Antipsychotic Seen to Work to Control Gut Inflammation in Early Study

Antipsychotic Seen to Work to Control Gut Inflammation in Early Study

The immune system of the nematode worm Caenorhabditis elegans can be manipulated with antipsychotic drugs — drugs that affect the nervous system — to control inflammation in the gut, researchers reported. The finding suggests that the gut-brain connection seen in worms may exist in people as well, and antipsychotics a way of manipulating the immune system of patients with conditions like inflammatory bowel disease (IBD).

The study, “Neural Inhibition of Dopaminergic Signaling Enhances Immunity in a Cell-Non-autonomous Manner,” was recently published in the journal Current Biology.

Conducted in the laboratory of Alejandro Aballay, PhD, a professor of molecular genetics and microbiology at Duke School of Medicine, the study aimed to understand how the neurotransmitter dopamine — well-known for its affects on the brain’s reward and pleasure centers — controls innate immune responses in the intestines of C. elegans, and how this signaling pathway is involved in the differentiation between good and bad microbial organisms living in the gut.

In a Duke press release, Aballay explains why using C. elegans as an experimental model was important. “Worms have evolved mechanisms to deal with colonizing bacteria. That is true for us as well,” he said. “Humans have trillions of microorganisms in our guts, and we have to be careful when activating antimicrobial defenses so that we mainly target potentially harmful microbes, without damaging our good bacteria — or even our own cells — in the process.”

To conduct this dopamine signaling assessment, Aballay and his team blocked the neurotransmitter’s normal mechanisms with the drug chlorpromazine, an antipsychotic drug most often prescribed to treat patients with schizophrenia and manic depression, in one set of C. elegans.

These animals were then compared to another set of worms kept as controls, which did not have their dopamine manipulated.

After a comparative analysis of both groups, the researchers found that:

  • C. elegans who received chlorpromazine were more resistant to infection by the common pathogen Pseudomonas aeruginosa than control worms
  • C. elegans whose dopamine levels were manipulated to be artificially high after chlorpromazine treatment were no longer resistant to Pseudomonas aeruginosa

The findings suggest that the dopamine signaling mechanism acts by dampening the body’s inflammatory response, so it does not exceed normal limits.

“We are talking about an existing set of drugs and drug targets that could open up the spectrum of potential therapeutic applications by targeting pathways that fine-tune the inflammatory response,” Aballay said. And, he added, “The nervous system appears to be the perfect system for integrating all these different physiological cues to keep the amount of damage in check.”

C. elegans’ intestinal and immune system anatomy and physiology is different and far less complex than that of a human’s. Knowing this, Aballay admits that it would be a “big leap” to assume that these results will be confirmed in clinical trials. But, if they were, it would mean that these drugs could potentially have a therapeutic impact in conditions associated with abnormal immune reactions within the gut, such as IBD.

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