Journal article
NR4A nuclear receptors support memory enhancement by histone deacetylase inhibitors
The Journal of clinical investigation, Vol.122(10), pp.3593-3602
10/01/2012
DOI: 10.1172/JCI64145
PMCID: PMC3461922
PMID: 22996661
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.
Details
- Title: Subtitle
- NR4A nuclear receptors support memory enhancement by histone deacetylase inhibitors
- Creators
- Joshua D Hawk - Neuroscience Graduate Group andAngie L Bookout - Neuroscience Graduate Group andShane G Poplawski - Neuroscience Graduate Group andMorgan Bridi - Neuroscience Graduate Group andAllison J Rao - Neuroscience Graduate Group andMichael E Sulewski - Neuroscience Graduate Group andBrian T Kroener - Neuroscience Graduate Group andDavid J Manglesdorf - Neuroscience Graduate Group andTed Abel - Neuroscience Graduate Group and
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.122(10), pp.3593-3602
- Publisher
- American Society for Clinical Investigation
- DOI
- 10.1172/JCI64145
- PMID
- 22996661
- PMCID
- PMC3461922
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Language
- English
- Date published
- 10/01/2012
- Academic Unit
- Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Biochemistry and Molecular Biology
- Record Identifier
- 9984065831702771
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