In psychosis, cortical interneurons overexpress DNA-methyltransferase 1
| Autor: | Ekrem Maloku, Marin Veldic, Alessandro Guidotti, John M. Davis, Erminio Costa |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Adult
DNA (Cytosine-5-)-Methyltransferase 1 Male medicine.medical_specialty Psychosis GABA Agents Cell Adhesion Molecules Neuronal medicine.medical_treatment Glutamate decarboxylase Nerve Tissue Proteins In situ hybridization Biology Interneurons Internal medicine medicine Humans DNA (Cytosine-5-)-Methyltransferases Bipolar disorder Antipsychotic In Situ Hybridization Aged Cerebral Cortex Genetics Extracellular Matrix Proteins Valproic Acid Multidisciplinary Glutamate Decarboxylase Serine Endopeptidases DNA Methylation Middle Aged Biological Sciences medicine.disease Isoenzymes Reelin Protein Endocrinology medicine.anatomical_structure Gene Expression Regulation Psychotic Disorders Schizophrenia Cerebral cortex embryonic structures Female Biomarkers Antipsychotic Agents medicine.drug |
| Zdroj: | Proceedings of the National Academy of Sciences. 102:2152-2157 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Cortical DNA-methyltransferase 1 (DNMT1) is preferentially expressed in interneurons secreting GABA where it very likely contributes to promoter CpG island hypermethylation, thus causing a down-regulation of promoter functions. To consolidate and expand on previous findings that, in the cortex of schizophrenia (SZ) brains, glutamic acid decarboxylase 67 (GAD 67 ) expression is down-regulated whereas that of DNMT1 is up-regulated, we studied both parameters in Brodmann's area (BA) 9 from the McLean 66 Cohort Collection (Harvard Brain Tissue Resource Center, Belmont, MA). In BA9 of SZ and bipolar disorder patients with psychosis, DNMT1 mRNA and protein expression preferentially increases in layer I, II, and IV interneurons, and this increase is paralleled by a decreased number of GAD 67 mRNA-positive neurons. The increase in DNMT1 and the decrease in GAD 67 -expressing neurons were unrelated to postmortem interval, pH, RNA quality, or to the presence, dose, or duration of antipsychotic (APS) medication, with the exception of a subgroup of SZ patients treated with a combination of valproate and APS in which the expression of DNMT1 failed to change. The DNMT1 increase and the GAD 67 decrease in BA9 interneurons are significant features of SZ and bipolar disorder with psychosis. Interestingly, the DNMT1 increase failed to occur when patients with psychosis received a combination of valproate and APS treatment but not APS monotherapy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|