Human exposure to environmental toxicants, such as phthalates, occurs throughout the lifespan. Phthalates are a group of synthetic chemicals added to plastics to increase their flexibility and durability, however they easily migrate out of the plastic product into the environment. Children and infants have a higher level of exposure to phthalates than adults, which is concerning as the majority of neurodevelopment occurs during this time period. Previous research has shown that early life exposure to di-(2ethylhexyl) phthalate (DEHP), the most commonly used phthalate worldwide, has resulted in altered neurodevelopment. DEHP was administered once daily from postnatal day (P) 18-23, a critical period of development of dopaminergic innervation to the PFC.Wildtype C57Bl/6 mice were used to assess behavioural effects. Transgenic AldHl1-L10:GFP mice were used to measure changes in astrocyte number and activation in the PFC. Behavioural and histological measurements were assessed at P29 and P49, to examine both short-term and long-term responses. Both males and females were assessed to determine whether sex differences exist in response to early-life DEHP exposure. Our results suggest that male mice exposed to DEHP exhibit a short-term hyperactive phenotype paralleled by a decrease in anxiety-like phenotype. The majority of these effects were not seen at P49, suggesting these effects are not long-lasting. No differences were seen at either time point in females, suggesting that males and females differentially respond to early-life DEHP exposure. No changes in astrocyte number or astrocyte activation were observed, suggesting astrocytes in the PFC are not affected by early-life DEHP exposure. In conclusion, early-life DEHP exposure appears to have acute anxiolytic effects only in males, and these effects do not seem to be mediated through astrocytic changes in the PFC.iii I would also like to express my gratitude towards my committee members, Alfonso Abizaid, Michael Hildebrand, and Maria DeRosa for their time and input on this project.
He received his doctorate from the University of Illinois at Urbana-Champaign. His areas of research include simplifying the outcomes assessment process, first-year engineering instruction, and the pedagogical aspects of writing computer games. Dr. Estell is a Senior Member of IEEE, and a member of ACM,
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