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Article

Innate Immune Pathways Promote Oligodendrocyte Progenitor Cell Recruitment to the Injury Site in Adult Zebrafish Brain

1
Institute of Stem Cell Research, Helmholtz Center Munich, 85764 Oberschleißheim, Germany
2
Department Biology II, University of Munich, 80539 München, Germany
3
Biomedical Center (BMC), Division of Cell Biology and Anatomy, Faculty of Medicine, LMU Munich, 80539 München, Germany
4
Graduate School Systemic Neurosciences, LMU, 80539 Munich, Germany
5
Reprogramming and Regeneration, Biomedical Center (BMC), Physiological Genomics, Faculty of Medicine, LMU Munich, 80539 München, Germany
6
Epigenetic Engineering, Institute of Stem Cell Research, Helmholtz Center Munich, 85764 Oberschleißheim, Germany
7
Department of Neurology, Justus-Liebig-University Giessen, Klinikstrasse 33, 35392 Giessen, Germany
8
Institute of Experimental Genetics, Helmholtz Center Munich, 85764 Oberschleißheim, Germany
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German Center for Diabetes Research (DZD e.V.), 85764 Neuherberg, Germany
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Chair of Experimental Genetics, School of Life Sciences Weihenstephan, Technical University Munich, 80333 München, Germany
11
Institute of Developmental Genetics, Helmholtz Center Munich, 85764 Oberschleißheim, Germany
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Munich Cluster for Systems Neurology SYNERGY, LMU, 80539 Munich, Germany
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Chair of Developmental Genetics c/o Helmholtz Zentrum München, School of Life Sciences Weihenstephan, Technical University Munich, 80333 München, Germany
14
German Center for Neurodegenerative Diseases (DZNE), Site Munich, 80539 Munich, Germany
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Department of Neurology, Ludwig-Maximilians University, Campus Grosshadern, 81377 Munich, Germany
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Biomedical Center (BMC), Bioinformatic Core Facility, Faculty of Medicine, LMU Munich, 80539 München, Germany
17
Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH8 9YL, UK
18
Biomedical Center (BMC), Division of Physiological Genomics, Faculty of Medicine, LMU Munich, 80539 München, Germany
*
Author to whom correspondence should be addressed.
Present address: Institute of Metabolism and Cell Death, Helmholtz Center, Munich, 85764 Neuherberg, Germany.
Academic Editors: Sepand Rastegar and Luisa Lübke
Cells 2022, 11(3), 520; https://doi.org/10.3390/cells11030520
Received: 26 December 2021 / Revised: 18 January 2022 / Accepted: 18 January 2022 / Published: 2 February 2022
(This article belongs to the Special Issue Neurogenesis and Regeneration in Teleost Central Nervous System)
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. View Full-Text
Keywords: brain regeneration; oligodendrocyte progenitors; reactive gliosis; innate immunity pathways; zebrafish; neurogenesis; brain injury brain regeneration; oligodendrocyte progenitors; reactive gliosis; innate immunity pathways; zebrafish; neurogenesis; brain injury
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MDPI and ACS Style

Sanchez-Gonzalez, R.; Koupourtidou, C.; Lepko, T.; Zambusi, A.; Novoselc, K.T.; Durovic, T.; Aschenbroich, S.; Schwarz, V.; Breunig, C.T.; Straka, H.; Huttner, H.B.; Irmler, M.; Beckers, J.; Wurst, W.; Zwergal, A.; Schauer, T.; Straub, T.; Czopka, T.; Trümbach, D.; Götz, M.; Stricker, S.H.; Ninkovic, J. Innate Immune Pathways Promote Oligodendrocyte Progenitor Cell Recruitment to the Injury Site in Adult Zebrafish Brain. Cells 2022, 11, 520. https://doi.org/10.3390/cells11030520

AMA Style

Sanchez-Gonzalez R, Koupourtidou C, Lepko T, Zambusi A, Novoselc KT, Durovic T, Aschenbroich S, Schwarz V, Breunig CT, Straka H, Huttner HB, Irmler M, Beckers J, Wurst W, Zwergal A, Schauer T, Straub T, Czopka T, Trümbach D, Götz M, Stricker SH, Ninkovic J. Innate Immune Pathways Promote Oligodendrocyte Progenitor Cell Recruitment to the Injury Site in Adult Zebrafish Brain. Cells. 2022; 11(3):520. https://doi.org/10.3390/cells11030520

Chicago/Turabian Style

Sanchez-Gonzalez, Rosario, 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, and Jovica Ninkovic. 2022. "Innate Immune Pathways Promote Oligodendrocyte Progenitor Cell Recruitment to the Injury Site in Adult Zebrafish Brain" Cells 11, no. 3: 520. https://doi.org/10.3390/cells11030520

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