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.

A mutation in the enzyme monoamine oxidase explains part of the Astyanax cavefish behavioural syndrome

“…In this species, MAO is inhibited by both clorgyline and deprenyl 45 (selective mammalian MAO-A and MAO-B inhibitors, respectively) and displays strong affinity for 5-HT but a modest one for DA, so that MAO inhibition by deprenyl strongly increases 5-HT but not DA and NA levels 37 . We therefore better characterized MAO properties in our model, using deprenyl.…”

“…1a). Conversely, and this is a notable exception, there is only one monoamine oxidase (MAO) gene in all teleosts examined so far (zebrafish, carp, trout and rainbow trout, pike and catfish [45][46][47][48][49][50] ), whereas two forms of this enzyme, MAO-A and MAO-B, are classically described and studied in mammals [51][52][53][54] .…”

Dopamine D2Receptor Activity Modulates Akt Signaling and Alters GABAergic Neuron Development and Motor Behavior in Zebrafish Larvae

“…Several components of the DA biosynthetic and signaling pathways are expressed in the zebrafish larval brain (Holzschuh et al, 2001;Boehmler et al, 2004Boehmler et al, , 2007McLean and Fetcho, 2004;Anichtchik et al, 2006;Li et al, 2007), but which intracellular pathways are modulated by DA and its role in mediating behavior, as well as how DA signaling regulates zebrafish brain development, is not well characterized. Previous studies have demonstrated that DA is involved in larval motor regulation and that this is mediated, in part, by cAMP signaling (Boehmler et al, 2007;Thirumalai and Cline, 2008).…”

Neuronal and glial localization of α2A‐adrenoceptors in the adult zebrafish (Danio rerio) brain

“…The catecholaminergic system of the zebrafish brain has been previously characterized (Ma, 1994a(Ma, ,b, 1997; Kaslin and Panula, 2001; Rink and Wullimann, 2001), and cerebral neurochemical studies have established the LC as the major noradrenergic projection center of the zebrafish (Ma, 1994a,b;Kaslin and Panula, 2001) and most teleosts (Parent, 1983;Ekström et al, 1986). The LC projection pattern (Ekström et al, 1986;Ma, 1994b) and recently the localization of the monoamine oxidase (MAO), the NA metabolic pathway enzyme (Anichtchik et al, 2006) have been reported for the zebrafish brain. Furthermore, ␣ 2 -ARs have been identified in zebrafish, by cloning and mapping of five distinct receptor genes (Ruuskanen et al, 2004), each coding for a functional receptor coupled to G-mediated second messenger signaling system, similar to the mammalian ␣ 2 -ARs (Ruuskanen et al, 2005a).…”