Reyes-Bravo D Y, Villalobos-Aguilera P, Almonte-Zepeda J T, Mendoza-Trejo M S, Giordano M, Orozco A, Rodríguez V M
Departamento de Neurobiología Conductual y Cognitiva, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, México.
Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, México.
Front Toxicol. 2022 Aug 22;4:933300. doi: 10.3389/ftox.2022.933300. eCollection 2022.
The herbicide atrazine (ATR; 2-chloro-4-ethylamino-6-isopropylamino-s-triazine) is widely used to destroy grasses and broadleaf weeds in crops and some fruits. Studies in rodents have shown that acute, repeated or chronic exposure to ATR is associated with alterations in the nigrostriatal dopaminergic pathway, whereas its effects on GABAergic and glutamatergic pathways have only recently been reported. Sprague-Dawley male rats were exposed daily to 1 or 10 mg ATR/kg of BW for 13 months to evaluate the ATR effects on GABAergic and glutamatergic systems. At the end of the ATR treatment, the levels of mRNA of several genes involved in the production, vesiculation, reuptake, and receptors of GABA and Glu in the striatum (STR), nucleus accumbens (NAcc), prefrontal cortex (PFC), ventral midbrain (vMID) and hippocampus (HIPP) were evaluated by absolute qPCR. For the GABAergic genes, increased expression of and in STR and/or vMID in rats exposed to 1 and/or 10 mg ATR were detected. With regard to the expression of genes involved in the glutamatergic system, and in HIPP of rats exposed to 1 and/or 10 mg ATR, increased as was in STR and PFC in the group exposed to 1 mg ATR. In the same fashion, expression and increased in STR of rats exposed to 1 and 10 mg ATR groups. The expression of the glutaminases (variants 1 and 2) was greater in STR, NAcc, HIPP, and PFC of rats exposed to 1 and/or 10 mg ATR. These findings show that the GABAergic and, especially glutamatergic systems are targets of ATR exposure.
除草剂阿特拉津（ATR；2-氯-4-乙氨基-6-异丙氨基-s-三嗪）被广泛用于杀灭农作物和一些水果中的杂草及阔叶杂草。对啮齿动物的研究表明，急性、反复或慢性接触ATR与黑质纹状体多巴胺能通路的改变有关，而其对γ-氨基丁酸能（GABAergic）和谷氨酸能通路的影响直到最近才被报道。将Sprague-Dawley雄性大鼠每天暴露于1或10毫克ATR/千克体重，持续13个月，以评估ATR对GABA能和谷氨酸能系统的影响。在ATR治疗结束时，通过绝对定量聚合酶链反应（qPCR）评估纹状体（STR）、伏隔核（NAcc）、前额叶皮质（PFC）、腹侧中脑（vMID）和海马体（HIPP）中参与GABA和谷氨酸（Glu）产生、囊泡形成、再摄取及受体的几个基因的mRNA水平。对于GABA能基因，在暴露于1和/或10毫克ATR的大鼠的STR和/或vMID中，检测到[具体基因1]和[具体基因2]的表达增加。关于参与谷氨酸能系统的基因表达，在暴露于1和/或10毫克ATR的大鼠的HIPP中，[具体基因3]和[具体基因4]增加，在暴露于1毫克ATR的组中，STR和PFC中的[具体基因5]也增加。同样，在暴露于1和10毫克ATR组的大鼠的STR中，[具体基因6]表达和[具体基因7]增加。在暴露于1和/或10毫克ATR的大鼠的STR、NAcc、HIPP和PFC中，谷氨酰胺酶（变体1和2）的表达更高。这些发现表明，GABA能系统，尤其是谷氨酸能系统是ATR暴露的靶点。
