ArticleToxicology and applied pharmacology2018
Valproic acid disrupts the oscillatory expression of core circadian rhythm transcription factors.
Article in Toxicology and applied pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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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.
The trial behind it
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
8 citing papers in PubMed, 28 citations in OpenAlex.
- Review
- Rapid-acting antidepressants and the circadian clock.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Review
- Circadian Rhythms, Disease and Chronotherapy.Journal of biological rhythms · 2021Review
- Patient fibroblast circadian rhythms predict lithium sensitivity in bipolar disorder.Molecular psychiatry · 2021Article
- Review
- Epilepsy and Its Interaction With Sleep and Circadian Rhythm.Frontiers in neurology · 2020Review
- Chronobiology of limbic seizures: Potential mechanisms and prospects of chronotherapy for mesial temporal lobe epilepsy.Neuroscience and biobehavioral reviews · 2019Review
- Disrupted Social Hierarchy in Prenatally Valproate-Exposed Autistic-Like Rats.Frontiers in behavioral neuroscience · 2019Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Valproic acid (VPA) is a well-established therapeutic used in treatment of seizure and mood disorders as well as migraines and a known hepatotoxicant. About 50% of VPA users experience metabolic disruptions, including weight gain, hyperlipidemia, and hyperinsulinemia, among others. Several of these metabolic abnormalities are similar to the effects of circadian rhythm disruption. In the current study, we examine the effect of VPA exposure on the expression of core circadian transcription factors that drive the circadian clock via a transcription-translation feedback loop. In cells with an unsynchronized clock, VPA simultaneously upregulated the expression of genes encoding core circadian transcription factors that regulate the positive and negative limbs of the feedback loop. Using low dose glucocorticoid, we synchronized cultured fibroblast cells to a circadian oscillatory pattern. Whether VPA was added at the time of synchronization or 12h later at CT12, we found that VPA disrupted the oscillatory expression of multiple genes encoding essential transcription factors that regulate circadian rhythm. Therefore, we conclude that VPA has a potent effect on the circadian rhythm transcription-translation feedback loop that may be linked to negative VPA side effects in humans. Furthermore, our study suggests potential chronopharmacology implications of VPA usage.
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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.