Transplacental effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on brain dopaminergic neurons in the mouse - An immunohistochemical study

S. Furune, K. Miura, K. Watanabe, Shizuko Nagao, H. Takahashi, M. Sakai, M. Spatz, I. Nagatsu

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Abstract

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.

Original languageEnglish
Pages (from-to)279-285
Number of pages7
JournalActa Neuropathologica
Volume79
Issue number3
DOIs
Publication statusPublished - 01-12-1989

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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Dopaminergic Neurons
Brain
Dopamine
Pregnancy
Aromatic-L-Amino-Acid Decarboxylases
Poisons
Tyrosine 3-Monooxygenase
Young Adult
Mothers
Staining and Labeling
Neurons

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

Furune, S. ; Miura, K. ; Watanabe, K. ; Nagao, Shizuko ; Takahashi, H. ; Sakai, M. ; Spatz, M. ; Nagatsu, I. / Transplacental effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on brain dopaminergic neurons in the mouse - An immunohistochemical study. In: Acta Neuropathologica. 1989 ; Vol. 79, No. 3. pp. 279-285.
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title = "Transplacental effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on brain dopaminergic neurons in the mouse - An immunohistochemical study",
abstract = "Immunohistochemical studies of monoamme neurons wer{\`e} 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.",
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Transplacental effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on brain dopaminergic neurons in the mouse - An immunohistochemical study. / Furune, S.; Miura, K.; Watanabe, K.; Nagao, Shizuko; Takahashi, H.; Sakai, M.; Spatz, M.; Nagatsu, I.

In: Acta Neuropathologica, Vol. 79, No. 3, 01.12.1989, p. 279-285.

Research output: Contribution to journalArticle

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T1 - Transplacental effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on brain dopaminergic neurons in the mouse - An immunohistochemical study

AU - Furune, S.

AU - Miura, K.

AU - Watanabe, K.

AU - Nagao, Shizuko

AU - Takahashi, H.

AU - Sakai, M.

AU - Spatz, M.

AU - Nagatsu, I.

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Y1 - 1989/12/1

N2 - 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.

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