The 5-HT₃ Receptor Affects Rotavirus-Induced Motility

Area of Science:

• Gastroenterology
• Neuroscience
• Virology

Background:

• Rotavirus infection is a leading cause of childhood diarrhea and vomiting.
• The enteric nervous system (ENS) and serotonin signaling are implicated in rotavirus pathophysiology.
• The precise role of the serotonin 5-HT₃ receptor in rotavirus-induced symptoms remains unclear.

Purpose of the Study:

• To investigate the role of the serotonin 5-HT₃ receptor in rotavirus-induced diarrhea, intestinal motility, electrolyte secretion, and vomiting reflex.
• To elucidate the involvement of the 5-HT₃ receptor in vagal nerve signaling to the brain during rotavirus infection.

Main Methods:

• Utilized a 5-HT₃ receptor knockout (KO) mouse model infected with rotavirus.
• Assessed diarrhea incidence and duration, intestinal transit time (FITC-dextran), and electrolyte secretion (Ussing chamber).
• Measured immediate early gene cFos expression in the brain and analyzed intestinal cytokine levels.

Main Results:

• Infected 5-HT₃ receptor KO mice exhibited significantly fewer diarrhea days and reduced intestinal motility compared to wild-type mice.
• No significant differences were observed in electrolyte secretion or vomiting center activation (cFos expression).
• Mice lacking the 5-HT₃ receptor showed a diminished inflammatory response in the intestine.

Conclusions:

• The serotonin 5-HT₃ receptor is a critical mediator of rotavirus-induced diarrhea, primarily through its influence on intestinal motility.
• Vagal nerve signaling to the vomiting center can occur independently of the 5-HT₃ receptor.
• Targeting the 5-HT₃ receptor may offer a therapeutic strategy for managing rotavirus diarrhea.