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Neurotoxicity of low-dose (developmental) exposure to mixtures of chemicals

 

Worldwide, serious concern has arisen about the increased incidence of cognitive and behavioral disorders in children. Exposure to neurotoxic chemicals during early brain development is expected to play an important role. This student’s project will take place within a large-scale EU project to investigate possible effects of acute, chronic and developmental exposure to environmental pollutants on neuronal and cognitive functions. This research focuses primarily on possible neurotoxic effects of pesticides, although other common environmental pollutants that are expected neurotoxicants are also included.

The aim of this student’s project is to investigate neurotoxicity of (sub)chronic exposure to a number of environmental pollutants in PC12 cells. This project focuses on the investigation of effects on calcium homeostasis and production of reactive oxygen species. Risk assessment is for most classes of chemicals still based on exposure and hazard assessment of single compounds, although people are exposed to a plethora of environmental pollutants. This project therefore additionally focuses on exposure to individual compounds as well as binary mixtures.

 

Approach / techniques:

Cell culture of rat PC12 (pheochromocytoma) 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; Structure-activity relations; Imaging of ROS production in cultured cells; Pharmacology & toxicology of intracellular signaling; Risk Assessment.

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