Acevedo-Huergo Triana, Sánchez-Yépez Jonathan, Mendoza-Trejo María Soledad, Hernández-Plata Isela, Giordano Magda, Rodríguez Verónica Mireya
Departamento de Neurobiología Conductual y Cognitiva, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, Mexico.
Front Toxicol. 2024 Aug 5;6:1416708. doi: 10.3389/ftox.2024.1416708. eCollection 2024.
The herbicide atrazine (ATR) has been one of the most widely used herbicides worldwide. However, due to its indiscriminate use, it has been considered an environmental contaminant. Several studies have classified ATR as an endocrine disruptor, and it has been found to have neurotoxic effects on behavior, along with alterations in the dopaminergic, GABAergic, and glutamatergic systems in the basal ganglia of male rodents. These findings suggest that these neurotransmitter systems are targets of this herbicide. However, there are no studies evaluating the neurotoxicity of ATR in female rodents. Our study aimed to assess the effects of repeated IP injections of 100 mg ATR/kg or a vehicle every other day for 2 weeks (six injections) on the locomotor activity, content of monoamines, GABA, glutamate, and glutamine in the striatum, nucleus accumbens, ventral midbrain, and prefrontal cortex, and tyrosine hydroxylase (TH) protein levels in striatum and nucleus accumbens of female rats. Repeated 100 mg ATR/kg injections immediately decreased all the locomotor activity parameters evaluated, and such hypoactivity persisted for at least 48 h after the last ATR administration. The ATR administration increased dopamine and DOPAC content in the nucleus accumbens and the dopamine and DOPAC and serotonin and 5-HIAA content in the ventral midbrain. In contrast, the TH protein levels in the striatum and nucleus accumbens were similar between groups. Meanwhile, GABA, glutamine, and glutamate levels remained unaltered in all brain regions evaluated. The observed behavioral alterations could be associated with the monoamine changes presented by the rats. These data reveal that the nucleus accumbens and ventral midbrain are susceptible to repeated ATR exposure in female rats.
除草剂阿特拉津（ATR）一直是全球使用最广泛的除草剂之一。然而，由于其滥用，它被视为一种环境污染物。多项研究已将ATR归类为内分泌干扰物，并且已发现它对行为具有神经毒性作用，同时雄性啮齿动物基底神经节中的多巴胺能、GABA能和谷氨酸能系统也会发生改变。这些发现表明这些神经递质系统是这种除草剂的作用靶点。然而，尚无研究评估ATR对雌性啮齿动物的神经毒性。我们的研究旨在评估每隔一天腹腔注射100 mg ATR/kg或溶剂，持续2周（共6次注射）对雌性大鼠的运动活动、纹状体、伏隔核、腹侧中脑和前额叶皮质中单胺、GABA、谷氨酸和谷氨酰胺的含量，以及纹状体和伏隔核中酪氨酸羟化酶（TH）蛋白水平的影响。重复注射100 mg ATR/kg后，所有评估的运动活动参数立即下降，并且这种活动减退在最后一次ATR给药后至少持续48小时。给予ATR增加了伏隔核中多巴胺和DOPAC的含量，以及腹侧中脑中多巴胺、DOPAC、血清素和5-HIAA的含量。相比之下，各组纹状体和伏隔核中的TH蛋白水平相似。同时，所有评估脑区中的GABA、谷氨酰胺和谷氨酸水平均未改变。观察到的行为改变可能与大鼠出现的单胺变化有关。这些数据表明，雌性大鼠的伏隔核和腹侧中脑易受反复ATR暴露的影响。
