| Valproic Acid Phase Shifts the Rhythmic Expression of PERIOD2::LUCIFERASE. | |
| | |
MedLine Citation:
|
PMID: 22215612 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
|
Valproic acid (VPA) is an anticonvulsant used to treat bipolar disorder, a psychiatric disease associated with disturbances in circadian rhythmicity. Little is known about how VPA affects circadian rhythms. The authors cultured tissues containing the master brain pacemaker for circadian rhythmicity, the suprachiasmatic nuclei (SCN), and skin fibroblasts from transgenic PERIOD2::LUCIFERASE (PER2::LUC) mice and studied the effect of VPA on the circadian PER2::LUC rhythm by measuring bioluminescence. VPA (1 mM) significantly phase advanced the PER2::LUC rhythm when applied at a time point corresponding to the lowest (trough, ~ZT 0) PER2::LUC expression but phase delayed the PER2::LUC rhythm when the drug was administered at the time of highest (peak, ~ZT 12) protein expression. In addition, it significantly increased the overall amplitude of PER2::LUC oscillations at time points at or close to ZT 12 but had no effect on period. Real-time PCR analyses on mouse and human fibroblasts revealed that expressions of other clock genes were increased after 2 h treatment with VPA. Because VPA is known to inhibit histone deacetylation, the authors treated cultures with an established histone deacetylation inhibitor, trichostatin A (TSA; 20 ng/mL), to compare the effect of VPA and TSA on molecular rhythmicity. They found that TSA had similar effects on the PER2::LUC rhythm as VPA. Furthermore, VPA and TSA significantly increased acetylation on histone H3 but in comparison little on histone H4. Lithium is another commonly used treatment for bipolar disorder. Therefore, the authors also studied the impact of lithium chloride (LiCl; 10 mM) on the PER2::LUC rhythm. LiCl delayed the phase, but in contrast to VPA and TSA, LiCl lengthened the PER2::LUC period and had no effect on histone acetylation. These results demonstrate that VPA can delay or advance the phase, as well as increase the amplitude, of the PERIOD2::LUCIFERASE rhythm depending on the circadian time of application. Furthermore, the authors show that LiCl delays the phase and lengthens the period of the PER2::LUC rhythm, confirming previous reports on circadian lithium effects. These different molecular effects may underlie differential chronotherapeutic effects of VPA and lithium. |
| | |
Authors:
|
Anne-Sofie Johansson; Johan Brask; Björn Owe-Larsson; Jerker Hetta; Gabriella B S Lundkvist |
Publication Detail:
|
Type: Journal Article |
Journal Detail:
|
Title: Journal of biological rhythms Volume: 26 ISSN: 1552-4531 ISO Abbreviation: J. Biol. Rhythms Publication Date: 2011 Dec |
Date Detail:
|
Created Date: 2012-01-04 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 8700115 Medline TA: J Biol Rhythms Country: United States |
Other Details:
|
Languages: eng Pagination: 541-51 Citation Subset: IM |
Affiliation:
|
*Swedish Medical Nanoscience Center, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Genetic interaction of Per1 and Dec1/2 in the regulation of circadian locomotor activity.
Next Document: Daily rhythms in olfactory discrimination depend on clock genes but not the suprachiasmatic nucleus.