title: Neural plasticity and proliferation in the generation of antidepressant effects: hippocampal implication.
abstract: 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.
authors.affiliation: Departamento de Fisiología y Farmacología, Instituto de Biomedicina y Biotecnología de Cantabria, Universidad de Cantabria-CSIC-IDICAN, Santander, Cantabria, Spain.
authors.forename: Fuencisla
authors.initials: F
authors.lastname: Pilar-Cuéllar
authors.forename: Rebeca
authors.initials: R
authors.lastname: Vidal
authors.forename: Alvaro
authors.initials: A
authors.lastname: Díaz
authors.forename: Elena
authors.initials: E
authors.lastname: Castro
authors.forename: Severiano
authors.initials: S
authors.lastname: dos Anjos
authors.forename: Jesús
authors.initials: J
authors.lastname: Pascual-Brazo
authors.forename: Raquel
authors.initials: R
authors.lastname: Linge
authors.forename: Veronica
authors.initials: V
authors.lastname: Vargas
authors.forename: Helena
authors.initials: H
authors.lastname: Blanco
authors.forename: Beatriz
authors.initials: B
authors.lastname: Martínez-Villayandre
authors.forename: Ángel
authors.initials: Á
authors.lastname: Pazos
authors.forename: Elsa M
authors.initials: EM
authors.lastname: Valdizán
mesh_terms: D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D000928:Antidepressive Agents