Department of Advanced Prosthodontics, Hiroshima University Graduate School of Biomedical & Health Sciences, Japan.
Behav Brain Res. 2013 Sep 1;252:318-25. doi: 10.1016/j.bbr.2013.06.015. Epub 2013 Jun 15.
Tooth loss is a known risk factor of Alzheimer's disease (AD). However, the association of tooth loss with the molecular pathogenesis of AD is still unknown. The hypothesis that the molecular pathogenesis of AD is enhanced by molar tooth loss was tested. Seventeen female transgenic mice (J20) were divided into the experimental (EX, n=10) and control (C, n=7) groups. In the EX group, maxillary bilateral molar teeth were extracted at the age of 6 months. In the C group, however, these teeth remained intact. Passive avoidance test was performed to evaluate learning and memory abilities right after tooth extraction (6 months old) and 4 months later (10 months old). After the test at 10 months, amyloid beta (Aβ) deposition and changes of neuronal cell number and area in the hippocampus were investigated using half of the brains. The other half was homogenized and used to determine Aβ40 and Aβ42 levels by ELISA. At the 10 months of age, learning and memory abilities were significantly impaired in the EX group compared to the C group (P<0.05). The neuronal cell number in the CA1 and CA3 regions was significantly lower in the EX group than in the C group (P<0.05). Total Aβ, Aβ40, and Aβ42 levels showed no significant intergroup difference. Molar tooth loss may cause neuronal cell loss in the hippocampus, leading to memory impairment; this process may be independent of the amyloid cascade.
牙齿缺失是阿尔茨海默病(AD)的已知危险因素。然而,牙齿缺失与 AD 的分子发病机制的关联尚不清楚。本研究旨在检验 AD 的分子发病机制是否因磨牙缺失而加重的假说。将 17 只雌性转基因小鼠(J20)分为实验组(EX,n=10)和对照组(C,n=7)。实验组在 6 月龄时拔除上颌双侧磨牙,对照组则保留这些牙齿。在拔牙后即刻(6 月龄)和 4 个月后(10 月龄)进行被动回避测试,以评估学习和记忆能力。在 10 月龄时,使用一半大脑研究海马区的淀粉样β(Aβ)沉积和神经元细胞数量及面积的变化,另一半大脑匀浆后通过 ELISA 法测定 Aβ40 和 Aβ42 水平。与对照组相比,实验组在 10 月龄时的学习和记忆能力显著受损(P<0.05)。实验组 CA1 和 CA3 区的神经元细胞数量明显低于对照组(P<0.05)。总 Aβ、Aβ40 和 Aβ42 水平在两组间无显著差异。磨牙缺失可能导致海马神经元细胞丢失,从而导致记忆障碍;这个过程可能与淀粉样蛋白级联无关。