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Subtoxic chlorpyrifos treatment resulted in differential expression of genes implicated in neurological functions and development

  • Toxicogenomics
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Abstract

Chlorpyrifos (CPF), a commonly used organophosphorus insecticide, induces acetylcholinesterase inhibition and cholinergic toxicity. Subtoxic exposure to CPF has long-term adverse effects on synaptic function/development and behavioral performance. To gain insight into the possible mechanism(s) of these observations, this study aims to investigate gene expression changes in the forebrain of rats treated with subtoxic CPF doses using DNA microarrays. Statistical analysis revealed that CPF treatment resulted in differential expression of 277 genes. Gene ontology and pathway analyses revealed that these genes have important roles in nervous system development and functions including axon guidance, dorso-ventral axis formation, long-term potentiation, synaptic transmission, and insulin signaling. The results of biological associated network analysis showed that Gsk3b is highly connected in several of these networks suggesting its potential role in cellular response to CPF exposure/neurotoxicity. These findings might serve as the basis for future mechanistic analysis of the long-term adverse effects of subtoxic CPF exposure.

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Acknowledgments

The authors would like the thank Major Diane Todd for the management of this research program, Dr. Nicolas DelRaso and Ms. Deirdre Mahle for coordinating and supervising of the animal study, and Drs. David Mattie and Peter Robinson for constructive discussion.

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Authors and Affiliations

  1. The Henry M. Jackson Foundation for the Advancement of Military Medicine, Applied Biotechnology Branch, Human Effectiveness Directorate, 711th Human Performance Wing, Wright-Patterson Air Force Base, Dayton, OH, USA

    Andrea R. Stapleton

  2. Applied Biotechnology Branch, Human Effectiveness Directorate, 711th Human Performance Wing, 2729 R Street, Wright-Patterson Air Force Base, Dayton, OH, 45433-5707, USA

    Victor T. Chan

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  1. Andrea R. Stapleton
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  2. Victor T. Chan
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Correspondence to Victor T. Chan.

Additional information

Dataset accession # GSE9751.

Electronic supplementary material

Below is the link to the electronic supplementary material.

204_2008_346_MOESM1_ESM.doc

Supplemental Table S1. The Affymetrix probe ID, gene name/description, and change direction of the entire list of 277 differential expressed genes (DOC 325 kb)

204_2008_346_MOESM2_ESM.doc

Supplemental Table S2. Complete lists of enriched gene ontology (GO) categories and pathways, number of genes in each of these GO categories/pathways and the statistical significance of enhancement generated using the gene lists of low-dose, high-dose and entire dose ranges as input data in DAVID analyses (DOC 279 kb)

204_2008_346_MOESM3_ESM.doc

Supplemental Table S3. The entire lists of pathways and the direction of gene expression changes involved in each of these pathways determined using GenMAPP (DOC 191 kb)

204_2008_346_MOESM4_ESM.doc

Supplemental Table S4. The entire list of genes and the direction of expression changes involved in the biological association networks of binding complexes, metabolism regulation, post-translational modification, small molecule interaction, transcription regulation, and transport regulation determined using PathwayArchitect (DOC 117 kb)

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Stapleton, A.R., Chan, V.T. Subtoxic chlorpyrifos treatment resulted in differential expression of genes implicated in neurological functions and development. Arch Toxicol 83, 319–333 (2009). https://doi.org/10.1007/s00204-008-0346-2

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