Abstract
In the last years it has been proposed that the antidepressant action is mediated not only by changes in monoamine levels but also in association with modifications involving cell proliferation and plasticity in some brain limbic areas as hippocampus, and also frontal cortex and amygdala. This leads to the merging of the classic “monoaminergic hypothesis of depression”, with the newer “neurotrophic hypothesis of depression”. Here we review two important signaling pathways: the Wnt/β-catenin pathway —implicated in cellular proliferation and synaptic plasticity— that is downregulated in major depression and upregulated after antidepressant treatment; and the mTOR pathway —controling synaptic plasticity— recently related to present disrupted functioning in major depression, and as the target of some drugs with fast-acting potential antidepressant action. These pieces of evidences are confirmed in a variety of animal models of depression and are predictive of antidepressant actions. We also review the role of another two important neurotrophic factors: brain derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) that mediate the antidepressant effects. All of the above intracellular pathways interact by a crosstalk mediated by Akt, a key regulator molecule that may underlie the fine tuning between proliferative and neuroplasticity changes induced by antidepressant drugs.
Keywords: β-catenin, GSK-3β, mTOR, BDNF, synaptic plasticity, neurogenesis, antidepressant drugs.
Current Pharmaceutical Design
Title:Signaling Pathways Involved in Antidepressant-Induced Cell Proliferation and Synaptic Plasticity
Volume: 20 Issue: 23
Author(s): Fuencisla Pilar-Cuellar, Rebeca Vidal, Alvaro Díaz, Elena Castro, Severiano dos Anjos, Veronica Vargas, Beatriz Romero and Elsa M. Valdizan
Affiliation:
Keywords: β-catenin, GSK-3β, mTOR, BDNF, synaptic plasticity, neurogenesis, antidepressant drugs.
Abstract: In the last years it has been proposed that the antidepressant action is mediated not only by changes in monoamine levels but also in association with modifications involving cell proliferation and plasticity in some brain limbic areas as hippocampus, and also frontal cortex and amygdala. This leads to the merging of the classic “monoaminergic hypothesis of depression”, with the newer “neurotrophic hypothesis of depression”. Here we review two important signaling pathways: the Wnt/β-catenin pathway —implicated in cellular proliferation and synaptic plasticity— that is downregulated in major depression and upregulated after antidepressant treatment; and the mTOR pathway —controling synaptic plasticity— recently related to present disrupted functioning in major depression, and as the target of some drugs with fast-acting potential antidepressant action. These pieces of evidences are confirmed in a variety of animal models of depression and are predictive of antidepressant actions. We also review the role of another two important neurotrophic factors: brain derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) that mediate the antidepressant effects. All of the above intracellular pathways interact by a crosstalk mediated by Akt, a key regulator molecule that may underlie the fine tuning between proliferative and neuroplasticity changes induced by antidepressant drugs.
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Pilar-Cuellar Fuencisla, Vidal Rebeca, Díaz Alvaro, Castro Elena, Anjos dos Severiano, Vargas Veronica, Romero Beatriz and Valdizan M. Elsa, Signaling Pathways Involved in Antidepressant-Induced Cell Proliferation and Synaptic Plasticity, Current Pharmaceutical Design 2014; 20 (23) . https://dx.doi.org/10.2174/13816128113196660736
DOI https://dx.doi.org/10.2174/13816128113196660736 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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