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Assessing cellular compartmentation of brain lactate using diffusion MR spectroscopy in vivo

Project description

Lactate distribution in the brain

Lactate is an important metabolite in the human body, and deregulation of its metabolism has been associated with neurodegenerative disorders. The EU-funded LactaDiff project aims at using new in vivo magnetic resonance methods to investigate how lactate distributes between neurons and astrocytes to meet neuronal energy needs. Scientists will quantify lactate in brain neurons and astrocytes initially in rodent models and subsequently in humans using a clinical MRI system. Collectively, the project's results will provide unprecedented knowledge on how lactate distribution changes during brain activity, plasticity and in Alzheimer's disease.

Objective

The idea has emerged that compartmentation of brain lactate, i.e. its distribution between different cell types and the extracellular space, plays a critical role in neurotransmission and brain plasticity. Dysregulations of lactate metabolism have also been reported in neurodegenerative diseases such as Alzheimer's disease. However, these notions remain challenged, and even fundamental mechanisms such as the astrocyte-to-neuron lactate shuttle, whereby astrocytes are supposed to export lactate to neurons to sustain neuronal energy needs, are still fiercely debated. This is largely due the lack of tools to evaluate cell-specific compartmentation of lactate in the living brain, in particular in Humans.
In this project, we will develop new nuclear magnetic resonance spectroscopy techniques to non-invasively measure lactate diffusion, including in cortical regions. We will then take advantage of the unique ability of these methods to differentiate between metabolites diffusing in different environments, based on diffusion properties imposed by the microstructure, to quantify lactate in the extracellular space and, most importantly, in neurons and astrocytes. After validation in rodent models, these methods will be transposed on a clinical MRI system at ultra-high magnetic field, to gain unprecedented access to lactate compartmentation in the Human brain and its modifications during brain activity, plasticity, and in Alzheimer's disease. This will open a new research field for magnetic resonance spectroscopy in vivo.

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Topic(s)

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ERC-COG - Consolidator Grant

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Call for proposal

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(opens in new window) ERC-2018-COG

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Host institution

COMMISSARIAT A L ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES
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.

€ 1 999 868,00
Address
RUE LEBLANC 25
75015 Paris
France

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Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
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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.

€ 1 999 868,00

Beneficiaries (1)

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