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Neuron-Derived Extracellular Vesicles Modulate Microglia Activation and Function

SIMPLE SUMMARY: In this study we investigated how neuron-derived extracellular vesicles (NDEVs) mediate neuroimmune regulation in primary cell culture systems. Rat cortical neurons released EVs that improved microglial survival and inhibited the expression of activation markers on microglia. Further...

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Autores principales: Peng, Hui, Harvey, Brock T., Richards, Christopher I., Nixon, Kimberly
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533634/
https://www.ncbi.nlm.nih.gov/pubmed/34681047
http://dx.doi.org/10.3390/biology10100948
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author Peng, Hui
Harvey, Brock T.
Richards, Christopher I.
Nixon, Kimberly
author_facet Peng, Hui
Harvey, Brock T.
Richards, Christopher I.
Nixon, Kimberly
author_sort Peng, Hui
collection PubMed
description SIMPLE SUMMARY: In this study we investigated how neuron-derived extracellular vesicles (NDEVs) mediate neuroimmune regulation in primary cell culture systems. Rat cortical neurons released EVs that improved microglial survival and inhibited the expression of activation markers on microglia. Furthermore, NDEVs reduced the LPS-induced proinflammatory response and promoted an anti-inflammatory response. Thus, neurons critically regulate microglia activity and control inflammation via EV-mediated neuron–glia communication. ABSTRACT: 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).
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spelling pubmed-85336342021-10-23 Neuron-Derived Extracellular Vesicles Modulate Microglia Activation and Function Peng, Hui Harvey, Brock T. Richards, Christopher I. Nixon, Kimberly Biology (Basel) Article SIMPLE SUMMARY: In this study we investigated how neuron-derived extracellular vesicles (NDEVs) mediate neuroimmune regulation in primary cell culture systems. Rat cortical neurons released EVs that improved microglial survival and inhibited the expression of activation markers on microglia. Furthermore, NDEVs reduced the LPS-induced proinflammatory response and promoted an anti-inflammatory response. Thus, neurons critically regulate microglia activity and control inflammation via EV-mediated neuron–glia communication. ABSTRACT: 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). MDPI 2021-09-22 /pmc/articles/PMC8533634/ /pubmed/34681047 http://dx.doi.org/10.3390/biology10100948 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Peng, Hui
Harvey, Brock T.
Richards, Christopher I.
Nixon, Kimberly
Neuron-Derived Extracellular Vesicles Modulate Microglia Activation and Function
title Neuron-Derived Extracellular Vesicles Modulate Microglia Activation and Function
title_full Neuron-Derived Extracellular Vesicles Modulate Microglia Activation and Function
title_fullStr Neuron-Derived Extracellular Vesicles Modulate Microglia Activation and Function
title_full_unstemmed Neuron-Derived Extracellular Vesicles Modulate Microglia Activation and Function
title_short Neuron-Derived Extracellular Vesicles Modulate Microglia Activation and Function
title_sort neuron-derived extracellular vesicles modulate microglia activation and function
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533634/
https://www.ncbi.nlm.nih.gov/pubmed/34681047
http://dx.doi.org/10.3390/biology10100948
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