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MitoDyaD

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

Total Cost €

EC-Contrib. €

Partnership

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Outcomes and
results

MitoDyaD project word cloud

Explore the words cloud of the MitoDyaD project. It provides you a very rough idea of what is the project "MitoDyaD" about.

resilient rodents data transcription differ showing resilience function individuals establishment contribution receptor glucocorticoid mental individual million model caused psychopathology 350 central chronic dysfunction people expression shown stress differences mediated physiological resistant mitochondria nucleus anxiety illness genes mitochondrial vulnerable idea activated accumbens behavior lastly prone observations mouse social linked pharmacological worldwide coping examine altered considerable gene counteracting depression hypothesis mitigate either structure behavioral animals hierarchies interestingly vulnerability trait correlating regulate performing suggest first risk therapeutics

Project "MitoDyaD" data sheet

The following table provides information about the project.

Coordinator	ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE Organization address address: BATIMENT CE 3316 STATION 1 city: LAUSANNE postcode: 1015 website: www.epfl.ch contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.
Coordinator Country	Switzerland [CH]
Total cost	187˙419 €
EC max contribution	187˙419 € (100%)
Programme	1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
Code Call	H2020-MSCA-IF-2016
Funding Scheme	MSCA-IF-EF-ST
Starting year	2017
Duration (year-month-day)	from 2017-05-01 to 2019-04-30

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE Organization address address: BATIMENT CE 3316 STATION 1 city: LAUSANNE postcode: 1015 website: www.epfl.ch contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	CH (LAUSANNE)	coordinator	187˙419.00

Map

Project 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.

Publications

List of publications.
year	authors and title	journal	last update
2018	Meltem Weger, Carmen Sandi High anxiety trait: A vulnerable phenotype for stress-induced depression published pages: 27-37, ISSN: 0149-7634, DOI: 10.1016/j.neubiorev.2018.01.012	Neuroscience & Biobehavioral Reviews 87	2019-09-25

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