Development of a system to analyze oral frailty associated with Alzheimer's disease using a mouse model.

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 3x Tg-AD mice and their non-transgenic counterpart (NonTg) of 3-4 months of age in the present study. Immunohistochemistry revealed amyloid-b deposition and excessive tau phosphorylation in the Vmes of 3x 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 3x 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 3x Tg-AD mice showed a significant delay In masticatory rhythm compared to Non Tgmice. 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 3cx g-AD mice eating sunflower seeds was predominantly smaller than that of Non Tgmice. 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 3x Tg-AD mice were not due to abnormality of the masseter. In conclusion, the decreased masticatory function observed in 3x 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. [ABSTRACT FROM AUTHOR]