Cargando…
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...
Autores principales: | , , |
---|---|
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 |
_version_ | 1783569232220389376 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7415932 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Leibniz Research Centre for Working Environment and Human Factors |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT chounchaysupanee microgliaenhancesproliferationofneuralprogenitorcellsinaninvitromodelofhypoxicischemicinjury AT noctorstephenc microgliaenhancesproliferationofneuralprogenitorcellsinaninvitromodelofhypoxicischemicinjury AT chutabhakdikulnuanchan microgliaenhancesproliferationofneuralprogenitorcellsinaninvitromodelofhypoxicischemicinjury |