Calò M, Iannöne M, Passafaro M, Nisticò G
Institute of Pharmacology, Faculty of Medicine, Policlinico Mater Domini, Catanzaro, Italy.
J Comp Pathol. 1990 Jul;103(1):73-8. doi: 10.1016/s0021-9975(08)80136-3.
The neuropathological effects of various doses of paraquat, a widely used herbicide, given directly into different areas of the rat brain, were studied. Paraquat, microinfused into the pars compacta of the substantia nigra (3.2, 16, 32 and 160 nmol), i.e. concentrations of 3.2 to 160 mmol l-1 applied at 1 microliter min-1 for 1 min, produced dose-dependent neuropathological lesions culminating in neuronal necrosis. A particular feature of paraquat neurotoxicity after its microinfusion into the substantia nigra (3.2 mmol per 1 at 1 microliter per min for 1 min) or into the ventral tegmental area (1.6 mmol per 1 at 1 microliter per min for 1 min), but not into other areas of the brain, was a selective vulnerability of hippocampal CA3 neurones consisting initially of a significant decrease of dendritic spines and later in neuronal degeneration and cell loss. No damage occurred after microinfusion of paraquat into other areas of the brain near or distant from the infusion sites. In addition, similar neuropathological alterations occurred in other non-dopaminergic areas, such as the locus coeruleus and some raphe nuclei after direct microinfusion of paraquat into these sites. In conclusion, the above neuropathological findings show that paraquat possesses marked neurotoxicity which, despite its chemical similarity to MPTP, is not selective for dopaminergic neurones.
研究了将广泛使用的除草剂百草枯直接注入大鼠脑内不同区域后，各种剂量的百草枯的神经病理学效应。将百草枯微量注入黑质致密部（3.2、16、32和160纳摩尔），即以1微升/分钟的速度注入1分钟，浓度为3.2至160毫摩尔/升，会产生剂量依赖性神经病理损伤，最终导致神经元坏死。将百草枯微量注入黑质（以1微升/分钟的速度注入1分钟，3.2毫摩尔/升）或腹侧被盖区（以1微升/分钟的速度注入1分钟，1.6毫摩尔/升）而非脑内其他区域后，百草枯神经毒性的一个特殊特征是海马CA3神经元的选择性易损性，最初表现为树突棘显著减少，随后出现神经元变性和细胞丢失。将百草枯微量注入脑内靠近或远离注射部位的其他区域后未出现损伤。此外，将百草枯直接微量注入蓝斑和一些中缝核等其他非多巴胺能区域后，也出现了类似的神经病理改变。总之，上述神经病理学发现表明，百草枯具有明显的神经毒性，尽管其化学结构与MPTP相似，但对多巴胺能神经元并无选择性。
