PUBLICATION
Vesicular monoamine transporter 2 (SLC18A2) regulates monoamine turnover and brain development in zebrafish
- Authors
- Baronio, D., Chen, Y.C., Decker, A.R., Enckell, L., Fernández-López, B., Semenova, S., Puttonen, H.A.J., Cornell, R.A., Panula, P.
- ID
- ZDB-PUB-210818-11
- Date
- 2021
- Source
- Acta physiologica (Oxford, England) 234(1): e13725 (Journal)
- Registered Authors
- Baronio, Diego, Cornell, Robert, Panula, Pertti, Puttonen, Henri, Semenova, Svetlana
- Keywords
- 5-hydroxytryptamine, dopamine, histamine, hypothalamus
- MeSH Terms
-
- Animals
- Brain/growth & development*
- Brain/metabolism
- Dopamine/metabolism*
- Solute Carrier Proteins
- Vesicular Monoamine Transport Proteins*/genetics
- Vesicular Monoamine Transport Proteins*/metabolism
- Zebrafish*/growth & development
- Zebrafish*/metabolism
- PubMed
- 34403568 Full text @ Acta Physiol. (Oxf).
Citation
Baronio, D., Chen, Y.C., Decker, A.R., Enckell, L., Fernández-López, B., Semenova, S., Puttonen, H.A.J., Cornell, R.A., Panula, P. (2021) Vesicular monoamine transporter 2 (SLC18A2) regulates monoamine turnover and brain development in zebrafish. Acta physiologica (Oxford, England). 234(1):e13725.
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, behavior and brain development using a novel zebrafish model.
Methods A zebrafish strain lacking functional Vmat2 was generated with the CRISPR/Cas9 system. Larval behavior and heart rate were monitored. Monoamines and their metabolites were analyzed with high-pressure liquid chromatography. Amine synthesizing and degrading enzymes, and genes essential for brain development, were analyzed with quantitative PCR, in situ hybridization and immunocytochemistry.
Results The 5-bp deletion in exon 3 caused an early frame-shift and was lethal within 2 weeks post-fertilization. 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-synthesizing 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-synthesizing enzymes, including histidine decarboxylase. Notch1a and pax2a, genes implicated in stem cell development, are downregulated in mutants. The zebrafish vmat2 mutant strain may be useful model to study how monoamine transport affects brain development and function, and for use in drug screening.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping