The DOI matches its Crossref record; 59 of the 59 references it cites were found in a registry or an index.
HDAC2 regulates atypical antipsychotic responses through the modulation of mGlu2 promoter activity
Open accessAbstract
Histone deacetylases (HDACs) compact chromatin structure and repress gene transcription. In schizophrenia, clinical studies demonstrate that HDAC inhibitors are efficacious when given in combination with atypical antipsychotics. However, the molecular mechanism that integrates a better response to antipsychotics with changes in chromatin structure remains unknown. Here we found that chronic atypical antipsychotics downregulated the transcription of metabotropic glutamate 2 receptor (mGlu2, also known as Grm2), an effect that was associated with decreased histone acetylation at its promoter in mouse and human frontal cortex. This epigenetic change occurred in concert with a serotonin 5-HT2A receptor–dependent upregulation and increased binding of HDAC2 to the mGlu2 promoter. Virally mediated overexpression of HDAC2 in frontal cortex decreased mGlu2 transcription and its electrophysiological properties, thereby increasing psychosis-like behavior. Conversely, HDAC inhibitors prevented the repressive histone modifications induced at the mGlu2 promoter by atypical antipsychotics, and augmented their therapeutic-like effects. These observations support the view of HDAC2 as a promising new target for schizophrenia treatment.
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Self-citationHDAC2 negatively regulates memory formation and synaptic plasticity
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Self-citationEpigenetic protein families: a new frontier for drug discovery
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Cited by
Histone acetylation: molecular mnemonics on the chromatin
Gräff, J., & Tsai, L.-H. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3427 · Cited by 680
Altering the course of schizophrenia: progress and perspectives
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Epigenetic basis of mental illness
Nestler, E. J., Peña, C. J., Kundakovic, M., Mitchell, A., & Akbarian, S. (2016) · The Neuroscientist · doi:10.1177/1073858415608147 · Cited by 342
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Millan, M. J. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.11.015 · Cited by 229
Metadata
- Authors
- Kurita, M., Holloway, T., García-Bea, A., Kozlenkov, A., Friedman, A. K., Moreno, J. L., Heshmati, M., Golden, S. A., Kennedy, P. J., Takahashi, N., Dietz, D. M., Mocci, G., Gabilondo, A. M., Hanks, J., Umali, A., Callado, L. F., Gallitano, A. L., Neve, R. L., Shen, L., Buxbaum, J. D., Han, M.-H., Nestler, E. J., Meana, J. J., Russo, S. J., & González-Maeso, J.
- Venue
- Nature Neuroscience
- Published
- 2012-08-05
- Volume
- 15
- Issue
- 9
- Pages
- 1245-1254
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W2134946659
- Cited by
- 285
- References
- 59
- FWCI
- 20.49
- Type
- journal article
- Language
- en
- Open access
- green
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- The paper
- Kurita, M., Holloway, T., García-Bea, A., Kozlenkov, A., Friedman, A. K., Moreno, J. L., Heshmati, M., Golden, S. A., Kennedy, P. J., Takahashi, N., Dietz, D. M., Mocci, G., Gabilondo, A. M., Hanks, J., Umali, A., Callado, L. F., Gallitano, A. L., Neve, R. L., Shen, L., . . . González-Maeso, J. (2012). HDAC2 regulates atypical antipsychotic responses through the modulation of mGlu2 promoter activity. Nature Neuroscience. https://doi.org/10.1038/nn.3181
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
