Permethrin pesticide-induced alterations in the dopaminergic system across time points and genders Public

Abstract

Dopamine (DA) is one of many neurotransmitters in the central nervous system. The dopaminergic system and dopamine are responsible for such bodily functions as motivational and emotional behavior, attention, executive function, reward, control of involuntary and rapid motor function, and neurosecretion associated with the rhythm of light, biological clock, and reproduction. Major regulators of the dopaminergic system are tyrosine hydroxylase (TH), dopamine transporter (DAT), vesicular monoamine transporter 2 (VMAT2), and D1-D5 receptors. Great interest in the dopaminergic system in humans results from the fact that dysfunctions of the system can result in serious neurological disorders, such as Parkinson’s disease (PD), attention deficit hyperactivity disorder (ADHD), addiction, and schizophrenia. It has long been known that exposure to pesticides and insecticides can induce such neurobehavioral effects in many species, including humans. Pyrethroid pesticides, including permethrin, are now the most commonly used pesticides for residential pest control and public health purposes. Previous studies have shown disruption to the dopamine system by permethrin and other pyrethroids, yet little is known about the selectivity and duration of exposure of these pesticides. Using both male and female mice, four exposure groups at day 1, day 8, and day 15 were used vs controls, where mice were sacrificed 24-hours after exposure. The protein levels of DAT, TH, and VMAT2 were then analyzed by Western blot. Analysis found a nearly 70% increase of DAT expression levels at day 15 in male mice (P=0.006) and a statistically significant difference in male day 15 mice vs female day 15 mice (P <0.0001), but no statistically significant increase in female mice. TH levels did not reach significance in either gender of mice, however, an initial decrease was followed by an increasing trend across exposure days. VMAT2 levels were found to be statistically significant in male day 15 vs female day 15 mice (P < 0.03), but no significance was found across exposure days. This study found a significant gender difference to permethrin exposure, and significant levels of DAT increase in male mice, helping elucidate further toxicity of permethrin pesticides, despite the belief that they are innocuous, warranting further research.    

Table of Contents

INTRODUCTION ..........................................................................................................................................2

DOPAMINE SYSTEM........................................................................................................................................2

DOPAMINE DYSFUNCTION..............................................................................................................................3

PYRETHROID PESTICIDES ...............................................................................................................................4

EFFECTS OF EXPOSURE...................................................................................................................................6

MATERIALS AND METHODS...................................................................................................................8

STUDY DESIGN...........................................................................................................................................9

ANIMAL TREATMENT .....................................................................................................................................9

IMMUNOBLOTTING ......................................................................................................................................10

STATISTICAL ANALYSIS ...............................................................................................................................10

RESULTS......................................................................................................................................................11

DOPAMINE TRANSPORTER............................................................................................................................11

Figure 1: DAT Results, grouped by gender............................................................................................12

Figure 2: DAT Results, not grouped by gender .....................................................................................13

TYROSINE HYDROXYLASE ...........................................................................................................................13

Figure 3: TH Results, grouped by gender ..............................................................................................14

Figure 4: TH Results, not grouped by gender ........................................................................................14

VESICULAR MONOAMINE TRANSPORTER 2...................................................................................................15

Figure 5: VMAT2 Results, grouped by gender.......................................................................................15

Figure 6: VMAT2 Results, not grouped by gender.................................................................................16

DISCUSSION................................................................................................................................................16

PYRETHROID PESTICIDES .............................................................................................................................16

MECHANISMS OF ACTION .............................................................................................................................17

DISCUSSION OF RESULTS..............................................................................................................................18

SUMMARY....................................................................................................................................................21 

About this Master's Thesis

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School	Rollins School of Public Health
Department	Environmental Health - MPH
Degree	M.P.H.
Submission	Master's Thesis
Language	English
Research Field	Biology, Neuroscience Health Sciences, Public Health
Mot-clé	permethrin
Committee Chair / Thesis Advisor	Caudle, William Michael, Emory University
Committee Members	Tolbert, Paige, Emory University
Partnering Agencies	Does not apply (no collaborating organization)

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