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PMID: 31186021 Published · epublish English Journal Article

Connexin30 and Connexin43 show a time-of-day dependent expression in the mouse suprachiasmatic nucleus and modulate rhythmic locomotor activity in the context of chronodisruption.

Cell communication and signaling : CCS ·Vol. 17 ·No. 1 ·2019-00-11 ·Pages 61

Ali AAH, Stahr A, Ingenwerth M, Theis M, Steinhäuser C, von Gall C

Abstract

The astroglial connexins Cx30 and Cx43 contribute to many important CNS functions including cognitive behaviour, motoric capacity and regulation of the sleep-wake cycle. The sleep wake cycle, is controlled by the circadian system. The central circadian rhythm generator resides in the suprachiasmatic nucleus (SCN). SCN neurons are tightly coupled in order to generate a coherent circadian rhythm. The SCN receives excitatory glutamatergic input from the retina which mediates entrainment of the circadian system to the environmental light-dark cycle. Connexins play an important role in electric coupling of SCN neurons and astrocytic-neuronal signalling that regulates rhythmic SCN neuronal activity. However, little is known about the regulation of Cx30 and Cx43 expression in the SCN, and the role of these connexins in light entrainment of the circadian system and in circadian rhythm generation. We analysed time-of-day dependent as well as circadian expression of Cx30 and Cx43 mRNA and protein in the mouse SCN by means of qPCR and immunohistochemistry. Moreover, we analysed rhythmic spontaneous locomotor activity in mice with a targeted deletion of Cx30 and astrocyte specific deletion of Cx43 (DKO) in different light regimes by means of on-cage infrared detectors. Fluctuation of Cx30 protein expression is strongly dependent on the light-dark cycle whereas fluctuation of Cx43 protein expression persisted in constant darkness. DKO mice entrained to the light-dark cycle. However, re-entrainment after a phase delay was slightly impaired in DKO mice. Surprisingly, DKO mice were more resilient to chronodisruption. Circadian fluctuation of Cx30 and Cx43 protein expression in the SCN is differently regulated. Cx30 and astroglial Cx43 play a role in rhythm stability and re-entrainment under challenging conditions.

Keywords
Circadian rhythm Constant darkness Constant light Entrainment Jet lag SCN cFOS
MeSH Terms
Animals Circadian Rhythm Connexin 30/genetics,metabolism Connexin 43/genetics,metabolism Locomotion Male Mice Mice, Inbred C57BL Suprachiasmatic Nucleus/metabolism,physiology
Chemicals
Connexin 30 Connexin 43 Gjb6 protein, mouse
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Ali Amira A H
Institute of Anatomy II, Medical Faculty, Heinrich-Heine-University, Merowinger Platz 1A, 40225, Düsseldorf, Germany.
Stahr Anna
Institute of Anatomy II, Medical Faculty, Heinrich-Heine-University, Merowinger Platz 1A, 40225, Düsseldorf, Germany.
Ingenwerth Marc
Institute of Pathology, Medical Faculty, University of Duisburg-Essen, Hufelandstrasse 55, 45147, Essen, Germany.
Theis Martin
Institute of Cellular Neurosciences, Medical Faculty, University Bonn, Sigmund Freud Str. 25, 53105, Bonn, Germany.
Steinhäuser Christian
Institute of Cellular Neurosciences, Medical Faculty, University Bonn, Sigmund Freud Str. 25, 53105, Bonn, Germany.
von Gall Charlotte ORCID
Institute of Anatomy II, Medical Faculty, Heinrich-Heine-University, Merowinger Platz 1A, 40225, Düsseldorf, Germany. charlotte.vongall@med.uni-duesseldorf.de.
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Article Info
Journal
Cell communication and signaling : CCS
Abbr.
Cell Commun Signal
ISSN
1478-811X
Published
2019-00-11
Epub
2019-00-11
Pages
61
Language
English
Region
England
NLM ID
101170464
PMCID
PMC6560876
Subset
IM
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