Li Yingxue, Yang Yao, Guan Xiaoyue, Liu Zhijun, Pan Lifei, Wang Yuting, Jia Xiangbin, Yang Jianmin, Hou Tiezhou
Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, China.
Department of Cariology and Endodontics, College of Stomatology, Xi'an Jiaotong University, Xi'an, China.
Oral Dis. 2024 Nov;30(8):5408-5420. doi: 10.1111/odi.14944. Epub 2024 Apr 3.
Emerging evidence supports the association between periodontitis and depression, although the mechanisms are unclear. This study investigated the role of SorCS2 in the pathogenesis of periodontitis-induced depression.
An experimental periodontitis model was established using SorCS2 knockout mice and their wild-type littermates, and depression-like behaviour was evaluated. The expression of proBDNF signalling, neuronal activity, and glutamate-associated signalling pathways were further measured by western blotting and immunofluorescence. In addition, neuroinflammatory status, astrocytic and microglial markers, and the expression of corticosterone-related factors were measured by immunofluorescence, western blotting, and enzyme-linked immunosorbent assays.
SorCS2 deficiency alleviated periodontitis-induced depression-like behaviour in mice. Further results suggested that SorCS2 deficiency downregulated the expression of pro-BDNF and glutamate signalling and restored neuronal activities in mice with periodontitis. Neuroinflammation in the mouse hippocampus was triggered by experimental periodontitis but was not affected by SorCS2 deficiency. The levels of corticosterone and the expression of glucocorticoid receptors were also not altered.
Our study, for the first time, reveals the critical role of SorCS2 in the pathogenesis of periodontitis-induced depression. The underlying mechanism involves proBDNF and glutamate signalling in the hippocampus, providing a novel therapeutic target for periodontitis-associated depression.
尽管机制尚不清楚，但新出现的证据支持牙周炎与抑郁症之间的关联。本研究调查了SorCS2在牙周炎诱导的抑郁症发病机制中的作用。
使用SorCS2基因敲除小鼠及其野生型同窝小鼠建立实验性牙周炎模型，并评估抑郁样行为。通过蛋白质免疫印迹法和免疫荧光进一步检测前体脑源性神经营养因子（proBDNF）信号传导、神经元活性和谷氨酸相关信号通路的表达。此外，通过免疫荧光、蛋白质免疫印迹法和酶联免疫吸附测定法测量神经炎症状态、星形胶质细胞和小胶质细胞标志物以及皮质酮相关因子的表达。
SorCS2缺乏减轻了小鼠牙周炎诱导的抑郁样行为。进一步的结果表明，SorCS2缺乏下调了pro-BDNF和谷氨酸信号传导的表达，并恢复了牙周炎小鼠的神经元活性。实验性牙周炎引发了小鼠海马体中的神经炎症，但不受SorCS2缺乏的影响。皮质酮水平和糖皮质激素受体的表达也未改变。
我们的研究首次揭示了SorCS2在牙周炎诱导的抑郁症发病机制中的关键作用。潜在机制涉及海马体中的proBDNF和谷氨酸信号传导，为牙周炎相关抑郁症提供了新的治疗靶点。
