RT Journal Article
SR Electronic
T1 Astrocytes and microglia play orchestrated roles and respect phagocytic territories during neuronal corpse removal in vivo
JF Science Advances
JO Sci Adv
FD American Association for the Advancement of Science
SP eaba3239
DO 10.1126/sciadv.aba3239
VO 6
IS 26
A1 Damisah, Eyiyemisi C.
A1 Hill, Robert A.
A1 Rai, Anupama
A1 Chen, Fuyi
A1 Rothlin, Carla V.
A1 Ghosh, Sourav
A1 Grutzendler, Jaime
YR 2020
UL http://advances.sciencemag.org/content/6/26/eaba3239.abstract
AB Cell death is prevalent throughout life; however, the coordinated interactions and roles of phagocytes during corpse removal in the live brain are poorly understood. We developed photochemical and viral methodologies to induce death in single cells and combined this with intravital optical imaging. This approach allowed us to track multicellular phagocytic interactions with precise spatiotemporal resolution. Astrocytes and microglia engaged with dying neurons in an orchestrated and synchronized fashion. Each glial cell played specialized roles: Astrocyte processes rapidly polarized and engulfed numerous small dendritic apoptotic bodies, while microglia migrated and engulfed the soma and apical dendrites. The relative involvement and phagocytic specialization of each glial cell was plastic and controlled by the receptor tyrosine kinase Mertk. In aging, there was a marked delay in apoptotic cell removal. Thus, a precisely orchestrated response and cross-talk between glial cells during corpse removal may be critical for maintaining brain homeostasis.