Comparison of different in vitro cell models for the assessment of pesticide-induced dopaminergic neurotoxicity

Abstract

Biomedical and (neuro) toxicity research on (neuro) degenerative diseases still relies strongly on animal models. However, the use of laboratory animals is often undesirable for both ethical and technical reasons. Current in vitro research thus largely relies on tumor derived- or immortalized cell lines. Notably, the suitability of cell lines for studying neurodegeneration is determined by their intrinsic properties. We therefore characterized PC12, SH-SY5Y, MES23.5 and N27 cells with respect to the presence of functional membrane ion channels and receptors as well as for the effects of five known neurotoxic pesticides on cytotoxicity, oxidative stress and parameters of intracellular calcium homeostasis using a combined alamar Blue/CFDA assay, a H2DCFDA assay and single cell fluorescent (Fura-2) calcium imaging, respectively. Although all pesticides demonstrated a certain level of functional neurotoxicity in the different cell lines, our results also demonstrate considerable differences in intrinsic properties and pesticide-induced effects between the cell lines. This clearly indicates that care should be taken when interpreting (neuro)toxicity data as the chosen cell model may greatly influence the outcome.