[Epigenetic regulation in alcohol-related brain damage].
Ethanol is a deleterious agent that causes various kinds of neuronal damage to both the developing and adult brain. Recent research on alcoholism implicates impaired function of neural stem cell (NSC) in the pathogenesis of ethanol-induced brain dysfunction. We previously reported that the differentiation of NSCs into neurons was significantly influenced by ethanol. We also found that neuron-restrictive silencer factor/repressor element 1-silencing transcription factor (NRSF/ REST) binding activity potentiated by ethanol underlies the mechanism of ethanol inhibition of neuronal differentiation. Epigenetics refers to post-translational modifications of DNA and nuclear proteins that produce lasting alterations in patterns of gene expression. Epigenetic mechanism plays a critical role of neuronal plasticity and there is clear evidence that dysfunction of epigenetic mechanism also contributes to neurological and psychiatric illness. We will review epigenetic regulation in pathogenesis of psychiatric illness including alcoholism. We also demonstrated that trichostatin A, histone deacetylase inhibitor, reduced the ethanol-induced suppression of neuronal differentiation of NSCs. We suggest that ethanol alters the function of neural differentiation through the mechanism of potentiation of NRSF/REST binding and histone modifications.
Ishii
Takao
T
Department of Occupational Therapy, Sapporo Medical University School of Health Sciences, S-1, W-17, Chuo-ku, Sapporo 060-8556, Japan.
Hashimoto
Eri
E
Ukai
Wataru
W
Tateno
Masaru
M
Yoshinaga
Toshihiro
T
Ono
Takahumi
T
Watanabe
Kimihiko
K
Saito
Satoshi
S
Saito
Toshikazu
T
D000437:Alcoholism / Q000150:complications*; D000818:Animals; D001925:Brain Damage, Chronic / Q000209:etiology* / Q000235:genetics*; D002454:Cell Differentiation / Q000187:drug effects*; D004247:DNA; D004791:Enzyme Inhibitors / Q000494:pharmacology; D044127:Epigenesis, Genetic / Q000502:physiology*; D000431:Ethanol / Q000009:adverse effects*; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000235:genetics; D009474:Neurons / Q000166:cytology*; D011499:Protein Processing, Post-Translational; D012097:Repressor Proteins / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*; D000099229:RE1-Silencing Transcription Factor
D004247:DNA; D004791:Enzyme Inhibitors; D000431:Ethanol; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D012097:Repressor Proteins; D000099229:RE1-Silencing Transcription Factor; C012589:trichostatin A