NSCMAIN · Identification of signalling Pathways controlling adult neural stem cell maintenance
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2007-03-01 → 2009-02-28
- EU contribution
- €80,000
- Participants
- 1
- Scheme
- IRG
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Results in brief
Final Activity Report Summary - NSCMAIN (Identification of Signalling Pathways Controlling Adult Neural Stem Cell Maintenance)
The hippocampus is a brain region, which is essential for learning and memory formation. One of the most exciting discoveries of the past decade was the finding that new neurons are continuously generated in the hippocampus throughout adulthood and that this process -which is also termed hippocampal neurogenesis - is important for hippocampal function. The importance of hippocampal neurogenesis is illustrated by the fact that age-related memory dysfunction is paralleled by a strong decrease in the generation of new neurons. New neurons originate from neural stem cells. These neural stem cells are immature cells, which have the ability to self-renew and to generate new neural stem cells on the one hand and to differentiate into neurons on the other hand. To ensure that hippocampal neurogenesis persists throughout adulthood self-renewal and differentiation have to be balanced. The objective of this project was to identify signals that control this balance. We have found several signals that are involved in the differentiation of neural stem cells into neurons. Among these are the transcription factors CREB and Sox11. Loss of CREB-function results in the loss of survival and differentiation, while gain of Sox11-function was sufficient to enhance neuronal differentiation of neural stem cells. We also identified a signalling pathway that regulates neural stem cell maintenance. Loss of this signal resulted in the increased differentiation of neural stem cells and consequently to a depletion of the neural stem cell pool. It has been estimated that because of a greatly increased average life span, the percentage of individuals older than 65 years will almost double during the next 30 years from approximately 15 % to 25 %. The concomitant rise in the prevalence of age-related diseases such as impairment of cognitive function and dementia (the extreme form of cognitive impairment) poses an increasing challenge to society and public health, and demands the development of new treatment strategies for these currently intractable diseases. Given the mounting evidence for a link between adult hippocampal neurogenesis and cognitive function, these results may significantly contribute to the design of novel therapeutic approaches to age-related cognitive impairment and dementia.
Data: CORDIS, © European Union
Project objective
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.
Original text from CORDIS.
Participants
- GSF-NATIONAL RESEARCH CENTRE FOR ENVIRONMENT AND HEALTH, GMBH · NEUHERBERGCoordinatorCity levelGermany
Links
Data: CORDIS, © European Union