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Neuregulin-1 Fosters Supportive Interactions between Microglia and Neural Stem/Progenitor Cells

Microglia play diverse roles in homeostasis and pathology of the central nervous system (CNS). Their response to injury or insult is critical for initiating neuroinflammation and tissue damage as well as resolution of inflammation and wound healing. Changes to the microenvironment of microglia appea...

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Autores principales: Shahriary, Ghazaleh M., Kataria, Hardeep, Karimi-Abdolrezaee, Soheila
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476022/
https://www.ncbi.nlm.nih.gov/pubmed/31089334
http://dx.doi.org/10.1155/2019/8397158
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author Shahriary, Ghazaleh M.
Kataria, Hardeep
Karimi-Abdolrezaee, Soheila
author_facet Shahriary, Ghazaleh M.
Kataria, Hardeep
Karimi-Abdolrezaee, Soheila
author_sort Shahriary, Ghazaleh M.
collection PubMed
description Microglia play diverse roles in homeostasis and pathology of the central nervous system (CNS). Their response to injury or insult is critical for initiating neuroinflammation and tissue damage as well as resolution of inflammation and wound healing. Changes to the microenvironment of microglia appear to be a key determinant of their phenotype and their role in the endogenous repair process in the injured or diseased CNS. Our recent findings have identified a positive role for neuregulin-1 (Nrg-1) in regulating immune response in spinal cord injury and focal demyelinating lesions. We show that increasing the tissue availability of Nrg-1 after injury can promote endogenous repair by modulating neuroinflammation. In the present study, we sought to elucidate the specific role of Nrg-1 in regulating microglial activity and more importantly their influence on the behavior of neural stem/progenitor cells (NPCs). Using injury-relevant in vitro systems, we demonstrate that Nrg-1 attenuates the expression of proinflammatory mediators in activated microglia. Moreover, we provide novel evidence that availability of Nrg-1 can restore the otherwise suppressed phagocytic ability of proinflammatory microglia. Interestingly, the presence of Nrg-1 in the microenvironment of proinflammatory microglia mitigates their inhibitory effects on NPC proliferation. Nrg-1 treated proinflammatory microglia also augment mobilization of NPCs, while they had no influence on their suppressive effects on NPC differentiation. Mechanistically, we show that Nrg-1 enhances the interactions of proinflammatory microglia and NPCs, at least in part, through reduction of TNF-α expression in microglia. These findings provide new insights into the endogenous regulation of microglia-NPC interactions and identify new potential targets for optimizing this important crosstalk during the regenerative process after CNS injury and neuroinflammatory conditions.
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spelling pubmed-64760222019-05-14 Neuregulin-1 Fosters Supportive Interactions between Microglia and Neural Stem/Progenitor Cells Shahriary, Ghazaleh M. Kataria, Hardeep Karimi-Abdolrezaee, Soheila Stem Cells Int Research Article Microglia play diverse roles in homeostasis and pathology of the central nervous system (CNS). Their response to injury or insult is critical for initiating neuroinflammation and tissue damage as well as resolution of inflammation and wound healing. Changes to the microenvironment of microglia appear to be a key determinant of their phenotype and their role in the endogenous repair process in the injured or diseased CNS. Our recent findings have identified a positive role for neuregulin-1 (Nrg-1) in regulating immune response in spinal cord injury and focal demyelinating lesions. We show that increasing the tissue availability of Nrg-1 after injury can promote endogenous repair by modulating neuroinflammation. In the present study, we sought to elucidate the specific role of Nrg-1 in regulating microglial activity and more importantly their influence on the behavior of neural stem/progenitor cells (NPCs). Using injury-relevant in vitro systems, we demonstrate that Nrg-1 attenuates the expression of proinflammatory mediators in activated microglia. Moreover, we provide novel evidence that availability of Nrg-1 can restore the otherwise suppressed phagocytic ability of proinflammatory microglia. Interestingly, the presence of Nrg-1 in the microenvironment of proinflammatory microglia mitigates their inhibitory effects on NPC proliferation. Nrg-1 treated proinflammatory microglia also augment mobilization of NPCs, while they had no influence on their suppressive effects on NPC differentiation. Mechanistically, we show that Nrg-1 enhances the interactions of proinflammatory microglia and NPCs, at least in part, through reduction of TNF-α expression in microglia. These findings provide new insights into the endogenous regulation of microglia-NPC interactions and identify new potential targets for optimizing this important crosstalk during the regenerative process after CNS injury and neuroinflammatory conditions. Hindawi 2019-04-07 /pmc/articles/PMC6476022/ /pubmed/31089334 http://dx.doi.org/10.1155/2019/8397158 Text en Copyright © 2019 Ghazaleh M. Shahriary et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Shahriary, Ghazaleh M.
Kataria, Hardeep
Karimi-Abdolrezaee, Soheila
Neuregulin-1 Fosters Supportive Interactions between Microglia and Neural Stem/Progenitor Cells
title Neuregulin-1 Fosters Supportive Interactions between Microglia and Neural Stem/Progenitor Cells
title_full Neuregulin-1 Fosters Supportive Interactions between Microglia and Neural Stem/Progenitor Cells
title_fullStr Neuregulin-1 Fosters Supportive Interactions between Microglia and Neural Stem/Progenitor Cells
title_full_unstemmed Neuregulin-1 Fosters Supportive Interactions between Microglia and Neural Stem/Progenitor Cells
title_short Neuregulin-1 Fosters Supportive Interactions between Microglia and Neural Stem/Progenitor Cells
title_sort neuregulin-1 fosters supportive interactions between microglia and neural stem/progenitor cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476022/
https://www.ncbi.nlm.nih.gov/pubmed/31089334
http://dx.doi.org/10.1155/2019/8397158
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