Sundström E, Strömberg I, Tsutsumi T, Olson L, Jonsson G
Brain Res. 1987 Mar 3;405(1):26-38. doi: 10.1016/0006-8993(87)90986-3.
The effect of the parkinsonism-inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on central catecholamine neurons in C57BL/6 mice has been studied employing neuro- and histochemical techniques. The number of dopamine (DA) cell bodies in substantia nigra pars compacta (SNC) was reduced by 70% in MPTP-treated C57BL/6 mice, as demonstrated both by tyrosine hydroxylase (TH) immunohistochemistry and conventional histology (Cresyl violet staining) and an almost complete loss of DA fibers in striatum was also found. A detailed analysis of the effects of MPTP on endogenous catecholamine levels in various brain regions revealed that MPTP caused a severe reduction of endogenous DA in substantia nigra and striatum (35 and 5% of control) which was accompanied by an increase in the 3,4-dihydroxyphenylacetic acid (DOPAC)/DA ratio. There was also a decrease of DA in nucleus accumbens and the olfactory tubercle to 41 and 44% of control, respectively, without any significant change in the DOPAC/DA ratio and density of TH-positive fibers. Small but significant decreases of the noradrenaline (NA) levels in septum, entorhinal cortex and frontal cortex were seen, although the uptake of [3H]NA in frontal cortex was not significantly changed. Minor MPTP-induced decreases of the serotonin levels in frontal cortex, occipital cortex and spinal cord were also seen. The MPTP treatment also induced a 55% increase of adrenaline levels in hypothalamus, while no changes were seen in pons-medulla and spinal cord. Comparing this with 3 other strains of mice, the MPTP-induced reduction of endogenous DA in striatum was most pronounced in C57BL/6, less in N.M.R.I. and CBA/Ca mice, and least in Swiss-Webster. Concerning the effect of MPTP on cortical NA levels, the same relation was at hand except for C57BL/6, where, as mentioned, the effect was merely detectable. No reduction of DA perikarya in SNC was seen in Swiss-Webster mice. These findings show that in mice major differences exist in sensitivity of catecholamine neurons to MPTP between different strains. The data show that MPTP can produce an almost complete, permanent and relatively selective degeneration of the nigrostriatal DA neurons in C57BL/6 mice similar to that seen in primates. This strain may therefore serve as a useful model for studies on various aspects of MPTP-induced parkinsonism.
采用神经化学和组织化学技术，研究了帕金森病诱导神经毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）对C57BL/6小鼠中枢儿茶酚胺能神经元的影响。酪氨酸羟化酶（TH）免疫组织化学和传统组织学（甲酚紫染色）均显示，MPTP处理的C57BL/6小鼠黑质致密部（SNC）中多巴胺（DA）细胞体数量减少了70%，并且还发现纹状体中DA纤维几乎完全丧失。对MPTP对不同脑区内源性儿茶酚胺水平影响的详细分析表明，MPTP导致黑质和纹状体中内源性DA严重减少（分别为对照的35%和5%），同时3,4-二羟基苯乙酸（DOPAC）/DA比值升高。伏隔核和嗅结节中的DA也分别降至对照的41%和44%，而DOPAC/DA比值和TH阳性纤维密度没有任何显著变化。虽然额叶皮质中[3H]NA的摄取没有显著变化，但在隔区、内嗅皮质和额叶皮质中去甲肾上腺素（NA）水平有小幅但显著的降低。在额叶皮质、枕叶皮质和脊髓中也观察到MPTP诱导的血清素水平有轻微降低。MPTP处理还使下丘脑肾上腺素水平升高了55%，而脑桥-延髓和脊髓中未见变化。与其他3种品系的小鼠相比，MPTP诱导的纹状体内源性DA减少在C57BL/6小鼠中最为明显，在N.M.R.I.和CBA/Ca小鼠中较少，在瑞士韦伯斯特小鼠中最少。关于MPTP对皮质NA水平的影响，除了C57BL/6小鼠（如前所述，其影响仅可检测到）外情况相同。在瑞士韦伯斯特小鼠中未观察到SNC中DA神经元胞体减少。这些发现表明，不同品系小鼠的儿茶酚胺能神经元对MPTP的敏感性存在重大差异。数据表明，MPTP可在C57BL/6小鼠中产生几乎完全、永久性且相对选择性的黑质纹状体DA神经元变性，类似于在灵长类动物中所见。因此，该品系可作为研究MPTP诱导帕金森病各个方面的有用模型。
