PUBLICATION
Distribution of microglia/immune cells in the brain of adult zebrafish in homeostatic and regenerative conditions: Focus on oxidative stress during brain repair
- Authors
- Narra, S.S., Rondeau, P., Fernezelian, D., Gence, L., Ghaddar, B., Bourdon, E., Lefebvre d'Hellencourt, C., Rastegar, S., Diotel, N.
- ID
- ZDB-PUB-221026-8
- Date
- 2022
- Source
- The Journal of comparative neurology 531(2): 238-255 (Journal)
- Registered Authors
- Rastegar, Sepand
- Keywords
- SOD, brain injury, immune cells, microglia, neurogenesis, oxidative stress, teleost
- MeSH Terms
-
- Animals
- Brain/metabolism
- Disease Models, Animal
- Endothelial Cells/metabolism
- Mammals
- Microglia*/metabolism
- Oxidative Stress
- Zebrafish*/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 36282721 Full text @ J. Comp. Neurol.
Citation
Narra, S.S., Rondeau, P., Fernezelian, D., Gence, L., Ghaddar, B., Bourdon, E., Lefebvre d'Hellencourt, C., Rastegar, S., Diotel, N. (2022) Distribution of microglia/immune cells in the brain of adult zebrafish in homeostatic and regenerative conditions: Focus on oxidative stress during brain repair. The Journal of comparative neurology. 531(2):238-255.
Abstract
Microglia are macrophage-like cells exerting determinant roles in neuroinflammatory and oxidative stress processes during brain regeneration. We used zebrafish as a model of brain plasticity and repair. First, by performing L-plastin (Lcp1) immunohistochemistry and using transgenic Tg(mpeg1.1:GFP) or Tg(mpeg1.1:mCherry) fish, we analyzed the distribution of microglia/immune cells in the whole brain. Specific regional differences were evidenced in terms of microglia/immune cell density and morphology (elongated, branched, highly branched, and amoeboid). Taking advantage of Tg(fli:GFP) and Tg(GFAP::GFP) enabling the detection of endothelial cells and neural stem cells (NSCs), we highlighted the association of elongated microglia/immune cells with blood vessels and rounded/amoeboid microglia with NSCs. Second, after telencephalic injury, we showed that L-plastin cells were still abundantly present at 5 days post-lesion (dpl) and were associated with regenerative neurogenesis. Finally, RNA-sequencing analysis from injured telencephalon (5 dpl) confirmed the upregulation of microglia/immune cell markers and highlighted a significant increase of genes involved in oxidative stress (nox2, nrf2a, and gsr). The analysis of antioxidant activities at 5 dpl also revealed an upregulation of superoxide dismutase and persistent H2 O2 generation in the injured telencephalon. Also, microglia/immune cells were shown to be a source of oxidative stress at 5 dpl. Overall, our data provide a better characterization of microglia/immune cell distribution in the healthy zebrafish brain, highlighting some evolutionarily conserved features with mammals. They also emphasize that 5 days after injury, microglia/immune cells are still activated and are associated to a persistent redox imbalance. Together, these data raise the question of the role of oxidative stress in regenerative neurogenesis in zebrafish.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping