Salama Mohamed, Lotfy Ahmed, Fathy Khaled, Makar Maria, El-Emam Mona, El-Gamal Aya, El-Gamal Mohamed, Badawy Ahmad, Mohamed Wael M Y, Sobh Mohamed
Medical Experimental Research Center, Mansura Medical School, Mansura University, Egypt; Toxicology Dept., Mansura Medical School, Mansura University, Egypt.
Medical Experimental Research Center, Mansura Medical School, Mansura University, Egypt.
Appl Transl Genom. 2015 Jul 29;7:13-8. doi: 10.1016/j.atg.2015.07.001. eCollection 2015 Dec.
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.
发育神经毒性（DNT）是指各种化学物质在儿童早期对大脑产生的毒性作用。由于人类大脑在此期间较为脆弱，各种化学物质在儿童早期会对大脑产生重大影响。一些有毒物质已被证实会对中枢神经系统产生发育毒性作用；然而，大多数物质尚无法确切鉴定。这是因为现有的动物模型并未涵盖中枢神经系统发育的整个阶段。一种能够克服传统技术大多数局限性的新方法是使用三维神经球系统。这个体外系统可以重现大脑发育期间的许多变化，使其成为预测发育神经毒性作用的理想模型。在本研究中，我们验证了马拉硫磷（一种有机磷农药，对哺乳期儿童可能有神经毒性作用）可能存在的发育神经毒性。在培养的神经球中使用了三种剂量的马拉硫磷（0.25μM、1μM和10μM），持续14天。发现马拉硫磷会影响神经球的增殖、分化和活力，这些影响与剂量和时间进程呈正相关。本研究证实了马拉硫磷对三维神经球模型的发育神经毒性作用。还需要进一步的流行病学研究将这些结果与人类接触和效应数据联系起来。
