PUBLICATION
Live imaging reveals a new role for the sigma-1 (σ1) receptor in allowing microglia to leave brain injuries
- Authors
- Moritz, C., Berardi, F., Abate, C., Peri, F.
- ID
- ZDB-PUB-150211-7
- Date
- 2015
- Source
- Neuroscience letters 591: 13-8 (Journal)
- Registered Authors
- Peri, Francesca
- Keywords
- Fluorescence microscopy, Microglia, Optical imaging, σ Receptor
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Brain Injuries/metabolism
- Brain Injuries/pathology*
- Cell Movement
- Embryo, Nonmammalian
- Guanidines/pharmacology
- Microglia/physiology*
- Microscopy, Confocal
- Piperidines/pharmacology
- Receptors, sigma/agonists
- Receptors, sigma/metabolism*
- Tetrahydronaphthalenes/pharmacology
- Zebrafish
- PubMed
- 25666889 Full text @ Neurosci. Lett.
Citation
Moritz, C., Berardi, F., Abate, C., Peri, F. (2015) Live imaging reveals a new role for the sigma-1 (σ1) receptor in allowing microglia to leave brain injuries. Neuroscience letters. 591:13-8.
Abstract
Microglial cells are responsible for clearing and maintaining the central nervous system (CNS) microenvironment. Upon brain damage, they move toward injuries to clear the area by engulfing dying neurons. However, in the context of many neurological disorders chronic microglial responses are responsible for neurodegeneration. Therefore, it is important to understand how these cells can be "switched-off" and regain their ramified state. Current research suggests that microglial inflammatory responses can be inhibited by sigma (σ) receptor activation. Here, we take advantage of the optical transparency of the zebrafish embryo to study the role of σ1 receptor in microglia in an intact living brain. By combining chemical approaches with real time imaging we found that treatment with PB190, a σ1 agonist, blocks microglial migration toward injuries leaving cellular baseline motility and the engulfment of apoptotic neurons unaffected. Most importantly, by taking a reverse genetic approach, we discovered that the role of σ1 in vivo is to "switch-off" microglia after they responded to an injury allowing for these cells to leave the site of damage. This indicates that pharmacological manipulation of σ1 receptor modulates microglial responses providing new approaches to reduce the devastating impact that microglia have in neurodegenerative diseases.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping