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BDNF expression in brain regions of Anorexia Nervosa mouse model, a biomarker of diagnostic and prognostic?
- N. Ramoz, J. Cao, C. Tezenas du Montcel, V. Tolle, P. Gorwood, O. Viltart
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S351-S352
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Introduction
Anorexia nervosa (AN) is a complex mental disorder mainly characterized by a voluntary food restriction and excessive physical activity resulting in dramatic weight loss. Changes in the brain-derived neurotropic factor (BDNF) have been reported in AN patients compared to controls. According to meta-analysis, functional variant rs6265 Val66Met of the BDNF gene has been found genetically associated to AN. We also reported an association of this functional variant and electrodermal response to images of thinness suggesting an association between rs6265 and a reward effect of weight loss in AN. In animal models, BDNF modulates negatively the central control of food intake and its injection in rodents induces weight loss and anorexia. Thus, besides its function on neuronal survival, synaptic plasticity and mood, BDNF was also reported to have a metabolic effect via both central nervous system and peripheral organs, which makes BDNF a good candidate for AN diagnosis biomarker.
ObjectivesOur study investigates the levels of expression of Bdnf, gene and protein, taking advantage of the mouse AN-like model by measuring Bdnf levels in specific brain areas and blood in food-restricted and refeed animals.
MethodsWe used a mouse AN-like model combining a phase of chronic food restriction (50%) during 15 days followed by an ad libitum refeeding period of one week. Female mice have or not access to a running with wheel to create a similar metabolic environment that those patients suffering from AN during restriction and recovery once hospitalised. The Bdnf mRNA and protein levels were measured in samples of blood and brain regions (prefrontal cortex, hippocampus, hypothalamus, dorsal striatum, nucleus Accumbens, ventral tegmental area and amygdala) using quantitative PCR and ELISA methods in the different groups of mice (ad libitum, ad libitum with wheel, food restriction and food restriction with wheel). Statistical analysis will compare the measures for different samples by one-way or two-way ANOVAs depending the group of animals or brain regions and blood.
ResultsTo date, no difference of the level of transcription for Bdnf was observed between the different groups of mice (ad libitum, ad libitum with wheel, food restriction and food restriction with wheel) in the prefrontal cortex, hippocampus and hypothalamus. We expect significant differences of Bdnf expression in the other brain regions of interest for the food restricted animals with or without the wheel compared to ad libitum animals. We expect also differences in the level of expression of Bdnf in fasted animals compared to the refeed animals.
ConclusionsThe BDNF could represent a potential biomarker of AN for the diagnostic and the prognosis in the evolution to the remission when weight recover and thus will allow a better understanding of the aetiology of AN. This study is supported by Fédération pour la Recherche sur le Cerveau.
Disclosure of InterestNone Declared
The role of dysregulated ghrelin/LEAP-2 balance in eating disorder: a translational study in anorexia nervosa
- C. Tezenas du Montcel, P. Duriez, J. Cao, N. Ramoz, O. Viltart, P. Gorwood, V. Tolle
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S103-S104
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Introduction
Anorexia nervosa (AN) is a complex psychiatric disorder characterized by a persistant decrease in food intake leading to dramatic weight loss and energy deficit. The ghrelin system is a key regulator of appetite and food intake across species. LEAP-2, a recently discovered ghrelin antagonist, appears to be up-regulated in obesity and opposes to the orexigenic drive of ghrelin. The evolution of LEAP-2 levels could be an interesting insight to reflect the regulation of appetite in eating disorders such as anorexia nervosa (AN).
ObjectivesWe tested this hypothesis and here provide the first study exploring the ghrelin and LEAP-2 regulation in long-term food restriction followed by refeeding in both mice and patients suffering from AN.
MethodsUsing a translational strategy, we compared the regulation of ghrelin and LEAP-2 concentrations in blood during food restriction and after refeeding i/ in female mice exposed to a 14 days protocol combining quantitative food restriction and running wheel activity followed by 10 days of progressive refeeding; ii/ in an ongoing longitudinal study of patients with AN evaluated before and after refeeding (n=30) as well as 6 months after hospital discharge to evaluate if the weight gain was stable (n=7) or unstable (n=10). Plasma concentrations of ghrelin and LEAP-2 were measured with selective immunoassays.
ResultsLong-term food restriction in mice was associated with increased ghrelin (p<0.001) and decreased LEAP-2 concentrations (p=0.006) compared to ad libitum fed controls. Refeeding led to a decrease in ghrelin (p<0.01) and increase in LEAP-2 concentrations (p<0.01). Patients with AN displayed increased ghrelin levels (p<0.01) but also higher LEAP-2 concentrations on admission than after refeeding (p=0.04). LEAP-2 decreased with refeeding. On 17 patients re-evaluated 6 months after discharge, patients with unstable weight gain exhibited a greater decrease of LEAP-2 concentrations during refeeding compared to patient with stable weight gain (p=0.02). Decreasing LEAP-2 concentrations was able to predict a negative outcome (i.e. unstable weight gain) in 80% of the cases.
ConclusionsWe provide evidence that the ghrelin/LEAP-2 system is not regulated according to the nutritional status in AN as it is in the case of a physiological adaptation to food restriction. Results from an ongoing longitudinal study exploring remission in AN suggest that the evolution of LEAP-2 concentrations during refeeding is opposed to data from preclinical model and could give new insights on the outcome of weight gain in AN.
Disclosure of InterestNone Declared
Contributors
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- By Ioannis P. Androulakis, Djillali Annane, Gérard Audibert, Lisa L. Barnes, Paolo Bartolomeo, Walter S. Bartynski, David A. Bennett, Nicolas Bruder, Nathan E. Brummel, Steve E. Calvano, Alain Cariou, F. Chretien, Jan Claassen, Colm Cunningham, Souhayl Dahmani, Robert Dantzer, Dimitry S. Davydow, Sanjay V. Desai, E. Wesley Ely, Frédéric Faugeras, Karen J. Ferguson, Brandon Foreman, Sadanand M. Gaikwad, Rebecca F. Gottesman, Maura A. Grega, Richard D. Griffiths, Marion Griton, Stefan D. Gurney, Hebah M. Hefzy, Michael T. Heneka, Dustin M. Hipp, Ramona O. Hopkins, Christopher G. Hughes, James C. Jackson, Christina Jones, Peter W. Kaplan, Keith W. Kelley, Raymond C. Koehler, Matthew A. Koenig, Jan Pieter Konsman, Felix Kork, John P. Kress, Stephen F. Lowry, Alawi Luetz, David Luis, Alasdair M. J. MacLullich, Guy M. McKhann, Jean Mantz, Panteleimon D. Mavroudis, Mervyn Maze, Bruno Mégarbane, Lionel Naccache, Dale M. Needham, Pratik P. Pandharipande, Jean-Francois Payen, V. Hugh Perry, Margaret Pisani, C. Rauturier, Benjamin Rohaut, Jennifer Ryan, Robert D. Sanders, Jeremy D. Scheff, Frederic Sedel, Ola A. Selnes, Tarek Sharshar, Martin Siegemund, Yoanna Skrobik, Jamie W. Sleigh, Romain Sonneville, Claudia D. Spies, Luzius A. Steiner, Robert D. Stevens, Raoul Sutter, Fabio Silvio Taccone, Richard E. Temes, Willem A. van Gool, Christel C. Vanbesien, F. Verdonk, Odile Viltart, Julia Wendon, Catherine N. Widmann, Robert S. Wilson
- Edited by Robert D. Stevens, Tarek Sharshar, E. Wesley Ely, Vanderbilt University, Tennessee
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- Book:
- Brain Disorders in Critical Illness
- Published online:
- 05 October 2013
- Print publication:
- 19 September 2013, pp viii-xii
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