Vagal stimulation ameliorates murine colitis by regulating SUMOylation DOI
Ayman Youssef,

Ata Ur Rehman,

Mohamed Elebasy

et al.

Science Translational Medicine, Journal Year: 2024, Volume and Issue: 16(774)

Published: Nov. 20, 2024

Inflammatory bowel diseases (IBDs) are chronic debilitating conditions without cure, the etiologies of which unknown, that shorten lifespans 7 million patients worldwide by nearly 10%. Here, we found decreased autonomic parasympathetic tone resulted in increased IBD susceptibility and mortality mouse models disease. Conversely, vagal stimulation restored neuromodulation ameliorated colitis inhibiting posttranslational modification SUMOylation through a mechanism independent canonical interleukin-10/α7 nicotinic cholinergic pathway. Colonic biopsies from with IBDs showed an increase small ubiquitin-like modifier (SUMO)2 SUMO3 during active In global genetic knockout models, deletion Sumo3 protected against development delayed onset disease, whereas Sumo1 halted progression colitis. Bone marrow transplants -knockout (KO) but not -KO mice into wild-type conferred protection Electric cervical vagus nerve before induction inhibited milder symptoms mice. Treatment TAK-981, first-in-class inhibitor SUMO-activating enzyme, disease three murine reduced intestinal permeability bacterial translocation severe model suggesting potential to reduce sepsis. These results reveal pathway reprograms endogenous stress-adaptive responses inhibition suggest as therapeutic target for IBD.

Language: Английский

Vagal Sensory Gut–Brain Pathways That Control Eating—Satiety and Beyond DOI
Rebeca Méndez‐Hernández,

Isadora Braga,

Avnika Bali

et al.

Comprehensive physiology, Journal Year: 2025, Volume and Issue: 15(2)

Published: April 1, 2025

ABSTRACT The vagus nerve is the body's primary sensory conduit from gut to brain, traditionally viewed as a passive relay for satiety signals. However, emerging evidence reveals far more complex system—one that actively encodes diverse aspects of meal‐related information, mechanical stretch nutrient content, metabolic state, and even microbial metabolites. This review challenges view vagal afferent neurons (VANs) simple meal‐termination sensors highlights their specialized subpopulations, modalities, downstream brain circuits, which shape feeding behavior, metabolism, cognition. We integrate recent advances single‐cell transcriptomics, neural circuit mapping, functional imaging examine how VANs contribute gut–brain communication beyond satiety, including roles in food reward memory formation. By synthesizing latest research highlighting directions field, this provides comprehensive update on pathways role integrators meal information.

Language: Английский

Citations

0
Vagal stimulation ameliorates murine colitis by regulating SUMOylation DOI
Ayman Youssef,

Ata Ur Rehman,

Mohamed Elebasy

et al.

Science Translational Medicine, Journal Year: 2024, Volume and Issue: 16(774)

Published: Nov. 20, 2024

Inflammatory bowel diseases (IBDs) are chronic debilitating conditions without cure, the etiologies of which unknown, that shorten lifespans 7 million patients worldwide by nearly 10%. Here, we found decreased autonomic parasympathetic tone resulted in increased IBD susceptibility and mortality mouse models disease. Conversely, vagal stimulation restored neuromodulation ameliorated colitis inhibiting posttranslational modification SUMOylation through a mechanism independent canonical interleukin-10/α7 nicotinic cholinergic pathway. Colonic biopsies from with IBDs showed an increase small ubiquitin-like modifier (SUMO)2 SUMO3 during active In global genetic knockout models, deletion Sumo3 protected against development delayed onset disease, whereas Sumo1 halted progression colitis. Bone marrow transplants -knockout (KO) but not -KO mice into wild-type conferred protection Electric cervical vagus nerve before induction inhibited milder symptoms mice. Treatment TAK-981, first-in-class inhibitor SUMO-activating enzyme, disease three murine reduced intestinal permeability bacterial translocation severe model suggesting potential to reduce sepsis. These results reveal pathway reprograms endogenous stress-adaptive responses inhibition suggest as therapeutic target for IBD.

Language: Английский

Citations

1