Molecular Regulation of Adult Neurogenesis
During my graduate studies with Dr. Ana Martin-Villalba, I characterized adult hippocampal neurogenesis in transgenic mouse models. I used molecular and cell biological methods to analyze neural stem cells in vitro and in vivo. We showed that the apoptosis-inducing receptor CD95 can also signal cell survival in neural stem cells (Corsini et al., 2009). In conditional CD95 mutants, neuronal differentiation was severely reduced in vivo and led to a deficit in working memory. I also investigated the effects of increased Wnt signalling on neurogenesis by blocking its antagonist Dkk1 in neural stem cells (Seib et al., 2013). This increased self-renewal of stem cells, dendritic complexity in new neurons, and hippocampal activity. Behaviourally, depressive behaviour was reduced and memory performance was increased due to increased Wnt signalling in stem cells. Findings in this study showed that blocking Dkk1 counteracts an age-related decrease in neurogenesis and ageing-associated cognitive decline. Dkk1 is expressed in the ageing brain and is a hot topic in Alzheimer’s Disease.
