Department of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy.
Institute of Neuroscience, National Research Council, Cagliari Section, University of Cagliari, Cagliari, Italy.
Behav Brain Res. 2020 Apr 20;384:112562. doi: 10.1016/j.bbr.2020.112562. Epub 2020 Feb 15.
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.
实验证据表明，苯吡唑类农药氟虫腈对啮齿动物的中枢神经系统具有神经毒性作用，特别是对黑质纹状体多巴胺能神经元，其退化众所周知会导致动物和人类的运动和非运动缺陷。为了更好地描述氟虫腈的中枢神经毒性作用，我们将氟虫腈（15 和 25 μg）溶解在二甲基亚砜（DMSO）中单侧注射到雄性大鼠的黑质中。将 DMSO 单侧注射到黑质的雄性大鼠用作对照。注射后 15 天，用不同的运动（即开阔场、旋转棒、尾巴拍打）和非运动测试（新物体识别、社交互动）测试对照和氟虫腈处理的大鼠。还使用多巴胺激动剂阿扑吗啡的全身挑战剂量来研究旋转行为的存在。在氟虫腈或 DMSO 单侧注射到黑质 16 天后，处死大鼠，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，氟虫腈单侧注射到黑质会导致黑质纹状体多巴胺能神经元变性，导致纹状体多巴胺含量和黑质 TH 免疫反应性下降约 50%。这与运动活动和协调能力以及疼痛感知的变化同时发生，但与识别记忆和社交互动无关，这是通过与其他破坏黑质纹状体多巴胺能神经元的化合物相比，在氟虫腈处理的大鼠中进行的行为实验的结果发现的。
