Motor Dysfunction in Drosophila Melanogaster as a Biomarker for Developmental Neurotoxicity

Abstract

Adequate alternatives to conventional animal testing are needed to study developmental neurotoxicity (DNT). Here, we show that detailed kinematic analysis can uncover DNT, using both known (chlorpyrifos, CPS) and putative (β-N-methylamino-L-alanine, BMAA) neurotoxic compounds. Drosophila melanogaster were exposed to these compounds during development and evaluated for survival and kinematic parameters using the FlyWalker system, a kinematics evaluation method. At concentrations that do not induce general toxicity, the solvent DMSO had a significant effect on kinematic parameters. Moreover, CPS not only induced developmental lethality but also significantly impaired coordination in comparison to DMSO. Interestingly, BMAA, which was not lethal during development, induced motor decay in young adult animals, phenotypically resembling aged flies. This effect was attenuated upon ageing, indicating an adaptive response. Furthermore, BMAA induced abnormal development of leg motor neuron projections.Our results suggest that our kinematic approach is a highly sensitive method to assess potential DNT of chemical compounds.