Early-life stress lastingly impacts microglial transcriptome and function under basal and immune-challenged conditions Article Swipe
Kitty Reemst
,
Laura Kracht
,
Janssen M. Kotah
,
Reza Rahimian
,
Astrid A.S. van Irsen
,
Gonzalo Congains Sotomayor
,
Laura N. Verboon
,
Nieske Brouwer
,
Sophie Simard
,
Gustavo Turecki
,
Naguib Mechawar
,
Susanne M. Kooistra
,
Bart J. L. Eggen
,
Anikó Kőrösi
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1101/2022.07.13.499949
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1101/2022.07.13.499949
Early-life stress (ELS) leads to increased vulnerability to psychiatric disorders including depression later in life. Neuroinflammatory processes have been implicated in ELS-induced negative health outcomes, but how ELS impacts microglia, the main tissue-resident macrophages of the central nervous system, is unknown. Here, we determined the effects of ELS induced by limited bedding and nesting material during the first week of life (postnatal days [P]2 – 9) on microglial i) morphology; ii) hippocampal gene expression; and iii) synaptosome phagocytic capacity in male pups (P9) and adult (P200) mice. The hippocampus of ELS-exposed adult mice displayed altered proportions of morphological subtypes of microglia, as well as microglial transcriptomic changes related to the tumor necrosis factor response and protein ubiquitination. ELS exposure leads to distinct gene expression profiles during microglial development from P9 to P200 and in response to an LPS challenge at P200. Functionally, synaptosomes from ELS-exposed mice were phagocytosed less by age-matched microglia. At P200, but not P9, ELS microglia showed reduced synaptosome phagocytic capacity when compared to CTRL microglia. Lastly, we confirmed the ELS-induced increased expression of the phagocytosis-related gene GAS6 that we observed in mice, in the dentate gyrus of individuals with a history of child abuse using in situ hybridization. These findings reveal persistent effects of ELS on microglial function and suggest that altered microglial phagocytic capacity is a key contributor to ELS-induced phenotypes.
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- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2022.07.13.499949
- https://www.biorxiv.org/content/biorxiv/early/2022/07/16/2022.07.13.499949.full.pdf
- OA Status
- green
- Cited By
- 2
- References
- 99
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4285677444
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4285677444Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2022.07.13.499949Digital Object Identifier
- Title
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Early-life stress lastingly impacts microglial transcriptome and function under basal and immune-challenged conditionsWork title
- Type
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preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
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2022Year of publication
- Publication date
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2022-07-16Full publication date if available
- Authors
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Kitty Reemst, Laura Kracht, Janssen M. Kotah, Reza Rahimian, Astrid A.S. van Irsen, Gonzalo Congains Sotomayor, Laura N. Verboon, Nieske Brouwer, Sophie Simard, Gustavo Turecki, Naguib Mechawar, Susanne M. Kooistra, Bart J. L. Eggen, Anikó KőrösiList of authors in order
- Landing page
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https://doi.org/10.1101/2022.07.13.499949Publisher landing page
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https://www.biorxiv.org/content/biorxiv/early/2022/07/16/2022.07.13.499949.full.pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
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-
greenOpen access status per OpenAlex
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https://www.biorxiv.org/content/biorxiv/early/2022/07/16/2022.07.13.499949.full.pdfDirect OA link when available
- Concepts
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Microglia, Transcriptome, Hippocampal formation, Biology, Dentate gyrus, Immune system, Hippocampus, Phagocytosis, Neuroscience, Basal (medicine), Phenotype, Gene expression, Immunology, Endocrinology, Gene, Inflammation, Genetics, InsulinTop concepts (fields/topics) attached by OpenAlex
- Cited by
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2Total citation count in OpenAlex
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2022: 2Per-year citation counts (last 5 years)
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99Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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