Innate Immune Pathways Promote Oligodendrocyte Progenitor Cell Recruitment to the Injury Site in Adult Zebrafish Brain
The oligodendrocyte progenitors (OPCs) are at the front of the glial reaction to the traumatic brain injury. However, regulatory pathways steering the OPC reaction as well as the role of reactive OPCs remain largely unknown. Here, we compared a long-lasting, exacerbated reaction of OPCs to the adult...
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MDPI AG
2022-02-01
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| Online Access: | https://www.mdpi.com/2073-4409/11/3/520 |
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| author | Rosario Sanchez-Gonzalez Christina Koupourtidou Tjasa Lepko Alessandro Zambusi Klara Tereza Novoselc Tamara Durovic Sven Aschenbroich Veronika Schwarz Christopher T. Breunig Hans Straka Hagen B. Huttner Martin Irmler Johannes Beckers Wolfgang Wurst Andreas Zwergal Tamas Schauer Tobias Straub Tim Czopka Dietrich Trümbach Magdalena Götz Stefan H. Stricker Jovica Ninkovic |
| author_facet | Rosario Sanchez-Gonzalez Christina Koupourtidou Tjasa Lepko Alessandro Zambusi Klara Tereza Novoselc Tamara Durovic Sven Aschenbroich Veronika Schwarz Christopher T. Breunig Hans Straka Hagen B. Huttner Martin Irmler Johannes Beckers Wolfgang Wurst Andreas Zwergal Tamas Schauer Tobias Straub Tim Czopka Dietrich Trümbach Magdalena Götz Stefan H. Stricker Jovica Ninkovic |
| author_sort | Rosario Sanchez-Gonzalez |
| collection | DOAJ |
| description | The oligodendrocyte progenitors (OPCs) are at the front of the glial reaction to the traumatic brain injury. However, regulatory pathways steering the OPC reaction as well as the role of reactive OPCs remain largely unknown. Here, we compared a long-lasting, exacerbated reaction of OPCs to the adult zebrafish brain injury with a timely restricted OPC activation to identify the specific molecular mechanisms regulating OPC reactivity and their contribution to regeneration. We demonstrated that the influx of the cerebrospinal fluid into the brain parenchyma after injury simultaneously activates the toll-like receptor 2 (Tlr2) and the chemokine receptor 3 (Cxcr3) innate immunity pathways, leading to increased OPC proliferation and thereby exacerbated glial reactivity. These pathways were critical for long-lasting OPC accumulation even after the ablation of microglia and infiltrating monocytes. Importantly, interference with the Tlr1/2 and Cxcr3 pathways after injury alleviated reactive gliosis, increased new neuron recruitment, and improved tissue restoration. |
| first_indexed | 2024-03-10T00:03:54Z |
| format | Article |
| id | doaj.art-ffd5f82ffd6646c5bfe4032d8fe5b8d0 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T00:03:54Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-ffd5f82ffd6646c5bfe4032d8fe5b8d02023-11-23T16:13:21ZengMDPI AGCells2073-44092022-02-0111352010.3390/cells11030520Innate Immune Pathways Promote Oligodendrocyte Progenitor Cell Recruitment to the Injury Site in Adult Zebrafish BrainRosario Sanchez-Gonzalez0Christina Koupourtidou1Tjasa Lepko2Alessandro Zambusi3Klara Tereza Novoselc4Tamara Durovic5Sven Aschenbroich6Veronika Schwarz7Christopher T. Breunig8Hans Straka9Hagen B. Huttner10Martin Irmler11Johannes Beckers12Wolfgang Wurst13Andreas Zwergal14Tamas Schauer15Tobias Straub16Tim Czopka17Dietrich Trümbach18Magdalena Götz19Stefan H. Stricker20Jovica Ninkovic21Institute of Stem Cell Research, Helmholtz Center Munich, 85764 Oberschleißheim, GermanyInstitute of Stem Cell Research, Helmholtz Center Munich, 85764 Oberschleißheim, GermanyInstitute of Stem Cell Research, Helmholtz Center Munich, 85764 Oberschleißheim, GermanyInstitute of Stem Cell Research, Helmholtz Center Munich, 85764 Oberschleißheim, GermanyInstitute of Stem Cell Research, Helmholtz Center Munich, 85764 Oberschleißheim, GermanyInstitute of Stem Cell Research, Helmholtz Center Munich, 85764 Oberschleißheim, GermanyInstitute of Stem Cell Research, Helmholtz Center Munich, 85764 Oberschleißheim, GermanyInstitute of Stem Cell Research, Helmholtz Center Munich, 85764 Oberschleißheim, GermanyReprogramming and Regeneration, Biomedical Center (BMC), Physiological Genomics, Faculty of Medicine, LMU Munich, 80539 München, GermanyDepartment Biology II, University of Munich, 80539 München, GermanyDepartment of Neurology, Justus-Liebig-University Giessen, Klinikstrasse 33, 35392 Giessen, GermanyInstitute of Experimental Genetics, Helmholtz Center Munich, 85764 Oberschleißheim, GermanyInstitute of Experimental Genetics, Helmholtz Center Munich, 85764 Oberschleißheim, GermanyInstitute of Developmental Genetics, Helmholtz Center Munich, 85764 Oberschleißheim, GermanyDepartment of Neurology, Ludwig-Maximilians University, Campus Grosshadern, 81377 Munich, GermanyBiomedical Center (BMC), Bioinformatic Core Facility, Faculty of Medicine, LMU Munich, 80539 München, GermanyBiomedical Center (BMC), Bioinformatic Core Facility, Faculty of Medicine, LMU Munich, 80539 München, GermanyCentre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH8 9YL, UKInstitute of Developmental Genetics, Helmholtz Center Munich, 85764 Oberschleißheim, GermanyInstitute of Stem Cell Research, Helmholtz Center Munich, 85764 Oberschleißheim, GermanyReprogramming and Regeneration, Biomedical Center (BMC), Physiological Genomics, Faculty of Medicine, LMU Munich, 80539 München, GermanyInstitute of Stem Cell Research, Helmholtz Center Munich, 85764 Oberschleißheim, GermanyThe oligodendrocyte progenitors (OPCs) are at the front of the glial reaction to the traumatic brain injury. However, regulatory pathways steering the OPC reaction as well as the role of reactive OPCs remain largely unknown. Here, we compared a long-lasting, exacerbated reaction of OPCs to the adult zebrafish brain injury with a timely restricted OPC activation to identify the specific molecular mechanisms regulating OPC reactivity and their contribution to regeneration. We demonstrated that the influx of the cerebrospinal fluid into the brain parenchyma after injury simultaneously activates the toll-like receptor 2 (Tlr2) and the chemokine receptor 3 (Cxcr3) innate immunity pathways, leading to increased OPC proliferation and thereby exacerbated glial reactivity. These pathways were critical for long-lasting OPC accumulation even after the ablation of microglia and infiltrating monocytes. Importantly, interference with the Tlr1/2 and Cxcr3 pathways after injury alleviated reactive gliosis, increased new neuron recruitment, and improved tissue restoration.https://www.mdpi.com/2073-4409/11/3/520brain regenerationoligodendrocyte progenitorsreactive gliosisinnate immunity pathwayszebrafishneurogenesis |
| spellingShingle | Rosario Sanchez-Gonzalez Christina Koupourtidou Tjasa Lepko Alessandro Zambusi Klara Tereza Novoselc Tamara Durovic Sven Aschenbroich Veronika Schwarz Christopher T. Breunig Hans Straka Hagen B. Huttner Martin Irmler Johannes Beckers Wolfgang Wurst Andreas Zwergal Tamas Schauer Tobias Straub Tim Czopka Dietrich Trümbach Magdalena Götz Stefan H. Stricker Jovica Ninkovic Innate Immune Pathways Promote Oligodendrocyte Progenitor Cell Recruitment to the Injury Site in Adult Zebrafish Brain Cells brain regeneration oligodendrocyte progenitors reactive gliosis innate immunity pathways zebrafish neurogenesis |
| title | Innate Immune Pathways Promote Oligodendrocyte Progenitor Cell Recruitment to the Injury Site in Adult Zebrafish Brain |
| title_full | Innate Immune Pathways Promote Oligodendrocyte Progenitor Cell Recruitment to the Injury Site in Adult Zebrafish Brain |
| title_fullStr | Innate Immune Pathways Promote Oligodendrocyte Progenitor Cell Recruitment to the Injury Site in Adult Zebrafish Brain |
| title_full_unstemmed | Innate Immune Pathways Promote Oligodendrocyte Progenitor Cell Recruitment to the Injury Site in Adult Zebrafish Brain |
| title_short | Innate Immune Pathways Promote Oligodendrocyte Progenitor Cell Recruitment to the Injury Site in Adult Zebrafish Brain |
| title_sort | innate immune pathways promote oligodendrocyte progenitor cell recruitment to the injury site in adult zebrafish brain |
| topic | brain regeneration oligodendrocyte progenitors reactive gliosis innate immunity pathways zebrafish neurogenesis |
| url | https://www.mdpi.com/2073-4409/11/3/520 |
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