Abnormal Enteric Nervous System Organization and Gastrointestinal Motility in Mice With Valproic Acid-Induced Neural...

Area of Science:

• Developmental biology
• Neuroscience
• Gastroenterology

Background:

• Neural tube defects (NTDs) are common congenital anomalies affecting the brain (anencephaly) or spine (spina bifida).
• Neurogenic bowel is a significant complication in spina bifida, but the impact on the gastrointestinal (GI) tract in other NTDs is unclear.
• The enteric nervous system (ENS), crucial for GI motility, organizes into distinct neuronal stripes during development.

Purpose of the Study:

• To investigate the relationship between NTDs and ENS organization.
• To determine if altered ENS structure correlates with GI motility defects in NTDs.

Main Methods:

• Prenatal valproic acid (VPA) exposure in mice to induce exencephaly, a cranial NTD.
• Immunohistochemistry and confocal imaging to analyze ENS structure (neuronal stripes).
• Ex vivo motility assays to assess GI function.

Main Results:

• VPA-induced NTDs led to thinner enteric neuronal stripes with narrower interstripe distances, increasing stripe count.
• GI tracts in affected fetuses contained blood.
• Abnormal GI motility was observed, characterized by increased contraction frequency and length.

Conclusions:

• ENS organization and GI motility are disrupted in mouse fetuses with VPA-induced NTDs.
• These findings suggest a link between cranial NTDs and GI dysfunction.
• This research has implications for understanding neurogenic bowel in CNS disorders like spina bifida.