DOCSLIB.ORG

Activity-Dependent Regulation of Neu Differentiation Factor/Neuregulin

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Activity-Dependent Regulation of Neu Differentiation Factor/Neuregulin Proc. Natl. Acad. Sci. USA Vol. 95, pp. 1888–1893, February 1998 Neurobiology Activity-dependent regulation of Neu differentiation factoryneuregulin expression in rat brain (central nervous systemyneural plasticityytyrosine kinase) RAYA EILAM*, RONIT PINKAS-KRAMARSKI†,BARRY J. RATZKIN‡,MENAHEM SEGAL*, AND YOSEF YARDEN†§ Departments of *Neurobiology and †Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel; and ‡Amgen Center, Thousand Oaks, CA 91320 Communicated by Michael Sela, Weizmann Institute of Science, Rehovot, Israel, December 16, 1997 (received for review September 3, 1997) ABSTRACT Neu differentiation factor (NDFyneuregulin) less, because NDFyneuregulin induces heterodimerization be- is widely expressed in the central and peripheral nervous tween ErbB-3 and ErbB-2, the latter can reconstitute signaling by systems, where it functions as a mediator of the interactions the neuregulins even in cells that do not express ErbB-4 (15, 16). between nerve cells and Schwann, glia, oligodendrocyte, and The NDFyneuregulin family is widely expressed during em- muscle cells, to control cellular proliferation, differentiation, bryonic development in two major locations: the nervous systems and migration. NDF binds to two receptor tyrosine kinases, and the mesenchymal portion of parenchymal organs (10, 17). ErbB-3 and ErbB-4. Here we demonstrate that NDF and its Both a and b isoforms are expressed in mesenchymal cells, where ErbB-4 receptor are highly reactive to changes in ambient they presumably function as mediators of mesenchyme–epithel neuronal activity in the rodent brain in a region-selective interactions. Likewise, the neural isoforms of the neuregulins, manner. Generation of epileptic seizures by using kainic acid, which are mostly of the b isoform, also play a role in cell-to-cell a potent glutamate analog, elevated levels of NDF transcripts interactions. Thus, the ARIA promotes synapse-specific gene in limbic cortical areas, hippocampus, and amygdala. Con- expression, thereby augmenting nerve–muscle interactions (7). comitantly, ErbB-4 mRNA was increased with a similar Other isoforms of NDFyneuregulin promote maturation of as- spatial distribution, but transcription of the other NDF troglia and Schwann cells (8, 18), as well as oligodendrocytes (19), receptor, ErbB-3, did not change. A more moderate stimula- and at the same time inhibit neuronal differentiation (20, 21). tion, forced locomotion, was accompanied by an increase in These observations, together with the abundant expression of NDF transcripts and protein in the hippocampus and in the NDFyneuregulins by brain neurons and astroglia (18, 22), suggest motor cortex. Similar changes were found with ErbB-4, but not that neuregulins are involved in the response of the brain to ErbB-3. Last, a pathway-specific tetanic stimulation of the environmental stimuli. Here we show that brain NDFy perforant path, which produced long-term potentiation, was neuregulin, along with one of its surface receptors, namely followed by induction of NDF expression in the ipsilateral ErbB-4, is induced by three types of stimuli: activation of general dentate gyrus and CA3 area of the hippocampus. Taken excitatory neurotransmission with a glutamate receptor agonist, together, these results indicate that NDF is regulated by locomotion, and tetanic stimulation. These observations imply physiological activity and may play a role in neural plasticity. that the NDFyneuregulin family of ligands plays an important role in activity-dependent brain processes and in neuronal plas- Polypeptide growth factors play a central role in a variety of ticity. environmentally induced structural changes in the cortex and hippocampus of adult brain (1–3). For example, various treat- MATERIALS AND METHODS ments that induce seizure cause an increase in the expression of Materials. A polyclonal rabbit antibody was raised against NGF in hippocampus (4). An even more dramatic and rapid bacterial recombinant NDF-a2 and found to recognize all elevation of brain-derived neurotrophic factor (BDNF) mRNA isoforms of the factor. The antiserum was purified over a was observed after limbic seizures (1). These observations raise column of recombinant rat NDF, and the acid-eluted Ig the question as to whether other polypeptide factors that are fraction was used after dilution (23). Rabbit antibodies to a expressed in the central nervous system are also affected by recombinant extracellular portion of ErbB-3 and an antibody physiological activity. This possibility is especially relevant to a to a synthetic peptide derived from human ErbB-4 were family of soluble factors, variably named Neu differentiation purchased from Santa Cruz Biotechnology. In preliminary factors (NDFs) (5), heregulins (6), acetylcholine receptor induc- experiments we verified that these antisera do not cross-react. ing protein (ARIA) (7), and GGF (8), collectively renamed MK-801 and CPP were from Tocris Neuramin (Bristol, U.K.). neuregulins (9), that has been recently identified as ligands of All other chemicals were from Sigma. ErbB receptor tyrosine kinase. All of the isoforms of NDFy Animals. Adult male Hooded or Wistar rats (3 months old, neuregulin are encoded by a single gene located on human 200–250 g body weight) were used in all experiments. Between chromosome 8 (10). However, alternative splicing generates more 5 and 10 animals were used in each experimental group. than 13 isoforms that differ in their mosaic structure. Most Immunohistochemistry. Following perfusion of the animals important is an intrinsic EGF-like domain that is sufficient for with 2.5% paraformaldehyde, brains were removed and stored receptor binding and has two variants: a and b. Both groups of for 5–10 days in 1% paraformaldehyde. Serial 35-mm-thick isoforms bind directly to two types of receptors, ErbB-3 (11, 12) coronal or sagittal sections were subjected to immunohisto- and ErbB-4 (12, 13). Whereas the cytoplasmic domain of ErbB-4 chemical analysis by using the avidin–biotin peroxidase tech- displays a tyrosine-specific kinase activity, the corresponding nique (Vector Laboratories), as described (24). portion of ErbB-3 is devoid of catalytic function (14). Neverthe- Abbreviations: BDNF, brain-derived neurotrophic factor; CPP, The publication costs of this article were defrayed in part by page charge 3-[(RS)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid; DG, den- tate gyrus; EPSP, excitatory postsynaptic potential; HFS, high- payment. This article must therefore be hereby marked ‘‘advertisement’’ in frequency stimulation; KA, kainic acid; LTP, long term potentiation; accordance with 18 U.S.C. §1734 solely to indicate this fact. NDF, Neu differentiation factor; NMDA, N-methyl-D-aspartate. © 1998 by The National Academy of Sciences 0027-8424y98y951888-6$2.00y0 §To whom reprint requests should be addressed. e-mail: liyarden@ PNAS is available online at http:yywww.pnas.org. weizmann.weizmann.ac.il. 1888 Downloaded by guest on September 26, 2021 Neurobiology: Eilam et al. Proc. Natl. Acad. Sci. USA 95 (1998) 1889 In Situ Hybridization Analysis. NDF-specific primers with the propyl-1-phosphonic acid (CPP) (10 mgykg) was injected 20 min following nucleotide sequences were synthesized: 59-oligonucle- before stimulation, which led to blockade of LTP expression. otide: 59-TGAAGAGCCAGGAGTCAGCTGCAGG-39 and 39- Statistics. Both changes in optical density values obtained oligonucleotide: 59-GGCTCGAGACTCTGAGGACACATA- for mRNA levels and changes in the number of NDF- GG-39. These were used as primers to amplify a 0.3-kb-long immunopositive cells were determined by using a two-way fragment of the rat NDF coding region from cDNA clone 44 (5). ANOVA. The accepted level of significance was 0.05. The amplification procedure was exactly as described before (10), and the resulting DNA was cloned into the Bluescript plasmid RESULTS (Stratagene). T3 and T7 RNA polymerases were used to generate Induction of NDF and ErbB-4 by Epileptic Seizures. As an a 35 [ -( S)thio]UTP-labeled sense and antisense transcripts that initial test of the possibility that transcription of brain NDFy were used as probes. Embedding, sectioning, postfixation, and neuregulin is dynamically regulated we used massive stimulation hybridization were performed as described (25). To prepare of brain activity with the seizure-producing glutamate analog, cRNA probes specific to erbB-3 and to erbB-4, we extracted RNA kainate, which is involved in de novo gene transcription (29, 30). from the cerebellum of a 22-day-old rat by using the guanidinium y KA was injected intraperitoneally, and changes in the expression thiocyanate LiCl method (26). erbB-3- and erbB-4-specific DNA of NDF, as well as its receptors, ErbB-3 and ErbB-4, were sequences were amplified by using the following oligonucleotides: 9 followed. In accordance with previous reports (18, 22), in situ erbB-3-specific primers: 5 -TCCTGGCCGCCCCACATGCAC- hybridization localized NDF transcripts to multiple sites in the AAC 39 [sense; nucleotides 1300–1323 of human erbB-4 (27)] 9 9 brain, including cerebral cortex, thalamus, hypothalamus, and and 5 -GTCACATTTGCCCTCTGCCA-3 (antisense; nucleo- amygdala (Fig. 1). Likewise, transcripts of erbB-3 and erbB-4 tides 1580–1599), and erbB-4-specific primers: 59-TGTGCGTG- were found to be widely expressed in adult rat brain, in agreement CCTGCCCTAGTTCCAAGATGG-39 [sense; nucleotides 945– with previous reports (21, 31): major sites of erbB-4 expression 973 of human erbB-4 (28)] and 59-CCTGTTATCTCTCTGAC- are
Load more

Recommended publications
  • Signalling Between Microvascular Endothelium and Cardiomyocytes Through Neuregulin Downloaded From
    Cardiovascular Research (2014) 102, 194–204 SPOTLIGHT REVIEW doi:10.1093/cvr/cvu021 Signalling between microvascular endothelium and cardiomyocytes through neuregulin Downloaded from Emily M. Parodi and Bernhard Kuhn* Harvard Medical School, Boston Children’s Hospital, 300 Longwood Avenue, Enders Building, Room 1212, Brookline, MA 02115, USA Received 21 October 2013; revised 23 December 2013; accepted 10 January 2014; online publish-ahead-of-print 29 January 2014 http://cardiovascres.oxfordjournals.org/ Heterocellular communication in the heart is an important mechanism for matching circulatory demands with cardiac structure and function, and neuregulins (Nrgs) play an important role in transducing this signal between the hearts’ vasculature and musculature. Here, we review the current knowledge regarding Nrgs, explaining their roles in transducing signals between the heart’s microvasculature and cardiomyocytes. We highlight intriguing areas being investigated for developing new, Nrg-mediated strategies to heal the heart in acquired and congenital heart diseases, and note avenues for future research. ----------------------------------------------------------------------------------------------------------------------------------------------------------- Keywords Neuregulin Heart Heterocellular communication ErbB -----------------------------------------------------------------------------------------------------------------------------------------------------------† † † This article is part of the Spotlight Issue on: Heterocellular signalling
    [Show full text]
  • RET Controls Sympathetic Innervation
    Development 128, 3963-3974 (2001) 3963 Printed in Great Britain © The Company of Biologists Limited 2001 DEV8811 RET signaling is essential for migration, axonal growth and axon guidance of developing sympathetic neurons Hideki Enomoto1, Peter A. Crawford1, Alexander Gorodinsky1, Robert O. Heuckeroth2,3, Eugene M. Johnson, Jr3 and Jeffrey Milbrandt1,* 1Departments of Pathology and Internal Medicine, Washington University School of Medicine, 660 South Euclid Avenue, Box 8118, St Louis, MO 63110, USA 2Department of Pediatrics, Washington University School of Medicine, 660 South Euclid Avenue, Box 8116, St Louis, MO 63110, USA 3Department of Molecular Biology and Pharmacology, Washington University School of Medicine, 660 South Euclid Avenue, Box 8113, St Louis, MO 63110, USA *Author for correspondence (e-mail: [email protected]) Accepted 26 July 2001 SUMMARY Sympathetic axons use blood vessels as an intermediate trunks and accelerated cell death of sympathetic neurons path to reach their final target tissues. The initial contact later in development. Artemin is expressed in blood vessels between differentiating sympathetic neurons and blood during periods of early sympathetic differentiation, and vessels occurs following the primary sympathetic chain can promote and attract axonal growth of the sympathetic formation, where precursors of sympathetic neurons ganglion in vitro. This analysis identifies RET and artemin migrate and project axons along or toward blood vessels. as central regulators of early sympathetic innervation. We demonstrate
    [Show full text]
  • Growth Factors Acting Via Endothelial Cell-Specific Receptor Tyrosine Kinases: Vegfs, Angiopoietins, and Ephrins in Vascular Development
    Downloaded from genesdev.cshlp.org on September 25, 2021 - Published by Cold Spring Harbor Laboratory Press REVIEW Growth factors acting via endothelial cell-specific receptor tyrosine kinases: VEGFs, Angiopoietins, and ephrins in vascular development Nicholas W. Gale1 and George D. Yancopoulos Regeneron Pharmaceuticals, Inc., Tarrytown, New York 10591-6707 USA The term ‘vasculogenesis’ refers to the earliest stages of since been shown to be a critical regulator of endothelial vascular development, during which vascular endotheli- cell development. Not surprisingly, the specificity of al cell precursors undergo differentiation, expansion, and VEGF-A for the vascular endothelium results from the coalescence to form a network of primitive tubules restricted distribution of VEGF-A receptors to these (Risau 1997). This initial lattice, consisting purely of en- cells. The need to regulate the multitude of cellular in- dothelial cells that have formed rather homogenously teractions involved during vascular development sug- sized interconnected vessels, has been referred to as the gested that VEGF-A might not be alone as an endothelial primary capillary plexus. The primary plexus is then re- cell-specific growth factor. Indeed, there has been a re- modeled by a process referred to as angiogenesis (Risau cent explosion in the number of growth factors that spe- 1997), which involves the sprouting, branching, and dif- cifically act on the vascular endothelium. This explosion ferential growth of blood vessels to form the more ma- involves the VEGF family, which now totals at least five ture appearing vascular patterns seen in the adult organ- members. In addition, an entirely unrelated family of ism. This latter phase of vascular development also in- growth factors, known as the Angiopoietins, recently has volves the sprouting and penetration of vessels into been identified as acting via endothelial cell-specific re- previously avascular regions of the embryo, and also the ceptors known as the Ties.
    [Show full text]
  • Differential Expression of Neuregulin-1 Isoforms and Downregulation of Erbin Are Associated with Erb B2 Receptor Activation in Diabetic Peripheral Neuropathy
    Differential expression of neuregulin-1 isoforms and downregulation of erbin are associated with Erb B2 receptor activation in diabetic peripheral neuropathy By Pan Pan Submitted to the graduate degree program in Pharmacology and Toxicology and the Graduate Faculty of the University of Kansas in partial fulfillment of the requirements for the degree of Doctor of Philosophy. ______________________________ Rick T. Dobrowsky, Ph.D., Chairperson _______________________________ Jeff Staudinger, Ph.D. _______________________________ Alexander Moise, Ph.D. _______________________________ Honglian Shi. Ph.D. ________________________________ Brian Ackley, Ph.D. Date Defended: April 18th The Dissertation Committee for Pan Pan certifies that this is the approved version of the following dissertation: Differential expression of neuregulin-1 isoforms and downregulation of erbin are associated with Erb B2 receptor activation in diabetic peripheral neuropathy By Pan Pan _______________________________ Rick T. Dobrowsky, Ph.D., Chairperson th Date approved: April 18 ii Table of Contents Table of Contents ......................................................................................................................... iii Abstract ......................................................................................................................................... vi Acknowledgements ..................................................................................................................... vii List of Tables and Figures ..........................................................................................................
    [Show full text]
  • NT-3 and CNTF Exert Dose-Dependent, Pleiotropic Effects
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Developmental Biology 297 (2006) 182–197 www.elsevier.com/locate/ydbio NT-3 and CNTF exert dose-dependent, pleiotropic effects on cells in the immature dorsal root ganglion: Neuregulin-mediated proliferation of progenitor cells and neuronal differentiation Sharon J. Hapner a, Katherine M. Nielsen a,b, Marta Chaverra a, Raymond M. Esper d, ⁎ Jeffrey A. Loeb c,d, Frances Lefcort a, a Department of Cell Biology and Neuroscience, Montana State University, Bozeman, MT 59717, USA b Science and Education Partnership, University of California, San Francisco, CA 94143, USA c Department of Neurology and Center for Molecular Medicine, Wayne State University, Detroit, MI 48201, USA d Genetics, Wayne State University, Detroit, MI 48201, USA Received for publication 3 May 2005; revised 1 May 2006; accepted 10 May 2006 Available online 19 May 2006 Abstract Neurons in the nascent dorsal root ganglia are born and differentiate in a complex cellular milieu composed of postmitotic neurons, and mitotically active glial and neural progenitor cells. Neurotrophic factors such as NT-3 are critically important for promoting the survival of postmitotic neurons in the DRG. However, the factors that regulate earlier events in the development of the DRG such as the mitogenesis of DRG progenitor cells and the differentiation of neurons are less defined. Here we demonstrate that both NT-3 and CNTF induce distinct dose-dependent responses on cells in the immature DRG: at low concentrations, they induce the proliferation of progenitor cells while at higher concentrations they promote neuronal differentiation.
    [Show full text]
  • Β1 Integrins Are Required for Normal CNS Myelination and Promote AKT-Dependent Myelin Outgrowth Claudia S
    RESEARCH ARTICLE 2717 Development 136, 2717-2724 (2009) doi:10.1242/dev.038679 β1 integrins are required for normal CNS myelination and promote AKT-dependent myelin outgrowth Claudia S. Barros1,*, Tom Nguyen2,*, Kathryn S. R. Spencer1, Akiko Nishiyama3, Holly Colognato2,† and Ulrich Müller1,† Oligodendrocytes in the central nervous system (CNS) produce myelin sheaths that insulate axons to ensure fast propagation of action potentials. β1 integrins regulate the myelination of peripheral nerves, but their function during the myelination of axonal tracts in the CNS is unclear. Here we show that genetically modified mice lacking β1 integrins in the CNS present a deficit in myelination but no defects in the development of the oligodendroglial lineage. Instead, in vitro data show that β1 integrins regulate the outgrowth of myelin sheaths. Oligodendrocytes derived from mutant mice are unable to efficiently extend myelin sheets and fail to activate AKT (also known as AKT1), a kinase that is crucial for axonal ensheathment. The inhibition of PTEN, a negative regulator of AKT, or the expression of a constitutively active form of AKT restores myelin outgrowth in cultured β1- deficient oligodendrocytes. Our data suggest that β1 integrins play an instructive role in CNS myelination by promoting myelin wrapping in a process that depends on AKT. KEY WORDS: β1 integrins, Myelination, Oligodendrocytes, Mouse INTRODUCTION myelination. In fact, genetic studies addressing the function of β1 In the vertebrate nervous system, myelin sheaths insulate axons integrins in oligodendrocytes have led to contradictory results. and limit membrane depolarization to the nodes of Ranvier, where Whereas oligodendrocyte-specific expression of a dominant- the machinery propagating action potentials is concentrated negative (DN) β1 integrin in a transgenic mouse model was (Sherman and Brophy, 2005).
    [Show full text]
  • Glial Growth Factor 2, a Soluble Neuregulin, Directly Increases Schwann Cell Motility and Indirectly Promotes Neurite Outgrowth
    The Journal of Neuroscience, August 1, 1996, 16(15):4673–4683 Glial Growth Factor 2, a Soluble Neuregulin, Directly Increases Schwann Cell Motility and Indirectly Promotes Neurite Outgrowth Nagesh K. Mahanthappa,1 Eva S. Anton,2 and William D. Matthew2 1Cambridge NeuroScience, Inc., Cambridge, Massachusetts 02139, and 2Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710 Schwann cells proliferate, migrate, and act as sources of neu- Schwann cells. At higher doses, GGF2 causes proliferation, as rotrophic support during development and regeneration of pe- described previously. In a new explant culture system designed ripheral nerves. Recent studies have demonstrated that neu- to emulate entubulation repair of transected peripheral nerves, regulins, a family of growth factors secreted by developing GGF2 concentrations greater than necessary to saturate the motor and peripheral neurons, influence Schwann cell devel- mitotic response induce the secretion by Schwann cells of opment. In this study, we use three distinct assays to show that activities that promote sympathetic neuron survival and out- glial growth factor 2 (GGF2), a secreted neuregulin, exerts growth. These findings support a model in which neuregulins multiple effects on mature Schwann cells in vitro. At doses secreted by peripheral neurons are key components of recip- submaximal for proliferation, GGF2 increases the motility of rocal neuron–glia interactions that are important for peripheral Schwann cells cultured on peripheral nerve cryosections. Fur- nerve development and regeneration. thermore, in a novel bioassay, focal application of GGF2 causes Key words: Schwann cell; nerve regeneration; neuregulin; directed migration in conventional monolayer cultures of glial growth factor; migration; neurotrophic activity Glial growth factor (GGF) was originally characterized as a single these studies support a model in which neuregulin expression by Schwann cell mitogen (Lemke and Brockes, 1984).
    [Show full text]
  • Neuregulin-1 Is Increased in Schizophrenia Patients with Chronic
    Schizophrenia Research 208 (2019) 473–474 Contents lists available at ScienceDirect Schizophrenia Research journal homepage: www.elsevier.com/locate/schres Letter to the Editor Neuregulin-1 is increased in schizophrenia As the distribution of continuous variables was not normal, Mann- patients with chronic cannabis abuse: Whitney U test was used to compare the group of chronically cannabis- Preliminary results abusing schizophrenia patients and the group of non-abusing patients. Neuregulin-1 was higher in the group of cannabis abusing schizophrenia patients (U = 462.5; p = 0.026) and members of this group were signif- Keywords: icantly younger (U = 482.0; p = 0.001), with a shorter duration of illness Neuregulin Neurotrophins (U = 534.0; p = 0.003). The two groups did not differ in PANSS total and Schizophrenia the three main subscales. The levels of BDNF, NGF and NRG-1 were not Cannabis correlated with PANSS, age or duration of illness. Cannabis consummation was more frequent in males (chi = 15.584; df = 1; p = 0.001). To the Editor, Logistic regression with cannabis consummation/non-consummation as the dependent variable and neurotrophicfactors,age,genderanddura- tion of illness were included in the model. Male gender, younger age and Plenty of studies have shown that cannabis increases the risk of de- higher values of NRG-1 were significant predictors of the model pre- veloping schizophrenia and that chronic cannabis abuse leads to prob- sented in Table 1. lems in learning, attention and a decrease in brain volume (Van Gastel Our results suggest that NRG-1 was increased in the group of chronic et al., 2014).
    [Show full text]
  • Neuregulin Expression at Neuromuscular Synapses Is Modulated by Synaptic Activity and Neurotrophic Factors
    The Journal of Neuroscience, March 15, 2002, 22(6):2206–2214 Neuregulin Expression at Neuromuscular Synapses Is Modulated by Synaptic Activity and Neurotrophic Factors Jeffrey A. Loeb,1 Abdelkrim Hmadcha,1 Gerald D. Fischbach,3 Susan J. Land,2 and Vaagn L. Zakarian1 1Department of Neurology and Center for Molecular Medicine and Genetics and 2Institute of Environmental Health Sciences, Wayne State University School of Medicine, Detroit, Michigan 48201, and 3Columbia University, College of Physicians and Surgeons, New York, New York 10032 The proper formation of neuromuscular synapses requires on- brain-derived neurotrophic factor and neurotrophin 3 expres- going synaptic activity that is translated into complex structural sion in muscle without appreciably changing the expression of changes to produce functional synapses. One mechanism by these same factors in spinal cord. Adding back these or other which activity could be converted into these structural changes neurotrophic factors restores synaptic neuregulin expression is through the regulated expression of specific synaptic regu- and maintains normal end plate band architecture in the pres- latory factors. Here we demonstrate that blocking synaptic ence of activity blockade. The expression of neuregulin protein activity with curare reduces synaptic neuregulin expression in a at synapses is independent of spinal cord and muscle neuregu- dose-dependent manner yet has little effect on synaptic agrin or lin mRNA levels, suggesting that neuregulin accumulation at a muscle-derived heparan sulfate proteoglycan. These changes synapses is independent of transcription. These findings sug- are associated with a fourfold increase in number and a twofold gest a local, positive feedback loop between synaptic regula- reduction in average size of synaptic acetylcholine receptor tory factors that translates activity into structural changes at clusters that appears to be caused by excessive axonal sprout- neuromuscular synapses.
    [Show full text]
  • Olfactory Ensheathing Glia: Drivers of Axonal Regeneration in the Central Nervous System?
    Journal of Biomedicine and Biotechnology • 2:1 (2002) 37–43 • PII. S1110724302000372 • http://jbb.hindawi.com REVIEW ARTICLE Olfactory Ensheathing Glia: Drivers of Axonal Regeneration in the Central Nervous System? M. Teresa Moreno-Flores,∗ Javier D´ıaz-Nido, Francisco Wandosell, and Jesus´ Avila Centro de Biolog´ıa Molecular “Severo Ochoa” (CSIC-UAM), Facultad de Ciencias, Universidad Autonoma´ de Madrid, 28049 Madrid, Spain Olfactory ensheathing glia (OEG) accompany olfactory growing axons in their entry to the adult mammalian central nervous system (CNS). Due to this special characteristic, considerable attention has been focused on the possibility of using OEG for CNS regener- ation. OEG present a large heterogeneity in culture with respect to their cellular morphology and expressed molecules. The specific characteristics of OEG responsible for their regenerative properties have to be defined. These properties probably result from the combination of several factors: molecular composition of the membrane (expressing adhesion molecules as PSA-NCAM, L1 and/or others) combined with their ability to reduce glial scarring and to accompany new growing axons into the host CNS. Their capacity to produce some neurotrophic factors might also account for their ability to produce CNS regeneration. INTRODUCTION it necessary to search for more effective regeneration media- tors. During the last few years the use of OEG for CNS regen- The olfactory system has remarkable distinctive prop- eration has received plenty of attention, due to their special erties within the adult mammalian central nervous system. properties [6]. Since OEG usually accompany growing olfac- Throughout the whole life of an organism, olfactory sensory tory axons into the adult mammalian CNS, it is reasonable neurons are renewed from progenitor cells present in the ol- to expect that they may facilitate axonal regeneration.
    [Show full text]
  • Treating Small Fiber Neuropathy by Topical Application of a Small
    Treating small fiber neuropathy by topical application SEE COMMENTARY of a small molecule modulator of ligand-induced GFRα/RET receptor signaling Kristian L. Hedstroma,b,1, Joshua C. Murtiea,b,1, Kathryn Albersc, Nigel A. Calcuttd, and Gabriel Corfasa,b,e,2 aF. M. Kirby Neurobiology Center, Children’s Hospital Boston, Harvard Medical School, Boston, MA 02115; Departments of bNeurology and eOtology and Laryngology, Harvard Medical School, Boston, MA 02115; cDepartment of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260; and dDepartment of Pathology, University of California, San Diego, La Jolla, CA 92093-0612 Edited* by Joseph Schlessinger, Yale University School of Medicine, New Haven, CT, and approved December 20, 2013 (received for review May 10, 2013) Small-fiber neuropathy (SFN) is a disorder of peripheral nerves two mouse models of progressive SFN. We found that GDNF commonly found in patients with diabetes mellitus, HIV infection, and skin overexpression and topical XIB4035 are equally effective in those receiving chemotherapy. The complexity of disease etiology treating SFN caused by dysfunction of nonmyelinating Schwann cells has led to a scarcity of effective treatments. Using two models of and that topical XIB4035 treatment also ameliorates SFN symptoms progressive SFN, we show that overexpression of glial cell line-derived in a mouse model of diabetic SFN. Furthermore, we establish that neurotrophic factor (GDNF) in skin keratinocytes or topical application XIB4035 is not a GDNF mimetic as previously reported, but rather of XIB4035, a reported nonpeptidyl agonist of GDNF receptor α1 a positive modulator that enhances ligand-induced GFL receptor (GFRα1), are effective treatments for SFN.
    [Show full text]
  • Differentiation of Motor Neuron-Like Cells from Tonsil-Derived
    International Journal of Molecular Sciences Article Differentiation of Motor Neuron-Like Cells from Tonsil-Derived Mesenchymal Stem Cells and Their Possible Application to Neuromuscular Junction Formation Saeyoung Park, Ji Yeon Kim, Seoha Myung, Namhee Jung, Yeonzi Choi and Sung-Chul Jung * Department of Biochemistry, College of Medicine, Ewha Womans University, Seoul 07804, Korea; [email protected] (S.P.); [email protected] (J.Y.K.); [email protected] (S.M.); [email protected] (N.J.); [email protected] (Y.C.) * Correspondence: [email protected]; Tel.: +82-2-6986-6199 Received: 15 April 2019; Accepted: 30 May 2019; Published: 1 June 2019 Abstract: Human tonsil-derived mesenchymal stem cells (T-MSCs) are newly identified MSCs and present typical features of MSCs, including having the differentiation capacity into the three germ layers and excellent proliferation capacity. They are easily sourced and are useful for stem cell therapy in various disease states. We previously reported that T-MSCs could be differentiated into skeletal myocytes and Schwann-like cells; therefore, they are a promising candidate for cell therapies for neuromuscular disease. Motor neurons (MNs), which regulate spontaneous behavior, are affected by a wide range of MN diseases (MNDs) for which there are no effective remedies. We investigated the differentiation potential of MN-like cells derived from T-MSCs (T-MSC-MNCs) for application to therapy of MNDs. After the process of MN differentiation, the expression of MN-related markers, including Islet 1, HB9/HLXB9 (HB9), and choline acetyltransferase (ChAT), was increased when compared with undifferentiated T-MSCs. The secretion of acetylcholine to the conditioned medium was significantly increased after MN differentiation.
    [Show full text]