Development of a system to analyze oral frailty associated with Alzheimer's disease using a mouse model.
Development of a system to analyze oral frailty associated with Alzheimer's disease using a mouse model.
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DOI：
10.3389/fnagi.2022.935033
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发表时间：
2022
影响因子：
4.8
通讯作者：
中科院分区：
文献类型：
--
作者：
人口的快速老龄化使得虚弱的检测和预防变得越来越重要。口腔脆弱被认为是一种新的脆弱表型，其定义为口腔功能下降与认知和身体功能下降并存。口腔脆弱与阿尔茨海默病（AD）有关，受到特别关注。然而，与AD相关的口腔脆弱的病理机制仍然未知。据推测，控制咀嚼的中脑三叉神经核（Vmes）受到AD病理学的影响，因此，咀嚼功能可能受损。为了研究这种可能性，我们在本研究中纳入了雄性3 × Tg-AD小鼠及其3-4月龄的非转基因对应小鼠（NonTg）。免疫组织化学显示3 × Tg-AD小鼠Vmes中淀粉样蛋白-β沉积和过度tau磷酸化。此外，囊泡谷氨酸转运体1免疫阳性轴突的静脉曲张，这是来自Vmes神经元，在三叉神经运动核的3 × Tg-AD小鼠显着减少。为了研究在VME中观察到的AD病理学是否影响咀嚼功能，我们分析了进食过程中咬肌的肌电图。与NonTg小鼠相比，3 × Tg-AD小鼠的咀嚼节律显著延迟。此外，我们还开发了一个系统，同时记录咬合力和咬肌肌电，并设计了一种新的方法来估计咬合力在小鼠咀嚼食物。由于咬肌的肌肉活动度与咬合力具有高度的相关性，因此可以通过肌肉活动度准确地估计咬合力。3 × Tg-AD小鼠吃向日葵籽的估计咬合力主要小于NonTg小鼠。然而，两组之间的咬肌重量或肌纤维横截面积没有差异，这表明在3 × Tg-AD小鼠中观察到的咬合力下降和咀嚼节律延迟不是由于咬肌异常。总之，在3 × Tg-AD小鼠中观察到的咀嚼功能下降最有可能是由Vmes中的AD病理引起的。因此，使用AD小鼠模型对咀嚼功能进行新的定量分析，能够全面了解口腔脆弱的发病机制。
The rapid aging of the population makes the detection and prevention of frailty increasingly important. Oral frailty has been proposed as a novel frailty phenotype and is defined as a decrease in oral function coexisting with a decline in cognitive and physical functions. Oral frailty has received particular attention in relation to Alzheimer's disease (AD). However, the pathomechanisms of oral frailty related to AD remain unknown. It is assumed that the mesencephalic trigeminal nucleus (Vmes), which controls mastication, is affected by AD pathology, and as a result, masticatory function may be impaired. To investigate this possibility, we included male 3 × Tg-AD mice and their non-transgenic counterpart (NonTg) of 3–4 months of age in the present study. Immunohistochemistry revealed amyloid-β deposition and excessive tau phosphorylation in the Vmes of 3 × Tg-AD mice. Furthermore, vesicular glutamate transporter 1-immunopositive axon varicosities, which are derived from Vmes neurons, were significantly reduced in the trigeminal motor nucleus of 3 × Tg-AD mice. To investigate whether the AD pathology observed in the Vmes affects masticatory function, we analyzed electromyography of the masseter muscle during feeding. The 3 × Tg-AD mice showed a significant delay in masticatory rhythm compared to NonTg mice. Furthermore, we developed a system to simultaneously record bite force and electromyography of masseter, and devised a new method to estimate bite force during food chewing in mice. Since the muscle activity of the masseter showed a high correlation with bite force, it could be accurately estimated from the muscle activity. The estimated bite force of 3 × Tg-AD mice eating sunflower seeds was predominantly smaller than that of NonTg mice. However, there was no difference in masseter weight or muscle fiber cross-sectional area between the two groups, suggesting that the decreased bite force and delayed mastication rhythm observed in 3 × Tg-AD mice were not due to abnormality of the masseter. In conclusion, the decreased masticatory function observed in 3 × Tg-AD mice was most likely caused by AD pathology in the Vmes. Thus, novel quantitative analyses of masticatory function using the mouse model of AD enabled a comprehensive understanding of oral frailty pathogenesis.
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DOI：
10.3233/jad-200257
发表时间：
2020
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Goto T;Kuramoto E;Dhar A;Wang RP;Seki H;Iwai H;Yamanaka A;Matsumoto SE;Hara H;Michikawa M;Ohyagi Y;Leung WK;Chang RC
通讯作者：
Chang RC
影响因子：
3.2
作者：
Dutt S;Li Y;Mather M;Nation DA;Alzheimer’s Disease Neuroimaging Initiative
通讯作者：
Alzheimer’s Disease Neuroimaging Initiative
影响因子：
2.5
作者：
DESSEM, D;TAYLOR, A
通讯作者：
TAYLOR, A
影响因子：
3.7
作者：
Ikebe K;Gondo Y;Kamide K;Masui Y;Ishizaki T;Arai Y;Inagaki H;Nakagawa T;Kabayama M;Ryuno H;Okubo H;Takeshita H;Inomata C;Kurushima Y;Mihara Y;Hatta K;Fukutake M;Enoki K;Ogawa T;Matsuda KI;Sugimoto K;Oguro R;Takami Y;Itoh N;Takeya Y;Yamamoto K;Rakugi H;Murakami S;Kitamura M;Maeda Y
通讯作者：
Maeda Y
影响因子：
3.3
作者：
Hioki, H;Fujiyama, F;Kaneko, T
通讯作者：
Kaneko, T