SELECTIVE VISUALIZATION OF RODENT LOCUS CERULEUS BY A RADIOLABELED N-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE ANALOG
SELECTIVE VISUALIZATION OF RODENT LOCUS CERULEUS BY A RADIOLABELED N-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE ANALOG
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DOI：
10.1111/j.1471-4159.1989.tb07356.x
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发表时间：
1989-08-01
影响因子：
4.7
通讯作者：
BILLINGS, J
中科院分区：
文献类型：
--
作者：
EFANGE, SMN;MASH, D;BILLINGS, J
N-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）的神经毒性代谢产物1-甲基-4-苯基吡啶盐通过多巴胺再摄取系统选择性地在多巴胺能神经元中蓄积。因此，无毒的放射性标记的MPTP类似物可能是潜在的有用的可视化体内的儿茶酚胺能神经元。N-甲基-4-（4-羟基-3-[125 I]碘苄基）-1，2，3，6-四氢吡啶（[125 I] MHTP）是无毒的N-甲基-4-苄基-1，2，3，6-四氢吡啶的类似物，已在大鼠和小鼠中进行了研究。啮齿类动物静脉注射[125 I] MHTP后，发现脑内放射性的初始蓄积与放射性标记的MPTP相当。静脉注射[125 I] MHTP后，啮齿动物脑的体内放射自显影显示蓝斑内[125 I] MHTP衍生放射性选择性蓄积;多巴胺能纤维和细胞体内无放射性示踪剂蓄积。蓝斑内的放射性的积累被阻断预处理与帕吉林，结果表明，MHTP代谢物形成的单胺氧化酶是负责本地化的放射性示踪剂在此结构内。放射性标记物的解剖学分布表明该代谢物在去甲肾上腺素能细胞体和构成蓝斑的纤维内选择性蓄积。这些研究结果进一步表明，MPTP的无毒代谢产物可能成为有用的在体内标记的选择群体的儿茶酚胺能神经元。
The neurotoxic metabolite of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 1-methyl-4-phenylpyridinium, selectively accumulates in dopaminergic neurons via the dopamine reuptake system. Consequently, nontoxic radiolabeled MPTP analogs may be potentially useful for visualizing catecholaminergic neurons in vivo. N-Methyl-4-(4-hydroxy-3-[125I]iodobenzyl)-1,2,3,6-tetrahydropyridine ([125I]MHTP), an analog of the nontoxic N-methyl-4-benzyl-1,2,3,6-tetrahydropyridine, has been studied in rats and mice. After intravenous administration of [125I]MHTP to rodents, the initial accumulation of radioactivity within the brain was found to be comparable to that of radiolabeled MPTP. Following intravenous administration of [125I]MHTP, in vivo autoradiographic visualization of the rodent brain revealed selective accumulation of [125I]MHTP-derived radioactivity within the locus ceruleus; there was no accumulation of the radiotracer within dopaminergic fibers and cell bodies. The accumulation of radioactivity within the locus ceruleus was blocked by pretreatment with pargyline, a result suggesting that an MHTP metabolite formed by monoamine oxidase was responsible for the localization of the radiotracer within this structure. The anatomical distribution of the radiolabel demonstrates selective accumulation of this metabolite within noradrenergic cell bodies and those fibers making up the locus ceruleus. These findings further suggest that nontoxic metabolites of MPTP may become useful for in vivo labeling of selected populations of catecholaminergic neurons.