Published May 16, 2022 - More info
Proper myelination of axons is crucial for normal sensory, motor, and cognitive function. Abnormal myelination is seen in brain disorders such as major depressive disorder (MDD), but the molecular mechanisms connecting demyelination with the pathobiology remain largely unknown. We observed demyelination and synaptic deficits in mice exposed to either chronic, unpredictable mild stress (CUMS) or LPS, 2 paradigms for inducing depression-like states. Pharmacological restoration of myelination normalized both synaptic deficits and depression-related behaviors. Furthermore, we found increased ephrin A4 receptor (EphA4) expression in the excitatory neurons of mice subjected to CUMS, and shRNA knockdown of EphA4 prevented demyelination and depression-like behaviors. These animal data are consistent with the decrease in myelin basic protein and the increase in EphA4 levels we observed in postmortem brain samples from patients with MDD. Our results provide insights into the etiology of depressive symptoms in some patients and suggest that inhibition of EphA4 or the promotion of myelination could be a promising strategy for treating depression.
Yuan Li, Ping Su, Yuxiang Chen, Jing Nie, Ti-Fei Yuan, Albert H.C. Wong, Fang Liu
Original citation: J Clin Invest. 2022;132(8):e152187. https://doi.org/10.1172/JCI152187
Citation for this corrigendum: J Clin Invest. 2022;132(10):e161559. https://doi.org/10.1172/JCI161559
Following the publication of this article, the authors became aware that an incorrect panel was used for Figure 3N. In addition, the molecular weight markers in Figure 9C were incorrect. The correct panels for Figures 3N and 9C are below. The article has also been corrected online.
The authors regret the error.
See the related article at The Eph receptor A4 plays a role in demyelination and depression-related behavior.