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Published on: April 17, 2019
Age-related changes in the neuromuscular development of the internal anal sphincter
Reiji Nakano1, Thambipillai Sri Paran, Udo Rolle
1The Children's Research Center, Our Lady's Children's Hospital, Dublin 12, Ireland.
Insights
The internal anal sphincter (IAS) shows age-related neuromuscular development. Immature IAS in premature infants may cause functional intestinal obstruction due to poor muscle and nerve development.
Area of Science:
- Gastroenterology
- Developmental Biology
- Neuroscience
Background:
- The internal anal sphincter (IAS) is crucial for bowel control.
- Dysfunction of the IAS is implicated in constipation and incontinence.
- Premature infants may experience functional bowel obstruction due to an underdeveloped IAS.
Purpose of the Study:
- To investigate the neuromuscular development of the IAS in pigs across different life stages.
- To test the hypothesis that a poorly developed IAS contributes to functional bowel obstruction in premature infants.
Main Methods:
- Immunohistochemical staining of IAS tissue from fetal, newborn, and adolescent pigs (E60, E90, 1 day, 4, and 12 weeks).
- Antibodies used included PGP9.5 (neurons), α-SMA, caldesmon, calponin, and desmin (smooth muscle components).
- Quantification of protein expression by grading immunostaining density.
Main Results:
- PGP9.5-positive ganglion cells were present in the IAS by E60, with increasing size and density with age.
- Significant differences in PGP9.5, α-SMA, desmin, caldesmon, and calponin immunoreactive fibers were observed between prenatal and postnatal periods.
- A gradual increase in fiber density was noted from birth to 12 weeks of age.
Conclusions:
- This study reveals age-related changes in IAS neuron and smooth muscle cell components.
- Reduced expression of contractile proteins and neurons in the perinatal period may cause motility dysfunction.
- This dysfunction could underlie functional intestinal obstruction observed in premature infants.
Purpose:
The internal anal sphincter (IAS) plays an important role in the pathophysiology of constipation and incontinence. We hypothesized that functional bowel obstruction in premature infants is because of a poorly developed IAS. We investigated the neuromuscular development of IAS in fetal, newborn, and adolescent pigs.
Methods:
Paraffin sections of IAS from 5 different age groups, E60, E90, 1 day, 4, and 12 weeks old, were stained with protein gene product 9.5 (PGP9.5), *-smooth muscle actin (*-SMA), caldesmon (CALD), calponin (CALP), and desmin (DES) antibodies. Quantification of results was performed by grading the density of immunostaining.
Results:
The PGP9.5-positive ganglion cells were observed in the myenteric and submucosal region of the entire length of the IAS at E60. An increase in ganglion cell size and density was observed with increasing age. There were striking differences in the density of PGP9.5, alpha-SMA, DES, CALD, and CALP immunoreactive fibers between prenatal and postnatal period with gradient increase in the number of fibers from after birth to 12 weeks of age.
Conclusion:
This study shows for the first time that there are age-related differences in the distribution of neurons and smooth muscle cell components in the IAS. The decreased expression of contractile and cytoskeleton proteins in smooth muscle cells together with decreased expression of neurons in the IAS in the perinatal period may lead to motility dysfunction causing functional intestinal obstruction seen in premature infants.
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