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.