Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

ACC 2024 Congress

Catch up on all the top stories and latest evidence in cardiology research with our ACC 2024 Congress hub page.
ADVANCED SEARCH
Log in
Top
Molecular Neurodegeneration
Published in: Molecular Neurodegeneration 1/2017

Open Access 01-12-2017 | Research article

Tissue-type plasminogen activator exerts EGF-like chemokinetic effects on oligodendrocytes in white matter (re)myelination

Authors: Camille Leonetti, Richard Macrez, Mathilde Pruvost, Yannick Hommet, Jérémie Bronsard, Antoine Fournier, Maxime Perrigault, Isabel Machin, Denis Vivien, Diego Clemente, Fernando De Castro, Eric Maubert, Fabian Docagne

Published in: Molecular Neurodegeneration | Issue 1/2017

Login to get access

Abstract

Background

The ability of oligodendrocyte progenitor cells (OPCs) to give raise to myelin forming cells during developmental myelination, normal adult physiology and post-lesion remyelination in white matter depends on factors which govern their proliferation, migration and differentiation. Tissue plasminogen activator (tPA) is a serine protease expressed in the central nervous system (CNS), where it regulates cell fate. In particular, tPA has been reported to protect oligodendrocytes from apoptosis and to facilitate the migration of neurons. Here, we investigated whether tPA can also participate in the migration of OPCs during CNS development and during remyelination after focal white matter lesion.

Methods

OPC migration was estimated by immunohistological analysis in spinal cord and corpus callosum during development in mice embryos (E13 to P0) and after white matter lesion induced by the stereotactic injection of lysolecithin in adult mice (1 to 21 days post injection). Migration was compared in these conditions between wild type and tPA knock-out animals. The action of tPA was further investigated in an in vitro chemokinesis assay.

Results

OPC migration along vessels is delayed in tPA knock-out mice during development and during remyelination. tPA enhances OPC migration via an effect dependent on the activation of epidermal growth factor receptor.

Conclusion

Endogenous tPA facilitates the migration of OPCs during development and during remyelination after white matter lesion by the virtue of its epidermal growth factor-like domain.
Appendix
Available only for authorised users
Literature
1.
Franklin RJM, ffrench-Constant C. Remyelination in the CNS: from biology to therapy. Nat Rev Neurosci. 2008;9:839–55.CrossRefPubMed
2.
Goldschmidt T, Antel J, König FB, Brück W, Kuhlmann T. Remyelination capacity of the MS brain decreases with disease chronicity. Neurology. 2009;72:1914–21.CrossRefPubMed
3.
Patrikios P, Stadelmann C, Kutzelnigg A, Rauschka H, Schmidbauer M, Laursen H, et al. Remyelination is extensive in a subset of multiple sclerosis patients. Brain. 2006;129:3165–72.CrossRefPubMed
4.
Bramow S, Frischer JM, Lassmann H, Koch-Henriksen N, Lucchinetti CF, Sørensen PS, et al. Demyelination versus remyelination in progressive multiple sclerosis. Brain. 2010;133:2983–98.CrossRefPubMed
5.
Kremer D, Göttle P, Hartung H-P, Küry P. Pushing forward: remyelination as the New frontier in CNS diseases. Trends Neurosci. 2016;39:246–63.CrossRefPubMed
6.
Stankoff B, Jadasz JJ, Hartung H-P, Küry P, Zalc B, Lubetzki C. Repair strategies for multiple sclerosis: challenges, achievements and perspectives. Curr Opin Neurol. 2016;29:286–92.CrossRefPubMed
7.
Zawadzka M, Rivers LE, Fancy SPJ, Zhao C, Tripathi R, Jamen F, et al. CNS-resident glial progenitor/stem cells produce Schwann cells as well as oligodendrocytes during repair of CNS demyelination. Cell Stem Cell. 2010;6:578–90.CrossRefPubMed
8.
Castro F de, Zalc B. Comprehensive Developmental Neuroscience: Cellular Migration and Formation of Neuronal Connections: Chapter 23. Migration of Myelin-Forming Cells in the CNS. St. Louis: Elsevier Inc. Chapters; 2013.
9.
Fancy SPJ, Chan JR, Baranzini SE, Franklin RJM, Rowitch DH. Myelin regeneration: a recapitulation of development? Annu Rev Neurosci. 2011;34:21–43.CrossRefPubMed
10.
de Castro F, Bribián A, Ortega MC. Regulation of oligodendrocyte precursor migration during development, in adulthood and in pathology. Cell Mol Life Sci. 2013;70:4355–68.CrossRefPubMed
11.
Correa F, Gauberti M, Parcq J, Macrez R, Hommet Y, Obiang P, et al. Tissue plasminogen activator prevents white matter damage following stroke. The Journal of Experimental Medicine. Rockefeller University Press. 2011;208:1229–42.
12.
Louessard M, Lacroix A, Martineau M, Mondielli G, Montagne A, Lesept F, et al. Tissue plasminogen activator expression is restricted to subsets of excitatory pyramidal glutamatergic neurons. Mol Neurobiol. 2015.
13.
Docagne F, Parcq J, Lijnen R, Ali C, Vivien D. Understanding the functions of endogenous and exogenous tissue-type plasminogen activator during stroke. Stroke J Cerebral Circulation. 2015;46:314–20.CrossRef
14.
Seeds NW, Basham ME, Haffke SP. Neuronal migration is retarded in mice lacking the tissue plasminogen activator gene. Proc Natl Acad Sci U S A. 1999;96:14118–23.CrossRefPubMedPubMedCentral
15.
Henry VJ, Lecointre M, Laudenbach V, Ali C, Macrez R, Jullienne A, et al. High t-PA release by neonate brain microvascular endothelial cells under glutamate exposure affects neuronal fate. Neurobiol Dis. 2013;50:201–8.CrossRefPubMed
16.
Aguirre A, Rizvi TA, Ratner N, Gallo V. Overexpression of the epidermal growth factor receptor confers migratory properties to nonmigratory postnatal neural progenitors. J Neurosci Soc Neurosci. 2005;25:11092–106.CrossRef
17.
Carmeliet P, Schoonjans L, Kieckens L, Ream B, Degen J, Bronson R, et al. Physiological consequences of loss of plasminogen activator gene function in mice. Nature. 1994;368:419–24.CrossRefPubMed
18.
McCarthy KD, de Vellis J. Preparation of separate astroglial and oligodendroglial cell cultures from rat cerebral tissue. The Journal of Cell Biology. Rockefeller University Press. 1980;85:890–902.
19.
Murcia-Belmonte V, Esteban PF, García-González D, De Castro F. Biochemical dissection of Anosmin-1 interaction with FGFR1 and components of the extracellular matrix. J Neurochem Blackwell Publishing Ltd. 2010;115:1256–65.CrossRef
20.
Rowitch DH. Glial specification in the vertebrate neural tube. Nature Rev Neurosci Nature Publishing Group. 2004;5:409–19.CrossRef
21.
Tsai H-H, Niu J, Munji R, Davalos D, Chang J, Zhang H, et al. Oligodendrocyte precursors migrate along vasculature in the developing nervous system. Science. 2016;351:379–84.CrossRefPubMed
22.
23.
Nait-Oumesmar B, Decker L, Lachapelle F, Avellana-Adalid V, Bachelin C. Van Evercooren AB-. Progenitor cells of the adult mouse subventricular zone proliferate, migrate and differentiate into oligodendrocytes after demyelination. European Journal of Neuroscience. Blackwell Science Ltd. 1999;11:4357–66.
24.
Raoult E, Bénard M, Komuro H, Lebon A, Vivien D, Fournier A, et al. Cortical-layer-specific effects of PACAP and tPA on interneuron migration during post-natal development of the cerebellum. J Neurochem. 2014;130:241–54.CrossRefPubMed
25.
Ling C, Zou T, Hsiao Y, Tao X, Chen Z-L, Strickland S, et al. Disruption of tissue plasminogen activator gene reduces macrophage migration. Biochem Biophys Res Commun. 2006;349:906–12.CrossRefPubMed
26.
Cao C, Lawrence DA, Li Y, Von Arnim CAF, Herz J, Su EJ, et al. Endocytic receptor LRP together with tPA and PAI-1 coordinates Mac-1-dependent macrophage migration. EMBO J. 2006;25:1860–70.CrossRefPubMedPubMedCentral
27.
Dung TD, Feng C-C, Kuo W-W, Pai P, Chung L-C, Chang S-H, et al. Suppression of plasminogen activators and the MMP-2/-9 pathway by a Zanthoxylum avicennae extract to inhibit the HA22T human hepatocellular carcinoma cell migration and invasion effects in vitro and in vivo via phosphatase 2A activation. Biosci Biotechnol Biochem. 2013;77:1814–21.CrossRefPubMed
28.
Achuta VS, Rezov V, Uutela M, Louhivuori V, Louhivuori L, Castrén ML. Tissue plasminogen activator contributes to alterations of neuronal migration and activity-dependent responses in fragile X mice. J Neurosci. 2014;34:1916–23.CrossRefPubMed
29.
Moyon S, Dubessy AL, Aigrot MS, Trotter M, Huang JK, Dauphinot L, et al. Demyelination causes adult CNS progenitors to revert to an immature state and express immune cues that support their migration. J Neurosci. 2015;35:4–20.CrossRefPubMed
30.
Liot G, Roussel BD, Lebeurrier N, Benchenane K, López-Atalaya JP, Vivien D, et al. Tissue-type plasminogen activator rescues neurones from serum deprivation-induced apoptosis through a mechanism independent of its proteolytic activity. J Neurochem. 2006;98:1458–64.CrossRefPubMed
31.
Lee H-Y, Hwang I-Y, Im H, Koh J-Y, Kim Y-H. Non-proteolytic neurotrophic effects of tissue plasminogen activator on cultured mouse cerebrocortical neurons. J Neurochem. 2007;101:1236–47.CrossRefPubMed
32.
Flavin MP, Zhao G. Tissue plasminogen activator protects hippocampal neurons from oxygen-glucose deprivation injury. J Neurosci Res. 2001;63:388–94.CrossRefPubMed
33.
Unachukwu UJ, Sauane M, Vazquez M, Redenti S. Microfluidic generated EGF-gradients induce chemokinesis of transplantable retinal progenitor cells via the JAK/STAT and PI3kinase signaling pathways. PLoS One. 2013;8:e83906.CrossRefPubMedPubMedCentral
34.
Aguirre A, Dupree JL, Mangin JM, Gallo V. A functional role for EGFR signaling in myelination and remyelination. Nature Neurosci Nature Publishing Group. 2007;10:990–1002.CrossRef
35.
Aguirre A, Gallo V. Reduced EGFR signaling in progenitor cells of the adult subventricular zone attenuates oligodendrogenesis after demyelination. Neuron glia biology. NIH Public Access. 2007;3:209–20.
36.
Scafidi J, Hammond TR, Scafidi S, Ritter J, Jablonska B, Roncal M, et al. Intranasal epidermal growth factor treatment rescues neonatal brain injury. Nature Publishing Group. 2014;506:230–4.
37.
Cohen ME, Fainstein N, Lavon I, Ben-Hur T. Signaling through three chemokine receptors triggers the migration of transplanted neural precursor cells in a model of multiple sclerosis. Stem Cell Res. 2014;13:227–39.CrossRefPubMed
38.
Ivkovic S, Canoll P, Goldman JE. Constitutive EGFR signaling in oligodendrocyte progenitors leads to diffuse hyperplasia in postnatal white matter. J Neurosci. 2008;28:914–22.CrossRefPubMedPubMedCentral
39.
Gonzalez-Perez O, Romero-Rodriguez R, Soriano-Navarro M, Garcia-Verdugo JM, Alvarez-Buylla A. Epidermal growth factor induces the progeny of subventricular zone type B cells to migrate and differentiate into oligodendrocytes. Stem cells (Dayton, Ohio). NIH Public Access. 2009;27:2032–43.
40.
Gonzalez-Perez O, Alvarez-Buylla A. Oligodendrogenesis in the subventricular zone and the role of epidermal growth factor. Brain research reviews. NIH Public Access. 2011;67:147–56.
41.
Galvez-Contreras AY, Quiñones-Hinojosa A, Gonzalez-Perez O. The role of EGFR and ErbB family related proteins in the oligodendrocyte specification in germinal niches of the adult mammalian brain. Frontiers in Cellular Neuroscience. Frontiers; 2013;7:258.
42.
Van’t Veer A, Du Y, Fischer TZ, Boetig DR, Wood MR, Dreyfus CF. Brain-derived neurotrophic factor effects on oligodendrocyte progenitors of the basal forebrain are mediated through trkB and the MAP kinase pathway. J Neurosci Res. 2009;87:69–78.CrossRef
43.
Ramos-Cejudo J, Gutiérrez-Fernández M, Otero-Ortega L, Rodríguez-Frutos B, Fuentes B, Vallejo-Cremades MT, et al. Brain-derived neurotrophic factor administration mediated oligodendrocyte differentiation and myelin formation in subcortical ischemic stroke. Stroke. 2015;46:221–8.CrossRefPubMed
44.
Suzuki Y, Nagai N, Yamakawa K, Muranaka Y, Hokamura K, Umemura K. Recombinant tissue-type plasminogen activator transiently enhances blood–brain barrier permeability during cerebral ischemia through vascular endothelial growth factor-mediated endothelial endocytosis in mice. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. Sage Publications. 2015;35:2021–31.
45.
Hayakawa K, Pham L-DD, Som AT, Lee BJ, Guo S, Lo EH, et al. Vascular endothelial growth factor regulates the migration of oligodendrocyte precursor cells. J Neurosci. 2011;31:10666–70.CrossRefPubMedPubMedCentral
46.
Hayakawa K, Seo JH, Pham L-DD, Miyamoto N, Som AT, Guo S, et al. Cerebral endothelial derived vascular endothelial growth factor promotes the migration but not the proliferation of oligodendrocyte precursor cells in vitro. Neurosci Lett. 2012;513:42–6.CrossRefPubMedPubMedCentral
47.
Le Bras B, Barallobre M-J, Homman-Ludiye J, Ny A, Wyns S, Tammela T, et al. VEGF-C is a trophic factor for neural progenitors in the vertebrate embryonic brain. Nat Neurosci. 2006;9:340–8.CrossRefPubMed
48.
Arai K, Lo EH. An oligovascular niche: cerebral endothelial cells promote the survival and proliferation of oligodendrocyte precursor cells. J Neurosci. 2009;29:4351–5.CrossRefPubMedPubMedCentral
49.
50.
Bovetti S, Hsieh Y-C, Bovolin P, Perroteau I, Kazunori T, Puche AC. Blood vessels form a scaffold for neuroblast migration in the adult olfactory bulb. The Journal of neuroscience : the official journal of the Society for Neuroscience. Soc Neurosci. 2007;27:5976–80.CrossRef
51.
Cayre M, Courtès S, Martineau F, Giordano M, Arnaud K, Zamaron A, et al. Netrin 1 contributes to vascular remodeling in the subventricular zone and promotes progenitor emigration after demyelination. Development (Cambridge, England). Comp of Biologists Limited. 2013;140:3107–17.
52.
Cuzner ML, Gveric D, Strand C, Loughlin AJ, Paemen L, Opdenakker G, et al. The expression of tissue-type plasminogen activator, matrix metalloproteases and endogenous inhibitors in the central nervous system in multiple sclerosis: comparison of stages in lesion evolution. J Neuropathol Exp Neurol. 1996;55:1194–204.CrossRefPubMed
53.
Maki T, Maeda M, Uemura M, Lo EK, Terasaki Y, Liang AC, et al. Potential interactions between pericytes and oligodendrocyte precursor cells in perivascular regions of cerebral white matter. Neurosci Lett. 2015;597:164–9.CrossRefPubMedPubMedCentral
54.
Lindahl P, Johansson BR, Levéen P, Betsholtz C. Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. Science. 1997;277:242–5.CrossRefPubMed
55.
Hellström M, Kalén M, Lindahl P, Abramsson A, Betsholtz C. Role of PDGF-B and PDGFR-beta in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse. Development. 1999;126:3047–55.PubMed
56.
Nakajima M, Yuasa S, Ueno M, Takakura N, Koseki H, Shirasawa T. Abnormal blood vessel development in mice lacking presenilin-1. Mech Dev. 2003;120:657–67.CrossRefPubMed
57.
Girolamo F, Coppola C, Ribatti D, Trojano M. Angiogenesis in multiple sclerosis and experimental autoimmune encephalomyelitis. Acta neuropathologica communications. BioMed Central Ltd. 2014;2:84.
58.
Lu W, Bhasin M, Tsirka SE. Involvement of tissue plasminogen activator in onset and effector phases of experimental allergic encephalomyelitis. The journal of neuroscience : the official journal of the society for neuroscience. Soc Neurosci. 2002;22:10781–9.
59.
Gveric D, Herrera B, Petzold A, Lawrence DA, Cuzner ML. Impaired fibrinolysis in multiple sclerosis: a role for tissue plasminogen activator inhibitors. J Neurology. 2003;126:1590–8.
Metadata
Title
Tissue-type plasminogen activator exerts EGF-like chemokinetic effects on oligodendrocytes in white matter (re)myelination
Authors
Camille Leonetti
Richard Macrez
Mathilde Pruvost
Yannick Hommet
Jérémie Bronsard
Antoine Fournier
Maxime Perrigault
Isabel Machin
Denis Vivien
Diego Clemente
Fernando De Castro
Eric Maubert
Fabian Docagne
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Molecular Neurodegeneration / Issue 1/2017
Electronic ISSN: 1750-1326
DOI
https://doi.org/10.1186/s13024-017-0160-5

Other articles of this Issue 1/2017

Molecular Neurodegeneration 1/2017 Go to the issue

Research article

TRPA1 channels promote astrocytic Ca2+ hyperactivity and synaptic dysfunction mediated by oligomeric forms of amyloid-β peptide

Research article

Glycine-alanine dipeptide repeat protein contributes to toxicity in a zebrafish model of C9orf72 associated neurodegeneration

Research article

A proteomic analysis of LRRK2 binding partners reveals interactions with multiple signaling components of the WNT/PCP pathway

Research article

Transient IKK2 activation in astrocytes initiates selective non-cell-autonomous neurodegeneration

Research article

Soluble oligomeric amyloid-β induces calcium dyshomeostasis that precedes synapse loss in the living mouse brain

Review

Tau PET imaging: present and future directions