ArticleMolecular medicine (Cambridge, Mass.)2024
M1 cholinergic signaling in the brain modulates cytokine levels and splenic cell sub-phenotypes following cecal ligation and puncture.
Article in Molecular medicine (Cambridge, Mass.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
5 citing papers in PubMed, 1 synthesis or guideline pooled it, 7 citations in OpenAlex.
- The core role of central nervous system in sepsis-related organ damage.Frontiers in immunology · 2025Pooled it
- Optimization of Preclinical Rodent Research Models of Human Shock: Part One Intra-Abdominal Sepsis.Shock (Augusta, Ga.) · 2026Review
- Loss of M1 Acetylcholine Receptor-mediated Orexinergic Activity Contributes to Immune Dysfunction in Experimental Sepsis.Research square · 2025Article
- Novel opportunities for treating complex neuropsychiatric and neurocognitive conditions based on recent developments with xanomeline.Frontiers in psychiatry · 2025Article
- The Modulation of Neuroimmune Responses in Peripheral Inflammation.Journal of inflammation research · 2025Review
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe contribution of the central nervous system to sepsis pathobiology is incompletely understood. In previous studies, administration of endotoxin to mice decreased activity of the vagus anti-inflammatory reflex. Treatment with the centrally-acting M1 muscarinic acetylcholine (ACh) receptor (M1AChR) attenuated this endotoxin-mediated change. We hypothesize that decreased M1AChR-mediated activity contributes to inflammation following cecal ligation and puncture (CLP), a mouse model of sepsis.
methodsIn male C57Bl/6 mice, we quantified basal forebrain cholinergic activity (immunostaining), hippocampal neuronal activity, serum cytokine/chemokine levels (ELISA) and splenic cell subtypes (flow cytometry) at baseline, following CLP and following CLP in mice also treated with the M1AChR agonist xanomeline.
resultsAt 48 h. post-CLP, activity in basal forebrain cells expressing choline acetyltransferase (ChAT) was half of that observed at baseline. Lower activity was also noted in the hippocampus, which contains projections from ChAT-expressing basal forebrain neurons. Serum levels of TNFα, IL-1β, MIP-1α, IL-6, KC and G-CSF were higher post-CLP than at baseline. Post-CLP numbers of splenic macrophages and inflammatory monocytes, TNFα
conclusionOur findings indicate that M1AChR-mediated responses modulate CLP-induced alterations in serum levels of some, but not all, cytokines/chemokines and affected splenic immune response phenotypes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.