ArticleFrontiers in immunology2019
Forebrain Cholinergic Signaling Regulates Innate Immune Responses and Inflammation.
Article in Frontiers in immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 77 citations in OpenAlex.
- Pyridostigmine reduces mortality of patients with severe SARS-CoV-2 infection: A phase 2/3 randomized controlled trial.Molecular medicine (Cambridge, Mass.) · 2022Trial
- The Cholinergic Drug Galantamine Alleviates Oxidative Stress Alongside Anti-inflammatory and Cardio-Metabolic Effects in Subjects With the Metabolic Syndrome in a Randomized Trial.Frontiers in immunology · 2021Trial
- Anticholinergic Burden and Progression to Kidney Replacement Therapy.Kidney international reports · 2026Article
- A lifespan staging model of basal forebrain cholinergic vulnerability.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- A Review of Vagus Nerve Stimulation for Disease: Comprehensive Theory and Evidence for Mechanisms of Action.Comprehensive physiology · 2026Review
- The orexin system as a pharmacological target in inflammation: peripheral mechanisms and safety implications.Frontiers in pharmacology · 2026Review
- The hallmarks of neuro-immune reprogramming in cancer.Frontiers in immunology · 2026Review
- Neuroimmune Interactions in Inflammatory Skin and Intestinal Diseases.Journal of inflammation research · 2026Review
- Cholinergic system in patients with chronic kidney disease: cognitive and renal implications.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Review
- Activation of Spinal Astrocyte α2A Adrenoceptors Protects Against Sepsis-Induced Heart Injury Through Inhibition of GABAergic Neuronal Necroptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The cholinergic drug galantamine ameliorates acute and subacute peripheral and brain manifestations of acute respiratory distress syndrome in mice.Scientific reports · 2025Article
- Loss of M1 Acetylcholine Receptor-mediated Orexinergic Activity Contributes to Immune Dysfunction in Experimental Sepsis.Research square · 2025Article
- The Modulation of Neuroimmune Responses in Peripheral Inflammation.Journal of inflammation research · 2025Review
- Novel opportunities for treating complex neuropsychiatric and neurocognitive conditions based on recent developments with xanomeline.Frontiers in psychiatry · 2025Article
- Nicotinic and Muscarinic Acetylcholine Receptor Agonists Counteract Cognitive Impairment in a Rat Model of Doxorubicin-Induced Chemobrain via Attenuation of Multiple Programmed Cell Death Pathways.Molecular neurobiology · 2024Article
- Electrical stimulation of the dorsal motor nucleus of the vagus in male mice can regulate inflammation without affecting the heart rate.Brain, behavior, and immunity · 2024Article
- M1 cholinergic signaling in the brain modulates cytokine levels and splenic cell sub-phenotypes following cecal ligation and puncture.Molecular medicine (Cambridge, Mass.) · 2024Article
- Sex-dependent cholinergic effects on amyloid pathology: A translational study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Activating α7nAChR suppresses systemic inflammation by mitigating neuroinflammation of the medullary visceral zone in sepsis in a rat model.Translational neuroscience · 2024Article
- A brain cytokine-independent switch in cortical activity marks the onset of sickness behavior triggered by acute peripheral inflammation.Journal of neuroinflammation · 2023Article
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 4 countries.
Funding
Abstract
The brain regulates physiological functions integral to survival. However, the insight into brain neuronal regulation of peripheral immune function and the neuromediator systems and pathways involved remains limited. Here, utilizing selective genetic and pharmacological approaches, we studied the role of forebrain cholinergic signaling in the regulation of peripheral immune function and inflammation. Forebrain-selective genetic ablation of acetylcholine release and vagotomy abolished the suppression of serum TNF by the centrally-acting cholinergic drug galantamine in murine endotoxemia. Selective stimulation of acetylcholine action on the M1 muscarinic acetylcholine receptor (M1 mAChR) by central administration of the positive allosteric modulator benzyl quinolone carboxylic acid (BQCA) suppressed serum TNF (TNFα) levels in murine endotoxemia. This effect was recapitulated by peripheral administration of the compound. BQCA also improved survival in murine endotoxemia and these effects were abolished in M1 mAChR knockout (KO) mice. Selective optogenetic stimulation of basal forebrain cholinergic neurons innervating brain regions with abundant M1 mAChR localization reduced serum TNF in endotoxemic mice. These findings reveal that forebrain cholinergic neurons regulate innate immune responses and inflammation, suggesting the possibility that in diseases associated with cholinergic dysfunction, including Alzheimer's disease this anti-inflammatory regulation can be impaired. These results also suggest novel anti-inflammatory approaches based on targeting forebrain cholinergic signaling in sepsis and other disorders characterized by immune dysregulation.
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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.