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Therefore, the present study examined the regeneration process of Ruffini endings in the periodontal ligament in <jats:italic>nt\u20104\/5<\/jats:italic>\u2010deficient and wildtype mice following transection of the inferior alveolar nerve by immunohistochemistry for protein gene product 9.5 (PGP 9.5), a general neuronal marker, and by computer\u2010assisted quantitative image analysis. Furthermore, rescue experiments by a continuous administration of recombinant NT\u20104\/5 were performed and analyzed quantitatively. At postoperative day 3 (PO 3d), almost all PGP 9.5\u2010positive neural elements had disappeared; they began to appear in both types of animals at PO 7d. At PO 10d, almost all nerve fibers showed a beaded appearance, with fewer ramifications in both types of mice. Although the regeneration proceeded in the wildtype, a major population of the periodontal Ruffini endings continued to display smooth outlines at PO 28d in the <jats:italic>nt\u20104\/5<\/jats:italic> homozygous mice. The reduction ratio of neural density reached a maximum at PO 3d, decreased at PO 10d, and later showed a plateau. In a rescue experiment, an administration of NT\u20104\/5 showed an acceleration of nerve regeneration in the homozygous mice. These findings indicate that the <jats:italic>nt\u20104\/5<\/jats:italic>\u2010depletion causes a delay in the regeneration of the periodontal Ruffini endings, but the delay is shortened by an exogenous administration of NT\u20104\/5. Combined with our previous findings of <jats:italic>bdnf<\/jats:italic>\u2010deficient mice (Harada et al. [<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"#bib30\">2003<\/jats:ext-link>] Arch Histol Cytol 66:183\u2013194), these morphological and numerical data suggest that multiple neurotrophins such as NT\u20104\/5 and brain\u2010derived neurotrophic factor (BDNF) play roles in their regeneration in a stage\u2010specific manner. J. Comp. Neurol. 501:400\u2013412, 2007. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/cne.21256","type":"journal-article","created":{"date-parts":[[2007,1,23]],"date-time":"2007-01-23T18:17:36Z","timestamp":1169576256000},"page":"400-412","source":"Crossref","is-referenced-by-count":9,"title":["Involvement of neurotrophin\u20104\/5 in regeneration of the periodontal Ruffini endings at the early 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