Evidence map›Paper›PMID 32094324›Full record

ArticleTranslational psychiatry2020

Discovery of suppressors of CRMP2 phosphorylation reveals compounds that mimic the behavioral effects of lithium on amphetamine-induced hyperlocomotion.

Wen-Ning Zhao, Brian T D Tobe, Namrata D Udeshi, Lucius L Xuan, Cameron D Pernia, Daniel P Zolg, Amanda J Roberts, Deepak Mani, Sarah R Blumenthal, Iren Kurtser and 8 more

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

Article in Translational psychiatry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.1field-weighted citation impact, top 27% 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

9 citing papers in PubMed, 15 citations in OpenAlex.

  1. Review
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  8. Clinical evidence that a dysregulated master neural network modulator may aid in diagnosing schizophrenia.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  9. Review
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

18 authors at 7 institutions in 3 countries.

Wen-Ning ZhaoChemical Neurobiology Laboratory, Center for Genomic Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA, 02114, USA.ORCID http://orcid.org/0000-0002-5824-2032
Brian T D TobeCenter for Stem Cells & Regenerative Medicine, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 92037, USA.
Namrata D UdeshiProteomics Platform, Broad Institute of MIT and Harvard University, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0001-5312-1402
Lucius L XuanChemical Neurobiology Laboratory, Center for Genomic Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA, 02114, USA.
Cameron D PerniaCenter for Stem Cells & Regenerative Medicine, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 92037, USA.
Daniel P ZolgChemical Neurobiology Laboratory, Center for Genomic Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA, 02114, USA.
Amanda J RobertsSanford Consortium for Regenerative Medicine, La Jolla, CA, 92037, USA.
Deepak ManiProteomics Platform, Broad Institute of MIT and Harvard University, Cambridge, MA, 02142, USA.
Sarah R BlumenthalChemical Neurobiology Laboratory, Center for Genomic Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA, 02114, USA.
Iren KurtserChemical Neurobiology Laboratory, Center for Genomic Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA, 02114, USA.
Debasis PatnaikChemical Neurobiology Laboratory, Center for Genomic Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA, 02114, USA.ORCID http://orcid.org/0000-0002-9829-3352
Irina GaisinaDepartment of Medicinal Chemistry & Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, 60612, USA.ORCID http://orcid.org/0000-0002-8668-3222
Joshua BishopChemical Neurobiology Laboratory, Center for Genomic Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA, 02114, USA.
Steven D SheridanChemical Neurobiology Laboratory, Center for Genomic Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA, 02114, USA.
Jasmin LalondeDepartment of Molecular and Cellular Biology, University of Guelph, 50 Stone Road, East, Guelph, ON, Canada, N1G 2W1.ORCID http://orcid.org/0000-0002-6797-1894
Steven A CarrProteomics Platform, Broad Institute of MIT and Harvard University, Cambridge, MA, 02142, USA.
Evan Y SnyderCenter for Stem Cells & Regenerative Medicine, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 92037, USA.
Stephen J HaggartyChemical Neurobiology Laboratory, Center for Genomic Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA, 02114, USA. shaggarty@mgh.harvard.edu.
Harvard University · USBroad Institute · USSanford Burnham Prebys Medical Discovery Institute · USMerck & Co., Inc., Rahway, NJ, USA (United States) · USSanford Consortium for Regenerative Medicine · USUniversity of Guelph · CAUniversity of Illinois Chicago · US

Funding

Genomics-Guided Characterization of iPS Cells from Common Mental IllnessesR33MH087896 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI HAGGARTY, STEPHEN J · 2011 to 2012
$872k
In vitro and in vivo study of simvastatin plus lithium in bipolar depressionR21MH093958 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI HAGGARTY, STEPHEN J, PERLIS, ROY H. · 2012 to 2013
$674k
NIMH NIH HHS R21 MH093958NIMH NIH HHS R33 MH087896U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) R33MH087896
6 · The paper itself

Abstract

The effective treatment of bipolar disorder (BD) represents a significant unmet medical need. Although lithium remains a mainstay of treatment for BD, limited knowledge regarding how it modulates affective behavior has proven an obstacle to discovering more effective mood stabilizers with fewer adverse side effects. One potential mechanism of action of lithium is through inhibition of the serine/threonine protein kinase GSK3β, however, relevant substrates whose change in phosphorylation may mediate downstream changes in neuroplasticity remain poorly understood. Here, we used human induced pluripotent stem cell (hiPSC)-derived neuronal cells and stable isotope labeling by amino acids in cell culture (SILAC) along with quantitative mass spectrometry to identify global changes in the phosphoproteome upon inhibition of GSK3α/β with the highly selective, ATP-competitive inhibitor CHIR-99021. Comparison of phosphorylation changes to those induced by therapeutically relevant doses of lithium treatment led to the identification of collapsin response mediator protein 2 (CRMP2) as being highly sensitive to both treatments as well as an extended panel of structurally distinct GSK3α/β inhibitors. On this basis, a high-content image-based assay in hiPSC-derived neurons was developed to screen diverse compounds, including FDA-approved drugs, for their ability to mimic lithium's suppression of CRMP2 phosphorylation without directly inhibiting GSK3β kinase activity. Systemic administration of a subset of these CRMP2-phosphorylation suppressors were found to mimic lithium's attenuation of amphetamine-induced hyperlocomotion in mice. Taken together, these studies not only provide insights into the neural substrates regulated by lithium, but also provide novel human neuronal assays for supporting the development of mechanism-based therapeutics for BD and related neuropsychiatric disorders.

Indexed as

Bipolar DisorderInduced Pluripotent Stem CellsAmphetamineAnimalsHumansLithiumLithium CompoundsMicePhosphorylationAmphetamineLithiumLithium Compounds

Identifiers

PMID32094324
PMCPMC7039883
OpenAlexW3007126611

What OpenQuestion holds

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Registered trials

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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.