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Characterization and Isolation of Mouse Primary Microglia by Density Gradient Centrifugation
Published on: February 16, 2018
Microglia through MFG-E8 signaling decrease the density of degenerating neurons and protect the brain from the
Eric Yuhsiang Wang1,2, Hank Szuhan Chen2, Meng-Chih Wu1,3
1Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
Abstract:
Neuronal loss is a hallmark of stroke and other neurodegenerative diseases, and as such, neuronal loss caused by microglia has been thought to be a contributing factor to disease progression. Here, we show that microglia indeed contribute significantly to neuronal loss in a mouse model of stroke, but this microglial-dependent process of neuronal clearance specifically targets stressed and degenerating neurons in the ischemic cortical region and not healthy non-ischemic neurons. Nonspecific stimulation of microglia decreased the density of neurons in the ischemic cortical region, whereas specific inhibition of MFG-E8 signaling, which is required for microglial phagocytosis of neurons, had the opposite effect. In both scenarios, the effects were microglia specific, as the same treatments had no effect in mice whose microglia were depleted prior to stroke. Finally, even though the inhibition of MFG-E8 signaling increased neuronal density in the ischemic brain region, it substantially exacerbated the development of cortical infarction. In conclusion, microglia through MFG-E8 signaling contribute to the loss of ischemic neurons and, in doing so, minimize the development of cortical infarction after stroke.
Insights
Microglia clear stressed neurons after stroke via MFG-E8 signaling, reducing brain damage. Inhibiting this process increases neuronal survival but worsens stroke infarction.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Neuronal loss is a key feature of stroke and neurodegenerative diseases.
- Microglia are implicated in neuronal loss during disease progression.
Purpose of the Study:
- To investigate the role of microglia in neuronal loss following stroke.
- To determine the specific mechanisms by which microglia contribute to neuronal clearance.
Main Methods:
- Utilized a mouse model of stroke.
- Manipulated microglial activity through nonspecific stimulation and specific inhibition of MFG-E8 signaling.
- Assessed neuronal density and cortical infarction size.
- Employed microglia-depleted mice to confirm microglia-specific effects.
Main Results:
- Microglia significantly contribute to neuronal loss in the ischemic region, targeting stressed/degenerating neurons.
- Nonspecific microglial stimulation decreased neuronal density; inhibiting MFG-E8 signaling increased it.
- MFG-E8 signaling is crucial for microglial phagocytosis of neurons.
- Inhibition of MFG-E8 signaling exacerbated cortical infarction, despite increasing neuronal density.
Conclusions:
- Microglia, via MFG-E8 signaling, clear ischemic neurons after stroke.
- This microglial-mediated clearance limits the extent of cortical infarction.
- Targeting microglial phagocytosis pathways may offer therapeutic strategies for stroke.
