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.

Towards a multi protein and mRNA expression of biological predictive and distinguish model for post stroke depression

“…Consistent evidence from biochemical studies in depressed patients reported alterations in peripheral levels of the neurotrophic factors of cell survival and plasticity [28, 29]. In this work, we found that VEGF transcriptional level, IGF-1R serum concentration, both the protein and mRNA level of VEGFR2, PIGF, IGF-1 have significant differences among different diseases.…”

Relationship Between Hippocampal Volume, Serum BDNF, and Depression Severity Following Electroconvulsive Therapy in Late-Life Depression

“…Although major depression is not generally considered to be a hippocampal disorder, both biochemical and structural abnormalities of the hippocampus are frequently associated with the illness (Pilar-Cuellar et al, 2013). Moreover, the hippocampus and brain regions that mediate emotional and cognitive regulation are anatomically connected, lending support to the role of the hippocampus in depressionrelated circuitry (Price and Drevets, 2010;Abbott et al, 2014).…”

The persisting effects of electroconvulsive stimulation on the hippocampal proteome

“…Like antidepressant pharmacotherapies, we found that ECS primarily induced changes in proteins with cytoskeletal and metabolic related functions (Guest et al, 2004;Marais et al, 2009), suggesting a role for proteins involved in synaptic plasticity, amongst others, as common to antidepressant efficacy (Fuchs et al, 2004;Khawaja et al, 2004;Pilar-Cuellar et al, 2013;Piubelli et al, 2011aPiubelli et al, , 2011bPiubelli et al, , 2011cPiubelli et al, , 2011d. Gene ontology analysis of acute, chronic and chronic þ4 weeks ECS-altered proteins showed that the cellular components of the identified proteins were mainly those with roles in the cytoskeleton, axon and in cell and neuron projection.…”