Neuron‐derived extracellular vesicles modulate microglia activation and function

Hui Peng, Brock T. Harvey, Christopher I. Richards, Kimberly Nixon

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Microglia act as the immune cells of the central nervous system (CNS). They play an important role in maintaining brain homeostasis but also in mediating neuroimmune responses to insult. The interactions between neurons and microglia represent a key process for neuroimmune regulation and subsequent effects on CNS integrity. However, the molecular mechanisms of neuron‐glia communication in regulating microglia function are not fully understood. One recently described means of this intercellular communication is via nano‐sized extracellular vesicles (EVs) that transfer a large diversity of molecules between neurons and microglia, such as proteins, lipids, and nucleic acids. To determine the effects of neuron‐derived EVs (NDEVs) on microglia, NDEVs were isolated from the culture supernatant of rat cortical neurons. When NDEVs were added to primary cultured rat microglia, we found significantly improved microglia viability via inhibition of apoptosis. Additionally, application of NDEVs to cultured microglia also inhibited the expression of activation surface markers on microglia. Furthermore, NDEVs reduced the LPS‐induced proinflammatory response in microglia according to reduced gene expression of proinflammatory cytokines (TNF‐α, IL‐6, MCP‐1) and iNOS, but increased expression of the anti‐inflammatory cytokine, IL‐10. These findings support that neurons critically regulate microglia activity and control inflammation via EV‐mediated neuron–glia communication. (Supported by R21AA025563 and R01AA025591).

Original languageEnglish
Article number948
Issue number10
StatePublished - Oct 2021

Bibliographical note

Funding Information:
Acknowledgments: We thank Younsoo Bae, Gregory Graf, and David Feola for contributing re‐ sources towards this work and James R. Pauly for critical reading of the manuscript. We gratefully acknowledge the National institute of Alcohol Abuse and Alcoholism; Grants R21AA025563 (HP/KN) and R01AA025591 (KN) and the University of Kentucky College of Pharmacy for support of this work.

Funding Information:
Funding: This research was funded by the National institute of Alcohol Abuse and Alcoholism, grant number R21AA025563 (HP/KN) and R01AA025591 (KN).

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (


  • Cytokine
  • Extracellular vesicle
  • Inflammation
  • Microglia activation
  • Neuron

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (all)
  • Immunology and Microbiology (all)
  • Agricultural and Biological Sciences (all)


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