Cited by 175Stress Responses and CortisolNeuropeptides and Animal PhysiologyAdrenal Hormones and Disorders

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Neural Regulation of the Stress Response: The Many Faces of Feedback

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Myers, Brent, McKlveen, Jessica M., Herman, James P.·2012·Cellular and Molecular Neurobiology

DOI 10.1007/s10571-012-9801-yPMC PMC3956711

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Abstract

The mammalian stress response is an integrated physiological and psychological reaction to real or perceived adversity. Glucocorticoids (GCs) are an important component of this response, acting to redistribute energy resources to both optimize survival in the face of challenge and restore homeostasis after the immediate threat has subsided. Release of GCs is mediated by the hypothalamo–pituitary–adrenocortical (HPA) axis, driven by a neural signal originating in the paraventricular nucleus (PVN). Stress levels of GCs bind to glucocorticoid receptors (GRs) in multiple body compartments, including brain, and consequently have wide-reaching actions. For this reason, GCs serve a vital function in feedback inhibition of their own secretion. Fast, non-genomic feedback inhibition of the HPA axis is mediated at least in part by GC signaling in the PVN, acting by a cannabinoid-dependent mechanism to rapidly reduce both neural activity and GC release. Delayed feedback termination of the HPA axis response is mediated by forebrain GRs, presumably by genomic mechanisms. GCs also act in the brainstem to attenuate neuropeptidergic excitatory input to the PVN via acceleration of mRNA degradation, providing a mechanism to attenuate future responses to stressors. Thus, rather than having a single defined feedback switch, GCs work through multiple neurocircuits and signaling mechanisms to coordinate HPA axis activity to suit the overall needs of multiple body systems.

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“…restore homeostasis by exerting negative feedback on the HPA axis via binding to glucocorticoid and mineralocorticoid receptors in key brain regions, thus inhibiting further hormone release (Herman et al., 2016; Herman et al., 2020; Myers et al., 2012, 2014; Ulrich-Lai and Herman, 2009).”
InfluentialSelf-citation

Authors: Myers, B., McKlveen, J. M., & Herman, J. P.
Affiliations: University of Cincinnati (US)
Corresponding author: Myers, Brent
ORCID: Myers, Brent
McKlveen, Jessica M.
Herman, James P.
Venue: Cellular and Molecular Neurobiology
Publisher: Springer Science and Business Media LLC
Published: 2012-02-01
Volume: 32
Issue: 5
Pages: 683-694
ISSN: 0272-4340 (ISSN-L)
1573-6830
DOI: 10.1007/s10571-012-9801-y
PMC: PMC3956711
OpenAlex: W2004982081
Semantic Scholar: ab6597d145f936c7638a64a02075f0bd9d576ebc
Cited by: 175
References: 151
Citations by year: 2026: 5 · 2025: 13 · 2024: 8 · 2023: 10 · 2022: 23 · 2021: 10 · 2020: 13 · 2019: 11 · 2018: 16 · 2017: 11 · 2016: 14 · 2015: 15 · 2014: 12 · 2013: 11 · 2012: 3
FWCI: 5.49
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Cellular and Molecular Neurobiology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
Funders: National Institutes of Health
National Institute of Mental Health (R01MH049698, R21MH090574, R01MH069860, R01MH069725)
National Institute of Diabetes and Digestive and Kidney Diseases (T32DK059803)
National Institute of Neurological Disorders and Stroke (T32NS007453)
Topics: Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Keywords: stress response, glucocorticoids, hypothalamic-pituitary-adrenal axis, paraventricular nucleus, glucocorticoid receptor, cannabinoid signaling, mRNA degradation, neuropeptide signaling, homeostasis, brainstem

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Neural Regulation of the Stress Response: The Many Faces of Feedback

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