Effects of acute dieldrin exposure on neurotransmitters and global gene transcription in largemouth bass (Micropterus salmoides) hypothalamus

Abstract

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 seven 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.

Toxicity induced by dieldrin and chlorpyrifos in the freshwater crayfish Cambarellus montezumae (Cambaridae)

“…The excessive generation of ROS causes damage to all vital macromolecules, including lipids, proteins and DNA. This indirect action of the chemicals on such molecules has been established by increases in thiobarbituric-acid-reactive species observed in various models, as well as by alterations of antioxidant defences, and elevation of DNA oxidation (Bagchi, Bagchi, Hassoun, & Stohs, 1995;Qiao, Seidler, & Slotkin, 2005;Martyniuk et al, 2010;Slotkin, & Seidler, 2010;Ozkan, Gündüz, Berköz, Hunt, & Yalin, 2012). Our present data showing a lipid peroxidation increase in crayfish by the insecticides agree with such findings, and suggest a relation of such damage with the observed DNA breakage.…”

“…Both insecticides have several common characteristics relevant to the aims of the present study: they are oxidative stress inducers, neurotoxicants in mammals and aquatic organisms, and are environmentally important contaminants because of their level of persistency (Martyniuk et al, 2010;Slotkin, & Seidler, 2010). In genotoxicology, it is highly recommended to apply various tests in order to determine the potentials of a particular chemical.…”

Reproductive health of yellow perch Perca flavescens in selected tributaries of the Chesapeake Bay

“…Extracts from both primary and secondary-treated effluent activated D2 receptors (Basu et al, 2009). A variety of environmental contaminants such as hepatochlor (Miller et al, 1999), dieldrin (Richardson et al, 2006), certain PCBs, organochlorine pesticides, metals and bisphenol A (Jones and Miller, 2008) have been shown to influence dopamine homeostasis in mammals and the hypothalamic-pituitary-gonadal axis in fishes (Khan and Thomas, 2006;Martyniuk et al, 2010;Page et al, 2011). Long-term dietary exposure of zebrafish to PCB mixtures mimicking environmental situations resulted in a decrease of maturing follicles and a reduction of fertilization rate (Daouk et al, 2011).…”

Dietary exposure of 17-alpha ethinylestradiol modulates physiological endpoints and gene signaling pathways in female largemouth bass (Micropterus salmoides)

“…All primers used for these transcripts are provided in Table SI-1. Primers for VTG , ESR1 , ESR2 , and GST and GPX were published previously (Martyniuk et al 2010a; Sabo-Attwood et al 2004). Absolute quantification was used in order to calculate the number of copies for each gene.…”

“…Standard curves using cloned plasmids for each gene were generated using seven points in a serial dilution from 1×10 2 through 1×10 9 copies with efficiencies ranging from 93 % to 104 %. Detailed methods for cloning, sequencing, and primer optimization for LMB genes have been previously described (Martyniuk et al 2010a; Sabo-Attwood et al 2004). Standards and experimental samples were run in duplicate, along with a “no reverse transcriptase (-RT)” control and a “no template control (NTC)”.…”