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Development. 2018 Jan 8;145(1). pii: dev153544. doi: 10.1242/dev.153544.

Revealing age-related changes of adult hippocampal neurogenesis using mathematical models.

Author information

1
Institute of Applied Mathematics, Heidelberg University, Heidelberg 69120, Germany.
2
German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.
3
German Cancer Research Center (DKFZ), Heidelberg 69120, Germany a.martin-villalba@dkfz.de anna.marciniak@iwr.uni-heidelberg.de.
4
Institute of Applied Mathematics, Heidelberg University, Heidelberg 69120, Germany a.martin-villalba@dkfz.de anna.marciniak@iwr.uni-heidelberg.de.
5
Interdisciplinary Center of Scientific Computing (IWR) and BIOQUANT, Heidelberg University, Heidelberg 69120, Germany.

Abstract

New neurons are continuously generated in the dentate gyrus of the adult hippocampus. This continuous supply of newborn neurons is important to modulate cognitive functions. Yet the number of newborn neurons declines with age. Increasing Wnt activity upon loss of dickkopf 1 can counteract both the decline of newborn neurons and the age-related cognitive decline. However, the precise cellular changes underlying the age-related decline or its rescue are fundamentally not understood. The present study combines a mathematical model and experimental data to address features controlling neural stem cell (NSC) dynamics. We show that available experimental data fit a model in which quiescent NSCs may either become activated to divide or may undergo depletion events, such as astrocytic transformation and apoptosis. Additionally, we demonstrate that old NSCs remain quiescent longer and have a higher probability of becoming re-activated than depleted. Finally, our model explains that high NSC-Wnt activity leads to longer time in quiescence while enhancing the probability of activation. Altogether, our study shows that modulation of the quiescent state is crucial to regulate the pool of stem cells throughout the life of an animal.

KEYWORDS:

Adult hippocampal neurogenesis; Aging; Mathematical model; Stem cells

PMID:
29229768
PMCID:
PMC5825879
DOI:
10.1242/dev.153544
[Indexed for MEDLINE]
Free PMC Article

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