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Differential BDNF Responses of Triple Versus Dual Reuptake Inhibition in Neuronal and Astrocytoma Cells as well as in Rat Hippocampus and Prefrontal Cortex

Monoamine reuptake inhibitors increase brain-derived neurotrophic factor (BDNF) activity, and this growth factor is regarded as an interesting target for developing new antidepressant drugs. The aims of this study were to evaluate whether monoaminergic reuptake inhibition increases BDNF in vivo and...

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Autores principales: Prickaerts, Jos, De Vry, Jochen, Boere, Janneke, Kenis, Gunter, Quinton, Maria S., Engel, Sharon, Melnick, Larry, Schreiber, Rudy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Humana Press Inc 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3413810/
https://www.ncbi.nlm.nih.gov/pubmed/22581450
http://dx.doi.org/10.1007/s12031-012-9802-9
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author Prickaerts, Jos
De Vry, Jochen
Boere, Janneke
Kenis, Gunter
Quinton, Maria S.
Engel, Sharon
Melnick, Larry
Schreiber, Rudy
author_facet Prickaerts, Jos
De Vry, Jochen
Boere, Janneke
Kenis, Gunter
Quinton, Maria S.
Engel, Sharon
Melnick, Larry
Schreiber, Rudy
author_sort Prickaerts, Jos
collection PubMed
description Monoamine reuptake inhibitors increase brain-derived neurotrophic factor (BDNF) activity, and this growth factor is regarded as an interesting target for developing new antidepressant drugs. The aims of this study were to evaluate whether monoaminergic reuptake inhibition increases BDNF in vivo and in vitro as predicted by the neurotrophic hypothesis of depression, and whether triple reuptake inhibition has a superior BDNF response compared to dual reuptake inhibition. Twenty-one days of oral treatment (30 mg/kg) with the dual serotonin/noradrenaline reuptake inhibitor duloxetine or the triple serotonin/noradrenaline/dopamine reuptake inhibitor DOV 216,303 restored BDNF protein levels in the rat hippocampus, which were initially decreased due to injection stress. The prefrontal cortex contained increased BDNF levels only after DOV 216,303 treatment. In vitro, neither duloxetine nor DOV 216,303 altered intracellular BDNF levels in murine HT22 neuronal cells. In contrast, BDNF release was more effectively decreased following treatment with DOV 216,303 in these cells. In rat C62B astrocytomas, both antidepressants increased intracellular BDNF levels at their highest nontoxic concentration. C62B astrocytomas did not release BDNF, even after antidepressant treatment. Increased BDNF levels support the neurotrophic hypothesis of depression, but our findings do not clearly evidence that the BDNF response after triple reuptake inhibitors is more effective than after dual reuptake inhibitors. Moreover, the data suggest that the role of BDNF in neurons and astrocytes is complex and likely depends on factors including specificity of cell types in different brain regions, cell–cell interactions, and different mechanisms of action of antidepressants used.
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spelling pubmed-34138102012-08-23 Differential BDNF Responses of Triple Versus Dual Reuptake Inhibition in Neuronal and Astrocytoma Cells as well as in Rat Hippocampus and Prefrontal Cortex Prickaerts, Jos De Vry, Jochen Boere, Janneke Kenis, Gunter Quinton, Maria S. Engel, Sharon Melnick, Larry Schreiber, Rudy J Mol Neurosci Article Monoamine reuptake inhibitors increase brain-derived neurotrophic factor (BDNF) activity, and this growth factor is regarded as an interesting target for developing new antidepressant drugs. The aims of this study were to evaluate whether monoaminergic reuptake inhibition increases BDNF in vivo and in vitro as predicted by the neurotrophic hypothesis of depression, and whether triple reuptake inhibition has a superior BDNF response compared to dual reuptake inhibition. Twenty-one days of oral treatment (30 mg/kg) with the dual serotonin/noradrenaline reuptake inhibitor duloxetine or the triple serotonin/noradrenaline/dopamine reuptake inhibitor DOV 216,303 restored BDNF protein levels in the rat hippocampus, which were initially decreased due to injection stress. The prefrontal cortex contained increased BDNF levels only after DOV 216,303 treatment. In vitro, neither duloxetine nor DOV 216,303 altered intracellular BDNF levels in murine HT22 neuronal cells. In contrast, BDNF release was more effectively decreased following treatment with DOV 216,303 in these cells. In rat C62B astrocytomas, both antidepressants increased intracellular BDNF levels at their highest nontoxic concentration. C62B astrocytomas did not release BDNF, even after antidepressant treatment. Increased BDNF levels support the neurotrophic hypothesis of depression, but our findings do not clearly evidence that the BDNF response after triple reuptake inhibitors is more effective than after dual reuptake inhibitors. Moreover, the data suggest that the role of BDNF in neurons and astrocytes is complex and likely depends on factors including specificity of cell types in different brain regions, cell–cell interactions, and different mechanisms of action of antidepressants used. Humana Press Inc 2012-05-13 2012 /pmc/articles/PMC3413810/ /pubmed/22581450 http://dx.doi.org/10.1007/s12031-012-9802-9 Text en © The Author(s) 2012 https://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
spellingShingle Article
Prickaerts, Jos
De Vry, Jochen
Boere, Janneke
Kenis, Gunter
Quinton, Maria S.
Engel, Sharon
Melnick, Larry
Schreiber, Rudy
Differential BDNF Responses of Triple Versus Dual Reuptake Inhibition in Neuronal and Astrocytoma Cells as well as in Rat Hippocampus and Prefrontal Cortex
title Differential BDNF Responses of Triple Versus Dual Reuptake Inhibition in Neuronal and Astrocytoma Cells as well as in Rat Hippocampus and Prefrontal Cortex
title_full Differential BDNF Responses of Triple Versus Dual Reuptake Inhibition in Neuronal and Astrocytoma Cells as well as in Rat Hippocampus and Prefrontal Cortex
title_fullStr Differential BDNF Responses of Triple Versus Dual Reuptake Inhibition in Neuronal and Astrocytoma Cells as well as in Rat Hippocampus and Prefrontal Cortex
title_full_unstemmed Differential BDNF Responses of Triple Versus Dual Reuptake Inhibition in Neuronal and Astrocytoma Cells as well as in Rat Hippocampus and Prefrontal Cortex
title_short Differential BDNF Responses of Triple Versus Dual Reuptake Inhibition in Neuronal and Astrocytoma Cells as well as in Rat Hippocampus and Prefrontal Cortex
title_sort differential bdnf responses of triple versus dual reuptake inhibition in neuronal and astrocytoma cells as well as in rat hippocampus and prefrontal cortex
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3413810/
https://www.ncbi.nlm.nih.gov/pubmed/22581450
http://dx.doi.org/10.1007/s12031-012-9802-9
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