Adan lab

Neural circuits underlying eating disorders

My team’s main focus is on identifying and targeting the neural circuits that underlie eating disorders. We use human genetics and scRNAseq data to identify cells that are underlying the processes that contribute to development of eating disorders. Viral vector tracers, optogenetics and electrophysiology are used to map neural circuits, calcium imaging (fiber photometry) is used to assess neuronal activity in awake animals and chemogenetics and pharmacology is used to unravel how specific neural circuits are implicated in regulating behaviors associated with eating disorders such as food reward seeking, feeding and hyperlocomotion.

Confocal images from a VTA section of dopaminergic neurons (green) and Leptin receptor expressing neurons (red)

The modulatory effect of leptin on the mesolimbic DA system
 

Prof. dr. Roger Adan

My main position is in the department of Translational Neuroscience, UMC Utrecht Brain Center. I am also a scientific advisor at Rintveld Eating disorder clinic, Altrecht, Zeist, guest professor at the department of Neuroscience and Physiology of Sahlgrenska Academy of the University of Gothenburg, and expert at EFSA’s working group “Added Sugars”.
My research focus is on deconstructing the mechanisms underlying eating behaviour, since this is a natural behaviour ideally suited to dissecting the neural circuits that underlie decision-making, anxiety, impulsivity and reward seeking. I am devoted to unravel mechanisms underlying eating disorders. Besides understanding what circuits underlie obesity, the main topic is to unravel the neurocircuitry that underlies Anorexia Nervosa.

 

Group members

Bart Lodder – PhD student supervised by Prof. Bernardo Sabatini, located at Harvard Medical school
My research aims to understand the heterogeneity of dopamine signaling in the nucleus accumbens and dorsal striatum, through development and implementation of novel optical methods like tapered photometry and Fluorescent lifetime photometry.

Dopamine, Nucleus accumbens, Dorsal striatum, Tapered photometry, Fluorescent lifetime photometry
Eileen Brouwer – PhD student
My research project aims to unravel neuronal alterations in Anorexia Nervosa using the activity-based anorexia mouse model.

Activity-based anorexia model, immunocytochemistry, scRNAseq
Fabien Ducrocq – Postdoc
My research aim at identifying neuronal populations that drive symptoms such as decreased feeding and hyperactivity linked to the development of Anorexia Nervosa in a laboratory mouse model.

Slice electrophysiology, Anorexia Nervosa mouse model, Reward processing

Iris Stoltenborg – PhD student
I’m conducting my research at Gothenburg University in Sweden, where Roger A. H. Adan is a guest professor. The aim of my research project in the lab of Suzanne Dickson (under the supervision of Roger) is to target and further unravel which neurons and pathways are engaged by orexigenic stimuli such as the hunger hormone ghrelin and food cues.

Transgenic mouse models, RNAscope, DREADDs
I.G. Wolterink-Donselaar
Research-technician for practical assistance of PhD-students and Postdocs in their scientific careers.

Karlijn Kooij – PhD candidate
My research aim is to unravel how the gut-brain axis – influences reward processing. I mainly focus on gut hormones and the (anorectic) microbiome. Additionally, I investigate whether a pharmacological intervention improves the outcome in an animal model for anorexia nervosa.

Fiber photometry, gut-brain axis, microbiome transplantation, anorexia rodent model

Mieneke Luijendijk – animal facility manager
My main task is that the work in the animal facility can continue. Important tasks are the laboratory animal administration, annual reporting to the IvD/NVWA on the number of animals used, supervising compliance with the rules, animal welfare, training of animal workers on new techniques and managing animal care and support staff. In addition, I support researchers in performing operations on rats and/or mice and conducting experiments.

Stereotactic surgery, Behavioral tasks, Anorexia Nervosa mouse model all in rats and mice

MoPriya Somai – master intern
The aim of the internship project is to investigate Conditioned Taste Aversion (CTA) in an Anorexia Based Activity mouse model. Snapshots of the neuronal activity in the brain of the mice, by fluorescently labeling the neurons activated during the CTA, will be analyzed.

Nick Papavoine – PhD candidate
My research focus is to unravel the effects of leptin on hyperactivity observed in Anorexia Nervosa. Therefore, I am aiming to identify the neuronal populations mediating leptins effect in observed hyperactivity in the Activity-based Anorexia mode

Fiber photometry, Activity-based anorexia model, pharmacological manipulations

 

Recent papers

  1. EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA), Turck D, Bohn T, Castenmiller J, de Henauw S, Hirsch-Ernst KI, Knutsen HK, Maciuk A, Mangelsdorf I, McArdle HJ, Naska A, Peláez C, Pentieva K, Siani A, Thies F, Tsabouri S, Adan R, Emmett P, Galli C, Kersting M, Moynihan P, Tappy L, Ciccolallo L, de Sesmaisons-Lecarré A, Fabiani L, Horvath Z, Martino L, Muñoz Guajardo I, Valtueña Martínez S, Vinceti M. Tolerable upper intake level for dietary sugars. EFSA J. 2022 Feb 28;20(2):e07074. doi: 10.2903/j.efsa.2022.7074. PMID: 35251356; PMCID: PMC8884083.
  2. Stoltenborg I, Peris-Sampedro F, Schéle E, Le May MV, Adan RAH, Dickson SL. TRAPing Ghrelin-Activated Circuits: A Novel Tool to Identify, Target and Control Hormone-Responsive Populations in TRAP2 Mice. Int J Mol Sci. 2022 Jan 5;23(1):559. doi: 10.3390/ijms23010559. PMID: 35008985; PMCID: PMC8745172.
  3. Omrani A, de Vrind VAJ, Lodder B, Stoltenborg I, Kooij K, Wolterink-Donselaar IG, Luijendijk-Berg MCM, Garner KM, Van’t Sant LJ, Rozeboom A, Dickson SL, Meye FJ, Adan RAH. Identification of Novel Neurocircuitry Through Which Leptin Targets Multiple Inputs to the Dopamine System to Reduce Food Reward Seeking. Biol Psychiatry. 2021 Feb 23:S0006-3223(21)00121-9. doi: 10.1016/j.biopsych.2021.02.017. Epub ahead of print. PMID: 33867112.
  4. Flores-Dourojeanni JP, van Rijt C, Vanden Munkhof MH, Boekhoudt L, Luijendijk MCM, Vanderschuren LJMJ, Adan RAH. Temporally specific roles of ventral tegmental area projections to the nucleus accumbens and prefrontal cortex in attention and impulse control. J Neurosci. 2021 Apr 7:JN-RM-0477-20. doi: 10.1523/JNEUROSCI.0477-20.2020. Epub ahead of print. PMID: 33837050.
  5. Yeo GSH, Chao DHM, Siegert AM, Koerperich ZM, Ericson MD, Simonds SE, Larson CM, Luquet S, Clarke I, Sharma S, Clément K, Cowley MA, Haskell-Luevano C, Van Der Ploeg L, Adan RAH. The melanocortin pathway and energy homeostasis: From discovery to obesity therapy. Mol Metab. 2021 Mar 6;48:101206. doi: 10.1016/j.molmet.2021.101206. Epub ahead of print. PMID: 33684608.
  6. Adan RAH, van der Beek EM, Buitelaar JK, Cryan JF, Hebebrand J, Higgs S, Schellekens H, Dickson SL. Nutritional psychiatry: Towards improving mental health by what you eat. Eur Neuropsychopharmacol. 2019 Dec;29(12):1321-1332. doi: 10.1016/j.euroneuro.2019.10.011. Epub 2019 Nov 14. PMID: 31735529.
  7. Watson HJ, Yilmaz Z, Thornton LM, Hübel C, Coleman JRI, Gaspar HA, Bryois J, Hinney A, Leppä VM, Mattheisen M, Medland SE, Ripke S, Yao S, Giusti-Rodríguez P; Anorexia Nervosa Genetics Initiative, Hanscombe KB, Purves KL; Eating Disorders Working Group of the Psychiatric Genomics Consortium, Adan RAH, Alfredsson L, Ando T, Andreassen OA, Baker JH, Berrettini WH, Boehm I, Boni C, Perica VB, Buehren K, Burghardt R, Cassina M, Cichon S, Clementi M, Cone RD, Courtet P, Crow S, Crowley JJ, Danner UN, Davis OSP, de Zwaan M, Dedoussis G, Degortes D, DeSocio JE, Dick DM, Dikeos D, Dina C, Dmitrzak-Weglarz M, Docampo E, Duncan LE, Egberts K, Ehrlich S, Escaramís G, Esko T, Estivill X, Farmer A, Favaro A, Fernández-Aranda F, Fichter MM, Fischer K, Föcker M, Foretova L, Forstner AJ, Forzan M, Franklin CS, Gallinger S, Giegling I, Giuranna J, Gonidakis F, Gorwood P, Mayora MG, Guillaume S, Guo Y, Hakonarson H, Hatzikotoulas K, Hauser J, Hebebrand J, Helder SG, Herms S, Herpertz-Dahlmann B, Herzog W, Huckins LM, Hudson JI, Imgart H, Inoko H, Janout V, Jiménez-Murcia S, Julià A, Kalsi G, Kaminská D, Kaprio J, Karhunen L, Karwautz A, Kas MJH, Kennedy JL, Keski-Rahkonen A, Kiezebrink K, Kim YR, Klareskog L, Klump KL, Knudsen GPS, La Via MC, Le Hellard S, Levitan RD, Li D, Lilenfeld L, Lin BD, Lissowska J, Luykx J, Magistretti PJ, Maj M, Mannik K, Marsal S, Marshall CR, Mattingsdal M, McDevitt S, McGuffin P, Metspalu A, Meulenbelt I, Micali N, Mitchell K, Monteleone AM, Monteleone P, Munn-Chernoff MA, Nacmias B, Navratilova M, Ntalla I, O’Toole JK, Ophoff RA, Padyukov L, Palotie A, Pantel J, Papezova H, Pinto D, Rabionet R, Raevuori A, Ramoz N, Reichborn-Kjennerud T, Ricca V, Ripatti S, Ritschel F, Roberts M, Rotondo A, Rujescu D, Rybakowski F, Santonastaso P, Scherag A, Scherer SW, Schmidt U, Schork NJ, Schosser A, Seitz J, Slachtova L, Slagboom PE, Slof-Op ‘t Landt MCT, Slopien A, Sorbi S, Świątkowska B, Szatkiewicz JP, Tachmazidou I, Tenconi E, Tortorella A, Tozzi F, Treasure J, Tsitsika A, Tyszkiewicz-Nwafor M, Tziouvas K, van Elburg AA, van Furth EF, Wagner G, Walton E, Widen E, Zeggini E, Zerwas S, Zipfel S, Bergen AW, Boden JM, Brandt H, Crawford S, Halmi KA, Horwood LJ, Johnson C, Kaplan AS, Kaye WH, Mitchell JE, Olsen CM, Pearson JF, Pedersen NL, Strober M, Werge T, Whiteman DC, Woodside DB, Stuber GD, Gordon S, Grove J, Henders AK, Juréus A, Kirk KM, Larsen JT, Parker R, Petersen L, Jordan J, Kennedy M, Montgomery GW, Wade TD, Birgegård A, Lichtenstein P, Norring C, Landén M, Martin NG, Mortensen PB, Sullivan PF, Breen G, Bulik CM. Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa. Nat Genet. 2019 Aug;51(8):1207-1214. doi: 10.1038/s41588-019-0439-2. Epub 2019 Jul 15. PMID: 31308545; PMCID: PMC6779477.
  8. Verharen JPH, van den Heuvel MW, Luijendijk M, Vanderschuren LJMJ, Adan RAH. Corticolimbic Mechanisms of Behavioral Inhibition under Threat of Punishment. J Neurosci. 2019 May 29;39(22):4353-4364. doi: 10.1523/JNEUROSCI.2814-18.2019. Epub 2019 Mar 22. PMID: 30902868; PMCID: PMC6538860.
  9. Verharen JPH, de Jong JW, Roelofs TJM, Huffels CFM, van Zessen R, Luijendijk MCM, Hamelink R, Willuhn I, den Ouden HEM, van der Plasse G, Adan RAH, Vanderschuren LJMJ. A neuronal mechanism underlying decision-making deficits during hyperdopaminergic states. Nat Commun. 2018 Feb 21;9(1):731. doi: 10.1038/s41467-018-03087-1. PMID: 29467419; PMCID: PMC5821846.
  10. van der Plasse G, van Zessen R, Luijendijk MC, Erkan H, Stuber GD, Ramakers GM, Adan RA. Modulation of cue-induced firing of ventral tegmental area dopamine neurons by leptin and ghrelin. Int J Obes (Lond). 2015 Dec;39(12):1742-9. doi: 10.1038/ijo.2015.131. Epub 2015 Jul 17. PMID: 26183405; PMCID: PMC4722241.
  11. Adan RA. Mechanisms underlying current and future anti-obesity drugs. Trends Neurosci. 2013 Feb;36(2):133-40. doi:10.1016/j.tins.2012.12.001. Epub 2013 Jan 8. PMID: 23312373.
  12. Meye FJ, Trezza V, Vanderschuren LJ, Ramakers GM, Adan RA. Neutral antagonism at the cannabinoid 1 receptor: a safer treatment for obesity. Mol Psychiatry. 2013 Dec;18(12):1294-301. doi: 10.1038/mp.2012.145. Epub 2012 Oct 16. PMID: 23070073.
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