Tail-Suspension Model of Simulated Microgravity-Induced Functional Dyspepsia in Rats: Behavioral, Motility, and...

Area of Science:

• Physiology
• Neuroscience
• Gastroenterology

Background:

• Animal models are crucial for understanding human diseases and advancing translational research.
• Simulated microgravity can induce functional dyspepsia (FD) through complex pathophysiological changes.
• The brain-gut axis plays a significant role in regulating gastrointestinal function and mood.

Purpose of the Study:

• To investigate simulated microgravity-induced functional dyspepsia (FD) using a rat tail-suspension model.
• To evaluate the utility of this model for preclinical to clinical translation of FD research.
• To assess the therapeutic effects of domperidone on FD phenotypes in this model.

Main Methods:

• Utilized a 21-day hindlimb unloading (HU) rat tail-suspension model to simulate microgravity.
• Assessed behavioral changes (sucrose preference, novelty-suppressed feeding), gastrointestinal motility, and serum brain-gut peptide levels.
• Analyzed gastric and hypothalamic gene expression via qRT-PCR and measured hippocampal BDNF and colonic 5-HT.

Main Results:

• The HU model successfully mimicked FD, showing anxiety/depression-like behaviors and impaired gastrointestinal motility.
• Systemic brain-gut peptide imbalance was observed, with altered levels of excitatory and inhibitory peptides.
• Domperidone treatment ameliorated behavioral and motility deficits, partially reversed peptide imbalances, and restored hippocampal BDNF.

Conclusions:

• The rat tail-suspension model is a reproducible platform for studying microgravity-induced FD and brain-gut axis dysregulation.
• This model demonstrates the potential for evaluating countermeasures against spaceflight-associated digestive dysfunction.
• Findings support the role of brain-gut axis dysregulation in FD pathophysiology and highlight domperidone's therapeutic potential.