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Neural Plasticity
Volume 2013, Article ID 537265, 21 pages
Review Article

Neural Plasticity and Proliferation in the Generation of Antidepressant Effects: Hippocampal Implication

1Departamento de Fisiología y Farmacología, Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC), Universidad de Cantabria-CSIC-IDICAN, Santander, Cantabria, Spain
2Centro de Investigación Biomédica en Red de SaludMental (CIBERSAM), Instituto de Salud Carlos III, Santander, Cantabria, Spain
3Stem Center, Clínica Palmaplanas, Camí dels Reis 308, Palma de Mallorca, Spain
4The Research Group for Neurobiology and Gene Therapy, KU Leuven, Leuven, Belgium
5Department of Physiology and Pharmacology, School of Medicine, Cardenal Herrera Oria s/n, University of Cantabria 39011 Santander, Spain

Received 4 March 2013; Revised 1 May 2013; Accepted 8 May 2013

Academic Editor: Chitra D. Mandyam

Copyright © 2013 Fuencisla Pilar-Cuéllar et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


It is widely accepted that changes underlying depression and antidepressant-like effects involve not only alterations in the levels of neurotransmitters as monoamines and their receptors in the brain, but also structural and functional changes far beyond. During the last two decades, emerging theories are providing new explanations about the neurobiology of depression and the mechanism of action of antidepressant strategies based on cellular changes at the CNS level. The neurotrophic/plasticity hypothesis of depression, proposed more than a decade ago, is now supported by multiple basic and clinical studies focused on the role of intracellular-signalling cascades that govern neural proliferation and plasticity. Herein, we review the state-of-the-art of the changes in these signalling pathways which appear to underlie both depressive disorders and antidepressant actions. We will especially focus on the hippocampal cellularity and plasticity modulation by serotonin, trophic factors as brain-derived neurotrophic factor (BDNF), and vascular endothelial growth factor (VEGF) through intracellular signalling pathways—cAMP, Wnt/β-catenin, and mTOR. Connecting the classic monoaminergic hypothesis with proliferation/neuroplasticity-related evidence is an appealing and comprehensive attempt for improving our knowledge about the neurobiological events leading to depression and associated to antidepressant therapies.