Repopulating Microglia Promote Brain Repair in an IL-6-Dependent Manner
File version
Author(s)
MacDonald, Kelli PA
Nguyen, Quan H
Garrido, Adahir Labrador
Gillespie, Ellen R
Harley, Samuel BR
Bartlett, Perry F
Schroder, Wayne A
Yates, Abi G
Anthony, Daniel C
Rose-John, Stefan
Ruitenberg, Marc J
Vukovic, Jana
Griffith University Author(s)
Primary Supervisor
Other Supervisors
Editor(s)
Date
Size
File type(s)
Location
License
Abstract
Cognitive dysfunction and reactive microglia are hallmarks of traumatic brain injury (TBI), yet whether these cells contribute to cognitive deficits and secondary inflammatory pathology remains poorly understood. Here, we show that removal of microglia from the mouse brain has little effect on the outcome of TBI, but inducing the turnover of these cells through either pharmacologic or genetic approaches can yield a neuroprotective microglial phenotype that profoundly aids recovery. The beneficial effects of these repopulating microglia are critically dependent on interleukin-6 (IL-6) trans-signaling via the soluble IL-6 receptor (IL-6R) and robustly support adult neurogenesis, specifically by augmenting the survival of newborn neurons that directly support cognitive function. We conclude that microglia in the mammalian brain can be manipulated to adopt a neuroprotective and pro-regenerative phenotype that can aid repair and alleviate the cognitive deficits arising from brain injury.
Journal Title
Cell
Conference Title
Book Title
Edition
Volume
180
Issue
5
Thesis Type
Degree Program
School
Publisher link
Patent number
Funder(s)
Grant identifier(s)
Rights Statement
Rights Statement
Item Access Status
Note
Access the data
Related item(s)
Subject
Biological sciences
Biomedical and clinical sciences
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Cell Biology
PROGENITOR-CELL
Persistent link to this record
Citation
Willis, EF; MacDonald, KPA; Nguyen, QH; Garrido, AL; Gillespie, ER; Harley, SBR; Bartlett, PF; Schroder, WA; Yates, AG; Anthony, DC; Rose-John, S; Ruitenberg, MJ; Vukovic, J, Repopulating Microglia Promote Brain Repair in an IL-6-Dependent Manner, Cell, 2020, 180 (5), pp. 833-+