23 Hippocampal Neurogenesis: Depression and Antidepressant Responses

Abstract

Basic research and clinical studies have provided evidence that stress and depression can result in structural alterations in limbic brain regions implicated in mood disorders, including atrophy and loss of neurons and glia. These studies also demonstrate that antidepressant (AD) treatments block or reverse these effects. Several mechanisms contribute to the structural alterations and loss of cells in response to stress and depression, but one of intense interest is the involvement of neurogenesis in the adult hippocampal formation. Basic research studies consistently demonstrate that stress and AD treatment exert opposing actions on neurogenesis in the hippocampal dentate gyrus (DG). The study of adult hippocampal neurogenesis has revealed it to be a robust phenomenon that is capable of conferring previously unrecognized forms of plasticity to the DG. The progression from neuronal stem cell to mature dentate granule neuron can be divided into discrete stages, each of which is defined by distinct physiological and morphological properties (Esposito et al. 2005; Song et al. 2005) and is influenced by a plethora of factors comprising growth factors, neurotrophins, and chemokines (Lledo et al. 2006). These factors act in concert with network activity to regulate the balance between proliferation, differentiation, and survival of neuronal stem cells in vivo. It is through this general mechanism that levels of adult hippocampal neurogenesis change in response to aversive and enriching experiences, such as stress and learning, respectively, and the physiological state of the organism. Recent studies relying on experimental approaches that ablate adult hippocampal neurogenesis in rodents have...