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Neural expression patterns and protein modeling of the GABAA receptor ζ subunit in the adult zebrafish (Danio rerio Hamilton, 1822)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology. (Svante Winberg)ORCID iD: 0000-0001-6226-7120
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology. (Helgi Schiöth)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology. (Svante Winberg)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology. (Svante Winberg)
2018 (English)In: Zebrafish, ISSN 1545-8547, E-ISSN 1557-8542Article in journal (Refereed) Submitted
Abstract [en]

 

The zebrafish has a repertoire of twenty-six GABAA receptor subunits, including the paralogues π and ζ, homologous to the mammalian π. The brain mRNA levels of the π subunit are low, but the ζ gene is actively transcribed in D. rerio central nervous system and retinas. With a combined quantitative and qualitative gene expression profiling approach, this research characterized the distribution of the ζ transcript in the brain and eyes of the adult zebrafish. It was demonstrated that there are regional brain differences in the production of this transcript, with the stratum periventriculare of the tecta mesencephali having the highest mRNA levels for ζ. In the adult zebrafish retinas the bipolar cell layer presented staining for the ζ transcript. The three-dimensional structure of the ζ subunit of the GABAA receptor in zebrafish was also calculated in this study, with the human β3 as template. It presented four transmembrane α-helices and an amino-terminal β-loop framed into a disulfide bridge. It was therefore possible to place ζ in the superfamily of Cys-loop membrane proteins, to which GABAA receptor subunits belong. The current study presented a thorough characterization of a unique fish GABAA receptor subunit, which might have specific functions only typical of fish.

Place, publisher, year, edition, pages
2018.
Keywords [en]
GABA signaling system, ζ subunit, neuroanatomy, retina anatomy, homologous subunits
National Category
Biochemistry and Molecular Biology
Research subject
Biochemistry
Identifiers
URN: urn:nbn:se:uu:diva-348420OAI: oai:DiVA.org:uu-348420DiVA, id: diva2:1197469
Funder
Swedish Research Council, 621-2012-4679Available from: 2018-04-12 Created: 2018-04-12 Last updated: 2018-04-17
In thesis
1. The γ-aminobutyric acid and proton signaling systems in the zebrafish brain: Characterization and effect of stress
Open this publication in new window or tab >>The γ-aminobutyric acid and proton signaling systems in the zebrafish brain: Characterization and effect of stress
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The central nervous system of vertebrates is continuously processing sensory information relayed from the periphery, integrating it and producing outputs transmitted to efferents. In the brain, neurons employ an array of messenger molecules to filter afferent information and finely regulate synaptic transmission. The γ-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the adult vertebrate central nervous system, synthesized from α, L-glutamate by the glutamate decarboxylases (GADs). GABA promotes fast hyperpolarization of target cells mediated by the ionotropic, chloride-conducting type A GABA (GABAA) receptors. Those channels are homo- or heteropentamers and, in the zebrafish, at least twenty-three genes encode for putative GABAA receptor subunits.

The present PhD thesis presents the expression levels of the almost complete panel of the GABA signaling machinery in the adult zebrafish brain and retinas. The results point toward GABA signaling modalities in zebrafish strikingly similar to those observed in mammals. The most common GABAA receptor subunit combinations in the whole brain were proposed to be α1β2γ2 and α1β2δ, and region-specific GABAA channels were also inferred. Those included telencephalic α2bβ3γ2, α2bβ3δ, α5β2γ2, α5β3γ2 and cerebellar α4β2γ2 and α4β2δ. A tissue specific expression was documented for the paralogues α6a and α6b; the former was abundantly transcribed in the retinas, the latter in the cerebellum. Proposed retinal GABAA receptors were α1βxγ2, α1βxδ, α6aβxγ2 and α6aβxδ, with either β2 or β3.

Focus was also placed on functional aspects of the GABA signaling system in the adult zebrafish brain, and specifically on the effects of stress on GABAA receptor subunits expression. Treated animals experienced social isolation and repeated confinement, and depicted increased mRNA levels of several GABAA receptor monomers. It was deduced that a higher number of extrasynaptic, tonic-current-mediating GABAA channels was synthesized in the brain following stress. As synaptic transmission promotes extracellular acidification, interest was also placed on the acid-sensing ion channel (ASIC) subunits. The overall results presented in this PhD thesis point toward GABA and proton signaling systems in the zebrafish brain that have many common points with those of mammals. Thus, fundamental signaling pathways appear to be conserved across vertebrates.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2018. p. 88
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1466
Keywords
g-aminobutyric acid (GABA), GABAA receptors, adult zebrafish, central nervous system, gene expression profiling, extracellular acidification.
National Category
Physiology
Research subject
Biochemistry
Identifiers
urn:nbn:se:uu:diva-348421 (URN)978-91-513-0344-4 (ISBN)
Public defence
2018-06-09, Auditorium Minus, Museum Gustavianum, Akademigatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Funder
Swedish Research Council, 621-2012-4679
Available from: 2018-05-16 Created: 2018-04-17 Last updated: 2018-05-30

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