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|Title:||Effect of pesticides on neuronal and Glial cell differentiation and maturation in primary culture|
|Authors:||PRICE Anna; HOGBERG Helena|
|Type:||Articles in periodicals and books|
|Abstract:||Pesticides are recognized as neurotoxic substances since most of them target neurochemical processes of insects that are similar to those of the human nervous system. There is substantial concern about the impact on children as the developing brain in foetuses and children is much more vulnerable to injury caused by different classes of substances, including pesticides, than the adult brain. This vulnerability is in part due to the fact that the adult brain is well protected against chemicals by the blood brain barrier (BBB) while children have increased absorption and a diminished ability to detoxify many exogenous compounds in comparison to that of adults (NRC, 2000). Moreover, the development of the central nervous system (CNS) is a very complex process involving proliferation, migration, differentiation of various cell types (neuronal, glial and endothelial cells) among other processes (Rice and Barone, 2000; Rodier, 1994). These events are occurring within a tightly controlled time frame and therefore create different windows of vulnerability to toxicity. We have evaluated DNT induced toxicity by pesticides using two in vitro models including primary neuronal culture of rat cerebellar granule cells (CGCs) and rat cortical neuronal cultures. Pesticide toxicity was studied at the level of key neuro-developmental processes such as cell proliferation, migration and neuronal/glial differentiation measured by gene expression, immuno-cytochemistry staining and neuronal electrical activity measured by MEAs (micro electrode arrays). The results suggested that adverse effects induced by studied pesticides (paraquat, parathion, dichlorvos, pentachlorophenol and cycloheximide) were mediated by multiple toxicity mechanisms. Indeed, this approach allowed us to determine which cell type (neuronal or glial) and at which stage of development (proliferation, differentiation or maturation) was affected by the exposure to the different pesticides. Pesticides induced toxicity, as identified by mRNA expression, was observed at lower concentrations than found in human plasma, suggesting that gene expression could be used as a sensitive endpoint for testing DNT effects of pesticides. The obtained results suggest that applied models (CGCs and cortical neuronal primary cultures) and endpoints (gene and protein expression) are relevant in vitro tools for neurodevelopmental toxicity evaluation induced by pesticides.|
|JRC Institute:||Institute for Health and Consumer Protection|
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