The Netrin-1/DCC Guidance Cue Pathway as a Molecular Target in Depression: Translational Evidence

Biol Psychiatry. 2020 Oct 15;88(8):611-624. doi: 10.1016/j.biopsych.2020.04.025. Epub 2020 May 11.

Abstract

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

Keywords: Adolescence; Biomarkers; Neurodevelopment; Prefrontal cortex; Resilience; microRNA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Axons
  • Cues
  • DCC Receptor / genetics
  • Depression
  • Depressive Disorder, Major* / genetics
  • Genome-Wide Association Study
  • Humans
  • MicroRNAs*
  • Netrin-1
  • Receptors, Cell Surface
  • Tumor Suppressor Proteins / genetics

Substances

  • DCC Receptor
  • DCC protein, human
  • MIRN218 microRNA, human
  • MicroRNAs
  • Receptors, Cell Surface
  • Tumor Suppressor Proteins
  • Netrin-1