Colitis-induced bladder afferent neuronal activation is regulated by BDNF through PLCγ pathway

Area of Science:

• Neuroscience
• Gastroenterology
• Urology

Background:

• Patients with inflammatory bowel disease (IBD) or irritable bowel syndrome (IBS) often exhibit bladder overactivity.
• Neurogenic bladder overactivity is linked to increased sensory responsiveness in the urinary bladder.

Purpose of the Study:

• To investigate the role of brain-derived neurotrophic factor (BDNF) and phospholipase C gamma (PLCγ) pathway in colitis-induced bladder hyperactivity.
• To elucidate the signaling mechanisms underlying colon-to-bladder sensory cross-sensitization.

Main Methods:

• Induction of colitis in rats using 2,4,6-trinitrobenzenesulfonic acid (TNBS).
• Assessment of phosphorylated cAMP responsive element-binding (p-CREB) protein levels in dorsal root ganglia (DRG) neurons.
• Physiological examination of urinary frequency in normal and BDNF-deficient (BDNF+/-) rats.
• In vivo and in vitro studies of the TrkB-PLCγ-CaMKII signaling cascade.

Main Results:

• Colitis increased p-CREB levels in bladder afferent neurons of the DRG.
• Reduced BDNF levels (BDNF+/-) prevented colitis-induced CREB activation and urinary frequency.
• BDNF-mediated colon-to-bladder sensory cross-activation involved the TrkB-PLCγ-CaMKII pathway.
• The PI3K/Akt pathway was not involved in BDNF-mediated bladder hyperactivity during colitis.

Conclusions:

• Up-regulation of BDNF in the DRG plays a crucial role in colon-to-bladder sensory cross-sensitization.
• The TrkB-PLCγ-CaMKII cascade is essential for mediating BDNF's effects on bladder afferent neurons during colitis.
• Targeting the BDNF-PLCγ pathway may offer therapeutic strategies for managing bladder dysfunction in IBD and IBS patients.