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Immunity of Fetal Mice to Prenatal Administration of the Dopaminergic Neurotoxin 1‐Methyl‐4‐Phenyl‐1,2,3,6‐Tetrahydropyridine
Author(s) -
Melamed Eldad,
Rosenthal Jutta,
Youdim Moussa B. H.
Publication year - 1990
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1990.tb03156.x
Subject(s) - mptp , offspring , neurotoxin , endocrinology , medicine , dopaminergic , fetus , dopamine , monoamine oxidase , in utero , striatum , pregnancy , biology , biochemistry , genetics , enzyme
Subcutaneous injection of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) HC1 (25 mg/kg) in pregnant female mice at the 17th day of gestation markedly depleted striatal dopamine (DA) concentrations in the mothers 24 h later and at 24 h and 28 days after delivery. By contrast, in the offspring of the female mice exposed to MPTP during pregnancy, fetal brain DA concentrations at 24 h after injection and at 24 h after birth and striatal DA levels at 14 and 28 days postnatally were unaffected and identical to those in age‐matched controls. The postnatal ontogenesis of striatal DA levels was identical in offspring of control vehicle‐ and MPTP‐treated pregnant mice. Also, prenatal challenge with MPTP did not make nigrostriatal DA neurons more vulnerable to a second postnatal treatment with the toxin. Striatal DA depletions were identical in 6‐week‐old mice given MPTP, whether they were exposed to MPTP or to vehicle in utero. Monoamine oxidase (EC 1.4.3.4; MAO) type B activity was extremely low in the fetal brain and, relatively, much lower than that of MAO‐A. Prenatal MPTP administration reduced maternal striatal and also embryonal brain MAO‐B activity at 24 h post treatment but did not alter the normal postnatal development of striatal MAO‐A and ‐B activities in the offspring. Study suggests that resistance of fetal DA neurons to the DA‐depleting effect of MPTP may be due, at least in part, to an absence in the embryonal brain of adequately developed MAO‐B activity required for the conversion of MPTP to its toxic metabolite, 1‐methyl‐4‐phenylpyridinium ion.