 |
||||
|
||||
|
||||
|
||||
The Journal of Neuroscience, July 2, 2003, 23(13):5708-5714
Previous Article | Next Article
Cyclic Estrogen Replacement Improves Cognitive Function in Aged Ovariectomized Rhesus Monkeys
Peter R. Rapp,1 John H. Morrison,1 andJeffrey A. Roberts2 1Kastor Neurobiology of Aging Laboratories, Fishberg Research Center for Neurobiology, Department of Geriatrics and Adult Development, Mount Sinai School of Medicine, New York, New York 10029-6574, and 2California National Primate Research Center, University of California, Davis, Davis, California 95616-8615
Among the identified risks and benefits of hormone-replacement therapy, the effects of treatment on cognitive function in postmenopausal women have proved difficult to define. Here we conducted a controlled, prospective analysis in a nonhuman primate model to test whether surgical menopause and estrogen replacement influence the cognitive outcome of normal aging. Sixteen aged rhesus monkeys were ovariectomized, and throughout the course of subsequent neuropsychological assessment, half received a regimen of low-dose, cyclic estradiol replacement. Hormone treatment substantially reversed the marked age-related impairment vehicle-injected monkeys exhibited on a delayed response test of spatial working memory. Modest improvement was also observed on a delayed nonmatching-to-sample recognition memory task. In contrast, ovariectomy exacerbated age-related deficits in object discrimination learning; the magnitude of this effect was equivalent among vehicle- and estrogen-treated monkeys. Together, these results demonstrate that ovarian hormone status can broadly influence normal cognitive aging in monkeys, affecting capacities mediated by multiple brain regions, including the prefrontal cortex and the medial temporal lobe memory system. The animal model established here should enable progress toward defining the neurobiological mechanisms that mediate the beneficial effects of estrogen on age-related cognitive decline in primates.
Key words: menopause; hormone replacement; cognitive aging; monkey; hippocampus; prefrontal cortex
Received Feb. 25, 2003; revised Apr. 24, 2003; accepted Apr. 24, 2003.
This article has been cited by other articles:
G. E. Alexander, K. Chen, M. Aschenbrenner, T. L. Merkley, L. E. Santerre-Lemmon, J. L. Shamy, W. E. Skaggs, M. H. Buonocore, P. R. Rapp, and C. A. Barnes
Age-Related Regional Network of Magnetic Resonance Imaging Gray Matter in the Rhesus Macaque
J. Neurosci., March 12, 2008; 28(11): 2710 - 2718.
[Abstract] [Full Text] [PDF]
J. Hao, P. R. Rapp, W. G. M. Janssen, W. Lou, B. L. Lasley, P. R. Hof, and J. H. Morrison
Interactive effects of age and estrogen on cognition and pyramidal neurons in monkey prefrontal cortex
PNAS, July 3, 2007; 104(27): 11465 - 11470.
[Abstract] [Full Text] [PDF]
M. Schumacher, R. Guennoun, A. Ghoumari, C. Massaad, F. Robert, M. El-Etr, Y. Akwa, K. Rajkowski, and E.-E. Baulieu
Novel Perspectives for Progesterone in Hormone Replacement Therapy, with Special Reference to the Nervous System
Endocr. Rev., June 1, 2007; 28(4): 387 - 439.
[Abstract] [Full Text] [PDF]
T. Hajszan, N. J. MacLusky, J. A. Johansen, C. L. Jordan, and C. Leranth
Effects of Androgens and Estradiol on Spine Synapse Formation in the Prefrontal Cortex of Normal and Testicular Feminization Mutant Male Rats
Endocrinology, May 1, 2007; 148(5): 1963 - 1967.
[Abstract] [Full Text] [PDF]
L. K. Marriott, K. R. McGann-Gramling, B. Hauss-Wegrzyniak, L. C. Sheldahl, R. A. Shapiro, D. M. Dorsa, and G. L. Wenk
Brain Infusion of Lipopolysaccharide Increases Uterine Growth as a Function of Estrogen Replacement Regimen: Suppression of Uterine Estrogen Receptor-{alpha} by Constant, But Not Pulsed, Estrogen Replacement
Endocrinology, January 1, 2007; 148(1): 232 - 240.
[Abstract] [Full Text] [PDF]
Y. R. Smith, T. Love, C. C. Persad, A. Tkaczyk, T. E. Nichols, and J.-K. Zubieta
Impact of Combined Estradiol and Norethindrone Therapy on Visuospatial Working Memory Assessed by Functional Magnetic Resonance Imaging
J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4476 - 4481.
[Abstract] [Full Text] [PDF]
J. H. Morrison, R. D. Brinton, P. J. Schmidt, and A. C. Gore
Estrogen, Menopause, and the Aging Brain: How Basic Neuroscience Can Inform Hormone Therapy in Women
J. Neurosci., October 11, 2006; 26(41): 10332 - 10348.
[Full Text] [PDF]
J. L. Turgeon, M. C. Carr, P. M. Maki, M. E. Mendelsohn, and P. M. Wise
Complex Actions of Sex Steroids in Adipose Tissue, the Cardiovascular System, and Brain: Insights from Basic Science and Clinical Studies
Endocr. Rev., October 1, 2006; 27(6): 575 - 605.
[Abstract] [Full Text] [PDF]
J. L. Downs and H. F. Urbanski
Neuroendocrine Changes in the Aging Reproductive Axis of Female Rhesus Macaques (Macaca mulatta)
Biol Reprod, October 1, 2006; 75(4): 539 - 546.
[Abstract] [Full Text] [PDF]
C. C. Smith and L. L. McMahon
Estradiol-Induced Increase in the Magnitude of Long-Term Potentiation Is Prevented by Blocking NR2B-Containing Receptors.
J. Neurosci., August 15, 2006; 26(33): 8517 - 8522.
[Abstract] [Full Text] [PDF]
J. Hao, P. R. Rapp, A. E. Leffler, S. R. Leffler, W. G. M. Janssen, W. Lou, H. McKay, J. A. Roberts, S. L. Wearne, P. R. Hof, et al.
Estrogen Alters Spine Number and Morphology in Prefrontal Cortex of Aged Female Rhesus Monkeys
J. Neurosci., March 1, 2006; 26(9): 2571 - 2578.
[Abstract] [Full Text] [PDF]
C. C. Smith and L. L. McMahon
Estrogen-Induced Increase in the Magnitude of Long-Term Potentiation Occurs Only When the Ratio of NMDA Transmission to AMPA Transmission Is Increased
J. Neurosci., August 24, 2005; 25(34): 7780 - 7791.
[Abstract] [Full Text] [PDF]
B. B. SHERWIN
Surgical Menopause, Estrogen, and Cognitive Function in Women: What Do the Findings Tell Us?
Ann. N.Y. Acad. Sci., June 1, 2005; 1052(1): 3 - 10.
[Abstract] [Full Text] [PDF]
P. J. SCHMIDT
Depression, the Perimenopause, and Estrogen Therapy
Ann. N.Y. Acad. Sci., June 1, 2005; 1052(1): 27 - 40.
[Abstract] [Full Text] [PDF]
R. D. BRINTON
Investigative Models for Determining Hormone Therapy-Induced Outcomes in Brain: Evidence in Support of a Healthy Cell Bias of Estrogen Action
Ann. N.Y. Acad. Sci., June 1, 2005; 1052(1): 57 - 74.
[Abstract] [Full Text] [PDF]
Z. Amin, T. Canli, and C. N. Epperson
Effect of Estrogen-Serotonin Interactions on Mood and Cognition
Behav Cogn Neurosci Rev, March 1, 2005; 4(1): 43 - 58.
[Abstract] [PDF]
A. C. Gore, B. M. Windsor-Engnell, and E. Terasawa
Menopausal Increases in Pulsatile Gonadotropin-Releasing Hormone Release in a Nonhuman Primate (Macaca mulatta)
Endocrinology, October 1, 2004; 145(10): 4653 - 4659.
[Abstract] [Full Text] [PDF]
Y. Xia and T. L. Krukoff
Estrogen Induces Nitric Oxide Production via Activation of Constitutive Nitric Oxide Synthases in Human Neuroblastoma Cells
Endocrinology, October 1, 2004; 145(10): 4550 - 4557.
[Abstract] [Full Text] [PDF]
Cognition and Dementia
Obstet. Gynecol., October 1, 2004; 104(4_suppl): 25S - 40S.
[Full Text] [PDF]
G. S. Roth, J. A. Mattison, M. A. Ottinger, M. E. Chachich, M. A. Lane, and D. K. Ingram
Aging in Rhesus Monkeys: Relevance to Human Health Interventions
Science, September 3, 2004; 305(5689): 1423 - 1426.
[Abstract] [Full Text] [PDF]
S. A. Shumaker, C. Legault, L. Kuller, S. R. Rapp, L. Thal, D. S. Lane, H. Fillit, M. L. Stefanick, S. L. Hendrix, C. E. Lewis, et al.
Conjugated Equine Estrogens and Incidence of Probable Dementia and Mild Cognitive Impairment in Postmenopausal Women: Women's Health Initiative Memory Study
JAMA, June 23, 2004; 291(24): 2947 - 2958.
[Abstract] [Full Text] [PDF]
M. A. Espeland, S. R. Rapp, S. A. Shumaker, R. Brunner, J. E. Manson, B. B. Sherwin, J. Hsia, K. L. Margolis, P. E. Hogan, R. Wallace, et al.
Conjugated Equine Estrogens and Global Cognitive Function in Postmenopausal Women: Women's Health Initiative Memory Study
JAMA, June 23, 2004; 291(24): 2959 - 2968.
[Abstract] [Full Text] [PDF]
S. A. Small, M. K. Chawla, M. Buonocore, P. R. Rapp, and C. A. Barnes
From The Cover: Imaging correlates of brain function in monkeys and rats isolates a hippocampal subregion differentially vulnerable to aging
PNAS, May 4, 2004; 101(18): 7181 - 7186.
[Abstract] [Full Text] [PDF]
C. Li, W. G. Brake, R. D. Romeo, J. C. Dunlop, M. Gordon, R. Buzescu, A. M. Magarinos, P. B. Allen, P. Greengard, V. Luine, et al.
Estrogen alters hippocampal dendritic spine shape and enhances synaptic protein immunoreactivity and spatial memory in female mice
PNAS, February 17, 2004; 101(7): 2185 - 2190.
[Abstract] [Full Text] [PDF]
Y. Tang, W. G.M. Janssen, J. Hao, J. A. Roberts, H. McKay, B. Lasley, P. B. Allen, P. Greengard, P. R. Rapp, J. H. Kordower, et al.
Estrogen Replacement Increases Spinophilin-immunoreactive Spine Number in the Prefrontal Cortex of Female Rhesus Monkeys
Cereb Cortex, February 1, 2004; 14(2): 215 - 223.
[Abstract] [Full Text] [PDF]
C. L. Koski, S. Hila, and G. E. Hoffman
Regulation of Cytokine-Induced Neuron Death by Ovarian Hormones: Involvement of Antiapoptotic Protein Expression and c-JUN N-Terminal Kinase-Mediated Proapoptotic Signaling
Endocrinology, January 1, 2004; 145(1): 95 - 103.
[Abstract] [Full Text] [PDF]
M. M. Adams and J. H. Morrison
Estrogen and the Aging Hippocampal Synapse
Cereb Cortex, December 1, 2003; 13(12): 1271 - 1275.
[Abstract] [Full Text] [PDF]
J. M. Choi, R. D. Romeo, W. G. Brake, C. L. Bethea, Z. Rosenwaks, and B. S. McEwen
Estradiol Increases Pre- and Post-Synaptic Proteins in the CA1 Region of the Hippocampus in Female Rhesus Macaques (Macaca mulatta)
Endocrinology, November 1, 2003; 144(11): 4734 - 4738.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|