NR4A nuclear receptors support memory enhancement by histone deacetylase inhibitors

Joshua D. Hawk, Angie L. Bookout, Shane G. Poplawski, Morgan Bridi, Allison J. Rao, Michael E. Sulewski, Brian T. Kroener, David J. Manglesdorf, Ted Abel

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

The formation of a long-lasting memory requires a transcription-dependent consolidation period that converts a short-term memory into a long-term memory. Nuclear receptors compose a class of transcription factors that regulate diverse biological processes, and several nuclear receptors have been implicated in memory formation. Here, we examined the potential contribution of nuclear receptors to memory consolidation by measuring the expression of all 49 murine nuclear receptors after learning. We identified 13 nuclear receptors with increased expression after learning, including all 3 members of the Nr4a subfamily. These CREB-regulated Nr4a genes encode ligand-independent "orphan" nuclear receptors. We found that blocking NR4A activity in memory-supporting brain regions impaired long-term memory but did not impact short-term memory in mice. Further, expression of Nr4a genes increased following the memory-enhancing effects of histone deacetylase (HDAC) inhibitors. Blocking NR4A signaling interfered with the ability of HDAC inhibitors to enhance memory. These results demonstrate that the Nr4a gene family contributes to memory formation and is a promising target for improving cognitive function.

Original languageEnglish (US)
Pages (from-to)3593-3602
Number of pages10
JournalJournal of Clinical Investigation
Volume122
Issue number10
DOIs
StatePublished - Oct 1 2012

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Histone Deacetylase Inhibitors
Cytoplasmic and Nuclear Receptors
Long-Term Memory
Short-Term Memory
Learning
Orphan Nuclear Receptors
Biological Phenomena
Aptitude
Cognition
Genes
Transcription Factors
Ligands
Gene Expression
Brain

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Hawk, J. D., Bookout, A. L., Poplawski, S. G., Bridi, M., Rao, A. J., Sulewski, M. E., ... Abel, T. (2012). NR4A nuclear receptors support memory enhancement by histone deacetylase inhibitors. Journal of Clinical Investigation, 122(10), 3593-3602. https://doi.org/10.1172/JCI64145

NR4A nuclear receptors support memory enhancement by histone deacetylase inhibitors. / Hawk, Joshua D.; Bookout, Angie L.; Poplawski, Shane G.; Bridi, Morgan; Rao, Allison J.; Sulewski, Michael E.; Kroener, Brian T.; Manglesdorf, David J.; Abel, Ted.

In: Journal of Clinical Investigation, Vol. 122, No. 10, 01.10.2012, p. 3593-3602.

Research output: Contribution to journalArticle

Hawk, JD, Bookout, AL, Poplawski, SG, Bridi, M, Rao, AJ, Sulewski, ME, Kroener, BT, Manglesdorf, DJ & Abel, T 2012, 'NR4A nuclear receptors support memory enhancement by histone deacetylase inhibitors', Journal of Clinical Investigation, vol. 122, no. 10, pp. 3593-3602. https://doi.org/10.1172/JCI64145
Hawk, Joshua D. ; Bookout, Angie L. ; Poplawski, Shane G. ; Bridi, Morgan ; Rao, Allison J. ; Sulewski, Michael E. ; Kroener, Brian T. ; Manglesdorf, David J. ; Abel, Ted. / NR4A nuclear receptors support memory enhancement by histone deacetylase inhibitors. In: Journal of Clinical Investigation. 2012 ; Vol. 122, No. 10. pp. 3593-3602.
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