Brain-derived neurotrophic factor accelerates gut motility in slow-transit constipation

Area of Science:

• Neuroscience
• Gastroenterology
• Molecular Biology

Background:

• Brain-derived neurotrophic factor (BDNF) is implicated in gut motility regulation.
• Slow-transit constipation (STC) is characterized by impaired gastrointestinal movement.

Purpose of the Study:

• To investigate the physiological effects of BDNF on gut motility in STC.
• To elucidate the molecular mechanisms underlying BDNF's role in gut motility.

Main Methods:

• Assessed BDNF expression and colonic nerve fiber density in STC patients.
• Examined BDNF's effects on gastrointestinal motility in BDNF(+/-) and loperamide-induced constipation mouse models.
• Investigated smooth muscle α-actin (α-SMA), nerve fiber, neuromuscular junction (NMJ), and smooth muscle cell (SMC) alterations.
• Explored the role of the TrkB-PLC/IP3 pathway in BDNF-mediated gut motility.

Main Results:

• STC patients exhibited decreased BDNF expression, nerve fiber density, and ultrastructural nerve degeneration.
• Reduced gut motility was observed in BDNF(+/-) and constipation mice, with BDNF dose-dependently enhancing motility.
• BDNF deficiency led to decreased α-SMA, nerve fiber density, and ultrastructural damage to nerves, NMJs, and SMCs.
• TrkB-PLC/IP3 pathway antagonists blocked BDNF's excitatory effect, and exogenous BDNF increased IP3 expression.

Conclusions:

• BDNF plays a significant regulatory role in gut motility within the context of STC.
• BDNF influences gut motility by modulating intestinal innervation and smooth muscle integrity.
• The TrkB-PLC/IP3 pathway is a key mediator of BDNF's effects on gut motility.