“Equipe FRM” awards – 2024

Congratulations to Pierre Trifilieff, “Equipe FRM” award winner.

Pierre Trifilieff

Team: Foodcircus – NutriNeuro

Contribution of lipid metabolism in the aetiology of psychiatric disorders: relevance of iPLA2β

Deficits in reward processing and executive functions belong to a common symptomatic frame across several psychiatric disorders such as schizophrenia, bipolar disorders and major depression, in relation with a dysfunction of mesocorticolimbic dopamine transmission. This suggests the existence of common pathogenic mechanisms underlying dopamine-related symptomatic dimensions. Converging evidence point to an alteration of polyunsaturated fatty acid (PUFA) metabolism that has been consistently described across psychiatric disorders. In accordance, we and others have demonstrated a unique vulnerability of dopamine transmission to decreased n-3 PUFA biostatus. However, the origin of n-3 PUFA deficiency in psychiatric disorders remains largely unclear, and the causal link with specific symptomatic dimensions remains to be established.

Herein, we will explore the impact of manipulations of the iPLA2β enzyme selectively in dopamine neurons, since iPLA2β is crucial for PUFA metabolism and polymorphisms in the gene coding for this enzyme are associated with the development of psychiatric symptoms. Using cutting-edge neuroscience techniques coupled with elaborated behavioral tasks in mice, we will identify how manipulations of iPLA2β impact reward-related behavioral dimensions, together with dopamine dynamics in the mesocorticolimbic pathway. In order to identify cellular and molecular targets, we will explore how manipulations of iPLA2β affect the translatome and synaptome of mesocorticolimbic projections. We will also assess to which extent n-3 PUFA supplementation alleviates behavioral alterations under manipulations of iPLA2β. This project will allow establishing causal relationship between activity of iPLA2β and behavioral dimensions relevant for the symptomatology of psychiatric disorders. Because PUFAs can be modified through dietary manipulation, such a project will pave the way for novel strategies to prevent or alleviate specific psychiatric symptoms.