Faculty of Medicine, UAE University, Al Ain, United Arab Emirates.
Physiol Res. 2013;62(3):313-21. doi: 10.33549/physiolres.932386. Epub 2013 Mar 14.
The use of the herbicide paraquat (1,1'-dimethyl-4,4'-bipyridylium dichloride; PQ) which is widely used in agriculture is known to cause dopaminergic neurotoxicity. However, the mechanisms underlying this effect are not fully understood. This present study investigated the behavioral manifestations, motor coordination, and dopaminergic neurodegeneration following exposure to PQ. Male rats were injected with PQ (10 mg/kg i.p.) daily for three weeks. Rotarod systems were used for measuring locomotor activity and motor coordination. The effects of PQ on dorsiflexor, electrophysiologically-induced muscle contraction were studied. Dopamine concentrations in the ventral mesencephalon were measured by high performance liquid chromatography and the number of dopaminergic neurons in substantia nigra pars compacta was estimated by tyrosine hydroxylase immunohistochemistry. PQ induced difficulty in movement and significant reduction in motor activity and twitch tension at the dorsiflexor skeletal muscle. The number of tyrosine hydroxylase positive neurons was significantly less in the substantia nigra pars compacta and nigral dopamine level was significantly reduced in PQ treated animals (20.4+/-3.4 pg/mg) when compared with control animals (55.0+/-2.4 pg/mg wet tissue). Daily treatment of PQ for three weeks induces selective dopaminergic neuronal loss in the substantia nigra and significant behavioral and peripheral motor deficit effects.
百草枯（1,1'-二甲基-4,4'-联吡啶二氯化物；PQ）是一种广泛应用于农业的除草剂，已知其具有多巴胺能神经毒性。然而，其作用机制尚未完全阐明。本研究探讨了暴露于百草枯后行为表现、运动协调和多巴胺能神经退行性变。雄性大鼠每天腹腔注射 PQ（10mg/kg），连续 3 周。旋转棒系统用于测量运动活动和运动协调。研究了 PQ 对背屈肌的影响，电生理诱导的肌肉收缩。通过高效液相色谱法测量腹侧中脑的多巴胺浓度，并通过酪氨酸羟化酶免疫组织化学法估计黑质致密部多巴胺能神经元的数量。百草枯引起运动困难，运动活动和背屈肌抽搐张力显著降低。与对照组动物（55.0+/-2.4pg/mg 湿组织）相比，PQ 处理动物黑质致密部酪氨酸羟化酶阳性神经元的数量明显减少（20.4+/-3.4pg/mg），黑质多巴胺水平明显降低。PQ 连续 3 周每天处理可导致黑质中多巴胺能神经元选择性丧失，并伴有明显的行为和周围运动功能障碍。
