title: Distinct structure and activity of monoamine oxidase in the brain of zebrafish (Danio rerio).
abstract: Monoamine oxidase (MAO) is a mitochondrial flavoprotein involved in the metabolism of, e.g., aminergic neurotransmitters and the parkinsonism-inducing neurotoxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP). We have reported earlier MPTP-related alterations of brain catecholaminergic system in zebrafish (Danio rerio) brain. Here we describe the structural and functional properties of zebrafish MAO and the distribution of MAO mRNA and activity in zebrafish brain. The gene is located in chromosome 9 and consists of 15 exons. The amino acid composition of the active center resembles both human MAO-A and MAO-B. The enzyme displayed the highest substrate specificity for tyramine, followed by serotonin, phenylethylamine, MPTP, and dopamine; isoform-specific antagonists blocked the activity of the enzyme with equal potency. Zebrafish MAO mRNA, which was present in several tissues, and enzyme displayed differential distribution in the brain; dopaminergic cell clusters had low to moderate levels of MAO activity, whereas the highest levels of MAO activity were detected in noradrenergic and serotonergic cell groups and the habenulointerpeduncular pathway, including its caudal projection to the medial ventral rhombencephalon. The results of this study confirm the presence of functionally active MAO in zebrafish brain and other tissues and characterize the neural systems that express MAO and areas of intense activity in the brain. They also suggest that MPTP toxicity not related to MAO may affect the zebrafish brain.
authors.affiliation: Neuroscience Center, Institute of Biomedicine/Anatomy, University of Helsinki, Biomedicum Helsinki, 00290 Helsinki, Finland.
authors.forename: Oleg
authors.initials: O
authors.lastname: Anichtchik
authors.forename: Ville
authors.initials: V
authors.lastname: Sallinen
authors.forename: Nina
authors.initials: N
authors.lastname: Peitsaro
authors.forename: Pertti
authors.initials: P
authors.lastname: Panula
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D015306:Biogenic Monoamines / Q000494:pharmacology; D001921:Brain / Q000033:anatomy & histology* / Q000187:drug effects / Q000201:enzymology*; D003001:Cloning, Molecular / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D008969:Molecular Sequence Data; D008995:Monoamine Oxidase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009498:Neurotoxins / Q000494:pharmacology; D011487:Protein Conformation; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D015027:Zebrafish / Q000378:metabolism*
chemical_list: D015306:Biogenic Monoamines; D009498:Neurotoxins; D012333:RNA, Messenger; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D008995:Monoamine Oxidase