Anxiety and depression have been suggested to increase the risk for post-traumatic stress disorders (PTSD). A link between all these mental illnesses, inflammation and oxidative stress is also well established. Recent behavior studies by our group clearly demonstrate a powerful anxiolytic and antidepressant-like effects of a novel growth hormone releasing hormone (GHRH) antagonist of MIAMI class, MIA-690, probably related to modulatory effects on the inflammatory and oxidative status. In the present work we investigated the potential beneficial effects of MIA-602, another recently developed GHRH antagonist, in mood disorders, as anxiety and depression, and the possible brain pathways involved in its protective activity, in adult mice. MIA-602 exhibited antinflammatory and antioxidant effects in ex vivo and in vivo experimental models, inducing anxiolytic and antidepressant-like behavior in mice subcutaneously treated for 4 weeks. The beneficial effect of MIA-602 on inflammatory and oxidative status and synaptogenesis resulting in anxiolytic and antidepressant-like effects could be related by increases of nuclear factor erythroid 2-related factor 2 (Nrf2) and of brain-derived neurotrophic factor (BDNF) signaling pathways in the hippocampus and prefrontal cortex. These results strongly suggest that GHRH analogs should be tried clinically for the treatment of mood disorders including PTSD.
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This work was supported by the University G. d’Annunzio of Chieti FAR 2020 (to Sheila Leone) and FAR 2020 (to Lucia Recinella). Work in Miami was supported by the Medical Research Service of the Department of Veterans Affairs and by the University of Miami Miller School of Medicine (to Andrew V. Schally).
AVS and RC are listed as co-inventors on patents for GHRH antagonists, assigned to the University of Miami, Miami, FL, and the Veterans Affairs Medical Center, Miami, FL. LR, AC, GO, CF, SV, AC, GDM, FD, IG, RG, WS, LB, and SL declare no potential conflict of interest.
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Recinella, L., Chiavaroli, A., Orlando, G. et al. Effects of growth hormone-releasing hormone receptor antagonist MIA-602 in mice with emotional disorders: a potential treatment for PTSD. Mol Psychiatry (2021). https://doi.org/10.1038/s41380-021-01228-5