Involvement of neurotrophin-4/5 in regeneration of the periodontal Ruffini endings at the early stage
Involvement of neurotrophin-4/5 in regeneration of the periodontal Ruffini endings at the early stage
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DOI：
10.1002/cne.21256
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发表时间：
2007-03-20
影响因子：
2.5
通讯作者：
Maeda, Takeyasu
中科院分区：
文献类型：
--
作者：
Jabbar, Shahiqul;Harada, Fumiko;Maeda, Takeyasu
神经营养素-4/5（NT-4/5）在机械感受器再生中的作用知之甚少。因此，本研究探讨了再生过程中的Ruffini结束在牙周膜中的NT-4/5缺陷和野生型小鼠下牙槽神经横断蛋白基因产物9.5（PGP 9.5），一般的神经元标记物，免疫组化，并通过计算机辅助定量图像分析。此外，通过连续施用重组NT-4/5进行拯救实验并进行定量分析。在术后第3天（PO 3d），几乎所有PGP 9.5阳性神经元素都消失了;它们在PO 7 d开始出现在两种类型的动物中。在PO 10 d，几乎所有的神经纤维都显示出串珠状外观，在两种类型的小鼠中分支较少。虽然再生在野生型中进行，但在nt-4/5纯合小鼠中，牙周Ruffini末端的主要群体在PO 28 d继续显示平滑的轮廓。神经密度下降率在术后3d达到最大值，术后10 d下降，以后趋于平稳。在拯救实验中，给予NT-4/5显示纯合子小鼠的神经再生加速。这些结果表明，NT-4/5耗尽导致牙周Ruffini末梢再生延迟，但通过外源性施用NT-4/5缩短了延迟。结合我们先前对bdnf缺陷小鼠的发现（Harada等人[2003] Arch HirongCytol 66：183-194），这些形态学和数值数据表明多种神经营养因子如NT-4/5和脑源性神经营养因子（BDNF）以阶段特异性方式在其再生中发挥作用。
Little is known about the role of neurotrophin-4/5 (NT-4/5) in the regeneration of mechano-receptors. 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-4/5depletion 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.