Role of CpG islands in the up-regulation of NMDA receptor NR2B gene expression following chronic ethanol treatment of cultured cortical neurons of mice

• Published in: Neurochemistry international Vol. 46; no. 4; pp. 313 - 327
• Main Authors: Marutha Ravindran, C.R., Ticku, Maharaj K.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.03.2005; Elsevier
• Subjects: Aging - genetics; Aging - metabolism; Alcohol-Induced Disorders, Nervous System - genetics; Alcohol-Induced Disorders, Nervous System - metabolism; Alcohol-Induced Disorders, Nervous System - physiopathology; Animals; Base Sequence - genetics; Biological and medical sciences; Cells, Cultured; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Cerebral Cortex - physiopathology; Chronic ethanol treatment; Cortical neurons; CpG; CpG Islands - drug effects; CpG Islands - genetics; Demethylation; Deoxyribonuclease I - genetics; Deoxyribonuclease I - pharmacology; Disease Models, Animal; DNA Methylation - drug effects; Drug Administration Schedule; Ethanol - pharmacology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Gene Expression Regulation - genetics; Hypersensitive sites; Mice; Mice, Inbred C57BL; Molecular Sequence Data; Neurons - drug effects; Neurons - metabolism; NMDAR2B gene; Receptors, N-Methyl-D-Aspartate - genetics; RNA, Messenger - drug effects; RNA, Messenger - metabolism; Transcriptional Activation - drug effects; Transcriptional Activation - genetics; Up-Regulation - drug effects; Up-Regulation - genetics; Vertebrates: nervous system and sense organs; NMDAR2B gene; Demethylation; Chronic ethanol treatment; CpG; Cortical neurons; Hypersensitive sites; Ethanol; Rodentia; Glutamate receptor; Gene expression; In vitro; Vertebrata; Chronic; Mammalia; Neuron; Mouse; Animal; NMDA receptor
• ISSN: 0197-0186; 1872-9754
• DOI: 10.1016/j.neuint.2004.10.004

Our earlier studies have indicated that chronic ethanol treatment produces an increase in the rate of NR2B gene expression but acute ethanol treatment doesn’t cause any change in the expression in adult cortex and cultured fetal cortical neurons. To determine the molecular mechanism involved in the up-regulation of NR2B gene expression, we studied methylation in CpG islands in the regions (5843–6276) and (6477–6763) in mouse fetal cortical cultured neurons. However, acute administration of ethanol (3.5 g/kg, i.p.) as a 25% solution diluted in 0.9% saline to the adult mice did not cause any change in the methylation status of the NR2B gene. Therefore, these observations indicate that chronic ethanol causes demethylation in CpG islands in the regions (5843–6276) and (6477–6763), thereby probably resulting in increased expression of the NR2B gene. In contrast, acute ethanol treatment did not cause any change in the NR2B gene expression or its demethylation. We also investigated the changes in hypersensitive sites in CpG islands and transcription initiation sites in the cortical cultured neurons following chronic ethanol treatment. These experiments revealed that chronic ethanol treatment does not alter the pattern of hypersensitive sites in adult cortex and cultured cortical neurons.