Venue: Centre Broca
Defense in english
Title
Implication of polyunsaturated fatty acid (PUFA) biostatus in dopamine transmission-related reward processing deficits
Résumé
Reward processing deficits underly shared symptomatic dimension across psychiatric disorders such as schizophrenia, bipolar disorder and major depression. These impairments are often linked to dysfunction of mesocorticolimbic dopaminergic pathway, suggesting shared underlying mechanisms. Interestingly, clinical studies have consistently described a decrease in n-3 polyunsaturated fatty acids (PUFA) in a subpopulation of patients with these disorders (Conklin et al., 2010; Messamore and McNamara, 2016). Here we show that developmental n-3 PUFA deficiency leads to an imbalance in the mesocorticolimbic pathway with cortical hypodopaminergia and striatal hyperdopaminergia, together with aberrant wiring of striatal dopamine terminals which relate to changes in gene networks involved in neuronal transmission and axon development in VTA DA neurons. Furthermore, DA dynamics in relation with action reinforcement and reward prediction in the mPFC and the NAc, respectively, were found to be altered under n-3 PUFA deficiency, potentially revealing reward processing deficits implicated in related impaired behaviors. Indeed, n-3 PUFA deficiency while sparing learning and flexible expression of action-outcome associations, leads to motivational deficits and increased choice impulsivity. Importantly, transgenic normalization of PUFA biostatus in DA neurons specifically was sufficient to prevent behavioral deficits, demonstrating the causal link between developmental n-3 PUFA deficiency, mesocorticolimbic imbalance and reward processing deficits, relevant to psychiatric disorders. By elucidating shared pathological mechanisms across diagnostic boundaries, this work might unravel neurodevelopmental and circuit level vulnerabilities under n-3 PUFA deficiency which could pave the way for early interventions, preventive strategies, and more personalized approaches to treatment in psychiatry with PUFA biostatus as a clinically relevant biomarker.
Keywords: Psychiatric Disorders, n-3 PUFA Deficiency, Reward Processing Deficits, Dopamine
Publications
Roman Walle, Anna Petitbon, Giulia R. Fois, Christophe Varin, Enrica Montalban, Lola Hardt, Andrea Contini, Maria Florencia Angelo, Mylène Potier, Rodrigue Ortole, Asma Oummadi, Véronique De Smedt-Peyrusse, Roger A Adan, Bruno Giros, Francis Chaouloff, Guillaume Ferreira, Alban de Kerchove d’Exaerde, Fabien Ducrocq, François Georges, Pierre Trifilieff.
Nucleus accumbens D1- and D2-expressing neurons control the balance between feeding and activity-mediated energy expenditure (2023)
doi: https://doi.org/10.1101/2022.05.05.490599
Alessia Costa, Eva Ducourneau, Lorenzo Curti, Alessio Masi, Guido Mannaioni, Lola Hardt, Essi F Biyong, Mylène Potier, Patrizio Blandina, Pierre Trifilieff, Gustavo Provensi, Guillaume Ferreira, M Beatrice Passani
Chemogenetic activation or inhibition of histaminergic neurons bidirectionally modulates recognition memory formation and retrieval in male and female mice (2023)
doi: https://doi.org/10.21203/rs.3.rs-3714805/v1
Jury
Dr BELUJON Pauline, Maîtresse de conférences, Laboratoire de Neurosciences Expérimentales et Cliniques, Rapporteure
Dr GEORGES François, Directeur de recherche, Insitut de Maladies Neurodégénérative, CNRS UMR 5293, Invité
Dr TRIFILIEFF Pierre, Directeur de recherche, Laboratoire NutriNeurO, UMR INRAE 1286, Directeur de Thèse
Dr CARNICELLA Sébastien, Directeur de recherche, Grenoble Institut des Neurosciences, Inserm U1216, Université Grenoble Alpes, Rapporteur
Dr VALJENT Emmanuel, Directeur de recherche, Institute For Neurosciences Of Montpellier, Examinateur
Dr FLORES Cecilia, Full professor, The Douglas Research Centre, Examinatrice