Effects of organophosphorus insecticides on brain neurotrophins and cell-specific markers in rats following postnatal exposure

The effects of repeated daily oral postnatal exposure to chlorpyrifos (CPS) and methyl parathion (MPS) on cholinesterase (ChE) activity and on mRNA expression and protein concentration of the neurotrophins nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) and the cell-specific markers for developing neurons (beta-III tubulin), astrocytes (glial fibrillary acidic protein, GFAP), and oligodendrocytes (myelin-associated glycoprotein, MAG) were investigated in the hippocampus and frontal cortex of rats. Daily exposure to CPS (1.5 or 3.0 mg/kg) from postnatal day 1 (PND1) through PND6 significantly reduced NGF and MAG mRNA on PND7 with both dosages of CPS, whereas beta-III tubulin mRNA remained unchanged and GFAP mRNA was significantly increased. In a second group, administered either CPS (4.0 or 6.0 mg/kg), MPS (0.6 or 0.9 mg/kg), or vehicle from PND10 through PND20, alteration of cholinergic activity occurred during the exposure as evidenced by increased c-fos mRNA expression and the inhibition of AChE observed in both the hippocampus and frontalcortex. Both CPS and MPS induced variable changes in NGF and BDNF mRNA expression and protein concentration in both brain regions during exposure (PND20) but following cessation of exposure (PND28), significant reductions were present suggesting a delayed effect. With respect to the cell markers on PND20 and PND28, the effects observed varied depending on compound, brain region, and age.; In different series of experiments, the in vitro effects of CPS on neurotrophin mRNA expression and hemeoxygenase-1 (HO-1) protein levels were determined using organotypic slice cultures. These studies demonstrated that OPs could alter neurotrophin expression and these effects seem to be mediated by both the cholinergic and glutamatergic system. In addition, CPS induced the expression of HO-1 in both hippocampal and cortical slices.; Our findings indicate that OP exposure can affect both the in vivo and in vitro expression of critical genes involved in brain development during the postnatal period in the rat and induce the expression of HO-1 which could indicate the induction of oxidative stress by these compounds.