Transplacental effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on brain dopaminergic neurons in the mouse. An immunohistochemical study.
Immunohistochemical studies of monoamine neurons were performed to evaluate toxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on young adult mice and compare them with those 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.
Furune
S
S
Department of Pediatrics, Nagoya University School of Medicine, Japan.
Miura
K
K
Watanabe
K
K
Nagao
S
S
Takahashi
H
H
Sakai
M
M
Spatz
M
M
Nagatsu
I
I
D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000032:analysis; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D002421:Caudate Nucleus / Q000473:pathology; D004298:Dopamine / Q000032:analysis; D005260:Female; D020267:MPTP Poisoning; D008431:Maternal-Fetal Exchange; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011699:Putamen / Q000473:pathology; D051381:Rats; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D014446:Tyrosine 3-Monooxygenase; D001142:Aromatic-L-Amino-Acid Decarboxylases; D004298:Dopamine