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牙周组织损伤诱导C57BL/6J小鼠三叉神经中脑核神经元细胞死亡及三叉神经运动核神经退行性变。

The Periodontium Damage Induces Neuronal Cell Death in the Trigeminal Mesencephalic Nucleus and Neurodegeneration in the Trigeminal Motor Nucleus in C57BL/6J Mice.

作者信息

Dhar Ashis, Kuramoto Eriko, Fukushima Makoto, Iwai Haruki, Yamanaka Atsushi, Goto Tetsuya

机构信息

Department of Oral Anatomy and Cell Biology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.

出版信息

Acta Histochem Cytochem. 2021 Feb 25;54(1):11-19. doi: 10.1267/ahc.20-00036. Epub 2021 Feb 16.

Abstract

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.

摘要

来自咀嚼器官和牙周韧带的本体感觉通过三叉神经中脑核(Vmes)传导。我们评估了牙齿缺失对Vmes和三叉神经运动核(Vmo)神经退行性变的影响。在麻醉下拔除2月龄C57BL/6J小鼠的双侧上颌磨牙。通过向拔牙窝逆行注射荧光金(FG)来确认Vmes向牙周组织的神经投射,并应用编码绿色荧光蛋白的腺相关病毒(AAV-GFP)进行顺行标记。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免疫反应性(IR)Vmes神经元数量显著减少。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,拔牙后1个月和2个月时,TDP-43的神经元胞质内含物(NCI)形成类型增加。这些表明小鼠中存在从Vmes到牙周组织的神经投射,并且牙齿缺失会诱导Vmes神经元死亡,随后在Vmo中出现TDP-43病理变化。因此,牙齿缺失会诱导Vmes神经元细胞死亡,导致Vmo神经退行性变,并可能影响咀嚼功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4679/7947638/5995e167eab1/AHC20-00036f01.jpg

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