Li Ting, Su Tao, He Yingge, Lu Jihui, Mo Weichuan, Wei Yan, He Rongqiao
1State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; 6University of Chinese Academy of Sciences, Beijing 100049, China.
1State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Aging Dis. 2016 Oct 1;7(5):561-584. doi: 10.14336/AD.2016.0323. eCollection 2016 Oct.
A promising strategy for the prevention of Alzheimer's disease (AD) is the identification of age-related changes that place the brain at risk for the disease. Additionally, AD is associated with chronic dehydration, and one of the significant changes that are known to result in metabolic dysfunction is an increase in the endogenous formaldehyde (FA) level. Here, we demonstrate that the levels of uric formaldehyde in AD patients were markedly increased compared with normal controls. The brain formaldehyde levels of wild-type C57 BL/6 mice increased with age, and these increases were followed by decreases in their drinking frequency and water intake. The serum arginine vasopressin (AVP) concentrations were also maintained at a high level in the 10-month-old mice. An intravenous injection of AVP into the tail induced decreases in the drinking frequency and water intake in the mice, and these decreases were associated with increases in brain formaldehyde levels. An ELISA assay revealed that the AVP injection increased both the protein level and the enzymatic activity of semicarbazide-sensitive amine oxidase (SSAO), which is an enzyme that produces formaldehyde. In contrast, the intraperitoneal injection of formaldehyde increased the serum AVP level by increasing the angiotensin II (ANG II) level, and this change was associated with a marked decrease in water intake behavior. These data suggest that the interaction between formaldehyde and AVP affects the water intake behaviors of mice. Furthermore, the highest concentration of formaldehyde in vivo was observed in the morning. Regular water intake is conducive to eliminating endogenous formaldehyde from the human body, particularly when water is consumed in the morning. Establishing good water intake habits not only effectively eliminates excess formaldehyde and other metabolic products but is also expected to yield valuable approaches to reducing the risk of AD prior to the onset of the disease.
预防阿尔茨海默病（AD）的一个有前景的策略是识别与年龄相关的、使大脑易患该疾病的变化。此外，AD与慢性脱水有关，已知会导致代谢功能障碍的一个显著变化是内源性甲醛（FA）水平升高。在此，我们证明AD患者的尿酸化甲醛水平与正常对照组相比显著升高。野生型C57 BL/6小鼠的脑甲醛水平随年龄增长而升高，随后其饮水频率和饮水量下降。10月龄小鼠的血清精氨酸加压素（AVP）浓度也维持在较高水平。向小鼠尾部静脉注射AVP会导致其饮水频率和饮水量下降，且这些下降与脑甲醛水平升高有关。酶联免疫吸附测定（ELISA）显示，注射AVP会增加氨基脲敏感胺氧化酶（SSAO，一种产生甲醛的酶）的蛋白水平和酶活性。相反，腹腔注射甲醛会通过增加血管紧张素II（ANG II）水平来提高血清AVP水平，且这种变化与饮水量行为的显著下降有关。这些数据表明甲醛与AVP之间的相互作用会影响小鼠的饮水行为。此外，在体内观察到甲醛的最高浓度出现在早晨。规律饮水有助于从人体中清除内源性甲醛，尤其是在早晨饮水时。养成良好的饮水习惯不仅能有效清除过量的甲醛和其他代谢产物，还有望在疾病发病前产生降低AD风险的有价值方法。
