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Characterization of the gamma-aminobutyric acid signaling system in the zebrafish (danio rerio hamilton) central nervous system by reverse transcription-quantitative polymerase chain reaction
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysiologi.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysiologi.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. Univ Western Australia, Ctr Evolutionary Biol, 35 Stirling Hwy, Crawley, WA 6009, Australia..
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2017 (Engelska)Ingår i: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 343, s. 300-321Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

In the vertebrate brain, inhibition is largely mediated by raminobutyric acid (GABA). This neurotransmitter comprises a signaling machinery of GABA(A), GABA(B) receptors, transporters, glutamate decarboxylases (gads) and 4-aminobutyrate aminotransferase (abat), and associated proteins. Chloride is intimately related to GABAA receptor conductance, GABA uptake, and GADs activity. The response of target neurons to GABA stimuli is shaped by chloride-cation co-transporters (CCCs), which strictly control Cl- gradient across plasma membranes. This research profiled the expression of forty genes involved in GABA signaling in the zebrafish (Danio rerio) brain, grouped brain regions and retinas. Primer pairs were developed for reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The mRNA levels of the zebrafish GABA system share similarities with that of mammals, and confirm previous studies in non-mammalian species. Proposed GABAA receptors are alpha(1)beta(2)gamma(2), alpha(1)beta(2)delta, alpha(2b)beta(3), alpha(2b)beta(3)delta, alpha(4)beta(2)gamma(2), alpha(4)beta(2)gamma, alpha(6b)beta(2)gamma(2) and alpha(6b)beta(2)delta. Regional brain differences were documented. Retinal hetero- or homomeric rho-composed GABAA receptors could exist, accompanying alpha(1)beta(y)gamma(2), alpha(1)beta(y)delta, alpha(6a)beta(y)gamma(2,) alpha(6a)beta(y)delta. Expression patterns of alpha(6a) and alpha(6b) were opposite, with the former being more abundant in retinas, the latter in brains. Given the stoichiometry alpha(6w)beta(y)gamma(z), alpha(6a-) or alpha(6b)-containing receptors likely have different regulatory mechanisms. Different gene isoforms could originate after the rounds of genome duplication during teleost evolution. This research depicts that one isoform is generally more abundantly expressed than the other. Such observations also apply to GABAB receptors, GABA transporters, GABA-related enzymes, CCCs and GABAA receptor associated proteins, whose presence further strengthens the proof of a GABA system in zebrafish.

Ort, förlag, år, upplaga, sidor
2017. Vol. 343, s. 300-321
Nyckelord [en]
GABA, comparative neuroscience, teleost, zebrafish, neurotransmitter systems, receptors
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
URN: urn:nbn:se:uu:diva-317583DOI: 10.1016/j.neuroscience.2016.07.018ISI: 000393269100030PubMedID: 27453477OAI: oai:DiVA.org:uu-317583DiVA, id: diva2:1084251
Forskningsfinansiär
VetenskapsrådetTillgänglig från: 2017-03-24 Skapad: 2017-03-24 Senast uppdaterad: 2018-04-17Bibliografiskt granskad
Ingår i avhandling
1. The γ-aminobutyric acid and proton signaling systems in the zebrafish brain: Characterization and effect of stress
Öppna denna publikation i ny flik eller fönster >>The γ-aminobutyric acid and proton signaling systems in the zebrafish brain: Characterization and effect of stress
2018 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
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.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis, 2018. s. 88
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1466
Nyckelord
g-aminobutyric acid (GABA), GABAA receptors, adult zebrafish, central nervous system, gene expression profiling, extracellular acidification.
Nationell ämneskategori
Fysiologi
Forskningsämne
Biokemi
Identifikatorer
urn:nbn:se:uu:diva-348421 (URN)978-91-513-0344-4 (ISBN)
Disputation
2018-06-09, Auditorium Minus, Museum Gustavianum, Akademigatan 3, Uppsala, 09:15 (Engelska)
Opponent
Handledare
Forskningsfinansiär
Vetenskapsrådet, 621-2012-4679
Tillgänglig från: 2018-05-16 Skapad: 2018-04-17 Senast uppdaterad: 2018-10-08

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