PMID- 24180397 OWN - NLM STAT- MEDLINE DCOM- 20150130 LR - 20190728 IS - 1873-4286 (Electronic) IS - 1381-6128 (Linking) VI - 20 IP - 23 DP - 2014 TI - Signaling pathways involved in antidepressant-induced cell proliferation and synaptic plasticity. PG - 3776-94 AB - 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/beta-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. FAU - Pilar-Cuellar, Fuencisla AU - Pilar-Cuellar F FAU - Vidal, Rebeca AU - Vidal R FAU - Diaz, Alvaro AU - Diaz A FAU - Castro, Elena AU - Castro E FAU - dos Anjos, Severiano AU - dos Anjos S FAU - Vargas, Veronica AU - Vargas V FAU - Romero, Beatriz AU - Romero B FAU - Valdizan, Elsa M AU - Valdizan EM AD - Departamento de Fisiologia y Farmacologia. IBBTEC. Facultad de Medicina. Herrera Oria s/n 39011 Santander. Cantabria. Spain. valdizae@unican.es. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - United Arab Emirates TA - Curr Pharm Des JT - Current pharmaceutical design JID - 9602487 RN - 0 (Antidepressive Agents) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Vascular Endothelial Growth Factor A) SB - IM MH - Amygdala/drug effects/metabolism/pathology MH - Animals MH - Antidepressive Agents/*pharmacology/therapeutic use MH - Brain-Derived Neurotrophic Factor/metabolism MH - Cell Proliferation/*drug effects MH - Depressive Disorder, Major/drug therapy/etiology/metabolism/pathology MH - Disease Models, Animal MH - Frontal Lobe/drug effects/metabolism/pathology MH - Hippocampus/drug effects/metabolism/pathology MH - Humans MH - Neurogenesis/drug effects MH - Neuronal Plasticity/*drug effects MH - Vascular Endothelial Growth Factor A/metabolism MH - Wnt Signaling Pathway/*drug effects EDAT- 2013/11/05 06:00 MHDA- 2015/01/31 06:00 CRDT- 2013/11/05 06:00 PHST- 2013/08/30 00:00 [received] PHST- 2013/10/23 00:00 [accepted] PHST- 2013/11/05 06:00 [entrez] PHST- 2013/11/05 06:00 [pubmed] PHST- 2015/01/31 06:00 [medline] AID - CPD-EPUB-57048 [pii] AID - 10.2174/13816128113196660736 [doi] PST - ppublish SO - Curr Pharm Des. 2014;20(23):3776-94. doi: 10.2174/13816128113196660736.