Vitamin E protects dopaminergic neurons against manganese-induced neurotoxicity through stimulation of CHRM1 and KCNJ4.

BACKGROUND: Manganese (Mn) overexposure can induce neurotoxicity and lead to manganism. Vitamin E (Vit E) has neuroprotective effects by acting as an ROS scavenger, preventing mitochondrial dysfunction and neuronal apoptosis. However, the effects of Vit E on Mn-induced nigrostriatal system lesions remains unknown. OBJECTIVES: We aim to investigate whether Vit E has protective effects on Mn-induced nigrostriatal system lesions and mRNA expression profiles in the SN of mice. METHODS: Sixty 8-week-old C57BL/6 male mice were randomly divided into the Control, MnCl2, MnCl2 +Vit E, and Vit E group. Twenty-four hours after the last injection, the behaviour test was performed. The numbers of dopaminergic neurons in Substantia nigra (SN), the contents of dopamine and its metabolite levels in striatium, and the morphology of mitochondria and nuclei in the dopaminergic neurons in SN were detected by immunofluorescence staining, high-performance liquid chromatography, and transmission electron microscopy. Transcriptome analysis was used to analyze the signaling pathways and RT-PCR was used to verify the mRNA levels. RESULTS: Vit E ameliorates behavioral disorders and attenuates the loss of nigral dopaminergic neurons in the Mn-induced mouse model. In addition, Vit E antagonized Mn-induced toxicity by restoring mitochondrial function. The results of transcriptome sequencing and RTPCR show that the protective effect of Vit E was related to the upregulation of CHRM1 and KCNJ4 mRNA in the SN. CONCLUSIONS: Vit E has neuroprotective effects on Mn-induced neurodegeneration in the nigrostriatal system. This effect may be related to the upregulation of CHRM1 and KCNJ4 mRNA stimulated by Vit E in the SN.

Correlation between dietary theobromine intake and low cognitive performance in older adults in the United States: A cross-sectional study based on the National Health and Nutrition Examination Survey.

BACKGROUND AND OBJECTIVES: Few studies have investigated the effects of dietary theobromine intake on the cognitive performance of older adults. Therefore, we investigated these effects in older adults in the United States. METHODS AND STUDY DESIGN: In this cross-sectional study, we used data (2011-2014) from the National Health and Nutrition Examination Survey. Intake of theobromine intake was obtained through two 24-h dietary recall interviews and was adjusted by energy. Cognitive performance was assessed using the animal fluency test, Consortium to Establish a Registry for Alzheimer's Disease Word Learning subtest (CERAD), and Digit Symbol Substitution Test (DSST). Logistic regression and restricted cubic spline models were constructed to evaluate the correlation between the dietary intake of theobromine from different sources and the likelihood of low cognitive performance. RESULTS: The fully adjusted model revealed that compared with the lowest quintile, the odds ratios (with 95% confidence intervals) of cognitive performance in the CERAD test were 0.42 (0.28-0.64), 0.34 (0.14-0.83), 0.25 (0.07-0.87), and 0.35 (0.13-0.95) for the highest quintile of total theobromine intake and that from chocolate, coffee, and cream, respectively. Dose-response relationship analysis indicated nonlinear correlations between the likelihood of low cognitive performance and die-tary theobromine (total intake and that from chocolate, coffee, and cream). An L-shaped relationship was ob-served between total theobromine intake and cognitive performance in the CERAD test. CONCLUSIONS: The dietary intakes of theobromine (total and that from chocolate, coffee, and cream) may protect older adults, particularly men, against low cognitive performance.

Association of lung function with functional limitation in older adults: A cross-sectional study.

INTRODUCTION: Impaired lung function is independently associated with higher rates of disability, however, few studies have examined the association between lung function and functional limitation. This study aimed to assess this association and dose-response relationship in older adults. METHODS: Data from the National Health and Nutrition Examination Survey (2007-2012) was used as a cross-sectional study. Lung function was determined by Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC). Functional limitation in older adults was identified by six self-reported questions on physical function. 3070 adults aged 60 and over were enrolled in our study. Logistic regression models and restricted cubic spline models were applied to examine the association between lung function and the risk of functional limitation. RESULTS: FEV1 and FVC were inversely associated with the risk of functional limitation. In the full adjusted model, compared with the lowest tertile of FEV1, the odds ratios (95% confidence intervals) of functional limitation for tertile 2 and tertile 3 were 0.5422 (0.3848-0.7639) and 0.4403 (0.2685-0.7220), and the odds ratios (95% confidence intervals) of functional limitation for tertile 2 and tertile 3 of FVC were 0.5243 (0.3503-0.7848) and 0.3726 (0.2072-0.6698). Furthermore, an inverse association persisted after stratified analysis by gender and sensitivity analysis. Dose-response analyses showed that the odds of functional limitation declined with increase in FEV1 and FVC in a nonlinear manner. CONCLUSIONS: Lung function was inversely associated with functional limitation among older adults.

Positive association between soil arsenic concentration and mortality from alzheimer's disease in mainland China.

OBJECTIVES: The current study was designed to investigate the relationship between the soil arsenic (As) concentration and the mortality from Alzheimer's disease (AD) in mainland China. STUDY DESIGN: Ecological study. METHODS: Twenty-two provinces and 3 municipal districts in mainland China were included in this study. The As concentrations in soil in 1990 was obtained from the China State Environmental Protection Bureau; the data on annual mortality of AD from 1991 to 2000 were obtained from the National Death Cause Surveillance Database of China. Using these data, we calculated the spearman correlation coefficient between soil As concentration and AD mortality, and the relative risk (RR) between soil As levels and AD mortality by quartile-dividing study groups. RESULTS: The spearman correlation coefficient between As concentration and AD mortality was 0.552 (p = 0.004), 0.616 (p = 0.001) and 0.622 (p = 0.001) in the A soil As (eluvial horizon), the C soil As (parent material horizon), and the Total soil As (A soil As + C soil As), respectively. When the A soil As concentration was over 9.05 mg/kg, 10.40 mg/kg and 13.10 mg/kg, the relative risk was 0.835 (95 % CI: 0.832, 0.838), 1.969 (95 %CI: 1.955, 1.982), and 2.939 (95 % CI: 2.920, 2.958), respectively; when the C soil As reached 9.45 mg/kg, 11.10 mg/kg and 13.55 mg/kg, the relative risk was 4.349 (95 % CI: 4.303, 4.396), 6.108 (95 % CI: 6.044, 6.172), and 9.125 (95 %CI: 9.033, 9.219), respectively. No correlation was found between lead, cadmium, and mercury concentration in the soil and AD mortality. CONCLUSION: There was an apparent soil As concentration dependent increase in AD mortality. Results of this study may provide evidence for a possible causal linkage between arsenic exposure and the death risk from AD.