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1.
Toxicol Lett ; 232(1): 293-300, 2015 Jan 05.
Article in English | MEDLINE | ID: mdl-25455458

ABSTRACT

Bisphenol A (BPA) is a compound released from plastics and other consumer products used in everyday life. BPA exposure early in fetal development is proposed to contribute to programming of chronic diseases like obesity and diabetes, by affecting DNA methylation levels. Previously, we showed that in utero and lactational exposure of C57BL/6JxFVB hybrid mice via maternal feed using a dose range of 0-3000µg/kg body weight/day resulted in a sex-dependent altered metabolic phenotype in offspring at 23 weeks of age. The most univocal effects were observed in females, with reduced body weights and related metabolic effects associated with perinatal BPA exposure. To identify whether the effects of BPA in females are associated with changes in DNA methylation, this was analyzed in liver, which is important in energy homeostasis. Measurement of global DNA methylation did not show any changes. Genome-wide DNA methylation analysis at specific CpG sites in control and 3000µg/kg body weight/day females with the digital restriction enzyme analysis of methylation (DREAM) assay revealed potential differences, that could, however, not be confirmed by bisulfite pyrosequencing. Overall, we demonstrated that the observed altered metabolic phenotype in female offspring after maternal exposure to BPA was not detectably associated with liver DNA methylation changes. Still, other tissues may be more informative.


Subject(s)
Benzhydryl Compounds/toxicity , DNA Methylation/drug effects , Energy Metabolism/drug effects , Environmental Pollutants/toxicity , Liver/drug effects , Phenols/toxicity , Age Factors , Animals , Chromatography, High Pressure Liquid , Computational Biology , CpG Islands , Databases, Genetic , Energy Metabolism/genetics , Female , Gestational Age , Liver/metabolism , Maternal Exposure , Mice, Inbred C57BL , Phenotype , Polymerase Chain Reaction , Pregnancy , Prenatal Exposure Delayed Effects , Sex Factors
2.
Behav Brain Res ; 267: 133-43, 2014 Jul 01.
Article in English | MEDLINE | ID: mdl-24680988

ABSTRACT

BACKGROUND: Epidemiological studies have shown associations between vitamin D, mental health and glucose homeostasis in the elderly. Causal evidence, however, is still lacking. OBJECTIVE: The objective of this study was to investigate the importance of vitamin D in the prevention of emotional disturbances and cognitive decline in aging C57BL/6 mice, with pre-diabetes type II as potential effect modifier. METHODS: Mice were exposed to one of four diets from 10 months till 24 months of age: low fat vitamin D adequate (LFD), LF vitamin D deficient (LF), moderate fat vitamin D adequate (MFD), and MF vitamin D deficient (MF). The MFD/MF diet was applied to induce a condition resembling pre-diabetes type II. Behavior was assessed twice in the same group of mice at 6-8 and at 22-23 months of age using the Open Field Test (OFT), Elevated Plus Maze (EPM), Object Recognition Test (ORT) and the Morris Water Maze (MWM). RESULTS: We successfully induced vitamin D deficiency in the LF/MF mice. Moreover, fasting glucose and fasting insulin levels were significantly higher in MFD/MF mice than in LFD/LF mice. A significant aging effect was observed for most behavioral parameters. A MF(D) diet was shown to delay or prevent the age-related increase in emotional reactivity in the EPM. No effect of vitamin D or vitamin D*fat on behavioral outcomes was measured. CONCLUSION: Aging significantly affected emotional reactivity and cognitive performance. Although other studies have shown effects of vitamin D on emotional reactivity and cognitive performance in mice, these findings could not be confirmed in aged C57BL/6 mice in this study.


Subject(s)
Affective Symptoms/physiopathology , Aging/physiology , Cognition Disorders/physiopathology , Diet , Vitamin D Deficiency/physiopathology , Animals , Blood Glucose , Body Weight , Cognition/physiology , Dietary Fats/administration & dosage , Emotions/physiology , Fasting/blood , Insulin/blood , Male , Maze Learning/physiology , Mice, Inbred C57BL , Random Allocation , Recognition, Psychology/physiology , Survival Analysis , Vitamin D/administration & dosage
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