Evidence map›Paper›PMID 25477781›Full record

ArticleFrontiers in cellular neuroscience2014

Clozapine promotes glycolysis and myelin lipid synthesis in cultured oligodendrocytes.

Johann Steiner, Daniel Martins-de-Souza, Kolja Schiltz, Zoltan Sarnyai, Sabine Westphal, Berend Isermann, Henrik Dobrowolny, Christoph W Turck, Bernhard Bogerts, Hans-Gert Bernstein and 3 more

Open access · goldAbstract read
In one paragraph

Article in Frontiers in cellular neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 1 pooled it
2.3field-weighted citation impact, top 12% 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

31 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.

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  11. Brain aerobic glycolysis and resilience in Alzheimer disease.Proceedings of the National Academy of Sciences of the United States of America · 2023
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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

13 authors at 7 institutions in 5 countries.

Johann SteinerDepartment of Psychiatry and Psychotherapy, University of Magdeburg Magdeburg, Germany ; Center for Behavioral Brain Sciences Magdeburg, Germany ; Pembroke College, University of Cambridge Cambridge, UK.
Daniel Martins-de-SouzaLaboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP) Campinas, Brazil.
Kolja SchiltzDepartment of Psychiatry and Psychotherapy, University of Magdeburg Magdeburg, Germany ; Center for Behavioral Brain Sciences Magdeburg, Germany.
Zoltan SarnyaiLaboratory of Psychiatric Neuroscience, James Cook University Townsville, QLD, Australia ; Comparative Genome Centre, James Cook University Townsville, QLD, Australia ; Centre for Biodiscovery and Molecular Development of Therapeutics, James Cook University Townsville, QLD, Australia ; Australian Institute of Tropical Health and Medicine, James Cook University Townsville, QLD, Australia.
Sabine WestphalInstitute of Clinical Chemistry and Pathobiochemistry, University of Magdeburg Magdeburg, Germany.
Berend IsermannInstitute of Clinical Chemistry and Pathobiochemistry, University of Magdeburg Magdeburg, Germany.
Henrik DobrowolnyDepartment of Psychiatry and Psychotherapy, University of Magdeburg Magdeburg, Germany.
Christoph W TurckDepartment of Translational Research in Psychiatry, Max Planck Institute of Psychiatry Munich, Germany.
Bernhard BogertsDepartment of Psychiatry and Psychotherapy, University of Magdeburg Magdeburg, Germany ; Center for Behavioral Brain Sciences Magdeburg, Germany.
Hans-Gert BernsteinDepartment of Psychiatry and Psychotherapy, University of Magdeburg Magdeburg, Germany.
Tamas L HorvathSection of Comparative Medicine, Yale University School of Medicine New Haven, CT, USA.
Lorenz SchildInstitute of Clinical Chemistry and Pathobiochemistry, University of Magdeburg Magdeburg, Germany.
Gerburg KeilhoffInstitute of Biochemistry and Cell Biology, University of Magdeburg Magdeburg, Germany.
University Hospital Magdeburg · DECenter for Behavioral Brain Sciences · DEJames Cook University · AUMax Planck Institute of Psychiatry · DEUniversidade Estadual de Campinas (UNICAMP) · BRUniversity of Cambridge · GBYale University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Clozapine displays stronger systemic metabolic side effects than haloperidol and it has been hypothesized that therapeutic antipsychotic and adverse metabolic effects of these drugs are related. Considering that cerebral disconnectivity through oligodendrocyte dysfunction has been implicated in schizophrenia, it is important to determine the effect of these drugs on oligodendrocyte energy metabolism and myelin lipid production. Effects of clozapine and haloperidol on glucose and myelin lipid metabolism were evaluated and compared in cultured OLN-93 oligodendrocytes. First, glycolytic activity was assessed by measurement of extra- and intracellular glucose and lactate levels. Next, the expression of glucose (GLUT) and monocarboxylate (MCT) transporters was determined after 6 and 24 h. And finally mitochondrial respiration, acetyl-CoA carboxylase, free fatty acids, and expression of the myelin lipid galactocerebroside were analyzed. Both drugs altered oligodendrocyte glucose metabolism, but in opposite directions. Clozapine improved the glucose uptake, production and release of lactate, without altering GLUT and MCT. In contrast, haloperidol led to higher extracellular levels of glucose and lower levels of lactate, suggesting reduced glycolysis. Antipsychotics did not alter significantly the number of functionally intact mitochondria, but clozapine enhanced the efficacy of oxidative phosphorylation and expression of galactocerebroside. Our findings support the superior impact of clozapine on white matter integrity in schizophrenia as previously observed, suggesting that this drug improves the energy supply and myelin lipid synthesis in oligodendrocytes. Characterizing the underlying signal transduction pathways may pave the way for novel oligodendrocyte-directed schizophrenia therapies.

Indexed as

clozapineglycolysishaloperidolmyelinoligodendrocytesschizophrenia

Identifiers

PMID25477781
PMCPMC4235405
OpenAlexW2171963007

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.