PUBLICATION

Microglial depletion after brain injury prolongs inflammation and impairs brain repair, adult neurogenesis and pro-regenerative signaling

Authors
Palsamy, K., Chen, J.Y., Skaggs, K., Qadeer, Y., Connors, M., Cutler, N., Richmond, J., Kommidi, V., Poles, A., Affrunti, D., Powell, C., Goldman, D., Parent, J.M.
ID
ZDB-PUB-230715-55
Date
2023
Source
Glia   71(11): 2642-2663 (Journal)
Registered Authors
Goldman, Dan, Parent, Jack
Keywords
brain injury, microglia, radial glia, regeneration, zebrafish
MeSH Terms
  • Animals
  • Inflammation
  • Catenins
  • Brain
  • Brain Injuries*
  • Zebrafish
  • Neurogenesis
  • Mammals
  • Microglia*
(all 9)
PubMed
37449457 Full text @ Glia
Abstract
The adult zebrafish brain, unlike mammals, has a remarkable regenerative capacity. Although inflammation in part hinders regeneration in mammals, it is necessary for zebrafish brain repair. Microglia are resident brain immune cells that regulate the inflammatory response. To explore the microglial role in repair, we used liposomal clodronate or colony stimulating factor-1 receptor (csf1r) inhibitor to suppress microglia after brain injury, and also examined regeneration in two genetic mutant lines that lack microglia. We found that microglial ablation impaired telencephalic regeneration after injury. Microglial suppression attenuated cell proliferation at the intermediate progenitor cell amplification stage of neurogenesis. Notably, the loss of microglia impaired phospho-Stat3 (signal transducer and activator of transcription 3) and ß-Catenin signaling after injury. Furthermore, the ectopic activation of Stat3 and ß-Catenin rescued neurogenesis defects caused by microglial loss. Microglial suppression also prolonged the post-injury inflammatory phase characterized by neutrophil accumulation, likely hindering the resolution of inflammation. These findings reveal specific roles of microglia and inflammatory signaling during zebrafish telencephalic regeneration that should advance strategies to improve mammalian brain repair.
Genes / Markers
Figures
Figure Gallery (8 images)
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Expression
No data available
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
gl22TgTransgenic Insertion
    gl23TgTransgenic Insertion
      j4e1
        Point Mutation
        kyu1TgTransgenic Insertion
          mi4TgTransgenic Insertion
            mi20TgTransgenic Insertion
              mi30TgTransgenic Insertion
                mi35TgTransgenic Insertion
                  mi47TgTransgenic Insertion
                    mi400kTgTransgenic Insertion
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                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      No data available
                      Fish
                      No data available
                      Antibodies
                      Orthology
                      No data available
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      CreEFGCre
                      d2EGFPEFGd2EGFP
                      EGFPEFGEGFP
                      GFPEFGGFP
                      LanYFPEFGLanYFP
                      mCherryEFGmCherry
                      1 - 6 of 6
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                      Mapping
                      No data available