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.

Keywords: arginine vasopressin; behavior; formaldehyde; semicarbazide-sensitive amine oxidase; water intake.

Figure 1.

Changes in quantity and frequency of water intake as well as the brain formaldehyde and AVP concentrations in mice at different ages. C57 BL/6 mice were maintained under pathogen-free conditions (22 ± 2°C, humidity 50%) and provided a regular diet and sterile water. Their drinking behaviors were recorded with an infrared camera, followed by counting the volume (ml/h) (A) and frequency (times/h) of water intake (B) at different ages (3, 6 and 10 months, n = 6). Their brain formaldehyde (μM) (C) and blood AVP (pg/ml) (D) levels were also measured at these ages (n = 8). The data are shown as the means ± SE; *, P < 0.05; **, P < 0.01

Figure 2.

Changes in the water quantities, drinking frequencies, and brain formaldehyde and serum AVP concentrations in mice after the AVP injection. The conditions were the same as Figure 1, except that the 3-month-old C57 mice (n = 8) were administered 100 μl of AVP (2 ng/kg, once at the beginning) through an intravenous injection in the tail, followed by measurements of their drinking quantities (A), frequencies (B), and brain formaldehyde (C) and AVP levels (D) for 24 hours. The data are shown as the means ± SE; *, P < 0.05; **, P <0.01; ***, P < 0.001.

Figure 3.

Concentrations and enzymatic activities of SSAO in the brain and serum of mice injected with AVP. The conditions were the same as for Figure 2. After an intravenous injection of AVP in the tail, we detected the concentrations and enzymatic activities of SSAO in the serum (A, B) and brain (C, D) by ELISA. The data are shown as the means ± SE; *, P < 0.05; **, P < 0.01; ***, P < 0.001.

Figure 4.

Changes in the water quantities, drinking frequencies, and brain formaldehyde and serum AVP concentrations in mice injected with formaldehyde. The conditions were the same as Figure 1, except that the 3-month-old C57 mice (n = 8) were intraperitoneally injected with formaldehyde (0.5 mg/kg, once daily) for 7 days, followed by measurements of their drinking frequencies (A), water quantities (B), and brain formaldehyde (C), serum AVP (D) and ANG II levels (E). The data are shown as the means ± SE; *, P < 0.05; **, P < 0.01.

Figure 5.

Changes in the concentrations of formaldehyde in humans subjected to water deprivation. The participants’ (n = 20) activities were prescribed as indicating in the recruiting requirements. Urine samples were collected in the morning before breakfast (8:00 a.m.), prior to lunch (12:30) and before going to sleep (11:00 p.m.) to measure the formaldehyde levels (FA/Urc ratios). The changes in the uric formaldehyde concentrations were measured for the participants who drank water according to their own daily habits (A), those who were forbidden from drinking water (B) and those who drank water in prescribed quantities from 8:30 to 12:30 (C). Comparison of the formaldehyde concentrations between the water-deprived group and the group with a prescribed water quantity (D). The concentration of formaldehyde in the morning was set to 100%. The data are shown as the means ± SE; *, P <0.05; **, P <0.01.