Potential mechanisms of development-dependent adverse effects of the herbicide paraquat in 3D rat brain cell cultures.

Details

Serval ID
serval:BIB_23DB00E03793
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Potential mechanisms of development-dependent adverse effects of the herbicide paraquat in 3D rat brain cell cultures.
Journal
Neurotoxicology
Author(s)
Sandström J., Broyer A., Zoia D., Schilt C., Greggio C., Fournier M., Do K.Q., Monnet-Tschudi F.
ISSN
1872-9711 (Electronic)
ISSN-L
0161-813X
Publication state
Published
Issued date
05/2017
Peer-reviewed
Oui
Volume
60
Pages
116-124
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Exposure to environmental toxicants during vulnerable windows of brain development is suspected to raise the prevalence for neurological dysfunctions at later stages in life. Differentiation processes and changes in morphology, as well as a lack of physiological barriers, might be reasons that render a developing brain more susceptible to neurotoxicants than an adult. However, also the intrinsic capacity of cells to combat toxicant induced cellular stress might differ between the immature- and mature brain. In order to study whether this intrinsic protection capacity differs between immature and maturated brain cells we chose to study the maturation-dependent adverse effects of the known neurotoxicant Paraquat Dichloride (PQ) in 3D rat brain cell cultures. This in vitro system consists of the major brain cell types - neurons, astrocytes, oligodendrocytes and microglia - and over the time in vitro cultured cells undergo differentiation and maturation into a tissue-like organization. PQ was applied repeatedly over ten days in the sub-micromolar range, and effects were evaluated on neurons and glial cells. We observed that despite a higher PQ-uptake in mature cultures, PQ-induced adverse effects on glutamatergic-, GABAergic- and dopaminergic neurons, as assessed by gene expression and enzymatic activity, were more pronounced in immature cultures. This was associated with a stronger astrogliosis in immature- as compared to mature cultures, as well as perturbations of the glutathione-mediated defense against oxidative stress. Furthermore we observed evidence of microglial activation only in mature cultures, whereas immature cultures appeared to down-regulate markers for neuroprotective M2-microglial phenotype upon PQ-exposure. Taken together our results indicate that immature brain cell cultures have less intrinsic capacity to cope with cellular stress elicited by PQ as compared to mature cells. This may render immature brain cells more susceptible to the adverse effects of PQ.

Keywords
Animals, Astrocytes/drug effects, Astrocytes/metabolism, Brain/drug effects, Brain/embryology, Brain/metabolism, Cells, Cultured, Encephalitis/chemically induced, Herbicides/toxicity, Inflammation Mediators, Microglia/drug effects, Microglia/metabolism, Neurons/drug effects, Neurons/metabolism, Oxidative Stress, Paraquat/toxicity, Rats, Sprague-Dawley, 3D rat brain cell cultures, Developmental neurotoxicity (DNT), Glutathione (GSH), M1/M2 microglial phenotypes, Neuroinflammation, Paraquat uptake
Pubmed
Web of science
Create date
09/05/2017 16:53
Last modification date
20/08/2019 13:01
Usage data