Takahata K, Shimazu S, Yoneda F, Ogawa M, Iida Y, Saji H
Research Institute and Development, Fujimoto Pharmaceutical Corporation, Osaka, Japan.
J Neural Transm (Vienna). 2003 Aug;110(8):859-69. doi: 10.1007/s00702-003-0003-0.
Diethyldithiocarbamate (DDC) is known to potentiate the neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The aims of the present study were to provide biochemical, pathological and behavioral evidence for the degeneration of dopamine (DA) neurons in C57BL/6 strain mice treated simultaneously with DDC and MPTP, and to evaluate the effects of monoamine oxidase (MAO) inhibitors on DDC-enhanced MPTP toxicity. DDC (400 mg/kg)+ MPTP (30 mg/kg) treatment decreased significantly the levels of striatal DA and its metabolites and induced bradykinesia. In mice treated with DDC+MPTP, degenerative areas were found in striatum, substantia nigra and tuberculum olfactorium by assessment of the binding of [125I]RTI-121, a DA transporter ligand. Pretreatment with a MAO-B inhibitor selegiline prior to the administration of DDC and MPTP completely inhibited the decrease in the levels of DA and its metabolites, bradykinesia and degeneration of dopaminergic nerve terminals. In contrast, the protective action of clorgyline was not clearly observed in this model system.
已知二乙基二硫代氨基甲酸盐（DDC）可增强1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）的神经毒性。本研究的目的是为同时用DDC和MPTP处理的C57BL/6品系小鼠中多巴胺（DA）神经元变性提供生化、病理和行为学证据，并评估单胺氧化酶（MAO）抑制剂对DDC增强的MPTP毒性的影响。DDC（400mg/kg）+MPTP（30mg/kg）处理显著降低了纹状体DA及其代谢产物的水平，并诱发了运动迟缓。通过评估DA转运体配体[125I]RTI-121的结合情况，发现在用DDC+MPTP处理的小鼠中，纹状体、黑质和嗅结节出现了退行性变区域。在给予DDC和MPTP之前用MAO-B抑制剂司来吉兰预处理，完全抑制了DA及其代谢产物水平的降低、运动迟缓和多巴胺能神经末梢的变性。相比之下，在该模型系统中未清楚观察到氯吉兰的保护作用。
