GABAergic promoter hypermethylation as a model to study the neurochemistry of schizophrenia vulnerability.
The neuronal GABAergic mechanisms that mediate the symptomatic beneficial effects elicited by a combination of antipsychotics with valproate (a histone deacetylase inhibitor) in the treatment of psychosis (expressed by schizophrenia or bipolar disorder patients) are unknown. This prompted us to investigate whether the beneficial action of this combination results from a modification of histone tail covalent esterification or is secondary to specific chromatin remodeling. The results suggest that clozapine, or sulpiride associated with valproate, by increasing DNA demethylation with an unknown mechanism, causes a chromatin remodeling that brings about a beneficial change in the epigenetic GABAergic dysfunction typical of schizophrenia and bipolar disorder patients.
Costa
Erminio
E
Psychiatric Institute, Department of Psychiatry, University of Illinois at Chicago, 1601 Taylor, Chicago, IL 60612, USA. ecosta@psych.uic.edu
Chen
Ying
Y
Dong
Erbo
E
Grayson
Dennis R
DR
Kundakovic
Marija
M
Maloku
Ekrem
E
Ruzicka
William
W
Satta
Rosalba
R
Veldic
Marin
M
Zhubi
Adrian
A
Guidotti
Alessandro
A
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D005968:Glutamate Decarboxylase / Q000235:genetics; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D000091042:Reelin Protein; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics*; D012697:Serine Endopeptidases / Q000235:genetics; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D014150:Antipsychotic Agents; D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; D005680:gamma-Aminobutyric Acid; D012697:Serine Endopeptidases; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1