Thus, CRS may cause a decrease in BDNF levels in the hippocampus, which leads to a decrease in Narp expression, resulting in depression-like behaviors in mice, whereas (2R,6R)-HNK exerts its antidepressant-like actions via BDNF/TrkB receptors and the Narp pathway in the hippocampus. This evidence concerns the gene NPTX2 and major depressive disorder.