Basal forebrain cholinergic signaling regulates peripheral cytokine responses (INC1P.349)
Bibliographic record
Abstract
Abstract Brain cholinergic signaling regulates peripheral cytokine release and inflammation (Nat Rev Endocrinol, 2012, 8:743). We have previously shown that the centrally-acting acetylcholinesterase inhibitor galantamine suppresses peripheral pro-inflammatory cytokine release through a brain muscarinic receptor-mediated and vagus nerve-dependent mechanism. Here, we provide insight into the brain mechanisms of this regulation. VAChTNkx21-Cre-flox/flox mice with selective, basal forebrain cholinergic neuron genetic ablation of the vesicular acetylcholine transporter (an important determinant of acetylcholine release), and control VAChTflox/flox mice, were treated with galantamine or saline and subjected to endotoxemia. Galantamine (3mg/kg) i.p. administration suppressed serum TNF levels in control mice only. In addition, serum TNF and IL-10 in VAChTNkx2 1-Cre-flox/flox mice were significantly higher (2.9-fold, P<0.05) and lower (57%, P<0.05) respectively, as compared to control mice. Furthermore, electrical stimulation of the medial septum, an important basal forebrain cholinergic region, significantly lowered serum TNF (79%, P<0.01) and other pro-inflammatory cytokine levels in endotoxemic mice, as compared to sham-stimulation. These results demonstrate a previously unrecognized role of basal forebrain cholinergic signaling in the regulation of peripheral inflammation.
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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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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".