Taslima Ferdous, Abdelhamid Mona, Zhou Chunyu, Chen Yuxin, Jung Cha-Gyun, Michikawa Makoto
Department of Biochemistry, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
J Alzheimers Dis Rep. 2022 Nov 3;6(1):663-675. doi: 10.3233/ADR-220053. eCollection 2022.
Tooth loss is closely associated with Alzheimer's disease (AD). Previously, we reported that tooth loss induced memory impairment in amyloid precursor protein knock-in mice by decreasing neuronal activity and synaptic protein levels and increasing glial activation, neuroinflammation, and pyramidal neuronal cell loss without altering amyloid-β levels in the hippocampus. However, the effects of tooth loss in young wild-type mice have not been explored yet.
We investigated the effects of tooth loss on memory impairment, neuronal activity, synaptic protein levels, glial activation, and pyramidal neuronal cell loss in young wild-type mice.
Two-month-old wild-type mice were randomly divided into control and tooth loss groups. In the tooth loss group, maxillary molar teeth on both sides were extracted, whereas no teeth were extracted in the control group. Two months after tooth extraction, we performed a novel object recognition test to evaluate memory function. Glial activation, neuronal activity, synaptic protein levels, and the number of pyramidal neurons were evaluated using immunofluorescence staining, immunohistochemistry, and western blotting.
The tooth loss group exhibited memory impairment and decreased neuronal activity and the levels of synaptic proteins in both the hippocampus and cortex. Moreover, tooth loss increased the activation of phosphorylated c-Jun N-terminal kinase (JNK), heat shock protein 90 (HSP90), and glial activation and reduced the number of pyramidal neurons in the hippocampus.
Tooth loss in the young wild-type mice will attenuate neuronal activity, decrease synaptic protein levels, and induce pyramidal neuronal loss, and eventually lead to memory impairment.
牙齿缺失与阿尔茨海默病（AD）密切相关。此前，我们报道牙齿缺失通过降低神经元活性和突触蛋白水平、增加胶质细胞活化、神经炎症以及锥体神经元细胞丢失，在淀粉样前体蛋白转基因小鼠中诱导记忆障碍，而不改变海马体中β淀粉样蛋白水平。然而，牙齿缺失对年轻野生型小鼠的影响尚未得到探索。
我们研究了牙齿缺失对年轻野生型小鼠记忆障碍、神经元活性、突触蛋白水平、胶质细胞活化和锥体神经元细胞丢失的影响。
将两个月大的野生型小鼠随机分为对照组和牙齿缺失组。在牙齿缺失组中，拔除双侧上颌磨牙，而对照组未拔牙。拔牙两个月后，我们进行了新物体识别测试以评估记忆功能。使用免疫荧光染色、免疫组织化学和蛋白质印迹法评估胶质细胞活化、神经元活性、突触蛋白水平和锥体神经元数量。
牙齿缺失组表现出记忆障碍，海马体和皮质中的神经元活性以及突触蛋白水平均降低。此外，牙齿缺失增加了磷酸化c-Jun氨基末端激酶（JNK）、热休克蛋白90（HSP90）的活化以及胶质细胞活化，并减少了海马体中锥体神经元的数量。
年轻野生型小鼠牙齿缺失会减弱神经元活性，降低突触蛋白水平，诱导锥体神经元丢失，并最终导致记忆障碍。
