School of Stomatology, Capital Medical University, Beijing, China.
Department of Prosthodontics, Beijing Stomatological Hospital, Capital Medical University, Beijing, China.
CNS Neurosci Ther. 2024 Jun;30(6):e14750. doi: 10.1111/cns.14750.
Tooth loss is closely related to cognitive impairment, especially affecting cognitive functions involving hippocampus. The most well-known function of the hippocampus is learning and memory, and the mechanism behind is neuroplasticity, which strongly depends on the level of brain-derived neurotrophic factor (BDNF). While research has delved into the possible mechanisms behind the loss of teeth leading to cognitive dysfunction, there are few studies on the plasticity of sensory neural pathway after tooth loss, and the changes in related indicators of synaptic plasticity still need to be further explored.
In this study, the bilateral maxillary molars were extracted in Sprague-Dawley rats of two age ranges (young and middle age) to establish occlusal support loss model; then, the spatial cognition was tested by Morris Water Maze (MWM). Quantitative real-time PCR (qPCR) and Western Blotting (WB) were used to detect BDNF, AKT, and functional proteins (viz., PSD95 and NMDAR) of hippocampal synapses. Golgi staining was used to observe changes in ascending nerve pathway. IF was used to confirm the location of BDNF and AKT expressed in hippocampus.
MWM showed that the spatial cognitive level of rats dropped after occlusal support loss. qPCR, WB, and IF suggested that the BDNF/AKT pathway was down-regulated in the hippocampus. Golgi staining showed the neurons of ascending sensory pathway decreased in numbers.
Occlusal support loss caused plastic changes in ascending nerve pathway and induced cognitive impairment in rats by down-regulating BDNF and synaptic plasticity.
牙齿缺失与认知功能障碍密切相关，尤其影响到涉及海马体的认知功能。海马体最著名的功能是学习和记忆，其机制是神经可塑性，而神经可塑性强烈依赖于脑源性神经营养因子（BDNF）的水平。虽然研究已经深入探讨了牙齿缺失导致认知功能障碍的可能机制，但关于牙齿缺失后感觉神经通路的可塑性的研究较少，突触可塑性相关指标的变化仍需要进一步探索。
本研究通过拔除 Sprague-Dawley 大鼠双侧上颌磨牙（幼龄和中年）建立咬合丧失模型；然后，通过 Morris 水迷宫（MWM）测试空间认知能力。采用实时定量 PCR（qPCR）和 Western Blotting（WB）检测海马突触的 BDNF、AKT 和功能蛋白（即 PSD95 和 NMDAR）。高尔基染色观察上行神经通路的变化。免疫荧光（IF）用于确认海马中表达的 BDNF 和 AKT 的位置。
MWM 显示咬合丧失后大鼠的空间认知水平下降。qPCR、WB 和 IF 表明海马体中的 BDNF/AKT 通路下调。高尔基染色显示上行感觉通路的神经元数量减少。
咬合丧失通过下调 BDNF 和突触可塑性导致上行神经通路的可塑性改变，并引起大鼠认知障碍。
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