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Antinflammatory, antioxidant, and behavioral effects induced by administration of growth hormone-releasing hormone analogs in mice

Growth hormone-releasing hormone (GHRH) antagonist MIA-690 and GHRH agonist MR-409, previously synthesized and developed by us have demonstrated potent antitumor effects. However, little is known about the effects of these analogs on brain functions. We investigated the potential antinflammatory and...

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Autores principales: Recinella, Lucia, Chiavaroli, Annalisa, Orlando, Giustino, Ferrante, Claudio, Diletta Marconi, Guya, Gesmundo, Iacopo, Granata, Riccarda, Cai, Renzhi, Sha, Wei, Schally, Andrew V., Brunetti, Luigi, Leone, Sheila
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6971229/
https://www.ncbi.nlm.nih.gov/pubmed/31959947
http://dx.doi.org/10.1038/s41598-019-57292-z
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author Recinella, Lucia
Chiavaroli, Annalisa
Orlando, Giustino
Ferrante, Claudio
Diletta Marconi, Guya
Gesmundo, Iacopo
Granata, Riccarda
Cai, Renzhi
Sha, Wei
Schally, Andrew V.
Brunetti, Luigi
Leone, Sheila
author_facet Recinella, Lucia
Chiavaroli, Annalisa
Orlando, Giustino
Ferrante, Claudio
Diletta Marconi, Guya
Gesmundo, Iacopo
Granata, Riccarda
Cai, Renzhi
Sha, Wei
Schally, Andrew V.
Brunetti, Luigi
Leone, Sheila
author_sort Recinella, Lucia
collection PubMed
description Growth hormone-releasing hormone (GHRH) antagonist MIA-690 and GHRH agonist MR-409, previously synthesized and developed by us have demonstrated potent antitumor effects. However, little is known about the effects of these analogs on brain functions. We investigated the potential antinflammatory and antioxidant effects of GHRH antagonist MIA-690 and GHRH agonist MR-409, on isolated mouse prefrontal cortex specimens treated with lipopolysaccharide (LPS). Additionally, we studied their effects on emotional behavior after chronic in vivo treatment. Ex vivo, MIA-690 and MR-409 inhibited LPS-induced inflammatory and pro-oxidative markers. In vivo, both MIA-690 and MR-409 induced anxiolytic and antidepressant-like effects, increased norepinephrine and serotonin levels and decreased nuclear factor-kB, tumor necrosis factor-α and interleukin-6 gene expression in prefrontal cortex. Increased nuclear factor erythroid 2–related factor 2 expression was also found in mice treated with MIA-690 and MR-409. MIA-690 showed higher efficacy in inhibiting all tested inflammatory and oxidative markers. In addition, MR-409 induced a down regulation of the gene and protein expression of pituitary-type GHRH-receptor in prefrontal cortex of mice after 4 weeks of treatment at 5 µg/day. In conclusion, our results demonstrate anxiolytic and antidepressant-like effects of GHRH analogs that could involve modulatory effects on monoaminergic signaling, inflammatory and oxidative status.
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spelling pubmed-69712292020-01-27 Antinflammatory, antioxidant, and behavioral effects induced by administration of growth hormone-releasing hormone analogs in mice Recinella, Lucia Chiavaroli, Annalisa Orlando, Giustino Ferrante, Claudio Diletta Marconi, Guya Gesmundo, Iacopo Granata, Riccarda Cai, Renzhi Sha, Wei Schally, Andrew V. Brunetti, Luigi Leone, Sheila Sci Rep Article Growth hormone-releasing hormone (GHRH) antagonist MIA-690 and GHRH agonist MR-409, previously synthesized and developed by us have demonstrated potent antitumor effects. However, little is known about the effects of these analogs on brain functions. We investigated the potential antinflammatory and antioxidant effects of GHRH antagonist MIA-690 and GHRH agonist MR-409, on isolated mouse prefrontal cortex specimens treated with lipopolysaccharide (LPS). Additionally, we studied their effects on emotional behavior after chronic in vivo treatment. Ex vivo, MIA-690 and MR-409 inhibited LPS-induced inflammatory and pro-oxidative markers. In vivo, both MIA-690 and MR-409 induced anxiolytic and antidepressant-like effects, increased norepinephrine and serotonin levels and decreased nuclear factor-kB, tumor necrosis factor-α and interleukin-6 gene expression in prefrontal cortex. Increased nuclear factor erythroid 2–related factor 2 expression was also found in mice treated with MIA-690 and MR-409. MIA-690 showed higher efficacy in inhibiting all tested inflammatory and oxidative markers. In addition, MR-409 induced a down regulation of the gene and protein expression of pituitary-type GHRH-receptor in prefrontal cortex of mice after 4 weeks of treatment at 5 µg/day. In conclusion, our results demonstrate anxiolytic and antidepressant-like effects of GHRH analogs that could involve modulatory effects on monoaminergic signaling, inflammatory and oxidative status. Nature Publishing Group UK 2020-01-20 /pmc/articles/PMC6971229/ /pubmed/31959947 http://dx.doi.org/10.1038/s41598-019-57292-z Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Recinella, Lucia
Chiavaroli, Annalisa
Orlando, Giustino
Ferrante, Claudio
Diletta Marconi, Guya
Gesmundo, Iacopo
Granata, Riccarda
Cai, Renzhi
Sha, Wei
Schally, Andrew V.
Brunetti, Luigi
Leone, Sheila
Antinflammatory, antioxidant, and behavioral effects induced by administration of growth hormone-releasing hormone analogs in mice
title Antinflammatory, antioxidant, and behavioral effects induced by administration of growth hormone-releasing hormone analogs in mice
title_full Antinflammatory, antioxidant, and behavioral effects induced by administration of growth hormone-releasing hormone analogs in mice
title_fullStr Antinflammatory, antioxidant, and behavioral effects induced by administration of growth hormone-releasing hormone analogs in mice
title_full_unstemmed Antinflammatory, antioxidant, and behavioral effects induced by administration of growth hormone-releasing hormone analogs in mice
title_short Antinflammatory, antioxidant, and behavioral effects induced by administration of growth hormone-releasing hormone analogs in mice
title_sort antinflammatory, antioxidant, and behavioral effects induced by administration of growth hormone-releasing hormone analogs in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6971229/
https://www.ncbi.nlm.nih.gov/pubmed/31959947
http://dx.doi.org/10.1038/s41598-019-57292-z
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