Live imaging reveals a new role for the sigma-1 (σ1) receptor in allowing microglia to leave brain injuries

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 () receptor activation. Here, we take advantage of the optical transparency of the zebrafish embryo to study the role of 1 receptor in microglia in an intact living brain. By combining chemical approaches with real time imaging we found that treatment with PB190, a 1 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 1 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 1 receptor modulates microglial responses providing new approaches to reduce the devastating impact that microglia have in neurodegenerative diseases.


Tutti gli autori

  • ABATE C.;BERARDI F.

Titolo volume/Rivista

Non Disponibile


Anno di pubblicazione

2015

ISSN

0304-3940

ISBN

Non Disponibile


Numero di citazioni Wos

Nessuna citazione

Ultimo Aggiornamento Citazioni

Non Disponibile


Numero di citazioni Scopus

16

Ultimo Aggiornamento Citazioni

Non Disponibile


Settori ERC

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Codici ASJC

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