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Journal article

cFOS expression in the prefrontal cortex correlates with altered cerebral metabolism in developing germ-free mice

Abstract:
IntroductionThe microbiota plays a critical role in modulating various aspects of host physiology, particularly through the microbiota-gut-brain (MGB) axis. However, the mechanisms that transduce and affect gut-to-brain communication are still not well understood. Recent studies have demonstrated that dysbiosis of the microbiome is associated with anxiety and depressive symptoms, which are common complications of metabolic syndrome. Germ-free (GF) animal models offer a valuable tool for studying the causal effects of microbiota on the host.MethodsWe employed gene expression and nuclear magnetic resonance (NMR)-based metabolomic techniques to investigate the relationships between brain plasticity and immune gene expression, peripheral immunity, and cerebral and liver metabolism in GF and specific pathogen-free (SPF) mice.ResultsOur principal findings revealed that brain acetate (p = 0.012) was significantly reduced in GF relative to SPF mice, whereas glutamate (p = 0.0013), glutamine (p = 0.0006), and N-acetyl aspartate (p = 0.0046) metabolites were increased. Notably, cFOS mRNA expression, which was significantly decreased in the prefrontal cortex of GF mice relative to SPF mice (p = 0.044), correlated with the abundance of a number of key brain metabolites altered by the GF phenotype, including glutamate and glutamine.DiscussionThese results highlight the connection between the GF phenotype, altered brain metabolism, and immediate-early gene expression. The study provides insight into potential mechanisms by which microbiota can regulate neurotransmission through modulation of the host’s brain and liver metabolome, which may have implications for stress-related psychiatric disorders such as anxiety.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.3389/fnmol.2023.1155620

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Institution:
University of Oxford
Role:
Author
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Institution:
University of Oxford
Role:
Author
ORCID:
0000-0003-1380-6655
More by this author
Institution:
University of Oxford
Role:
Author
ORCID:
0000-0001-8781-7459


Publisher:
Frontiers Media
Journal:
Frontiers in Molecular Neuroscience More from this journal
Volume:
16
Pages:
1155620-1155620
Article number:
1155620
Publication date:
2023-04-20
DOI:
EISSN:
1662-5099
ISSN:
1662-5099


Language:
English
Keywords:
Pubs id:
1340510
Local pid:
pubs:1340510
Source identifiers:
W4366548066
Deposit date:
2026-05-07
ARK identifier:
This ORA record was generated from metadata provided by an external service. It has not been edited by the ORA Team.

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