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The γ-aminobutyric acid and proton signaling systems in the zebrafish brain [Elektronisk resurs] Characterization and effect of stress

Cocco, Arianna (författare)
Winberg, Svante (preses)
Norton, William H. J. (opponent)
Uppsala universitet Medicinska och farmaceutiska vetenskapsområdet (utgivare)
Svante Winberg (medarbetare)
Uppsala Acta Universitatis Upsaliensis 2018
Engelska 88
Serie: Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 1651-6206
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  • E-bokAvhandling(Diss. (sammanfattning) Uppsala : Uppsala universitet, 2018)
Sammanfattning Ämnesord
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  • 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 (GABA A ) receptors. Those channels are homo- or heteropentamers and, in the zebrafish, at least twenty-three genes encode for putative GABA A 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 GABA A receptor subunit combinations in the whole brain were proposed to be α 1 β 2 γ 2 and α 1 β 2 δ, and region-specific GABA A channels were also inferred. Those included telencephalic α 2b β 3 γ 2 , α 2b β 3 δ, α5β 2 γ 2 , α 5 β 3 γ 2 and cerebellar α 4 β 2 γ 2 and α 4 β 2 δ. A tissue specific expression was documented for the paralogues α 6a and α 6b ; the former was abundantly transcribed in the retinas, the latter in the cerebellum. Proposed retinal GABA A receptors were α 1 β x γ 2 , α 1 β x δ, α 6a β x γ 2 and α 6a β x δ, with either β 2 or β 3 . 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 GABA A receptor subunits expression. Treated animals experienced social isolation and repeated confinement, and depicted increased mRNA levels of several GABA A receptor monomers. It was deduced that a higher number of extrasynaptic, tonic-current-mediating GABA A 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. 

Ämnesord

Medical and Health Sciences  (hsv)
Basic Medicine  (hsv)
Physiology  (hsv)
Medicin och hälsovetenskap  (hsv)
Medicinska och farmaceutiska grundvetenskaper  (hsv)
Fysiologi  (hsv)
Biokemi  (uu)
Biochemistry  (uu)

Indexterm och SAB-rubrik

g-aminobutyric acid (GABA)
GABAA receptors
adult zebrafish
central nervous system
gene expression profiling
extracellular acidification.
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