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Neuronal integrity and complement control synaptic material clearance by microglia after CNS injury

Geoffrey T Norris1,2,3, Igor Smirnov1,2, Anthony J Filiano1,2

  • 1Center for Brain Immunology, and Glia (BIG), University of Virginia, Charlottesville, VA.

The Journal of Experimental Medicine
|June 27, 2018
PubMed

Insights

Microglia clear synaptic debris after optic nerve injury, a crucial process for brain repair. This study identifies key molecules involved in microglial phagocytosis and debris clearance in the injured adult brain.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Microglial phagocytosis is vital for CNS development and function.
  • Microglial roles in clearing debris in the injured adult brain are not fully understood.
  • Distinguishing resident microglia from infiltrating myeloid cells complicates injury site analysis.

Purpose of the Study:

  • To investigate microglial phagocytosis of synaptic debris in an injured adult brain model.
  • To identify molecular mechanisms and physiological roles of microglial debris clearance.
  • To establish a model for studying microglial function post-injury without myeloid cell interference.

Main Methods:

  • Optic nerve crush injury model in adult mice.
  • Pharmacological depletion of microglia.
  • Genetic manipulation (C1qa and Itgam knockout mice).
  • RNA sequencing.
  • Assessing synaptic debris accumulation.

Main Results:

  • Microglia are the dominant phagocytes of synaptic debris after optic nerve injury.
  • Microglial phagocytosis is not triggered by neuronal activity post-injury.
  • C1q and CD11b/CR3 (encoded by Itgam) are involved in debris clearance.
  • C1qa and Itgam deficient mice show impaired debris clearance.

Conclusions:

  • Microglia effectively clear neurodegenerative synaptic debris in the injured adult brain.
  • This study provides a model to investigate microglial phagocytosis mechanisms and roles.
  • C1q and CD11b/CR3 are critical for efficient debris removal by microglia post-injury.

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