Microglia are not necessary for maintenance of blood-brain barrier properties in health, but PLX5622 alters brain endothelial cholesterol metabolism
Microglia, the resident immune cells of the central nervous system, are intimately involved in the brain's most basic processes, from pruning neural synapses during development to preventing excessive neuronal activity throughout life. Studies have reported both helpful and harmful roles for microglia at the blood-brain barrier (BBB) in the context of disease. However, less is known about microglia-endothelial cell interactions in the healthy brain. To investigate the role of microglia at a healthy BBB, we used the colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX5622 to deplete microglia and analyzed the BBB ultrastructure, permeability, and transcriptome. Interestingly, we found that, despite their direct contact with endothelial cells, microglia are not necessary for the maintenance of BBB structure, function, or gene expression in the healthy brain. However, we found that PLX5622 treatment alters brain endothelial cholesterol metabolism. This effect was independent from microglial depletion, suggesting that PLX5622 has off-target effects on brain vasculature.
Authors
- Caterina P. Profaci (ORCID: https://orcid.org/0000-0002-4073-2164)
- Dimitrios Davalos (ORCID: https://orcid.org/0000-0001-9038-6688)
- Carleigh A. O’Brien (ORCID: https://orcid.org/0000-0003-4549-0640)
- Aaron Longworth (ORCID: https://orcid.org/0000-0003-1893-3880)
- Hayk Davtyan (ORCID: https://orcid.org/0000-0001-8554-6456)
- Kelsey M Nemec (ORCID: https://orcid.org/0000-0003-3036-254X)
- Fabrice Dabertrand (ORCID: https://orcid.org/0000-0003-2541-9185)
- Richard Daneman (ORCID: https://orcid.org/0000-0002-7749-6353)
- Danielle A Jeffrey (ORCID: https://orcid.org/0000-0002-9576-9458)
- Devon A. Lawson (ORCID: https://orcid.org/0000-0003-1692-0517)
- Thomas D. Arnold (ORCID: https://orcid.org/0000-0002-7310-5597)
- Kaja Bajc
- Sean Harvey (ORCID: https://orcid.org/0000-0002-2153-8235)
- Mathew Blurton‐Jones (ORCID: https://orcid.org/0000-0002-7770-7157)
- F. Chris Bennett (ORCID: https://orcid.org/0000-0003-2570-0620)
- Joia Kai Capocchi (ORCID: https://orcid.org/0000-0002-3433-5904)
- Timothy P McMullen (ORCID: https://orcid.org/0000-0003-4077-7036)
- Gabriel L. McKinsey (ORCID: https://orcid.org/0000-0002-5503-2830)
- Jessica G Gonzalez
- Alexander Z Zhang
- Tony Z Zhang
Institutions
- University of California, San Francisco (US)
- University of California, Irvine (US)
- Cleveland Clinic Lerner College of Medicine (US)
- University of Colorado Anschutz Medical Campus (US)
- University of Pennsylvania (US)
Publication Details
- Journal
- Neuron
- Published
- 2024-08-13
- DOI
- https://doi.org/10.1016/j.neuron.2024.07.015
- Citations
- 39
- Primary Topic
- Neuroinflammation and Neurodegeneration Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 9.65
Funders
- Plexxikon
- National Institutes of Health
- University of California, San Diego