Histone deacetylase inhibitors improve learning consolidation in young and in KA-induced-neurodegeneration and SAMP-8-mutant mice

Fontán‐Lozano, Ángela; Romero-Granados, Rocío; Troncoso, Julieta; Múnera, Alejandro; Delgado‐García, José M.; Carrión, Ángel Manuel

doi:10.1016/j.mcn.2008.06.009

Cited by 98 publications

(72 citation statements)

References 57 publications

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“…Immediately after training, mice were administered either vehicle or sodium butyrate (NaBut) and given a retention test 24 h later. We and others have shown that a single systemic injection of NaBut enhances memory (17,19) associated with increases in histone acetylation in the brain (20). As shown in Fig.…”

Section: Hdac Inhibition Transforms a Learning Event That Would Not Nmentioning

confidence: 71%

Modulation of long-term memory for object recognition via HDAC inhibition

Stefanko

Barrett

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

369

329

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Histone acetylation is a chromatin modification critically involved in gene regulation during many neural processes. The enzymes that regulate levels of histone acetylation are histone acetyltransferases (HATs), which activate gene expression and histone deacetylases (HDACs), that repress gene expression. Acetylation together with other histone and DNA modifications regulate transcription profiles for specific cellular functions. Our previous research has demonstrated a pivotal role for cyclicAMP response element binding protein (CREB)-binding protein (CBP), a histone acetyltransferase, in long-term memory for novel object recognition (NOR). In fact, every genetically modifiedCbp mutant mouse characterized thus far exhibits impaired long-term memory for NOR. These results suggest that long-term memory for NOR is especially sensitive to alterations in CBP activity. Thus, in the current study, we examined the role of HDACs in memory for NOR. We found that inducing a histone hyperacetylated state via HDAC inhibition transforms a learning event that would not normally result in long-term memory into an event that is now remembered long-term. We have also found that HDAC inhibition generates a type of long-term memory that persists beyond a point at which normal memory for NOR fails. This result is particularly interesting because one alluring aspect of examining the role of chromatin modifications in modulating transcription required for long-term memory processes is that these modifications may provide potentially stable epigenetic markers in the service of activating and/or maintaining transcriptional processes.CBP ͉ chromatin ͉ epigenetic ͉ acetylation ͉ CREB

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Section: Hdac Inhibition Transforms a Learning Event That Would Not Nmentioning

confidence: 71%

Modulation of long-term memory for object recognition via HDAC inhibition

Stefanko

Barrett

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

369

329

View full text Add to dashboard Cite

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“…Thus, our study strongly suggests that p300 is a key player in this mechanism. Fontan-Lozano and colleagues showed that the levels of acetylated H3 are significantly increased in the perirhinal cortex after training in the novel object recognition task (Fontan-Lozano et al 2008). Another study showed that infusion of a HDAC inhibitor into the insular cortex leads to enhanced novel object recognition (Roozendaal et al 2010).…”

Section: Discussionmentioning

confidence: 99%

“…For histones, acetylation is modeled to facilitate transcription by reducing the repression imposed by chromatin structure and by influencing the binding of transcriptional proteins recruited to chromatin. Studies have shown that memory consolidation correlates with increases in histone acetylation (Levenson et al 2004;Fontan-Lozano et al 2008) and that inhibition of histone deacetylases (HDACs) facilitates learning and synaptic plasticity (Fischer et al 2007;Vecsey et al 2007;Stefanko et al 2009;Roozendaal et al 2010). Consistent with these findings, genetically modified mice expressing mutant HAT proteins have memory impairments.…”

mentioning

confidence: 84%

Subregion-specific p300 conditional knock-out mice exhibit long-term memory impairments

Oliveira¹,

Estévez²,

Hawk³

et al. 2011

Learn. Mem.

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Histone acetylation plays a critical role during long-term memory formation. Several studies have demonstrated that the histone acetyltransferase (HAT) CBP is required during long-term memory formation, but the involvement of other HAT proteins has not been extensively investigated. The HATs CBP and p300 have at least 400 described interacting proteins including transcription factors known to play a role in long-term memory formation. Thus, CBP and p300 constitute likely candidates for transcriptional coactivators in memory formation. In this study, we took a loss-of-function approach to evaluate the role of p300 in long-term memory formation. We used conditional knock-out mice in which the deletion of p300 is restricted to the postnatal phase and to subregions of the forebrain. We found that p300 is required for the formation of long-term recognition memory and long-term contextual fear memory in the CA1 area of the hippocampus and cortical areas.

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“…*p Ͻ 0.05; **p Ͻ 0.01; ***p Ͻ 0.001. ever, some more recent studies have examined the role of changes in chromatin structure induced by the alterations to epigenetic factors during cognitive processes (Roth and Sweatt, 2009). Thus, histone acetylation and histone methylation have been demonstrated to be critical processes in regulating gene expression during learning and memory (Alarcó n et al, 2004;Korzus et al, 2004;Levenson et al, 2004a;Wood et al, 2005;Vecsey et al, 2007;Fontán-Lozano et al, 2008;Gupta et al, 2010). Changes in DNA methylation during learning and memory processes have also been described as critical steps in gene expression (Miller et al, 2007;Lubin et al, 2008;Feng et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Although many studies have focused on the activation of transcription factors in memory consolidation (Alberini, 2009), recent studies have demonstrated the role of chromatin remodeling in cognitive processes (Roth and Sweatt, 2009). In mammals, alterations to the core histone acetylation-deacetylation balance (Levenson et al, 2004a;Vecsey et al, 2007;Fontán-Lozano et al, 2008), in histone methylation (Gupta et al, 2010), and of DNA methylation (Miller and Sweatt, 2007;Lubin et al, 2008) have been demonstrated that can alter memory consolidation.…”

Section: Introductionmentioning

confidence: 99%