Clozapine Promotes Glycolysis And Myelin Lipid Synthesis In Cultured Oligodendrocytes.

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.

Desenvolvimento e avaliação de uma servoválvula de baixo custo para a aplicação de insumos líquidos

The present work aimed the development of a low cost servo-valve that answers to an electronic control signal, for variable rates liquid inputs application. A literature research to define which valve type should be used was made. A mechanically activated proportional valve with an electronically controlled servo-engine was designed and evaluated. Since developed the servo-valve, the system was submited to a number of tests .The evaluation of its behavior was obtained in terms of repeatability, hystheresis and linearity. The test was accomplished in a bench, specially developed for this aim. As a result, were obtained three curves of opening percentage as function of flow rate, describing three opening and closing increments in two different work pressures. The servo-valve presented a good repeatability, reasonable hysteresis and a typically quadratic curve. This one maintained the low cost target. These results were very satisfied because the non-linearity and the hysteresis could be easily corrected by software.