Effects of acute dieldrin exposure on neurotransmitters and global gene transcription in largemouth bass (Micropterus salmoides) hypothalamus.
Exposure to dieldrin induces neurotoxic effects in the vertebrate CNS and disrupts reproductive processes in teleost fish. Reproductive impairment observed in fish by dieldrin is likely the result of multiple effects along the hypothalamic-pituitary-gonadal axis, but the molecular signaling cascades are not well characterized. To better elucidate the mode of action of dieldrin in the hypothalamus, this study measured neurotransmitter levels and examined the transcriptomic response in female largemouth bass (LMB) to an acute treatment of dieldrin. Male and female LMB were injected with either vehicle or 10 mg dieldrin/kg and sacrificed after 7 days. There were no significant changes in dopamine or DOPAC concentrations in the neuroendocrine brain of males and females after treatment but GABA levels in females were moderately increased 20-30% in the hypothalamus and cerebellum. In the female hypothalamus, there were 227 transcripts (p<0.001) identified as being differentially regulated by dieldrin. Functional enrichment analysis revealed transcription, DNA repair, ubiquitin-proteasome pathway, and cell communication, 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 also associated with the etiology of human neurological disorders.
Martyniuk
Christopher J
CJ
Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611, USA. cmartyn@unb.ca
Feswick
April
A
Spade
Daniel J
DJ
Kroll
Kevin J
KJ
Barber
David S
DS
Denslow
Nancy D
ND
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001492:Bass / Q000235:genetics* / Q000378:metabolism*; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D004026:Dieldrin / Q000633:toxicity*; D004298:Dopamine / Q000378:metabolism; D005260:Female; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008957:Models, Genetic; D018377:Neurotransmitter Agents / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012727:Sex Characteristics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013687:Telencephalon / Q000187:drug effects / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D014874:Water Pollutants, Chemical / Q000633:toxicity; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018377:Neurotransmitter Agents; D014874:Water Pollutants, Chemical; D015102:3,4-Dihydroxyphenylacetic Acid; D005680:gamma-Aminobutyric Acid; D004026:Dieldrin; D004298:Dopamine