Exposure to a real traffic environment impairs brain cognition in aged mice.

Traffic-related air pollution (TRAP) has been a common public health problem, which is associated with central nervous system dysfunction according to large-scale epidemiological studies. Current studies are mostly limited to artificial laboratory exposure environments and specific genetic mechanisms remain unclear. Therefore, we chose a real-world transportation environment to expose aged mice, transporting them from the laboratory to a 1-m-high dry platform inside the campus and tunnel, and the mice were exposed daily from 7 a.m. to 7 p.m. for 2, 4 and 12 weeks respectively. Compared with the control group (in campus), the memory function of mice in the experimental group (in tunnel) was significantly impaired in the Morris water maze test. TRAP exposure increased the number of activated microglia in the hippocampal DG, CA1, CA3 regions and dorsolateral prefrontal cortex (dPFC). And neuroinflammation and oxidative stress levels were up-regulated in both hippocampus and dPFC of aged mice. By screening the risk genes of Alzheimer's disease, we found the mRNA and protein levels of ABCA7 were down-regulated and those of PYK2 were up-regulated. The DNA methylation ratios increased in four CpG sites of abca7 promoter region and decreased in one CpG site of pyk2 promoter region, which were consistent with the altered expression of ABCA7 and PYK2. In conclusion, exposure to the real traffic environment impaired memory function and enhanced neuroinflammation and oxidative stress responses, which could be relevant to the altered expression and DNA methylation levels of ABCA7 and PYK2. Our work provides a new and promising understanding of the pathological mechanisms of cognitive impairment caused by traffic-related air pollution.

Dose- and time- effect responses of DNA methylation and histone H3K9 acetylation changes induced by traffic-related air pollution.

As an important risk factor of respiratory disorders, traffic-related air pollution (TRAP) has caused extensive concerns. Epigenetic change has been considered a link between TRAP and respiratory diseases. However, the exact effects of TRAP on epigenetic changes are still unclear. Here we investigated the dose- and time- effect responses of TRAP on DNA methylations and H3K9 acetylation (H3K9ac) in both blood and lung tissues of rats. The findings showed that every 1 µg/m3 increase of TRAP components were associated with changes in %5 mC (95% CI) in LINE-1, iNOS, p16CDKN2A, and APC ranging from -0.088% (-0.150, -0.026) to 0.102 (0.049, 0.154), as well as 0.276 (0.053, 0.498) to 0.475 (0.103, 0.848) ng/mg increase of H3K9ac. In addition, every 1 more day exposure at high level of TRAP (in tunnel) also significantly changed the levels of DNA methylation (ranging from -0.842% to 0.248%) and H3K9ac (16.033 and 15.718 ng/mg pro in PBMC and lung tissue, respectively) changes. Season and/or sex could interact with air pollutants in affecting DNA methylation and H3K9ac. The findings showed that TRAP exposure is dose- and time- dependently associated with the changes of DNA methylation and H3K9ac.

[Effects of Traffic-related Air Pollution Exposure on DNA Methylation].

The goal of the present study was to explore the effects of traffic-related air pollution exposure on DNA methylation. Into five groups of 6, 30 healthy Wistar rats were randomly divided. Three groups of rats were then exposed to traffic-related air pollution at high (tunnel), moderate (crossroad), and low (control) pollution levels for 7 d, whereas the two other groups were exposed in the tunnel for 14 d/28 d. The levels of PM10 and NO2 were measured during the exposure. The study was performed in spring and autumn, and lung tissue and blood were collected after the exposure. Promoter methylation levels of p 53 , MGMT, and MAGE-A 4 were quantified via pyrosequencing. The levels of PM10 and NO2 in the crossroad and tunnel groups were significantly higher than those in the control group. After 7 d exposure in autumn, promoter methylation levels of p 53 and MGMT in lung tissue significantly decreased, and the methylation status continued to decrease with increasing exposure time; MAGE-A 4 was highly methylated and showed no difference among the three groups. DNA methylation in lung tissue was more likely to be changed compared with that in blood during 7 d exposure. As the exposure time increased, DNA methylation changes between blood and lung tissue started to coincide. In lung tissue, PM10 exposure was significantly associated with decreased p 53 promoter methylation (r=-0.347, P=0.038) and NO2 exposure was significantly associated with decreased promoter methylation of p 53, MGMT, and MAGE-A 4 (r=-0.482, -0.444, and -0.346, respectively; P< 0.05). In blood, PM10 and NO2 were significantly and positively associated with MAGE-A 4 promoter methylation (r=0.395 and 0.431, respectively; P< 0.05). Traffic-related air pollution exposure may induce promoter hypomethylation of p 53 and MGMT.

Higher Levels of Magnesium and Lower Levels of Calcium in Whole Blood Are Positively Correlated with the Metabolic Syndrome in a Chinese Population: A Case-Control Study.

Magnesium (Mg) and calcium (Ca) are essential for numerous kinds of metabolisms in human body. To investigate the associations between Mg and Ca and the ratio of Ca to Mg (Ca/Mg) in whole blood with metabolic syndrome (MetS) in a Chinese population, a matched case-control study including 204 MetS patients and 204 healthy controls (aged 48-89) was carried out in 2011. MetS were diagnosed according to the criteria of Chinese Diabetes Society. Controls had no abnormal metabolic components and were matched with cases by age, gender and region. Blood samples were collected in the morning after an overnight fast. Whole blood Mg and Ca were determined by flame atomic absorption spectrometry. Subjects who were male constituted 44.1% of the part of this study. The average age was 64.0 ± 7.18, and the average body mass index was 24.3 ± 3.75. The MetS group showed significantly higher Mg and lower Ca and Ca/Mg as compared with the control group. Comparing with the bottom tertile (T1) of Mg, increased ORs for MetS were found in median tertile (T2) and top tertile (T3) of Mg. For Ca, T2 and T3 were negatively associated with MetS. Inverse relationship was also found between Ca/Mg ratio and MetS. Our findings suggested that increased Mg and decreased Ca and Ca/Mg in whole blood were correlated with MetS in Chinese adults.

High levels of plasma selenium are associated with metabolic syndrome and elevated fasting plasma glucose in a Chinese population: A case-control study.

BACKGROUND: Selenium is important for human health and involved in various metabolic processes. Deficiency of selenium associates with increased risk for cancer and cardiovascular diseases. There has been an increase use of selenium supplements for the treatment of autoimmune thyroid conditions. However, the potential biological effects of selenium overload arouse the public concern. The aim of this study was to investigate the associations of plasma selenium concentrations of adults with metabolic syndrome (MS) in Chinese population. METHODS: A matched case-control study including 204 metabolic syndrome patients and 204 healthy controls was conducted in 2012. The MS cases were defined according to the criteria of Chinese Diabetes Society (CDS). Healthy controls without abnormality of metabolic components were matched with cases in age, gender and region. Plasma concentrations of selenium were determined by graphite furnace atomic absorption spectrometry (GFAAS). Fasting plasma glucose (FPG), total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL), and low density lipoprotein cholesterol (LDL) were detected by automatic biochemical analyzer. RESULTS: The median levels of plasma selenium in MS group were 146.3 (107.3-199.4)µg/L, which were significantly higher than that in the control group (127.4: 95.7-176.0)µg/L; Plasma levels of selenium were related to the risk of MS in dose-response manner. Risk of MS was significantly higher in subjects with plasma selenium in the highest tertile (T3: ≥176.0µg/L) compared to those in the lowest tertile (T1: <95.7µg/L) [odds ratio (OR)=2.416 (95% CI: 1.289-4.526)]. The plasma levels of selenium were positively correlated with fasting plasma glucose (FPG) (rs=0.268, P<0.001). Plasma selenium at the median (T2: 95.7-176.0µg/L) or upper tertile (T3: ≥176.0µg/L) was associated with increased risk of elevated FPG (defined by FPG≥6.1mmol/L) as compared with the lowest tertile (T1: ≤95.7µg/L) [T2 vs. T1, OR=3.487 (1.738-6.996); T3 vs. T1, OR=6.245 (3.005-12.981)]. CONCLUSIONS: Higher levels of plasma selenium might increase the risk of metabolic syndrome and elevated fasting plasma glucose. Selenium supplements should be used with prudence for CVD and cancer prevention.

Citric acid reduces the decline in P300 amplitude induced by acute alcohol consumption in healthy adults.

Event-related potential (ERP) is a reliable neuroelectric measure of brain activity that helps to confirm the assessment of mental status and cognitive impairment. Many studies have reported that alcoholics show a significantly lower ERP P300 amplitude than the norm. In the present study, ERP P300 waves were measured to evaluate the effect of citric acid on cognitive function during excessive alcohol consumption in healthy adults. Five volunteers were selected through clinical interview, physical examination, and psychiatric assessment for participation in this study. In a double-blind placebo-controlled before-after design, each subject was treated with 5 ml/kg body weight alcohol, 5 ml/kg body weight alcohol and 1 mg citric acid, or a placebo on three separate occasions, one week apart. ERP P300, blood biochemical indicators, blood alcohol concentrations (BACs) and acetaldehyde concentrations were assessed. Repeated measure analysis of variance (ANOVA) with a within-subjects factor was used to evaluate differences in blood biochemical indicators, BACs, blood acetaldehyde concentrations, and ERP P300 in the three sessions of assessments. Several blood biochemical indicators showed significant differences between treatments, including the levels of cholinesterase (CHE), total bile acid (TBA), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), and glycylproline dipeptidyl aminopeptidase (GPDA). BACs after consumption of alcohol alone or citric acid with alcohol were significantly higher compared to those after placebo treatment (P<0.05). There were no significant differences in blood acetaldehyde concentrations between the treatments. The P300 amplitudes on the frontal (Fz), central (Cz), and parietal (Pz) regions of the scalp after consumption of alcohol were significantly lower than those after consumption of the placebo or citric acid with alcohol (P<0.05), while there were no significant differences between the latter two treatments. The results of this study suggest that citric acid could reduce the decline in ERP P300 amplitude and cognitive ability induced by acute alcohol consumption. It may also affect some blood biochemical indicators, but the specific mechanisms need further research.