title: Involvement of monoamine oxidase-B in the acute neurotoxicity of MPTP in embryonic and newborn mice.
abstract: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces damage to the nigrostriatal system and subventricular zone (SVZ) of mice. While there have been many researches on the neurotoxicity of MPTP in adult mice, there have been few reports concerning that in embryonic and newborn mice. Very recently, we revealed that such neurotoxicity of MPTP and 1-methyl-4-phenylpyridinium (MPP(+)), a metabolite of MPTP, is observed not only in adult mice but also in embryonic and newborn mice; however, the mechanism of acute toxicity is not well elucidated. In the present study, we attempted to reveal the involvement of monoamine oxidase B (MAO-B) in the metabolism of MPTP to MPP(+) and dopamine transporter (DAT) in the neuronal cellular uptake of MPP(+) during the acute toxicity of MPTP in both embryonic and newborn mice. Immunohistochemistry and double-labeling immunofluorescent staining demonstrated an increase of MAO-B-positive glial cells in the brain only in MPTP-treated mice, indicating the involvement of MAO-B in the metabolism of MPTP to MPP(+) during the acute neurotoxicity of MPTP in both embryonic and newborn mice. The expression of DAT was not observed in the nigrostriatal zone of embryonic mice and in the zone and SVZ of newborn mice. The mechanism of how MPP(+) is taken up into those neuronal cells remains unknown. In conclusion, MAO-B is involved in the acute neurotoxicity of MPTP in embryonic and newborn mice.
authors.affiliation: Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan. Takafumi_Sai@nts.toray.co.jp
authors.forename: Takafumi
authors.initials: T
authors.lastname: Sai
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Uchida
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakayama
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000378:metabolism*; D015655:1-Methyl-4-phenylpyridinium / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D004622:Embryo, Mammalian; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D020267:MPTP Poisoning / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008995:Monoamine Oxidase / Q000378:metabolism*
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D008995:Monoamine Oxidase; D015655:1-Methyl-4-phenylpyridinium