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.
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References
Burns RS, Chiuech CC, Markey SP, Ebert MH, Jacobowitz DM, Kopin IJ (1983) A primate model of parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Proc Natl Acad Sci USA 80:4546–4550
Chiueh CC, Markey SP, Burns RS, Johannessen JN, Jacobowitz DM, Kopin IJ (1983) N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, a parkinsonian causing agent in man and monkey, produces different effects in guinea pig and rat. Pharmaclogist 25:131
D'Amato RJ, Lipman ZP, Snyder SH (1986) Selectivity of the parkinsonian neurotoxin MPTP: toxic metabolite MPP+ binds to neuromelanin. Science 231:987–989
Davis CG, Williams AC, Markey SP, Ebert MH, Caine ED, Reichert CM, Kopin IJ (1979) Chronic parkinsonism secondary to intravenous injection of meperidine analogues. Psychiatry Res 1:249–254
Gupta M, Felten DL, Gash DM (1984) MPTP alters central catecholamine neurons in addition to the nigrostriatal system. Brain Res Bull 13:737–742
Hallman H, Lange J, Olson L, Strömberg I, Jonsson G (1985) Neurochemical and histochemical characterization of neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine on brain catecholamine neurones in the mouse. J Neurochem 44:117–127
Heikkila RE, Cabbat FS, Manzino L, Duvoisin RC (1984) Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine on neostriatal dopamine in mice. Neuropharmacology 23:711–713
Heikkila RE, Hess A, Duvoisin RC (1984) Dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice. Science 224:1451–1453
Johannessen JN, Chiueh CC, Burns RS, Markey SP (1985) Differences in the metabolism of MPTP in the rodent and primate parallel differences in sensitivity to its neurotoxic effects. Life Sci 36:219–224
Kosaka T, Nagatsu I, Wu J-Y, Hama K (1986) Use of high concentration of glutaraldehyde for immunocytochemistry of transmitter-synthesizing enzymes in the central nervous system. Neuroscience 18:975–990
Langston JW, Ballard P, Tetrud JW, Kopin IJ (1983) Chronic parkinsonism in humans due to a product of meperidine-analog synthesis. Science 219:979–980
Langston JW, Forno LS, Rebert CS, Irwin I (1984) Selective nigral toxicity after systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the squirrel monkey. Brain Res 292:390–394
Mogi M, Harada M, Kojima K, Kiuchi K, Nagatsu I, Nagatsu T (1987) Effects of repeated systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on striatal tyrosine hydroxylase activity in vitro and tyrosine hydroxylase content. Neurosci Lett 80:213–218
Mori S, Fujitake J, Kuno S, Sano Y (1988) Immunohistochemical evaluation of the neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on dopaminergic nigrostriatal neurons of young adult mice using dopamine and tyrosine hydroxylase antibodies. Neurosci Lett 90:57–62
Nagatsu I, Sakai M, Yoshida M, Nagatsu T (1988) Aromatic l-amino acid decarboxylase-immunoreactive neurons in and around the cerebrospinal fluid-contacting neurons of the central canal do not contain dopamine or serotonine in the mouse and rat spinal cord. Brain Res 475:91–102
Nagatsu I, Furune S, Sakai M, Watanabe K (1988) Quantitative analysis of changes of tyrosine hydroxylase, aromatic-l-amino acid decarboxylase-, and dopamine-like immunoreactive nerve terminals and cell bodies of MPTP-treated mice. J Histochem Cytochem 36:921
Nagatsu I, Furune S, Ichinose H, Spatz M, Nagatsu T (1988) Quantitative analysis of reduction of aromatic l-amino acid decarboxylase- and tyrosine hydroxylase-like immunoreactivities in the nigrostriatal dopaminergic neurons of MPTP-treated mice. Biogen Amin 6:263–277
Naoi M, Takahashi T, Ichinose H, Nagatsu T (1988) Inhibition of aromatic l-amino acid decarboxylase in clonal pheochromocytoma PC12h cells by N-methyl-4-phenyl-pyridinium ion (MPP+). Biochem Biophys Res Commun 152:15–21
Ohya Y, Naoi M, Ochi N, Mizutani N, Watanabe K, Nagatsu T (1989) Uptake of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and the N-methyl-4-phenylpyridinium ion (MPP+) into fetal mouse brain through the placenta. Neurosci Lett (in press)
Riachi NJ, Harik SI (1988) Strain differences in systemic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity in mice correlate best with monoamine oxidase activity at the blood-brain barrier. Life Sci 42:2359–2363
ricaurte GA, Langston JW, Irwin I, DeLanney LE, Forno LS (1985) The neurotoxic effect of MPTP on dopaminergic cells in the substantia nigra of mice is age related. Soc Neurosci Abstr 11:631
ricaurte GA, Langston JW, Delanney LE, Irwin I, Peroutka SJ, Forno LS (1986) Fate of nigrostriatal neurons in young mature mice given 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: a neurochemical and morphological reassessment. Brain Res 376:117–124
Saitoh T, Niijima K, Mizuno Y (1987) Long-term effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on striatal dopamine content in young and mature mice. J Neurol Sci 77:229–235
Schneider JS, Markham CH (1986) Neurotoxic effects of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the cat. Tyrosine hydroxylase immunohistochemistry. Brain Res 373:258–267
Sershen H, Reith MEA, Hashim A, Lajtha A (1984) Reduction of dopamine uptake and cocaine binding in mouse striatum by MPTP. Eur J Pharmacol 102:175–178
Sundstrom E, Stromberg I, Tsutsumi T, Olson L, Jonsson G (1987) Studies on the effect of 1-methy-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on central catecholamine neurons in C57BL/6 mice. Comparison with three other strains of mice. Brain Res 405:26–38
Willis GL, Donnan GA (1987) Histochemical, biochemical and behavioural consequences of MPTP treatment in C-57 black mice. Brain Res 402:269–274
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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
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Furune, S., Miura, K., Watanabe, K. et al. Transplacental effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on brain dopaminergic neurons in the mouse. Acta Neuropathol 79, 279–285 (1989). https://doi.org/10.1007/BF00294662
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DOI: https://doi.org/10.1007/BF00294662