Department of Orthodontic Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan.
Department of Orthodontic Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan.
Neuropeptides. 2023 Dec;102:102370. doi: 10.1016/j.npep.2023.102370. Epub 2023 Aug 17.
Binding of brain-derived neurotrophic factor (BDNF) to its receptor tyrosine kinase B (TrkB) is essential for the development of the hippocampus, which regulates memory and learning. Decreased masticatory stimulation during growth reportedly increases BDNF expression while decreasing TrkB expression in the hippocampus. Increased BDNF expression is associated with Wnt family member 3A (Wnt3a) expression and decreased expression of Rho GTPase Activating Protein 33 (ARHGAP33), which regulates intracellular transport of TrkB. TrkB expression may be decreased at the cell surface and affects the hippocampus via BDNF/TrkB signaling. Mastication affects cerebral blood flow and the neural cascade that occurs through the trigeminal nerve and hippocampus. In the current study, we hypothesized that decreased masticatory stimulation reduces memory/learning in mice due to altered Wnt3a and ARHGAP33 expression, which are related to memory/learning functions in the hippocampus. To test this hypothesis, we fed mice a powdered diet until 14 weeks of age and analyzed the BDNF and TrkB mRNA expression in the right hippocampus using real-time polymerase chain reaction and Wnt3a and ARHGAP33 levels in the left hippocampus using western blotting. Furthermore, we used staining to assess BDNF and TrkB expression in the hippocampus and the number of nerve cells, the average size of each single cell and the area of intercellular spaces of the trigeminal ganglion (TG). We found that decreased masticatory stimulation affected the expression of BDNF, Wnt3a, ARHGAP33, and TrkB proteins in the hippocampus, as well as memory/learning. The experimental group showed significantly decreased numbers of neurons and increased the area of intercellular spaces in the TG. Our findings suggest that reduced masticatory stimulation during growth induces a decline in memory/learning by modulating molecular transmission mechanisms in the hippocampus and TG.
脑源性神经营养因子（BDNF）与受体酪氨酸激酶 B（TrkB）的结合对于海马体的发育至关重要，而海马体则调节着记忆和学习。据报道，生长过程中咀嚼刺激减少会增加海马体中的 BDNF 表达，同时减少 TrkB 表达。BDNF 表达增加与 Wnt 家族成员 3A（Wnt3a）表达增加有关，同时 Rho GTPase 激活蛋白 33（ARHGAP33）表达减少，后者调节 TrkB 的细胞内转运。TrkB 表达可能在细胞表面减少，并通过 BDNF/TrkB 信号影响海马体。咀嚼会影响大脑血流和通过三叉神经和海马体发生的神经级联反应。在当前研究中，我们假设由于与海马体记忆/学习功能相关的 Wnt3a 和 ARHGAP33 表达改变，咀嚼刺激减少会导致小鼠记忆/学习能力下降。为了验证这一假设，我们给小鼠喂食粉末状饮食，直到它们 14 周大，然后使用实时聚合酶链反应分析右海马体中的 BDNF 和 TrkB mRNA 表达，使用 Western blot 分析左海马体中的 Wnt3a 和 ARHGAP33 水平。此外，我们使用染色来评估海马体中的 BDNF 和 TrkB 表达以及神经细胞数量、每个单个细胞的平均大小和三叉神经节（TG）细胞间隙的面积。我们发现，咀嚼刺激减少会影响海马体中 BDNF、Wnt3a、ARHGAP33 和 TrkB 蛋白的表达，以及记忆/学习能力。实验组显示神经元数量明显减少，TG 细胞间隙面积增加。我们的研究结果表明，生长过程中咀嚼刺激减少会通过调节海马体和 TG 中的分子传递机制，导致记忆/学习能力下降。
