Involvement of neurotrophin-4/5 in regeneration of the periodontal Ruffini endings at the early stage.
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. [2003] 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.
Jabbar
Shahiqul
S
Division of Oral Anatomy, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Harada
Fumiko
F
Aita
Megumi
M
Ohishi
Megumi
M
Saito
Isao
I
Kawano
Yoshiro
Y
Suzuki
Akiko
A
Nozawa-Inoue
Kayoko
K
Maeda
Takeyasu
T
D000818:Animals; D020209:Cranial Nerve Injuries / Q000201:enzymology; D003714:Denervation / Q000379:methods; D007150:Immunohistochemistry; D008340:Mandibular Nerve / Q000378:metabolism*; D008465:Mechanoreceptors / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D009416:Nerve Regeneration / Q000502:physiology*; D018696:Neuroprotective Agents / Q000378:metabolism; D010513:Periodontal Ligament / Q000166:cytology / Q000294:innervation / Q000378:metabolism*; D061221:Trigeminal Nerve Injuries
D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; C071951:neurotrophin 5; C073922:neurotrophin 4