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Related Experiment Video

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Microglia control small vessel calcification via TREM2.

Yvette Zarb1,2, Sucheta Sridhar1,2, Sina Nassiri3

  • 1Department of Neurosurgery, Clinical Neurocentre, Zurich University Hospital, Zurich University, Zürich, Switzerland.

Science Advances
|February 27, 2021
PubMed
Summary
This summary is machine-generated.

Microglia play a crucial role in preventing the expansion of brain vascular calcification. Their activity, particularly via TREM2, is beneficial in central nervous system (CNS) disease.

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Area of Science:

  • Neuroscience
  • Immunology
  • Vascular Biology

Background:

  • Microglia are key immune cells in the central nervous system (CNS), involved in development, homeostasis, and disease.
  • The role of microglia in the neurovascular unit (NVU) and CNS vascular pathology remains underexplored.

Purpose of the Study:

  • To investigate the function of microglia in the calcification of the neurovascular unit (NVU).
  • To explore the mechanisms by which microglia regulate vascular calcification in a mouse model of primary familial brain calcification.

Main Methods:

  • Utilized a mouse model of primary familial brain calcification (Pdgfb).
  • Employed pharmacological ablation of microglia using the CSF1R inhibitor PLX5622.
  • Investigated the role of TREM2 in microglial regulation of vascular calcification.

Main Results:

  • Identified distinct activation phenotypes in microglia associated with vessel calcifications (calcification-associated microglia).
  • Demonstrated that pharmacological ablation of microglia exacerbates vessel calcification.
  • Showed that microglia require functional TREM2 to control vascular calcification.

Conclusions:

  • Microglial activity is beneficial in pathological vascular calcification within the CNS.
  • Microglia possess a previously unrecognized function in halting the expansion of vascular calcification.
  • Targeting microglial function, potentially via TREM2, could be a therapeutic strategy for CNS vascular calcification.