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Neurotoxicity Research

Erschienen in:

01.08.2012

Dexamethasone Enhances Oxidative Stress-Induced Cell Death in Murine Neural Stem Cells

verfasst von: Henricus A. M. Mutsaers, Roshan Tofighi

Erschienen in: Neurotoxicity Research | Ausgabe 2/2012

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Abstract

Glucocorticoids (GCs) are essential for normal brain development; however, there is consistent evidence that prenatal exposure of the fetal brain to excess GCs permanently modifies the phenotype of neuronal cells. In this paper, the murine-derived multipotent stem cell line C17.2 was used, as an in vitro model, to investigate the impact of GCs on neural stem cell survival. Our results indicate that dexamethasone (Dex) increases the sensitivity of murine neural stem cells (NSCs) to 2,3-methoxy-1,4-naphthoquinone-induced apoptosis, and this effect could be blocked by the glucocorticoid-receptor (GR) antagonist mifepristone, strongly suggesting the involvement of the GR. Furthermore, our results show that Dex decreases cell number and induces a G1-arrest. We hypothesized that the mitochondria are the main target of Dex. Interestingly, after treatment with Dex, 72% of the investigated genes involved in the mitochondrial respiratory chain are down-regulated, as well as 29% of the genes encoding for antioxidant enzymes. In conclusion, using the C17.2 cell line as a model to study developmental neurotoxicity in vitro, we have shown that GCs can increase cellular sensitivity to oxidative stress and alter the phenotype of NCSs.

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Titel: Dexamethasone Enhances Oxidative Stress-Induced Cell Death in Murine Neural Stem Cells
verfasst von: Henricus A. M. Mutsaers
Roshan Tofighi
Publikationsdatum: 01.08.2012
Verlag: Springer-Verlag
Erschienen in: Neurotoxicity Research / Ausgabe 2/2012
Print ISSN: 1029-8428
Elektronische ISSN: 1476-3524
DOI: https://doi.org/10.1007/s12640-012-9308-9

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