Brenna Parke

Date of Award

Spring 2020

Document Type

Open Access Thesis

Department

Chemistry and Biochemistry

First Advisor

Parastoo Hashemi

Abstract

Despite being a known toxin for several centuries, lead (Pb2+) is still utilized in commercial products including leaded gasoline, paint, and modern cosmetics. This presence has caused (Pb2+) to pollute the environment, including public drinking water sources. The recent outbreaks of elevated levels of (Pb2+) in the drinking water in Flint, Michigan and Washington D.C. have caused large populations to be exposed to the heavy metal for months at a time, raising a public health concern over the implications of widespread, long-term (Pb2+) exposure. Young children are most susceptible to the effects of (Pb2+) toxicity, exhibiting symptoms of cognitive and behavioral impairments. These symptoms are closely related to those exhibited by autism spectrum disorder (ASD) patients. ASD is of unknown etiology but is thought to be caused by a mixture of genetic factors and environmental toxins. ASD is also linked to abnormal serotonin functionality due to a large population being treated with selective serotonin reuptake inhibitors (SSRIs) to decrease anxiolytic behaviors. Serotonin (5-HT) is a neurotransmitter heavily involved in development, mood, and sleep. Despite the connection between ASD-like symptoms and (Pb2+) exposure,

there have been no studies chronicling the effects of (Pb2+)exposure on the serotonergic system in vivo. We hypothesize that serotonergic neurotransmission will be altered as a direct result of Pb exposure. In vivo measurements require high temporal resolution, selectivity, and sensitivity; all achieved with fast-scan cyclic voltammetry (FSCV) and microelectrodes. Due to (Pb2+)exposure greatly affecting and serotonin’s critical role in proper development, the medial prefrontal cortex (mPFC) was chosen due to its dense population of serotonin neurons as well as being the last region to fully develop. In this study, mature mice were exposed to (Pb2+)in three experimental paradigms: acute, chronic, and perinatal studies. Behavioral tests were performed on the perinatal cohort prior to voltammetric measurements to observe any behavioral alterations as a result of Pb consumption. It was found that (Pb2+)affected the amplitude, but not the reuptake of evoked 5-HT in the acute cohort. There were no significant changes in voltammetric measurements nor behaviors after chronic and perinatal exposures. This work has shown that acute (Pb2+)exposure does alter serotonergic neurotransmission in the mPFC, but symptoms were not observed after long-term exposure to 15 ppb Pb2+

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© 2020, Brenna Parke

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