Kaneko_2007_Nihon.Shinkei.Seishin.Yakurigaku.Zasshi_27_215

Production of new neurons in the subventricular zone (SVZ) and in the dentate gyrus (DG) continues into adulthood. In this paper, we will review our recent studies on migration and survival of new neurons in the adult mouse brain. Neuroblasts generated in the SVZ migrate in chains rostrally toward the olfactory bulb (OB), where they are differentiated into olfactory interneurons. The precise mechanisms controlling neuroblast migration remain unclear. We have recently demonstrated that neuroblast migration parallels cerebrospinal fluid flow caused by integrated beating of ependymal cilia. While SVZ neuroblasts migrate only toward the OB under physiological conditions, we found that they could reach striatum in a mouse model of focal ischemia. The majority of these newly-generated neurons die before they are integrated into the neuronal circuit, even under physiological conditions. We found that long-term administration of donepezil, an acetylcholinesterase inhibitor clinically used for the treatment of Alzheimer's disease, promotes the survival of newly-generated neurons in the OB and the DG. Although there are a lot of subjects to be elucidated, understanding the comprehensive mechanism of adult neurogenesis should be useful for developing successful regenerative therapies for neuropsychological diseases in the future.