Palombo E, Porrino L J, Crane A M, Bankiewicz K S, Kopin I J, Sokoloff L
Laboratory of Cerebral Metabolism, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland.
J Neurochem. 1991 May;56(5):1639-46. doi: 10.1111/j.1471-4159.1991.tb02062.x.
The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces dopaminergic cell death in the substantia nigra pars compacta (SNpc) and clinical parkinsonism in humans and experimental animals. Pretreatment with monoamine oxidase inhibitors prevents this cell death and associated parkinsonism by blocking the oxidation of MPTP to a toxic intermediate. The 2-deoxyglucose method was used to study the acute effects of MPTP in the monkey brain and the effects of monoamine oxidase inhibition on local cerebral glucose utilization in both normal and MPTP-treated monkeys. MPTP administration alone caused a major increase in glucose utilization in the SNpc and smaller increases in some subnuclei within the ventral tegmental area in which eventual dopaminergic cell loss also occurs. Pretreatment with pargyline abolished these metabolic increases, a finding suggesting both that the oxidized product of MPTP generates the metabolic increases and that the increased glucose consumption may contribute to cell toxicity. On the other hand, in most cortical, thalamic, striatal, brainstem, and cerebellar areas MPTP alone caused reductions in glucose utilization, and pargyline failed to prevent these effects. Pargyline alone depressed metabolism in the locus coeruleus and a few other monoaminergic structures.
神经毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）可导致黑质致密部（SNpc）中的多巴胺能细胞死亡，并在人类和实验动物中引发临床帕金森症。单胺氧化酶抑制剂预处理可通过阻断MPTP氧化为有毒中间体来预防这种细胞死亡及相关的帕金森症。采用2-脱氧葡萄糖法研究了MPTP对猴脑的急性影响，以及单胺氧化酶抑制对正常猴和经MPTP处理的猴局部脑葡萄糖利用的影响。单独给予MPTP会导致SNpc中的葡萄糖利用大幅增加，以及腹侧被盖区内一些亚核中的葡萄糖利用较小幅度增加，而这些亚核最终也会出现多巴胺能细胞丢失。用帕吉林预处理可消除这些代谢增加，这一发现表明MPTP的氧化产物既产生了代谢增加，又表明增加的葡萄糖消耗可能导致细胞毒性。另一方面，在大多数皮质、丘脑、纹状体、脑干和小脑区域，单独使用MPTP会导致葡萄糖利用减少，而帕吉林无法预防这些影响。单独使用帕吉林会降低蓝斑及其他一些单胺能结构的代谢。
