The pseudounipolar cells of trigeminal ganglion are surrounded by a capsule formed by satellite glial cells. These satellite glial cells play important role in maintaining normal functions of the neuron. Aim & Objective: To localise GFAP in satellite glial cells of trigeminal ganglion. Material & Methods: Six male wistar albino rats trigeminal ganglion were collected and immunohistochemically stained for GFAP in six male wistar albino rats. Result: GFAP was localised in the cytoplasm of satellite glial cells surrounding the neurons. GFAP was also localised around Schwaan cells of an axon. Discussion: GFAP is an intermediate protein which can get up regulated due to peripheral axonal injury. This GFAP can trigger mediators of inflammation and create a neuralgia or migraine like conditions. Conclusion: This study concluded that satellite cells are type of glial cells that express GFAP. This GFAP was also expressed by Schwaan cells surrounding the axon. Keywords: GFAP, Trigeminal ganglion, Satellite glial cells, Pseudounipolar
    [Show full text]
  • Characterization of the Satellite Glial Cell (SGC) in the Extrinsic Sensory Innervation of the Gut in Rodent High-Fat Diet-Induced Obesity (DIO)
    Characterization of the satellite glial cell (SGC) in the extrinsic sensory innervation of the gut in rodent high-fat diet-induced obesity (DIO) Grace England STAR Mentor: Dr. Helen Raybould 11 August 2016 Obesity epidemic warrants scientific attention •In the U.S., 39.4% of adults were obese in 2011-2012 (68.6% overweight or obese)1 •Canine obesity rates average 34-59% in developed nations 2 •Feline obesity rates average 19-52% in developed nations 3 •Obesity co-morbidities are often very detrimental to quality of life. •Therefore, the study of physiological regulation of food intake is relevant for understanding obesity onset and identifying treatments. The vagal afferent pathway communicates information about contents of the gut lumen to the hypothalamus •Gut hormones target vagal afferent terminals, which relay sensory information to the brain. Hypothalamus Anorexigenic hormones (eg leptin) • Anorexigenic: signal satiety. Cholecystokinin Glucagon-like •However, consumption of a high-fat peptide 1 diet (HFD) leads to leptin resistance in Peptide YY3-36 vagal afferent neurons (VAN). Leptin Leptin resistance is characterized by cellular and electrophysiological changes in VAN • Leptin is ineffective in communicating the “fed” state of the gut to the brain. • Changes in neuronal plasticity “lock” VAN in an orexigenic phenotype, and hyperphagia ensues.4,5 Satellite glial cells (SGCs) envelop neuronal cell bodies in 3D space Neuron cell body Satellite Glial Cells http://philschatz.com/anatomy-book/resources/1210_Glial_Cells_of_the_PNS.jpg
    [Show full text]