Betancourt Angela M, Filipov Nikolay M, Carr Russell L
Center for Environmental Health Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762, USA.
Toxicol Sci. 2007 Dec;100(2):445-55. doi: 10.1093/toxsci/kfm248. Epub 2007 Sep 24.
Exposure to either chlorpyrifos (CPS) or methyl parathion (MPS) results in the inhibition of acetylcholinesterase 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 messenger RNA (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.
接触毒死蜱（CPS）或甲基对硫磷（MPS）会导致乙酰胆碱酯酶受到抑制，并导致神经元活动改变，而神经元活动通常会调节关键基因，如神经营养因子神经生长因子（NGF）和脑源性神经营养因子（BDNF）。研究了出生后接触CPS和MPS对大鼠额叶大脑皮层（皮层）和海马体中NGF和BDNF的信使核糖核酸（mRNA）表达及蛋白质水平的影响。从出生后第10天（PND10）至PND20，每天经口给予CPS（4.0或6.0毫克/千克）、MPS（0.6或0.9毫克/千克）或红花油载体。接触对生长和胆碱酯酶活性产生了显著影响。在PND20时，海马体中观察到NGF蛋白质水平升高，但皮层中未观察到，且在两个区域的PND28时均出现了一定程度的下降。这些变化与NGF mRNA的变化不相关。在PND20和PND28时，两个区域的BDNF mRNA均增加，而BDNF蛋白质水平在PND20时增加。在PND12时，神经元激活标志物c-fos mRNA在两个区域均增加。海马体中总BDNF蛋白质增加，但皮层中减少。未观察到NGF蛋白质有变化。这些结果表明，出生后反复接触有机磷农药会改变皮层和海马体中的NGF和BDNF，且这些改变的模式在不同区域有所不同。
