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Human in vitro models to study organophosphate-induced neurotoxicity


Following high dose exposure, organophosphate insecticides are well-known to induce acute neurotoxicity characterized by overexcitation due to excess amounts of the neurotransmitter acetylcholine. These excitatory effects are primarily due to inhibition of the metabolizing enzyme acetylcholine-esterase, though effects on calcium homeostasis and neurotransmitter receptors may also be involved. In addition to these acute effects, organophosphates can induce delayed as well as developmental neurotoxicity, though these effects have been more difficult to study in vitro.

Within this project we therefore want to develop and characterize an in vitro-based testing approach to assess acute as well as delayed and developmental neurotoxicity induced by organophosphates using human cell lines. The results from these studies may aid in replacing animal testing and provide important data for human risk assessment of organophosphates.


Approach / techniques:

Cell culture of human SH-SY5Y neuroblastoma cells; Imaging of intracellular calcium in cultured cells loaded with calcium-sensitive fluorescent dyes (Fura-2) using a fluorescence microscope equipped with a highly sensitive CCD camera; Biochemical determination of cytotoxicity and levels of neurotransmitters and enzymes; Structure-activity relations; Pharmacology & toxicology of intracellular signaling.