Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, Republic of Korea.
Dental Research Institute and Department of Neurobiology and Physiology, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
J Dent Res. 2021 Aug;100(9):960-967. doi: 10.1177/00220345211000263. Epub 2021 Mar 14.
Alzheimer's disease (AD) shows various symptoms that reflect cognitive impairment and loss of neural circuit integrity. Sensory dysfunctions such as olfactory and ocular pathology are also observed and used as indicators for early detection of AD. Although mastication is suggested to correlate with AD progression, changes in the masticatory system have yet to be established in transgenic animal models of AD. In the present study, we have assessed pathologic hallmarks of AD with the masticatory behavior of 5XFAD mice. We found that masticatory efficiency and maximum biting force were decreased in 5XFAD mice, with no significant change in general motor function. Immunohistochemical analysis revealed significant accumulation of Aβ (amyloid β), increased microglia number, and cell death in Vmo (trigeminal motor nucleus) as compared with other cranial motor nuclei that innervate the orofacial region. Masseter muscle weight and muscle fiber size were also decreased in 5XFAD mice. Taken together, our results demonstrate that Aβ accumulation in Vmo contributes to masticatory dysfunction in 5XFAD mice, suggesting a close association between masticatory dysfunction and dementia.
阿尔茨海默病(AD)表现出各种反映认知障碍和神经回路完整性丧失的症状。还观察到嗅觉和眼部病理学等感觉功能障碍,并将其用作 AD 早期检测的指标。尽管咀嚼被认为与 AD 进展相关,但 AD 转基因动物模型中咀嚼系统的变化尚未确定。在本研究中,我们通过 5XFAD 小鼠的咀嚼行为评估了 AD 的病理特征。我们发现 5XFAD 小鼠的咀嚼效率和最大咬合力降低,而一般运动功能没有明显变化。免疫组织化学分析显示,与支配口面区域的其他颅神经核相比,Vmo(三叉运动核)中 Aβ(淀粉样 β)的积累、小胶质细胞数量的增加和细胞死亡显著增加。5XFAD 小鼠的咬肌重量和肌纤维大小也减少。综上所述,我们的研究结果表明,Vmo 中的 Aβ 积累导致 5XFAD 小鼠咀嚼功能障碍,提示咀嚼功能障碍与痴呆之间存在密切关联。