Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China.
Environ Sci Pollut Res Int. 2013 Mar;20(3):1823-30. doi: 10.1007/s11356-012-1151-2. Epub 2012 Sep 6.
Previous studies have not examined the adverse effects of microcystin-LR (MC-LR) at environmental relevant concentrations on the development and functions of nervous system. The neurotoxic effects of MC-LR exposure on neurotransmitter systems were investigated in Caenorhabditis elegans. After exposing L1 larvae to 0.1, 1, 10, and 100 μg l(-1) of MC-LR for 8 and 24 h, the adverse effects on GABAergic, cholinergic, serotonergic, dopaminergic, and glutamatergic neurons were examined. The expression levels of genes required for development and functions of GABAergic neurons were further investigated. Body bend frequency and head thrash frequency decreased significantly after MC-LR exposure for 8 h at concentrations more than 1 μg l(-1) and after MC-LR exposure for 24 h at concentrations more than 0.1 μg l(-1). Loss of GABAergic neurons increased significantly in a dose-dependent manner after MC-LR exposure at concentrations more than 0.1 μg l(-1). In contrast, no obvious neuronal losses or morphologic changes were observed in cholinergic, serotonergic, dopaminergic, and glutamatergic neurons in MC-LR-exposed nematodes. Quantitative real-time PCR assay further showed that expression levels of unc-30, unc-46, unc-47, and exp-1 genes required for development and function of GABAergic neurons decreased significantly in nematodes exposed to MC-LR at concentrations more than 0.1 or 1 μg l(-1). MC-LR at environmental relevant concentrations caused neurobehavioral defects, which may be largely due to the neuronal loss and the alterations of expression level of genes required for GABAergic neurotransmitter system in C. elegans.
先前的研究并未考察环境相关浓度的微囊藻毒素-LR(MC-LR)对神经系统发育和功能的不良影响。本研究采用秀丽隐杆线虫研究了 MC-LR 暴露对神经递质系统的神经毒性作用。将 L1 幼虫分别暴露于 0.1、1、10 和 100μg/L 的 MC-LR 中 8 和 24 h,检测其对 GABA 能、胆碱能、血清素能、多巴胺能和谷氨酸能神经元的不良影响,并进一步研究了 GABA 能神经元发育和功能所需基因的表达水平。暴露于 1μg/L 以上浓度的 MC-LR 8 h 后,线虫的体弯曲频率和头部摆动频率显著降低;暴露于 0.1μg/L 以上浓度的 MC-LR 24 h 后,上述频率也显著降低。MC-LR 暴露剂量依赖性地增加 GABA 能神经元的缺失。相比之下,在 MC-LR 暴露的线虫中,未观察到胆碱能、血清素能、多巴胺能和谷氨酸能神经元的明显神经元缺失或形态变化。实时定量 PCR 分析进一步显示,暴露于 0.1 或 1μg/L 以上 MC-LR 浓度的线虫中,发育和 GABA 能神经递质系统功能所需的 unc-30、unc-46、unc-47 和 exp-1 基因的表达水平显著降低。环境相关浓度的 MC-LR 引起神经行为缺陷,这可能主要归因于线虫中 GABA 能神经元的缺失和表达水平的改变。