Cited by 103Circadian rhythm and melatoninCircular RNAs in diseasesSleep and Wakefulness Research

Effect of lithium on the circadian rhythms of locomotor activity and glycogen synthase kinase-3 protein expression in the mouse suprachiasmatic nuclei

Iwahana, Eiko, Akiyama, Masashi, Miyakawa, Kazuko, Uchida, Ayumi, Kasahara, Jiro, Fukunaga, Kohji, Hamada, Toshiyuki, Shibata, Shigenobu·2004·European Journal of Neuroscience

Abstract

A circadian clock located in the suprachiasmatic nucleus (SCN) regulates the period of physiological and behavioural rhythms to approximately 24 h. Lithium can lengthen the period of circadian rhythms in most organisms although little is known about the underlying mechanism. In the present study, we examined Drosophila shaggy ortholog glycogen synthase kinase-3 (GSK-3) protein expression in the SCN after lithium treatment. When locomotor activity was assessed, we found an association between the effect of lithium and the period of circadian oscillation as well as the level of GSK-3 protein expression. The decreased expression of GSK-3 and increased expression of phosphorylated GSK-3 (pGSK-3) resulted in an antiphasic circadian rhythm between the two in the SCN of lithium-treated mice housed under both light-dark and constant dark conditions. The enzyme activity of GSK-3 in the SCN was low when the level of pGSK-3 protein was high, as examined by immunoblotting analysis. Thus, GSK-3 enzyme activity has a correlation with the expression of GSK-3 protein in the SCN. Although both GSK-3 and pGSK-3 proteins are also expressed in the arcuate nucleus, lithium did not affect their expression. Based on the association that we found between lengthened circadian period and GSK-3 protein and GSK-3 activity in the SCN, we suggest that GSK-3 plays a role in regulating the period of the mammalian circadian pacemaker.

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Crossref · 10.1111/j.0953-816x.2004.03322.x

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  • The effect of lithium and valproate on circadian rhythms likely involves the inhibition of GSK3β, which modifies multiple members of the molecular clock.

    “This effect on circadian rhythms likely involves the inhibition of GSK3β which modifies multiple members of the molecular clock (Iwahana et al., 2004; Padiath et al., 2004; Gould and Manji, 2005; Iitaka et al., 2005; Yin et al., 2006).”

    From Circadian genes, rhythms and the biology of mood disorders (2007) · cites this paper as Iwahana et al., 2004

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Authors
Iwahana, E., Akiyama, M., Miyakawa, K., Uchida, A., Kasahara, J., Fukunaga, K., Hamada, T., & Shibata, S.
Affiliations
  • Waseda University (JP)
  • Tohoku University (JP)
  • Advanced Research Center for Human Sciences, Waseda University (JP)
Corresponding author
Shibata, Shigenobu
Venue
European Journal of Neuroscience
Publisher
Wiley
Published
2004-04
Volume
19
Issue
8
Pages
2281-2287
ISSN
  • 0953-816X (ISSN-L)
  • 1460-9568
OpenAlex
W2048211404
Cited by
103
References
27
Citations by year
2026: 2 · 2025: 1 · 2023: 3 · 2022: 5 · 2021: 5 · 2020: 3 · 2019: 4 · 2018: 2 · 2017: 8 · 2016: 5 · 2015: 3 · 2014: 5 · 2013: 4 · 2012: 7
FWCI
3.12
Type
journal article
Language
en
Open access
closed
Locations
  • European Journal of Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Circular RNAs in diseases
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
Keywords
lithium, circadian rhythm, suprachiasmatic nucleus, glycogen synthase kinase-3, GSK3 phosphorylation, locomotor activity, circadian period, circadian pacemaker, arcuate nucleus, enzyme activity
MeSH terms
Animals, Circadian Rhythm, Enzyme Activation, Male, Mice, Inbred C57BL, Motor Activity, Suprachiasmatic Nucleus, Up-Regulation, Gene Expression Regulation, Enzymologic, Lithium Carbonate, Glycogen Synthase Kinase 3, Mice

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