Developmental neurotoxic effects of Malathion on 3D neurosphere system

Abstract

Developmental neurotoxicity (DNT) refers to the toxic effects induced by various chemicals on brain during the early childhood period. As human brains are vulnerable during this period, various chemicals would have significant effects on brains during early childhood. Some toxicants have been confirmed to induce developmental toxic effects on CNS; however, most of agents cannot be identified with certainty. This is because available animal models do not cover the whole spectrum of CNS developmental periods. A novel alternative method that can overcome most of the limitations of the conventional techniques is the use of 3D neurosphere system. This in-vitro system can recapitulate many of the changes during the period of brain development making it an ideal model for predicting developmental neurotoxic effects. In the present study we verified the possible DNT of Malathion, which is one of organophosphate pesticides with suggested possible neurotoxic effects on nursing children. Three doses of Malathion (0.25 μM, 1 μM and 10 μM) were used in cultured neurospheres for a period of 14 days. Malathion was found to affect proliferation, differentiation and viability of neurospheres, these effects were positively correlated to doses and time progress. This study confirms the DNT effects of Malathion on 3D neurosphere model. Further epidemiological studies will be needed to link these results to human exposure and effects data.

Keywords: Acetylcholinesterase; Developmental neurotoxicity; Differentiation; Malathion; Neural progenitor cells; Neurospheres; Pesticides; Proliferation.

Fig. 1

Image of plated neurospheres after 1 week. Panel A (control × 40) shows distinct neuronal morphology with fasciculation of neurites that radiate from the central aggregation of neuronal perikarya. In contrast, panel B (Malathion 1 and 10 μM × 20) shows the absence of such neurological differentiation with neurospheres of the same appearance as in day 0. Scale bar: 100 μm.