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Content archived on 2024-06-18

Mechanisms of stem cell proliferation and senescence in the aged and damaged mouse brain

Objective

Stem cell self-renewal is a consequence of the ability to proliferate indefinitely while maintaining pluripotency. In the adult brain, neural stem cells continuously produce neurons, and its importance for memory and repair after neurodegeneration and brain damage has been extensively investigated. However, adult neurogenesis is limited and significantly decreases throughout life. With aging, increased senescence greatly restrains the neurogenic potential of aged stem cells. Senescence induction is critically controlled by the INK4a/Arf locus, but the mechanisms of senescence induction are largely unknown. It is essential to understand the mechanisms involved in the control of stem cell proliferation and senescence for the development of stem cell-based therapies. The host laboratory identified that embryonic and peripheral neural stem cell proliferation is regulated by a novel mechanism that involves S-phase cell cycle arrest, GABA signaling and the histone variant H2AX (Andäng et al Nature 2008). This proposal aims to investigate whether GABAAR and H2AX-mediated modulation of stem cell proliferation is a factor in age-related decline in neurogenesis, and if this pathway could be modulated towards boosting neurogenesis following neurodegeneration or damage. H2AX is also involved in senescence, being activated following telomere erosion. We propose to investigate the mechanisms of senescence induction and the interaction between critical regulators of cell cycle. This will provide new information on the conserved and unique pathways involved in the control of stem cell proliferation and senescence. The investigation of the mechanisms involved in age-related neurogenic decline and how neurogenesis can be boosted may open the way for new clinically relevant strategies increasing self-repair following brain damage and neurodegeneration.

Fields of science (EuroSciVoc)

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Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

FP7-PEOPLE-2010-IEF
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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

MC-IEF - Intra-European Fellowships (IEF)

Coordinator

KAROLINSKA INSTITUTET
EU contribution
€ 195 766,40
Address
NOBELS VAG 5
171 77 STOCKHOLM
Sweden

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Region
Östra Sverige Stockholm Stockholms län
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

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