Dissertation
Lower chlorinated polychlorinated biphenyls and their neurological effects
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Autumn 2023
DOI: 10.25820/etd.006963
Abstract
The ubiquitous and persistent nature of polychlorinated biphenyls (PCBs) can lead to many adverse health effects in humans, including neurodevelopmental deficits. Despite their ban and reduced production, these compounds persist in the environment, reaching alarming levels, particularly in air samples from inadvertent sources such as paint pigments. However, airborne PCBs have received less attention to date because researchers have primarily focused on exposure to traditional PCB mixtures through diet. Existing research has primarily centered around dietary exposure to traditional PCB mixtures (Aroclors), leaving a significant gap in our understanding of the neurological implications of airborne exposure, particularly during the crucial period of adolescent brain development. Utilizing rodent models, this dissertation aims to unravel the intricate interplay between inhalation exposure to volatile lower chlorinated PCBs (LC-PCBs) and the resulting disruption of brain development during adolescence. A comprehensive review of the literature identified four studies meeting stringent inclusion criteria, forming the cornerstone for exploring neurotoxic outcomes associated with adolescent PCB exposure. Key findings from acute (4 h) inhalation exposure to 2,2ꞌ,5,5ꞌ-tetrachlorobiphenyl (PCB52) revealed its distribution in pivotal tissues, emphasizing its presence in white adipose, brain, intestinal content, lung, liver, and serum. Nontargeted liquid chromatography-mass spectrometry (Nt-LC/MS) analysis unveiled a diverse array of metabolites, including sulfated, methoxylated, and dechlorinated derivatives of PCB52. Subsequently, a chronic (28-day) inhalation exposure to PCB52 uncovered sex-specific differences in brain weights, PCB52 and metabolite levels, gene expression in the striatum and cerebellum, and neurobehavioral responses (Y-maze, HBT, OFT, and EPM). Three weeks post intraperitoneal injection of PCB52 in female Sprague Dawley rats to 0, 1, 10, or 100 mg/kg BW demonstrated no significant effects on overall body weight, with notable concentrations of hydroxylated, sulfated, and methylated PCB metabolites identified in serum and liver following exposure to the highest dose. Finally, for translational relevance, data was collected from orally exposed female mice to different doses (0, 0.1, 1, or 6 mg/kg body weight) of the MARBLES mixture over a 7-week period. Based on gene expression, the liver was the most impacted by PCB exposure followed by the striatum and prefrontal cortex. Exposure to lower-chlorinated PCBs during adolescence and early adulthood resulted in observed neurological alterations such as differences in brain weights, gene expression, neurobehavioral responses, and PCB metabolite disposition. This thesis research deepens our understanding of PCB-related neurodevelopmental and neurological outcomes and lays the foundation for further investigation into the intricate interplay between PCB exposure and brain health.
Details
- Title: Subtitle
- Lower chlorinated polychlorinated biphenyls and their neurological effects
- Creators
- Amanda J. Bullert
- Contributors
- Hans-Joachim Lehmler (Advisor)Michael Dailey (Committee Member)Jonathan Doorn (Committee Member)Hanna Stevens (Committee Member)Kai Wang (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Neuroscience
- Date degree season
- Autumn 2023
- DOI
- 10.25820/etd.006963
- Publisher
- University of Iowa
- Number of pages
- xxi, 311 pages
- Copyright
- Copyright 2023 Amanda Bullert
- Grant note
- The National Institute of Environmental Health Sciences/National Institutes of Health supported the project through grants R01ES014901, R01ES031098, P30ES005605, and P42ES013661. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies listed above. (122)
- Language
- English
- Date submitted
- 12/01/2023
- Description illustrations
- Illustrations, tables, graphs, charts
- Description bibliographic
- Includes bibliographical references (pages 165-211).
- Public Abstract (ETD)
Polychlorinated biphenyls (PCBs) are pollutants in the indoor air of schools. Despite bans and reduced production, PCBs persist in the environment, with alarming levels found in air samples, particularly from inadvertent sources like paint pigments. It is unknown how exposure to lower chlorinated PCBs (LC-PCBs) affects the developing adolescent brain. This project utilizes rodent models to determine if PCBs, such as PCB52 and its metabolites, are present in the brain following exposure by inhalation or other routes of exposure and if PCB brain levels are associated with neurotoxic outcomes, including changes in gene expression, immunochemical measures, and behavioral outcomes. Key findings from acute inhalation exposure to 2,2ꞌ,5,5ꞌ-tetrachlorobiphenyl (PCB52) highlight its distribution in pivotal tissues, including the brain, emphasizing the need for attention to airborne PCBs. Chronic inhalation exposure to PCB52 reveals sex-specific differences in brain weights, gene expression, and neurobehavioral responses. Further investigations involve intraperitoneal injection of PCB52 in female rats and oral exposure of female mice to a complex human-relevant PCB mixture. The results show notable concentrations of PCB metabolites, impacting the liver, striatum, and prefrontal cortex. This research deepens our understanding of PCB-related neurodevelopmental and neurological outcomes, emphasizing observed alterations in brain weights, gene expression, and neurobehavioral responses.
- Academic Unit
- Interdisciplinary Graduate Program in Neuroscience
- Record Identifier
- 9984546541402771
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