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- Högberg, Helena T., 1975-, et al.
(författare)
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Gene expression as a sensitive endpoint to evaluate cell differentiation andmaturation of the developing central nervous system in primary cultures of ratcerebellar granule cells (CGCs) exposed to pesticides
- 2009
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Ingår i: Toxicology and Applied Pharmacology. - : Elsevier BV. - 0041-008X .- 1096-0333. ; 235, s. 268-286
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Tidskriftsartikel (refereegranskat)abstract
- The major advantage of primary neuronal cultures for developmental neurotoxicity (DNT) testing is their ability to replicate the crucial stages of neurodevelopment. In our studies using primary culture of cerebellar granule cells (CGCs) we have evaluated whether the gene expression relevant to the most critical developmental processes such as neuronal differentiation (NF-68 and NF-200) and functional maturation (NMDA and GABA presence of neural precursor cells (nestin and Sox10) could be used as an endpoint for in vitro DNT. The expression of these genes was assessed after exposure to various pesticides (paraquat parathion, dichlorvos, pentachlorophenol and cycloheximide) that could induce developmental neurotoxicity through different mechanisms. All studied pesticides signi different stages of neuronal and/or glial cell development and maturation. The most signi observed after exposure to paraquat and parathion (i.e. down-regulation of mRNA expression of NF-68 and NF-200, NMDA and GABA expression of NF-68 and GABA as signi astrocyte marker (S100 multiple pathways of neurodevelopment can be identi in different stages of cell development and maturation, and that gene expression could be used as a sensitive endpoint for initial screening to identify the compounds with the potential to cause developmental neurotoxicity. A receptors), proliferation and differentiation of astrocytes (GFAP and S100β) as well as theficantly modified the expression of selected genes, related to theficant changes wereA receptors). Similarly, dichlorvos affected mainly neurons (decreased mRNAA receptors) whereas cycloheximide had an effect on neurons and astrocytes,ficant decreases in the mRNA expression of both neurofilaments (NF-68 and NF-200) and theβ) were observed. Our results suggest that toxicity induced by pesticides that targetfied by studying expression of genes that are involved
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| 2. |
- Högberg, Helena T., 1975-, et al.
(författare)
-
mRNA Expression is a Relevant Tool to Identify Developmental Neurotoxicants Using an In Vitro Approach
- 2009
-
Ingår i: Toxicological Sciences. - : Oxford university press. - 1096-6080 .- 1096-0929. ; 113:1, s. 95-115
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Tidskriftsartikel (refereegranskat)abstract
- So far, only a few industrial chemicals have been identified as developmental neurotoxicants. Because the current developmental neurotoxicity (DNT) guideline (Organisation for Economic Cooperation and Development TG 426) is based entirely on in vivo studies that are both time consuming and costly, there is a need to develop alternative in vitro methods for initial screening to prioritize chemicals for further DNT testing. In this study, 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 downregulation of the mRNA level for the neuronal markers (NF- 68, NF-200, N-methyl D-aspartate glutamate receptor, and gamma amino butyric acid receptor) 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 (glial fibrillary acidic protein [GFAP] and S100b) was unchanged. In contrast, exposure to lead chloride significantly decreased the mRNA level of the astrocytic marker GFAP, whereas 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.
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