ABSTRACT

In mammals, it had been believed that neurogenesis did not continue in the adult brain. However, recent studies have overturned that theory and have shown that a supply of new neurons is continued even into adulthood in two distinct regions of the brain: the subventricular zone of lateral ventricles (SVZ) and the dentate gyrus of the hippocampus. Neural stem cells are defi ned as cells having the capacity to self-renew and to diff erentiate into neurons, astrocytes and oligodendrocytes, and are considered to exist in the SVZ, although the prospective isolation of NSCs has not been achieved because of the lack of NSC-specifi c markers. It has been reported that the diff erentiation capacity of the NSCs in the SVZ is skewed only towards neurons (but not towards astrocytes and oligodendrocytes) in the adult brain, whereas there is a report showing that oligodendrocytes are also generated from these NSCs (Menn et al. 2006). Th e NSC-niche in the SVZ is composed of several types of cells (Fig. 2): slow-proliferating/glial fi brillary acidic protein (GFAP)-positive astrocytes (considered as NSCs), rapidly proliferating/transientamplifying precursors (derived from the NSCs), neuronal progenitors migrating towards the olfactory bulb (immature neurons) and ependymal cells lining the lateral ventricles. Th e ependymal cells are epithelial cells and come into close contact with the NSCs expressing Notch and integrin β1 (CD29). Th e ependymal cells are therefore regarded as niche cells. Campos et al. (2006) reported that integrin β1 aff ected the Notch signaling pathway through its interaction with the Notch intracellular domain. In the dentate gyrus of the hippocampus, GFAP-positive neuron precursors can be found and these cells are considered to have a limited self-renewal and diff erentiation capacity. Recent studies have shown that neuronal progenitors migrating towards the olfactory bulb (immature neurons) express integrin β1 and polysiaric acid-binding NCAM (PSA-NCAM), and that these adhesion molecules contribute to their smooth migration in the restral migratory stream (Cazal et al. 2000, Belvindrah et al. 2007). Th us, adhesion molecules contribute greatly to both the generation of neurons and the migration of the immature neurons towards the olfactory bulb.