Molecular characterization of dieldrin in the zebrafish hypothalamus
University of New Brunswick
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 day sand a global gene expression analysis was performed to characterize cellular processes and pathways affected by dieldrin. Signaling pathways associated with T-cell receptors and several interleukin receptors were significantly down regulated in both the 0.15 and 1.8 μg/g treatment groups. Moreover, transcripts related to mitochondrial function were significantly down-regulated in the hypothalamus following dieldrin treatments. The dysregulation of immune related transcripts raises the possibility that altered immune system function may be a mechanism underlying dieldrin induced neurotoxicity and neurodegeneration.