PUBLICATION
Innate Immune Pathways Promote Oligodendrocyte Progenitor Cell Recruitment to the Injury Site in Adult Zebrafish Brain
- Authors
- 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.
- ID
- ZDB-PUB-220216-7
- Date
- 2022
- Source
- Cells 11(3): (Journal)
- Registered Authors
- Czopka, Tim
- Keywords
- brain injury, brain regeneration, innate immunity pathways, neurogenesis, oligodendrocyte progenitors, reactive gliosis, zebrafish
- Datasets
- GEO:GSE98217
- MeSH Terms
-
- Animals
- Brain
- Gliosis/metabolism
- Immunity, Innate
- Oligodendrocyte Precursor Cells*/metabolism
- Zebrafish
- PubMed
- 35159329 Full text @ Cells
Citation
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. (2022) Innate Immune Pathways Promote Oligodendrocyte Progenitor Cell Recruitment to the Injury Site in Adult Zebrafish Brain. Cells. 11(3):.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping