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Advanced Neurology

ORIGINAL RESEARCH ARTICLE
Proteomic analysis of exosomes derived from

detrimental and protective microglia

2
Lingyun Bai 1 , Fangyu Chen 2 , Shengnan Xia , and Xiang Cao 1,2,3 *
1 Department of Neurology, Joint Institute of Nanjing Drum Tower Hospital for Life and Health, College
of Life Science, Nanjing Normal University, Nanjing, Jiangsu, China
2 Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School,
Nanjing University, Nanjing, Jiangsu, China
3 State Key Laboratory of Pharmaceutical Biotechnology, Institute of Translational Medicine for Brain
Critical Diseases, Nanjing University, Nanjing, Jiangsu, China
(This article belongs to the Special Issue: Advances in stroke research and therapy)

Abstract

Microglia, the primary resident immune cells in the brain, exhibit two distinct
functional states: The detrimental (M1) phenotype and the protective (M2) phenotype.
Exosomes, which are released by various cell types, play crucial roles in intercellular
communication. While existing studies have shown that exosomes from microglia
with different activation states can affect neuronal survival following ischemic stroke,
a comprehensive exploration of the differences between these microglial phenotypes
is still lacking. In this study, we treated primary microglia with lipopolysaccharide
(LPS) or interleukin-4 (IL-4) to induce the M1 or M2 phenotype, respectively, and
investigated the characteristics of the resulting exosomes. These microglia-derived
*Corresponding author: exosomes can be internalized by neurons. Specifically, exosomes derived from M1
Xiang Cao microglia (M1-EXOs) exacerbated ischemia-induced neuronal apoptosis both in vivo
(caoxiang@njglyy.com) and in vitro, while exosomes from M2 microglia (M2-EXOs) exhibited a protective
Citation: Bai L, Chen F, Xia S, effect. Subsequently, we conducted a quantitative proteomic analysis of M1-EXOs
Cao X. Proteomic analysis of and M2-EXOs, characterizing 1129 proteins. Notably, M1-EXO proteins were primarily
exosomes derived from detrimental associated with inflammatory responses, neutrophil chemotaxis, and complement
and protective microglia.
Adv Neuro. 2024;3(3):3166. activation. In contrast, M2-EXO proteins were predominantly involved in protein
doi: 10.36922/an.3166 transport and cellular proliferation. In addition, we analyzed key proteins, including
Received: March 14, 2024 IL-6, SAA3, CCL5, CCL9, C3, CFB, SRGN, and sphingosine-1-phosphate phosphatase 1,
which play central roles in the protein-protein interaction network. Overall, this dataset
Accepted: June 14, 2024
provides valuable insights into the proteomic profiles of exosomes derived from
Published Online: August 7, 2024 microglia with distinct phenotypes, enhancing our understanding of the mechanisms
Copyright: © 2024 Author(s). underlying microglial involvement in central nervous system diseases.
This is an Open-Access article
distributed under the terms of the
Creative Commons Attribution Keywords: Microglia; Exosomal proteins; Ischemic stroke; Proteomics
License, permitting distribution,
and reproduction in any medium,
provided the original work is
properly cited.
1. Introduction
Publisher’s Note: AccScience
Publishing remains neutral with Stroke, a leading cause of global morbidity and mortality, imposes a substantial economic
regard to jurisdictional claims in 1
published maps and institutional burden on patients’ families. Ischemic stroke, the most common form of stroke, occurs
affiliations. due to obstruction of blood flow, leading to deprivation of oxygen and glucose in brain

Volume 3 Issue 3 (2024) 1 doi: 10.36922/an.3166