NSC maintenance in the adult murine brain is an intricate mechanism highly dependent on the proper internal and external mechanisms. In long-chase experiments the NSCs were then reactivated by either the resulting induced changes from the amplifying progenitors or a delay in NSC response. It was the amplifying progenitor pool that responded. On the other hand, administration of antidepressants left the NSCs unaffected initially. These quiescent NSCs have the capacity to replenish the active NSC pool upon induction of epileptic seizures. In the geriatric SGZ active NSCs were lost and the NSCs that remained were quiescent. In order to address this question we characterized the SGZ in great detail at different ages. The differential signal requirement for the maintenance of quiescent and active NSCs raises the question, whether these distinct cell populations might have unique functions in response to external physiological and/or pathological stimuli. The loss of Notch2 led to the activation of quiescent NSCs and an increased production of neuroblasts. We addressed NSC identity also in the second neurogenic niche, the SGZ, where the receptors are also coexpressed by NSCs. In the SVZ the receptors Notch1 and Notch2 are coexpressed on NSCs. Thus an intricate interplay between Notch1 and Notch2 is needed for adult NSC maintenance in both neurogenic niches. ( 1999 ) Subventricular zone astrocytes are neural stem cells in the adult. In both the human and the rodent brain, the primary progenitor of adult SVZ is a subpopulation of astrocytes that have stem-cell-like features. If Notch1 was deleted in addition to Notch2, quiescent and active NSCs are no longer maintained properly and will differentiate to a neural fate. 17 Doetsch F, Caille I, Lim DA, Garcia - Verdugo JM, Alvarez - Buylla A. Adult neurogenesis is primary confined to the subventricular zone (SVZ) of the forebrain and the subgranular zone of the dentate gyrus within the hippocampus. The loss of this Notch paralogue led to the activation of quiescent NSCS and a prolonged and abnormal activation, followed by NSCs exhaustion in the long term.
I was able to show that in the adult mouse brain, Notch2 is the gatekeeper of quiescent NSCs in both neurogenic niches, the SVZ and the SGZ. (3) What are the capacities of distinct subtypes of NSCs and progenitors to respond to external stimuli? (2) Do NSCs have similar maintenance factors in the SVZ and the SGZ? (1) What are the differences between active and quiescent NSCs? Over the course of my PhD studies I addressed three major questions of adult NSC maintenance. Over the last three decades the field of neurogenesis has expanded, but there are still open questions with regards to adult NSC maintenance and potential capacity. These cells can either be found in a dormant, non-dividing state (quiescent) or in a proliferating state (active). At the base of adult neurogenesis lie adult neural stem cells (NSCs). Adult neurogenesis continues throughout life in the subventricular zone (SVZ) and the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG) of mammals.
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