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Current Neuropharmacology

Editor-in-Chief

ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

Review Article

Ghrelin, Neuroinflammation, Oxidative Stress, and Mood Disorders: What Are the Connections?

In Press, (this is not the final "Version of Record"). Available online 22 July, 2024
Author(s): Jessica Mingardi, Ramona Meanti, Caterina Paoli, Carlo Cifani, Antonio Torsello, Maurizio Popoli* and Laura Musazzi*
Published on: 22 July, 2024

DOI: 10.2174/1570159X22999240722095039

Price: $95

Abstract

Ghrelin is a gut peptide hormone associated with feeding behavior and energy homeostasis. Acylated ghrelin binds to the growth hormone secretagogue receptor 1a subtype (GHS-R1a) in the hippocampus, leading to GH release from the anterior pituitary. However, in recent years, ghrelin and its receptor have also been implicated in other processes, including the regulation of cardiomyocyte function, muscle trophism, and bone metabolism. Moreover, GHS-R1a is distributed throughout the brain and is expressed in brain areas that regulate the stress response and emotional behavior. Consistently, a growing body of evidence supports the role of ghrelin in regulating stress response and mood. Stress has consistently been shown to increase ghrelin levels, and despite some inconsistencies, both human and rodent studies suggested antidepressant effects of ghrelin. Nevertheless, the precise mechanism by which ghrelin influences stress response and mood remains largely unknown. Intriguingly, ghrelin and GHS-R1a were consistently reported to exert anti-inflammatory, antioxidant, and neurotrophic effects both in vivo and in vitro, although this has never been directly assessed in relation to psychopathology. In the present review we will discuss available literature linking ghrelin with the stress response and depressive-like behavior in animal models as well as evidence describing the interplay between ghrelin and neuroinflammation/oxidative stress. Although further studies are required to understand the mechanisms involved in the action of ghrelin on mood, we hypothesize that the antiinflammatory and anti-oxidative properties of ghrelin may give a key contribution.

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