The extracellular signal-regulated kinase pathway may play an important role in mediating antidepressant-stimulated hippocampus neurogenesis in depression

Abstract

Understanding the reasons for the delayed action of antidepressants in patients with depression is an important step in the effort to understand the etiology and course of this disabling condition. Researches using animal models of depression find that depression is associated with impaired neurogenesis and structural plasticity in specific regions of the brain. Chronic treatment with antidepressants increases neurogenesis and reduces animal behaviors that are associated with depression. Other studies suggests that neurogenesis is an important component of the mechanism of action of both antidepressants and mood stabilizers. Moreover, the time course of increased neurogenesis is parallel to that of the behavioral effects, and animals with higher baseline hippocampus neurogenesis have a more rapid response to antidepressants. However, the molecular mechanisms that link antidepressants, neurogenesis and behavioral changes remain unknown. Previous research has shown that the extracellular signal-regulated kinase (ERK) signaling pathway plays an important role in regulating neurogenesis and synaptic plasticity in the brain and is activated by antidepressants and mood stabilizers. We hypothesize that the ERK pathway is the mechanism by which antidepressants regulate neurogenesis in the hippocampus and, thus, should be considered a potential target for the development of new antidepressants.