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

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. Overall design: 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.

狄氏剂（Dieldrin）是一种老旧农药，具备多种作用模式（Mode of Action，MOA），包括作为雌激素受体激动剂、γ-氨基丁酸（GABA）受体拮抗剂，以及可破坏线粒体功能的化学物质。现有研究证据表明，狄氏剂暴露与人类神经退行性疾病的发病风险升高存在显著关联。
本研究旨在阐明狄氏剂对斑马鱼（Danio rerio）下丘脑——大脑主要的神经内分泌区域——的影响。将斑马鱼喂食含有0.03、0.15或1.8 µg/g狄氏剂的颗粒饲料，持续21天，随后开展全基因组基因表达分析，以表征狄氏剂所影响的细胞过程与信号通路。
实验整体设计：实验所用的性成熟成年斑马鱼（4~6月龄）购自加拿大魁北克省蒙特利尔的Mirdo Inc.。斑马鱼饲养于加拿大新不伦瑞克省圣约翰的加拿大河流研究所（Canadian Rivers Institute）的20L水族箱中。经过3周的驯化期后，将斑马鱼按实验组分为9个水族箱，共计36个水族箱，每个水箱内均添加活性炭作为额外防护措施，以尽可能降低斑马鱼通过水体接触狄氏剂的风险。每个水族箱投放5条斑马鱼，目标维持雌雄性比为3:2。指定水箱中的斑马鱼每日投喂两次0.065g对照饲料或三种污染饲料之一，每日总投喂量为0.13g，约为单个水箱内斑马鱼总体重的4%。每日投喂时间固定为上午10时与下午4时。