<p>Neurological disorders are a
major public health concern due to prevalence, severity of symptoms, and impact
on caregivers and economic losses. While genetic susceptibility likely has a
role in most cases, exposure to toxicants can lead to neurotoxicity, including
potentially developmental origins of adult disease or increased risk of disease
onset. These exposures are not necessarily large, acute exposures, but could
accumulate, with a chronic low-dose exposure, causing toxicity. This research
focuses on the potential neurotoxicity of two classes of dietary toxins/toxicants,
heterocyclic aromatic amines (HAAs) and per- and polyfluoroalkyl substances
(PFAS). HAAs, such as PhIP, harmane, and harmine, are formed in charred or
overcooked meat, coffee, tobacco, and other foods. PFAS are largely used in
making household materials, but are found in small amounts in eggs and dairy
products and largely in contaminated water. While these two classes are diverse
in terms of structure, common neurotoxic targets and mechanisms often exist. Therefore,
we tested the effects of these chemicals on cell viability and neurotoxicity. In
the first aim, we aimed to elucidate the mechanism of toxicity of harmane and
harmine, focusing on their ability to cause mitochondrial dysfunction. The
second aim was to determine the effects of either harmane or PhIP on the nigrostriatal
motor systems and motor function of rats and mice, respectively. The third aim
determined the effects of PFAS on neurodevelopment of Northern leopard frogs,
focusing on changes in neurotransmitter levels and accumulation in the brain. Harmane
did not cause motor dysfunction, but potentially affected the nigro-striatal
motor system in an age- or sex-dependent manner. PhIP had differential effects
on dopamine levels over time and caused motor dysfunction after subchronic
exposure in mice. Perfluorooctane sulfonate (PFOS) accumulated in the brains of
frogs and PFAS caused changes in neurotransmitter levels that were dose- and
time-dependent. Overall, this research shows that toxins/toxicants humans are
exposed to over their whole lives through their diet and contaminated water can
cause neurotoxicity, potentially leading to or increasing risk of disease
states. </p>
| Identifer | oai:union.ndltd.org:purdue.edu/oai:figshare.com:article/12919016 |
| Date | 16 December 2020 |
| Creators | Rachel M Foguth (9343949) |
| Source Sets | Purdue University |
| Detected Language | English |
| Type | Text, Thesis |
| Rights | CC BY 4.0 |
| Relation | https://figshare.com/articles/thesis/Identification_of_Neurotoxic_Targets_of_Diverse_Chemical_Classes_of_Dietary_Neurotoxins_Neurotoxicants/12919016 |
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