RTN4R and major depressive disorder: In this study, we investigated the neuroprotective effects and the underlying mechanisms of NGR1 on HG-induced HT22 hippocampal neurons injury, and oxidative stress [26, 27] and DEP in db/db mice, which display T2DM characteristic, including hyperglycemia, obesity, hyperinsulinemia, and insulin resistance and show neurobehavioral deficits, including cognitive dysfunction, depression, and anxiety [4, 5, 28, 29].