Cited by 154Stress Responses and CortisolMemory and Neural MechanismsNeurogenesis and neuroplasticity mechanisms

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Effect of Chronic High-Dose Exogenous Cortisol on Hippocampal Neuronal Number in Aged Nonhuman Primates

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Leverenz, James B., Wilkinson, Charles W., Wamble, Molly, Corbin, Shannon, Grabber, Jo Ellen, Raskind, Murray A., Peskind, Elaine R.·1999·The Journal of Neuroscience

DOI 10.1523/jneurosci.19-06-02356.1999PMC PMC6782558

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Abstract

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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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)
ORCID: Leverenz, James B.
Wilkinson, Charles W.
Raskind, Murray A.
Peskind, Elaine R.
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
DOI: 10.1523/jneurosci.19-06-02356.1999
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: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 184 d)
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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Effect of Chronic High-Dose Exogenous Cortisol on Hippocampal Neuronal Number in Aged Nonhuman Primates

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