Serotonin signaling in plasticity and disease

Leader

Research center

17 rue du Fer à Moulin
75005 Paris

Institution

Inserm
Université Pierre et Marie Curie
ED394
Université Pierre et Marie Curie

Laboratory

Marianne Coutures
Phone: 01 45 87 61 35
UMRS 839
ANR

Keywords

addiction
dopamine
impulsivity
serotonin
 

Publications

Ebrahimkhani M, Oakley F, Murphy L, Mann J, Moles A, Perugorria M, Ellis E, Burt A, Douglass A, Wright M, White S, Jaffré F, Maroteaux L, Mann D. Stimulating healthy tissue regeneration by targeting the 5-HT2B receptor in chronic liver disease. Nature Medicine. 2011 Nov 27;17(12):1668-73.

El Oussini H, Bayer H, Scekic-Zahirovic J, Vercruysse P, Sinniger J, Dirrig-Grosch S, Dieterlé S, Echaniz-Laguna A, Larmet Y, Müller K, Weishaupt JH, Thal DR, van Rheenen W, van Eijk K, Lawson R, Monassier L, Maroteaux L, Roumier A, Wong PC, van den Berg LH, Ludolph AC, Veldink JH, Witting A, Dupuis L. Serotonin 2B receptor slows disease progression and prevents degeneration of spinal cord mononuclear phagocytes in amyotrophic lateral sclerosis. Acta Neuropathol. 2016 vol. 131 (3) pp. 465-80.

Li Y, Hadden C, Singh P, Mercado CP, Murphy P, Dajani NK, Lowery CL, Roberts DJ, Maroteaux L, Kilic F. GDM-associated insulin deficiency hinders the dissociation of SERT from ERp44 and down-regulates placental 5-HT uptake. Proc Natl Acad Sci U S A. 2014 Dec 30;111(52):E5697-705.

Launay, J.-M., Hervé, P., Callebert, J., Mallat, Z., Collet, C., Doly, S., Belmer, A., Diaz, S.L., Hatia, S., Côté, F., Humbert, M., and Maroteaux, L. (2012). Serotonin 5-HT2B receptors are required for bone-marrow contribution to pulmonary arterial hypertension. Blood 2012 Feb;119(7):1772-1780.

Diaz, SL, Doly, S, Narboux-Nême, N, Fernandez, S, Mazot, P, Banas, SM, Boutourlinsky, K, Moutkine, I, Belmer, A, Roumier, A, and Maroteaux, L, 5-HT2B receptors are required for serotonin-selective antidepressant actions Molecular Psychiatry 2012 Feb;17(2):154-63.

 

Fields of research

Neuropharmacology / cell signaling

Research Theme

Our present work started from our observation that serotonin tone can be controlled by a feed-forward mechanism via 5-HT2B receptors. Recent independent investigations and our unpublished results indicate that this same serotonergic receptor may also impact local dopamine levels. The absence of 5-HT2B receptors, DA-targeting drugs induce a reduced increase in extracellular DA in NAcc, but a normal increase in dorsal striatum, thus an imbalance that could underlie addictive behaviors. Other unpublished evidence (in collaboration with D. Goldman, NIH) indicates that 5-HT2B receptor haplotypes, which correspond to lower expressing individuals, segregate with cocaine abuser. These data support again in Humans our finding in mice that this receptor inactivation is favoring addictive behaviors. Recent independent investigations, and our unpublished results indicate a control of microglia by serotonin, but its potential physiological implications has never been investigated. Our preliminary data indicate that microglia express mainly one type of numerous serotonin receptors, the 5-HT2B, which had not been studied before. Our work now intends to unravel links between serotonin and dopamine system in relation to impulsivity, compulsivity and addiction and to identify the cellular basis of these actions (dopamine and/or serotonin neurons and/or microglia).

Team members

ROUMIER Anne
MOUTKINE Imane
DIAZ Silvina
BANAS Sophie
KOLODZIEJCZA Marta
QUENTIN Emily
SANDULACHE Miriam

Lab rotation

Identification of protein complexes that positively regulate serotonergic neurons

Team leader: 

MAROTEAUX Luc

Dates: 

January 2, 2018 - June 29, 2018

Application deadline: 

June 29, 2018

Period

~ Jan-March 2018

~ April-June 2018

Project

Knowing that serotonin 5-HT2B receptors are expressed by serotonin neurons and can modulate positively their firing activity, we propose to thest the hypothesis that this receptor can interact with partners including ion channels, synaptic vesicle proteins and/or other receptor subtypes. Identifying these interactions are likely to unravel new pathways that regulate serotonin neuron activity together with associated behaviors and pathologies.

Contact

Institut du Fer à Moulin - 17, rue du Fer à Moulin 75005 Paris - +33 1 45 87 61 23 - Luc.maroteaux@upmc.fr

Supervisor: 

MAROTEAUX Luc