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Exploration and promotion of neurogenesis in the adult brain

Objective

It is now well established that new neurons are added to certain regions of the adult brain. There is today considerable interest in the development of regenerative therapies based on modulating endogenous neurogenesis, but it is necessary to better understand these events to assess whether this is rational and realistic.
This application takes its initiation in two recent discoveries that we have made: that astrocytes in the mouse striatum give rise to new neurons after stroke or inhibition of Notch signaling (Magnusson et al., Science, 2014) and that neurogenesis is a continuous process in the human striatum throughout adulthood (Ernst et al., Cell, 2014). We propose to characterize the molecular regulation of neurogenesis from striatal astrocytes in detail, and compare these astrocytes with those in other regions to understand why striatal astrocytes are uniquely neurogenic and whether astrocytes in other parts of the brain can be induced to give rise to new neurons. We will, moreover, assess the role of integration of new neurons in the striatal circuitry by inducing neurogenesis in the striatum in adult mice by blocking Notch signaling or by inducing stroke and modulate the activity of the new neurons by optogenetics and chemogenetics. We will, furthermore, study whether striatal neurogenesis is altered in human neurological diseases by retrospective birth dating by measuring the integration of 14C from nuclear bomb tests. We will assess whether inducing striatal neurogenesis in corresponding mouse models of neurological diseases has therapeutic potential.
This project will elucidate the molecular regulation of neurogenesis from astrocytes and the neurogenic potential of astrocytes in different parts of the brain, reveal the role of new neurons in the striatum, answer whether striatal neurogenesis is altered in common neurological conditions in humans and reveal whether inducing striatal neurogenesis may have therapeutic potential.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

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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.

ERC-ADG - Advanced Grant

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Call for proposal

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

(opens in new window) ERC-2015-AdG

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Host institution

KAROLINSKA INSTITUTET
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 2 500 000,00
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.

€ 2 500 000,00

Beneficiaries (1)

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