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Title:Perinatal high-fat diet and Bisphenol A: effects on behavior, gene expression and neuroanatomy in the medial prefrontal cortex
Author(s):Wise, Leslie Megan
Director of Research:Juraska, Janice M.
Doctoral Committee Chair(s):Juraska, Janice M.
Doctoral Committee Member(s):Schantz, Susan; Flaws, Jodi; Gulley, Joshua; Liang, Nu-Chu
Department / Program:Psychology
Degree Granting Institution:University of Illinois at Urbana-Champaign
endocrine disruptor
maternal behavior
gene expression
Abstract:Bisphenol A (BPA) is a synthetic industrial compound that is used to create polycarbonate plastics and epoxy resins. When BPA is consumed, most commonly through food and drink, it can act as an endocrine disruptor binding to estrogen-related, estrogen, androgen, and thyroid receptors. Abnormal binding of these receptors could alter normal brain development and cause lasting changes in gene expression, behavior and neuroanatomy. Additionally, perinatal HFD has been reported to cause long-term alterations in anxiety behavior and gene expression in the brain. Given that BPA and HFD are both ubiquitous in the environment and Western society, it is important to understand the possible effects and interactions on the brain. In the current study, I investigate the long-term impact of environmentally relevant exposure to BPA and a 45% fat diet during perinatal development. Zero (control), 40 or 400 μg/kg/day BPA was orally dosed to pregnant dams from gestational day 2 through birth, and then directly to each pup from postnatal day 1-10. The dams were fed either a control (15.8% kcal/fat) or a high fat diet (45% kcal/fat) during the same time period. After birth, the dams were observed for maternal care interactions with the litter. At postnatal day 10, tissue was collected from pups for gene expression and cytokine analysis. Littermates were observed for changes in periadolescent play behavior from postnatal day 26- 40, elevated plus maze (EPM) and social recognition in adulthood. Further, the cortex was collected in adulthood to assess gene expression, and the number of neurons, glia, synapses and microglia. Significant alterations were found in maternal care, inflammatory markers, gene expression, play behavior and the elevated plus maze. Perinatal BPA exposure showed a trend toward a decrease in positive maternal care and increased the levels of inflammatory markers in the medial prefrontal cortex (mPFC) at P10, while perinatal HFD increased positive maternal care and decreased the level of IL-6 in the mPFC at P10. Perinatal BPA exposure also altered periadolescent play behavior, with the control animals spending more time engaged in play behavior, the animals exposed to 40 µg/kg/day BPA spending the most time alone, and the animals exposed to 400µg/kg/day BPA spending the most time in passive contact. Additionally, perinatal BPA in the control diet groups produced anxiolytic behavior in males on the EPM, but did not affect female anxiety behavior. Perinatal HFD exposure did not alter the offspring’s behavior in any of the tasks. Perinatal BPA and HFD both altered the gene expression of several hormone-related and pro-inflammatory genes. No significant changes were found in any of the measured aspects of the structure of the medial prefrontal cortex (number of neurons, glia, microglia, synapses, the volume of white matter under the prefrontal cortex and synapses per neuron). However, the pattern of the increases in the number of neurons and glia and the volume of white matter under the cortex was similar to those previously found by Sadowski et al. (2014). These results suggest that perinatal HFD and BPA generally do not have interactive effects, but perinatal BPA exposure does produce lasting effects on behavior, while structural effects in the medial prefrontal cortex are not robust.
Issue Date:2017-12-06
Rights Information:Copyright 2018 Leslie Wise
Date Available in IDEALS:2018-09-04
Date Deposited:2018-05

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