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

Arch Toxicol. 2009 Apr;83(4):319-33. doi: 10.1007/s00204-008-0346-2. Epub 2008 Jul 31.


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.

MeSH terms

  • Administration, Oral
  • Animals
  • Chlorpyrifos / toxicity*
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental / drug effects*
  • Glycogen Synthase Kinase 3 / genetics
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • Insecticides / toxicity*
  • Male
  • Oligonucleotide Array Sequence Analysis
  • Prosencephalon / drug effects*
  • Prosencephalon / metabolism
  • Prosencephalon / pathology
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Inbred F344
  • Toxicity Tests


  • Insecticides
  • RNA, Messenger
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, rat
  • Glycogen Synthase Kinase 3
  • Chlorpyrifos