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Cited by 64Circadian rhythm and melatoninBipolar Disorder and TreatmentCircular RNAs in diseases

Glycogen Synthase Kinase 3β as a Likely Target for the Action of Lithium on Circadian Clocks

Padiath, Quasar Saleem, Paranjpe, Dhanashree, Jain, Sanjeev, Sharma, Vijay Kumar·2004·Chronobiology International
DOI 10.1081/cbi-120027981
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Abstract

Although lithium is one of the most commonly used drugs in the prophylaxis and treatment of bipolar disorder, the mechanisms underlying its therapeutic action are still unclear. Together with its mood-stabilizing effects, lithium is also known to influence the circadian clocks of several organisms including man. Circadian rhythms are altered in patients with bipolar disorder, and it is believed that these rhythms may play an important role in disease mechanisms. It is therefore possible that some of the therapeutic actions of lithium may be related to its effect on circadian clocks. Identifying the targets for lithium's action on circadian clocks would therefore be important both for understanding the mechanisms of its therapeutic effect and also in further understanding disease mechanisms in bipolar disorders. Using Drosophila melanogaster as a model system, we show that long-term administration of lithium results in lengthening of the free-running period (tau) of circadian locomotor activity rhythm of flies in constant darkness (DD). This effect occurs at concentrations similar to the plasma levels of lithium used in the treatment of bipolar disorder. The lithium-treated flies also show reduced activity of one of the previously reported targets of lithium action, Glycogen Synthase Kinase 3beta (GSK 3beta). GSK 3beta has been shown to be involved in the regulation of circadian clocks as the down regulation of this protein results in an elongation of tau. The tau elongation resembles the effect seen with lithium administration in a number of organisms including man, and taken together with the earlier observations our results suggest that lithium inhibits the activity of GSK 3beta to produce its effect on circadian clocks.

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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 Padiath et al., 2004

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Authors
Padiath, Q. S., Paranjpe, D., Jain, S., & Sharma, V. K.
Affiliations
  • National Centre for Biological Sciences (IN)
  • Jawaharlal Nehru Centre for Advanced Scientific Research (IN)
  • National Institute of Mental Health and Neurosciences (IN)
Corresponding author
Sharma, Vijay Kumar
ORCID
Venue
Chronobiology International
Publisher
Informa UK Limited
Published
2004-01
Volume
21
Issue
1
Pages
43-55
ISSN
  • 0742-0528 (ISSN-L)
  • 1525-6073
DOI
10.1081/cbi-120027981
OpenAlex
W1997045509
Cited by
64
References
40
Citations by year
2025: 1 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 3 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 8 · 2015: 4 · 2014: 2 · 2013: 3 · 2012: 2
FWCI
1.52
Type
journal article
Language
en
Open access
closed
Locations
  • Chronobiology International (publishedVersion)
  • PubMed (publishedVersion)
Funders
California State Polytechnic University, Pomona
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
  • Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Circular RNAs in diseases
Keywords
lithium, glycogen synthase kinase-3β, circadian clock, free-running period, Drosophila melanogaster, bipolar disorder, mood stabilizers, circadian rhythm disruption
MeSH terms
Glycogen Synthase Kinase 3 beta, Animals, Biological Clocks, Bipolar Disorder, Circadian Rhythm, Cytoskeletal Proteins, Drosophila melanogaster, Humans, Lithium, Male, Motor Activity, Transcription Factors, Trans-Activators, Drosophila Proteins, Glycogen Synthase Kinase 3, beta Catenin, Armadillo Domain Proteins

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