Hernández-Plata Isela, Giordano Magda, Díaz-Muñoz Mauricio, Rodríguez Verónica M
Departamento de Neurobiología Conductual y Cognitiva, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Boulevard Juriquilla 3001, Querétaro, Querétaro 76230, Mexico.
Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Boulevard Juriquilla 3001, Querétaro, Querétaro 76230, Mexico.
Neurotoxicology. 2015 Jan;46:79-91. doi: 10.1016/j.neuro.2014.12.001. Epub 2014 Dec 15.
Glyphosate (Glyph) is the active ingredient of several herbicide formulations. Reports of Glyph exposure in humans and animal models suggest that it may be neurotoxic. To evaluate the effects of Glyph on the nervous system, male Sprague-Dawley rats were given six intraperitoneal injections of 50, 100, or 150 mg Glyph/kg BW over 2 weeks (three injections/week). We assessed dopaminergic markers and their association with locomotor activity. Repeated exposure to Glyph caused hypoactivity immediately after each injection, and it was also apparent 2 days after the last injection in rats exposed to the highest dose. Glyph did not decrease monoamines, tyrosine hydroxylase (TH), or mesencephalic TH+ cells when measured 2 or 16 days after the last Glyph injection. In contrast, Glyph decreased specific binding to D1 dopamine (DA) receptors in the nucleus accumbens (NAcc) when measured 2 days after the last Glyph injection. Microdialysis experiments showed that a systemic injection of 150 mg Glyph/kg BW decreased basal extracellular DA levels and high-potassium-induced DA release in striatum. Glyph did not affect the extracellular concentrations of 3,4-dihydroxyphenylacetic acid or homovanillic acid. These results indicate that repeated Glyph exposure results in hypoactivity accompanied by decreases in specific binding to D1-DA receptors in the NAcc, and that acute exposure to Glyph has evident effects on striatal DA levels. Additional experiments are necessary in order to unveil the specific targets of Glyph on dopaminergic system, and whether Glyph could be affecting other neurotransmitter systems involved in motor control.
草甘膦（Glyph）是几种除草剂配方中的活性成分。关于人类和动物模型中草甘膦暴露的报告表明，它可能具有神经毒性。为了评估草甘膦对神经系统的影响，雄性Sprague-Dawley大鼠在2周内接受了6次腹腔注射，剂量分别为50、100或150 mg草甘膦/千克体重（每周3次注射）。我们评估了多巴胺能标志物及其与运动活动的关联。重复暴露于草甘膦会在每次注射后立即导致活动减少，并且在接受最高剂量的大鼠中，最后一次注射后2天这种情况也很明显。在最后一次注射草甘膦后2天或16天测量时，草甘膦并未降低单胺、酪氨酸羟化酶（TH）或中脑TH +细胞的水平。相比之下，在最后一次注射草甘膦后2天测量时，草甘膦降低了伏隔核（NAcc）中D1多巴胺（DA）受体的特异性结合。微透析实验表明，全身注射150 mg草甘膦/千克体重会降低纹状体中基础细胞外DA水平以及高钾诱导的DA释放。草甘膦不影响3,4-二羟基苯乙酸或高香草酸的细胞外浓度。这些结果表明，重复暴露于草甘膦会导致活动减少，同时伴随着NAcc中D1-DA受体特异性结合的降低，并且急性暴露于草甘膦对纹状体DA水平有明显影响。为了揭示草甘膦在多巴胺能系统上的特定靶点，以及草甘膦是否会影响参与运动控制的其他神经递质系统，还需要进行额外的实验。
