Document Detail

Effects of acute dieldrin exposure on neurotransmitters and global gene transcription in largemouth bass (Micropterus salmoides) hypothalamus.
MedLine Citation:
PMID:  20438755     Owner:  NLM     Status:  MEDLINE    
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.
Christopher J Martyniuk; April Feswick; Daniel J Spade; Kevin J Kroll; David S Barber; Nancy D Denslow
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-05-11
Journal Detail:
Title:  Neurotoxicology     Volume:  31     ISSN:  1872-9711     ISO Abbreviation:  Neurotoxicology     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-06-07     Completed Date:  2010-09-16     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  7905589     Medline TA:  Neurotoxicology     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  356-66     Citation Subset:  IM    
Copyright Information:
(c) 2010 Elsevier Inc. All rights reserved.
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MeSH Terms
3,4-Dihydroxyphenylacetic Acid / metabolism
Bass / genetics*,  metabolism*
Cerebellum / drug effects,  metabolism
Dieldrin / toxicity*
Dopamine / metabolism
Hypothalamus / drug effects,  metabolism*
Models, Genetic
Neurotransmitter Agents / metabolism*
Oligonucleotide Array Sequence Analysis / methods
Sex Characteristics
Signal Transduction / drug effects,  genetics
Telencephalon / drug effects,  metabolism
Transcription, Genetic / drug effects*
Water Pollutants, Chemical / toxicity
gamma-Aminobutyric Acid / metabolism
Grant Support
K99 ES016767/ES/NIEHS NIH HHS; K99 ES016767-01A1/ES/NIEHS NIH HHS; K99 ES016767-01A1/ES/NIEHS NIH HHS; R01 ES015449/ES/NIEHS NIH HHS; R01 ES015449-03/ES/NIEHS NIH HHS
Reg. No./Substance:
0/Neurotransmitter Agents; 0/Water Pollutants, Chemical; 102-32-9/3,4-Dihydroxyphenylacetic Acid; 56-12-2/gamma-Aminobutyric Acid; I0246D2ZS0/Dieldrin; VTD58H1Z2X/Dopamine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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