Vesicular monoamine transporter 2 (SLC18A2) regulates monoamine turnover and brain development in zebrafish

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Baronio , D , Chen , Y-C , Decker , A R , Enckell , L , Fernandez-Lopez , B , Semenova , S , Puttonen , H A J , Cornell , R A & Panula , P 2022 , ' Vesicular monoamine transporter 2 (SLC18A2) regulates monoamine turnover and brain development in zebrafish ' , Acta Physiologica , vol. 234 , no. 1 , 13725 . https://doi.org/10.1111/apha.13725

Title: Vesicular monoamine transporter 2 (SLC18A2) regulates monoamine turnover and brain development in zebrafish
Author: Baronio, Diego; Chen, Yu-Chia; Decker, Amanda R.; Enckell, Louise; Fernandez-Lopez, Blanca; Semenova, Svetlana; Puttonen, Henri A. J.; Cornell, Robert A.; Panula, Pertti
Contributor organization: Department of Anatomy
Faculty of Medicine
Vertebrate Evolution, Development and Regeneration Group
Medicum
Helsinki In Vivo Animal Imaging Platform (HAIP)
Pertti Panula / Principal Investigator
Neuroscience Center
Date: 2022-01
Language: eng
Number of pages: 16
Belongs to series: Acta Physiologica
ISSN: 1748-1708
DOI: https://doi.org/10.1111/apha.13725
URI: http://hdl.handle.net/10138/340525
Abstract: Aim We aimed at identifying potential roles of vesicular monoamine transporter 2, also known as Solute Carrier protein 18 A2 (SLC18A2) (hereafter, Vmat2), in brain monoamine regulation, their turnover, behaviour and brain development using a novel zebrafish model. Methods A zebrafish strain lacking functional Vmat2 was generated with the CRISPR/Cas9 system. Larval behaviour and heart rate were monitored. Monoamines and their metabolites were analysed with high-pressure liquid chromatography. Amine synthesising and degrading enzymes, and genes essential for brain development, were analysed with quantitative PCR, in situ hybridisation and immunocytochemistry. Results The 5-bp deletion in exon 3 caused an early frameshift and was lethal within 2 weeks post-fertilisation. Homozygous mutants (hereafter, mutants) displayed normal low locomotor activity during night-time but aberrant response to illumination changes. In mutants dopamine, noradrenaline, 5-hydroxytryptamine and histamine levels were reduced, whereas levels of dopamine and 5-hydroxytryptamine metabolites were increased, implying elevated monoamine turnover. Consistently, there were fewer histamine, 5-hydroxytryptamine and dopamine immunoreactive cells. Cellular dopamine immunostaining, in wild-type larvae more prominent in tyrosine hydroxylase 1 (Th1)-expressing than in Th2-expressing neurons, was absent in mutants. Despite reduced dopamine levels, mutants presented upregulated dopamine-synthesising enzymes. Further, in mutants the number of histidine decarboxylase-expressing neurons was increased, notch1a and pax2a were downregulated in brain proliferative zones. Conclusion Lack of Vmat2 increases monoamine turnover and upregulates genes encoding amine-synthesising enzymes, including histidine decarboxylase. Notch1a and pax2a, genes implicated in stem cell development, are downregulated in mutants. The zebrafish vmat2 mutant strain may be a useful model to study how monoamine transport affects brain development and function, and for use in drug screening.
Subject: 5-hydroxytryptamine
dopamine
histamine
hypothalamus
HYDROXYLASE MESSENGER-RNA
HISTAMINERGIC SYSTEM
DOPAMINERGIC-NEURONS
PARKINSONS-DISEASE
MICE DISPLAY
VMAT2 GENE
DEPLETION
MODEL
MANF
PROLIFERATION
3111 Biomedicine
1184 Genetics, developmental biology, physiology
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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