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Social interaction-induced activation of RNA splicing in the amygdala of microbiome-deficient mice
Open accessAbstract
Social behaviour is regulated by activity of host-associated microbiota across multiple species. However, the molecular mechanisms mediating this relationship remain elusive. We therefore determined the dynamic, stimulus-dependent transcriptional regulation of germ-free (GF) and GF mice colonised post weaning (exGF) in the amygdala, a brain region critically involved in regulating social interaction. In GF mice the dynamic response seen in controls was attenuated and replaced by a marked increase in expression of splicing factors and alternative exon usage in GF mice upon stimulation, which was even more pronounced in exGF mice. In conclusion, we demonstrate a molecular basis for how the host microbiome is crucial for a normal behavioural response during social interaction. Our data further suggest that social behaviour is correlated with the gene-expression response in the amygdala, established during neurodevelopment as a result of host-microbe interactions. Our findings may help toward understanding neurodevelopmental events leading to social behaviour dysregulation, such as those found in autism spectrum disorders (ASDs).
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“In response to social interaction, there are profound alterations in the transcriptome and spliceosome in the amygdala of GF mice, which may contribute to the social deficits observed (Stilling et al., 2018).”
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“as well as enhanced expression of gene splicing factors and alternative exon usage (Stilling et al., 2018).”
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“Moreover, while a conventionally colonized mouse will prefer to spend more time interacting with a novel conspecific over a familiar one, GF mice are unable to distinguish between either animal, which represents a cognitive deficit in the identification of social novelty (Desbonnet et al., 2014;Stilling et al., 2018).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Stilling et al., 2018
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Metadata
- Authors
- Stilling, R. M., Moloney, G. M., Ryan, F. J., Hoban, A. E., Bastiaanssen, T. F., Shanahan, F., Clarke, G., Claesson, M. J., Dinan, T. G., & Cryan, J. F.
- Affiliations
- University College Cork (IE)
- Corresponding author
- Stilling, Roman M
- Cryan, John F
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2018-05-29
- Volume
- 7
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC5995540
- OpenAlex
- W2805802451
- Cited by
- 106
- References
- 90
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 8 · 2023: 10 · 2022: 13 · 2021: 21 · 2020: 26 · 2019: 15 · 2018: 3
- FWCI
- 5.78
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Arrow@dit (Dublin Institute of Technology) (acceptedVersion)
- Cork Open Research Archive (University College Cork, Ireland) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
- Funders
- Science Foundation Ireland (12/RC/2273)
- Irish Research Council (GOIPD/2014/355)
- Irish Health Board
- National Alliance for Research on Schizophrenia and Depression (20771)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- host microbiome, germ-free mice, amygdala, RNA splicing, social interaction, social behavior, splicing factors, alternative exon usage, host-microbe interactions, brain development, autism spectrum disorder, gene expression regulation
- MeSH terms
- Autism Spectrum Disorder, Gastrointestinal Microbiome, RNA Splicing Factors, Amygdala, Animals, Animal Communication, Disease Models, Animal, Germ-Free Life, Male, Nerve Tissue Proteins, RNA Splicing, Weaning, Mice, Neurogenesis
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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