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

C. Wang, M.J. Houghton, P.P.K.M. Gamage, H.E. Collins, Bhavik Patel, Mark Yeoman, R.N. Ranson, M.J. Saffrey

Research output: Contribution to journalArticle

Abstract

BACKGROUND: 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. METHODS: 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.
Original languageEnglish
JournalNeurogastroenterology and Motility
Volume25
Issue number7
Publication statusPublished - 1 May 2013

Keywords

  • aging
  • calcitonin gene-related peptide
  • internal anal sphincter
  • nitric oxide synthase
  • substance P
  • vasoactive intestinal polypeptide

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