Overexpression of mineralocorticoid and transdominant glucocorticoid receptor blocks the impairing effects of glucocorticoids on memory

Deveroux Ferguson, Robert Sapolsky

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

It is well established that mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) influence hippocampal-dependent spatial memory. MRs are saturated in the presence of low corticosterone (CORT) levels; consequently receptor protein levels play a rate-limiting role in regulating the positive effects of MR-mediated gene transcription. In this study, viral vector-mediated transgene expression was used to simultaneously manipulate both MR and GR signaling. This approach allowed us to investigate the effects of spatially restricted overexpression of MR and a negative transdominant GR (TD) in the dentate gyrus (DG) subfield of the hippocampus, on short term and long term spatial memory in animals overexpressing one copy of MR or TD, two copies of MR ("MR/MR"), or one copy of each ("MR/TD"). Expression of transgenes did not influence the acquisition (learning) phase of the Morris water maze task. However, we found an overall enhancing effect of MR/MR expression on short term memory performance. In addition, rats expressing TD and MR/TD blocked the high CORT-induced impairments on long term spatial memory retrieval. These findings illustrate the potential beneficial effects of increasing MR signaling or decreasing GR signaling to enhance specific aspects of cognitive function.

Original languageEnglish (US)
Pages (from-to)1103-1111
Number of pages9
JournalHippocampus
Volume18
Issue number11
DOIs
StatePublished - Nov 1 2008
Externally publishedYes

Keywords

  • Corticosterone
  • Glucocorticoid receptor
  • Learning and memory
  • Mineralocorticoid receptor
  • Spatial memory
  • Viral-vector

ASJC Scopus subject areas

  • Cognitive Neuroscience

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