Altered Regulation of Gene and Protein Expression of Hypothalamic‐Pituitary‐Adrenal Axis Components in an Immature Rat Model of Chronic Stress
Open accessAbstract
Chronic stress early in postnatal life influences hormonal and behavioural responses to stress persistently, but the mechanisms and molecular cascades that are involved in this process have not been clarified. To approach these issues, a chronic stress paradigm for the neonatal rat, using limited bedding material to alter the cage environment, was devised. In 9-day-old rats subjected to this chronic stress for 1 week, significant and striking changes in the expression and release patterns of key molecules that govern the neuroendocrine stress responses were observed. The presence of sustained stress was evident from enhanced activation of peripheral elements of the neuroendocrine stress response, i.e. increased basal plasma corticosterone concentrations, high adrenal weight and decreased body weight. Central regulatory elements of the neuroendocrine stress response were perturbed, including reduced expression of hypothalamic corticotropin-releasing hormone that, surprisingly, was accompanied by reduced glucocorticoid receptor expression. Thus, the effects of chronic sustained stress in the neonatal rat on the hypothalamic-pituitary-adrenal axis included substantial changes in the expression and activity of major regulators of this axis. Importantly, the changes induced by this chronic stress differed substantially from those related to acute or recurrent stress, providing a novel model for studying the long-term effects of chronic, early life stress on neuroendocrine function…
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The decreased hypothalamic CRF expression occurs earlier in development than the difference in hippocampal GR expression, suggesting that the difference in CRF expression develops independent of GR regulation.
“However, in these studies the decreased hypothalamic CRF expression occurs earlier in development than does the difference in hippocampal GR expression, suggesting that the difference in CRF expression develops independent of GR regulation.”
From Early life adversity and the epigenetic programming of hypothalamic-pituitary-adrenal function (2014) · cites this paper as [114]
The maternally regulated decrease in CRF expression is accompanied by an increase in hippocampal GR expression.
“Baram and colleagues114 showed that this maternally regulated decrease in CRF expression is accompanied by an increase in hippocampal GR expression.”
From Early life adversity and the epigenetic programming of hypothalamic-pituitary-adrenal function (2014) · cites this paper as [114]
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- Authors
- Avishai‐Eliner, S., Gilles, E. E., Eghbal‐Ahmadi, M., Bar‐El, Y., & Baram, T. Z.
- Affiliations
- University of California, Irvine (US)
- University of Minnesota (US)
- Kaplan Medical Center (IL)
- Corresponding author
- Baram, T. Z.
- ORCID
- Baram, T. Z.
- Venue
- Journal of Neuroendocrinology
- Publisher
- Wiley
- Published
- 2001-09
- Volume
- 13
- Issue
- 9
- Pages
- 799-807
- ISSN
- 0953-8194 (ISSN-L)
- 1365-2826
- PMC
- PMC3100736
- OpenAlex
- W1487001307
- Cited by
- 139
- References
- 5
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 7 · 2023: 6 · 2022: 7 · 2021: 6 · 2020: 7 · 2019: 5 · 2018: 6 · 2017: 7 · 2016: 15 · 2015: 7 · 2014: 15 · 2013: 7 · 2012: 8
- FWCI
- 0.46
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Neuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (NS 28912, R01NS028912, NS 39307, R01NS039307)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- chronic stress, early life stress, hypothalamic-pituitary-adrenal axis, corticotropin-releasing factor, glucocorticoid receptor, corticosterone, neonatal rats, neuroendocrine stress response, gene expression, protein expression, adrenal weight
- MeSH terms
- Adrenal Glands, Animals, Animals, Newborn, Bedding and Linens, Chronic Disease, Corticosterone, Corticotropin-Releasing Hormone, Female, Frontal Lobe, Gene Expression Regulation, Hippocampus, Hypothalamo-Hypophyseal System, Male, Nerve Tissue Proteins, Organ Size, Paraventricular Hypothalamic Nucleus, Pituitary-Adrenal System, Receptors, Glucocorticoid, RNA, Messenger, Stress, Physiological, Receptors, Corticotropin-Releasing Hormone, Rats
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