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Characterization of macrophages from schizophrenia patients

Genetic, epidemiological and post mortem studies have described an association between schizophrenia (SCZ) and the immune system. Microglia, the tissue-resident macrophages of the brain, not only play an essential role in inflammatory processes, but also in neurodevelopment and synapse refinement. I...

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Autores principales: Ormel, Paul R., van Mierlo, Hans C., Litjens, Manja, Strien, Miriam E. van, Hol, Elly M., Kahn, René S., de Witte, Lot D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5686077/
https://www.ncbi.nlm.nih.gov/pubmed/29138398
http://dx.doi.org/10.1038/s41537-017-0042-4
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author Ormel, Paul R.
van Mierlo, Hans C.
Litjens, Manja
Strien, Miriam E. van
Hol, Elly M.
Kahn, René S.
de Witte, Lot D.
author_facet Ormel, Paul R.
van Mierlo, Hans C.
Litjens, Manja
Strien, Miriam E. van
Hol, Elly M.
Kahn, René S.
de Witte, Lot D.
author_sort Ormel, Paul R.
collection PubMed
description Genetic, epidemiological and post mortem studies have described an association between schizophrenia (SCZ) and the immune system. Microglia, the tissue-resident macrophages of the brain, not only play an essential role in inflammatory processes, but also in neurodevelopment and synapse refinement. It has therefore been hypothesized that aberrant functioning of these myeloid immune cells is involved in SCZ pathogenesis. Until now cellular research into the role of myeloid cells in SCZ has been limited to monocytes and functional assays are lacking. In this study we used monocyte-derived macrophages (mo-MΦs) as a model for macrophages and microglia in the CNS and examined two main functions: Inflammatory responses and expression and regulation of synapse refinement molecules. The expression of 24 genes involved in these key functions was assessed. Mo-MΦs were generated from 15 SCZ patients and 15 healthy controls. The cells were exposed to pro-inflammatory and anti-inflammatory stimuli (LPS, R848, IL-4 and dexamethasone), and the response was measured by qPCR and ELISA analyses. One of the genes of interest, P2RX7 that is associated with psychiatric diseases, was significantly reduced in expression after LPS stimulation in SCZ patients. None of the other assessed characteristics were different in this functional screen between mo-MΦs from SCZ patients compared to controls. Although these data suggest that overall the function of macrophages in SCZ is not impaired, further studies with larger groups that enable the possibility to study clinical subgroups and perform additional screenings to asses the full phenotype of the mo-MΦs are needed to strengthen this conclusion.
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spelling pubmed-56860772017-11-17 Characterization of macrophages from schizophrenia patients Ormel, Paul R. van Mierlo, Hans C. Litjens, Manja Strien, Miriam E. van Hol, Elly M. Kahn, René S. de Witte, Lot D. NPJ Schizophr Article Genetic, epidemiological and post mortem studies have described an association between schizophrenia (SCZ) and the immune system. Microglia, the tissue-resident macrophages of the brain, not only play an essential role in inflammatory processes, but also in neurodevelopment and synapse refinement. It has therefore been hypothesized that aberrant functioning of these myeloid immune cells is involved in SCZ pathogenesis. Until now cellular research into the role of myeloid cells in SCZ has been limited to monocytes and functional assays are lacking. In this study we used monocyte-derived macrophages (mo-MΦs) as a model for macrophages and microglia in the CNS and examined two main functions: Inflammatory responses and expression and regulation of synapse refinement molecules. The expression of 24 genes involved in these key functions was assessed. Mo-MΦs were generated from 15 SCZ patients and 15 healthy controls. The cells were exposed to pro-inflammatory and anti-inflammatory stimuli (LPS, R848, IL-4 and dexamethasone), and the response was measured by qPCR and ELISA analyses. One of the genes of interest, P2RX7 that is associated with psychiatric diseases, was significantly reduced in expression after LPS stimulation in SCZ patients. None of the other assessed characteristics were different in this functional screen between mo-MΦs from SCZ patients compared to controls. Although these data suggest that overall the function of macrophages in SCZ is not impaired, further studies with larger groups that enable the possibility to study clinical subgroups and perform additional screenings to asses the full phenotype of the mo-MΦs are needed to strengthen this conclusion. Nature Publishing Group UK 2017-11-14 /pmc/articles/PMC5686077/ /pubmed/29138398 http://dx.doi.org/10.1038/s41537-017-0042-4 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Ormel, Paul R.
van Mierlo, Hans C.
Litjens, Manja
Strien, Miriam E. van
Hol, Elly M.
Kahn, René S.
de Witte, Lot D.
Characterization of macrophages from schizophrenia patients
title Characterization of macrophages from schizophrenia patients
title_full Characterization of macrophages from schizophrenia patients
title_fullStr Characterization of macrophages from schizophrenia patients
title_full_unstemmed Characterization of macrophages from schizophrenia patients
title_short Characterization of macrophages from schizophrenia patients
title_sort characterization of macrophages from schizophrenia patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5686077/
https://www.ncbi.nlm.nih.gov/pubmed/29138398
http://dx.doi.org/10.1038/s41537-017-0042-4
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