Evidence map›Paper›PMID 26171981›Full record

ArticleTranslational psychiatry2015

Search for common targets of lithium and valproic acid identifies novel epigenetic effects of lithium on the rat leptin receptor gene.

R S Lee, M Pirooznia, J Guintivano, M Ly, E R Ewald, K L Tamashiro, T D Gould, T H Moran, J B Potash

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Translational psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 2 pooled it
1.8field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 2 syntheses or guidelines pooled it, 43 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Epigenetic Neuropharmacology: Drugs Affecting the Epigenome in the Brain.Annual review of pharmacology and toxicology · 2021
    Review
  14. Article
  15. Review
  16. Genomics of Lithium Action and Response.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2017
    Review
  17. Review
  18. Article
  19. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

R S LeeJohns Hopkins Mood Disorders Center of the Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA.
M PiroozniaJohns Hopkins Mood Disorders Center of the Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA.ORCID 0000000242106458
J Guintivano1] Johns Hopkins Mood Disorders Center of the Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA [2] Graduate Program in Human Genetics, University of Maryland School of Medicine, Baltimore, MD, USA.
M LyJohns Hopkins Mood Disorders Center of the Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA.
E R EwaldJohns Hopkins Mood Disorders Center of the Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA.
K L TamashiroJohns Hopkins Mood Disorders Center of the Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA.
T D GouldDepartments of Psychiatry, Pharmacology, and Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA.
T H MoranJohns Hopkins Mood Disorders Center of the Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA.
J B PotashDepartment of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
Johns Hopkins University · USUniversity of Maryland, Baltimore · USUniversity of Iowa · US

Funding

Influences of the prenatal environment on metabolic programmingR00HD055030 · NICHD · JOHNS HOPKINS UNIVERSITY · PI TAMASHIRO, KELLIE L. K. · 2009 to 2011
$782k
NICHD NIH HHS R00 HD055030
6 · The paper itself

Abstract

Epigenetics may have an important role in mood stabilizer action. Valproic acid (VPA) is a histone deacetylase inhibitor, and lithium (Li) may have downstream epigenetic actions. To identify genes commonly affected by both mood stabilizers and to assess potential epigenetic mechanisms that may be involved in their mechanism of action, we administered Li (N = 12), VPA (N = 12), and normal chow (N = 12) to Brown Norway rats for 30 days. Genomic DNA and mRNA were extracted from the hippocampus. We used the mRNA to perform gene expression analysis on Affymetrix microarray chips, and for genes commonly regulated by both Li and VPA, we validated expression levels using quantitative real-time PCR. To identify potential mechanisms underlying expression changes, genomic DNA was bisulfite treated for pyrosequencing of key CpG island 'shores' and promoter regions, and chromatin was prepared from both hippocampal tissue and a hippocampal-derived cell line to assess modifications of histones. For most genes, we found little evidence of DNA methylation changes in response to the medications. However, we detected histone H3 methylation and acetylation in the leptin receptor gene, Lepr, following treatment with both drugs. VPA-mediated effects on histones are well established, whereas the Li effects constitute a novel mechanism of transcriptional derepression for this drug. These data support several shared transcriptional targets of Li and VPA, and provide evidence suggesting leptin signaling as an epigenetic target of two mood stabilizers. Additional work could help clarify whether leptin signaling in the brain has a role in the therapeutic action of Li and VPA in bipolar disorder.

Indexed as

AnimalsDNA MethylationEpigenesis, GeneticGene Expression RegulationGenesLithium CompoundsMaleOligonucleotide Array Sequence AnalysisRatsRats, Inbred BNReal-Time Polymerase Chain ReactionReceptors, LeptinTranscriptomeValproic AcidLithium CompoundsReceptors, LeptinValproic Acid

Identifiers

PMID26171981
PMCPMC5068731
OpenAlexW900740758

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.