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Revealing Age-Related Changes of Adult Hippocampal Neurogenesis

View ORCID ProfileFrederik Ziebell, Sascha Dehler, View ORCID ProfileAna Martin-Villalba, Marciniak-Czochra Anna
doi: https://doi.org/10.1101/112128
Frederik Ziebell
1Institute of Applied Mathematics, University of Heidelberg
2German Cancer Research Center (DKFZ), Heidelberg
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Sascha Dehler
2German Cancer Research Center (DKFZ), Heidelberg
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Ana Martin-Villalba
2German Cancer Research Center (DKFZ), Heidelberg
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Marciniak-Czochra Anna
1Institute of Applied Mathematics, University of Heidelberg
3Interdisciplinary Center of Scientific Computing (IWR) and BIOQUANT, University of Heidelberg
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Abstract

In the adult hippocampus, neural stem cells (NSCs) continuously produce new neurons that integrate into the neuronal network to modulate learning and memory. The amount and quality of newly generated neurons decline with age, which can be counteracted by increasing intrinsic Wnt activity in NSCs. However, the precise cellular changes underlying this age-related decline or its rescue through Wnt remain unclear. The present study combines development of a mathematical model and experimental data to address features controlling stem cell dynamics. We show that available experimental data fit a model in which quiescent NSCs can either become activated to divide or undergo depletion events, consisting of astrocytic transformation and apoptosis. Additionally, we demonstrate that aged NSCs remain longer in quiescence and have a higher probability to become re-activated versus being depleted. Finally, our model explains that high NSC-Wnt activity leads to longer time in quiescence while augmenting the probability of activation.

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Posted February 27, 2017.
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Revealing Age-Related Changes of Adult Hippocampal Neurogenesis
Frederik Ziebell, Sascha Dehler, Ana Martin-Villalba, Marciniak-Czochra Anna
bioRxiv 112128; doi: https://doi.org/10.1101/112128
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Revealing Age-Related Changes of Adult Hippocampal Neurogenesis
Frederik Ziebell, Sascha Dehler, Ana Martin-Villalba, Marciniak-Czochra Anna
bioRxiv 112128; doi: https://doi.org/10.1101/112128

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