The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
HDAC2 negatively regulates memory formation and synaptic plasticity
Open accessAbstract
Chromatin modifications, especially histone-tail acetylation, have been implicated in memory formation. Increased histone-tail acetylation induced by inhibitors of histone deacetylases (HDACis) facilitates learning and memory in wild-type mice as well as in mouse models of neurodegeneration. Harnessing the therapeutic potential of HDACis requires knowledge of the specific HDAC family member(s) linked to cognitive enhancement. Here we show that neuron-specific overexpression of HDAC2, but not that of HDAC1, decreased dendritic spine density, synapse number, synaptic plasticity and memory formation. Conversely, Hdac2 deficiency resulted in increased synapse number and memory facilitation, similar to chronic treatment with HDACis in mice. Notably, reduced synapse number and learning impairment of HDAC2-overexpressing mice were ameliorated by chronic treatment with HDACis. Correspondingly, treatment with HDACis failed to further facilitate memory formation in Hdac2-deficient mice. Furthermore, analysis of promoter occupancy revealed an association of HDAC2 with the promoters of genes implicated in synaptic plasticity and memory formation. Taken together, our results suggest that HDAC2 functions in modulating synaptic plasticity and long-lasting changes of neural circuits, which in turn negatively regulates learning and memory. These observations encourage the development and testing of HDAC2-selective inhibitors for human diseases associated with memory impairment.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“However, prolonged administration of HDAC inhibitors improved synapse number and learning impairment.134”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [134]
The cited source says what the claim attributes to it.
In the citing paper
“The overexpression of HDAC2 specifically in neurons resulted in a decrease in dendritic spine density, synapse number, synaptic plasticity, and memory formation in mice.”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [134]
The cited source says what the claim attributes to it.
In the citing paper
“a promoter occupancy analysis has revealed a link between HDAC2 and the promoters of genes that play a role in synaptic plasticity and memory formation.134”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [134]
In the citing paper
“HDAC2 overexpression reduces dendritic spine density, and impairs synaptic plasticity and memory by blocking expression of genes related to neuroplasticity, whereas downregulation or inhibition of HDACs has been proven successful in restoring synaptic and cognitive function in AD animal models [508, 509].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [509]
In the citing paper
“Conversely, Guan et al. 52 found that HDAC2 overexpression reduced synapse number, decreased synaptic plasticity, and impaired memory.”
From Epigenetic mechanisms of major depression: Targeting neuronal plasticity (2018) · cites this paper as [52]
In the citing paper
“This group also demonstrated that HDAC2 bound to the promoters of several genes involved in synaptic plasticity or whose expression was activity dependent.”
From Epigenetic mechanisms of major depression: Targeting neuronal plasticity (2018) · cites this paper as [52]
In the citing paper
“Importantly, the detrimental effects of HDAC2 overexpression on plasticity and memory are reversed by the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA), whereas SAHA was unable to further enhance memory in HDAC2 knockout mice.”
From Epigenetic mechanisms of major depression: Targeting neuronal plasticity (2018) · cites this paper as [52]
In the citing paper
“HDACs have been implicated in diverse biology including metabolism, inflammation, circadian rhythm, as well as neurological development and brain function (Guan et al., 2009; Villagra et al., 2009; Gräff et al., 2012; Jakovcevski and Akbarian, 2012; Falkenberg and Johnstone, 2014; Tough et al., 2016).”
From Histone deacetylase 11 is an ε-N-Myristoyllysine hydrolase (2018) · cites this paper as Guan et al., 2009
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Place navigation impaired in rats with hippocampal lesions
Morris, R. G. M., Garrud, P., Rawlins, J. N. P., & O'Keefe, J. (1982) · Nature · doi:10.1038/297681a0 · Cited by 6,340
Synaptic Plasticity and Memory: An Evaluation of the Hypothesis
Martin, S. J., Grimwood, P. D., & Morris, R. G. M. (2000) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.23.1.649 · Cited by 2,794
Epigenetics: A landscape takes shape
Goldberg, A. D., Allis, C. D., & Bernstein, E. (2007) · Cell · doi:10.1016/j.cell.2007.02.006 · Cited by 2,466
HDAC6 is a microtubule-associated deacetylase
Hubbert, C., Guardiola, A., Shao, R., Kawaguchi, Y., Ito, A., Nixon, A., Yoshida, M., Wang, X.-F., & Yao, T.-P. (2002) · Nature · doi:10.1038/417455a · Cited by 2,403
Self-citationReducing Endogenous Tau Ameliorates Amyloid ß-Induced Deficits in an Alzheimer's Disease Mouse Model
Roberson, E. D., Scearce-Levie, K., Palop, J. J., Yan, F., Cheng, I. H., Wu, T., Gerstein, H., Yu, G.-Q., & Mucke, L. (2007) · Science · doi:10.1126/science.1141736 · Cited by 1,892
Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action
Tsankova, N. M., Berton, O., Renthal, W., Kumar, A., Neve, R. L., & Nestler, E. J. (2006) · Nature Neuroscience · doi:10.1038/nn1659 · Cited by 1,780
Recovery of learning and memory is associated with chromatin remodelling
Fischer, A., Sananbenesi, F., Wang, X., Dobbin, M., & Tsai, L.-H. (2007) · Nature · doi:10.1038/nature05772 · Cited by 1,227
Self-citationRegulation of histone acetylation during memory formation in the hippocampus
Levenson, J. M., O'Riordan, K. J., Brown, K. D., Trinh, M. A., Molfese, D. L., & Sweatt, J. D. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m402229200 · Cited by 1,131
Calcium regulation of neuronal gene expression
West, A. E., Chen, W., Dalva, M. B., Dolmetsch, R. E., Kornhauser, J. M., Shaywitz, A. J., Takasu, M. A., Xu, T., & Greenberg, M. E. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.191352298 · Cited by 1,047
CREB: A Major Mediator of Neuronal Neurotrophin Responses
Finkbeiner, S. M., Tavazoie, S. F., Maloratsky, A., Jacobs, K. M., Harris, K. M., & Greenberg, M. E. (1997) · Neuron · doi:10.1016/s0896-6273(00)80395-5 · Cited by 959
Flagged first, then by citations
Research works printed but not linked: 2
- Breslow, R., Marks, P., Rifkind, R. & Jursic, B. Novel Potent Inducers of Terminal Differentiation and Methods Thereof. US Patent WO/1993/007148 (1993)
- Ramon-Molinier, E. Contemporary Research Methods in Neuroanatomy Synaptic Plasticity: Multiple Forms and Mechanisms (Springer, 1970)
Cited by
Sorted by citations
Items 101–114 of 114
Cadena-del-Castillo, C., Valdes-Quezada, C., Carmona-Aldana, F., Arias, C., Bermúdez-Rattoni, F., & Recillas-Targa, F. (2014) · Journal of Alzheimer's Disease · doi:10.3233/jad-132285 · Cited by 35
Histone Deacetylases 1 and 2 in Memory Function
Pao, P.-C., & Tsai, L.-H. (2022) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.1c00775 · Cited by 34
Self-citationSodium butyrate as a selective cognitive enhancer for weak or impaired memory
Vinarskaya, A. K., Balaban, P. M., Roshchin, M. V., & Zuzina, A. B. (2021) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2021.107414 · Cited by 29
Dai, Y., Wei, T., Huang, Y., Bei, Y., Lin, H., Shen, Z., Yu, L., Yang, M., Xu, H., He, W., et al. (2023) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-023-04945-y · Cited by 22
Class I HDAC inhibition is a novel pathway for regulating astrocytic apoE secretion
Dresselhaus, E., Duerr, J. M., Vincent, F., Sylvain, E. K., Beyna, M., Lanyon, L. F., LaChapelle, E., Pettersson, M., Bales, K. R., & Ramaswamy, G. (2018) · PLOS ONE · doi:10.1371/journal.pone.0194661 · Cited by 25
The molecular basis of depression: implications of sex-related differences in epigenetic regulation
Kawatake-Kuno, A., Murai, T., & Uchida, S. (2021) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.708004 · Cited by 23
Hirata, Y., Sasaki, T., Kanki, H., Choong, C.-J., Nishiyama, K., Kubo, G., Hotei, A., Taniguchi, M., Mochizuki, H., & Uesato, S. (2018) · Scientific Reports · doi:10.1038/s41598-018-19664-9 · Cited by 20
Scott, H., Smith, A. E., Barker, G. R., Uney, J. B., & Warburton, E. C. (2017) · Neuroepigenetics · doi:10.1016/j.nepig.2017.02.001 · Cited by 18
Association of histone modification with the development of schizophrenia
Chen, Y.-Z., Zhu, X.-M., Lv, P., Hou, X.-K., Pan, Y., Li, A., Du, Z., Xuan, J.-F., Guo, X., Xing, J.-X., et al. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.116747 · Cited by 18
Song, J. M., Sung, Y. M., Nam, J. H., Yoon, H., Chung, A., Moffat, E., Jung, M., Pak, D. T. S., Kim, J., & Hoe, H.-S. (2016) · Journal of Alzheimer's Disease · doi:10.3233/jad-150717 · Cited by 18
K V, A., Madhana, R. M., Bais, A. K., Singh, V. B., Malik, A., Sinha, S., Lahkar, M., Kumar, P., & Samudrala, P. K. (2020) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.0c00315 · Cited by 15
Freire-Cobo, C., & Wang, J. (2020) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2020.173362 · Cited by 11
Yadav, A., Dogra, S., Boda, A. K., Kumari, P., Kumar, A., Dash, M. K., & Yadav, P. N. (2024) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.4c00175 · Cited by 9
Enhancement of psychotherapy using epigenetic modulating drugs
Gavin, D. P., Chase, K. A., & Sharma, R. P. (2011) · Medical Hypotheses · doi:10.1016/j.mehy.2011.03.042 · Cited by 6
Metadata
- Authors
- Guan, J.-S., Haggarty, S. J., Giacometti, E., Dannenberg, J.-H., Joseph, N., Gao, J., Nieland, T. J. F., Zhou, Y., Wang, X., Mazitschek, R., Bradner, J. E., DePinho, R. A., Jaenisch, R., & Tsai, L.-H.
- Affiliations
- Broad Institute (US)
- Whitehead Institute for Biomedical Research (US)
- Harvard University (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Tsai, Li-Huei
- ORCID
- Venue
- Nature
- Published
- 2009-05
- Volume
- 459
- Issue
- 7243
- Pages
- 55-60
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3498958
- OpenAlex
- W2090760765
- Cited by
- 1,644
- References
- 33
- Citations by year
- 2026: 60 · 2025: 63 · 2024: 82 · 2023: 70 · 2022: 69 · 2021: 87 · 2020: 104 · 2019: 84 · 2018: 99 · 2017: 91 · 2016: 113 · 2015: 110 · 2014: 149 · 2013: 140 · 2012: 105
- FWCI
- 43.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (n01co12400-79-0-22)
- National Institute on Drug Abuse (R01DA028301)
- National Cancer Institute (N01-CO-012400, R01CA087869, R37CA084198)
- National Institute of Neurological Disorders and Stroke (R01NS051874)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- HDAC2, HDAC1, histone deacetylase inhibitors, histone acetylation, chromatin modification, memory formation, synaptic plasticity, dendritic spine density, synapse number, learning disabilities, promoter binding, memory impairment
- MeSH terms
- Vorinostat, Animals, Butyrates, Female, Gene Expression Regulation, Hippocampus, Histone Deacetylases, Hydroxamic Acids, Learning, Male, Memory, Mice, Inbred C57BL, Neurons, Promoter Regions, Genetic, Repressor Proteins, Sodium, Mice, Knockout, Dendritic Spines, Mice, Electrical Synapses, Histone Deacetylase 1, Histone Deacetylase 2, Histone Deacetylase Inhibitors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
