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Selective visualization of rodent locus ceruleus by a radiolabeled N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine analog.

Abstract：

: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.

journal_name

J Neurochem

journal_title

Journal of neurochemistry

authors

Efange SM,Mash D,Hefti F,Kung HF,Billings J

doi

10.1111/j.1471-4159.1989.tb07356.x

subject

Has Abstract

pub_date

1989-08-01 00:00:00

pages

459-64

issue

2

eissn

0022-3042

issn

1471-4159

journal_volume

53

pub_type

杂志文章

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