Differential brain ADRA2A and ADRA2C gene expression and epigenetic regulation in schizophrenia. Effect of antipsychotic drug treatment

• DOI: 10.1038/s41398-021-01762-4
• Publication Date: 2021-12-20T18:02:43Z
• Authors: Iria Brocos-Mosquera; Patricia Miranda-...; Carolina Muguruza; Virginia Corzo-Monje; Benito Morentin; J. Javier Meana; Luis F. Callado; Guadalupe Rivero
• Keywords: bipolar disorder; 0301 basic medicine; dorsolateral prefrontal cortex; dna hypermethylation; alpha(2)-adrenoceptor subtypes; Brain; Gene Expression; Neurosciences. Biological psychiatry. Neuropsychiatry; Article; Epigenesis, Genetic; Rats; 03 medical and health sciences; Dorsolateral Prefrontal Cortex; messenger-rna; Gene Expression Regulation; agonist binding; Schizophrenia; Animals; histone methylation; restrictive epigenome; polymorphisms; postmortem interval; RC321-571; Antipsychotic Agents

Abstract Postsynaptic α 2A -adrenoceptor density is enhanced in the dorsolateral prefrontal cortex (DLPFC) of antipsychotic-treated schizophrenia subjects. This alteration might be due to transcriptional activation, and could regulated by epigenetic mechanisms such as histone posttranslational modifications (PTMs). The aim this study was evaluate ADRA2A ADRA2C gene expression (codifying for 2 subtypes), permissive repressive PTMs at promoter regions DLPFC subjects with matched controls ( n = 24 pairs). We studied effect antipsychotic (AP) treatment AP-free 12) AP-treated subgroups rats acutely chronically treated typical atypical antipsychotics. mRNA selectively upregulated (+93%) whereas all (+53%) regardless treatment. Acute chronic clozapine did not alter brain Adra2a but increased Adra2c expression. Both showed modification methylation acetylation human DLPFC. upregulation related observed bivalent chromatin region (depicted H3K4me3 H3K27me3) triggered H4K16ac promoter. In conclusion, predisposition differentially modulated