The Eph receptor A4-mediated demyelination in depression

Accumulating evidence reveals that major depressive disorder, one of the most common mental illnesses, is characterized by abnormal myelination. However, the relationship between demyelination and depression-related behaviors and the molecular mechanism underlying demyelination and synaptic deficits in depression is largely unknown. In a recent study, Li and his colleagues found that the ephrin A4 receptor (EphA4), a member of the Eph family of receptor tyrosine kinases, was essential to mediate demyelination and regulate synap- togenesis in depression. Using the chronic, unpredictable mild stress (CUMS) exposure or lipopolysaccharide (LPS) administration-induced animal model of depression, the authors found that depression could induce demyelination, and the increased EphA4 levels mediate demyelination and depression-like behaviors. In this commentary, we reviewed this critical finding and discussed future directions on this topic.