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The pesticide fipronil injected into the substantia nigra of male rats decreases striatal dopamine content: A neurochemical, immunohistochemical and behavioral study.
Behavioural Brain Research ( IF 2.6 ) Pub Date : 2020-02-15 , DOI: 10.1016/j.bbr.2020.112562
Rahul Bharatiya 1 , Jessica Bratzu 1 , Carla Lobina 2 , Giulia Corda 3 , Cristina Cocco 3 , Philippe De Deurwaerdere 4 , Antonio Argiolas 5 , Maria Rosaria Melis 6 , Fabrizio Sanna 1
Affiliation  

Experimental evidence shows that the phenylpyrazole pesticide fipronil exerts neurotoxic effects at central level in rodents, and in particular on nigrostriatal dopaminergic neurons, whose degeneration is well known to cause motor and non-motor deficits in animals and in humans. In order to characterize better the central neurotoxic effect of fipronil, we injected fipronil (15 and 25 μg) dissolved in dimethyl sulfoxide (DMSO) unilaterally into the substantia nigra of male rats. Male rats injected with DMSO unilaterally into the substantia nigra were used as controls. Control and fipronil-treated rats were then tested in different motor (i.e., open field arena, rotarod, tail flick) and non motor tests (novel object recognition, social interaction) 15 days after injection. A systemic challenge dose of the dopamine-agonist apomorphine was also used to study the presence of a rotational behavior. Sixteen days after fipronil or DMSO injection into the substantia nigra, rats were sacrificed, and either striatal dopamine content or substantia nigra tyrosine hydroxylase (TH) immunoreactivity were measured. The results confirm that the unilateral injection of fipronil into the substantia nigra caused the degeneration of nigrostriatal dopaminergic neurons, which leads to a decrease around 50 % in striatal dopamine content and substantia nigra TH imunoreactivity. This occurred together with changes in motor activity and coordination, and in nociception but not in recognition memory and in social interaction, as revealed by the results of the behavioral experiments performed in fipronil-treated rats compared to vehicle-treated rats 15 days after treatment, as found with other compounds that destroy nigrostriatal dopaminergic neurons.

中文翻译:

将杀虫剂氟虫腈注射到雄性大鼠黑质中会降低纹状体多巴胺含量:一项神经化学,免疫组化和行为研究。

实验证据表明,苯基吡唑农药氟虫腈在啮齿动物中,尤其是对黑纹状体多巴胺能神经元,在啮齿类动物的中枢水平发挥神经毒性作用,众所周知,黑质纹状体多巴胺能神经元的退化会引起动物和人类的运动和非运动缺陷。为了更好地表征氟虫腈的中枢神经毒性作用,我们将溶解在二甲基亚砜(DMSO)中的氟虫腈(15和25μg)单侧注射到雄性大鼠的黑质中。单侧注射黑质DMSO的雄性大鼠用作对照。然后在注射后15天,在不同的运动(即,旷野竞技场,旋转臂,尾翼甩动)和非运动性测试(新物体识别,社交互动)中对对照和氟虫腈治疗的大鼠进行测试。多巴胺激动剂阿扑吗啡的全身激发剂量也用于研究旋转行为的存在。将氟虫腈或DMSO注射入黑质后16天,处死大鼠,并测量纹状体多巴胺含量或黑质酪氨酸羟化酶(TH)免疫反应性。结果证实,单侧注射氟虫腈到黑质中会引起黑纹状体多巴胺能神经元的变性,从而导致纹状体多巴胺含量降低约50%,黑质TH的反应性降低。这与运动活动和协调能力的变化,伤害感受的变化有关,但在认知记忆和社交互动中却没有变化,
更新日期:2020-02-20
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