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Transplacental effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on brain dopaminergic neurons in the mouse
Authors:S. Furune  K. Miura  K. Watanabe  S. Nagao  H. Takahashi  M. Sakai  M. Spatz  I. Nagatsu
Affiliation:(1) Department of Pediatrics, Nagoya University School of Medicine, Nagoya, Japan;(2) Animal Center Laboratory, Institute for Comprehensive Medical Science, Fujita-Gakuen Health University, 470-11 Toyoake, Aichi, Japan;(3) Department of Anatomy, School of Medicine, Fujita-Gakuen Health University, 470-11 Toyoake, Aichi, Japan;(4) Laboratory of Neuropathology and Neuroanatomical Sciences, NINCDS, National Institutes of Health, 20205 Bethesda, MD, USA
Abstract:
Summary Immunohistochemical studies of monoamme neurons werè performed to evaluate toxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on young adult mice and compare them with chose of their offspring. Mice, 9–11 weeks old (C57BL/6J), injected subcutaneously with a large dose of MPTP (17 mg/kg per day) during pregnancy on Day 9 and 12 of gestation (G9 and G12) miscarried and were examined at 13 weeks of age. Conversely, mice treated during pregnancy with sequential low dose of MPTP (2.8 mg/kg per day at G9–G17 for 8 days) successfully delivered their babies and were examined at the age of 15 weeks. Baby mice were examined at 1 and 6 weeks of age. The tyrosine hydroxylase-, aromatic l-amino acid decarboxylase-and dopamine (DA)-immunoreactive density of caudoputamen was reduced in 13-week-old mice treated with high dose of MPTP but not in the 15-week-old mothers exposed to a low dose of MPTP as compared to their respective controls. The DA-immunoreactive density of the caudoputamen was the only staining that was reduced in both 1- and 6-week-old baby mice. In conclusion, these results demonstrate that MPTP injected to pregnant mice causes a DA depletion in the striatum of their offspring indicating a transplacental effect of MPTP. The findings also indicate that fetal brain is more susceptible to MPTP toxicity than the brain of young pregnant mice.Supported by Grant-in-Aid for Scientific Research on Priority Areas, Ministry of Education, Science and Culture, Japan (62623002, 62480226), and by a Fujita-Gakuen Health University Grant, Japan
Keywords:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)  C57BL/6J mouse  Tyrosine hydroxylase  Aromatic l-amino acid decarboxylase  Dopamine
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