The adult hippocampus plays a central role in learning and memory. Hippocampal dysfunction is a main cause of cognitive impairment during aging and in Alzheimer's disease. There is increasing evidence that the generation of new neurons (neurogenesis) from neural stem cells (NSCs) in the adult hippocampus significantly contributes to hippocampal function. Indeed, progressive loss of NSCs in the aging hippocampus due to incomplete maintenance of the NSC population and the resulting decrease in neurogenesis are associated with a decline in cognitive function.
The aim of this project is to identify the extrinsic signals that control the maintenance and self-renewal of NSCs through the regulation of the transcription factor Sox2. The rationale for this approach is the fact that Sox2 expression is essential for maintenance and self-renewal of adult hippocampal NSCs. Experimentally candidate signals will be identified by a combination of in silico, in vitro, and in vivo experiments. Functional studies in vitro and in vivo will test the involvement of the candidates in the control of Sox2 expression. These studies will not only promote our basic understanding of the signalling networks underlying NSC maintenance in the hippocampus but may also significantly contribute to the design of novel therapies for cognitive impairment and dementia given the link between hippocampal neurogenesis and cognitive function.
In this regard, the proposal displays significant overlap with the priority of the FP6 to combat chronic diseases and will substantially strengthen European research activities in this area. The project will also allow the re-integration of the applicant, who has received outstanding postdoctoral training in NSC-biology in a third country (USA), and will enable the transfer of his scientific knowledge into the European Research Area as well as the development of lasting co-operations between the German host institute and a leading research institute in the USA.
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