Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Mammalian premolars and molars (cheek teeth) are teeth with multiple cusps, which are important characteristics of mammals. Endothermic mammals have high basal metabolic rates and must take in much energy by efficient mastication of food using their multicuspid cheek teeth. From the phylogenetic (evolutionary) perspective, the mammalian multicuspid teeth are derived from the reptilian unicuspid teeth with a single cone by adding new cusps around the original cone. Nearly 100 million years of long geological time were required for the unicuspid tooth to transform into a tribosphenic molar, which is the prototype of all molars in modern mammals. From the ontogenetic (developmental) perspective, the shape of the tooth germ becomes complex by adding the secondary enamel knots repeatedly in a short embryonic period. The secondary enamel knots are signaling centers that determine the future cusp positions. HIGHLIGHT: Here we first reviewed the evolutionary process of the tribosphenic molar in the Mesozoic Era (the age of dinosaurs), and cusp homologies in the fossil record. Next, we reviewed the developmental mechanisms controlling the patterning of secondary enamel knots, which determine the final cusp patterns of molars in modern mammals. Finally, we discussed the possible relationship between the two processes from the extremely different time scales. CONCLUSION: A parallel relationship between ontogeny and phylogeny of the mammalian multicuspid teeth was expected.

DOI： 10.1016/j.job.2022.03.007

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.3389/fnagi.2022.935033

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PubMed

Language：Japanese   Publishing type：Research paper (scientific journal)  

BACKGROUND: Macrophages in the peripheral nervous system are key players in the repair of nerve tissue and the development of neuropathic pain due to peripheral nerve injury. However, there is a lack of information on the origin and morphological features of macrophages in sensory ganglia after peripheral nerve injury, unlike those in the brain and spinal cord. We analyzed the origin and morphological features of sensory ganglionic macrophages after nerve ligation or transection using wild-type mice and mice with bone-marrow cell transplants. METHODS: After protecting the head of C57BL/6J mice with lead caps, they were irradiated and transplanted with bone-marrow-derived cells from GFP transgenic mice. The infraorbital nerve of a branch of the trigeminal nerve of wild-type mice was ligated or the infraorbital nerve of GFP-positive bone-marrow-cell-transplanted mice was transected. After immunostaining the trigeminal ganglion, the structures of the ganglionic macrophages, neurons, and satellite glial cells were analyzed using two-dimensional or three-dimensional images. RESULTS: The number of damaged neurons in the trigeminal ganglion increased from day 1 after infraorbital nerve ligation. Ganglionic macrophages proliferated from days 3 to 5. Furthermore, the numbers of macrophages increased from days 3 to 15. Bone-marrow-derived macrophages increased on day 7 after the infraorbital nerve was transected in the trigeminal ganglion of GFP-positive bone-marrow-cell-transplanted mice but most of the ganglionic macrophages were composed of tissue-resident cells. On day 7 after infraorbital nerve ligation, ganglionic macrophages increased in volume, extended their processes between the neurons and satellite glial cells, and contacted these neurons. Most of the ganglionic macrophages showed an M2 phenotype when contact was observed, and little neuronal cell death occurred. CONCLUSION: Most of the macrophages that appear after a nerve injury are tissue-resident, and these make direct contact with damaged neurons that act in a tissue-protective manner in the M2 phenotype. These results imply that tissue-resident macrophages signal to neurons directly through physical contact.

DOI： 10.1186/s12974-021-02283-z

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOCIETY OF HISTOCHEMISTRY AND CYTOCHEMISTRY  

<p>Proprioception from masticatory apparatus and periodontal ligaments comes through the trigeminal mesencephalic nucleus (Vmes). We evaluated the effects of tooth loss on neurodegeneration of the Vmes and trigeminal motor nucleus (Vmo). Bilateral maxillary molars of 2-month-old C57BL/6J mice were extracted under anesthesia. Neural projections of the Vmes to the periodontium were confirmed by injecting Fluoro-Gold (FG) retrogradely into the extraction sockets, and for the anterograde labeling adeno-associated virus encoding green fluorescent protein (AAV-GFP) was applied. For immunohistochemistry, Piezo2, ATF3, Caspase 3, ChAT and TDP-43 antibodies were used. At 1 month after tooth extraction, the number of Piezo2-immunoreactive (IR) Vmes neurons were decreased significantly. ATF3-IR neurons were detected on day 5 after tooth extraction. Dead cleaved caspase-3-IR neurons were found among Vmes neurons on days 7 and 12. In the Vmo, neuronal cytoplasmic inclusions (NCIs) formation type of TDP-43 increased at 1 and 2 months after extraction. These indicate the existence of neural projections from the Vmes to the periodontium in mice and that tooth loss induces the death of Vmes neurons followed by TDP-43 pathology in the Vmo. Therefore, tooth loss induces Vmes neuronal cell death, causing Vmo neuro­degeneration and presumably affecting masticatory function.</p>

DOI： 10.1267/ahc.20-00036

PubMed

Language：Japanese   Publisher：Journal of Alzheimer's Disease  

DOI： 10.3233/JAD-200257

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Language：English Book type：Scholarly book

Language：Japanese Book type：Scholarly book

Language：Japanese Book type：Scholarly book

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：English   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Event date： 2019.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：新潟市  

Event date： 2019.3

Language：Japanese   Presentation type：Poster presentation  

Event date： 2018.9

Language：Japanese   Presentation type：Poster presentation  

Event date： 2017.9

Language：Japanese   Presentation type：Oral presentation (general)  

Event date： 2016.8

Language：Japanese   Presentation type：Oral presentation (general)