Microglia are not necessary for maintenance of blood-brain barrier properties in health, but PLX5622 alters brain endothelial cholesterol metabolism.

Autor:	Profaci CP; Department of Pharmacology, University of California, San Diego, La Jolla, San Diego, CA, USA; Department of Neurosciences, University of California, San Diego, La Jolla, San Diego, CA, USA. Electronic address: cprofaci@scripps.edu., Harvey SS; Department of Pharmacology, University of California, San Diego, La Jolla, San Diego, CA, USA; Department of Neurosciences, University of California, San Diego, La Jolla, San Diego, CA, USA., Bajc K; Department of Pharmacology, University of California, San Diego, La Jolla, San Diego, CA, USA; Department of Neurosciences, University of California, San Diego, La Jolla, San Diego, CA, USA., Zhang TZ; Department of Pharmacology, University of California, San Diego, La Jolla, San Diego, CA, USA; Department of Neurosciences, University of California, San Diego, La Jolla, San Diego, CA, USA., Jeffrey DA; Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Zhang AZ; Department of Pharmacology, University of California, San Diego, La Jolla, San Diego, CA, USA; Department of Neurosciences, University of California, San Diego, La Jolla, San Diego, CA, USA., Nemec KM; Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Davtyan H; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, USA; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA, USA., O'Brien CA; Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., McKinsey GL; Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA., Longworth A; Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA., McMullen TP; Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA., Capocchi JK; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, USA; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA, USA., Gonzalez JG; Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA., Lawson DA; Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA., Arnold TD; Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA., Davalos D; Department of Neurosciences, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA., Blurton-Jones M; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, USA; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA, USA; Department of Neurobiology & Behavior, University of California, Irvine, Irvine, CA, USA., Dabertrand F; Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Bennett FC; Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Daneman R; Department of Pharmacology, University of California, San Diego, La Jolla, San Diego, CA, USA; Department of Neurosciences, University of California, San Diego, La Jolla, San Diego, CA, USA.
Jazyk:	angličtina
Zdroj:	Neuron [Neuron] 2024 Sep 04; Vol. 112 (17), pp. 2910-2921.e7. Date of Electronic Publication: 2024 Aug 13.
DOI:	10.1016/j.neuron.2024.07.015
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu