1. Young microglia restore amyloid plaque clearance of aged microglia.
- Author
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Daria A, Colombo A, Llovera G, Hampel H, Willem M, Liesz A, Haass C, and Tahirovic S
- Subjects
- Animals, Cell Proliferation, Coculture Techniques, Culture Media, Conditioned, Mice, Microglia physiology, Organ Culture Techniques, Alzheimer Disease pathology, Brain pathology, Disease Models, Animal, Microglia metabolism, Plaque, Amyloid metabolism
- Abstract
Alzheimer's disease (AD) is characterized by deposition of amyloid plaques, neurofibrillary tangles, and neuroinflammation. In order to study microglial contribution to amyloid plaque phagocytosis, we developed a novel ex vivo model by co-culturing organotypic brain slices from up to 20-month-old, amyloid-bearing AD mouse model (APPPS1) and young, neonatal wild-type (WT) mice. Surprisingly, co-culturing resulted in proliferation, recruitment, and clustering of old microglial cells around amyloid plaques and clearance of the plaque halo. Depletion of either old or young microglial cells prevented amyloid plaque clearance, indicating a synergistic effect of both populations. Exposing old microglial cells to conditioned media of young microglia or addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) was sufficient to induce microglial proliferation and reduce amyloid plaque size. Our data suggest that microglial dysfunction in AD may be reversible and their phagocytic ability can be modulated to limit amyloid accumulation. This novel ex vivo model provides a valuable system for identification, screening, and testing of compounds aimed to therapeutically reinforce microglial phagocytosis., (© 2016 The Authors.)
- Published
- 2017
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