Chronic gut inflammation differentially modulates mitochondrial and antioxidant transcriptional programs in limbic brain structures
Bibliographic record
Abstract
Chronic inflammatory diseases are frequently comorbid with depression and anxiety, often persisting during periods of inflammatory remission. This suggests functional changes to neural circuits involved in the contextual regulation of motivation and threat processing. Here, we test how chronic gut inflammation evoked by dextran sodium sulfate (DSS) affects gene expression in several limbic brain structures associated with these functions. We assessed post-mortem expression of mRNA transcripts in the anterior cingulate cortex (ACC), CA1 hippocampus, nucleus accumbens (NAc), and primary motor cortex (M1) as a non-limbic control. The levels of mRNA associated with mitochondrial function, inflammation, and synaptic connectivity were altered in DSS-treated animals, but the specific pattern of changes was heterogeneous among brain structures. Chronic gut inflammation affected transcript expression in the CA1 and NAc more so than in the ACC and M1. These differences involved genes related to antioxidant systems and mitochondrial function. For example, expression of the cytochrome oxidase 1 gene mt-co1, which is necessary for oxidative phosphorylation, was reduced in ACC and NAc of DSS animals, suggesting reduced capacity for ATP production in these regions. Markers of gut inflammation correlated with expression of several transcripts in the ACC, including markers of synapses and GABA synthesis. The NAc showed strong correlations of mitochondrial function and measures of mitochondrial fission, inflammation, synaptic connectivity, and GABA synthesis. In sum, the effects of chronic relapsing gut inflammation on mitochondrial and antioxidant transcriptional programs were heterogeneous across key limbic brain structures.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".