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Neuronal PRDX-2-Mediated ROS Signaling Regulates Food Digestion via peripheral UPRmt Activation.

Yating Liu1, Qian Li1, Guojing Tian1

  • 1Southwest United Graduate School, Yunnan Key Laboratory of Cell Metabolism and Diseases, State Key Laboratory of Conservation and Utilization of Bio-resources in Yunnan Center for Life Sciences, School of Life Sciences, Yunnan University, Kunming, China.

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Brain-gut signals involving neuronal reactive oxygen species (ROS) suppress digestion. This pathway, mediated by PRDX-2 and neuropeptide NLP-1, highlights free radicals

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Area of Science:

  • Neurobiology
  • Gastroenterology
  • Cellular Stress Response

Background:

  • Organism survival depends on efficient food digestion.
  • The brain-gut axis plays a crucial role in regulating digestion.
  • Mechanisms linking neuronal signals to intestinal digestive processes remain incompletely understood.

Purpose of the Study:

  • To elucidate the brain-gut signaling pathway that regulates digestion in response to neuronal signals.
  • To investigate the role of reactive oxygen species (ROS) in modulating digestive function.
  • To identify key molecular mediators of this brain-gut communication.

Main Methods:

  • Utilized a C. elegans model for studying digestion.
  • Performed genetic screening to identify genes involved in ROS balance and digestion.
  • Investigated the effects of gene knockout (PRDX-2), neuropeptide manipulation (NLP-1), and neuronal ablation (AWC) on digestive capacity and cellular stress responses.

Main Results:

  • Reduced genes maintaining ROS balance led to increased free radicals and decreased digestion.
  • PRDX-2 knockout in olfactory neurons (AWC) elevated ROS, reducing digestive capacity via neuropeptide NLP-1 and activating the mitochondrial unfolded protein response (UPRmt) in the intestine.
  • Overexpression of nlp-1 or ablation of AWC neurons induced UPRmt and inhibited digestion.

Conclusions:

  • A novel brain-gut pathway is identified where neuronal ROS signaling suppresses digestion.
  • Neuronal PRDX-2-mediated ROS acts through NLP-1 and UPRmt to inhibit intestinal digestion.
  • This highlights a critical role for free radicals in shutting down digestion to alleviate stress and reduce food intake.