{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:03:28Z","timestamp":1791201808142,"version":"4.2.0"},"reference-count":40,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2013,5,1]],"date-time":"2013-05-01T00:00:00Z","timestamp":1367366400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2013,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The innervation of the mouse internal anal sphincter (<jats:styled-content style=\"fixed-case\">IAS<\/jats:styled-content>) 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 <jats:styled-content style=\"fixed-case\">IAS<\/jats:styled-content> and underlying mucosa in 3\u2010, 12\u2010 to 13\u2010, 18\u2010 and 24\u2010 to 25\u2010month\u2010old male C57BL\/6 mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Nerve fibers were immunolabeled with antibodies against protein gene product 9.5 (<jats:styled-content style=\"fixed-case\">PGP9.5<\/jats:styled-content>), neuronal nitric oxide synthase (n<jats:styled-content style=\"fixed-case\">NOS<\/jats:styled-content>), vasoactive intestinal polypeptide (<jats:styled-content style=\"fixed-case\">VIP<\/jats:styled-content>), substance <jats:styled-content style=\"fixed-case\">P<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">SP<\/jats:styled-content>), calcitonin gene\u2010related peptide (<jats:styled-content style=\"fixed-case\">CGRP<\/jats:styled-content>), and calretinin (<jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content>). Immunoreactivity in nerve fibers in the circular muscle and mucosa was quantified using Image J software.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>In young adult (3\u00a0month) mice, n<jats:styled-content style=\"fixed-case\">NOS<\/jats:styled-content>\u2010immunoreactive (<jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content>) nerve fibers were densely distributed in the circular muscle, but relatively few in the mucosa; <jats:styled-content style=\"fixed-case\">VIP<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content> nerve fibers were abundant in the circular muscle and common in the mucosa; <jats:styled-content style=\"fixed-case\">SP<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content> nerve fibers were common in circular muscle and mucosa; <jats:styled-content style=\"fixed-case\">CGRP<\/jats:styled-content>\u2010 and <jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content> nerve fibers were dense in mucosa and sparse in circular muscle. The density of <jats:styled-content style=\"fixed-case\">PGP9.5<\/jats:styled-content> immunoreactivity (<jats:styled-content style=\"fixed-case\">IRY<\/jats:styled-content>) was not significantly reduced with age, but a significant reduction in n<jats:styled-content style=\"fixed-case\">NOS<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">IRY<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">SP<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">IRY<\/jats:styled-content> with age was found in the <jats:styled-content style=\"fixed-case\">IAS<\/jats:styled-content> circular muscle. Neuronal nitric oxide synthase\u2010, <jats:styled-content style=\"fixed-case\">VIP<\/jats:styled-content>\u2010, and <jats:styled-content style=\"fixed-case\">SP<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">IRY<\/jats:styled-content> in the anal mucosa were significantly reduced with age. <jats:styled-content style=\"fixed-case\">CGRP<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">IRY<\/jats:styled-content> in both circular muscle and mucosa was increased in 18\u2010month\u2010old animals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions &amp; Inferences<\/jats:title><jats:p>The density of immunoreactivity of markers for some types of <jats:styled-content style=\"fixed-case\">IAS<\/jats:styled-content> nerve fibers decreases during aging, which may contribute to age\u2010related ano\u2010rectal dysfunction.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.12144","type":"journal-article","created":{"date-parts":[[2013,5,2]],"date-time":"2013-05-02T09:30:34Z","timestamp":1367487034000},"source":"Crossref","is-referenced-by-count":16,"title":["Changes in the innervation of the mouse internal anal sphincter during aging"],"prefix":"10.1111","volume":"25","author":[{"given":"C.","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Life, Health and Chemical Sciences The Open University Milton Keynes UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. J.","family":"Houghton","sequence":"additional","affiliation":[{"name":"Department of Life, Health and Chemical Sciences The Open University Milton Keynes UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. P. K. M.","family":"Gamage","sequence":"additional","affiliation":[{"name":"Department of Life, Health and Chemical Sciences The Open University Milton Keynes UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. E.","family":"Collins","sequence":"additional","affiliation":[{"name":"Department of Life, Health and Chemical Sciences The Open University Milton Keynes UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. A.","family":"Patel","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Biomolecular Sciences University of Brighton Brighton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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