Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/201908
Type: Artigo de periódico
Title: Clozapine Promotes Glycolysis And Myelin Lipid Synthesis In Cultured Oligodendrocytes.
Author: Steiner, Johann
Martins-de-Souza, Daniel
Schiltz, Kolja
Sarnyai, Zoltan
Westphal, Sabine
Isermann, Berend
Dobrowolny, Henrik
Turck, Christoph W
Bogerts, Bernhard
Bernstein, Hans-Gert
Horvath, Tamas L
Schild, Lorenz
Keilhoff, Gerburg
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.
Subject: Clozapine
Glycolysis
Haloperidol
Myelin
Oligodendrocytes
Schizophrenia
Rights: aberto
Identifier DOI: 10.3389/fncel.2014.00384
Address: http://www.ncbi.nlm.nih.gov/pubmed/25477781
Date Issue: 2014
Appears in Collections:Unicamp - Artigos e Outros Documentos

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