Aβ Accumulation in Vmo Contributes to Masticatory Dysfunction in 5XFAD Mice

Kim, H B; Kim, D; Kim, W; Chung, Sunwoo; Lee, S H; Kim, H R; Oh, Seunghee

doi:10.1177/00220345211000263

Cited by 5 publications

(6 citation statements)

References 36 publications

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“…Conversely, the decline in cognitive function because of AD progression may contribute to oral deterioration. The results of the present study and the recent study by Kim et al ( 2021 ) suggest that the Vmes and Vmo are damaged by AD pathology, thereby directly impairing masticatory function. Using CLEF analysis developed in the present study, we were able to quantitatively evaluate the decline in bite force and energy, a component of oral frailty, in mice and to analyze its relationship with AD pathology.…”

Section: Discussionsupporting

confidence: 73%

“…Sample sizes for behavioral, electrophysiological, and morphological analyses were deduced from previously published studies (Goto et al, 2020 ; Kim et al, 2021 ). We used the following mice to perform each experiment: for immunostaining of Aβ and p-tau, 2-month-old 3 × Tg-AD mice ( n = 3), 3-month-old 3 × Tg-AD mice ( n = 3), 2-month-old NonTg mice ( n = 3), and 3-month-old NonTg mice ( n = 3); for immunofluorescent staining of VGluT1 and ChAT, 3-month-old 3 × Tg-AD mice ( n = 5) and 3-month-old NonTg mice ( n = 4); and for bite force and EMG recording, 3–4-month-old 3 × Tg-AD mice ( n = 10) and 3–4-month-old NonTg mice ( n = 10) (mainly due to a broken wire, we could not record EMG from all animals).…”

Section: Methodsmentioning

confidence: 99%

“…Assessment items for oral function include maximum occlusal force, masticatory capacity (an indicator of general masticatory ability), maximum tongue pressure, repeated saliva drinking test, tongue-lip motor function test (oral diadochokinesis) with three sounds (pa, ta, and ka), and oral wetting level (Tanaka et al, 2018 ). In mice, the oral function is particularly difficult to assess, and only a few studies have measured maximum bite force (Okuda-Akabane et al, 1997 ; Kim et al, 2021 ). It remains unclear whether the maximum bite force of mice is an adequate assessment of oral function, because the maximum bite force is strongly influenced by the emotion and personality of mice (Kuchiiwa and Kuchiiwa, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

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

Kuramoto

Kitawaki

Yagi

et al. 2022

Front. Aging Neurosci.

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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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Section: Discussionsupporting

confidence: 73%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Kuramoto

Kitawaki

Yagi

et al. 2022

Front. Aging Neurosci.

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“…There is a very limited number of studies that investigated the relationship between the trigeminal nervous system and AD using transgenic AD mice. Recently, studies using 5xFAD mice, a type of AD model mice, revealed that at the age of 5 months Aβ is prominently accumulated in the trigeminal motor nucleus, resulting in cell death and atrophy of myofibers in the jaw-closing muscle ( Kim et al, 2021 ). This finding indicates that masticatory function may be impaired following the development of AD.…”

Section: Current Status Of the Research On The Relationship Between T...mentioning

confidence: 99%

Search for unknown neural link between the masticatory and cognitive brain systems to clarify the involvement of its impairment in the pathogenesis of Alzheimer’s disease

Kang,

Toyoda,

Saito

2024

Front. Cell. Neurosci.

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Brain degenerations in sporadic Alzheimer’s disease (AD) are observed earliest in the locus coeruleus (LC), a population of noradrenergic neurons, in which hyperphosphorylated tau protein expression and β-amyloid (Aβ) accumulation begin. Along with this, similar changes occur in the basal forebrain cholinergic neurons, such as the nucleus basalis of Meynert. Neuronal degeneration of the two neuronal nuclei leads to a decrease in neurotrophic factors such as brain-derived neurotrophic factor (BDNF) in the hippocampus and cerebral cortex, which results in the accumulation of Aβ and hyperphosphorylated tau protein and ultimately causes neuronal cell death in those cortices. On the other hand, a large number of epidemiological studies have shown that tooth loss or masticatory dysfunction is a risk factor for dementia including AD, and numerous studies using experimental animals have also shown that masticatory dysfunction causes brain degeneration in the basal forebrain, hippocampus, and cerebral cortex similar to those observed in human AD, and that learning and memory functions are impaired accordingly. However, it remains unclear how masticatory dysfunction can induce such brain degeneration similar to AD, and the neural mechanism linking the trigeminal nervous system responsible for mastication and the cognitive and memory brain system remains unknown. In this review paper, we provide clues to the search for such “missing link” by discussing the embryological, anatomical, and physiological relationship between LC and its laterally adjoining mesencephalic trigeminal nucleus which plays a central role in the masticatory functions.

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“…However, it is difficult to apply these methods to mice without modification. In mice, oral function is particularly difficult to assess, with only a few previous studies measuring maximum bite force under restraint stress conditions [7]. In order to evaluate the natural oral function of mice, it is best to evaluate the bite during food chewing.…”

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confidence: 99%

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2023

Aging

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Aβ Accumulation in Vmo Contributes to Masticatory Dysfunction in 5XFAD Mice

Cited by 5 publications

References 36 publications

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

Search for unknown neural link between the masticatory and cognitive brain systems to clarify the involvement of its impairment in the pathogenesis of Alzheimer’s disease

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