Neural Stem Cells in Development and Aging

Abstract

Neural stem cells (NSCs) are most abundant during embryonic and early postnatal development but persist into adulthood. There is evidence that adult neurogenesis contributes to the maintenance of learning and memory in the adult brain. NSC maintenance and adult neurogenesis decline during aging in various species. Some molecular mechanisms have been delineated that can lead to a defect in NSC quiescence and accelerated NSC depletion during aging in mouse models, e.g. p21 deletion. However, the natural causes of NSC depletion during aging remain to be defined. The understanding of molecular mechanisms that regulate quiescence, self-renewal, asymmetric division, and differentiation of NSCs during embryogenesis and in the adult brain could provide a rational basis to understand how these processes may influence brain aging. Some potentially relevant mechanisms were discussed during the 3rd Else Kröner-Fresenius Symposium on Stem Cell Aging including: (i) the regulation of ‘Inscuteable’ – an evolutionarily conserved protein, which is asymmetrically distributed to daughter cells and essential for correct orientation of the mitotic spindle of dividing NSCs, and (ii) the regulation of the transcription factors Pax6 and FoxO3 influencing NSC maintenance and aging.