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Regulation of synaptic connectivity in schizophrenia spectrum by mutual neuron-microglia interaction
The examination of post-mortem brain tissue suggests synaptic loss as a central pathological hallmark of schizophrenia spectrum (SCZ), which is potentially related to activated microglia and increased inflammation. Induced pluripotent stem cells serve as a source for neurons and microglia-like cells...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10147621/ https://www.ncbi.nlm.nih.gov/pubmed/37117634 http://dx.doi.org/10.1038/s42003-023-04852-9 |
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author | Breitmeyer, Ricarda Vogel, Sabrina Heider, Johanna Hartmann, Sophia-Marie Wüst, Richard Keller, Anna-Lena Binner, Anna Fitzgerald, Julia C. Fallgatter, Andreas J. Volkmer, Hansjürgen |
author_facet | Breitmeyer, Ricarda Vogel, Sabrina Heider, Johanna Hartmann, Sophia-Marie Wüst, Richard Keller, Anna-Lena Binner, Anna Fitzgerald, Julia C. Fallgatter, Andreas J. Volkmer, Hansjürgen |
author_sort | Breitmeyer, Ricarda |
collection | PubMed |
description | The examination of post-mortem brain tissue suggests synaptic loss as a central pathological hallmark of schizophrenia spectrum (SCZ), which is potentially related to activated microglia and increased inflammation. Induced pluripotent stem cells serve as a source for neurons and microglia-like cells to address neuron-microglia interactions. Here, we present a co-culture model of neurons and microglia, both of human origin, to show increased susceptibility of neurons to microglia-like cells derived from SCZ patients. Analysis of IBA-1 expression, NFκB signaling, transcription of inflammasome-related genes, and caspase-1 activation shows that enhanced, intrinsic inflammasome activation in patient-derived microglia exacerbates neuronal deficits such as synaptic loss in SCZ. Anti-inflammatory pretreatment of microglia with minocycline specifically rescued aberrant synapse loss in SCZ and reduced microglial activation. These findings open up possibilities for further research in larger cohorts, focused clinical work and longitudinal studies that could facilitate earlier therapeutic intervention. |
format | Online Article Text |
id | pubmed-10147621 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-101476212023-04-30 Regulation of synaptic connectivity in schizophrenia spectrum by mutual neuron-microglia interaction Breitmeyer, Ricarda Vogel, Sabrina Heider, Johanna Hartmann, Sophia-Marie Wüst, Richard Keller, Anna-Lena Binner, Anna Fitzgerald, Julia C. Fallgatter, Andreas J. Volkmer, Hansjürgen Commun Biol Article The examination of post-mortem brain tissue suggests synaptic loss as a central pathological hallmark of schizophrenia spectrum (SCZ), which is potentially related to activated microglia and increased inflammation. Induced pluripotent stem cells serve as a source for neurons and microglia-like cells to address neuron-microglia interactions. Here, we present a co-culture model of neurons and microglia, both of human origin, to show increased susceptibility of neurons to microglia-like cells derived from SCZ patients. Analysis of IBA-1 expression, NFκB signaling, transcription of inflammasome-related genes, and caspase-1 activation shows that enhanced, intrinsic inflammasome activation in patient-derived microglia exacerbates neuronal deficits such as synaptic loss in SCZ. Anti-inflammatory pretreatment of microglia with minocycline specifically rescued aberrant synapse loss in SCZ and reduced microglial activation. These findings open up possibilities for further research in larger cohorts, focused clinical work and longitudinal studies that could facilitate earlier therapeutic intervention. Nature Publishing Group UK 2023-04-29 /pmc/articles/PMC10147621/ /pubmed/37117634 http://dx.doi.org/10.1038/s42003-023-04852-9 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Breitmeyer, Ricarda Vogel, Sabrina Heider, Johanna Hartmann, Sophia-Marie Wüst, Richard Keller, Anna-Lena Binner, Anna Fitzgerald, Julia C. Fallgatter, Andreas J. Volkmer, Hansjürgen Regulation of synaptic connectivity in schizophrenia spectrum by mutual neuron-microglia interaction |
title | Regulation of synaptic connectivity in schizophrenia spectrum by mutual neuron-microglia interaction |
title_full | Regulation of synaptic connectivity in schizophrenia spectrum by mutual neuron-microglia interaction |
title_fullStr | Regulation of synaptic connectivity in schizophrenia spectrum by mutual neuron-microglia interaction |
title_full_unstemmed | Regulation of synaptic connectivity in schizophrenia spectrum by mutual neuron-microglia interaction |
title_short | Regulation of synaptic connectivity in schizophrenia spectrum by mutual neuron-microglia interaction |
title_sort | regulation of synaptic connectivity in schizophrenia spectrum by mutual neuron-microglia interaction |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10147621/ https://www.ncbi.nlm.nih.gov/pubmed/37117634 http://dx.doi.org/10.1038/s42003-023-04852-9 |
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