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Changes in the innervation of the mouse internal anal sphincter during aging

Wang, C.; Houghton, M. J.; Gamage, P. P.K.M; Collins, H. E.; Patel, B. A.; Yeoman, M. S.; Ranson, R. N. and Saffrey, M. J. (2013). Changes in the innervation of the mouse internal anal sphincter during aging. Neurogastroenterology and Motility, 25(7) e469-e477.

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The innervation of the mouse internal anal sphincter (IAS) has been little studied, and how it changes during aging has not previously been investigated. The aim of this study was therefore to characterize the distribution and density of subtypes of nerve fibers in the IAS and underlying mucosa in 3-, 12- to 13-, 18- and 24- to 25-month-old male C57BL/6 mice.


Nerve fibers were immunolabeled with antibodies against protein gene product 9.5 (PGP9.5), neuronal nitric oxide synthase (nNOS), vasoactive intestinal polypeptide (VIP), substance P (SP), calcitonin gene-related peptide (CGRP), and calretinin (CR). Immunoreactivity in nerve fibers in the circular muscle and mucosa was quantified using Image J software. Key Results In young adult (3 month) mice, nNOS-immunoreactive (IR) nerve fibers were densely distributed in the circular muscle, but relatively few in the mucosa; VIP-IR nerve fibers were abundant in the circular muscle and common in the mucosa; SP-IR nerve fibers were common in circular muscle and mucosa; CGRP- and CR-IR nerve fibers were dense in mucosa and sparse in circular muscle. The density of PGP9.5 immunoreactivity (IRY) was not significantly reduced with age, but a significant reduction in nNOS-IRY and SP-IRY with age was found in the IAS circular muscle. Neuronal nitric oxide synthase-, VIP-, and SP-IRY in the anal mucosa were significantly reduced with age. CGRP-IRY in both circular muscle and mucosa was increased in 18-month-old animals.

Conclusions & Inferences

The density of immunoreactivity of markers for some types of IAS nerve fibers decreases during aging, which may contribute to age-related ano-rectal dysfunction.

Item Type: Journal Item
Copyright Holders: 2013 John Wiley & Sons Ltd
ISSN: 1365-2982
Project Funding Details:
Funded Project NameProject IDFunding Body
Aging bladder and bowelBB/G015988/1BBSRC (Biotechnology and Biological Sciences Research Council)
Keywords: aging; calcitonin gene-related peptide; internal anal sphincter; nitric oxide synthase; substance P; vasoactive intestinal polypeptide
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM)
Item ID: 37543
Depositing User: Jill Saffrey
Date Deposited: 03 May 2013 08:52
Last Modified: 07 Dec 2018 10:15
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