Role of paraventricular nucleus glutamate signaling in regulation of HPA axis stress responses
Open accessAbstract
The hypothalamus-pituitary-adrenal (HPA) axis is the main neuroendocrine arm of the stress response, activation of which leads to the production of glucocorticoid hormones. Glucocorticoids are steroid hormones that are secreted from the adrenal cortex, and have a variety of effects on the body, including modulation of the immune system, suppression of reproductive hormones maintenance of blood glucose levels, and maintenance of blood pressure. Glutamate plays an important role in coordination of HPA axis output. There is strong evidence that glutamate drives HPA axis stress responses through excitatory signaling via ionotropic glutamate receptor signaling. However, glutamate signaling via kainate receptors and group I metabotropic receptors inhibit HPA drive, probably via presynaptic inhibitory mechanisms. Notably, kainate receptors are also localized in the median eminence, and appear to play an excitatory role in control of CRH release at the nerve terminals. Finally, glutamate innervation of the PVN undergoes neuroplastic changes under conditions of chronic stress, and may be involved in sensitization of HPA axis responses. Altogether, the data suggest that glutamate plays a complex role in excitation of CRH neurons, acting at multiple levels to both drive HPA axis responses and limit over-activation.
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Glutamate signaling has been associated with both activation and inhibition of the HPA axis through inotropic and kainite/group I metabotropic receptors respectively.
“glutamate signaling has been associated with both activation and inhibition of the HPA axis through inotropic and kainite/group I metabotropic receptors respectively (224).”
From Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma (2019) · cites this paper as [224]
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- Authors
- EVANSON, N. K., & HERMAN, J. P.
- Affiliations
- Cincinnati Children's Hospital Medical Center (US)
- University of Cincinnati (US)
- Venue
- Interdisciplinary Information Sciences
- Published
- 2015
- Volume
- 21
- Issue
- 3
- Pages
- 253-260
- ISSN
- 1340-9050 (ISSN-L)
- 1347-6157
- PMC
- PMC4603839
- OpenAlex
- W2418285440
- Cited by
- 48
- References
- 66
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 3 · 2023: 4 · 2022: 8 · 2021: 6 · 2020: 3 · 2019: 4 · 2018: 3 · 2017: 8 · 2016: 4
- FWCI
- 2.60
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Interdisciplinary Information Sciences (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Cincinnati
- National Institute of Mental Health (R01MH069725)
- National Institute of Diabetes and Digestive and Kidney Diseases (T32DK059803)
- National Institute of Neurological Disorders and Stroke (T32NS007453)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (K12HD001097)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- paraventricular nucleus, glutamate signaling, hypothalamic-pituitary-adrenal axis, stress response, glucocorticoids, ionotropic glutamate receptors, kainate receptors, group I metabotropic glutamate receptors, CRH neurons, median eminence, presynaptic inhibition, chronic stress, neuroplasticity, hypothalamus
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