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