Enhancing cognition after stress with gene therapy

Andrea Nicholas, Carolina D. Munhoz, Deveroux Ferguson, Laura Campbell, Robert Sapolsky

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)11637-11643
Number of pages7
JournalJournal of Neuroscience
Volume26
Issue number45
DOIs
StatePublished - Nov 8 2006
Externally publishedYes

Fingerprint

Genetic Therapy
Cognition
Glucocorticoids
Brain-Derived Neurotrophic Factor
Estrogens
Hormones
Glucocorticoid Receptors
Transgenes
Immobilization
Estrogen Receptors
Intercellular Signaling Peptides and Proteins
Steroids
Water
DNA
Genes
Spatial Memory

Keywords

  • BDNF
  • Behavior
  • Dentate gyrus
  • Estrogen (estradiol)
  • Glucocorticoid
  • Hippocampal function
  • Learning and memory
  • Memory formation
  • Spatial cognition
  • Spatial memory
  • Stress

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Nicholas, A., Munhoz, C. D., Ferguson, D., Campbell, L., & Sapolsky, R. (2006). Enhancing cognition after stress with gene therapy. Journal of Neuroscience, 26(45), 11637-11643. https://doi.org/10.1523/JNEUROSCI.3122-06.2006

Enhancing cognition after stress with gene therapy. / Nicholas, Andrea; Munhoz, Carolina D.; Ferguson, Deveroux; Campbell, Laura; Sapolsky, Robert.

In: Journal of Neuroscience, Vol. 26, No. 45, 08.11.2006, p. 11637-11643.

Research output: Contribution to journalArticle

Nicholas, A, Munhoz, CD, Ferguson, D, Campbell, L & Sapolsky, R 2006, 'Enhancing cognition after stress with gene therapy', Journal of Neuroscience, vol. 26, no. 45, pp. 11637-11643. https://doi.org/10.1523/JNEUROSCI.3122-06.2006
Nicholas, Andrea ; Munhoz, Carolina D. ; Ferguson, Deveroux ; Campbell, Laura ; Sapolsky, Robert. / Enhancing cognition after stress with gene therapy. In: Journal of Neuroscience. 2006 ; Vol. 26, No. 45. pp. 11637-11643.
@article{7f6c91c145fa4c52af07225eeada8958,
title = "Enhancing cognition after stress with gene therapy",
abstract = "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.",
keywords = "BDNF, Behavior, Dentate gyrus, Estrogen (estradiol), Glucocorticoid, Hippocampal function, Learning and memory, Memory formation, Spatial cognition, Spatial memory, Stress",
author = "Andrea Nicholas and Munhoz, {Carolina D.} and Deveroux Ferguson and Laura Campbell and Robert Sapolsky",
year = "2006",
month = "11",
day = "8",
doi = "10.1523/JNEUROSCI.3122-06.2006",
language = "English (US)",
volume = "26",
pages = "11637--11643",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "45",

}

TY - JOUR

T1 - Enhancing cognition after stress with gene therapy

AU - Nicholas, Andrea

AU - Munhoz, Carolina D.

AU - Ferguson, Deveroux

AU - Campbell, Laura

AU - Sapolsky, Robert

PY - 2006/11/8

Y1 - 2006/11/8

N2 - 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.

AB - 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.

KW - BDNF

KW - Behavior

KW - Dentate gyrus

KW - Estrogen (estradiol)

KW - Glucocorticoid

KW - Hippocampal function

KW - Learning and memory

KW - Memory formation

KW - Spatial cognition

KW - Spatial memory

KW - Stress

UR - http://www.scopus.com/inward/record.url?scp=33751111177&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33751111177&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.3122-06.2006

DO - 10.1523/JNEUROSCI.3122-06.2006

M3 - Article

C2 - 17093085

AN - SCOPUS:33751111177

VL - 26

SP - 11637

EP - 11643

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 45

ER -