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ToxSci Advance Access published online on September 24, 2007
Toxicological Sciences, doi:10.1093/toxsci/kfm248
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© The Author 2007. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Alteration of Neurotrophins in the Hippocampus and Cerebral Cortex of Young Rats Exposed to Chlorpyrifos and Methyl Parathion

Angela M. Betancourt, Nikolay M. Filipov and Russell L. Carr1

Center for Environmental Health Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762

1 Send correspondence to: Russell L. Carr, Center for Environmental Health Sciences, College of Veterinary Medicine, Box 6100, Mississippi State University, Mississippi State, MS 39762-6100 USA, Phone: 662-325-1039, Fax: 662-325-1031 rlcarr{at}cvm.msstate.edu

Received July 17, 2007; revision received September 18, 2007; accepted September 19, 2007


  Abstract

Exposure to either chlorpyrifos (CPS) or methyl parathion (MPS) results in the inhibition of acetylcholinesterase (AChE) and leads to altered neuronal activity which normally regulates critical genes such as the neurotrophins nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF). The effects of postnatal exposure to CPS and MPS on the expression of mRNA and protein levels for NGF and BDNF were investigated in the frontal cerebral cortex (cortex) and hippocampus of rats. Oral administration of CPS (4.0 or 6.0 mg/kg), MPS (0.6 or 0.9 mg/kg), or the safflower oil vehicle was performed daily from postnatal day 10 (PND10) through PND20. Exposure induced significant effects on growth and cholinesterase activity. Increased NGF protein levels were observed in the hippocampus but not the cortex on PND20 with some reduction occurring on PND28 in both regions. These changes did not correlate with the changes in NGF mRNA. BDNF mRNA was increased in both regions on PND20 and PND28 whereas BDNF protein levels were increased on PND20. On PND12, c-fos mRNA, a marker of neuronal activation, was increased in both regions. Total BDNF protein was increased in the hippocampus but decreased in the cortex. No changes in NGF protein were observed. These results indicate that repeated developmental OP exposure during the postnatal period alters NGF and BDNF in the cortex and the hippocampus and the patterns of these alterations differ between regions.


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R. L. Carr and C. A. Nail
Effect of Different Administration Paradigms on Cholinesterase Inhibition following Repeated Chlorpyrifos Exposure in Late Preweanling Rats
Toxicol. Sci., November 1, 2008; 106(1): 186 - 192.
[Abstract] [Full Text] [PDF]


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