The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
Ghrelin Regulates the Hypothalamic-Pituitary-Adrenal Axis and Restricts Anxiety After Acute Stress
Open accessAbstract
Background Ghrelin plays important roles in glucose metabolism, appetite, and body weight regulation, and recent evidence suggests ghrelin prevents excessive anxiety under conditions of chronic stress.Methods We used ghrelin knockout (ghr-/-) mice to examine the role of endogenous ghrelin in anxious behavior and hypothalamic-pituitary-adrenal axis (HPA) responses to acute stress.Results Ghr-/- mice are more anxious after acute restraint stress, compared with wild-type (WT) mice, with three independent behavioral tests. Acute restraint stress exacerbated neuronal activation in the hypothalamic paraventricular nucleus and medial nucleus of the amygdala in ghr-/- mice compared with WT, and exogenous ghrelin reversed this effect. Acute stress increased neuronal activation in the centrally projecting Edinger-Westphal nucleus in WT but not ghr-/- mice. Ghr-/- mice exhibited a lower corticosterone response after stress, suggesting dysfunctional glucocorticoid negative feedback in the absence of ghrelin. We found no differences in dexamethasone-induced Fos expression between ghr-/- and WT mice, suggesting central feedback was not impaired. Adrenocorticotropic hormone replacement elevated plasma corticosterone in ghr-/-, compared with WT mice, indicating increased adrenal sensitivity. The adrenocorticotropic hormone response to acute stress was significantly reduced in ghr-/- mice, compared with control subjects. Pro-opiomelanocortin anterior pituitary cells express significant growth hormone secretagogue receptor.Conclusions Ghrelin reduces anxiety after acute stress by stimulating the HPA axis at the level of the anterior pituitary. A novel neuronal growth hormone secretagogue receptor circuit involving urocortin 1 neurons in the centrally projecting Edinger-Westphal nucleus promotes an appropriate stress response. Thus, ghrelin regulates acute stress and offers potential therapeutic efficacy in human mood and stress disorders.
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“Ghrelin is a 28 amino-acid stomach-derived peptide known for its powerful physiological orexigenic and adipogenic effects, as well as for its contribution toward the stress response, anxiety, and depression [293][294][295][296][297].”
From Anxiety, depression, and the microbiome: A role for gut peptides (2018) · cites this paper as [295]
In the citing paper
“Mice lacking endogenous ghrelin have a dampened circulating glucocorticoid response following an acute stressor due a deficit in the PVN response needed to stimulate ACTH from the pituitary [295,311].”
From Anxiety, depression, and the microbiome: A role for gut peptides (2018) · cites this paper as [295]
Citations
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The orexigenic hormone ghrelin defends against depressive symptoms of chronic stress
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Müller, T. D., Nogueiras, R., Andermann, M. L., Andrews, Z. B., Anker, S. D., Argente, J., Batterham, R. L., Benoit, S. C., Bowers, C. Y., Broglio, F., et al. (2015) · Molecular Metabolism · doi:10.1016/j.molmet.2015.03.005 · Cited by 1,034
Self-citationAnxiety, depression, and the microbiome: A role for gut peptides
Lach, G., Schellekens, H., Dinan, T. G., & Cryan, J. F. (2018) · Neurotherapeutics · doi:10.1007/s13311-017-0585-0 · Cited by 573
How might circadian rhythms control mood? Let me count the ways
McClung, C. A. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.02.019 · Cited by 507
“Moreover, ghrelin (Ghr −/−) knock-out mice are more anxious after acute restraint stress and this is likely due to a problem with the normal glucocorticoid feedback in response to stress (68).”
BackgroundDiet, Stress and Mental Health
Bremner, J. D., Moazzami, K., Wittbrodt, M. T., Nye, J. A., Lima, B. B., Gillespie, C. F., Rapaport, M. H., Pearce, B. D., Shah, A. J., & Vaccarino, V. (2020) · Nutrients · doi:10.3390/nu12082428 · Cited by 421
“Stress increases ghrelin levels in the plasma [218,219], and ghrelin mediates the stress-induced increase in food intake associated with exposure to chronic stress [220] as well as behavioral responses to stress [219].”
BackgroundEating behavior and stress: a pathway to obesity
Sominsky, L., & Spencer, S. J. (2014) · Frontiers in Psychology · doi:10.3389/fpsyg.2014.00434 · Cited by 361
“…(Kristenssson et al., 2006) and probably acts at the level of the anterior pituitary as well as higher brain regions, such as the centrally projecting Edinger Westphal nucleus (EWcp), to modulate ACTH release from the pituitary and regulate glucocorticoid negative feedback (Spencer et al., 2012).”
Background
Metadata
- Authors
- Spencer, S. J., Xu, L., Clarke, M. A., Lemus, M., Reichenbach, A., Geenen, B., Kozicz, T., & Andrews, Z. B.
- Affiliations
- Monash University (AU)
- Radboud University Nijmegen (NL)
- Corresponding author
- Andrews, Zane B.
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2012-09
- Volume
- 72
- Issue
- 6
- Pages
- 457-465
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2068804599
- Cited by
- 241
- References
- 54
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 23 · 2023: 11 · 2022: 15 · 2021: 20 · 2020: 15 · 2019: 16 · 2018: 13 · 2017: 23 · 2016: 22 · 2015: 16 · 2014: 21 · 2013: 22 · 2012: 4
- FWCI
- 8.36
- Type
- journal article
- Language
- en
- Open access
- green
- figshare.com
- Licence
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- RMIT Research Repository (RMIT University Library) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- National Health and Medical Research Council of Australia (1011274)
- Australian Research Council (DP109339)
- Monash Fellowship (FT100100966)
- National Health and Medical Research Council Peter Doherty Research Fellowship (465167)
- Endocrine Society of Australia Postdoctoral Fellowship (FT110100084)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- ghrelin, hypothalamic-pituitary-adrenal axis, anxiety, acute stress, restraint stress, corticosterone, glucocorticoid negative feedback, ACTH, anterior pituitary, growth hormone secretagogue receptor, proopiomelanocortin, Edinger-Westphal nucleus, urocortin 1, paraventricular nucleus, amygdala, stress response
- MeSH terms
- Adrenocorticotropic Hormone, Analysis of Variance, Animals, Anxiety, Corticosterone, Corticotropin-Releasing Hormone, Dexamethasone, Hypothalamo-Hypophyseal System, Pituitary-Adrenal System, Restraint, Physical, Stress, Psychological, Mice, Knockout, Mice, Ghrelin, Receptors, Ghrelin
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