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Clozapine and sulpiride but not haloperidol or olanzapine activate brain DNA demethylation
Open accessAbstract
Cortical GABAergic dysfunction, a hallmark of both schizophrenia (SZ) and bipolar (BP) disorder pathophysiologies may relate to the hypermethylation of GABAergic gene promoters (i.e., reelin and GAD67). Benefits elicited by a combination of atypical antipsychotics with valproate (VPA) (a histone deacetylase inhibitor that may also activate brain DNA demethylation) in SZ or BP disorder treatment prompted us to investigate whether the beneficial action of this association depends on induction of a putative DNA demethylase activity. To monitor this activity, we measured the ratio of 5-methyl cytosine to unmethylated cytosine in reelin and GAD67 promoters in the mouse frontal cortex and striatum. We compared normal mice with mice pretreated with l -methionine (5.2 mmol/kg s.c. twice a day for 7 days) to hypermethylate promoters, including reelin and GAD67. Clinically relevant doses of clozapine (CLZ) (3.8 to 15 μmol/kg twice a day s.c. for 3 days) and sulpiride (SULP) (12.5 to 50 μmol/kg twice a day for 3 days) but not clinically relevant doses of haloperidol (HAL) (1.3 to 4 μmol/kg twice a day s.c. for 3 days) or olanzapine (OLZ) (4 to 15 μmol/kg twice a day for 3 days) exhibited dose-related increases in the cortical and striatal demethylation of hypermethylated reelin and GAD67 promoters. These effects of CLZ and SULP were dramatically potentiated by a clinically relevant VPA dose (0.5 mmol/kg twice a day for 3 days). By activating a DNA demethylase, the association of CLZ or SULP with VPA may facilitate a chromatin remodeling that normalizes the GABAergic gene expression down-regulation detected in the telencephalic regions of SZ and BP patients.
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Cites
Cortical inhibitory neurons and schizophrenia
Lewis, D. A., Hashimoto, T., & Volk, D. W. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1648 · Cited by 2,297
Guidotti, A., Auta, J., Davis, J. M., Gerevini, V. D., Dwivedi, Y., Grayson, D. R., Impagnatiello, F., Pandey, G., Pesold, C., Sharma, R., et al. (2000) · Archives of General Psychiatry · doi:10.1001/archpsyc.57.11.1061 · Cited by 1,206
Self-citationAkbarian, S. (1995) · Archives of General Psychiatry · doi:10.1001/archpsyc.1995.03950160008002 · Cited by 1,002
Epigenomic Profiling Reveals DNA-Methylation Changes Associated with Major Psychosis
Mill, J., Tang, T., Kaminsky, Z., Khare, T., Yazdanpanah, S., Bouchard, L., Jia, P., Assadzadeh, A., Flanagan, J., Schumacher, A., et al. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2008.01.008 · Cited by 773
Weaver, I. C. G., Meaney, M. J., & Szyf, M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0507526103 · Cited by 771
A mammalian protein with specific demethylase activity for mCpG DNA
Bhattacharya, S. K., Ramchandani, S., Cervoni, N., & Szyf, M. (1999) · Nature · doi:10.1038/17533 · Cited by 620
The social environment and the epigenome
Szyf, M., McGowan, P., & Meaney, M. J. (2008) · Environmental and Molecular Mutagenesis · doi:10.1002/em.20357 · Cited by 531
Woo, T.-U. W., Walsh, J. P., & Benes, F. M. (2004) · Archives of General Psychiatry · doi:10.1001/archpsyc.61.7.649 · Cited by 411
Huang, H.-S., Matevossian, A., Whittle, C., Kim, S. Y., Schumacher, A., Baker, S. P., & Akbarian, S. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.3272-07.2007 · Cited by 352
GABAergic dysfunction in schizophrenia: new treatment strategies on the horizon
Guidotti, A., Auta, J., Davis, J. M., Dong, E., Grayson, D. R., Veldic, M., Zhang, X., & Costa, E. (2005) · Psychopharmacology · doi:10.1007/s00213-005-2212-8 · Cited by 262
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Dnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens
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Dempster, E. L., Pidsley, R., Schalkwyk, L. C., Owens, S., Georgiades, A., Kane, F., Kalidindi, S., Picchioni, M., Kravariti, E., Toulopoulou, T., et al. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr416 · Cited by 460
HDAC2 regulates atypical antipsychotic responses through the modulation of mGlu2 promoter activity
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., et al. (2012) · Nature Neuroscience · doi:10.1038/nn.3181 · Cited by 285
Epigenetic Signatures of Autism: Trimethylated H3K4 Landscapes in Prefrontal Neurons
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Metadata
- Authors
- Dong, E., Nelson, M., Grayson, D. R., Costa, E., & Guidotti, A.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2008-09-09
- Volume
- 105
- Issue
- 36
- Pages
- 13614-13619
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2162086299
- Cited by
- 286
- References
- 26
- FWCI
- 12.74
- Type
- journal article
- Language
- en
- Open access
- green
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