Molecular and Cellular Mechanisms Regulating Quiescence and Division of Hippocampal Stem Cells

Abstract

Abstract—Neurogenesis in the dentate gyrus of the hippocampus occurs throughout the life of mammals, including humans. A common view is that integration of newborn neurons provides a high level of plasticity in the hippocampal neuronal network. This is important for cognitive brain function, memory formation, and emotions. Neurogenesis is supported by the pool of stem cells located in the subgranular zone of the dentate gyrus. These cells spend most of their life in a state of mitotic quiescence. During aging, the reservoir of stem cells gradually decreases due to division and irreversible differentiation into astrocytes. The kinetics of spending the pool of stem cells is determined by the balance between quiescence and division. The question on the molecular mechanisms regulating this balance is one of the key issues in the biology of brain stem cells. This is important not only in order to understand the fundamental principles of regulation of neurogenesis, but also in developing new strategies for using the internal reservoir of stem cells to ameliorate hippocampal plasticity deficit in various brain pathologies and aging. To date a lot of new and interesting data have been accumulated on multiple mechanisms involved in the regulation of stem cell quiescence and division. In this review, we overview current knowledge on the signal molecules and cellular receptors participating in the maintenance of the quiescent state of stem cells, the mechanisms of the shift from the quiescent state to proliferation at the level of gene transcription, and the roles of components of the stem cell niche, such as neuronal connections, macro- and microglia, and the extracellular matrix, in the regulation of the balance between quiescence and division of stem cells and in the maintenance and exhaustion of their pool.