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Neuron secrete exosomes containing miR-9-5p to promote polarization of M1 microglia in depression
BACKGROUND: Neuroinflammation is an important component mechanism in the development of depression. Exosomal transfer of MDD-associated microRNAs (miRNAs) from neurons to microglia might exacerbate neuronal cell inflammatory injury. RESULTS: By sequence identification, we found significantly higher...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8905830/ https://www.ncbi.nlm.nih.gov/pubmed/35264203 http://dx.doi.org/10.1186/s12951-022-01332-w |
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author | Xian, Xian Cai, Li-Li Li, Yang Wang, Ran-Chao Xu, Yu-Hao Chen, Ya-Jie Xie, Yu-Hang Zhu, Xiao-Lan Li, Yue-Feng |
author_facet | Xian, Xian Cai, Li-Li Li, Yang Wang, Ran-Chao Xu, Yu-Hao Chen, Ya-Jie Xie, Yu-Hang Zhu, Xiao-Lan Li, Yue-Feng |
author_sort | Xian, Xian |
collection | PubMed |
description | BACKGROUND: Neuroinflammation is an important component mechanism in the development of depression. Exosomal transfer of MDD-associated microRNAs (miRNAs) from neurons to microglia might exacerbate neuronal cell inflammatory injury. RESULTS: By sequence identification, we found significantly higher miR-9-5p expression levels in serum exosomes from MDD patients than healthy control (HC) subjects. Then, in cultured cell model, we observed that BV2 microglial cells internalized PC12 neuron cell-derived exosomes while successfully transferring miR-9-5p. MiR-9-5p promoted M1 polarization in microglia and led to over releasing of proinflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), which exacerbated neurological damage. Furthermore, we identified suppressor of cytokine signaling 2 (SOCS2) as a direct target of miR-9-5p. Overexpression of miR-9-5p suppressed SOCS2 expression and reactivated SOCS2-repressed Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathways. Consistently, we confirmed that adeno-associated virus (AAV)-mediated overexpression of miR-9-5p polarized microglia toward the M1 phenotype and exacerbated depressive symptoms in chronic unpredictable mild stress (CUMS) mouse mode. CONCLUSION: MiR-9-5p was transferred from neurons to microglia in an exosomal way, leading to M1 polarization of microglia and further neuronal injury. The expression and secretion of miR-9-5p might be novel therapeutic targets for MDD. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-022-01332-w. |
format | Online Article Text |
id | pubmed-8905830 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-89058302022-03-18 Neuron secrete exosomes containing miR-9-5p to promote polarization of M1 microglia in depression Xian, Xian Cai, Li-Li Li, Yang Wang, Ran-Chao Xu, Yu-Hao Chen, Ya-Jie Xie, Yu-Hang Zhu, Xiao-Lan Li, Yue-Feng J Nanobiotechnology Research BACKGROUND: Neuroinflammation is an important component mechanism in the development of depression. Exosomal transfer of MDD-associated microRNAs (miRNAs) from neurons to microglia might exacerbate neuronal cell inflammatory injury. RESULTS: By sequence identification, we found significantly higher miR-9-5p expression levels in serum exosomes from MDD patients than healthy control (HC) subjects. Then, in cultured cell model, we observed that BV2 microglial cells internalized PC12 neuron cell-derived exosomes while successfully transferring miR-9-5p. MiR-9-5p promoted M1 polarization in microglia and led to over releasing of proinflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), which exacerbated neurological damage. Furthermore, we identified suppressor of cytokine signaling 2 (SOCS2) as a direct target of miR-9-5p. Overexpression of miR-9-5p suppressed SOCS2 expression and reactivated SOCS2-repressed Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathways. Consistently, we confirmed that adeno-associated virus (AAV)-mediated overexpression of miR-9-5p polarized microglia toward the M1 phenotype and exacerbated depressive symptoms in chronic unpredictable mild stress (CUMS) mouse mode. CONCLUSION: MiR-9-5p was transferred from neurons to microglia in an exosomal way, leading to M1 polarization of microglia and further neuronal injury. The expression and secretion of miR-9-5p might be novel therapeutic targets for MDD. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-022-01332-w. BioMed Central 2022-03-09 /pmc/articles/PMC8905830/ /pubmed/35264203 http://dx.doi.org/10.1186/s12951-022-01332-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Xian, Xian Cai, Li-Li Li, Yang Wang, Ran-Chao Xu, Yu-Hao Chen, Ya-Jie Xie, Yu-Hang Zhu, Xiao-Lan Li, Yue-Feng Neuron secrete exosomes containing miR-9-5p to promote polarization of M1 microglia in depression |
title | Neuron secrete exosomes containing miR-9-5p to promote polarization of M1 microglia in depression |
title_full | Neuron secrete exosomes containing miR-9-5p to promote polarization of M1 microglia in depression |
title_fullStr | Neuron secrete exosomes containing miR-9-5p to promote polarization of M1 microglia in depression |
title_full_unstemmed | Neuron secrete exosomes containing miR-9-5p to promote polarization of M1 microglia in depression |
title_short | Neuron secrete exosomes containing miR-9-5p to promote polarization of M1 microglia in depression |
title_sort | neuron secrete exosomes containing mir-9-5p to promote polarization of m1 microglia in depression |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8905830/ https://www.ncbi.nlm.nih.gov/pubmed/35264203 http://dx.doi.org/10.1186/s12951-022-01332-w |
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