Involvement of neurotrophin-4/5 in regeneration of the periodontal Ruffini endings at the early stage
Article first published online: 23 JAN 2007
Copyright © 2007 Wiley-Liss, Inc.
Journal of Comparative Neurology
Volume 501, Issue 3, pages 400–412, 20 March 2007
How to Cite
Jabbar, S., Harada, F., Aita, M., Ohishi, M., Saito, I., Kawano, Y., Suzuki, A., Nozawa-Inoue, K. and Maeda, T. (2007), Involvement of neurotrophin-4/5 in regeneration of the periodontal Ruffini endings at the early stage. J. Comp. Neurol., 501: 400–412. doi: 10.1002/cne.21256
- Issue published online: 23 JAN 2007
- Article first published online: 23 JAN 2007
- Manuscript Accepted: 26 OCT 2006
- Manuscript Revised: 7 AUG 2006
- Manuscript Received: 17 JUN 2006
- Japan Society for the Promotion of Science. Grant Numbers: 18390488, 17791519, 17-921
- nerve injury;
Little is known about the role of neurotrophin-4/5 (NT-4/5) in the regeneration of mechanoreceptors. Therefore, the present study examined the regeneration process of Ruffini endings in the periodontal ligament in nt-4/5-deficient 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-assisted quantitative image analysis. Furthermore, rescue experiments by a continuous administration of recombinant NT-4/5 were performed and analyzed quantitatively. At postoperative day 3 (PO 3d), almost all PGP 9.5-positive 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 nt-4/5 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-4/5 showed an acceleration of nerve regeneration in the homozygous mice. These findings indicate that the nt-4/5-depletion causes a delay in the regeneration of the periodontal Ruffini endings, but the delay is shortened by an exogenous administration of NT-4/5. Combined with our previous findings of bdnf-deficient mice (Harada et al.  Arch Histol Cytol 66:183–194), these morphological and numerical data suggest that multiple neurotrophins such as NT-4/5 and brain-derived neurotrophic factor (BDNF) play roles in their regeneration in a stage-specific manner. J. Comp. Neurol. 501:400–412, 2007. © 2007 Wiley-Liss, Inc.