Brain Formaldehyde is Related to Water Intake behavior

Abstract

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.

Formaldehyde produced from d-ribose under neutral and alkaline conditions

“…The concentration of endogenous formaldehyde is positively correlated with the severity of cognitive impairments in Alzheimer’s disease (AD) patients [21], which is due to the metabolic imbalance between synthesis and degradation of formaldehyde [16,34]. The average pathological concentration of formaldehyde in the urine of AD patients is 13.70 ± 5.17 μM, i.e., the pathological urine formaldehyde concentration for AD is ˜1.4 times as much as the physiological concentration (9.61 ± 2.90 μM) in age-matched normal participants [24]. Accumulation of a pathological concentration of endogenous formaldehyde (15 μM) induced chronic damage to N2a cells [24,51], especially the impairment of neuronal processes and neurites, which may result from Tau hyperphosphorylation [51].…”

“…The average pathological concentration of formaldehyde in the urine of AD patients is 13.70 ± 5.17 μM, i.e., the pathological urine formaldehyde concentration for AD is ˜1.4 times as much as the physiological concentration (9.61 ± 2.90 μM) in age-matched normal participants [24]. Accumulation of a pathological concentration of endogenous formaldehyde (15 μM) induced chronic damage to N2a cells [24,51], especially the impairment of neuronal processes and neurites, which may result from Tau hyperphosphorylation [51]. As described previously [52], the elevation of brain formaldehyde levels resulted from the administration of d -ribose may lead to cognitive impairment.…”

“…Formaldehyde, the simplest aldehyde [16], is a severe cytotoxic agent [[17], [18], [19], [20]] and is implicated in aging and a variety of diseases, such as neurodegenerative diseases [[21], [22], [23], [24], [25]], diabetes [[26], [27], [28]], pulmonary fibrosis [29], chronic heart disorders and cancers [30,31]. Formaldehyde in the human body comes from endogenous and exogenous sources [32].…”

Early multidomain intervention to stave off Alzheimer’s disease

“…慢性脱水损害认知功能, 继而又 使患者忘记饮水而加重脱水 [48] . 值得注意的是, 内源 甲 醛 浓 度 显著 低 于 饮 水剥 夺 组 [51] . 这 些 结 果 表明 , 按照《中国居民膳食营养素参考摄入量》所建议的饮 水量, 特别是在早晨醒来后饮水(成年男性350 mL, 成年女性300 mL), 可以显著降低甲醛在人体内的浓 度.…”

The Antioxidant Cofactor Alpha-Lipoic Acid May Control Endogenous Formaldehyde Metabolism in Mammals

“…It has been suggested that FA toxicity is related to the main hallmarks of age-related neuronal damage and Alzheimer's disease pathology (Tong et al, 2011 , 2013a , b , 2017 ; Liu et al, 2013 ). The elevated levels of FA found in Alzheimer's disease (Tang et al, 2013a , b ; Tong et al, 2013a , 2017 ) may play important roles in β-amyloid (Aβ) aggregation and cerebral amyloid angiopathy (Li et al, 2016b ).…”