Specific Effects of Chronic Dietary Exposure to Chlorpyrifos on Brain Gene Expression-A Mouse Study

Int J Mol Sci. 2017 Nov 20;18(11):2467. doi: 10.3390/ijms18112467.

Abstract

chlorpyrifos (CPF) is an organophosphate insecticide used to control pests on a variety of food and feed crops. In mammals, maternal exposure to CPF has been reported to induce cerebral cortex thinning, alteration of long-term brain cognitive function, and Parkinson-like symptoms, but the mechanisms of these processes are not fully understood. In this study, we aimed to gain a deeper understanding of the alterations induced in the brains of mice chronically exposed to CPF by dietary intake. For our purpose, we analysed F1 offspring (sacrificed at 3 and 8 months) of Mus musculus, treated in utero and postnatally with 3 different doses of CPF (0.1-1-10 mg/kg/day). Using RT² Profiler PCR Arrays, we evaluated the alterations in the expression of 84 genes associated with neurodegenerative diseases. In the brains of exposed mice, we evidenced a clear dose-response relationship for AChE inhibition and alterations of gene expression. Some of the genes that were steadily down-regulated, such as Pink1, Park 2, Sv2b, Gabbr2, Sept5 and Atxn2, were directly related to Parkinson's onset. Our experimental results shed light on the possibility that long-term CPF exposure may exert membrane signalling alterations which make brain cells more susceptible to develop neurodegenerative diseases.

Keywords: Mus musculus; PCR-array; Parkinson’s disease; chlorpyrifos; developmental neurotoxicity; neurodegenerative diseases; organophosphate insecticides.

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism*
  • Brain / pathology
  • Chlorpyrifos / toxicity*
  • Dietary Exposure / adverse effects
  • Female
  • Gene Expression Regulation / drug effects
  • Humans
  • Insecticides / toxicity
  • Maternal Exposure / adverse effects*
  • Mice
  • Parkinson Disease, Secondary / chemically induced
  • Parkinson Disease, Secondary / genetics*
  • Parkinson Disease, Secondary / pathology
  • Protein Biosynthesis / drug effects

Substances

  • Insecticides
  • Chlorpyrifos