Abstract
Historically, only few chemicals have been identified as neurodevelopmental toxicants, however, concern remains, and has recently increased, based upon the association between chemical exposures and increased developmental disorders. Diminution in motor speed and latency has been reported in preschool children from agricultural communities. Organophosphorus compounds (OPs) are pesticides due to their acute insecticidal effects mediated by the inhibition of acetylcholinesterase, although other esterases as neuropathy target esterase (NTE) can also be inhibited. Other neurological and neurodevelopmental toxic effects with unknown targets have been reported after chronic exposure to OPs in vivo. We studied the initial stages of retinoic acid acid-triggered differentiation of pluripotent cells towards neural progenitors derived from human embryonal carcinoma stem cells to determine if neuropathic OP, mipafox, and non-neuropathic OP, paraoxon, are able to alter differentiation of neural precursor cells in vitro. Exposure to 1 μM paraoxon (non-cytotoxic concentrations) altered the expression of different genes involved in signaling pathways related to chromatin assembly and nucleosome integrity. Conversely, exposure to 5 μM mipafox, a known inhibitor of NTE activity, showed no significant changes on gene expression. We conclude that 1 μM paraoxon could affect the initial stage of in vitro neurodifferentiation possibly due to a teratogenic effect, while the absence of transcriptional alterations by mipafox exposure did not allow us to conclude a possible effect on neurodifferentiation pathways at the tested concentration.
Highlights
Organophosphorus compounds (OPs) have been used worldwide as pesticides for insect control.In Europe alone, OP insecticide production was close to 31,000 tons in 2010 [1]
Because of the similarity of neurochemical processes, these compounds are likely to be neurotoxic to human brain, especially to the developing nervous system which is inherently much more vulnerable to injury caused by toxic agents than the brain of adults [3,4,5]
The main mechanism of action of OPs is based on irreversible enzyme inactivation caused by the phosphorylation of the active centre of esterases located in the neurons of the central and peripheral nervous systems [8]
Summary
Organophosphorus compounds (OPs) have been used worldwide as pesticides for insect control.In Europe alone, OP insecticide production was close to 31,000 tons in 2010 [1]. Organophosphorus compounds (OPs) have been used worldwide as pesticides for insect control. Many OPs target the nervous system of insect pests. Because of the similarity of neurochemical processes, these compounds are likely to be neurotoxic to human brain, especially to the developing nervous system which is inherently much more vulnerable to injury caused by toxic agents than the brain of adults [3,4,5]. There are evidences that pesticides reduce motor activity, latency and cause visuospatial deficits after high exposure [6,7]. The main mechanism of action of OPs is based on irreversible enzyme inactivation caused by the phosphorylation of the active centre of esterases located in the neurons of the central and peripheral nervous systems [8]
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