Assessing the effects of adolescent PCB exposure on executive functions in humans and animals

Monaikul, Supida

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Description

Title

Assessing the effects of adolescent PCB exposure on executive functions in humans and animals

Author(s)

Monaikul, Supida

Issue Date

2015-04-22

Director of Research (if dissertation) or Advisor (if thesis)

Schantz, Susan L.

Doctoral Committee Chair(s)

Schantz, Susan L.

Committee Member(s)

• Gulley, Joshua M.
• Juraska, Janice M.
• Raetzman, Lori T.

Department of Study

School of Molecular & Cell Bio

Discipline

Neuroscience

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• Adolescent
• polychlorinated biphenyl (PCB)
• Executive

Abstract

Converging evidence from studies in animal models and humans suggests that early developmental exposure to polychlorinated biphenyls (PCBs), a class of persistent organic pollutants, leads to deficits in cognitive functions such as cognitive flexibility and inhibitory control. These cognitive processes are mediated to a large extent by the prefrontal cortex (PFC). The dopamine (DA) system is a neurochemical system thought to play a critical role in modulating these cognitive functions, and the cognitive deficits seen with early PCB exposure may be mediated by DA dysfunction. Previous PCB studies have focused on the perinatal period as a critical period of exposure, and little or no research has examined the effects of exposure during another critical period of brain development – adolescence. During this period, the PFC and DA innervation of the PFC are undergoing marked maturation. Thus, executive functions mediated by the PFC, including cognitive flexibility and response inhibition, may be especially sensitive to disruption during adolescence. The goal of this research was to investigate the effects of adolescent PCB exposure on cognitive flexibility and response inhibition using parallel human and animal studies. In the animal study, the goal was to examine the long-term effects of adolescent PCB exposure on cognitive flexibility, using an operant set-shifting task, and response inhibition, using a differential reinforcement of low rates of responding (DRL) task. An additional goal was to determine whether exposure during this period would lead to long-lasting changes in dopamine transporter (DAT) expression that could underlie changes in cognitive performance that were observed. One male and one female pup from each of 14 litters were assigned to each of three treatment groups, 0, 3 or 6 mg/kg/day PCBs. Rats were orally dosed daily from postnatal day (PND) 27-50 to capture the whole period of adolescence in rats, and cognitive testing began at PND 90. In the set-shifting task, we saw a sex-specific effect of PCBs on the reversal phase with PCB-exposed males performing better in this phase, possibly due to these rats employing a simpler, more “habit-based” response strategy rather than learning the actual response reversal relevant to the task. In the DRL task, we found no effect of PCB-exposure. The PCB-related effects in performance on these two cognitive tasks were not as robust as hypothesized, and, perhaps not-surprisingly then, there were no significant differences in DAT expression in the orbital frontal cortex - which is important for reversal learning - or the striatum. To explore effects of PCB exposure in human adolescents, data were collected from 115 12-18 year old children of sport anglers in Green Bay, Wisconsin, where this population is exposed to PCBs through consumption of fish from contaminated waters. PCB concentrations were measured in the childrens’ serum and assessed in relation to performance on computerized tasks of cognitive flexibility, using the CANTAB Intradimensional/Extradimensional (ID/ED) set-shifting task, and response inhibition, using the Integrated Visual and Auditory (IVA) Continuous Performance Task. Behaviors associated with ADHD were assessed using the Conner-Wells’ Behavior Rating Scale Parent Report. PCB exposure was not associated with scores on the Conners’ scales, but higher PCB exposure was associated with more total trials to complete the ID/ED test in males. Higher PCB exposure, however, was not associated with a difference in performance on the response inhibition measure in boys or in girls. In summary, the results of these studies suggest there are subtle sex-specific disruptions in cognitive flexibility associated with PCB exposure during adolescence in both male rats and humans.

Graduation Semester

2015-5

Type of Resource

text

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Copyright and License Information

Copyright 2015 Supida Monaikul

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