Papel de las vías de señalización de mTOR y B-catenina como dianas moleculares para el desarrollo de antidepresivos de acción rápida

Abstract

Major depression is a disease of unknown cause, and the dysregulation of the proliferation/neuroplasticity in certain brain areas has been postulated, among others, as a mechanism associated with its etiopathogeny. As the main limitation of the current antidepressant drugs is their delayed effect, pathways involved in proliferation and plasticity present a great potential in the development of new therapeutic targets. The aim of this work is to study the role of Wnt/β-catenin and mTOR signalling pathways in depression. Here, we have eliminated or stabilized the activity of these pathways, in biologically relevant areas for the etiopathogeny of depression, as well as in the antidepressant effect. The removal of β-catenin or mTOR in hippocampus or infralimbic cortex, respectively, induced an anxious/depressive-like behaviour, and changes in neuroplasticity and the serotonergic system parallel to those associated to depression. On contrast, β-catenin stabilization promotes an antidepressant-like effect, and a pro-resilient phenotype.