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

Animals Anti-Anxiety Agents Anti-Inflammatory Agents Antidepressive Agents Antioxidants Behavior, Animal / drug effects Emotions / drug effects Gene Expression / drug effects Growth Hormone-Releasing Hormone / agonists Interleukin-6 / genetics Mice NF-kappa B / genetics Norepinephrine / metabolism Prefrontal Cortex / metabolism Receptors, Neuropeptide / genetics Receptors, Pituitary Hormone-Regulating Hormone / genetics Sermorelin / analogs & derivatives Serotonin / metabolism Tumor Necrosis Factor-alpha / genetics

Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
20 01 2020
Historique:
received: 26 07 2019
accepted: 20 12 2019
entrez: 22 1 2020
pubmed: 22 1 2020
medline: 26 11 2020
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41598-019-57292-z PMID: 31959947 PMC: PMC6971229
pubmed: 31959947
doi: 10.1038/s41598-019-57292-z
pii: 10.1038/s41598-019-57292-z
pmc: PMC6971229
doi:

Substances chimiques

Anti-Anxiety Agents 0
Anti-Inflammatory Agents 0
Antidepressive Agents 0
Antioxidants 0
Interleukin-6 0
N-Me-Tyr1,D-Ala2,Asn8,Arg29-NHCH3-JI-38 0
NF-kappa B 0
Receptors, Neuropeptide 0
Receptors, Pituitary Hormone-Regulating Hormone 0
Tumor Necrosis Factor-alpha 0
Serotonin 333DO1RDJY
Sermorelin 86168-78-7
Growth Hormone-Releasing Hormone 9034-39-3
somatotropin releasing hormone receptor F8L0ODC9D7
Norepinephrine X4W3ENH1CV

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

732

Commentaires et corrections

Type : ErratumIn

Références

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Auteurs

Lucia Recinella (L)

Department of Pharmacy, G. d'Annunzio University, Chieti, Italy.

Annalisa Chiavaroli (A)

Department of Pharmacy, G. d'Annunzio University, Chieti, Italy.

Giustino Orlando (G)

Department of Pharmacy, G. d'Annunzio University, Chieti, Italy.

Claudio Ferrante (C)

Department of Pharmacy, G. d'Annunzio University, Chieti, Italy.

Guya Diletta Marconi (GD)

Department of Pharmacy, G. d'Annunzio University, Chieti, Italy.

Iacopo Gesmundo (I)

Division of Endocrinology, Diabetes and Metabolism, Department of Medical Sciences, University of Turin and Città Della Salute e Della Scienza Hospital, Turin, 10126, Italy.
ORCID: 0000-0003-4901-4764

Riccarda Granata (R)

Division of Endocrinology, Diabetes and Metabolism, Department of Medical Sciences, University of Turin and Città Della Salute e Della Scienza Hospital, Turin, 10126, Italy.

Renzhi Cai (R)

Veterans Affairs Medical Center, Miami, FL, 33125, USA.
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA.
Division of Medical/Oncology, Department of Pathology, Sylvester Comprehensive Cancer Center, Miami, FL, 33136, USA.

Wei Sha (W)

Veterans Affairs Medical Center, Miami, FL, 33125, USA.
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA.
Division of Medical/Oncology, Department of Pathology, Sylvester Comprehensive Cancer Center, Miami, FL, 33136, USA.

Andrew V Schally (AV)

Veterans Affairs Medical Center, Miami, FL, 33125, USA.
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA.
Division of Medical/Oncology, Department of Pathology, Sylvester Comprehensive Cancer Center, Miami, FL, 33136, USA.

Luigi Brunetti (L)

Department of Pharmacy, G. d'Annunzio University, Chieti, Italy. luigi.brunetti@unich.it.

Sheila Leone (S)

Department of Pharmacy, G. d'Annunzio University, Chieti, Italy. sheila.leone@unich.it.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Antinflammatory, antioxidant, and behavioral...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Agents du système nerveux central › Psychoanaleptiques › Tranquillisants › Anxiolytiques › Antinflammatory, antioxidant, and behavioral...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Anti-inflammatoires › Antinflammatory, antioxidant, and behavioral...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Agents du système nerveux central › Psychoanaleptiques › Antidépresseurs › Antinflammatory, antioxidant, and behavioral...
questionsmedicales.fr › Actions chimiques et utilisations › Utilisations spécialisées de produits chimiques › Agents protecteurs › Antioxydants › Antinflammatory, antioxidant, and behavioral...
questionsmedicales.fr › Comportement et mécanismes comportementaux › Comportement › Comportement animal › Antinflammatory, antioxidant, and behavioral...
questionsmedicales.fr › Comportement et mécanismes comportementaux › Émotions › Antinflammatory, antioxidant, and behavioral...
questionsmedicales.fr › Phénomènes génétiques › Expression des gènes › Antinflammatory, antioxidant, and behavioral...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Neuropeptides › Hormones hypothalamiques › Hormones hypophysiotropes libératrices › Hormone de libération de l'hormone de croissance › Antinflammatory, antioxidant, and behavioral...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Interleukines › Interleukine-6 › Antinflammatory, antioxidant, and behavioral...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Antinflammatory, antioxidant, and behavioral...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteur de transcription NF-kappa B › Antinflammatory, antioxidant, and behavioral...
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questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Prosencéphale › Télencéphale › Cerveau › Cortex cérébral › Lobe frontal › Cortex préfrontal › Antinflammatory, antioxidant, and behavioral...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs peptidiques › Récepteur aux neuropeptides › Antinflammatory, antioxidant, and behavioral...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs peptidiques › Récepteur hormones hypothalamiques hypophysotropes régulatrices › Antinflammatory, antioxidant, and behavioral...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Neuropeptides › Hormones hypothalamiques › Hormones hypophysiotropes libératrices › Hormone de libération de l'hormone de croissance › Sermoréline › Antinflammatory, antioxidant, and behavioral...
questionsmedicales.fr › Facteurs biologiques › Médiateurs de l'inflammation › Autacoïdes › Sérotonine › Antinflammatory, antioxidant, and behavioral...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Facteurs de nécrose tumorale › Facteur de nécrose tumorale alpha › Antinflammatory, antioxidant, and behavioral...