The Orexigenic Hormone Ghrelin Defends Against Depressive Symptoms of Chronic Stress

Overview

Journal Nat Neurosci

Date 2008 Jun 17

PMID 18552842

Citations 261

Authors

Michael Lutter

Ichiro Sakata

Sherri Osborne-Lawrence

Sherry A Rovinsky

Jason G Anderson

Saendy Jung

Shari Birnbaum

Masashi Yanagisawa

Joel K Elmquist

Eric J Nestler

Jeffrey M Zigman

Affiliations

Soon will be listed here.

Abstract

We found that increasing ghrelin levels, through subcutaneous injections or calorie restriction, produced anxiolytic- and antidepressant-like responses in the elevated plus maze and forced swim test. Moreover, chronic social defeat stress, a rodent model of depression, persistently increased ghrelin levels, whereas growth hormone secretagogue receptor (Ghsr) null mice showed increased deleterious effects of chronic defeat. Together, these findings demonstrate a previously unknown function for ghrelin in defending against depressive-like symptoms of chronic stress.

Citing Articles

Stress-induced GHS-R1a expression in medial prefrontal cortical neurons promotes vulnerability to anxiety in mice.

Yang L, Zhang M, Sun X, Du A, Jia J, Li N Commun Biol. 2025; 8(1):430.

PMID: 40082560 PMC: 11906648. DOI: 10.1038/s42003-025-07802-9.

A Modular Customizable Ligand-Conjugate (LC) System Targeting Ghrelin -Acyltransferase.

Ford A, Taft C, Sprague-Getsy A, Carlson G, Mate N, Sieburg M Biomolecules. 2025; 15(2).

PMID: 40001510 PMC: 11852496. DOI: 10.3390/biom15020204.

Diet Supplementation Influences Ghrelin System Expression in the Skin Appendages of the Sheep.

Maranesi M, DallAglio C, Moscatelli S, Palmioli E, Coliolo P, Marini D Vet Sci. 2025; 12(1).

PMID: 39852916 PMC: 11769205. DOI: 10.3390/vetsci12010041.

Ghrelin Inhibits Inflammasomes Activation in Astrocytes, Alleviates Pyroptosis, and Prevents Lipopolysaccharide-induced Depression-like Behavior in Mice.

Han X, Fu X, Guo W, Liu Y, Sun J, Wang T Inflammation. 2024; .

PMID: 39702621 DOI: 10.1007/s10753-024-02190-4.

Ghrelin in Depression: A Promising Therapeutic Target.

Kore M, Mamsa R, Patil D, Bhatt L Mol Neurobiol. 2024; 62(4):4237-4249.

PMID: 39424690 DOI: 10.1007/s12035-024-04554-1.

References

Lawrence C, Snape A, Luckman S . Acute central ghrelin and GH secretagogues induce feeding and activate brain appetite centers. Endocrinology. 2001; 143(1):155-62. DOI: 10.1210/endo.143.1.8561. View

Krishnan V, Han M, Graham D, Berton O, Renthal W, Russo S . Molecular adaptations underlying susceptibility and resistance to social defeat in brain reward regions. Cell. 2007; 131(2):391-404. DOI: 10.1016/j.cell.2007.09.018. View

Asakawa A, Inui A, Kaga T, Yuzuriha H, Nagata T, Fujimiya M . A role of ghrelin in neuroendocrine and behavioral responses to stress in mice. Neuroendocrinology. 2001; 74(3):143-7. DOI: 10.1159/000054680. View

Lutter M, Krishnan V, Russo S, Jung S, McClung C, Nestler E . Orexin signaling mediates the antidepressant-like effect of calorie restriction. J Neurosci. 2008; 28(12):3071-5. PMC: 2713756. DOI: 10.1523/JNEUROSCI.5584-07.2008. View

Diano S, Farr S, Benoit S, McNay E, Silva I, Horvath B . Ghrelin controls hippocampal spine synapse density and memory performance. Nat Neurosci. 2006; 9(3):381-8. DOI: 10.1038/nn1656. View

Mundinger T, Cummings D, Taborsky Jr G . Direct stimulation of ghrelin secretion by sympathetic nerves. Endocrinology. 2006; 147(6):2893-901. DOI: 10.1210/en.2005-1182. View

Kristenssson E, Sundqvist M, Astin M, Kjerling M, Mattsson H, Dornonville de la Cour C . Acute psychological stress raises plasma ghrelin in the rat. Regul Pept. 2006; 134(2-3):114-7. DOI: 10.1016/j.regpep.2006.02.003. View

Zigman J, Elmquist J . Minireview: From anorexia to obesity--the yin and yang of body weight control. Endocrinology. 2003; 144(9):3749-56. DOI: 10.1210/en.2003-0241. View

Abizaid A, Liu Z, Andrews Z, Shanabrough M, Borok E, Elsworth J . Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite. J Clin Invest. 2006; 116(12):3229-39. PMC: 1618869. DOI: 10.1172/JCI29867. View

10.

Zigman J, Nakano Y, Coppari R, Balthasar N, Marcus J, Lee C . Mice lacking ghrelin receptors resist the development of diet-induced obesity. J Clin Invest. 2005; 115(12):3564-72. PMC: 1297251. DOI: 10.1172/JCI26002. View

11.

Jimerson D, Wolfe B . Neuropeptides in eating disorders. CNS Spectr. 2004; 9(7):516-22. DOI: 10.1017/s1092852900009603. View

12.

Yamanaka A, Beuckmann C, Willie J, Hara J, Tsujino N, Mieda M . Hypothalamic orexin neurons regulate arousal according to energy balance in mice. Neuron. 2003; 38(5):701-13. DOI: 10.1016/s0896-6273(03)00331-3. View