Epigenetic regulation of memory by acetylation and methylation of chromatin: implications in neurological disorders, aging, and addiction.
Synaptic plasticity is one of the most fundamental properties of neurons that underlie the formation of the memory in brain. In recent years, epigenetic modification of both DNA and histones such as DNA methylation and histone acetylation and methylation emerges as a potential regulatory mechanism that governs the transcription of several genes responsible for memory formation and behavior. Furthermore, the recent identification of nitrosylation of proteins has shown to either activate or repress gene transcription by modulating histone methylation or acetylation status in mature neuron. Recent studies suggest that the use of major substrates of abuse, e.g., cocaine, induces alterations in molecular and cellular mechanisms of epigenetics that underlie long-term memories in the striatum and prefrontal cortex. Moreover, downregulation of genes due to alterations in epigenetics leads to cognitive deficiencies associated with neurological disorders such as Alzheimer's disease, Huntington's disease, psychiatric disorder such as Rett's syndrome and aging. In this review, I will discuss the evidence for several epigenetic mechanisms in the coordination of complex memory formation and storage. In addition, I will address the current literature highlighting the role of acetylation and methylation of chromatin in memory impairment associated with several neurological disorders, aging, and addiction.
Department of Neuroscience and Regenerative Medicine, Georgia Regents University, 1120 15th Street, CA 2018, Augusta, GA, 30912, USA, nsen@gru.edu.
Nilkantha
N
Sen
D000107:Acetylation; D000375:Aging / Q000235:genetics / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002843:Chromatin / Q000235:genetics*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D042421:Histone Code; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006655:Histone Deacetylases / Q000502:physiology; D006657:Histones / Q000378:metabolism; D006801:Humans; D008568:Memory / Q000502:physiology*; D008745:Methylation; D009414:Nerve Growth Factors / Q000502:physiology; D009422:Nervous System Diseases / Q000235:genetics / Q000378:metabolism; D009473:Neuronal Plasticity / Q000235:genetics; D009569:Nitric Oxide / Q000502:physiology; D015538:Nitrosation; D011499:Protein Processing, Post-Translational; D019966:Substance-Related Disorders / Q000235:genetics / Q000378:metabolism
D002843:Chromatin; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D009414:Nerve Growth Factors; D009569:Nitric Oxide; D006655:Histone Deacetylases