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Related Concept Videos

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Cholinergic Neurons: Neurotransmission

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Cholinergic neurotransmission involves the synthesis and the release of acetylcholine (ACh) in order to transmit nerve impulses across the synapse. The process begins with the synthesis of acetyl CoA, a precursor for ACh, from ATP, acetate, and coenzyme A in the mitochondria. Choline, another vital precursor, is transported inside the neuron through choline transporters, including high-affinity choline transporter CHT1, low-affinity choline transporter CTL1, and lower-affinity choline...
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Related Experiment Video

Updated: Jul 9, 2025

Increased Recovery Time and Decreased LPS Administration to Study the Vagus Nerve Stimulation Mechanisms in Limited Inflammatory Responses
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Circulating extracellular choline acetyltransferase regulates inflammation.

Arielle H Gabalski1,2, Aisling Tynan1, Tea Tsaava1

  • 1Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research, Manhasset, New York, USA.

Journal of Internal Medicine
|November 27, 2023
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Extracellular choline acetyltransferase (ChAT) activity in plasma increases during inflammation and helps reduce inflammatory responses. This suggests ChAT could be a potential therapeutic target for inflammatory conditions.

Keywords:
acetylcholineanti-inflammatoryinflammatory bowel diseaseinflammatory reflexsepsis

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Area of Science:

  • Neuroscience
  • Immunology
  • Biochemistry

Background:

  • Choline acetyltransferase (ChAT) is crucial for acetylcholine synthesis, a key mediator in the cholinergic anti-inflammatory pathway.
  • While cytoplasmic ChAT in neurons is well-studied, its extracellular presence and function remain largely unknown.

Purpose of the Study:

  • To investigate if extracellular ChAT activity responds to inflammation and modulates cytokine production.
  • To evaluate ChAT as a potential regulator of inflammation and a therapeutic agent.

Main Methods:

  • Developed novel methods to quantify ChAT activity in plasma.
  • Assessed changes in plasma ChAT activity following inflammatory challenges in mice.
  • Utilized recombinant ChAT (r-ChAT) and anti-ChAT antibodies to study ChAT's role in inflammation.
  • Examined plasma ChAT levels in human sepsis patients.

Main Results:

  • Active ChAT circulates in mouse plasma and its activity increases in response to endotoxin and vagus nerve stimulation.
  • Increased plasma ChAT activity correlates with decreased tumor necrosis factor (TNF) levels.
  • Administering r-ChAT reduced TNF production and inflammatory bowel disease activity in a preclinical model.
  • Elevated plasma ChAT levels were observed in human sepsis patients.

Conclusions:

  • Extracellular ChAT activity acts as a counter-regulator of inflammation.
  • ChAT holds potential as a therapeutic agent for inflammatory diseases.