QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, November 8, 2006, 26(45):11637-11643; doi:10.1523/JNEUROSCI.3122-06.2006

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Nicholas, A. Articles by Sapolsky, R. Search for Related Content PubMed PubMed Citation Articles by Nicholas, A. Articles by Sapolsky, R.

 Previous Article  |  Next Article 

Behavioral/Systems/Cognitive
Enhancing Cognition after Stress with Gene Therapy

Andrea Nicholas,¹ Carolina D. Munhoz,^1,2 Deveroux Ferguson,¹ Laura Campbell,¹ and Robert Sapolsky^1,3

¹Department of Biological Sciences, Stanford University, Stanford, California 94305, ²Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, 05311-970 São Paulo, Brazil, and ³Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305

Correspondence should be addressed to Andrea Nicholas, Department of Biological Sciences, Stanford University, Gilbert Laboratory, MC 5020, Stanford, CA 94305-5020. Email: anichola{at}stanford.edu

Hippocampal function is essential for the acquisition, consolidation, and retrieval of spatial memory. High circulating levels of glucocorticoids (GCs), the adrenal steroid hormones secreted during stress, have been shown to impair both acquisition and retrieval and can either impair or enhance consolidation, depending on experimental conditions. In contrast, estrogen can enhance spatial memory performance and can block the deleterious effects of GCs on such performance. We therefore constructed a chimeric gene ("ER/GR") containing the hormone-binding domain of the GC receptor and the DNA binding domain of the estrogen receptor; as a result, ER/GR transduces deleterious GC signals into beneficial estrogenic ones. We show here that acute immobilization stress, before acquisition and retrieval phases, increases latencies for male rats in a hidden platform version of the Morris water maze. This impairment is blocked by hippocampal expression of the ER/GR transgene. ER/GR expression also blocks decreases in platform crossings caused by acute stress, either after acquisition or before retrieval. Three days of stress before acquisition produces an estrogen-like enhancement of performance in ER/GR-treated rats. Moreover, ER/GR blocks the suppressive effects of GCs on expression of brain-derived neurotrophic factor (BDNF), a growth factor central to hippocampal-dependent cognition and plasticity, instead producing an estrogenic increase in BDNF expression. Thus, ER/GR expression enhances spatial memory performance and blocks the impairing effects of GCs on such performance.

Key words: BDNF; behavior; dentate gyrus; estrogen (estradiol); glucocorticoid; hippocampal function; learning and memory; memory formation; spatial cognition; spatial memory; stress

---

Received April 19, 2006; revised Sept. 26, 2006; accepted Oct. 5, 2006.

Correspondence should be addressed to Andrea Nicholas, Department of Biological Sciences, Stanford University, Gilbert Laboratory, MC 5020, Stanford, CA 94305-5020. Email: anichola{at}stanford.edu

This article has been cited by other articles:

				A. Hossain, K. Hajman, K. Charitidi, S. Erhardt, U. Zimmermann, M. Knipper, and B. Canlon Prenatal Dexamethasone Impairs Behavior and the Activation of the BDNF Exon IV Promoter in the Paraventricular Nucleus in Adult Offspring Endocrinology, December 1, 2008; 149(12): 6356 - 6365. [Abstract] [Full Text] [PDF]

				X.-Y. Wang, M. Zhao, U. E. Ghitza, Y.-Q. Li, and L. Lu Stress Impairs Reconsolidation of Drug Memory via Glucocorticoid Receptors in the Basolateral Amygdala J. Neurosci., May 21, 2008; 28(21): 5602 - 5610. [Abstract] [Full Text] [PDF]

				R. S. Wilson, S. E. Arnold, T. L. Beck, J. L. Bienias, and D. A. Bennett Change in Depressive Symptoms During the Prodromal Phase of Alzheimer Disease Arch Gen Psychiatry, April 1, 2008; 65(4): 439 - 445. [Abstract] [Full Text] [PDF]

				D. Ferguson and R. Sapolsky Mineralocorticoid Receptor Overexpression Differentially Modulates Specific Phases of Spatial and Nonspatial Memory J. Neurosci., July 25, 2007; 27(30): 8046 - 8052. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help