Serotonergic mediation of the brain-wide neurogenesis: Region-dependent and receptor-type specific roles on neurogenic cellular transformation

Abstract

Brain serotonin (5-hydroxytryptamine, 5-HT) is a key molecule for the mediation of depression-related brain states, but the neural mechanisms underlying 5-HT mediation need further investigation. A possible mechanism of the therapeutic antidepressant effects is neurogenic cell production, as stimulated by 5-HT signaling. Neurogenesis, the proliferation of neural stem cells (NSCs), and cell differentiation and maturation occur across brain regions, particularly the hippocampal dentate gyrus and the subventricular zone, throughout one's lifespan. 5-HT plays a major role in the mediation of neurogenic processes, which in turn leads to the therapeutic effect on depression-related states. In this review article, we aim to identify how the neuronal 5-HT system mediates the process of neurogenesis, including cell proliferation, cell-type differentiation and maturation. First, we will provide an overview of the neurogenic cell transformation that occurs in brain regions containing or lacking NSCs. Second, we will review brain region-specific mechanisms of 5-HT-mediated neurogenesis by comparing regions localized to NSCs, i.e., the hippocampus and subventricular zone, with those not containing NSCs. Highlighting these 5-HT mechanisms that mediate neurogenic cell production processes in a brain-region-specific manner would provide unique insights into the role of 5-HT in neurogenesis and its associated effects on depression.