Circadian Regulation of GluA2 mRNA Processing in the Rat Suprachiasmatic Nucleus and Other Brain Structures
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Circadian Regulation of GluA2 mRNA Processing in the Rat Suprachiasmatic Nucleus and Other Brain Structures Hana Míková 1 & Viktor Kuchtiak 2 & Irena Svobodová 2 & Veronika Spišská 1 & Dominika Pačesová 1,3 & Aleš Balík 1,2,4 Zdeňka Bendová 1,3
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Received: 20 July 2020 / Accepted: 17 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract The mammalian circadian system consists of a major circadian pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus and peripheral clocks in the body, including brain structures. The SCN depends on glutamatergic neurotransmission for transmitting signals from the retina, and it exhibits spontaneous 24-h rhythmicity in neural activity. The aim of this work was to evaluate the degree and circadian rhythmicity of AMPA receptor GluA2 subunit R/G editing and alternative flip/flop splicing in the SCN and other brain structures in Wistar rats. Our data show that the circadian rhythmicity in the SCN’s GluA2 mRNA level was highest at dawn, while the circadian rhythm in R/G editing peaked at CT10 and the rhythmic flip varied with the acrophase at the late subjective night. The circadian rhythmicity was confirmed for R/G editing and splicing in the CA3 hippocampal area, and rhythmic variation of the flip isoform was also measured in the olfactory bulbs and cerebellum. The correlations between the R/G editing and alternative flip/flop splicing revealed a structure-dependent direction. In the hippocampus, the edited (G)-form level was positively correlated with the flip variant abundance, in accord with published data; by contrast, in the SCN, the flip variant was in associated more with the unedited (R) form. The edited (G) form and flop isoform also predominated in the retina and cerebellum. Keywords Circadian clock . GluA2 subunit . R/G editing . Rat . Suprachiasmatic nucleus
Introduction The suprachiasmatic nucleus (SCN) serves as a central circadian clock in mammals and coordinates the daily rhythms in biochemical and molecular processes underlying the majority of physiological and behavioural functions. It generates selfsustained rhythms in gene expression and electrical activity Hana Míková and Viktor Kuchtiak contributed equally to this work. * Aleš Balík [email protected] * Zdeňka Bendová [email protected] 1
Faculty of Science, Department of Physiology, Charles University, Viničná 7, 128 43 Prague 2, Czech Republic
2
Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic
3
National Institute of Mental Health, Klecany, Czech Republic
4
Department of Cellular Neurophysiology, Institute of Physiology, Czech Academy of Sciences, BIOCEV, Prumyslova 595, 252 50 Vestec, Czech Republic
and produces the humoral or electrical timing signals that orchestrate the subsidiary circadian clocks in nearly every cell throughout the body [1]. Thus, daily oscillations in gene expression and various physiological parameters have been identified in many brain regions, including the cerebe
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