 |
 Previous Article | Next Article 
Journal of Neuroscience, Vol 10, 2897-2902, Copyright © 1990 by Society for Neuroscience
Hippocampal damage associated with prolonged glucocorticoid exposure in primates
RM Sapolsky, H Uno, CS Rebert and CE Finch
Department of Biological Sciences, Stanford University, California 94305.
In the laboratory rat and guinea pig, glucocorticoids (GCs), the adrenal
steroids that are secreted during stress, can damage the hippocampus and
exacerbate the hippocampal damage induced by various neurological insults.
An open question is whether GCs have similar deleterious effects in the
primate hippocampus. In fact, we showed that sustained and fatal stress was
associated with preferential hippocampal damage in the vervet monkey;
however, it was not possible to determine whether the excessive GC
secretion that accompanied such stress was the damaging agent. The present
study examines this possibility. Pellets of cortisol (the principal GC of
primates) were stereotaxically implanted into hippocampi of 4 vervet
monkeys; contralateral hippocampi were implanted with cholesterol pellets
as a control. One year later at postmortem, preferential damage occurred in
the cortisol-implanted side. In the cholesterol side, mild cell layer
irregularity was noted in 2 of 4 cases. By contrast in the cortisol-exposed
hippocampi, all cases had at least 2 of the following neuropathologic
markers: cell layer irregularity, dendritic atrophy, soma shrinkage and
condensation, or nuclear pyknosis. Damage was severe in some cases, and was
restricted to the CA3/CA2 cellfield. This anatomical distribution of
damage, and the cellular features of the damage agree with that observed in
instances of GC-induced toxicity in the rodent hippocampus, and of
stress-induced toxicity in the primate hippocampus. These observations
suggest that sustained GC exposure (whether due to stress, Cushings
syndrome or exogenous administration) might damage the human hippocampus.
This article has been cited by other articles:
|
|
|
|
 
C. F. Weems and V. G. Carrion
Brief Report: Diurnal Salivary Cortisol in Youth--Clarifying the Nature of Posttraumatic Stress Dysregulation
J. Pediatr. Psychol.,
August 9, 2008;
(2008)
jsn087v1.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. T. Kodl and E. R. Seaquist
Cognitive Dysfunction and Diabetes Mellitus
Endocr. Rev.,
June 1, 2008;
29(4):
494 - 511.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. I. Geerlings, T. den Heijer, P. J. Koudstaal, A. Hofman, and M.M.B. Breteler
History of depression, depressive symptoms, and medial temporal lobe atrophy and the risk of Alzheimer disease
Neurology,
April 8, 2008;
70(15):
1258 - 1264.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K J Rademaker, L S de Vries, C S P M Uiterwaal, F Groenendaal, D E Grobbee, and F van Bel
Postnatal hydrocortisone treatment for chronic lung disease in the preterm newborn and long-term neurodevelopmental follow-up
Arch. Dis. Child. Fetal Neonatal Ed.,
January 1, 2008;
93(1):
F58 - F63.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Felder-Puig, C. Scherzer, M. Baumgartner, M. Ortner, C. Aschenbrenner, C. Bieglmayer, T. Voigtlander, E. R. Panzer-Grumayer, W. J.E. Tissing, J. W. Koper, et al.
Glucocorticoids in the Treatment of Children with Acute Lymphoblastic Leukemia and Hodgkin's Disease: A Pilot Study on the Adverse Psychological Reactions and Possible Associations with Neurobiological, Endocrine, and Genetic Markers
Clin. Cancer Res.,
December 1, 2007;
13(23):
7093 - 7100.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. D. Taylor, S. Zuchner, D. R. McQuoid, D. C. Steffens, M. C. Speer, and K. R. R. Krishnan
Allelic Differences in the Brain-Derived Neurotrophic Factor Val66Met Polymorphism in Late-Life Depression
Am J Geriatr Psychiatry,
October 1, 2007;
15(10):
850 - 857.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. G. Carrion, C. F. Weems, and A. L. Reiss
Stress Predicts Brain Changes in Children: A Pilot Longitudinal Study on Youth Stress, Posttraumatic Stress Disorder, and the Hippocampus
Pediatrics,
March 1, 2007;
119(3):
509 - 516.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. C. Yang, C. H. Lin, and E. H. Y. Lee
Serum- and Glucocorticoid-Inducible Kinase 1 (SGK1) Increases Neurite Formation through Microtubule Depolymerization by SGK1 and by SGK1 Phosphorylation of tau
Mol. Cell. Biol.,
November 15, 2006;
26(22):
8357 - 8370.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. K. Adam, L. C. Hawkley, B. M. Kudielka, and J. T. Cacioppo
Day-to-day dynamics of experience-cortisol associations in a population-based sample of older adults
PNAS,
November 7, 2006;
103(45):
17058 - 17063.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Vermetten, C. Schmahl, S. Lindner, R. J. Loewenstein, and J. D. Bremner
Hippocampal and Amygdalar Volumes in Dissociative Identity Disorder
Am J Psychiatry,
April 1, 2006;
163(4):
630 - 636.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. D. Conrad
What Is the Functional Significance of Chronic Stress-Induced CA3 Dendritic Retraction Within the Hippocampus?
Behav Cogn Neurosci Rev,
March 1, 2006;
5(1):
41 - 60.
[Abstract]
[PDF]
|
|
|
|
|
|
|
S. Gil, Y. Caspi, I. Z. Ben-Ari, D. Koren, and E. Klein
Does Memory of a Traumatic Event Increase the Risk for Posttraumatic Stress Disorder in Patients With Traumatic Brain Injury? A Prospective Study
Am J Psychiatry,
May 1, 2005;
162(5):
963 - 969.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. D. Taylor, D. C. Steffens, M. E. Payne, J. R. MacFall, D. A. Marchuk, I. K. Svenson, and K. R. R. Krishnan
Influence of Serotonin Transporter Promoter Region Polymorphisms on Hippocampal Volumes in Late-Life Depression
Arch Gen Psychiatry,
May 1, 2005;
62(5):
537 - 544.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. P. Merke, J. N. Giedd, M. F. Keil, S. L. Mehlinger, E. A. Wiggs, S. Holzer, E. Rawson, A. C. Vaituzis, C. A. Stratakis, and G. P. Chrousos
Children Experience Cognitive Decline Despite Reversal of Brain Atrophy One Year After Resolution of Cushing Syndrome
J. Clin. Endocrinol. Metab.,
May 1, 2005;
90(5):
2531 - 2536.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. D. Bremner, T. Mletzko, S. Welter, S. Quinn, C. Williams, M. Brummer, S. Siddiq, L. Reed, C. M. Heim, and C. B. Nemeroff
Effects of phenytoin on memory, cognition and brain structure in post-traumatic stress disorder: a pilot study
J Psychopharmacol,
March 1, 2005;
19(2):
159 - 165.
[Abstract]
[PDF]
|
|
|
|
|
|
|
R. Brunner, D. Schaefer, K. Hess, P. Parzer, F. Resch, and S. Schwab
Effect of corticosteroids on short-term and long-term memory
Neurology,
January 25, 2005;
64(2):
335 - 337.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. M. MacQueen, S. Campbell, B. S. McEwen, K. Macdonald, S. Amano, R. T. Joffe, C. Nahmias, and L. T. Young
Course of Illness, Hippocampal Function, and Hippocampal Volume in Major Depression
Focus,
January 1, 2005;
3(1):
146 - 155.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Winter and E. Irle
Hippocampal Volume in Adult Burn Patients With and Without Posttraumatic Stress Disorder
Am J Psychiatry,
December 1, 2004;
161(12):
2194 - 2200.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Erwin, X. T. Tigno, G. Gerzanich, and B. C. Hansen
Age-Related Changes in Fasting Plasma Cortisol in Rhesus Monkeys: Implications of Individual Differences for Pathological Consequences
J. Gerontol. A Biol. Sci. Med. Sci.,
May 1, 2004;
59(5):
B424 - B432.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Campbell, M. Marriott, C. Nahmias, and G. M. MacQueen
Lower Hippocampal Volume in Patients Suffering From Depression: A Meta-Analysis
Am J Psychiatry,
April 1, 2004;
161(4):
598 - 607.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. D. Bremner, M. Vythilingam, E. Vermetten, V. Vaccarino, and D. S. Charney
Deficits in Hippocampal and Anterior Cingulate Functioning During Verbal Declarative Memory Encoding in Midlife Major Depression
Am J Psychiatry,
April 1, 2004;
161(4):
637 - 645.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. D. Bremner, M. Vythilingam, E. Vermetten, S. M. Southwick, T. McGlashan, A. Nazeer, S. Khan, L. V. Vaccarino, R. Soufer, P. K. Garg, et al.
MRI and PET Study of Deficits in Hippocampal Structure and Function in Women With Childhood Sexual Abuse and Posttraumatic Stress Disorder
Am J Psychiatry,
May 1, 2003;
160(5):
924 - 932.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. P. Merke, J. D. Fields, M. F. Keil, A. C. Vaituzis, G. P. Chrousos, and J. N. Giedd
Children with Classic Congenital Adrenal Hyperplasia Have Decreased Amygdala Volume: Potential Prenatal and Postnatal Hormonal Effects
J. Clin. Endocrinol. Metab.,
April 1, 2003;
88(4):
1760 - 1765.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Roozendaal, Q. K. Griffith, J. Buranday, D. J.-F. de Quervain, and J. L. McGaugh
The hippocampus mediates glucocorticoid-induced impairment of spatial memory retrieval: Dependence on the basolateral amygdala
PNAS,
February 4, 2003;
100(3):
1328 - 1333.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. M. MacQueen, S. Campbell, B. S. McEwen, K. Macdonald, S. Amano, R. T. Joffe, C. Nahmias, and L. T. Young
Course of illness, hippocampal function, and hippocampal volume in major depression
PNAS,
February 4, 2003;
100(3):
1387 - 1392.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Nakano, M. Wenner, M. Inagaki, A. Kugaya, T. Akechi, Y. Matsuoka, Y. Sugahara, S. Imoto, K. Murakami, and Y. Uchitomi
Relationship Between Distressing Cancer-Related Recollections and Hippocampal Volume in Cancer Survivors
Am J Psychiatry,
December 1, 2002;
159(12):
2087 - 2093.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. R. Weinberger and R. K. McClure
Neurotoxicity, Neuroplasticity, and Magnetic Resonance Imaging Morphometry: What Is Happening in the Schizophrenic Brain?
Arch Gen Psychiatry,
June 1, 2002;
59(6):
553 - 558.
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. M. Lyons, C. Yang, A. M. Sawyer-Glover, M. E. Moseley, and A. F. Schatzberg
Early Life Stress and Inherited Variation in Monkey Hippocampal Volumes
Arch Gen Psychiatry,
December 1, 2001;
58(12):
1145 - 1151.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. N. Starkman, B. Giordani, S. Berent, M. A. Schork, and D. E. Schteingart
Elevated Cortisol Levels in Cushing's Disease Are Associated With Cognitive Decrements
Psychosom Med,
November 1, 2001;
63(6):
985 - 993.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Pacak and M. Palkovits
Stressor Specificity of Central Neuroendocrine Responses: Implications for Stress-Related Disorders
Endocr. Rev.,
August 1, 2001;
22(4):
502 - 548.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. J. Lucassen, M. B. Muller, F. Holsboer, J. Bauer, A. Holtrop, J. Wouda, W. J. G. Hoogendijk, E. R. De Kloet, and D. F. Swaab
Hippocampal Apoptosis in Major Depression Is a Minor Event and Absent from Subareas at Risk for Glucocorticoid Overexposure
Am. J. Pathol.,
February 1, 2001;
158(2):
453 - 468.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Driessen, J. Herrmann, K. Stahl, M. Zwaan, S. Meier, A. Hill, M. Osterheider, and D. Petersen
Magnetic Resonance Imaging Volumes of the Hippocampus and the Amygdala in Women With Borderline Personality Disorder and Early Traumatization
Arch Gen Psychiatry,
December 1, 2000;
57(12):
1115 - 1122.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. M. Sanchez, L. J. Young, P. M. Plotsky, and T. R. Insel
Distribution of Corticosteroid Receptors in the Rhesus Brain: Relative Absence of Glucocorticoid Receptors in the Hippocampal Formation
J. Neurosci.,
June 15, 2000;
20(12):
4657 - 4668.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Narayan, J. D. Bremner, and A. Kumar
Neuroanatomic Substrates of Late-Life Mental Disorders
J Geriatr Psychiatry Neurol,
October 1, 1999;
12(3):
95 - 106.
[Abstract]
[PDF]
|
|
|
|
|
|
|
N. B. Hastings, M. Orchinik, M. V. Aubourg, and B. S. McEwen
Pharmacological Characterization of Central and Peripheral Type I and Type II Adrenal Steroid Receptors in the Prairie Vole, a Glucocorticoid-Resistant Rodent
Endocrinology,
October 1, 1999;
140(10):
4459 - 4469.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
C. A. Roca, P. J. Schmidt, and D. R. Rubinow
Review : Gonadal Steroids and Affective Illness
Neuroscientist,
July 1, 1999;
5(4):
227 - 237.
[Abstract]
[PDF]
|
|
|
|
|
|
|
Y. I. Sheline, M. Sanghavi, M. A. Mintun, and M. H. Gado
Depression Duration But Not Age Predicts Hippocampal Volume Loss in Medically Healthy Women with Recurrent Major Depression
J. Neurosci.,
June 15, 1999;
19(12):
5034 - 5043.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. B. Leverenz, C. W. Wilkinson, M. Wamble, S. Corbin, J. E. Grabber, M. A. Raskind, and E. R. Peskind
Effect of Chronic High-Dose Exogenous Cortisol on Hippocampal Neuronal Number in Aged Nonhuman Primates
J. Neurosci.,
March 15, 1999;
19(6):
2356 - 2361.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. H. S. hassan, V. K. Patchev, P. V. Rosenstiel, F. Holsboer, and O. F. X. Almeida
Plasticity of hippocampal corticosteroid receptors during aging in the rat
FASEB J,
January 1, 1999;
13(1):
115 - 122.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
S. Kalmijn, L. J. Launer, R. P. Stolk, F. H. de Jong, H. A. P. Pols, A. Hofman, M. M. B. Breteler, and S. W. J. Lamberts
A Prospective Study on Cortisol, Dehydroepiandrosterone Sulfate, and Cognitive Function in the Elderly
J. Clin. Endocrinol. Metab.,
October 1, 1998;
83(10):
3487 - 3492.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
J. C. Leza, E. Salas, G. Sawicki, J. C. Russell, and M. W. Radomski
The Effects of Stress on Homeostasis in JCR-LA-cp Rats: The Role of Nitric Oxide
J. Pharmacol. Exp. Ther.,
September 1, 1998;
286(3):
1397 - 1403.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
R. Soufer, J. D. Bremner, J. A. Arrighi, I. Cohen, B. L. Zaret, M. M. Burg, and P. Goldman-Rakic
Cerebral cortical hyperactivation in response to mental stress in patients with coronary artery disease
PNAS,
May 26, 1998;
95(11):
6454 - 6459.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Jenkins, P. J. Langlais, D. Delis, and R. Cohen
Learning and Memory in Rape Victims With Posttraumatic Stress Disorder
Am J Psychiatry,
February 1, 1998;
155(2):
278 - 279.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
R. M. Uht, C. M. Anderson, P. Webb, and P. J. Kushner
Transcriptional Activities of Estrogen and Glucocorticoid Receptors Are Functionally Integrated at the AP-1 Response Element
Endocrinology,
July 1, 1997;
138(7):
2900 - 2908.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. A. Glod and G. McEnany
The Neurobiology of Posttraumatic Stress Disorder
Journal of the American Psychiatric Nurses Association,
December 1, 1995;
1(6):
196 - 199.
[PDF]
|
|
|
|
|
|
|
R. S. Duman, V. A. Vaidya, M. Nibuya, S. Morinobu, and L. R. Fitzgerald
Review : Stress, Antidepressant Treatments, and Neurotrophic Factors: Molecular and Cellular Mechanisms
Neuroscientist,
November 1, 1995;
1(6):
351 - 360.
[Abstract]
[PDF]
|
|
|
|
