P2Y6 receptor inhibition aggravates ischemic brain injury by reducing microglial phagocytosis.

CNS Neuroscience & Therapeutics
Ruo-Xue WenZhi-Jun Zhang

Abstract

Clearance of damaged cells and debris is beneficial for the functional recovery after ischemic brain injury. However, the specific phagocytic receptor that mediates microglial phagocytosis after ischemic stroke is unknown. To investigate whether P2Y6 receptor-mediated microglial phagocytosis is beneficial for the debris clearance and functional recovery after ischemic stroke. The expression of the P2Y6 receptor in microglia increased within 3 days after transient middle cerebral artery occlusion. Inhibition of microglial phagocytosis by the selective inhibitor MRS2578 enlarged the brain atrophy and edema volume after ischemic stroke, subsequently aggravated neurological function as measured by modified neurological severity scores and Grid walking test. MRS2578 treatment had no effect on the expression of IL-1α, IL-1β, IL-6, IL-10, TNF-α, TGF-β, and MPO after ischemic stroke. Finally, we found that the expression of myosin light chain kinase decreased after microglial phagocytosis inhibition in the ischemic mouse brain, which suggested that myosin light chain kinase was involved in P2Y6 receptor-mediated phagocytosis. Our results indicate that P2Y6 receptor-mediated microglial phagocytosis plays a beneficial role during the acu...Continue Reading

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Citations

Jan 4, 2021·CNS Neuroscience & Therapeutics·Liyun WangJian Shen
Jan 20, 2021·CNS Neuroscience & Therapeutics·Justin ChoCesar V Borlongan
Feb 4, 2021·International Journal of Molecular Sciences·Muhammad AslamRainer Schulz
Mar 3, 2021·CNS Neuroscience & Therapeutics·Junxuan LyuXiaoyan Jiang
Apr 9, 2021·Bioorganic & Medicinal Chemistry Letters·Young-Hwan JungKenneth A Jacobson
Jul 3, 2021·International Journal of Molecular Sciences·Chiara PorroTeresa Trotta
Sep 4, 2021·Purinergic Signalling·Christa E Müller, Vigneshwaran Namasivayam
Oct 14, 2021·Proceedings of the National Academy of Sciences of the United States of America·Pablo IzquierdoDavid Attwell

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Methods Mentioned

BETA
electrophoresis
Assay
confocal microscopy
flow cytometry
PCR

Software Mentioned

GraphPad Prism

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