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Fluoxetine regulates the expression of neurotrophic/growth factors and glucose metabolism in astrocytes

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Abstract

Rationale

The pharmacological actions of most antidepressants are ascribed to the modulation of serotonergic and/or noradrenergic transmission in the brain. During therapeutic treatment for major depression, fluoxetine, one of the most commonly prescribed selective serotonin reuptake inhibitor (SSRI) antidepressants, accumulates in the brain, suggesting that fluoxetine may interact with additional targets. In this context, there is increasing evidence that astrocytes are involved in the pathophysiology of major depression.

Objectives

The aim of this study was to examine the effects of fluoxetine on the expression of neurotrophic/growth factors that have antidepressant properties and on glucose metabolism in cultured cortical astrocytes.

Results

Treatment of astrocytes with fluoxetine and paroxetine, another SSRI antidepressant, upregulated brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and VGF mRNA expression. In contrast, the tricyclic antidepressants desipramine and imipramine did not affect the expression of these neurotrophic/growth factors. Analysis of the effects of fluoxetine on glucose metabolism revealed that fluoxetine reduces glycogen levels and increases glucose utilization and lactate release by astrocytes. Similar data were obtained with paroxetine, whereas imipramine and desipramine did not regulate glucose metabolism in this glial cell population. Our results also indicate that the effects of fluoxetine and paroxetine on glucose utilization, lactate release, and expression of BDNF, VEGF, and VGF are not mediated by serotonin-dependent mechanisms.

Conclusions

These data suggest that, by increasing the expression of specific astrocyte-derived neurotrophic factors and lactate release from astrocytes, fluoxetine may contribute to normalize the trophic and metabolic support to neurons in major depression.

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Acknowledgments

The authors are grateful to Cendrine Barrière Borgioni and Evelyne Ruchti for valuable technical assistance. This work was supported by the Swiss National Science Foundation grants 31003A-124783 (to JLM) and 3100AO-108336/1 (to PJM), the Désirée and Niels Yde's Foundation (to JLM and PJM), and the Swiss Academy of Medical Sciences (to JLM and PJM). The authors have no financial relationship with the Swiss National Science Foundation, the Désirée and Niels Yde's Foundation, and the Swiss Academy of Medical Sciences. All experiments comply with the Swiss federal act on animal protection and the Swiss animal protection ordinance.

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Authors and Affiliations

  1. Laboratory of Neuroenergetics and Cellular Dynamics, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, CH-1015, Switzerland

    Igor Allaman & Pierre J. Magistretti

  2. Department of Physiology, University of Lausanne, Rue du Bugnon 7, 1005, Lausanne, Switzerland

    Hubert Fiumelli & Jean-Luc Martin

  3. Department of Psychiatry-CHUV, Center for Psychiatric Neuroscience, 1008, Prilly-Lausanne, Switzerland

    Pierre J. Magistretti & Jean-Luc Martin

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  1. Igor Allaman
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  2. Hubert Fiumelli
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  3. Pierre J. Magistretti
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  4. Jean-Luc Martin
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Correspondence to Jean-Luc Martin.

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Allaman, I., Fiumelli, H., Magistretti, P.J. et al. Fluoxetine regulates the expression of neurotrophic/growth factors and glucose metabolism in astrocytes. Psychopharmacology 216, 75–84 (2011). https://doi.org/10.1007/s00213-011-2190-y

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  • DOI: https://doi.org/10.1007/s00213-011-2190-y

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