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The role of the glucocorticoid receptor in dopaminoceptive neurons in mitochondrial dysfunction and vulnerability to depression

Objective

Depression is considered as a common mental illness worldwide affecting around 350 million people. Chronic stress is a major risk factor for its development. Interestingly, individuals can differ in the way of coping with chronic stress and are either prone (vulnerable) or resistant (resilient) to develop depression. High anxiety-trait is a vulnerability factor to develop stress-induced depression. Furthermore, it was also linked with mitochondrial dysfunction in the nucleus accumbens and in the establishment of social hierarchies in rodents. These observations suggest an important role of mitochondria in the vulnerability to develop stress-induced depression. The glucocorticoid receptor that is activated upon stress was recently shown to regulate mitochondrial function and gene transcription. Our own data show that expression of the glucocorticoid receptor is altered in animals with high anxiety-trait correlating with the expression of several mitochondrial genes. Thus, our central hypothesis is that vulnerability to develop depression is caused by a glucocorticoid receptor-mediated dysfunction of mitochondria in the nucleus accumbens. This project will address this idea in the mouse model showing considerable individual differences in stress-induced psychopathology-like behavior. We will first examine the role of the glucocorticoid receptor in vulnerability to stress-induced depression by performing comprehensive behavioral studies. We will then evaluate the impact of the glucocorticoid receptor on mitochondrial function and structure. Lastly, we will apply a pharmacological approach aiming to mitigate stress-induced depression caused by physiological changes given by the glucocorticoid receptor. This will lead to the understanding of the contribution of the glucocorticoid receptor in the nucleus accumbens to define vulnerability and resilience to develop stress-induced depression, and might lead to novel therapeutics for counteracting stress-induced depression.

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.

MSCA-IF-EF-ST - Standard EF

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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) H2020-MSCA-IF-2016

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Coordinator

ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
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.

€ 187 419,60
Address
BATIMENT CE 3316 STATION 1
1015 LAUSANNE
Switzerland

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Region
Schweiz/Suisse/Svizzera Région lémanique Vaud
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.

€ 187 419,60
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