Microglia through MFG-E8 signaling decrease the density of degenerating neurons and protect the brain from the development of cortical infarction after stroke
Eric Yuhsiang Wang, Hank Szuhan Chen, Meng-Chih Wu, Ya Lan Yang, Hwai-Lee Wang, Che-Wei Liu, Ted Weita Lai
Abstract
Neuronal loss is a hallmark of stroke and other neurodegenerative diseases, and as such, neuronal loss caused by microglia has been thought to be a contributing factor to disease progression.
Introduction
As one of the primary phagocytes in the brain, microglia play key roles in the clearance of neurons [1] and cell debris [2–4] and in the pruning of synapses throughout development and in neurological diseases [5–10]. Furthermore, several findings have supported the idea that microglial phagocytosis of neurons is a major contributing factor to neuronal loss and overall disease progression in neurodegenerative diseases.
Materials and methods
Male C57BL/6 mice (8–12 weeks old; 21–30 g) were used for the in vivo experiments, and neonatal mice (E14–E16) were used to prepare the primary cortical cultures.
Results
We first asked whether the depletion of microglia from the mouse brain would have an effect on the density of neurons in the ischemic cortex.
Discussion
Microglia and other tissue-resident macrophages are known to phagocytose viable neurons and apoptotic cells through their interactions via the RGD (arginine-glycine-aspartate) domain of the extracellular MFG-E8 protein [13, 38].
Acknowledgments
We thank the Medical Research Core Facilities Center, Office of Research & Development, China Medical University (Taichung, Taiwan), where the experiments and data analyses were, in part, performed.
Citation: Wang EY, Chen HS, Wu M-C, Yang YL, Wang H-L, Liu C-W, et al. (2024) Microglia through MFG-E8 signaling decrease the density of degenerating neurons and protect the brain from the development of cortical infarction after stroke. PLoS ONE 19(8): e0308464. https://doi.org/10.1371/journal.pone.0308464
Editor: Alexander A. Mongin, Albany Medical College, UNITED STATES OF AMERICA
Received: May 15, 2024; Accepted: July 22, 2024; Published: August 7, 2024
Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the manuscript and its Supporting information files.
Funding: This study was supported by research grants from the Healthy Longevity Global Grand Challenge (AS-HLGC-110-05), the China Medical University (CMU102-NSC-S1), the National Science and Technology Council (NSTC113-2320-B-039-015-MY3), the National Health Research Institutes (NHRI-EX112-10803NI), and the ‘Drug Development Center, China Medical University’ from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education in Taiwan. EYW, HSC, MCW, and CWL were supported by undergraduate student research awards from the Ministry of Science and Technology (110-2813-C-039-027-B and 112-2813- C-039-068-B to EYW; 112-2813-C-039-069-B to HSC; 108-2813-C-039-127-B, 109-2813- C-039-115-B, 110-2813-C-039-026-B, and 111-2813-C-039-070-B to MCW; 105-2815-C039-046-B, 106-2813-C-039-066-B, and 108-2813-C-039-125-B to CWL) and by a LongTerm Scholarship for Gifted Students from the Hsing Tian Kung Culture and Education Development Foundation (to EYW). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Source: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0308464#abstract0
