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

出生后360天，正常小鼠中脑核(Me5)和三叉神经节(Tg)的神经元数量以及三叉神经感觉核复合体(TSNC)的初级传入终末较30日龄小鼠显著减少。在拔牙小鼠中，40天时下牙槽神经(IAN)严重变性，60~360天拔牙侧ME5和TG神经元数量显著减少。在拔牙侧，TSNC的初级传入终末也严重减少。在中枢神经系统(CNS)的不同区域，在出生后第10天，星形胶质细胞中已发现酸性成纤维细胞生长因子(AFGF)，其水平逐渐升高，而在整个实验过程中，神经元中出现了稳定的碱性成纤维细胞生长因子(Basic FGF)。然而，与老年小鼠咀嚼感觉神经元减少有关的它们水平的任何明显变化都没有被检测到。因此，下一个假设是外周功能障碍可能导致神经元减少，因为在拔牙小鼠的Me5和TG神经元数量减少之前，肯定检测到拔牙小鼠同侧Ian的严重变性。不出所料，一次向拔牙槽内注射aFGF可以恢复受拔牙影响的TSNC的Me5、TG神经元和初级传入终末。此外，我们还发现在成年小鼠中枢神经系统中有一种特殊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，但神经和神经胶质的形成可能与中枢神经系统的可塑性和再生有关，但到目前为止，这种作用是特定的。

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.