The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Why stress is bad for your brain
Sapolsky, R. M. (1996) · Science · doi:10.1126/science.273.5276.749 · Cited by 1,306 · cited 1×
“Based on these observations, concern has been raised that prolonged elevation of endogenous GCs caused by chronic stress or pharmacological doses of GCs commonly administered to humans with inflammatory or bronchospastic diseases might produce hippocampal neuronal loss and resultant cognitive impairment, particularly…”
BackgroundStress induces atrophy of apical dendrites of hippocampal CA3 pyramidal neurons
Watanabe, Y., Gould, E., & McEwen, B. S. (1992) · Brain Research · doi:10.1016/0006-8993(92)91597-8 · Cited by 1,212
Unbiased stereological estimation of the number of neurons in the human hippocampus
West, M. J., & Gundersen, H. J. G. (1990) · Journal of Comparative Neurology · doi:10.1002/cne.902960102 · Cited by 1,153 · cited 2×
“None of these exogenous GC administration studies used stereological counting methods to determine neuronal numbers in a manner unbiased by neuron size, shape, or volumetric changes (West and Gundersen, 1990).”
BackgroundMethodProlonged glucocorticoid exposure reduces hippocampal neuron number: implications for aging
Sapolsky, R., Krey, L., & McEwen, B. (1985) · The Journal of Neuroscience · doi:10.1523/jneurosci.05-05-01222.1985 · Cited by 1,129
Hippocampal damage associated with prolonged glucocorticoid exposure in primates
Sapolsky, R., Uno, H., Rebert, C., & Finch, C. (1990) · The Journal of Neuroscience · doi:10.1523/jneurosci.10-09-02897.1990 · Cited by 1,103
Woolley, C. S., Gould, E., & McEwen, B. S. (1990) · Brain Research · doi:10.1016/0006-8993(90)90778-a · Cited by 1,020
New stereological methods for counting neurons
West, M. J. (1993) · Neurobiology of Aging · doi:10.1016/0197-4580(93)90112-o · Cited by 940
Starkman, M. N., Gebarski, S. S., Berent, S., & Schteingart, D. E. (1992) · Biological Psychiatry · doi:10.1016/0006-3223(92)90079-f · Cited by 840
(1992) · Cited by 777
Hippocampal damage associated with prolonged and fatal stress in primates
Uno, H., Tarara, R., Else, J., Suleman, M., & Sapolsky, R. (1989) · The Journal of Neuroscience · doi:10.1523/jneurosci.09-05-01705.1989 · Cited by 728
Research works printed but not linked: 1
- Schimmer BP Parker KL (1996) Adrenocorticotropic hormone, adrenocortical steroids and their synthetic analogs: inhibitors of the synthesis and actions of adrenocortical hormones. in Goodman & Gilman’s the pharmacological basis of therapeutics, Ed 9, eds Hardman JG Limbird LE (McGraw-Hill, New York), pp 1459–1485.
Cited by
Sorted by citations
Items 101–154 of 154
Cortisol/DHEA ratio and hippocampal volume: A pilot study in major depression and healthy controls
Jin, R. O., Mason, S., Mellon, S. H., Epel, E. S., Reus, V. I., Mahan, L., Rosser, R. L., Hough, C. M., Burke, H. M., Mueller, S. G., et al. (2016) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2016.06.017 · Cited by 41
Willette, A. A., Coe, C. L., Colman, R. J., Bendlin, B. B., Kastman, E. K., Field, A. S., Alexander, A. L., Allison, D. B., Weindruch, R. H., & Johnson, S. C. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2011.10.006 · Cited by 41
Hippocampal Volume in Healthy Controls Given 3-Day Stress Doses of Hydrocortisone
Brown, E. S., Jeon‐Slaughter, H., Lu, H., Jamadar, R., Issac, S., Shad, M. U., Denniston, D., Tamminga, C. A., Nakamura, A., & Thomas, B. P. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.307 · Cited by 43
Nonhuman Primate Models of Cognitive Aging
Agnès Lacreuse, A., & Herndon, J. G. (2008) · Humana Press eBooks · doi:10.1007/978-1-59745-422-3_2 · Cited by 42
Effects of stress hormones on the structure and function of the human brain
Wolf, O. T. (2006) · Expert Review of Endocrinology & Metabolism · doi:10.1586/17446651.1.5.623 · Cited by 41
Schubert, M. I., Kalisch, R., Sotiropoulos, I., Catania, C., Sousa, N., Almeida, O. F. X., & Auer, D. P. (2008) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2007.10.003 · Cited by 38
Llorens-Martı́n, M., & Trejo, J. L. (2011) · PLoS ONE · doi:10.1371/journal.pone.0028376 · Cited by 38
Anti-inflammatory therapy for Alzheimer's disease: implications of the prednisone trial
Aisen, P. S. S. (2000) · Acta Neurologica Scandinavica · doi:10.1034/j.1600-0404.2000.00312.x · Cited by 36
The glucocorticoid hormone: from pedestal to dust and back
Angelucci, L. (2000) · European Journal of Pharmacology · doi:10.1016/s0014-2999(00)00547-1 · Cited by 35
Витальевич, П. В., & Omanska-Klusek, A. (2004) · Journal of Neurobiology · doi:10.1002/neu.20069 · Cited by 31
Turlejski, K., & Djavadian, R. L. (2002) · Progress in brain research · doi:10.1016/s0079-6123(02)36006-0 · Cited by 31
Bremner, J. D. (2007) · Cambridge University Press eBooks · doi:10.1017/cbo9780511500008.010 · Cited by 28
Taxonomic Separation of Hippocampal Networks: Principal Cell Populations and Adult Neurogenesis
van Dijk, R. M., Huang, S., Slomianka, L., & Amrein, I. (2016) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2016.00022 · Cited by 27
Attenuation of the Effects of Corticosteroids on Declarative Memory with Lamotrigine
Brown, E. S., Wolfshohl, J., Shad, M. U., Vazquez, M., & Osuji, I. J. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301627 · Cited by 27
Metabolic and endocrinological causes of dementia
Flicker, L. A., & Ames, D. J. (2005) · International Psychogeriatrics · doi:10.1017/s1041610205001961 · Cited by 21
Involvement of Ghrelin Dynamics in Stress-Induced Eating Disorder: Effects of Sex and Aging
Yamada, C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222111695 · Cited by 20
McMillan, P. J., Wilkinson, C. W., Greenup, L., Raskind, M. A., Peskind, E. R., & Leverenz, J. B. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02760.x · Cited by 20
Self-citationSerra, M., Salgado‐Pineda, P., Delaveau, P., Fakra, É., Gastó, C., & Blin, O. J. (2006) · Clinical Neuropharmacology · doi:10.1097/01.wnf.0000214799.25044.ea · Cited by 18
Endangerment of the brain by glucocorticoids: Experimental and clinical evidence
Gubba, E. M., Netherton, C. M., & Herbert, J. (2000) · Journal of Neurocytology · doi:10.1023/a:1007177610378 · Cited by 14
Colon-Emeric, C. S., Walston, J. D., Bartolomucci, A., Carroll, J., Picard, M. A., Salmon, A., Suglia, S. F., Whitson, H. E., & Abadir, P. M. (2024) · Journal of the American Geriatrics Society · doi:10.1111/jgs.19246 · Cited by 11
Linking maternal disrupted interaction and infant limbic volumes: The role of infant cortisol output
Khoury, J. E., Ahtam, B., Ou, Y., Jenkins, E., Klengel, T., Enlow, M. B., Grant, P. E., & Lyons‐Ruth, K. (2023) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2023.106379 · Cited by 11
Brown, E. S., Lu, H., Denniston, D., Uh, J., Thomas, B. P., Carmody, T. J., Auchus, R. J., Diaz-Arrastia, R., & Tamminga, C. (2013) · Journal of Affective Disorders · doi:10.1016/j.jad.2013.01.038 · Cited by 11
Marshall, A. G., McCarthy, M., Brishnehan, K. M., Rao, V., Batia, L. M., Gupta, M., Das, S., Mitra, N. K., & Chaudhuri, J. D. (2009) · Alcohol · doi:10.1016/j.alcohol.2008.12.004 · Cited by 11
Kim, K.-N., Kim, B.-T., Kim, Y., Lee, J.-H., & Jahng, J. W. (2014) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2014.02.017 · Cited by 10
Glucocorticoids and the Aging Brain: Cause or Consequence?
Lucassen, P. J., & de Kloet, E. R. (2001) · Elsevier eBooks · doi:10.1016/b978-012351830-9/50064-0 · Cited by 10
Child sex moderates the relationship between cortisol stress reactivity and symptoms over time
Daoust, A. R., Kotelnikova, Y., Kryski, K. R., Sheikh, H. I., Singh, S. M., & Hayden, E. P. (2018) · Comprehensive Psychiatry · doi:10.1016/j.comppsych.2018.10.009 · Cited by 10
Jahng, J. W., & Lee, J.-H. (2015) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2015.10.052 · Cited by 8
The Adrenals and Pituitary—Stress, Adaptation, and Longevity
Timiras, P. S., & Gersten, O. (2007) · CRC Press eBooks · doi:10.3109/9781420007091-15 · Cited by 7
Szot, P., Wilkinson, C. W., White, S. S., Leverenz, J. B., Greenup, J. L., Colasurdo, E. A., Peskind, E. R., & Raskind, M. A. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.03.030 · Cited by 6
Self-citationMechanisms of Glucocorticoid Actions in Stress and Brain Aging
Porter, N. M., Herman, J. P., & Landfield, P. W. (2001) · Comprehensive physiology · doi:10.1002/cphy.cp070414 · Cited by 6
Abelson, K., & Grøndahl, C. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-822215-7.00015-9 · Cited by 4
Fuchs, E., Czéh, B., & Flügge, G. (2005) · Drug Development Research · doi:10.1002/ddr.20032 · Cited by 4
Festini, S. B., & McDonough, I. M. (2024) · Cognitive Affective & Behavioral Neuroscience · doi:10.3758/s13415-024-01246-0 · Cited by 3
Liang, K. J., Colasurdo, E. A., Li, G., Shofer, J. B., Galasko, D. R., Quinn, J. F., Farlow, M. R., & Peskind, E. R. (2024) · Journal of the Endocrine Society · doi:10.1210/jendso/bvae220 · Cited by 3
Self-citationFerrari, E., Cravello, L., Bonacina, M., Salmoiraghi, F., & Magri, F. (2005) · Techniques in the behavioral and neural sciences · doi:10.1016/s0921-0709(05)80064-1 · Cited by 3
Vollmann-Honsdorf, G. K. (2001) · Publikationen an der Universität Bielefeld (Universität Bielefeld) · Cited by 2
Ferroptosis in depression: mechanisms, association, and therapeutic strategies
Zhang, C., Chen, S. Y., Yan, C., Jiang, Y., Wang, Y., Yu, Z., Xie, T., Tian, M., Yao, G., Yan, Y., et al. (2026) · Journal of Neural Transmission · doi:10.1007/s00702-026-03248-3 · Cited by 1
Methodological Considerations when Studying the Aging Process in the Nonhuman Primate Brain
Keuker, J. I. H., Michaelis, T., de Biurrun, G., Luiten, P. G. M., Witter, M. P., & Fuchs, E. (2002) · KARGER eBooks · doi:10.1159/000061460 · Cited by 1
Ghasemabad, S. H. A., Sadeghi, Y., & Haghir, H. (2008) · Iranian journal of pathology · Cited by 1
Azcoitia, Í., & García‐Segura, L. M. (2012) · Elsevier eBooks · doi:10.1016/b978-0-12-375097-6.10026-5 · Cited by 1
Wolf, O. T., & Kirschbaum, C. (2003) · Psychologische Rundschau · doi:10.1026//0033-3042.54.3.150 · Cited by 1
The New Neurobiology of Depression
Kim, Y. K. (2001) · Saengmul jeongsin euihag/Saengmul jeongsin uihak · Cited by 1
DeMarco, G. J. (2008) · Elsevier eBooks · doi:10.1016/b978-012373898-1.50030-9
Anti-inflammatory and Antioxidant Therapies in Alzheimer's Disease
Aisen, P. S. S., & Pasinetti, G. M. (2001) · Elsevier eBooks · doi:10.1016/b978-012351830-9/50035-4
Stress, Cortisol und Gedächtnisleistung im Alter
Wolf, O. T. (2011) · Zeitschrift für Medizinische Psychologie · doi:10.3233/zmp-2011-2026
Chronic Stress and Hippocampus Vulnerability to Functional Changes and Health in the Adult
Conrad, C. D. (2011) · Wiley eBooks · doi:10.1002/9781118083222.ch16
NEUROBIOLOGICAL PERSPECTIVES ON TRAUMA
Kirmayer, L. J., Lemelson, R., & Barad, M. (2007) · Cambridge University Press eBooks · doi:10.1017/cbo9780511500008.004 · Cited by 1
Emotion, Temperament, Vulnerability, and Development: Evidence from Nonhuman Primate Models
Erickson, K., Higley, J. D., & Schulkin, J. A. (2007) · Cambridge University Press eBooks · doi:10.1017/cbo9780511499791.013
The rewarding and cognitive effects of corticosterone in mice
Ebada, M. E. (2012) · Nottingham ePrints (University of Nottingham)
Differential Na+/K+ Pump Isoform Expression in Higher and Lower Brain Regions of the Mouse
Lowry, C. A. (2017) · QSpace (Queen's University Library)
Daoust, A. R. (2018) · Scholarship@Western (Western University)
Mechanisms of Glucocorticoid Actions in Stress and Brain Aging
Porter, N. M., Herman, J. P., & Landfield, P. W. (2000) · Comprehensive physiology · doi:10.1002/j.2040-4603.2000.tb01519.x
Role of astrocytes in the development and progression of major depressive disorder
Jing, P., Sun, C., Xiao-peng, Y. I. N., Liu, X.-C., Tian, Q., & (673328), X.-B. Z. (2026) · World Journal of Psychiatry · doi:10.5498/wjp.v16.i5.115794
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
