Neurogenic colonic motility patterns and gut transit disrupted in a mouse model of Rett Syndrome

Gastrointestinal dysfunction, marked by slow gut transit times and constipation, is a prominent symptom in neurodevelopmental disorders, including Rett syndrome. The specific cause of this dysfunction remains unclear, as it is unknown which system within the body is primarily responsible for this issue. In a study focusing on the Mecp2 mouse model, a neurodevelopmental disorder characterized by severe gut motility problems, researchers have discovered that the mouse exhibits both slowed gut transit times and constipation, both in vivo and ex vivo.

Additionally, the study reveals that the mouse's colon displays significant alterations in the pattern of neurogenic contractions.

Selective elimination of Mecp2 in neurons resulted in the same dysmotility abnormalities observed in the Mecp2 mouse model. This suggests that neuronal involvement is a key factor in gastrointestinal dysfunction in Rett syndrome. Furthermore, analysis of the colonic external muscle, which houses the myenteric compartment of the enteric nervous system, uncovered significant changes in the expression of specific neurochemical signaling pathways.

Interestingly, pharmacological modulation of the M1 acetylcholine receptor, a component of the muscarinic signaling pathway, was able to normalize the abnormal neurogenic contractile phenotype in both mutant and wild-type mice. This finding could potentially lead to the development of treatments targeting neuronal muscarinic signaling as a means to address gastrointestinal dysmotility in neurodevelopmental disorders.