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Brain alterations in GABA, glutamate and glutamine markers after chronic atrazine exposure in the male albino rat.
Archives of Toxicology ( IF 6.1 ) Pub Date : 2020-06-19 , DOI: 10.1007/s00204-020-02806-2
M E Chávez-Pichardo 1 , D Y Reyes-Bravo 1 , M S Mendoza-Trejo 1 , A G Marín-López 1 , M Giordano 1 , N Hernández-Chan 2 , K Domínguez-Marchan 1 , L C Ortega-Rosales 1 , V M Rodríguez 1
Affiliation  

Atrazine (ATR; 2-chloro-4-ethylamino-6-isopropylamino-s-triazine) is an herbicide widely used to kill annual grasses and broadleaf weeds in crops such as corn, sorghum, and sugarcane. Studies in rodents have shown that chronic ATR exposure is associated with alterations in the nigrostriatal dopaminergic pathway such as hyperactivity, decreased striatal dopamine levels, and diminished numbers of tyrosine hydroxylase positive cells in substantia nigra pars compacta. However, the effects of ATR on neurotransmitters such as GABA and glutamate have been scarcely studied. To evaluate the impact of ATR on motor and anxiety tasks, tissue levels of GABA, glutamate, glutamine, and extracellular and potassium-evoked release of glutamate in the striatum, we daily exposed Sprague–Dawley male rats to 1 or 10 mg ATR/kg of body weight for 12–14 months. As previously reported, chronic ATR exposure causes hyperactivity in the group exposed to 10 mg ATR/kg and increased anxiety in both groups exposed to ATR. GABA, glutamate, and glutamine levels were differentially altered in brain regions related to nigrostriatal and mesolimbic systems, the amygdala, and the prefrontal cortex. The groups exposed to 10 mg ATR/kg showed increased extracellular levels and release of glutamate in the striatum. These neurochemical alterations could underlie the behavioral changes observed in rats. These results indicate that chronic exposure to the herbicide ATR disrupts the neurochemistry of several brain structures and could be a risk factor for the development of neurodegenerative diseases.



中文翻译:

长期暴露于雄性白化病大鼠中的阿特拉津后,GABA,谷氨酸和谷氨酰胺标志物的大脑变化。

阿特拉津(ATR; 2-氯-4-乙基氨基-6-异丙基氨基-s-三嗪)是一种除草剂,广泛用于杀死玉米,高粱和甘蔗等农作物中的一年生禾本科和阔叶杂草。在啮齿动物中的研究表明,长期暴露于ATR与黑质纹状体多巴胺能途径的改变有关,例如活动过度,纹状体多巴胺水平降低,黑质致密部酪氨酸羟化酶阳性细胞数量减少。然而,很少研究ATR对神经递质如GABA和谷氨酸的影响。为了评估ATR对运动和焦虑任务,组织水平的GABA,谷氨酸,谷氨酰胺以及纹状体中谷氨酸的细胞外和钾诱发的谷氨酸释放的影响,我们每天将Sprague–Dawley雄性大鼠暴露于1或10 mg ATR / kg体重持续12-14个月。如先前报道的,长期暴露于ATR会导致暴露于10 mg ATR / kg的组多动,并导致两组暴露于ATR的焦虑增加。GABA,谷氨酸和谷氨酰胺水平在与黑纹状体和中脑边缘系统,杏仁核和前额叶皮层相关的大脑区域中差异地变化。暴露于10 mg ATR / kg的组显示出增加的细胞外水平和纹状体中谷氨酸的释放。这些神经化学改变可能是在大鼠中观察到的行为改变的基础。这些结果表明,长期暴露于除草剂ATR会破坏几种大脑结构的神经化学,并且可能是神经退行性疾病发展的危险因素。长期暴露于ATR会导致暴露于10 mg ATR / kg的组过度活跃,并且暴露于ATR的两组患者的焦虑都会增加。GABA,谷氨酸和谷氨酰胺水平在与黑纹状体和中脑边缘系统,杏仁核和前额叶皮层相关的大脑区域中差异地变化。暴露于10 mg ATR / kg的组显示出增加的细胞外水平和纹状体中谷氨酸的释放。这些神经化学改变可能是在大鼠中观察到的行为改变的基础。这些结果表明,长期暴露于除草剂ATR会破坏几种大脑结构的神经化学,并且可能是神经退行性疾病发展的危险因素。长期暴露于ATR会导致暴露于10 mg ATR / kg的组过度活跃,并且暴露于ATR的两组患者的焦虑都会增加。GABA,谷氨酸和谷氨酰胺水平在与黑纹状体和中脑边缘系统,杏仁核和前额叶皮层相关的大脑区域中差异地变化。暴露于10 mg ATR / kg的组显示出增加的细胞外水平和纹状体中谷氨酸的释放。这些神经化学改变可能是在大鼠中观察到的行为改变的基础。这些结果表明,长期暴露于除草剂ATR会破坏几种大脑结构的神经化学,并且可能是神经退行性疾病发展的危险因素。杏仁核和前额叶皮层。暴露于10 mg ATR / kg的组显示出增加的细胞外水平和纹状体中谷氨酸的释放。这些神经化学改变可能是在大鼠中观察到的行为改变的基础。这些结果表明,长期暴露于除草剂ATR会破坏几种大脑结构的神经化学,并且可能是神经退行性疾病发展的危险因素。杏仁核和前额叶皮层。暴露于10 mg ATR / kg的组显示出增加的细胞外水平和纹状体中谷氨酸的释放。这些神经化学改变可能是在大鼠中观察到的行为改变的基础。这些结果表明,长期暴露于除草剂ATR会破坏几种大脑结构的神经化学,并且可能是神经退行性疾病发展的危险因素。

更新日期:2020-06-19
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