ArticleNeuroscience2012
Disruption of circadian rhythmicity and suprachiasmatic action potential frequency in a mouse model with constitutive activation of glycogen synthase kinase 3.
Article in Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed, 49 citations in OpenAlex.
- Early-Life Ventral Hippocampal Lesion and Circadian Disruption Result in Altered Behavior in Adult Mice in a Sex-Dependent Manner.The European journal of neuroscience · 2025Article
- High-Salt Diet Increases Suprachiasmatic Neuronal Excitability Through Endothelin Receptor Type B Signaling.Function (Oxford, England) · 2025Article
- Translational implications of circadian activity alterations in an experimental model of late-onset depression induced by prenatal excess of glucocorticoids.Frontiers in behavioral neuroscience · 2025Review
- Crosstalk between Circadian Rhythm Dysregulation and Tumorigenesis, Tumor Metabolism and Tumor Immune Response.Aging and disease · 2024Review
- Sex Differences in Long-term Outcome of Prenatal Exposure to Excess Glucocorticoids-Implications for Development of Psychiatric Disorders.Molecular neurobiology · 2023Article
- Kv12-encoded K+ channels drive the day-night switch in the repetitive firing rates of SCN neurons.The Journal of general physiology · 2023Article
- Ribosomal S6 Kinase Regulates the Timing and Entrainment of the Mammalian Circadian Clock Located in the Suprachiasmatic Nucleus.Neuroscience · 2023Article
- Kv12-Encoded KbioRxiv : the preprint server for biology · 2023Article
- Circadian disruption of hippocampus in an early senescence male mouse model.Pharmacology, biochemistry, and behavior · 2022Article
- Neurobiological and behavioral mechanisms of circadian rhythm disruption in bipolar disorder: A critical multi-disciplinary literature review and agenda for future research from the ISBD task force on chronobiology.Bipolar disorders · 2022Review
- Inhibition of glycogen synthase kinase 3 by lithium, a mechanism in search of specificity.Frontiers in molecular neuroscience · 2022Review
- Lithium orotate: A superior option for lithium therapy?Brain and behavior · 2021Review
- A Crosstalk between the Biorhythms and Gatekeepers of Longevity: Dual Role of Glycogen Synthase Kinase-3.Biochemistry. Biokhimiia · 2021Review
- Glucagon receptor signaling regulates weight loss via central KLB receptor complexes.JCI insight · 2021Article
- Glycogen Synthase Kinase-3 Inhibitors: Preclinical and Clinical Focus on CNS-A Decade Onward.Frontiers in molecular neuroscience · 2021Review
- The GSK-3β-FBXL21 Axis Contributes to Circadian TCAP Degradation and Skeletal Muscle Function.Cell reports · 2020Article
- Molecular Mechanisms Underlying the Circadian Rhythm of Blood Pressure in Normotensive Subjects.Current hypertension reports · 2020Review
- A Symphony of Signals: Intercellular and Intracellular Signaling Mechanisms Underlying Circadian Timekeeping in Mice and Flies.International journal of molecular sciences · 2019Review
- Behavioral and SCN neurophysiological disruption in the Tg-SwDI mouse model of Alzheimer's disease.Neurobiology of disease · 2018Article
- GSK3 activity regulates rhythms in hippocampal clock gene expression and synaptic plasticity.Hippocampus · 2017Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Glycogen synthase kinase 3 (GSK3) is a serine/threonine kinase that has been implicated in psychiatric diseases, neurodevelopment, and circadian regulation. Both GSK3 isoforms, α and β, exhibit a 24-h variation of inhibitory phosphorylation within the suprachiasmatic nucleus (SCN), the primary circadian pacemaker. We examined the hypothesis that rhythmic GSK3 activity is critical for robust circadian rhythmicity using GSK3α(21A/21A)/β(9A/9A) knock-in mice with serine-alanine substitutions at the inhibitory phosphorylation sites, making both forms constitutively active. We monitored wheel-running locomotor activity of GSK3 knock-in mice and used loose-patch electrophysiology to examine the effect of chronic GSK3 activity on circadian behavior and SCN neuronal activity. Double transgenic GSK3α/β knock-in mice exhibit disrupted behavioral rhythmicity, including significantly decreased rhythmic amplitude, lengthened active period, and increased activity bouts per day. This behavioral disruption was dependent on chronic activation of both GSK3 isoforms and was not seen in single transgenic GSK3α or GSK3β knock-in mice. Underlying the behavioral changes, SCN neurons from double transgenic GSK3α/β knock-in mice exhibited significantly higher spike rates during the subjective night compared to those from wild-type controls, with no differences detected during the subjective day. These results suggest that constitutive activation of GSK3 results in the loss of the typical day/night variation of SCN neuronal activity. Together, these results implicate GSK3 activity as a critical regulator of circadian behavior and neurophysiological rhythms. Because GSK3 has been implicated in numerous pathologies, understanding how GSK3 modulates circadian rhythms and neurophysiological activity may lead to novel therapeutics for pathological disorders and circadian rhythm dysfunction.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.