The Netrin-1/DCC guidance cue pathway as a molecular target in depression: Translational evidence

Abstract The Netrin-1/DCC guidance cue pathway plays a critical role in guiding growing axons towards the prefrontal cortex (PFC) during adolescence and in the maturational organization and adult plasticity of PFC connectivity. In this review we put forward the idea that alterations in PFC architecture and function, which are intrinsically linked to the development of major depressive disorder (MDD), originate in part from the dysregulation of the Netrin-1/DCC pathway by a mechanism that involves the microRNA, miR-218. We discuss evidence derived from mouse models of stress and human postmortem brain and genome-wide association studies (GWAS), indicating an association between the Netrin-1/DCC pathway and MDD. We propose a potential role of circulating miR-218 as a biomarker of stress vulnerability and MDD.