mRNA Expression is a Relevant Tool to Identify Developmental Neurotoxicants Using an In Vitro Approach

Due to lack of knowledge only a few industrial chemicals have been identified as developmental neurotoxicants so far. Since the current developmental neurotoxicity (DNT) guidelines (OECD TG 426) are based entirely on in vivo studies that are both time consuming and costly, there is a high demand to develop alternative in vitro methods for initial screening to prioritise chemicals for further DNT testing. Here, the gene expression at the mRNA level was evaluated to determine whether this could be a suitable endpoint to detect potential developmental neurotoxicants. Primary cultures of rat cerebellar granule cells (CGCs) were exposed to well known (developmental) neurotoxicants (methyl mercury chloride, lead chloride, valproic acid and tri-methyl tin chloride) for different time periods. A significant down-regulation of the mRNA level for the neuronal markers (NF-68, NF-200, NMDA-R and GABAA-R) was observed after exposure to methyl mercury chloride, valproic acid and tri-methyl tin chloride. Moreover, a significant increase of the neural precursor marker nestin mRNA was also observed. The mRNA expression of the astrocytic markers (GFAP and S100ß) was unchanged. In contrast, exposure to lead chloride significantly decreased the mRNA level of the astrocytic marker GFAP while the neuronal markers were less affected. These results suggest that gene expression could be used as a sensitive tool for the initial identification of DNT effects induced by different mechanisms of toxicity in both cell types (neuronal and glial) and at various stages of cell development and maturation.

HOGBERG Helena;  KINSNER-OVASKAINEN Agnieszka;  COECKE Sandra;  HARTUNG Thomas;  PRICE Anna; 

2010-01-25

OXFORD UNIV PRESS

JRC52913

1096-6080,   

http://toxsci.oxfordjournals.org/cgi/content/abstract/kfp175,    https://publications.jrc.ec.europa.eu/repository/handle/JRC52913,   

10.1093/toxsci/kfp175,