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Microglia enhances proliferation of neural progenitor cells in an in vitro model of hypoxic-ischemic injury

Microglial cells are the primary immune cells in the central nervous system. In the mature brain, microglia perform functions that include eliminating pathogens and clearing dead/dying cells and cellular debris through phagocytosis. In the immature brain, microglia perform functions that include syn...

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Autores principales: Chounchay, Supanee, Noctor, Stephen C., Chutabhakdikul, Nuanchan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Leibniz Research Centre for Working Environment and Human Factors 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415932/
https://www.ncbi.nlm.nih.gov/pubmed/32788909
http://dx.doi.org/10.17179/excli2020-2249
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author Chounchay, Supanee
Noctor, Stephen C.
Chutabhakdikul, Nuanchan
author_facet Chounchay, Supanee
Noctor, Stephen C.
Chutabhakdikul, Nuanchan
author_sort Chounchay, Supanee
collection PubMed
description Microglial cells are the primary immune cells in the central nervous system. In the mature brain, microglia perform functions that include eliminating pathogens and clearing dead/dying cells and cellular debris through phagocytosis. In the immature brain, microglia perform functions that include synapse development and the regulation of cell production through extensive contact with and phagocytosis of neural progenitor cells (NPCs). However, the functional role of microglia in the proliferation and differentiation of NPCs under hypoxic-ischemic (HI) injury is not clear. Here, we tested the hypothesis that microglia enhance NPCs proliferation following HI insult. Primary NPCs cultures were divided into four treatment groups: 1) normoxic NPCs (NN); 2) normoxic NPCs cocultured with microglia (NN+M); 3) hypoxic NPCs (HN); and 4) hypoxic NPCs cocultured with microglia (HN+M). Hypoxic-ischemic injury was induced by pretreatment of the cell cultures with 100 µM deferoxamine mesylate (DFO). NPCs treated with 100 µM DFO (HN groups) for 24 hours had significantly increased expression of hypoxia-inducible factor 1 alpha (HIF-1α), a marker of hypoxic cells. Cell number, protein expression, mitosis, and cell cycle phase were examined, and the data were compared between the four groups. We found that the number of cells expressing the NPCs marker Sox2 increased significantly in the HN+M group and that the number of PH3-positive cells increased in the HN+M group; flow cytometry analysis showed a significant increase in the percentage of cells in the G2/M phase in the HN+M group. In summary, these results support the concept that microglia enhance the survival of NPCs under HI injury by increasing NPCs proliferation, survival, and differentiation. These results further suggest that microglia may induce neuroprotective effects after hypoxic injury that can be explored to develop novel therapeutic strategies for the treatment of HI injury in the immature brain.
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spelling pubmed-74159322020-08-11 Microglia enhances proliferation of neural progenitor cells in an in vitro model of hypoxic-ischemic injury Chounchay, Supanee Noctor, Stephen C. Chutabhakdikul, Nuanchan EXCLI J Original Article Microglial cells are the primary immune cells in the central nervous system. In the mature brain, microglia perform functions that include eliminating pathogens and clearing dead/dying cells and cellular debris through phagocytosis. In the immature brain, microglia perform functions that include synapse development and the regulation of cell production through extensive contact with and phagocytosis of neural progenitor cells (NPCs). However, the functional role of microglia in the proliferation and differentiation of NPCs under hypoxic-ischemic (HI) injury is not clear. Here, we tested the hypothesis that microglia enhance NPCs proliferation following HI insult. Primary NPCs cultures were divided into four treatment groups: 1) normoxic NPCs (NN); 2) normoxic NPCs cocultured with microglia (NN+M); 3) hypoxic NPCs (HN); and 4) hypoxic NPCs cocultured with microglia (HN+M). Hypoxic-ischemic injury was induced by pretreatment of the cell cultures with 100 µM deferoxamine mesylate (DFO). NPCs treated with 100 µM DFO (HN groups) for 24 hours had significantly increased expression of hypoxia-inducible factor 1 alpha (HIF-1α), a marker of hypoxic cells. Cell number, protein expression, mitosis, and cell cycle phase were examined, and the data were compared between the four groups. We found that the number of cells expressing the NPCs marker Sox2 increased significantly in the HN+M group and that the number of PH3-positive cells increased in the HN+M group; flow cytometry analysis showed a significant increase in the percentage of cells in the G2/M phase in the HN+M group. In summary, these results support the concept that microglia enhance the survival of NPCs under HI injury by increasing NPCs proliferation, survival, and differentiation. These results further suggest that microglia may induce neuroprotective effects after hypoxic injury that can be explored to develop novel therapeutic strategies for the treatment of HI injury in the immature brain. Leibniz Research Centre for Working Environment and Human Factors 2020-07-03 /pmc/articles/PMC7415932/ /pubmed/32788909 http://dx.doi.org/10.17179/excli2020-2249 Text en Copyright © 2020 Chounchay et al. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (http://creativecommons.org/licenses/by/4.0/) You are free to copy, distribute and transmit the work, provided the original author and source are credited.
spellingShingle Original Article
Chounchay, Supanee
Noctor, Stephen C.
Chutabhakdikul, Nuanchan
Microglia enhances proliferation of neural progenitor cells in an in vitro model of hypoxic-ischemic injury
title Microglia enhances proliferation of neural progenitor cells in an in vitro model of hypoxic-ischemic injury
title_full Microglia enhances proliferation of neural progenitor cells in an in vitro model of hypoxic-ischemic injury
title_fullStr Microglia enhances proliferation of neural progenitor cells in an in vitro model of hypoxic-ischemic injury
title_full_unstemmed Microglia enhances proliferation of neural progenitor cells in an in vitro model of hypoxic-ischemic injury
title_short Microglia enhances proliferation of neural progenitor cells in an in vitro model of hypoxic-ischemic injury
title_sort microglia enhances proliferation of neural progenitor cells in an in vitro model of hypoxic-ischemic injury
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415932/
https://www.ncbi.nlm.nih.gov/pubmed/32788909
http://dx.doi.org/10.17179/excli2020-2249
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AT chutabhakdikulnuanchan microgliaenhancesproliferationofneuralprogenitorcellsinaninvitromodelofhypoxicischemicinjury