| 研究実績の概要 |
Chromosome 15q duplication Syndrome is a neurodevelopmental disorder. Approximately 80% of individuals with 15q duplications (15q dup) have gastrointestinal (GI) dysfunction, with frequent symptoms including gastroesophageal reflux and constipation. The duplicated region consists of genes encoding for GABA receptor A subunits and GABA is an important neurotransmitter in the Enteric Nervous System (ENS). The gut produces over 90% of the body's serotonin, and serotonin plays a vital role in the enteric neuronal circuitry that regulates gut motility. We investigated GI dysfunction and serotonin-mediated neurotransmission in the ENS. Both male and female adult 15q dup mice had delayed GI transit. We investigated colonic motility using a video imaging approach in which colonic contractions were assessed ex vivo using a video camera and in-house software. When 15q dup mice were treated with Bicuculine, colonic contractions were slower and traveled for a shorter distance. Since the 15q dup neurons were under a hypo-serotonin condition, the potential of Prucalopride to restore the delayed GI transit was investigated. Prucalopride reversed the delayed GI transit in 15q dup mice. The results suggest that enteric neurons in 15q dup mice are more susceptible to GABA receptor inhibition and targeting serotonin receptors is an effective way to treat GI dysfunction in 15q dup syndrome.
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