Neural stem cells persist throughout life in specific regions of the brain of most mammals. In the hippocampus, these adult neural stem cells (NSCs) generate new neurons that integrate into the existing neuronal network and play important roles in memory and mood regulation. The number of new neurons generated in the hippocampus sharply declines with age and is influenced by a variety of systemic stimuli such as diet, stress or exercise. The key regulatory step of adult neurogenesis is the recruitment of normally quiescent neural stem cells to enter the cell cycle. However, very little is known about how age or systemic signals influence the transition from quiescence to activation of neural stem cells.

This is a complex question to answer, given that ageing alters both neural stem cells and systemic signals, meaning that the effects of systemic stimuli on neurogenesis change over time.

At the Urban group at the Institute of Molecular Biotechnology, we are interested in understanding how age modulates the response of NSCs to defined systemic stimuli. We are currently exploring the effects of different types of diets on neurogenesis and, in particular focus on the transition of adult NSCs from quiescence to activation. We use transgenic mouse models in combination with dietary interventions and tailored label retention experiments to determine the response of adult neural stem cells to diet-induced systemic cues.

Working together with the Tessmar, Edenhofer and Hippenmeyer groups, we aim to identify temporal changes in the responsivity of neural stem cells to diet-induced external cues. We are setting up a new lineage tracing method that will allow us to monitor the behavior of NSCs through different developmental times and ageing. We will generate a model of human neural stem cell quiescence with which we can explore how age-related information is maintained in cultured cells from different temporal points, including in human neural stem cells. To facilitate our work, we will employ new tools and techniques, from within the SFB F78 “Neuro Stem Modulation” consortium such as tissue clearing, single cell RNA sequencing or complex sequencing analyses that were developed by the Tanaka and von Haeseler groups.

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