Involvement of monoamine oxidase-B in the acute neurotoxicity of MPTP in embryonic and newborn mice. 2013

Takafumi Sai, and Kazuyuki Uchida, and Hiroyuki Nakayama
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

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.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008995 Monoamine Oxidase An enzyme that catalyzes the oxidative deamination of naturally occurring monoamines. It is a flavin-containing enzyme that is localized in mitochondrial membranes, whether in nerve terminals, the liver, or other organs. Monoamine oxidase is important in regulating the metabolic degradation of catecholamines and serotonin in neural or target tissues. Hepatic monoamine oxidase has a crucial defensive role in inactivating circulating monoamines or those, such as tyramine, that originate in the gut and are absorbed into the portal circulation. (From Goodman and Gilman's, The Pharmacological Basis of Therapeutics, 8th ed, p415) EC 1.4.3.4. Amine Oxidase (Flavin-Containing),MAO,MAO-A,MAO-B,Monoamine Oxidase A,Monoamine Oxidase B,Type A Monoamine Oxidase,Type B Monoamine Oxidase,Tyramine Oxidase,MAO A,MAO B,Oxidase, Monoamine,Oxidase, Tyramine
D004622 Embryo, Mammalian The entity of a developing mammal (MAMMALS), generally from the cleavage of a ZYGOTE to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the FETUS. Embryonic Structures, Mammalian,Mammalian Embryo,Mammalian Embryo Structures,Mammalian Embryonic Structures,Embryo Structure, Mammalian,Embryo Structures, Mammalian,Embryonic Structure, Mammalian,Embryos, Mammalian,Mammalian Embryo Structure,Mammalian Embryonic Structure,Mammalian Embryos,Structure, Mammalian Embryo,Structure, Mammalian Embryonic,Structures, Mammalian Embryo,Structures, Mammalian Embryonic
D005455 Fluorescent Antibody Technique Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy. Antinuclear Antibody Test, Fluorescent,Coon's Technique,Fluorescent Antinuclear Antibody Test,Fluorescent Protein Tracing,Immunofluorescence Technique,Coon's Technic,Fluorescent Antibody Technic,Immunofluorescence,Immunofluorescence Technic,Antibody Technic, Fluorescent,Antibody Technics, Fluorescent,Antibody Technique, Fluorescent,Antibody Techniques, Fluorescent,Coon Technic,Coon Technique,Coons Technic,Coons Technique,Fluorescent Antibody Technics,Fluorescent Antibody Techniques,Fluorescent Protein Tracings,Immunofluorescence Technics,Immunofluorescence Techniques,Protein Tracing, Fluorescent,Protein Tracings, Fluorescent,Technic, Coon's,Technic, Fluorescent Antibody,Technic, Immunofluorescence,Technics, Fluorescent Antibody,Technics, Immunofluorescence,Technique, Coon's,Technique, Fluorescent Antibody,Technique, Immunofluorescence,Techniques, Fluorescent Antibody,Techniques, Immunofluorescence,Tracing, Fluorescent Protein,Tracings, Fluorescent Protein
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000831 Animals, Newborn Refers to animals in the period of time just after birth. Animals, Neonatal,Animal, Neonatal,Animal, Newborn,Neonatal Animal,Neonatal Animals,Newborn Animal,Newborn Animals
D015632 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine A dopaminergic neurotoxic compound which produces irreversible clinical, chemical, and pathological alterations that mimic those found in Parkinson disease. MPTP,N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
D015655 1-Methyl-4-phenylpyridinium An active neurotoxic metabolite of 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE. The compound reduces dopamine levels, inhibits the biosynthesis of catecholamines, depletes cardiac norepinephrine and inactivates tyrosine hydroxylase. These and other toxic effects lead to cessation of oxidative phosphorylation, ATP depletion, and cell death. The compound, which is related to PARAQUAT, has also been used as an herbicide. Cyperquat,1-Methyl-4-phenylpyridine,1-Methyl-4-phenylpyridinium Chloride,1-Methyl-4-phenylpyridinium Ion,N-Methyl-4-phenylpyridine,N-Methyl-4-phenylpyridinium,1 Methyl 4 phenylpyridine,1 Methyl 4 phenylpyridinium,1 Methyl 4 phenylpyridinium Chloride,1 Methyl 4 phenylpyridinium Ion,N Methyl 4 phenylpyridine
D050483 Dopamine Plasma Membrane Transport Proteins Sodium chloride-dependent neurotransmitter symporters located primarily on the PLASMA MEMBRANE of dopaminergic neurons. They remove DOPAMINE from the EXTRACELLULAR SPACE by high affinity reuptake into PRESYNAPTIC TERMINALS and are the target of DOPAMINE UPTAKE INHIBITORS. Dopamine Plasma Membrane Transporter Proteins,Neurotransmitter Transport Proteins, Dopamine-Specific,Neurotransmitter Transporters, Dopamine-Specific,DAT Dopamine Transporter,DAT Dopamine Transporter Proteins,Dopamine Carriers,Dopamine Transporter,Dopamine Transporter Proteins,Dopamine Uptake Complex,SLC6A3 Protein,Solute Carrier Family 6 (Neurotransmitter Transporter), Member 3 Protein,Carriers, Dopamine,Dopamine Transporter, DAT,Dopamine-Specific Neurotransmitter Transporters,Neurotransmitter Transport Proteins, Dopamine Specific,Neurotransmitter Transporters, Dopamine Specific,Protein, SLC6A3,Transporter Proteins, Dopamine,Transporter, DAT Dopamine,Transporter, Dopamine,Transporters, Dopamine-Specific Neurotransmitter

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