Transcriptional response of rat frontal cortex following acute <it>In Vivo </it>exposure to the pyrethroid insecticides permethrin and deltamethrin
<p>Abstract</p> <p>Background</p> <p>Pyrethroids are neurotoxic pesticides that interact with membrane bound ion channels in neurons and disrupt nerve function. The purpose of this study was to characterize and explore changes in gene expression that occur in the rat fr...
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doaj-336b8b4056c64e43a7ef9f6860f326612020-11-24T21:24:56ZengBMCBMC Genomics1471-21642008-11-019154610.1186/1471-2164-9-546Transcriptional response of rat frontal cortex following acute <it>In Vivo </it>exposure to the pyrethroid insecticides permethrin and deltamethrinTornero-Velez RogelioMundy William RRadio Nicholas MWright Fred ALi ZhenHarrill Joshua ACrofton Kevin M<p>Abstract</p> <p>Background</p> <p>Pyrethroids are neurotoxic pesticides that interact with membrane bound ion channels in neurons and disrupt nerve function. The purpose of this study was to characterize and explore changes in gene expression that occur in the rat frontal cortex, an area of CNS affected by pyrethroids, following an acute low-dose exposure.</p> <p>Results</p> <p>Rats were acutely exposed to either deltamethrin (0.3 – 3 mg/kg) or permethrin (1 – 100 mg/kg) followed by collection of cortical tissue at 6 hours. The doses used range from those that cause minimal signs of intoxication at the behavioral level to doses well below apparent no effect levels in the whole animal. A statistical framework based on parallel linear (SAM) and isotonic regression (PIR) methods identified 95 and 53 probe sets as dose-responsive. The PIR analysis was most sensitive for detecting transcripts with changes in expression at the NOAEL dose. A sub-set of genes (<it>Camk1g</it>, <it>Ddc</it>, <it>Gpd3</it>, <it>c-fos </it>and <it>Egr1</it>) was then confirmed by qRT-PCR and examined in a time course study. Changes in mRNA levels were typically less than 3-fold in magnitude across all components of the study. The responses observed are consistent with pyrethroids producing increased neuronal excitation in the cortex following a low-dose <it>in vivo </it>exposure. In addition, Significance Analysis of Function and Expression (SAFE) identified significantly enriched gene categories common for both pyrethroids, including some relating to branching morphogenesis. Exposure of primary cortical cell cultures to both compounds resulted in an increase (~25%) in the number of neurite branch points, supporting the results of the SAFE analysis.</p> <p>Conclusion</p> <p>In the present study, pyrethroids induced changes in gene expression in the frontal cortex near the threshold for decreases in ambulatory motor activity <it>in vivo</it>. The penalized regression methods performed similarly in detecting dose-dependent changes in gene transcription. Finally, SAFE analysis of gene expression data identified branching morphogenesis as a biological process sensitive to pyrethroids and subsequent <it>in vitro </it>experiments confirmed this predicted effect. The novel findings regarding pyrethroid effects on branching morphogenesis indicate these compounds may act as developmental neurotoxicants that affect normal neuronal morphology.</p> http://www.biomedcentral.com/1471-2164/9/546 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tornero-Velez Rogelio Mundy William R Radio Nicholas M Wright Fred A Li Zhen Harrill Joshua A Crofton Kevin M |
spellingShingle |
Tornero-Velez Rogelio Mundy William R Radio Nicholas M Wright Fred A Li Zhen Harrill Joshua A Crofton Kevin M Transcriptional response of rat frontal cortex following acute <it>In Vivo </it>exposure to the pyrethroid insecticides permethrin and deltamethrin BMC Genomics |
author_facet |
Tornero-Velez Rogelio Mundy William R Radio Nicholas M Wright Fred A Li Zhen Harrill Joshua A Crofton Kevin M |
author_sort |
Tornero-Velez Rogelio |
title |
Transcriptional response of rat frontal cortex following acute <it>In Vivo </it>exposure to the pyrethroid insecticides permethrin and deltamethrin |
title_short |
Transcriptional response of rat frontal cortex following acute <it>In Vivo </it>exposure to the pyrethroid insecticides permethrin and deltamethrin |
title_full |
Transcriptional response of rat frontal cortex following acute <it>In Vivo </it>exposure to the pyrethroid insecticides permethrin and deltamethrin |
title_fullStr |
Transcriptional response of rat frontal cortex following acute <it>In Vivo </it>exposure to the pyrethroid insecticides permethrin and deltamethrin |
title_full_unstemmed |
Transcriptional response of rat frontal cortex following acute <it>In Vivo </it>exposure to the pyrethroid insecticides permethrin and deltamethrin |
title_sort |
transcriptional response of rat frontal cortex following acute <it>in vivo </it>exposure to the pyrethroid insecticides permethrin and deltamethrin |
publisher |
BMC |
series |
BMC Genomics |
issn |
1471-2164 |
publishDate |
2008-11-01 |
description |
<p>Abstract</p> <p>Background</p> <p>Pyrethroids are neurotoxic pesticides that interact with membrane bound ion channels in neurons and disrupt nerve function. The purpose of this study was to characterize and explore changes in gene expression that occur in the rat frontal cortex, an area of CNS affected by pyrethroids, following an acute low-dose exposure.</p> <p>Results</p> <p>Rats were acutely exposed to either deltamethrin (0.3 – 3 mg/kg) or permethrin (1 – 100 mg/kg) followed by collection of cortical tissue at 6 hours. The doses used range from those that cause minimal signs of intoxication at the behavioral level to doses well below apparent no effect levels in the whole animal. A statistical framework based on parallel linear (SAM) and isotonic regression (PIR) methods identified 95 and 53 probe sets as dose-responsive. The PIR analysis was most sensitive for detecting transcripts with changes in expression at the NOAEL dose. A sub-set of genes (<it>Camk1g</it>, <it>Ddc</it>, <it>Gpd3</it>, <it>c-fos </it>and <it>Egr1</it>) was then confirmed by qRT-PCR and examined in a time course study. Changes in mRNA levels were typically less than 3-fold in magnitude across all components of the study. The responses observed are consistent with pyrethroids producing increased neuronal excitation in the cortex following a low-dose <it>in vivo </it>exposure. In addition, Significance Analysis of Function and Expression (SAFE) identified significantly enriched gene categories common for both pyrethroids, including some relating to branching morphogenesis. Exposure of primary cortical cell cultures to both compounds resulted in an increase (~25%) in the number of neurite branch points, supporting the results of the SAFE analysis.</p> <p>Conclusion</p> <p>In the present study, pyrethroids induced changes in gene expression in the frontal cortex near the threshold for decreases in ambulatory motor activity <it>in vivo</it>. The penalized regression methods performed similarly in detecting dose-dependent changes in gene transcription. Finally, SAFE analysis of gene expression data identified branching morphogenesis as a biological process sensitive to pyrethroids and subsequent <it>in vitro </it>experiments confirmed this predicted effect. The novel findings regarding pyrethroid effects on branching morphogenesis indicate these compounds may act as developmental neurotoxicants that affect normal neuronal morphology.</p> |
url |
http://www.biomedcentral.com/1471-2164/9/546 |
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