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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
35
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pubmed:dateCreated |
2005-8-31
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pubmed:abstractText |
Reduction of prefrontal cortex glutamic acid decarboxylase (GAD67) and reelin (mRNAs and proteins) expression is the most consistent finding reported by several studies of postmortem schizophrenia (SZ) brains. Converging evidence suggests that the reduced GAD67 and reelin expression in cortical GABAergic interneurons of SZ brains is the consequence of an epigenetic hypermethylation of RELN and GAD67 promoters very likely mediated by the overexpression of DNA methyltransferase 1 in cortical GABAergic interneurons. Studies of the molecular mechanisms (DNA methylation plus related chromatin remodeling factors) that cause the down-regulation of reelin and GAD67 in SZ brains have important implications not only to understand the disease pathogenesis but also to improve present pharmacological interventions to treat SZ. The mouse treated with l-methionine models some of the molecular neuropathologies detected in SZ, including the hypermethylation of RELN promoter CpG islands and the down-regulation of reelin and GAD67 expression. We now report that in these mice, RELN and GAD67 promoters express an increased recruitment of methyl-CpG binding domain proteins. In these mice the histone deacetylase inhibitor valproate, which increases acetylated histone content in cortical GABAergic interneurons, also prevents MET-induced RELN promoter hypermethylation and reduces the methyl-CpG binding domain protein binding to RELN and GAD67 promoters. These findings suggest that DNA hypermethylation and the associated chromatin remodeling may be critically important in mediating the epigenetic down-regulation of reelin and GAD67 expression detected in cortical GABAergic interneurons of SZ patients.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/16113080-10077664,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16113080-10725375,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16113080-10725376,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16113080-10891470,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16113080-11074872,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/16113080-11248103,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16113080-11430798,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16113080-11592844,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16113080-11592848,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16113080-12044194,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16113080-12087179,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16113080-12167620,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16113080-12269861,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16113080-12481028,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16113080-12504019,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16113080-12707415,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/16113080-7715726,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/16113080-9871412
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cell Adhesion Molecules, Neuronal,
http://linkedlifedata.com/resource/pubmed/chemical/Chromosomal Proteins, Non-Histone,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Matrix Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Globins,
http://linkedlifedata.com/resource/pubmed/chemical/Glutamate Decarboxylase,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Mecp2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Methionine,
http://linkedlifedata.com/resource/pubmed/chemical/Methyl-CpG-Binding Protein 2,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Serine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/gamma-Aminobutyric Acid,
http://linkedlifedata.com/resource/pubmed/chemical/glutamate decarboxylase 1,
http://linkedlifedata.com/resource/pubmed/chemical/reelin protein
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
30
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pubmed:volume |
102
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
12578-83
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
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