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.

来自咀嚼器和牙周膜的本体感受通过三叉神经中脑核（Vmes）来进行。我们评估了牙齿脱落对Vmes和三叉神经运动神经核（Vmo）神经变性的影响。在麻醉下提取2个月大的C57BL / 6J小鼠的双侧上颌磨牙。通过将氟金（FG）逆行注入提取套中，证实了Vmes对牙周的神经投射，并且对顺行标记应用了编码绿色荧光蛋白（AAV-GFP）的腺相关病毒。对于免疫组织化学，使用了Piezo2，ATF3，Caspase 3，ChAT和TDP-43抗体。拔牙后1个月，Piezo2免疫反应（IR）Vmes神经元的数量明显减少。拔牙后第5天检测到ATF3-IR神经元。在第7天和第12天，在Vmes神经元中发现了裂解的caspase-3-IR死亡神经元。在Vmo中，提取后1和2个月，TDP-43的神经元胞浆内含物（NCI）形成类型增加。这些表明小鼠中存在从Vmes到牙周膜的神经投射，牙齿脱落会导致Vmes神经元的死亡，然后是Vmo中的TDP-43病理。因此，牙齿脱落会导致Vmes神经元细胞死亡，从而导致Vmo神经变性，并可能影响咀嚼功能。这些表明小鼠中存在从Vmes到牙周膜的神经投射，牙齿脱落会导致Vmes神经元的死亡，然后是Vmo中的TDP-43病理。因此，牙齿脱落会导致Vmes神经元细胞死亡，从而导致Vmo神经变性，并可能影响咀嚼功能。这些表明小鼠中存在从Vmes到牙周膜的神经投射，牙齿脱落会导致Vmes神经元的死亡，然后是Vmo中的TDP-43病理。因此，牙齿脱落会导致Vmes神经元细胞死亡，从而导致Vmo神经变性，并可能影响咀嚼功能。