ACTH(6-9)-Pro-Gly-Pro ameliorates anxiety-like and depressive-like behaviour and gut mucosal microbiota composition in rats under conditions of chronic restraint stress. (June 2022)

• Record Type: Journal Article
• Authors: Vorvul, Anton O.; Bobyntsev, Igor I.; Medvedeva, Olga A.; Mukhina, Alexandra Y.; Svishcheva, Maria V.; Azarova, Iuliia E.; Andreeva, Lyudmila A.; Myasoedov, Nikolay F.
• Is Part Of: Neuropeptides. Volume 93(2022)
• Publication Date: 2022-06
• Subjects: ACTH(6–9)-Pro-Gly-Pro -- Chronic restraint stress -- Gut-brain axis -- Anxiety-like behaviour -- Depressive-like behaviour -- Gut microbiota; ACTH adrenocorticotropic hormone -- BBB blood-brain barrier -- CFU colony-forming unit -- CN coagulase-negative -- CNS central nervous system -- CRS chronic restraint stress -- EPM elevated plus-maze -- FST forced swimming test -- GBA gut-brain axis -- HPA hypothalamic-pituitary-adrenal axis -- LEA low enzymatic activity -- MALDI-ToF MS matrix-assisted laser desorption/ionization coupled to time-of-flight mass spectrometry -- MCR melanocortin receptor -- NEA normal enzymatic activity -- OFT open field test; Neuropeptides -- Periodicals; Neuropeptides; Neuropeptides -- Périodiques; Neuropeptides; Electronic journals; Periodicals; 572.65
• DOI: 10.1016/j.npep.2022.102247
• Languages: English
• ISSNs: 0143-4179

Abstract

Abstract: The effects of the peptide ACTH(6–9)-Pro-Gly-Pro at doses of 5; 50; 500 μg/kg on the Wistar rats' behaviour and gut mucosal microbiota composition under conditions of chronic immobilization stress (CRS) were studied. CRS increased anxiety-like and depressive-like behaviour, disturbances in locomotor activity and gut dysbiosis. Administration of ACTH(6–9)-Pro-Gly-Pro showed many phenotypic results. Peptide demonstrated anti-depressant activity at doses of 5 and 500 μg/kg by a decrease in the total immobile time in the FST. ACTH(6–9)-Pro-Gly-Pro administered at a dose of 50 μg/kg resulted in an anxiolytic effect which is shown by an increase in the time in the open arms of EPM (p < 0.05) and a decrease in the time in the closed arms (p < 0.05). Moreover, the peptide led to a decrease in alpha- and beta-diversity of the gut microbiota (p < 0.01). Correlation and linear regression analysis demonstrated central mechanisms of ACTH(6–9)-Pro-Gly-Pro anxiolytic activity and both central and peripheral ones in an anti-depressant effect. In this way, peptide ACTH(6–9)-Pro-Gly-Pro could prevent the development of behavioural disturbances and gut dysbiosis caused by chronic restraint stress.