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Published on: June 25, 2019
Distinct structure and activity of monoamine oxidase in the brain of zebrafish (Danio rerio)
Oleg Anichtchik1, Ville Sallinen, Nina Peitsaro
1Neuroscience Center, Institute of Biomedicine/Anatomy, University of Helsinki, Biomedicum Helsinki, 00290 Helsinki, Finland.
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.
Insights
Zebrafish possess functional monoamine oxidase (MAO) in their brain and other tissues. This enzyme shows varied activity across neural systems, impacting neurotransmitter metabolism and potentially MPTP neurotoxicity.
Area of Science:
- Neuroscience
- Biochemistry
- Zebrafish model systems
Background:
- Monoamine oxidase (MAO) is crucial for metabolizing neurotransmitters and toxins like MPTP.
- Previous studies noted MPTP effects on zebrafish catecholaminergic systems.
- Understanding zebrafish MAO is key to its use as a model for neurodegenerative research.
Purpose of the Study:
- To characterize the structural and functional properties of zebrafish MAO.
- To map the distribution of MAO mRNA and enzyme activity in the zebrafish brain.
- To investigate the substrate specificity and inhibition of zebrafish MAO.
Main Methods:
- Gene sequencing and analysis of zebrafish MAO.
- Enzyme activity assays with various substrates and inhibitors.
- In situ hybridization and activity mapping in zebrafish brain tissues.
Main Results:
- Zebrafish MAO gene comprises 15 exons on chromosome 9.
- The enzyme exhibits substrate specificity for tyramine, serotonin, and MPTP.
- MAO activity is highest in noradrenergic and serotonergic cell groups and the habenulointerpeduncular pathway.
Conclusions:
- Zebrafish possess functionally active MAO in the brain and other tissues.
- MAO distribution in the zebrafish brain is differential, with high activity in specific neural pathways.
- MPTP neurotoxicity in zebrafish may involve MAO-independent mechanisms.
