O.V. Dolotov, E.V. Dubynina, L.S. Inozemtseva, D.D. Markov, K.A. Yatsenko, I.A. Grivennikov
Melanocortin peptides perform a broad spectrum of physiological activities, includingly, they are known to be effective neuroprotectors. In this study, we showed that α-MSH, an endogenous melanocortin peptide, and its stabilized analogue Semax both increased the amount of brain derived neurotrophic factor (BDNF) in primary culture of rat hippocampal neurons. This effect was blocked by preincubation with the selective MC4R antagonist HS028. We showed that α-MSH and Semax stimulated BDNF expression in cultured rat hippocampal astrocytes in an hour after application. We also showed that α-MSH stimulated expression of vascular endothelial growth factor (VEGF) in the same type of cell culture, and this effect was blocked by pretreatment with HS028.
Overall, these data suggest that the neuroprotective effects of melanocortin peptides may be mediated by stimulating production of growth / neurotrophic factors in hippocampal cells through MC4R pathway.