Fundamental study on medical treatment development for rescuing functional depressing induced with aging, and by tooth loss in the masticatory system

拯救因衰老和咀嚼系统牙齿脱落引起的功能性抑制的药物开发基础研究

• 批准号: 17591913
• 负责人: MAEDA Norihiko
• 金额: $ 2.24万
• 依托单位: HIROSHIMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591913/
• 关键词: masticatory system; aging; neurogenesis; FGF; Regenerative medicine; central nervous system; 中枢神経系; ニユーロン; BrdU; 細胞新生

In intact mice, significant reductions were detected in the number of neurons of mesencephalic nucleus (Me5) and trigeminal ganglion (TG), and primary afferent terminals in the trigeminal sensory nuclear complex (TSNC) after 360th postnatal day, as compared with those in 30-day-old mice. In tooth-extracted mice, we observed severe degeneration of the inferior alveolar nerve (IAN) on day 40, and significant decrease in the number of Me5 and TG neurons from 60th to 360th postnatal day on the tooth-extracted side. Primary afferent terminals diminished severely in the TSNC were also observed on the tooth-extracted side.In various areas of the central nervous system (CNS) acidic FGF (aFGF) was found to exist by the 10th postnatal day in astrocytes, and its level was gradually increased, while steady state levels of basic FGF, which appeared in neurons, were observed throughout experiments. While, any distinct changes in their levels, associated, with the reduction in the masticatory sensory neurons in aged mice, could not be detected. So, it was next hypothesized that the peripheral disability may result in the neuronal reduction, because severe degeneration of the ipsilateral IAN in the tooth-extracted mouse was certainly detected prior to a decrease in the number of Me5 and TG neurons in tooth-extracted mice. Expectedly, single injection of aFGF into the tooth-extracted socket restored the Me5, TG neurons and the primary afferent terminals of the TSNC affected by the tooth-extraction.We additionally found a specific but more widespread distribution of proliferating cells in the adult mouse CNS. Although we can not explain the differentiation of all proliferating cells, thus neuro- and glio- genesis might be associated with a specific but hitherto role of plasticity and regeneration in the CNS.

正常小鼠生后360 d中脑核（Me5）和三叉神经节（TG）神经元数目及三叉神经感觉核复合体（TSNC）初级传入终末数目较30 d明显减少。在拔牙小鼠中，我们观察到严重的变性下齿槽神经（IAN）在40天，和Me5和TG神经元的数量显着减少，从60日至360日出生后拔牙侧。在中枢神经系统（CNS）的各个区域，酸性FGF（aFGF）在出生后第10天在星形胶质细胞中存在，并且其水平逐渐增加，而碱性FGF在神经元中出现的稳态水平在整个实验过程中观察到。而老年小鼠咀嚼感觉神经元数量减少时，其含量无明显变化。因此，接下来假设外周残疾可能导致神经元减少，因为在拔牙小鼠中Me5和TG神经元数量减少之前，确实检测到拔牙小鼠同侧IAN的严重变性。实验结果表明，在拔牙窝内注射aFGF可恢复受拔牙影响的TSNC的Me5、TG神经元和初级传入纤维终末，并在成年小鼠CNS内发现了特异性但更广泛的增殖细胞分布。虽然我们不能解释所有增殖细胞的分化，因此神经元和胶质细胞的发生可能与CNS中的可塑性和再生的特定但迄今为止的作用有关。