Molecular Characterization of Dieldrin in the Zebrafish (Danio rerio) Hypothalamus

Dieldrin is a legacy pesticide that has multiple modes of action (MOA) that include being an estrogen receptor agonist, GABA receptor antagonist, and a chemical that disrupts mitochondrial function. There is also evidence that dieldrin exposure is significantly associated with an increased risk for neurodegeneration in humans. The objective of this thesis was to clarify the effects of dieldrin in the hypothalamus, the major neuroendocrine region of the brain, in the zebrafish (Danio rerio). Zebrafish were fed pellets containing 0.03, 0.15, or 1.8 µg/g dieldrin for 21 days and a global gene expression analysis was performed to characterize cellular processes and pathways affected by dieldrin. Reproductive adult zebrafish (4-6 months of age) were obtained from Mirdo Inc. (Montréal, QC, Canada). Zebrafish were housed at the Canadian Rivers Institute (Saint John, NB, Canada) in 20 L tanks. After an acclimation period of 3 weeks, zebrafish were divided into 9 tanks per experimental group giving a total of 36 tanks, each with active carbon within the tank as an extra precaution to minimize any exposure to water-borne dieldrin. Five fish were added to each tank, with the goal of maintaining a 3 to 2 female to male sex ratio. Zebrafish in designated tanks were fed 0.065 g of the control or one of the three contaminated feeds twice a day representing a daily intake of 0.13 g (approximately 4% of fish body weight per tank). Feeding took place at 10 am and 4 pm each day.