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Cited by 143Stress Responses and CortisolNeuropeptides and Animal PhysiologyMemory and Neural Mechanisms

Chronic overexpression of corticotropin-releasing factor from the central amygdala produces HPA axis hyperactivity and behavioral anxiety associated with gene-expression changes in the hippocampus and paraventricular nucleus of the hypothalamus

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Flandreau, Elizabeth I., Ressler, Kerry J., Owens, Michael J., Nemeroff, Charles B.·2012·Psychoneuroendocrinology
DOI 10.1016/j.psyneuen.2011.04.014PMC PMC3164918
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Abstract

Environmental stress has been demonstrated to increase susceptibility for mood and anxiety disorders, and hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, the primary endocrine response to stress, is often observed in these patients. HPA axis activation is initiated by corticotropin-releasing factor (CRF) from the hypothalamus, leading to the hypothesis that hypothalamic CRF overexpression contributes to HPA axis hyperactivity in psychiatric patients. In addition, elevated CRF in cerebrospinal fluid is observed in mood and anxiety disorder patients, suggesting that CRF is also being overproduced from extrahypothalamic sources such as the central amygdala (CeA) and overactivity of the amygdala in neuroimaging studies is a consistent finding in anxiety and depression patients. Due to the importance of CRF and the amygdala in the etiology of stress-sensitive psychiatric disorders, the present study sought to further dissect the impact of CRF overexpression (OE) in the amygdala on downstream behavioral, endocrine, and gene-expression changes typically associated with chronic stress. To test the hypothesis that elevated CRF output from the amygdala would reproduce HPA axis hyperactivity and behavioral symptoms of chronic stress, we developed a lentiviral vector in which 3.0kb of the CRF promoter drives overexpression of CRF (LVCRFp3.0CRF). In adult male rats, Experiment-1 examined behavioral consequences of chronic CRF overexpression from the amygdala; the dexamethasone (Dex)/CRF test was used to measure HPA axis reactivity. Experiment-2 focused on HPA axis disruptions; the dexamethasone-suppression and CRF-stimulation tests as well as the Dex/CRF test were used. In both experiments, expression of HPA-axis related transcripts were assessed.

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  • Stimulation to central nuclei of the amygdala causes overexpression of CRH resulting in an increase in HPA axis activity.

    “Stimulation to central nuclei causes overexpression of CRH resulting in an increase in HPA axis activity (68–70).”

    From Childhood Trauma, the HPA Axis and Psychiatric Illnesses: A Targeted Literature Synthesis (2022) · cites this paper as [69]

    The Results (HPA Axis Reactivity; page unavailable) report that ten weeks of experimentally induced CRF overexpression in the central amygdala produced HPA-axis hyperactivity in rats. The paper does not show that stimulation of the central amygdala causes CRF overexpression; it induced overexpression with a lentiviral vector. The same section reports no significant HPA-axis difference after six weeks of overexpression. (LLM, conf=0.88)

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Authors
Flandreau, E. I., Ressler, K. J., Owens, M. J., & Nemeroff, C. B.
Affiliations
  • Salk Institute for Biological Studies (US)
  • Howard Hughes Medical Institute (US)
  • Emory University (US)
  • University of Miami (US)
Corresponding author
Flandreau, Elizabeth I.
ORCID
Venue
Psychoneuroendocrinology
Publisher
Elsevier BV
Published
2012-01
Volume
37
Issue
1
Pages
27-38
ISSN
0306-4530 (ISSN-L)
DOI
10.1016/j.psyneuen.2011.04.014
PMC
PMC3164918
OpenAlex
W1972308065
Cited by
143
References
2
Citations by year
2026: 11 · 2025: 9 · 2024: 5 · 2023: 10 · 2022: 10 · 2021: 7 · 2020: 7 · 2019: 11 · 2018: 6 · 2017: 11 · 2016: 9 · 2015: 11 · 2014: 9 · 2013: 16 · 2012: 10
FWCI
4.52
Type
journal article
Language
en
Open access
Licence
Locations
  • Psychoneuroendocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute of Mental Health (R01MH042088, F31MH079667, P50MH058922, MH39415, MH58922, MH42088, MH-77083, P50MH077083, MH079667A)
  • National Institute on Drug Abuse (DA01962)
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords
corticotropin-releasing factor, central amygdala, HPA axis hyperactivity, anxiety, chronic stress, lentiviral overexpression, hippocampus, paraventricular nucleus, gene expression, dexamethasone suppression test
MeSH terms
Amygdala, Animals, Anxiety Disorders, Corticotropin-Releasing Hormone, Dexamethasone, Disease Models, Animal, Genetic Vectors, Hippocampus, Humans, Hypothalamo-Hypophyseal System, Male, Paraventricular Hypothalamic Nucleus, Pituitary-Adrenal Function Tests, Pituitary-Adrenal System, Lentivirus, Rats, Wistar, Gene Expression Profiling, Rats

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