Neuronal extracellular microRNAs miR-124 and miR-9 mediate cell-cell communication between neurons and microglia.
HDL
extracellular miRNA
macrophages
miR-124
microglia
Journal
Journal of neuroscience research
ISSN: 1097-4547
Titre abrégé: J Neurosci Res
Pays: United States
ID NLM: 7600111
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
14
06
2018
revised:
27
09
2018
accepted:
28
09
2018
pubmed:
28
10
2018
medline:
2
7
2020
entrez:
28
10
2018
Statut:
ppublish
Résumé
In contrast to peripheral macrophages, microglia in the central nervous system (CNS) exhibit a specific deactivated phenotype; however, it is not clear how this phenotype is maintained. Two alternative hypotheses were postulated recently: (a) microglia differ from peripheral macrophages being derived from the yolk sac (YS), whereas peripheral macrophages originate from bone marrow (BM); (b) microglia acquire a specific phenotype under the influence of the CNS microenvironment. We have previously shown that microglia express miR-124, which was also induced in BM-derived macrophages co-cultured with a neurons. We here investigated the possibility of horizontal transfer of the neuron-specific microRNAs miR-124 and miR-9 from primary neurons to microglia/macrophages. We found that after incubation with neuronal conditioned media (NCM), macrophages downregulated activation markers MHC class II and CD45. Neither cultured adult microglia nor YS- and BM-derived macrophages demonstrated intrinsic levels of miR-124 expression. However, after incubation with NCM, miR-124 was induced in both YS- and BM-derived macrophages. Biochemical analysis demonstrated that the NCM contained miR-124 and miR-9 in complex with small proteins, large high-density lipoproteins (HDLs), and exosomes. MiR-124 and miR-9 were promptly released from neurons, and this process was inhibited by tetrodotoxin, indicating an important role of neuronal electric activity in secretion of these microRNAs. Incubation of macrophages with exogenous miR-124 resulted in efficient translocation of miR-124 into the cytoplasm. This study demonstrates an important role of neuronal miRNAs in communication of neurons with microglia, which favors the hypothesis that microglia acquire a specific phenotype under the influence of the CNS microenvironment.
Identifiants
pubmed: 30367726
doi: 10.1002/jnr.24344
pmc: PMC6587827
doi:
Substances chimiques
Lipoproteins
0
MIRN9 microRNA, mouse
0
MicroRNAs
0
Mirn124 microRNA, mouse
0
Leukocyte Common Antigens
EC 3.1.3.48
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
162-184Informations de copyright
© 2018 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.
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