Acute Dieldrin Exposure on Global Gene Transcription in Largemouth bass (Micropterus salmoides) Hypothalamus

Female largemouth bass were injected with 10mg/kg dieldrin and sacrificed after 7 days. Hypothalami were dissected and total RNA extracted for microarray analysis. Exposure to dieldrin induces neurotoxic effects in the vertebrate CNS and disrupts reproductive processes in teleost fish. Reproductive impairment observed in fish is likely the result of multiple mechanisms of action along the hypothalamic-pituitary-gonadal axis. To better elucidate the mode of action of dieldrin in the hypothalamus, we measured neurotransmitter levels and examined the transcriptomic response of female largemouth bass (LMB) to an acute treatment of dieldrin. Female LMB were injected with either vehicle or 10 mg/kg dieldrin and sacrificed after seven days. The neurotransmitter γ-aminobutyric acid was significantly elevated by approximately 25-30% in the hypothalamus and cerebellum but there was no change in dopamine levels in the hypothalamus, telencephalon, or cerebellum. We identified 270 transcripts (p<0.001) as being differentially regulated by dieldrin. Functional enrichment analysis identified transcription, DNA repair, ubiquitin pathway, cell communication, and phosphorylation as biological processes over-represented in the microarray analysis. Pathway analysis identified DNA damage, inflammation, regeneration, and Alzheimer’s disease as major cell processes and diseases affected by dieldrin. Using multiple bioinformatics approaches, this study demonstrates that the teleostean hypothalamus is a target for dieldrin-induced neurotoxicity and provides mechanistic evidence that dieldrin activates similar cell pathways and biological processes that are involved in the etiology of human neurological disorders. Key words: ubiquitin-proteasome pathway, mutagenicity, neurodegeneration, apoptosis, DNA damage Largemouth bass injected with single i.p. with 10 mg/kg diedrin; sacrificed 7 days later, hypothalamic tissue studied