title: 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 (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 σ1in 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.
authors: European Molecular Biology Laboratory, Developmental Biology Unit, Meyerhofstr. 1, 69117 Heidelberg, Germany.
authors: Christian
authors: C
authors: Moritz
authors: Dipartimento di Farmacia - Scienze del Farmaco, Università degli Studi di Bari ALDO MORO, Via Orabona 4, I-70125 Bari, Italy.
authors: Francesco
authors: F
authors: Berardi
authors: Dipartimento di Farmacia - Scienze del Farmaco, Università degli Studi di Bari ALDO MORO, Via Orabona 4, I-70125 Bari, Italy. Electronic address: carmen.abate@uniba.it.
authors: Carmen
authors: C
authors: Abate
authors: European Molecular Biology Laboratory, Developmental Biology Unit, Meyerhofstr. 1, 69117 Heidelberg, Germany. Electronic address: peri@embl.de.
authors: Francesca
authors: F
authors: Peri
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement; D004625:Embryo, Nonmammalian; D006146:Guanidines / Q000494:pharmacology; D017628:Microglia / Q000502:physiology*; D018613:Microscopy, Confocal; D010880:Piperidines / Q000494:pharmacology; D017480:Receptors, sigma / Q000819:agonists / Q000378:metabolism*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D015027:Zebrafish
chemical_list: C000595923:4-methyl-1-(4-(6-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)butyl)piperidine; D006146:Guanidines; D010880:Piperidines; D017480:Receptors, sigma; D013764:Tetrahydronaphthalenes; C050232:1,3-ditolylguanidine
keywords: Fluorescence microscopy; Microglia; Optical imaging; σ Receptor