[Neuronal migration in the adult brain].
Production of new neurons in the subventricular zone (SVZ) continues into adulthood. Neuroblasts generated in the SVZ migrate in chains rostrally toward the olfactory bulb (OB), where they are differentiated into olfactory interneurons. In this paper, we will review our recent studies on production, migration and survival of newly-generated neurons in the adult mouse brain. Although the precise mechanisms controlling the migration of neuroblasts remain unclear, some molecules related to cell adhesion, cytoskeletal regulation or attractive/repulsive cues have been shown to be involved in this process. 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 using blood vessels as their scaffold. The majority of the newly-generated neurons are known to die before they are integrated into neuronal circuits. However, we found that their survival could be promoted by the long-term administration of donepezil, an acetylcholinesterase inhibitor that is widely used for the treatment of Alzheimer's disease. Understanding more precise and comprehensive mechanisms of adult neurogenesis should lead to future development of regenerative therapies for neuropsychiatric diseases.
Department of Developmental and Regenerative Biology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601 Japan.
Naoko
N
Kaneko
Kazunobu
K
Sawamoto
D053687:Adult Stem Cells / Q000166:cytology* / Q000502:physiology*; D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D002465:Cell Movement; D002470:Cell Survival / Q000187:drug effects; D002552:Cerebral Ventricles / Q000166:cytology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000077265:Donepezil; D015195:Drug Design; D006801:Humans; D007189:Indans / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D009416:Nerve Regeneration / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000502:physiology*; D009830:Olfactory Bulb / Q000166:cytology; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use
D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil