Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
Neuromolecular Med. 2011 Sep;13(3):197-203. doi: 10.1007/s12017-011-8151-0. Epub 2011 Jul 13.
Amyloid-β plays a causative role in Alzheimer's disease. Occlusal disharmony causes chronic psychological stress, and psychological stress increases amyloid-β accumulation. The purpose of the present study was to investigate whether occlusal disharmony-induced psychological stress affects the accumulation of amyloid-β and its related gene expressions in the rat hippocampus. Eight-week-old male Wistar rats (n = 18) were divided into three groups of six rats each: (1) a control group that received no treatment for 8 weeks; (2) an occlusal disharmony group that underwent cutoff maxillary molar cusps for 8 weeks; and (3) a recovered group that underwent cutoff maxillary molar cusps for 4 weeks followed by recovery for 4 weeks. Occlusal disharmony increased plasma corticosterone levels in a time-dependent manner. Levels of amyloid-β 40 and 42, glucocorticoid receptor (Gr) protein, and cleaved caspase 3 (Casp3) as well as gene expressions of amyloid precursor protein, beta-secretase, Casp3, and Gr in the hippocampus in the occlusal disharmony group were significantly higher than those in the control group (P < 0.016). These findings were significantly improved by recovery of occlusion (P < 0.016). These results indicate that psychological stress induced by occlusal disharmony reversibly induces amyloid-β 40 and 42 in the rat hippocampus through the glucocorticoid signal.
淀粉样蛋白-β在阿尔茨海默病中起致病作用。咬合失调会导致慢性心理应激,而心理应激会增加淀粉样蛋白-β的积累。本研究旨在探讨咬合失调引起的心理应激是否会影响大鼠海马区淀粉样蛋白-β及其相关基因的表达。将 8 周龄雄性 Wistar 大鼠(n=18)分为三组,每组 6 只:(1)对照组,8 周内不进行任何处理;(2)咬合失调组,8 周内切断上颌磨牙牙尖;(3)恢复组,切断上颌磨牙牙尖 4 周后恢复 4 周。咬合失调使血浆皮质酮水平呈时间依赖性增加。咬合失调组大鼠海马区淀粉样蛋白-β 40 和 42、糖皮质激素受体(Gr)蛋白和裂解型半胱天冬酶 3(Casp3)水平以及淀粉样前体蛋白、β-分泌酶、Casp3 和 Gr 的基因表达均明显高于对照组(P<0.016)。咬合恢复后这些变化明显改善(P<0.016)。这些结果表明,咬合失调引起的心理应激通过糖皮质激素信号可逆地诱导大鼠海马区淀粉样蛋白-β 40 和 42 的产生。