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Microglia and astrocytes mediate synapse engulfment in a MER tyrosine kinase-dependent manner after traumatic brain injury

Summary

After a traumatic brain injury, brain cells called microglia and astrocytes overzealously consume synapses (connections between neurons), which prevents the brain from healing properly. This study shows that these brain cells use a specific protein called MERTK to do this unwanted cleanup. When researchers blocked MERTK in these cells, the mice recovered better motor and cognitive function, had smaller brain injuries, and maintained more healthy synapses.

Background

Traumatic brain injury (TBI) leads to significant neurological impairment and is a major risk factor for dementia. Microglia and astrocytes can mediate synaptic phagocytosis through MER proto-oncokinase in developmental and stroke models, but its role in TBI remains unclear.

Objective

To investigate whether microglia/macrophages and astrocytes mediate synapse engulfment through MER proto-oncokinase expression in a mouse model of traumatic brain injury and to determine if inhibiting this process could improve neurological outcomes.

Results

Both microglia/macrophages and astrocytes phagocytosed synapses 14 days after TBI with increased MERTK expression. Specific MERTK knockout in either cell type markedly reduced injury volume, improved neurobehavioral function, decreased synapse phagocytosis, and increased dendritic spine density. Both inhibitory and excitatory synapses were engulfed through lysosome-mediated degradation.

Conclusion

MER proto-oncokinase expression in microglia/macrophages and astrocytes plays an important role in detrimental synaptic phagocytosis after TBI. Inhibiting MERTK-mediated synapse engulfment represents a novel therapeutic strategy for promoting synaptic recovery and improving neurological outcomes following traumatic brain injury.
  • Published in:Neural Regeneration Research,
  • Study Type:Animal Model Study,
  • Source: PMID: 36751804, DOI: 10.4103/1673-5374.363187
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