Abstract:
:Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset neurodegenerative disorder affecting motor neurons (MNs). Evidences indicate that ALS is a non-cell autonomous disease in which glial cells participate in both disease onset and progression. Exosomal transfer of mutant copper-zinc superoxide dismutase 1 (mSOD1) from cell-to-cell was suggested to contribute to disease dissemination. Data from our group and others showed that exosomes from activated cells contain inflammatory-related microRNAs (inflamma-miRNAs) that recapitulate the donor cell. While glia-derived exosomes and their effects in neurons have been addressed by several studies, only a few investigated the influence of motor neuron (MN)-derived exosomes in other cell function, the aim of the present study. We assessed a set of inflamma-miRs in NSC-34 MN-like cells transfected with mutant SOD1(G93A) and extended the study into their derived exosomes (mSOD1 exosomes). Then, the effects produced by mSOD1 exosomes in the activation and polarization of the recipient N9 microglial cells were investigated. Exosomes in coculture with N9 microglia and NSC-34 cells [either transfected with either wild-type (wt) human SOD1 or mutant SOD1(G93A)] showed to be transferred into N9 cells. Increased miR-124 expression was found in mSOD1 NSC-34 cells and in their derived exosomes. Incubation of mSOD1 exosomes with N9 cells determined a sustained 50% reduction in the cell phagocytic ability. It also caused a persistent NF-kB activation and an acute generation of NO, MMP-2, and MMP-9 activation, as well as upregulation of IL-1β, TNF-α, MHC-II, and iNOS gene expression, suggestive of induced M1 polarization. Marked elevation of IL-10, Arginase 1, TREM2, RAGE, and TLR4 mRNA levels, together with increased miR-124, miR-146a, and miR-155, at 24 h incubation, suggest the switch to mixed M1 and M2 subpopulations in the exosome-treated N9 microglial cells. Exosomes from mSOD1 NSC-34 MNs also enhanced the number of senescent-like positive N9 cells. Data suggest that miR-124 is translocated from the mSOD1 MNs to exosomes, which determine early and late phenotypic alterations in the recipient N9-microglial cells. In conclusion, modulation of the inflammatory-associated miR-124, in mSOD1 NSC-34 MNs, with potential benefits in the cargo of their exosomes may reveal a promising therapeutic strategy in halting microglia activation and associated effects in MN degeneration.
journal_name
Front Neuroscijournal_title
Frontiers in neuroscienceauthors
Pinto S,Cunha C,Barbosa M,Vaz AR,Brites Ddoi
10.3389/fnins.2017.00273subject
Has Abstractpub_date
2017-05-17 00:00:00pages
273eissn
1662-4548issn
1662-453Xjournal_volume
11pub_type
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journal_title:Frontiers in neuroscience
pub_type: 杂志文章
doi:10.3389/fnins.2013.00246
更新日期:2013-12-20 00:00:00
abstract::[This retracts the article on p. 303 in vol. 10, PMID: 27445673.]. ...
journal_title:Frontiers in neuroscience
pub_type: 杂志文章,撤回出版物
doi:10.3389/fnins.2016.00465
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journal_title:Frontiers in neuroscience
pub_type: 杂志文章
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journal_title:Frontiers in neuroscience
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doi:10.3389/fnins.2019.00322
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abstract:Purpose:To evaluate the effect of resolution on iron content using quantitative susceptibility mapping (QSM); to verify the consistency of QSM across field strengths and manufacturers in evaluating the iron content of deep gray matter (DGM) of the human brain using subjects from multiple sites; and to establish a susce...
journal_title:Frontiers in neuroscience
pub_type: 杂志文章
doi:10.3389/fnins.2020.607705
更新日期:2021-01-06 00:00:00
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pub_type: 杂志文章,评审
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pub_type: 杂志文章
doi:10.3389/fnins.2020.570744
更新日期:2020-09-25 00:00:00
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journal_title:Frontiers in neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnins.2020.00719
更新日期:2020-07-08 00:00:00
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journal_title:Frontiers in neuroscience
pub_type: 杂志文章
doi:10.3389/fnins.2020.00464
更新日期:2020-05-19 00:00:00
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journal_title:Frontiers in neuroscience
pub_type: 杂志文章
doi:10.3389/fnins.2016.00158
更新日期:2016-04-19 00:00:00
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journal_title:Frontiers in neuroscience
pub_type: 杂志文章
doi:10.3389/fnins.2016.00206
更新日期:2016-05-18 00:00:00
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journal_title:Frontiers in neuroscience
pub_type: 杂志文章
doi:10.3389/fnins.2015.00526
更新日期:2016-01-19 00:00:00
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journal_title:Frontiers in neuroscience
pub_type: 杂志文章
doi:10.3389/fnins.2018.00040
更新日期:2018-02-02 00:00:00
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journal_title:Frontiers in neuroscience
pub_type: 杂志文章
doi:10.3389/fnins.2018.00067
更新日期:2018-02-13 00:00:00
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journal_title:Frontiers in neuroscience
pub_type: 杂志文章
doi:10.3389/fnins.2017.00049
更新日期:2017-02-14 00:00:00
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journal_title:Frontiers in neuroscience
pub_type: 杂志文章
doi:10.3389/fnins.2017.00129
更新日期:2017-03-17 00:00:00
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journal_title:Frontiers in neuroscience
pub_type: 杂志文章
doi:10.3389/fnins.2018.00332
更新日期:2018-06-20 00:00:00
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journal_title:Frontiers in neuroscience
pub_type: 杂志文章
doi:10.3389/fnins.2019.01167
更新日期:2019-10-31 00:00:00
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journal_title:Frontiers in neuroscience
pub_type: 杂志文章
doi:10.3389/fnins.2018.00699
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pub_type: 杂志文章,评审
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journal_title:Frontiers in neuroscience
pub_type: 杂志文章
doi:10.3389/fnins.2015.00273
更新日期:2015-08-04 00:00:00
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journal_title:Frontiers in neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnins.2018.00597
更新日期:2018-08-23 00:00:00
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journal_title:Frontiers in neuroscience
pub_type: 杂志文章
doi:10.3389/fnins.2020.00777
更新日期:2020-09-23 00:00:00
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journal_title:Frontiers in neuroscience
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doi:10.3389/fnins.2018.01036
更新日期:2019-02-04 00:00:00
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journal_title:Frontiers in neuroscience
pub_type: 杂志文章
doi:10.3389/fnins.2015.00163
更新日期:2015-05-05 00:00:00
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pub_type: 杂志文章
doi:10.3389/fnins.2020.00423
更新日期:2020-07-07 00:00:00
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journal_title:Frontiers in neuroscience
pub_type: 杂志文章
doi:10.3389/fnins.2020.00061
更新日期:2020-02-21 00:00:00