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Effect of Chronic High-Dose Exogenous Cortisol on Hippocampal Neuronal Number in Aged Nonhuman Primates
Open accessAbstract
Chronic exposure to increased glucocorticoid concentrations appears to lower the threshold for hippocampal neuronal degeneration in the old rat. It has been proposed that increased brain exposure to glucocorticoids may lower the threshold for hippocampal neuronal degeneration in human aging and Alzheimer's disease. Here, we asked whether chronic administration of high-dose cortisol to older nonhuman primates decreases hippocampal neuronal number as assessed by unbiased stereological counting methodology. Sixteen Macaca nemestrina (pigtailed macaques) from 18 to 29 years of age were age-, sex-, and weight-matched into pairs and randomized to receive either high-dose oral hydrocortisone (cortisol) acetate (4-6 mg/kg/d) or placebo in twice daily palatable treats for 12 months. Hypothalamic-pituitary-adrenal activity was monitored by measuring plasma adrenocorticotropin and cortisol, 24 hr urinary cortisol, and CSF cortisol. Urinary, plasma, and CSF cortisol were elevated, and plasma adrenocorticotropin was reduced in the active treatment group. Total hippocampal volume, subfield volumes, subfield neuronal density, and subfield total neuronal number did not differ between the experimental groups. These findings suggest that chronically elevated cortisol concentrations, in the absence of stress, do not produce hippocampal neuronal loss in nonhuman primates.
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“Given these results with rodents, it is not so surprising that a relatively modest regimen of cortisol treatment for 12 months did not cause outright neuronal loss in the pigtail macaque hippocampus (Leverenz et al., 1999).”
From Central effects of stress hormones in health and disease: understanding the protective and damaging effects of stress and stress mediators (2008) · cites this paper as Leverenz et al., 1999
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Metadata
- Authors
- Leverenz, J. B., Wilkinson, C. W., Wamble, M., Corbin, S., Grabber, J. E., Raskind, M. A., & Peskind, E. R.
- Affiliations
- University of Washington (US)
- VA Puget Sound Health Care System (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1999-03-15
- Volume
- 19
- Issue
- 6
- Pages
- 2356-2361
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6782558
- OpenAlex
- W2158732391
- Cited by
- 154
- References
- 28
- Citations by year
- 2026: 2 · 2024: 3 · 2023: 2 · 2021: 1 · 2018: 2 · 2017: 2 · 2016: 4 · 2015: 2 · 2014: 3 · 2013: 3 · 2012: 3
- FWCI
- 7.80
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- ResearchWorks at the University of Washington (University of Washington) (submittedVersion)
- Funders
- U.S. Department of Veterans Affairs
- Alzheimer's Association
- National Institutes of Health
- National Institute on Aging (AGO6136)
- National Center for Research Resources (P51RR000166)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- glucocorticoids, hippocampal neurodegeneration, aging, non-human primates, macaque, cortisol, hypothalamic-pituitary-adrenal axis, ACTH, hippocampal subfields, Alzheimer's disease
- MeSH terms
- Aging, Animals, Cell Count, Dose-Response Relationship, Drug, Endocrine System, Female, Hippocampus, Hydrocortisone, Macaca nemestrina, Male, Neurons, Time Factors
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